68th Annual Meeting, Miami Beach, Fla., March 5

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Supplement to
Journal of the American Academy of Dermatology
JAAD
March 2010
Volume 62 • Number 3
www.eblue.org
Poster Abstracts
American Academy of Dermatology
68th Annual Meeting
March 5–9, 2010
Miami, Florida
March 2010
Supported by
Galderma Laboratories, L.P.
Vol. 62 No. 3 (pages AB1-AB204)
SUPPLEMENT TO
JAAD
www.eblue.org
Journal of the
American
Academy of
Dermatology
March 2010
/ Volume 62
/
Number 3
Poster Exhibit Task Force
The Posters Exhibit Task Force enhances the educational value of the
Academy Meetings by administering poster exhibits, poster discussion
sessions, and poster awards. Poster abstracts are solicited, blind reviewed,
and graded by peer review for selection as poster exhibits or poster
discussions. The Task Force develops guidelines and monitors posters for
quality educational content.
Task Force Members:
Brian Berman, MD, PhD, FAAD, Chair
Mark A. Bechtel, MD, FAAD
Carrie Ann R. Cusack, MD, FAAD
Vincent Anthony DeLeo, MD, FAAD
Peter G. Ehrnstrom, MD, FAAD
Tammie C. Ferringer, MD, FAAD
Abel D. Jarell, MD
Barbara M. Mathes, MD, FAAD
Khalid Mohd Al Aboud, MD
Eduardo D. Poletti-Vazquez, MD
William D. Posten, MD, FAAD
Adam Rubin, MD, FAAD
Youwen Zhou, MD, FAAD
2011 Annual Meeting Program Submissions
Visit http://www.aad.org for information regarding program
participation for the 69th Annual Meeting, February 4-8, 2011
in New Orleans, Louisiana.
SUPPLEMENT TO
JAAD
www.eblue.org
Journal of the
American
Academy of
Dermatology
March 2010
/
Volume 62
Poster Abstracts
68th Annual Meeting
March 5-9, 2010
Miami, Florida
Supported by
Galderma Laboratories, L.P.
/
Number 3
SUPPLEMENT TO
JAAD
Journal of the
American
Academy of
Dermatology
March 2010
www.eblue.org
/
Volume 62
/ Number 3
CONTENTS
Poster Abstracts
Supported by Galderma Laboratories, L.P.
AB1
PD01—Acne
AB3
PD02—Psoriasis and Hair
AB5
PD03—Oncology and Surgery
AB7
PD04—Melanoma, Squamous Cell Carcinoma, Infection
AB9
PD05—Atopic Dermatitis and Pediatric Dermatology
AB11
PD06—Blistering and Systemic Diseases, and Teledermatology
AB13
Acne
AB18
Aging/Geriatrics
AB22
Art, History, and Humanities of Dermatology
AB22
Basic Science
AB26
Clinical Dermatology and Other Cutaneous Disorders
AB43
Connective Tissue Disease
AB45
Dermatitis, Atopic
AB48
Dermatitis, Contact and Allergic Irritants
AB51
Dermatopathology
AB54
Dermatopharmacology/Cosmeceuticals
AB63
Digital/Electronic Technology
AB65
Education and Community Service
Continued on page A8
Copyright ª 2010 by the American Academy of Dermatology, Inc. The opinions or views expressed in this professional education supplement are those of the authors and do not
necessarily reflect the opinions or recommendations of the society, editor(s), or publisher.
Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may reflect their clinical experience or may be derived from the
professional literature or other clinical sources. Because of the differences between in vitro and in vivo systems and between laboratory animal models and clinical data in humans,
in vitro and animal data may not necessarily correlate with clinical results.
Future citation agreement/How to cite abstracts from this supplement: Author(s) agree(s) that citations to poster abstracts published in the Journal
of the American Academy of Dermatology will adhere to the format of the examples given below, which clearly indicate that the cited item has been published in abstract
form.
Authors. Title of abstract (abstract). J Am Acad Dermatol 2009;60:AB page number. Abstract number.
Kavand S. The effect of isotretinoin therapy in plasma homocystein levels in acne vulgaris (abstract). J Am Acad Dermatol 2010;62:AB1. Abstract P100.
J AM ACAD DERMATOL
MARCH 2010
A7
Contents continued
AB66
Epidemiology and Health Services Administration
AB70
Genodermatoses
AB74
Hair and Nail Disorders
AB77
Immunodermatology and Blistering Disorders
AB80
Infection (Bacterial & Parasitic)
AB83
Infection (Fungal)
AB88
Infection (Viral)
AB91
Internal Medicine Dermatology
AB95
Lymphoma, Cutaneous/Mycosis Fungoides
AB98
Melanoma and Pigmented Lesions
AB102 Nonmelanoma Skin Cancer
AB109 Pediatric Dermatology
AB114 Photobiology, Phototherapy, and Photosensitivity Diseases
AB118 Pigmentary Disorders and Vitiligo
AB123 Psoriasis and Other Papulosquamous Disorders
AB141 Surgery (Cosmetic)
AB144 Surgery (Dermatologic)
AB147 Surgery (Laser)
AB150 Wound Healing and Ulcers
AB152 Author Disclosures
AB175 Author Index
AB184 Subject Index
A8
MARCH 2010
J AM ACAD DERMATOL
SUPPLEMENT TO
JAAD
Journal of the
American
Academy of
Dermatology
Editor Bruce H. Thiers, MD
Editorial Office
Melissa Derby, Managing Editor
482 Southbridge Street, Ste #266
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Medical University of South Carolina
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Editor
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Geisinger Medical Center
Danville, Pennsylvania
Associate Editors
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Denver, Colorado
Medical Dermatology
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Augusta, Georgia
Medical Dermatology
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Pediatric Dermatology
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Minneapolis, Minnesota
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Smithtown, New York
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David A. Mehregan, MD
Officers
Board of Directors
David M. Pariser, MD President
Evan R. Farmer, MD Vice President
William D. James, MD
President-Elect
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Robert D. Greenberg, MD
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C. William Hanke, MD
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Brian Berman, MD, PhD
Brett M. Coldiron, MD
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Victor J. Marks, MD
Ronald L. Moy, MD
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Mobile, Alabama
Editors Emeritus
Editorial Board
Christopher J. Miller, MD
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Ulrich Mrowietz, MD
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Neil S. Sadick, MD
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Ekin Savk, MD
Kathryn Schwarzenberger, MD
Alexander J. Stratigos, MD
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Charles R. Taylor, MD
Antonio Torrelo, MD
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Mirjana Ziemer, MD
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J AM ACAD DERMATOL
Executive Staff
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AB Chair
Frank C. Powell, MD
International Board Observer
Clarence W. Brown, Jr, MD
Young Physicians Observer
Jennifer Lucas, MD
Resident Observer
Ronald A. Henrichs, CAE
Executive Director and CEO
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Phone: 847-330-0230
Fax: 847-330-0050
MARCH 2010
A11
PD01-ACNE
P100
The effect of isotretinoin therapy in plasma homocystein levels in acne
vulgaris
Sima Kavand, MD, Skin Research Center of Shohada ye Tajresh Hospital, Tehran,
Iran
Background: Isotretinoin revolutionized the treatment of acne by improving the
cosmetic outcome and decreasing the psychological damage. The use of isotretinoin
is associated with significant side effects, such as mucocutaneous involvement,
dyslipidemia, and increased liver enzymes. Because liver enzymes (SGOT, SGPT, etc)
were found elevated during isotretinoin treatment, which is the sign of liver
dysfunction, the responsible enzyme for homocysteine metabolism, cystathionineb-synthase, might be affected. Hyperhomocysteinemia is an independent risk factor
for thrombovascular diseases.
Objective: The aim of study was the evaluation of Hcy levels and the responsible
vitamins for its metabolism in patients with moderate to severe acne vulgaris on
isotretinoin treatment.
Methods: Forty-seven (n ¼ 47) patients with acne had liver function tests, folate,
vitamin B12, Hcy, and serum lipids evaluations. Before (value 1) and on the second
month (value 2) of treatment with isotretinoin (0.5mg/kg/day), Hcy was evaluated
by HPLC methods.
Results: Hcy levels (value 1: 11.8 6 5.3mol/L; value 2: 13.6 6 7.4mol/L; P \.001)
were statically significantly increased in patients on treatment. Lipids and liver
enzymes increased, but no significant correlation between Hcy levels, vitamins, and
liver enzymes was found.
Conclusion: Elevated Hcy levels in patients after 2 months on isotretinoin therapy
were found in this study. Vitamin supplementation along with frequent evaluations
of Hcy blood levels is recommended for the prevention of a premature occlusive
disease.
Commercial support: None identified.
P102
Treatment with adapalene 0.1%-bpo 2.5% and doxycycline 100 mg/day
resulted in rapid and sustained decrease in Propionibacterium acnes
Michael Jarratt, MD, DermResearch, Inc, Austin, UT, United States; Alicia D. Bucko,
DO, Academic Dermatology Associates, Albuquerque, New Mexico, United States;
Didier Zugaj, Galderma Research and Development, Sophia-Antipolis, France;
Jean-Charles Dhuin, Galderma Research and Development, Sophia-Antipolis,
France
Propionibacterium acnes (P acnes) is a Gram-positive organism commonly found
on normal skin. P acnes is believed to play a major role in the pathogenesis of acne.
Most topical antiacne drugs, such as benzoyl peroxide and topical antibiotics, exert
their therapeutic effect through the elimination of P acnes. Some strains of P acnes
are resistant to erythromycin, clindamycin, and/or drugs in the tetracycline family as
a result of topical and systemic antibiotic usage as acne treatment over the past
several decades. Adapalene 0.1%/benzoyl peroxide 2.5% gel (adapalene-BPO) is a
unique, antibiotic-free combination of a well-tolerated and efficacious topical
retinoid (adapalene 0.1%), and a well established antimicrobial agent at a low
concentration (BPO 2.5%).
A large, multicenter, randomized trial of 459 patients was conducted to compare
adapalene-bpo 1 doxycycline to vehicle gel 1 doxycycline for efficacy and safety in
acne patients. A subset of patients (n ¼ 38) was randomly selected from this patient
pool to undergo fluorescence photoimaging using the Visia photography system.
Fluorescent photography images were analyzed from 18 adapalene-bpo 1 doxycycline patients and from 20 vehicle gel 1 doxycyline patients. After the first 4 weeks
of treatment, a mean 60.3% reduction in P acnes was observed in the adapaleneBPO 1 doxycycline group compared to a 22% reduction in P acnes observed in the
vehicle 1 doxycycline group. In the adapalene-BPO 1 doxycycline group, the
reduction at week 8 was furthered to 72.9% and was sustained at week 12 (73.6%).
In the vehicle 1 doxycycline group, the mean percent reduction from baseline was
16% at week 8 and 14% at week 12. The reduction in P acnes seen in this subgroup
correlates well with the improved lesion reduction and clinical benefit that was
observed in the adapalene-BPO 1 doxycycline group compared to the vehicle 1
doxycycline group as part of the study’s primary endpoint. Taken together, these
data suggest that adapalene-BPO 1 doxycycline is an effective regimen whose
mechanism may be partly related to a decrease in P acnes on the skin.
Commercial support: Study and poster support provided by Galderma
Laboratories, L.P.
P101
Investigation of the relationship between acne and diet in Korean patients
Dae Hun Suh, MD, PhD, Acne Research Laboratory, Seoul National University
Hospital, Department of Dermatology, Seoul National University College of
Medicine, Seoul, South Korea; Jae Yoon Jung, MD, Acne Research Laboratory,
Seoul National University Hospital, Department of Dermatology, Seoul National
University College of Medicine, Seoul, South Korea; Mi Young Yoon, Acne
Research Laboratory, Seoul National University Hospital, Department of
Dermatology, Seoul National University College of Medicine, Seoul, South
Korea; Seong Uk Min, MD, Acne Research Laboratory, Seoul National
University Hospital, Department of Dermatology, Seoul National University
College of Medicine, Seoul, South Korea
There has been much controversy about the relationship between acne and foods.
Some researchers contended that acne may be provoked or aggravated by some
foods. However, the more general consensus was that acne was not affected by
foods. They said there is no relationship between acne severity and total calorie
intake, carbohydrates, lipids, proteins, minerals, and amino acids. Recently, some
researchers awakened our interest by concluding that there is a positive relationship
between acne and foods in their analytic studies. From their epidemiologic data, it
was suggested there is a causative relationship between acne and foods.
A hypothetical mechanism was also suggested. We enrolled 783 patients with
acne and 502 control subjects. For the patients with acne, blood tests for IGF-1,
IGFBP-3, PP2, DHEA-S, and testosterone were performed. The acne patients were
divided into an ‘‘aggravated by food’’ group (AF) and a ‘‘not aggravated by food’’
group (NAF). All participants were asked to fill out a questionnaire.
The frequency of vegetable and fish intake was significantly higher in the control
group than in the acne group. Intake of instant noodles, junk food, carbonated
drinks, snacks, processed cheeses, pork (braised), pork (roasted), chicken (fried),
chicken (stewed), nuts, and seaweed were significantly higher in the acne patients
than in the controls. Intake of roasted pork, fried chicken, and nuts was significantly
higher in the AF group than in the NAF group. In addition, the regularity of intermeal
intervals and breakfast intake were significantly lower in the acne patients.
IGF-1 and IGFBP-3 showed gender difference.
This study showed that a high glycemic load diet, dairy food intake, high fat diet, and
iodine in Korean foods appear to play a role in acne exacerbation. In addition, it is
suggested that irregular dietary patterns may also aggravate acne.
P103
Azelaic acid gel alters kallikrein 5 and cathelicidin expression in epidermal keratinocytes, critical elements in the pathogenesis of rosacea
Richard Gallo, MD, PhD, VA San Diego Medical Center, San Diego, CA, United
States; Kenshi Yamasaki, MD, PhD, Division of Dermatology, La Jolla, CA, United
States
Recent observations have shown that facial skin from patients with rosacea
produces excess amounts of the serine protease kallikrein 5 (KLK5), and abnormal
forms of the antimicrobial peptide cathelicidin (CAMP).1 In mice, abnormal CAMP
and KLK5 expression influences inflammation, and administration of the forms of
human CAMP found in rosacea results in inflammation, angiogenesis, and vascular
ectasia. In this study, we sought to further confirm the critical role of KLK5 and
CAMP in rosacea by examining if the effects of a current human beneficial therapy
correlated with changes in the expression of these genes. We measured KLK5 in
cultured normal human epidermal keratinocytes (NHEKs) and found that differentiated keratinocytes in high calcium media (1.6mM) greatly increased both KLK5
mRNA and protein compared to undifferentiated cells. The addition of azelaic acid
(AzA; 10-8 to 10-9M) to differentiated NHEKs significantly decreased KLK5 in media
(vehicle; 91.26 6 22.58 ng/mL, 10-8M AzA; 41.69 6 15.08 ng/mL). Total protease
activity was also significantly less in media recovered from keratinocytes treated
with 10-8M AzA. Furthermore, mice treated once a day for 9 days with topical
application of AzA gel 15% (Intendis; Berlin, Germany) showed significantly less
KLK5 and CAMP mRNA compared with mouse skin treated with the vehicle alone
(relative expression of KLK5 and CAMP was 55% and 32% of control, respectively).
In conclusion, because an excess of KLK5 and cathelicidin has been hypothesized to
contribute to the development of rosacea, finding that an effective treatment for
rosacea can decrease expression of these molecules further supports the involvement of KLK5 and cathelicidin in the pathogenesis of this disease.
REFERENCE
1. Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, et al. Increased
serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat
Med 2007;13:975-80.
Commercial support: This study was funded by Intendis.
MARCH 2010
J AM ACAD DERMATOL
ABS 5.0 DTD YMJD6683_6688_proof 4 February 2010 11:24 pm
AB1
P104
P106
Hexamidine, a protease inhibitor, promotes stratum corneum lipid biomarkers in vitro
Bradley Jarrold, MS, Procter & Gamble Beauty, Cincinnati, OH, United States; Jay
Tiesman, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States; Michael
Robinson, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States; Robert
Binder, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States; Rosemarie
Osborne, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States
Background: Skin aging has been described as a cumulative process resulting from
unrepaired damage and age-related physiologic changes. The damaging factors that
accelerate skin aging can be divided into intrinsic factors, such as free radicals, and
extrinsic factors, with ultraviolet light (UV) exposure being the most important.
Within the current study, we examined the effects of both intrinsic and photoaging
on the expression of stratum corneum (SC) lipid metabolism pathways. Human skin
equivalent (SE) cultures were used to monitor these pathways in response to
hexamidine, a protease inhibitor.
Objective: To evaluate the effects of intrinsic and photoaging on gene expression of
SC lipid metabolism pathways in vivo and monitor these pathways in SEs in response
to hexamidine.
Expression of IL-10 and TGF-b1 in cultured fibroblasts after IPL treatment
or ALA-IPL photodynamic treatment
Ji Yeon Byun, MD, Department of Dermatology, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, South Korea; Hae Young
Choi, MD, Department of Dermatology, School of Medicine, Ewha Womans
University, Seoul, South Korea; Ki Bum Myung, MD, Department of Dermatology,
School of Medicine, Ewha Womans University, Seoul, South Korea; Sang Woo Lee, MD,
Department of Dermatology, School of Medicine, Ewha Womans University,
Seoul, South Korea; You Won Choi, MD, Department of Dermatology, School
of Medicine, Ewha Womans University, Seoul, South Korea
Method: RNA was purified from full thickness skin biopsies from individual study
subjects’ [young (18-20 yrs of age) or older (60-67 yrs of age) females] buttocks (UV
protected) and outer forearm (UV exposed). RNA was labeled and hybridized to
Affymetrix Gene Chips (Affymetrix, Santa Clara, CA). After statistical analysis,
bioinformatics focused on expression of genes specific to metabolism of SC lipids.
SEs treated topically with 0.1% hexamidine for 24 hours were processed for gene
chip analysis as stated above.
Results: In intrinsically and photoaged skin, there was an expressional downregulation of genes involved in SC lipid biosynthesis and metabolism. As compared
to young skin, the epidermal cholesterol, fatty acid, and sphingolipid synthetic
pathway genes were downregulated. In addition, the major cholesterol and fatty
acid uptake pathways were downregulated, while the major cholesterol efflux
pathway was upregulated. In contrast, SE treated with hexamidine showed the
opposite effect with upregulation of these pathways.
Conclusions: The coordinated downregulation of these pathways is consistent with
previously reported global decreases in SC lipids in aging skin, and likely contributes
to the decreased capacity of aged skin to maintain and repair the epidermal barrier.
The coordinate upregulation of these pathways in response to hexamidine suggests
that there are increased levels of these key lipids available for maintenance and
repair.
Depending on the light dose and the concentration of photosensitizer for photodynamic treatment (PDT), a continuum of dose-related events is demonstrable in
PDT-treated cells from tumor destruction by cytotoxic effects when highlight and
drug doses are applied to immunomodulation when lower sublethal doses are
applied. The mechanism of immunomodulation is not clearly identified, but the
alteration of cytokine expression is suspected to be involved. We have previously
reported the induction of interleukin (IL)-10 and transforming growth factor beta
(TGF-b1) after PDT using 5-aminolevulic acid (ALA) and intense pulsed light (IPL)
treatment at sublethal doses in cultured keratinocytes (HaCaT cells). The purpose of
this study was to investigate the expression of IL-10 and TGF-b1 in cultured
fibroblasts after IPL treatment or ALA-IPL PDT at sublethal doses. Cultured
fibroblasts were treated either IPL-only (4, 8, and 12 J/cm2) or ALA-IPL PDT
(1 mol/L of ALA; 0, 4, 8, and 12 J/cm2 of IPL). The expression of IL-10, TGF-b1, and
tumor necrosis factor-alfa (TNF-a) was investigated by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. IL-10 protein was
induced up to 5.18-fold after IPL treatment and up to 2.74-fold after PDT. The
induction of IL-10 may contribute to the antiinflammatory effect, which explains the
therapeutic benefit of PDT for inflammatory dermatoses. The finding that IL-10 was
induced more markedly after IPL treatment than after PDT suggests that other
mechanisms than IL-10 induction may participate in the antiinflammatory effect of
PDT. TGF-b1 mRNA and protein were reduced down to 0.92- and 0.86-fold,
respectively, after IPL treatment and down to 0.52- and 0.63-fold, respectively, after
PDT. The reduction of TGF-b1 may be related to the antisclerotic effect of PDT
observed in vivo. In comparison to IPL treatment, the reduction was more marked
after PDT and, therefore, a better antisclerotic effect is expected after PDT than after
IPL treatment. We believe that these findings may contribute to a better understanding of the immunologic effects of PDT and that further studies including in vivo
studies are required.
Commercial support: 100% sponsored by Procter & Gamble.
P107
P105
In vitro activity of resveratrol against Propionibacterium acnes
Emma Taylor, MD, UCLA Division of Dermatology, Los Angeles, CA, United States;
Jackson Champer, UCLA Division of Dermatology, Los Angeles, CA, United States;
Jenny Kim, MD, PhD, UCLA Division of Dermatology, Los Angeles, CA, United
States
Multicenter, randomized, parallel-group, double-blind, vehicle-controlled
study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel,
0.05% in patients with actinic keratoses on nonhead locations
Neil Swanson, MD, Oregon Health & Science University, Portland, OR, United
States
Phase II studies suggest that PEP005 (ingenol mebutate) gel 0.05% applied to actinic
keratoses (AK) lesions once daily for 2 days may be the appropriate concentration
and dosage regimen. We conducted a phase III study to assess further the efficacy
and safety of 0.05% ingenol mebutate gel for 2 days in patients with AK on nonhead
locations. A total of 255 patients were randomized to treatment with 0.05% ingenol
mebutate gel or vehicle. Patients were evaluated on days 3, 8, 15, 29, and 57. Efficacy
was assessed by complete clearance (primary endpoint) and partial clearance
(secondary endpoint) of AK lesions. Safety was assessed by the incidence rate of
adverse events (AEs), serious AEs, and AEs leading to discontinuation and also by the
incidence rate and grade of local skin responses (LSR), pigmentation, and scarring.
Complete clearance of AK lesions across all anatomic nonhead sites at day 57 was
observed in 32 (27.4%) patients treated with 0.05% ingenol mebutate gel and 6
(5.1%) in the vehicle group (P ¼.0001). For individual anatomic locations, complete
clearance rates for active treatment were 0% (0/2) for the back, 16.0% (4/25) for the
back of the hand, 16.7% (1/6) for legs, 25.3% (19/75) for the arms, and 88.9% (8/9)
for the chest. Partial clearance was noted in 52 (44.4%) of patients in the 0.05%
ingenol mebutate gel group and nine (7.6%) in the vehicle group (P \.0001). A
66.7% median percentage reduction in AK lesion count from baseline across all
anatomic nonhead sites was noted in the 0.05% ingenol mebutate gel group
compared with 0% in the vehicle group (P \.0001). AEs were generally mild to
moderate and resolved by day 57. The most common treatment emergent AEs
(TEAEs) were application site irritation and pruritus. One patient experienced pain
in the treatment area that led to discontinuation after one application. There were
no serious TEAEs. Erythema and flaking/scaling were the most frequently reported
LSRs in the active treatment group. A total of seven patients in the 0.05% ingenol
mebutate gel group had pigmentation changes: four reported improvement and
three reported worsening of pigmentation. No patient experienced worsening of
scarring. The results show that 0.05% ingenol mebutate gel for two consecutive days
was significantly more effective than vehicle with respect to complete and partial
clearance of AK lesions and was also well tolerated. There were no drug-related
serious AEs, and 98% of patients applied both doses.
Methods: Colony forming unit (CFU) and growth inhibition assays for P acnes
incubated with resveratrol were performed to assess the bactericidal and bacteriostatic properties of resveratrol, respectively. In addition, a qualitative polymerase
chain reaction study was performed to determine if resveratrol affected the
production of matrix metalloproteinases (MMPs) in monocytes stimulated with
P acnes. Enzyme linked immunosorbent assays were run under identical conditions
to examine resveratrol modulation of cytokine production.
Results: At low concentrations, resveratrol reduced the growth of P acnes as
compared to control (1% DMSO) in a dose-dependent manner. CFU assays of
resveratrol against P acnes displayed bactericidal activity at higher concentrations in
a dose-dependent manner. Primary human monocytes stimulated with P acnes
induced MMP1 and MMP9 mRNA, which were downregulated in the presence of
resveratrol. In addition, resveratrol inhibited interleukin-12 production in human
monocytes induced by P acnes.
Conclusion: Resveratrol showed antimicrobial activity against P acnes and also
antiinflammatory properties induced by P acnes, suggesting that it may be a novel
therapeutic option for the treatment of acne vulgaris.
Commercial support: 65% sponsored by Peplin Ltd.
AB2
Background: Resveratrol (3,5,4’-trihydroxystilbene) is a polyphenol found in red
wine, colored berries, and nonedible parts of the peanut plant. Resveratrol has
multiple biologic effects, including antitumor, estrogenic, antimicrobial, and
antiinflammatory properties. Acne is caused by several factors, including hyperproliferation and abnormal differentiation of keratinocytes, impaction of follicles
forming a keratinaceous plug, increased androgens and sebum production,
Propionibacterium acnes, and proinflammatory mediators. Because resveratrol
has both antimicrobial and antiinflammatory properties, we investigated its effect
on P acnes growth, survival, and ability to induce release of proinflammatory
mediators. We hypothesized that resveratrol might offer a novel therapeutic
option for the treatment of acne vulgaris.
Objectives: To evaluate the in vitro antibacterial, matrix-preservation, and antiinflammatory properties of resveratrol.
J AM ACAD DERMATOL
MARCH 2010
PD02- PSORIASIS AND HAIR
P200
Classical and nonclassical calciphylaxis, and a lesson in chemistry
Suyin Ong, MBBCh, Department of Dermatology, Burnley General Hospital,
Burnley, Lancashire, United Kingdom; Caroline Owen, MBChB, Department of
Dermatology, Royal Blackburn Hospital, Blackburn, Lancashire, United Kingdom;
Ian H Coulson, MBBS, Department of Dermatology, Burnley General Hospital,
Burnley, Lancashire, United Kingdom
Calciphylaxis occurs when calcium salts are deposited in the microvascular
network, causing an obliterative vasculopathy. In the skin, this appears as reticulate
purpura that breaks down to form painful ulcers as the skin undergoes ischaemic
necrosis. Calciphylaxis classically occurs because of secondary hyperparathyroidism in chronic kidney disease, but it is now recognized that calciphylaxis can also
occur in patients with normal parathyroid and renal function. The overall mortality
of calciphylaxis is greater than 80%. We present two contrasting cases who both
presented with leg ulcers: a 63-year-old woman with calciphylaxis caused by
primary hyperparathyroidism but normal renal function, and a 79-year-old woman in
whom the syndrome occurred despite normal renal and parathyroid function. In
both cases, the leg ulcers had surrounding livedo reticularis and were exquisitely
painful. The nonclassical case in particular required high-dose opioids in addition to
amitryptiline, gabapentin, and a lumbar sympathectomy for analgesia. Histology
confirmed luminal obliteration and calcification of subcutaneous vessel walls
in both patients. The classical case responded to parathyroid adenectomy, conventional treatment with intravenous pamidronate infusions, broad-spectrum
antibiotics, and surgical debridement. The nonclassical case however, was
normocalcaemic and had no renal dysfunction. Because warfarin and amlodipine
have been associated with nonclassical calciphylaxis, they were switched to aspirin
and ramipril, respectively. Intravenous pamidronate did not halt the worsening
ulceration. Intravenous sodium thiosulfate infusions (25 g via peripherally inserted
central catheter over 60 min, thrice weekly) were administered intermittently over a
6-month period. She received intensive wound care. Her ulcers became less painful
over the first 2 months and healed completely over the next 8 months. Sodium
thiosulfate (Na2S2O3) liberates calcium ions from calcium salt deposits by forming
calcium thiosulfate, which is 250 to 100000 times more soluble in aqueous solution
compared to other calcium salts (phosphate, sulphate, citrate, and oxalate). The
obliterative vasculopathy caused by calcification therefore improves when calcium
thiosulfate is renally excreted or dialyzed. These two cases illustrate the management of classical and nonclassical calciphylaxis with cutaneous ulceration and
support the use of sodium thiosulfate in the treatment of this life- and limbthreatening condition.
P202
Comorbidity risks increase over time in patients with psoriasis
Alexa Kimball, Harvard Medical School, Boston, MA, United States; Andrew Yu,
Analysis Group, Boston, MA, United States; Parvez Mulani, Abbott Laboratories,
Abbott Park, IL, United States; Yanjun Bao, Abbott Laboratories, Abbott Park, IL,
United States
Objective: To assess the comorbidity burden over time for patients (pts) with
psoriasis (Ps) versus pts without Ps and to determine whether Ps-associated
comorbidity risks increase over time.
Methods: The MarketScan claims database (2000-2006) was used to identify new pts
with Ps using the following criteria: those with $ 2 Ps diagnosis codes (ICD-9-CM:
696.1x) whose first diagnosis was $ 1 year after the beginning of eligibility and who
did not receive a diagnosis of psoriatic arthritis (ICD-9-CM: 696.0x) or any biologic
treatment before their first Ps diagnosis. The index date was defined as the date of
the first Ps diagnosis plus 180 days. Each pt with Ps was matched 1:1 to a Ps-free
control pt based on age, sex, and region of residence. Control pts were assigned a
random index date that achieved $ 180 days of preindex (baseline) eligibility. All pts
were continuously enrolled for $ 2 years and had $ 1 medical claim after the index
date. Pts were followed from the index date until the end of eligibility or the
initiation of a biologic treatment, whichever occurred first. Chi-square tests and
Kaplan-Meier survival analyses were used to compare the prevalence rates of
comorbidities over time.
Results: A total of 5723 pts with Ps and 5723 controls were selected. At baseline, pts
with Ps had a greater prevalence of comorbidities compared with Ps-free control pts.
During the study period, pts with Ps had significantly greater rates of hypertension
(relative risk ratio [RRR] ¼ 1.1), cardiovascular diseases (RRR ¼ 1.2), depression
(RRR ¼ 1.1), diabetes mellitus (RRR ¼ 1.1), hyperlipidemia (RRR ¼ 1.1), and obesity
(RRR ¼ 1.5; all P \ .05). Over time, pts with Ps had a consistently greater
comorbidity prevalence than pts who did not have Ps. Furthermore, Kaplan-Meier
estimates showed that the differences in comorbidity rates increased over a 4-year
period, with the greatest differences for hyperlipidemia (3.0 percentage point
increase), obesity (1.2 percentage point increase), and depression (1.1 percentage
point increase). For depression and obesity, the rate differences between Ps and
non-Ps patients increased each year. Ascertainment biases and other biases may
affect this analysis.
Conclusions: Over time, pts with Ps are at increased risk of developing major
comorbidities, particularly hyperlipidemia, depression, and obesity.
Commercial support: This study is sponsored by Abbott Laboratories.
P203
P201
Potential drugedrug interactions of oral systemic therapies for psoriasis
have adverse outcomes in a real-world setting
Jean-Hilaire Saurat, Hôpital Cantonal Universitaire de Genève, Geneva,
Switzerland; Annie Guérin, Analysis Group, Boston, MA, United States; Parvez
Mulani, Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott
Laboratories, Abbott Park, IL, United States
Objective: To investigate the health care outcomes associated with methotrexate
(MTX) or cyclosporine (CYC) used concurrently with medications that could have
potential drugedrug interactions (PDDI drugs).
Methods: The Ingenix Impact National Managed Care Database (1999-2007) was
used to select continuously enrolled adult patients with psoriasis who initiated
MTX/CYC (ie, index). Two groups were stratified: (1) the at-risk (AR) group, which
included patients using PDDI drugs within 30 days before and 30 days after index;
and (2) the not-at-risk (NAR) group, which included patients without concurrent use
of PDDI drugs during the 30 days before the index and the 6-month study period
after the index. Study outcomes included adverse events (AEs) of toxicities, resource
utilization, and health care costs. Adjusted odds ratios (ORs), incidence rate ratios
(IRRs), and incremental costs between the two groups were estimated using logistic
regression models, negative binomial models, and gamma regression models with
log link function, respectively; all controlled for age, sex, baseline comorbidities,
resource utilization, and psoriasis therapies.
Cost per responder for biologic treatment of psoriasis: Matching-adjusted
comparisons of adalimumab with etanercept, infliximab, and ustekinumab
James Signorovitch, Analysis Group, Boston, MA, United States; Parvez Mulani,
Abbott Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott
Laboratories, Abbott Park, IL, United States; Yanjun Bao, Abbott Laboratories,
Abbott Park, IL, United States
Objectives: No randomized trial has directly compared adalimumab with other
biologic treatments for moderate to severe psoriasis. Accounting for differences in
patient populations across trials, this study provided matching-adjusted indirect
comparisons of the cost per responder of adalimumab with that of etanercept,
infliximab, and ustekinumab.
Results: The analysis included 7955 patients with psoriasis using MTX/CYC (42.4%
NAR and 57.6% AR). Nonsteroidal antiinflammatory drugs and antibiotics were the
most commonly used PDDI drugs. Compared with the NAR group, the AR group was
significantly more likely to experience renal toxicity (OR: 2.86; P ¼ .0064),
gastrointestinal toxicity (OR: 1.42; P ¼ .0075), and pulmonary toxicity (OR: 1.28;
P ¼ .0064). The AR group also used significantly more resources, such as
hospitalizations (IRR: 1.61; P \ .0001) and emergency department visits (IRR:
1.31; P ¼.0022), and incurred $1722 (P \.0001) greater adjusted total health care
costs than the NAR group ($711 greater pharmacy costs and $539 greater outpatient
costs [both P \.0001]).
Conclusions: More than half of patients with psoriasis treated with MTX/CYC used
PDDI drugs concurrently. These patients were at greater risk of AEs, used more
resources, and incurred greater health care costs.
Methods: Patient-level data from two placebo-controlled trials of adalimumab
(REVEAL and M02-528) were reweighted in separate analyses to exactly match
their average baseline characteristics and placebo-group responses to those from
published placebo-controlled trials of etanercept (Leonardi et al, 2003), infliximab
(Reich et al, 2005), and ustekinumab (Leonardi et al, 2008; Papp et al, 2008). For
each comparison of adalimumab with another biologic, the characteristics matched
included patient age, sex, psoriasis duration, Psoriasis Area and Severity Index (PASI)
score, percentage of affected body surface area, percentage of patients with
psoriatic arthritis, and treatment history. After matching, cost per patient achieving
$ 75% reduction in PASI score was compared for adalimumab versus etanercept and
ustekinumab at week 12 and versus infliximab at week 10 (using published PASI 75
response rates for nonadalimumab biologics). Total quantity of adalimumab used in
REVEAL and M02-528 was calculated using the observed number of injections. Total
drug use in the other biologic trials was estimated from published rates of dropout.
Canadian Wholesale Acquisition Costs as of December 2008 were used for each
drug. Statistical significance was assessed using the bootstrap method.
Results: After matching, drug costs per PASI 75 responder were less for adalimumab
than for etanercept, infliximab, and ustekinumab (all P \.0001). Adalimumab cost
per PASI 75 responder was Can $8996 less than that of etanercept (Can $7707 vs Can
$16703), Can $8292 less than that of infliximab (Can $7625 vs Can $15917), Can
$5630 less than that of ustekinumab 45 mg (Can $7666 vs Can $13296), Can $16880
less than that of full-price ustekinumab 90 mg (Can $7666 vs Can $24546), and Can
$4607 less than that of ustekinumab 90 mg priced the same as ustekinumab 45 mg
(Can $7666 vs Can $12273).
Conclusions: After matching average baseline characteristics and placebo group
responses, adalimumab therapy for moderate to severe psoriasis had the lowest cost
per PASI 75 responder compared with etanercept, infliximab, and ustekinumab.
Commercial support: This study is sponsored by Abbott Laboratories
MARCH 2010
J AM ACAD DERMATOL
AB3
P204
P206
Insulin resistance, nitric oxide, and fibrinogen levels in white hirsute
women: Defining a new paradigm based on translational research
Afshin Sadighha, MD, Ilam Medical University, Ilam, Iran; Gita Meshkat Razavi, MD,
Shahid Beheshti Medical University, Tehran, Iran
Impact of ustekinumab on quality of life and sexual difficulties associated
with psoriasis: Results from phase III clinical trials
Lynn Guenther, MD, Guenther Dermatology Research Centre, London, Ontario,
Canada; Chenglong Han, PhD, Johnson & Johnson Pharmaceutical Services,
Malvern, PA, United States; Howard L Sofen, MD, Dermatology Associates, Los
Angeles, CA, United States; Yves Poulin, MD, Centre Dermatologique du Quebec
Metropolitain, Sainte Foy, Quebec, Canada
Objective: To determine if sexual difficulties associated with psoriasis were
associated with disease severity and if they improved as the skin improved during
treatment with ustekinumab.
Methods: In the PHOENIX I and II trials, patients with moderate to severe psoriasis
(N ¼ 1996) were randomized to ustekinumab (45 or 90 mg; N ¼ 1334) at weeks 0, 4,
and every 12 weeks thereafter; or placebo (N ¼ 662) at weeks 0 and 4 with crossover
to ustekinumab (45 or 90 mg) at week 12. Psoriasis severity was assessed using the
Psoriasis Area and Severity Index (PASI) and quality of life with the Dermatology Life
Quality Index (DLQI). Question nine in the DLQI was used to explore sexual
difficulties. Impaired sexual function was defined as skin disease causing either
‘‘very much’’ or ‘‘a lot’’ of sexual difficulties.
Results: At baseline, the mean DLQI was 12.0, indicating a very large negative effect
on patient life. Impaired sexual function was reported by 22.6% (27.1% of
females and 20.8% of males) and was significantly associated with psoriasis severity.
At week 12, patients treated with ustekinumab had greater improvement in DLQI
(e9.13 vs e0.53 with placebo; P \.001) and impaired sexual function decreased
from 22.4% to 2.7% compared to no change observed in the placebo group
(P \ .001). Those patients who showed a greater improvement in PASI also
experienced greater reduction of sexual difficulties. A similar pattern of improved
sexual function was observed at weeks 24 to 28 in the placebo group who crossed
over to ustekinumab at week 12.
Background: Idiopathic hirsutism (IH) is characterized by hirsutism associated with
normal ovulatory function and normal circulating serum androgen concentrations.
Hyperandrogenism is also closely associated with insulin resistance, which has been
associated with impaired production or release of endothelium-derived nitric oxide
(NO), endothelial dysfunction, and increased levels of endothelin-1, all of which are
markers of vascular disease.
Objective: This study was designed to assess the presence or absence of insulin
resistance and hyperinsulinemia, especially in nonobese women with IH.
Meanwhile fibrinogen levels and nitrite/nitrate concentration as an index of
endothelium-derived NO would be evaluated in four groups.
Methods: One hundred sixty white females in four groups were recruited. After full
consideration, 31 obese women with polycystic ovary syndrome (PCOS), 32
nonobese women with PCOS, 33 nonobese women with IH, and 35 nonobese
controls met the criteria for participation in study. Obesity was defined as body mass
index (BMI) [30 kg/m2. The diagnosis of PCOS was performed according to the
Rotterdam 2003 criteria. Plasma fibrinogen levels were measured by the clotting
Clauss method with Fibri-Prest Automate. NO production was assessed by measuring the plasma concentration of NO3 and NO2 with the nitrate reductase-Griess
method.
Results: While no significant differences were observed between IH and control
subjects in terms of age, BMI, waist to hip ratio, and FerrimaneGallwey hirsutism
score, nitrite/nitrate concentration was significantly lower and fibrinogen plasma
levels were meaningfully higher in the IH group. It should be emphasized that
nitrite/nitrate concentration and fibrinogen plasma levels were similar in IH and
both PCO groups. Fasting insulin level, HOMA, and free androgen in the IH group
were higher than control subjects and lower than both PCO groups (obese and
nonobese), although the differences between IH and control groups were not
meaningful but between PCO and IH were significantly meaningful. Glucose
concentrations were similar among four groups. There were no cases of diabetes.
Conclusions: Impaired sexual function is a common comorbidity in patients with
moderate to severe psoriasis. Treatment with ustekinumab was associated with a
significant improvement in patient’s sexual function and quality of life.
Commercial support: Johnson & Johnson Pharmaceutical Services, L.L.C.
Conclusions: In our study, women with nonobese PCOS had significantly higher
basal insulin levels and HOMA scores than women with nonobese IH and controls.
Interestingly, there was no statistically significant difference with regard to insulin
levels or HOMA scores between women with obese and nonobese PCOS. This
founding let us to draw a new paradigm based on translational research.
P207
Incidence of serious infectious events with methotrexate treatment:
Metaanalysis of randomized controlled trials
Jennifer Powers, MD, Grand Rapids Medical Education and Research Center,
Grand Rapids, MI, United States; Richard Martin, MD, Michigan State University
College of Human Medicine, East Lansing, MI, United States
P205
Urinary symptoms in patients with androgenetic alopecia
Salvador Arias-Santiago, MD, San Cecilio Clinical Hospital, Granada, Spain;
Husein Husein-ElAhmed, MD, San Cecilio Clinical Hospital, Granada, Spain;
Marı́a Sierra Girón-Prieto, MD, Virgen de las Nieves Hospital, Granada, Spain;
Miguel Arrabal-Martı́n, PhD, San Cecilio Clinical Hospital, Granada, Spain; Miguel
A Arrabal-Polo, MD, San Cecilio Clinical Hospital, Granada, Spain
Introduction: Androgenetic alopecia (AGA) or male pattern hair loss affects
approximately 50% of the male population. AGA and benign prostatic hyperplasia
are both androgen-dependent disorders which are successfully treated with antiandrogens (5-a reductase inhibitors). This study sought to that identify if a true
relationship exists between benign prostatic hyperplasia, prostate symptom, and
AGA. Men between 35 and 65 years of age with early onset alopecia (\30 yrs) and
Ebling degree III or above are studied.
Background: On April 8, 2009, the US Food and Drug Administration announced
Genentech’s voluntary phased withdrawal of efalizumab from the US market
because of increasing concerns of a link to progressive multifocal leukoencephalopathy. Biologic agents have transformed psoriasis treatment, but they are associated with increased serious infectious events and significant expense, which revives
interest in the comparative efficacy of standard versus new therapies. The feasibility
of standard therapies like methotrexate (MTX) as psoriasis treatment hinges on a
more accurate measurement of serious adverse events such as serious infectious
events (SIEs).
Objective: To estimate the incidence of SIEs occurring in randomized trials of MTX
for psoriasis, psoriatic arthritis (PSA), and rheumatoid arthritis (RA) by performing a
metaanalysis.
Methods: This is a case control study that includes 50 patients with early-onset AGA
diagnosed in the dermatology unit and 50 controls. Prostate volume calculated with
transrectal ultrasound, testosterone, albumin, sexual hormoneebinding globulin
(SHBG), prostate specific antigen (PSA), urinary flow, and international prostate
symptom score test (IPSS) were measured in both groups.
Results: The mean age was 53.1 years in the patient group and 51.8 years in the
control group (P [.05). No significant differences between testosterone, albumin,
and SHBG levels were found. Significant differences between groups (patients and
control group, respectively) were found in mean prostate volume (30.73 cc vs 21.03
cc; P \.05), maximum urinary flow (14.1 mL/s vs 21.1 mL/s; P \.01), IPSS (5.68 vs
2.13; P \.05), and PSA (1.56 ng/mL vs 0.89 ng/mL; P \.05).
Methods: A systematic literature search of EMBASE, MEDLINE, CINAHL, and
Cochrane Library was conducted from January 2005 through May 2009. We
included randomized, placebo-controlled trials of oral MTX (7.5-30 mg/wk) used
for 12 weeks or more in patients with psoriasis, PSA, and RA aged [18 years with
established disease. The primary outcome was serious infectious events (events per
100 patient-years). Two authors independently extracted data and assessed study
quality using standardized instruments. Consensus was reached by conference.
A metaanalysis using a random effects model was performed using Comprehensive
Metaanalysis (v 2; Biostat, Englewood, NJ) to calculate a pooled estimate of
incidence of SIEs with MTX for psoriasis, PSA, and RA.
Results: Seventy-nine potential articles were reviewed (11 psoriasis, 11 PSA, and 57
RA). Metaanalysis of five relevant psoriasis studies showed 2.2 SIEs per 100 patientyears (95% CI, e1.3-5.8; P ¼ .220). Metaanalysis of five relevant PSA studies
demonstrated 0.9 SIEs per 100 patient-years (95% CI, e0.7-2.5; P ¼ .263).
Metaanalysis of 17 relevant RA studies revealed 2.3 SIEs per 100 patient-years
(95% CI, 1.3-3.3; P\.001) with heterogeneity statistics of Q ¼ 29.210, P ¼.023, I2 ¼
45.225, and tau ¼ 0.011.
Discussion: The association between AGA and urinary symptoms related to prostate
growth can be explained by similar androgen-dependent physiopathology.
Screening of urinary symptoms in AGA patients would be useful in order to start
preventive treatment. It remains to be seen if the long-term use of antiandrogens
(finasteride) for AGA will lower the incidence of benign prostatic hyperplasia.
Conclusions: Data on SIEs from MTX in psoriasis and psoriatic arthritis is limited and
cannot provide meaningful conclusions. However, metaanalysis of randomized trials
of MTX in rheumatoid arthritis estimates rate of SIEs to be approximately two per
100 patient-year exposures. This is consistent with past large observational studies.
The results allow accurate comparison of risks between MTX and biologic therapies.
AB4
J AM ACAD DERMATOL
MARCH 2010
PD03-ONCOLOGY AND SURGERY
P300
Extramammary Paget disease: A review of associated underlying
malignancies
Mohammad Diab, MD, The Ohio State University College of Medicine, Columbus,
OH, United States; Mark Bechtel, MD, The Ohio State University College of
Medicine, Columbus, OH, United States; Jacquelyn Coloe, MD, The Ohio State
University College of Medicine, Columbus, OH, United States; Jessica Moennich, MD,
The Ohio State University College of Medicine, Columbus, OH, United States
Extramammary Paget disease (EMPD) is plagued with a scarcity of knowledge
because of its rarity. Consensus on management and prognosis is difficult, and the
association of additional malignancies with EMPD continues to be underanalyzed.
There has only been one other review of associated underlying cancers, published in
1985 by Chanda et al. The purpose of this review is to review the reported
associations of EMPD with other underlying malignancies since 1985, and to
compare our results with those published by Chanda et al. An extensive search was
conducted on PubMed for all articles regarding EMP published in English from 1985
to the present. Each article was then evaluated for the presence of cases reported in
the text. If a specific case (or cases) were discussed, it was assessed for the presence
of an underlying malignancy and for the specific site of that malignancy. In some
cases, the presence of an underlying malignancy was not able to be determined.
These tallies were recorded and showed that of the 381 cases reported from 1985 to
the present, 18.1% presented with an underlying malignancy, 60.9% were found to
not have an underlying malignancy, and in 21% of the cases there was not enough
information to determine if there was an underlying malignancy. Our incidence of
18.1% of cases presenting with an underlying malignancy is lower than that reported
by Chanda et al, who analyzed 196 cases reported between 1962 and 1982 and
found that 44 cases (29%) presented with an underlying internal malignancy. In
regards to the specific site of underlying malignancy, our search found that rectal
adenocarcinoma was the most frequently diagnosed, accounting for 39.1% of the
total. The remaining cancers were found much less frequently, with bladder,
prostate, and breast cancer accounting for 14.5%, 8.7%, and 7.2%, respectively.
Interestingly, Chanda et al’s research found the highest incidence to be breast
cancer, occurring in 11 of 44 cases (25%). When results of the studies are combined,
encompassing all reported cases of EMP between 1962 and 1982 and 1985 to the
present, the highest incidence of underlying malignancy associated with EMP is
found to be in the rectum, occurring in 35 of 113 cases, and in the breast, occurring
in 16 out of 113 cases. This is an important point, and can target cancer screening
initially to the breast or rectum in patients diagnosed with EMP. Iterestingly, our
search found that 21% of the cases reported in the literature did not have enough
information to determine whether or not there was an underlying malignancy
associated with the diagnosis of EMP. Our data on this point is supported by Chanda
et al’s search, which found that 44 of 197 cases did not provide the necessary
information. In conclusion, our search found that the incidence of EMP associated
with underlying malignancy as reported in the literature from 1985 to the present is
approximately 18%. This is in contrast to Chanda et al’s search of the literature
between 1962 and 1982, which found that 29% of cases will present with
malignancy. The reason for this discrepancy is not clear. Nevertheless, both reviews
found that a significant amount of patients diagnosed with EMP will present with a
hidden cancer, most commonly occurring in the rectum or breast. Both searches
found that 21% of the articles did not contain adequate information to assess for the
presence or absence of an underlying malignancy. This may have been beecause of
the lack of a through cancer work-up in these patients. Physicians should be
encouraged to give all patients a thorough screening that is aimed specifically at
rectal adenocarcinoma and breast cancer. Other sites to pay particular attention to in
a malignancy screening include the prostate and bladder. While our reviews should
not be interpreted as the actual incidence of EMP cases associated with an
underlying malignancy, both reviews highlight the importance of screening all
patients presenting with EMP for an underlying cancer.
P301
Primary cutaneous CD 301 large cell lymphoma in a patient of atopic
eczema on long-term cyclosporine treatment
R. Yogendra Prasad Hunasehally, MD, MBBS, Welsh Institute of Dermatology,
Cardiff, South Glamorgan, United Kingdom; Krishnan Bhagwandas, MBBS,
Dermatology Department, Neath Port Talbot Hospital, Port Talbot, South
Wales, United Kingdom
Lymphoproliferative disorders occurring on a background of immunosuppression,
such as posttransplant patients, has been well described. Most such lymphomas are
B cell type and occur in association with EpsteineBarr virus infection.
Posttransplant cutaneous T-cell lymphomas (CTCLs) are very rare and even rarer
is the occurrence of primary CTCL in dermatology patients treated with systemic
immunosuppressive drugs. We present a case report of primary cutaneous CD 301
large cell lymphoma occurring on a background of atopic eczema on long-term
cyclosporine treatment. A 32-year-old male with eczema since infancy presented
with a rapidly enlarging mass on the right mandibular region with indurated plaques
on the overlying skin. He had been on cyclosporine at a dose of 3.5 mg/kg for about
5.5 years before presentation and the dose had been increased to 5 mg/kg in the last
6 months. Past treatments for eczema included emollients, topical corticosteroids,
narrowband ultraviolet B light phototherapy, and azathioprine. An ultrasound scan
confirmed enlarged lymphnodes in the right submandibular and deep cervical
chain. A skin biopsy specimen from the plaque showed sheets of large, atypical,
dissociative, markedly pleomorphic cells with abundant cytoplasm and prominent
nucleoli admixed with eosinophils and few neutrophils. Mitotic figures were easily
found and there were occasional Reed-Sternberg like cells. Immunohistochemistry
revealed the atypical cells to be CD31, CD41, CD7e, CD8e, CD301, CD451, and
ALK-1 negative. A lymph node biopsy revealed extensive infiltration by sheets of
large atypical cells similar to those in skin biopsy, admixed with lymphocytes and
eosinophils. Ki-67 proliferation fraction was 75%. ALK-1 and EMA were negative.
A bone marrow examination was normal and a staging CT scan showed bilateral
axillary and inguinal lymphadenopathy which was confirmed to be dermatopathic
lymphadenitis.
He was diagnosed with primary cutaneous CD301 large cell lymphoma and received
six cycles of CHOP chemotherapy. A repeat CT scan confirmed complete resolution
of facial disease. Given the aggressive nature of his lymphoma, he was treated with
high-dose BEAM chemotherapy followed by autologous stem cell transplant. The
cyclosporine was discontinued on diagnosis of the lymphoma. His eczema is
currently managed with topical steroids and emollients with reasonable success. His
lymphoma is in remission 18 months after the stem cell transplant. To our
knowledge, there have been only four publications (seven patients) of cutaneous
CD301 lymphoproliferative disorders occurring on a background of atopic eczema.
Four of these patients had treatment with cyclosporine. Given the rarity of CD301
lymphoproliferative disorders in association with atopic eczema, the relation
between these two conditions is likely to be multifactorial and the development
of lymphoma seems to be aided by immunosupression in some of these cases.
P302
Clinicopathologic features of malignant tumors in patients affected with
Brooke-Spiegler syndrome, including the multiple familial trichoepitheliomas variant
Dmitry V. Kazakov, MD, PhD, Sikl’s Department of Pathology, Charles University,
Medical Faculty Hospital, Pilsen, Czech Republic; Denisa Kacerovska, MD, PhD,
Sikl’s Department of Pathology, Charles University, Medical Faculty Hospital,
Pilsen, Czech Republic; Michal Michal, MD, Sikl’s Department of Pathology,
Charles University, Medical Faculty Hospital, Pilsen, Czech Republic; Tomas
Vanecek, PhD, Bioptical Laboratory, Pilsen, Czech Republic
Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease
characterized by the development of multiple adnexal cutaneous neoplasms
including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma.
Some patients present only with multiple trichoepitheliomas, without any other
adnexal neoplasms. This clinical phenotype is usually referred to as multiple familial
trichoepitheliomas (MFT). Malignant transformation of these benign tumors is rare.
We studied five individuals affected with the variant of classical BSS and one patient
with the MTF phenotype, all of whom were diagnosed with malignant cutaneous
neoplasms. The five patients with classical BSS (4 female, 1 male; age range, 66-72
yrs) presented with multiple, often grouped or confluent papules, nodules, or
tumors, ranging in size from 0.2 to 6 cm. These were benign lesions that had
appeared around puberty or in early adolescence, on the background of which the
malignant lesions later developed as large, either rapidly growing, bleeding, or
ulcerated tumors. Locations included the head and neck area (2) and back (1); the
remaining two patients manifested involvement of almost the entire integument.
The MTF patient, a 38-year-old male, presented with multiple, discrete, and also
confluent, skin-colored, firm 3- to 15-mm nodules preferentially involving the
nasolabial folds, some of which showed recent faster growth. Family histories
disclosed similar lesions involving relatives of all six patients. Microscopically, in all
five classical BSS cases, a residuum of an unequivocally benign neoplasm (spiradenoma or cylindroma) was present. The malignant tumors arising from preexisting
benign neoplasms manifested morphologic appearances best compared to basal cell
adenocarcinoma of salivary glands, either low-grade (3) or high-grade (2). Both
patients with the high-grade tumors died of disease, whereas those with the lowgrade variety were alive, except for one patient who died of an unrelated cause. In
one of these five patients, a second pattern was identified, namely infiltrative
adenocarcinoma. In the MTF patient, there were multiple trichoepitheliomas, some
of which showed a gradual transition to areas consistent with basal cell carcinoma of
small nodular or infundibulocystic types. This study shows a morphologic heterogeneity of the malignant neoplasm occurring in BSS.
Commercial support: This study was supported in part by the Internal Grant
Agency (IGA) of the Ministry of Health of the Czech Republic (NS 9734).
MARCH 2010
J AM ACAD DERMATOL
AB5
P303
P305
Histopathologic and immunohistochemical differences between lapatinib,
a dual ErbB1/2 epidermal growth factor receptor inhibitor, and cetuximab, erlotinib, and panitumumab
Beatrice Nardone, MD, Northwestern University Department of Dermatology,
Chicago, IL, United States; Kimberly Nicholson, MD, Northwestern University
Department of Dermatology, Chicago, IL, United States; Mario Lacouture, MD,
Northwestern University Department of Dermatology, Chicago, IL, United States;
Marissa Newman, MD, Northwestern University Department of Dermatology,
Chicago, IL, United States
Ultraviolet A-1 phototherapy for mycosis fungoides
Kee Suck Suh, Department of Dermatology, Kosin University College of
Medicine, Busan, South Korea; Jae Woo Baek, MD, Department of
Dermatology, Kosin University College of Medicine, Busan, South Korea; Sang
Tae Kim, MD, Department of Dermatology, Kosin University College of Medicine,
Busan, South Korea; Tae Kwon Kim, MD, Department of Dermatology, Kosin
University College of Medicine, Busan, South Korea; Young Seung Jeon, MD,
Department of Dermatology, Kosin University College of Medicine, Busan, South
Korea
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and
many clinical histologic variants have been reported. Current treatment options of
MF include topical therapy, single or combination systemic therapy, immunotherapy, radiation therapy, and phototherapy, but a standard or definite treatment
regimen has not yet been documented. Broadband ultraviolet B light, narrowband
ultraviolet B light, and psoralen plus ultraviolet A light phototherapy have all been
used as conventional phototherapies for cutaneous T-cell lymphoma. Recently, the
biochemical effectiveness of ultraviolet A-1 (UVA-1) phototherapy raises the possibility as a novel modality for T cellemediated skin diseases. The purpose of this
study was to assess the efficacy and difference of low (10-30 J/cm2), medium (40-70
J/cm2), and high (100-130 J/cm2) dose UVA-1 phototherapy for MF. This study
included 13 patients who had been clinically and histologically diagnosed as MF (10
with stage IA, 2 with IB, and 1 with IVB). Exclusion criteria were history of abnormal
UVA sensitivity and the use of systemic photosensitizing agents. For low dose UVA1 radiation, SUPUVASUN 3000 (Mutzhas, Munich, Germany) was used, and medium
and high doses were delivered by Sellamed 3000 (Sellas, Gevelsberg, Germany).
Eleven patients showed complete remission (8 with stage IA, 2 with stage IB, and
1 with stage IVB). Two patients showed partial remission (2 with stage IA). Overall
response, including complete (11/13) and partial remission (2/13), was achieved
regardless of whether the low, medium, or high dose regimen had been used. The
difference of effectiveness between the three dosages was not statistically significant. There was positive correlation between duration of MF and number of UVA1 irradiation. During the follow-up period (2-56 months), 11 of 13 patients remained
in stable remission. No serious adverse effects were observed besides hyperpigmentation. We propose that UVA-1 phototherapy is an effective and well tolerated
treatment and low dose UVA-1 may be equally effective to medium and high dose
regimen for patients with MF.
Background: Epidermal growth factor receptor inhibitors (EGFRIs) have shown to
be effective against a wide variety of solid tumors. Inhibition of EGFR activity in the
skin often results in disabling papulopustular rash (PPR) that may lead to dose
modification or interruption in therapy. Lapatinib, a dual ErbB1/2 inhibitor that
targets both EGFR and human epidermal growth factor receptor 2, has been shown
to result in milder PPR. We evaluated differences in histologic and immunohistochemical (IHC) alterations in the skin between four currently available EGFRIs:
lapatinib (L), cetuximab (C), erlotinib (E), and panitumumab (P), the latter three of
which are single ErbB1 inhibitors.
Methods: Skin punch biopsy specimens were collected from eight patients with PPR
for each EGFRI (n ¼ 32). Two dermatopathologists performed blinded independent
analysis of epidermis, dermis, follicle, and inflammatory infiltrates. In addition,
specimens were stained for KRT1, HLA-DR, ERK1, K16, Ki67, p27, pAKT, EGFR,
CD68, CD54, CD20, CD11b, CD8, CD4, CD1a, Stat3, and pEGFR. Blinded IHC
analysis was conducted to determine percentage and intensity of expression for
each biomarker and compared between EGFRIs.
Results: IHC analysis revealed a statistically significant increase in the expression of
pAKT in the epidermis and dermis for lapatinib as compared to the three single Erb1
inhibitors (P ¼ .0007). Moreover, evidence of decreased of epidermal atrophy was
observed in two of eight patients for lapatinib as compared to five of eight, seven of
eight, and four of eight for the three single Erb1 inhibitors (erlotinib, cetuximab, and
panimumab).
Conclusions: Although our findings show lapatinib expressing pAKT at nearly twofold higher levels than E, this has been reported by others to show increased pAKT
expression associated with an absence or decreased severity of skin toxicity.
Increased expression of pAKT, which is downstream in EGFR pathway, may result in
improved cell differentiation and normalization of keratinization eventuating in less
atrophy. Thus increased pAKT may lead to a more benign pattern of PPR with L.
Inhibitor such as L may therefore prove to cause a profoundly higher expression of
pAKT than the single Erb1 inhibitors, including E, and may improve the quality of
life of—and decrease the economic burden for—patients undergoing therapy with
EGFRIs.
Commercial support: 100% of this study was supported by Glaxo-Smith Kline.
P304
Biomimetic signaling technology generated by a bimineral complex
shows efficacy in reducing clinical photoaging in a 12-week placebocontrolled study
Jeannette Chantalat, MS, MBA, Johnson & Johnson Consumer & Personal
Products Worldwide, Skillman, NJ, United States; Elizabeth Bruning, Johnson &
Johnson Consumer & Personal Products Worldwide, Skillman, NJ, United States;
Jue-Chen Liu, PhD, Johnson & Johnson Consumer & Personal Products
Worldwide, Skillman, NJ, United States; Ying Sun, PhD, Johnson & Johnson
Consumer & Personal Products Worldwide, Skillman, NJ, United States
The clinical signs of photoaging are a persistent concern for many patients. Intrinsic
factors and cumulative exposure to extrinsic factors such as ultraviolet light lead to
the development of skin laxity, fine lines, wrinkles, hyperpigmentation, and
sallowness. A proprietary bimineral complex of elemental zinc and copper that
produces biomimetic signals has demonstrated antiinflammatory activity and
upregulation of collagen and elastin gene expression. This bimineral complex has
been clinically proven to be safe for topical use through Human Repeat Insult Patch
Tests (RIPT) in more than 800 subjects. In addition, the bimineral complex has low
potential for eye irritation as shown through testing in a human-derived epidermal
keratinocyte corneal model (EpiOcularÔ). A 12-week, double-blind, placebo-controlled clinical study was performed to evaluate the efficacy and tolerability of a
topical composition containing the bimineral complex in reducing the clinical signs
of facial photoaging, including the delicate periorbital area. The study consisted of
three treatment groups: (1) placebo moisturizer; (2) bimineral complex moisturizer;
and (3) bimineral complex moisturizer with activator. The study population
consisted of 94 healthy women 40 to 65 years of age with Fitzpatrick skin types II
to IV and mild to moderate photoaging. Subjects applied the bimineral complex
twice daily: in the morning and evening. Evaluations included clinical grading of
safety and efficacy parameters, high-resolution digital imaging, and subject selfassessments. All measures were taken at baseline and weeks 2, 4, 8, and 12. Both
treatment groups using the bimineral complex showed statistically significant (P \
.05) clinical improvement versus placebo and versus baseline starting as early as
week 2 in several parameters and continued to improve versus placebo through
week 12. The bimineral complex performed significantly (P \ .05) better than
placebo and baseline in overall appearance, under eye bags, under eye wrinkles,
cheek wrinkles, pigmentation, radiance, fine lines, and global lifting/firming. There
were no adverse events related to the treatments in this clinical study, and the
bimineral complex and placebo were all shown to be well tolerated throughout the
12-week study.
Commercial support: 100% is sponsored by Johnson & Johnson Consumer &
Personal Products Worldwide.
AB6
P306
Primary cutaneous CD301 lymphoproliferative disorders: A review of the
patient population at the Vanderbilt Cutaneous Lymphoma Clinic
Casey Wilford, MD, Vanderbilt University Division of Dermatology, Nashville, TN,
United States; John Zic, MD, Vanderbilt University Division of Dermatology,
Nashville, TN, United States
Cutaneous T-cell lymphomas (CTCLs) manifest as many different morphologies,
including primary cutaneous CD301 lymphoproliferative disorders (CD301 LPDs).
The three conditions that constitute the spectrum of CD301 LPDs are lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PCALCL),
and mixed CD301 LPDs. These diseases are characterized by indolent clinical
courses with only a small percentage of patients progressing to more advanced
lymphoma. Given the relative rarity of these disorders, information regarding
prognosis and treatment options is limited. For this study we reviewed 65 cases of
primary cutaneous CD301 LPDs seen at the Vanderbilt Cutaneous Lymphoma Clinic
between 1996 and 2006. The 65 patients included 34 patients with LyP, 28 with
PCALCL, and 3 with mixed primary cutaneous LPD. The average length of follow up
was 68 months. The demographic data and clinical presentation of the patients were
consistent with previous reports, with CD301 LPDs presenting most commonly in
white middle aged males on the extremities. The disease course for most patients
was relapsing and remitting, as expected. However, 17% of patients experienced
progression of disease, which is greater than previous reports. Overall disease
specific survival was excellent at 97%. Multiple treatment modalities were used for
these patients, including steroids, ultraviolet light phototherapy, radiation, immunosuppressants, retinoids, chemotherapy, and stem cell transplant. Approximately
half of the patients were treated with methotrexate, based on published reports of
its efficacy in CD301 LPDs. Methotrexate was very successful in our patient
population, with 64.7% of patients achieving a complete response. Only five serious
adverse events occurred which led to treatment failure. Importantly, no patients
progressed to worse disease while being treated with methotrexate. Patients with
LyP were significantly less likely to have progression of disease while on methotrexate (P ¼.002), while patients with PCALCL followed a similar trend but did not
achieve statistical significance (P ¼ .14). In this review, we provide additional data
confirming the clinical presentation of CD301 LPDs and present other data which
may indicate a higher risk of developing serious disease in these patients. We show
excellent efficacy and safety with long-term methotrexate therapy and preliminary
evidence that it may also slow progression of disease.
J AM ACAD DERMATOL
MARCH 2010
P307
P401
A comparison study of the tensile strength of sutures used in dermatologic
surgery before and after exposure to wound care products
Vidya Rajpara, MD, University of Miami Miller School of Medicine, Miami, FL,
United States; Brian Berman, MD, PhD, University of Miami Miller School of
Medicine, Miami, FL, United States; Martha Viera, MD, University of Miami Miller
School of Medicine, Miami, FL, United States; Sadegh Amini, MD, University of
Miami Miller School of Medicine, Miami, FL, United States
Background: Sutures for closing wounds have been used since ancient times. Since
then, they have evolved to improve several characteristics including, memory,
absorbability, reactivity, and tensile strength (TS). TS is the necessary weight to
break a suture divided by the suture’s cross sectional area in mm2. It represents the
amount of stress applied at the suture’s breaking point at which it can no longer
maintain its integrity. Postsurgical wound care typically involves wound cleansing,
antibiotics, and protectants, and occasionally patients also use unprescribed
products, such as hydrogen peroxide. We evaluated the effect of various wound
care products on the TS of sutures commonly used in dermatologic surgery.
Objective: To measure the TS of sutures commonly used in dermatologic surgery
before and after their continuous exposure to various wound care products for 7 days.
Drug-induced hypersensitivity syndrome associated with hepatitis A virus
and hepatitis E virus
Chun Yin Johnny Chan, MBBS, The University of Hong Kong, Hong Kong, China;
Chi Keung Yeung, MBBS, The University of Hong Kong, Hong Kong, China; Hin
Lee Henry Chan, MBBS, The University of Hong Kong, Hong Kong, China
Methods: Various sutures, including 4-0 and 6-0 nylon, 4-0 and 6-0 polypropylene, 30 and 5-0 polyglactin 910, 3-0 and 5-0 polydioxanone, and 3-0 poliglecaprone 25
were incubated 7 days with each of three wound care products chosen for the study:
petrolatum ointment, triclosan antibacterial soap, and hydrogen peroxide 3%. After
the incubation period, each suture was evaluated with a tensometer to asses TS.
Three measurements of TS were performed for each suture to account for possible
suture material defects and the accuracy of the tensometer readings. Statistical
analysis included unpaired t test for the comparison of individual sutures, paired t
test for comparison of exposed sutures to baseline, and mean percent reductions in
suture strength compared to baseline.
Results: At baseline, polypropylene sutures were significantly stronger than nylon
(P ¼ .02 and .01), the strongest absorbable suture was poliglecaprone (P # .001
compared to polyglactin and polydioxanone, and the absorbable suture with the
least TS was polydioxanone. After exposure, vaseline did not affect TS of any suture
studied; hydrogen peroxide led to a greater percentage reduction of the TS of nylon
sutures, and was significant for size 4-0 (P ¼ .02); and hydrogen peroxide also
significantly decreased the TS of 3-0 polyglactin (P ¼ .047) and polydioxanone
(P ¼.01) sutures. Triclosan significantly decreased the TS of 4-0 nylon (P ¼.04), 3-0
polyglactin (P # .001), 5-0 polydioxanone (P ¼ .04), and 3-0 poliglecaprone
(P ¼.047). Polypropylene suture’s TS was not altered by any of the products tested.
Conclusions: The ex vivo effect of wound care products on common sutures’ TS was
measured. Evaluation of the interaction of these products with human skin and its
effect on suture’s TS was not performed; therefore, extrapolations with clinical
significance are not possible. Petroleum jelly did not alter the TS of any of the
sutures. Polypropylene sutures had higher TS than nylon sutures and were not
altered by any product. Hydrogen peroxide should be avoided with nylon sutures
because it decreases its TS. To assess the effects of exposure to human skin on suture
material, further testing may be performed following suture incubation with wound
fluid rich in proteolytic enzymes or following placement in vivo.
PD04-MELANOMA, SQUAMOUS CELL
CARCINOMA, INFECTION
P400
Drug hypersensitivity syndrome (DHS) is an acute, distinct, and severe idiosyncratic
reaction associated with drug. It is characterized by the triad of fever, rash, and
visceral involvement, with significant mortality of 8% to 10%. Common causative
agents include aromatic antiepileptics, allopurinol, and sulphonamides.
Concomitant viral infection has been hypothesized to play a role in the pathogenesis
of hypersensitivity syndrome. Reactivation of HHV-6 has been widely reported to be
associated with DHS. Some authors also reported clinical association with other
human herpes viruses, namely cytomegalovirus and EpsteineBarr virus. Hepatitis A
virus (HAV) and hepatitis E virus (HEV), the two common causative agents of acute
viral hepatitis in developing countries, have seldom been reported to be associated
with DHS. We describe two cases of DHS associated with infection by the two
hepatotrophic viruses mentioned. The first case was a 49-year-old male with
phenobarbital-induced hypersensitivity syndrome associated with HAV infection.
He developed fever, generalized erythematous eruption, peripheral eosinophilia,
and cholestatic hepatitis. Concomitant hepatitis A virus infection was confirmed
with detection of HAV-specific IgM within the first week of onset of clinical
symptoms. The second case was a 28-year-old male with minocycline-induced
hypersensitivity syndrome associated with HEV infection. He presented with high
fever, generalized confluent erythematous eruption, peripheral eosinophilia, cervical lymphadenopathy, hepatomegaly, and cholestatic hepatitis. Hepatitis E virus
infection was confirmed with detection of HEV-specific IgM within the first week of
onset of clinical symptoms. Both cases required commencement of systemic steroid
and there were complete resolution of skin eruption and biochemical abnormalities.
We suggest that concomitant HAV or HEV infection may contribute, at least in some
cases, to the development of drug hypersensitivity syndrome.
P402
Prospective multicenter study of an objective computer-vision system for
early melanoma detection
Gary Monheit, MD, Total Skin and Beauty Dermatology Center, P.C., Birmingham,
AL, United States; Armand Cognetta, MD, Dermatology Associates, Tallahassee,
FL, United States; Dina Gutkowicz-Krusin, PhD, Electro-Optical Sciences,
Irvington, NY, United States; Laura Korb Ferris, MD, University of Pittsburgh
Medical Center, Pittsburgh, PA, United States
Background: An objective noninvasive multispectral computer-vision system
intended to aid in the early detection of cutaneous melanoma has been developed.
Objectives: A prospective nonsignificant risk study was designed to show that this
computer-vision system is safe and effective, using sensitivity to melanoma and
specificity as metrics. The diagnostic performance of the system and of study
clinicians was evaluated using diagnoses of lesions by dermatopathologists as the
reference standard. The aims of this study were to establish that the sensitivity of the
computer-vision system to melanoma is at least 95% at 95% confidence level and its
specificity is superior to the specificity of study clinicians (P \.05).
Discussion: Given the immunosuppressed status of patients taking MMF, it is prudent
to consider herpes viral infection in those complaining of nonspecific symptoms of
fever, weakness, or fatigue. The therapeutic dilemma remains in balancing control of
dermatologic disease with risk of viral infection. Rituximab has been reported to be a
successful therapy for EBV-related lymphoproliferative disease and as such it may be
a viable option in the management of PV patients with positive EBV serologies.
Methods: Seven clinical sites with expertise in early melanoma detection and
management of pigmented skin lesions participated in the study. All lesions included
in this study had to meet specified inclusion/exclusion criteria and were biopsied
after imaging. Histologic slides from lesions underwent central dermatopathology
review. The results of the computer-vision system, dermatologic diagnoses, and
dermatopathology interpretations were masked from each other.
Results: A total of 1383 patients were enrolled from January 2007 to July 2008. There
were no adverse device events. Data were acquired on 1831 pigmented skin lesions
of which 1632 lesions (including 127 melanomas, 45% in situ; median Breslow
thickness of invasive lesions, 0.365 mm) were eligible and evaluable for endpoints.
The measured sensitivity of the computer-vision system was 98.4% (125 of 127
melanomas) with 95% LCB of 95.6%. The measured specificity was 9.4%, which was
significantly superior (P ¼ .02) to the specificity of the study investigators (3.7%).
The biopsy ratios of the system and clinicians were 10.8:1 and 11.3:1, respectively.
When the positive lesion set included all 175 melanomas and borderline lesions
(high-grade dysplastic nevus, atypical melanocytic proliferation, or hyperplasia), the
sensitivity of the computer-vision system was 98.3%, the specificity was 9.9%
(superior to clinicians at 3.7% with P ¼.02), and the biopsy ratio was 7.6:1 (7.9:1 for
clinicians).
Conclusions: This very high sensitivity to early melanoma and specificity superior to
the study clinicians satisfy the prospective criteria set for this study, thus demonstrating that this computer-vision system is a safe and effective tool for evaluation of
pigmented skin lesions.
Additional authors: Harold Rabinovitz, MD, University of Miami, Miami, FL, Kenneth
Gross, MD, University of California, San Diego, CA, Mary Martini, MD, PhD,
Northwestern University, Evanston, IL, James Grichnik, MD, PhD, University of
Miami, Miami, FL, Martin C. Mihm, MD, Harvard University, Boston, MA, Paul Googe,
MD, University of Tennessee Medical Center, Nashville, TN, Roy King, MD,
University of Tennessee Medical Center, Nashville, TN, Victor G. Prieto, MD, PhD,
University of Texas MD Anderson Cancer Center, Houston, TX.
Q1
Commercial support: Electro-Optical Sciences.
Reactivation of EpsteineBarr virus infection complicating mycophenolate
mofetil therapy for pemphigus vulgaris
Michael Bernardi, MD, University of Louisville, Division of Dermatology,
Louisville, KY, United States; Jeffrey Callen, MD, University of Louisville,
Division of Dermatology, Louisville, KY, United States
Introduction: Mycophenolate mofetil (MMF) is a corticosteroid sparing, immunosuppressive medication used to treat pemphigus vulgaris (PV). Severe adverse
reactions are not common. Opportunistic infections while using MMF, most
commonly cytomegalovirus (CMV), are well documented. Reactivation of dormant
EpsteineBarr virus (EBV) infection and EBV-related lymphoma have also been
reported in patients taking MMF.
Observation: A 60-year-old male was diagnosed with PV approximately 1 year
previously. His disease was clinically well controlled with MMF 1.5 g twice daily and
prednisone 2.5 mg daily. The prednisone dosage had been successfully tapered from
40 mg daily to 2.5 mg daily over a period of 8 months. He began to complain of
muscle weakness and fatigue. He denied fevers, chills, or weight loss. Laboratory
studies revealed an EBV early antigen antibody (Ab) of 0.4 (normal, 0.0-0.8), EBV
viral capsid IgG Ab of [8.0 (normal, 0.0-0.8), and EBV nuclear antigen IgG Ab of
[8.0 (normal, 0.0-0.8). EBV PCR was negative. CMV IgG Ab was high at 14.7
(negative range of \0.9). HHV-6, HIV, and HSV-2 studies were negative, while HSV1 IgG was positive. A complete blood count and comprehensive metabolic panel
were within normal limits. Despite clinical inactivity of his oral PV, his antidesmoglein 3 antibodies were elevated at 120 (normal, \ 9).
MARCH 2010
J AM ACAD DERMATOL
AB7
Q2
P403
Signet ring cell melanoma, Brenner sign, and elevated VEGF
Jacqueline Russo, MD, University of Florida College of Medicine, Department of
Pathology & Laboratory Medicine, Gainesville, FL, United States; Keira Barr, MD,
University of California, Davis Health System, Departments of Dermatology and
Pathology, Sacramento, CA, United States; Larissa Scanlan, MD, Voluntary Faculty
at the University of Miami School of Medicine and Private Practice in Delray, FL,
Delray Beach, FL, United States; Vladimir Vincek, MD, PhD, University of Florida
College of Medicine, Department of Pathology & Laboratory Medicine,
Gainesville, FL, United States
Introduction: We present a patient with metastatic signet ring cell melanoma with
unknown primary site who presented with Brenner sign and markedly elevated
vascular endothelial growth factor (VEGF). We discuss the possible relatedness
between Brenner sign and VEGF and their potential utility.
Clinical history: A 41-year-old white male presented with a rapidly growing
subcutaneous supraclavicular mass with an overlying erythematous macule, consistent with Brenner sign, which extended to the anterior chest wall. A CT scan
revealed a 5.0-cm well circumscribed solid mass. Fine needle aspiration and core
biopsy showed signet ring cells immunoreactive for HMB-45 and S100 protein;
cytokeratin was negative. A subsequent excision and nodal neck dissection revealed
a 7.0-cm melanoma with 60 negative lymph nodes. A skin ellipse from the Brenner
sign overlying the tumor mass was taken in search of a cutaneous primary site, but
revealed only mild spongiotic dermatitis. A CT scan, PET scan, ocular examination,
laryngoscopy, bronchoscopy, and esophagoscopy failed to reveal a primary site. The
diagnosis of metastatic signet ring cell melanoma was made. At diagnosis, serum
VEGF levels were elevated measuring 1117 pg/mL (normal, 31-86 pg/mL) with
elevation of white blood cell (WBC) counts to 19.7 3 103 U/L, of which 81% were
neutrophils. Clinically, the patient was afebrile with no signs of infection. Once the
tumor was removed, WBC and neutrophil counts rapidly returned to normal ranges.
Likewise, the Brenner sign disappeared. Unfortunately, VEGF levels postetumor
resection were not repeated. Two years later, the patient presented with axillary
lymphadenopathy. Axillary lymph node dissection confirmed 2 of 33 lymph nodes
positive for metastatic disease.
Discussion: Signet ring melanoma is an unusual variant accounting for only 0.5% of
melanomas. They present as progressively enlarging pigmented or erythematous
plaques. The cells have signet ring histomorphology. Similar morphology can occur
in a variety of other cutaneous and noncutaneous neoplasms requiring immunophenotyping for accurate diagnosis. Although rare, patients with melanoma can
develop erythematous eruptions at the site of, or at a distance from, their primary
melanocytic lesion, termed Brenner sign. It is reported that this sign may be useful
for early diagnosis of melanoma. It is hypothesized that the erythema of Brenner sign
can be explained by factors responsible for angiogenesis. VEGF is a potent initiator
of angiogenesis. In malignancy, angiogenesis is precipitated by an increase in oxygen
demand by tumor cells. Newly created vasculature serve to better meet the
increased oxygen demand of the tumor while creating an avenue for metastasis.
The elevated VEGF in our patient supports previous observations of increased VEGF
in patients with melanoma. We present an unusual case of metastatic signet ring cell
melanoma with an unknown primary site, in association with Brenner sign and
elevated serum VEGF. This case illustrates that elevated growth factors in patients
with melanoma may help stratify high risk patients with a worse prognosis, and may
provide a useful follow-up marker for disease progression. Further studies into the
clinical application of this marker are needed.
P404
Sentinel lymph node biopsy for cutaneous melanoma: The Washington
Cancer Institute experience in 472 patients, 1997-2008
Suzanne Berkman, MD, Washington Cancer Institute/Washington Hospital
Center, WA, DC, United States; Gary Peck, MD, Washington Cancer
Institute/Washington Hospital Center, WA, DC, United States; Marc Boisvert,
MD, Washington Cancer Institute, WA, DC, United States; Rodolfo Chirinos, MD,
Washington Cancer Institute/Washington Hospital Center, WA, DC, United
States; Saurabh Singh, MD, Washington Hospital Center, WA, DC, United States
Background: Lymph node status is the most powerful independent prognostic factor
in patients with clinically node-negative melanoma. The staging guidelines of the
American Joint Committee on Cancer recommend sentinel lymph node biopsy
(SLNB) for melanomas [1.0 mm in Breslow depth (BD) (or \1.0 mm if adverse
histopathologic factors are present). Since 1997, we have routinely performed
SLNBs for melanomas $ 0.76 mm (or \0.76 mm with adverse histopathologic
factors).
Objective: To determine the rate of SLNB positivity among 472 patients who
underwent SLNB between 1997 and 2008. Secondary goals were to elucidate which
factors best predict the risk for SLN metastasis and clarify which patients with thin
melanomas (BD \1.0 mm) should undergo SLNB.
Methods: We reviewed the Washington Cancer Institute melanoma database and
analyzed histopathologic and survival data.
Results: Among 472 patients (mean BD, 2.11 mm), 55 (11.7%) patients (mean BD,
3.26 mm) had positive SLNB. Three hundred thirty patients (69.9%) had tumors
[1.0 mm (mean BD, 2.68 mm), of which 52 (15.8%) had positive SLNB (mean BD,
3.4 mm) and 278 (84.2%) were negative (mean BD, 2.55 mm; P ¼ .021). One
hundred forty-two patients (30.1%) had thin melanomas (mean BD, 0.77 mm), three
(2.1%) of which had positive SLNB (mean BD, 0.81mm; no adverse histopathologic
AB8
features reported). The rate of SLNB positivity increased with increasing depth of
invasion. BD, Clark level, and nodular subtype were found to be significantly
associated with SLNB positivity; ulceration status approached statistical significance. Forty-three of 472 patients (9.1%) developed local or distant recurrence
(mean BD, 4.19 mm; mean follow-up, 44.5 months). Of these, 17 (39.5%) survived
(mean BD, 3.76 mm; mean follow-up, 57.5 months) and 26 (60.5%) died (mean BD,
4.47 mm; mean follow-up, 35.9 months). Of 417 patients with negative SLNB, 29
(7%), developed recurrence (including 1 thin melanoma) versus 14 (25.4%) of 55
patients with positive SLNB (including 1 thin melanoma). Twelve of 417 (2.9%)
SLNB-negative patients and 7 of 55 (12.7%) SLNB-positive patients developed distant
metastases (P ¼ .003). Death occurred in 17 (4.1%) SLNB-negative patients and in
nine (16.4%) SLNB-positive patients (P ¼.001).
Conclusions: SLN positivity is a function of BD, which correlates with disease
progression and survival. Given the low rate (2.1%) of positive SLNB in patients with
thin melanomas, the decision to perform SLNB in this group should depend on the
presence of adverse histopathologic factors.
P405
Aberrant methylation of tumor suppressor genes as potential molecular
markers for cutaneous squamous cell carcinoma
Alice Chuang, MD, Johns Hopkins University, Baltimore, MD, United States;
David Sidransky, MD, Johns Hopkins University, Baltimore, MD, United States;
Joseph Califano, MD, Johns Hopkins University, Baltimore, MD, United States;
Nanette Liegeois, MD, PhD, Johns Hopkins University, Baltimore, MD, United
States
Purpose: Cutaneous squamous cell carcinoma (cSCC) is the second most common
type of skin cancer in the United States. Advanced or metastatic cSCC is associated
with high morbidity and mortality. Similar to other tumor types, identification of
molecular markers has the potential diagnostic and/or prognostic value.
Experimental design: We have examined the promoter methylation of 12 candidate
genes in 54 primary cSCC tumors and 41 normal skin tissues. Quantitative
methylation-specific PCR (QMSP) was applied to determine the methylation status
of each gene in all tissue samples. DLC-1 mRNA expression was evaluated by
quantitative real-time reverse transcription-PCR. Restoration of DLC-1 expression in
vitro was performed by the demethylating agent 5-aza-2’-deoxycytidine (5-Aza-dC)
and tumor suppressor properties were tested after ectopic expression in cSCC cell
lines.
Results: Promoter methylation of the TSGs was more frequently observed among
cSCC samples than normal skin samples. The data have demonstrated the value of
high sensitivity and specificity in multigene approach in detection of aberrant
methylation in cSCC. Additional studies were performed on DLC-1 because QMSP
results showed that the DLC1 promoter was methylated in 26 of 54 (48.1%) primary
cSCC tumors versus eight of 41 (19.5%) in normal skin tissues. We also found that the
expression of DLC-1 was downregulated in cSCC primary tissues. Reactivation of
DLC-1 expression was observed after treatment of demethylating agent 5-Aza-dC in
cSCC cell lines, confirmed epigenetic inactivation as one major mechanism of DLC1 regulation in cSCC. Moreover, induction of exogenous expression of DLC-1 inhibits
cSCC cell proliferation, colony formation, and invasive activities.
Conclusion: We have identified a panel of methylated TSGs in primary cSCC tissues
that were not reported previously. Early detection of potential aggressive behavior of
premalignant skin lesions based on a panel of molecular markers is valuable for
minimizing morbidity and mortality of patients. Transcriptional silencing of DLC1 through aberrant methylation may be one of the mechanism in the pathogenesis of
cSCC and could have a potential therapeutic application.
J AM ACAD DERMATOL
MARCH 2010
P406
Expression analysis of peroxisome proliferator-activated receptors (PPARs),
hypoxia-inducible factor (HIF), and fasting-induced adipose factor (FIAF) in
squamous cell carcinoma (SCC), its precursors, and normal perilesional skin
Jiun Yit Pan, MBBS, National Skin Centre, Singapore; Andrew Tan, PhD, Nanyang
Technological University, Singapore; Melvin Ee, MBChB, National Skin Centre,
Singapore; Suat Hoon Tan, MBBS, National Skin Centre, Singapore
Introduction: Peroxisome proliferatoreactivated receptors (PPARs) are a group of
nuclear hormone receptor proteins which serve as on/off switches for gene
transcription within the cell nucleus. PPAR ligands have been shown to control
cell differentiation, proliferation, and apoptosis. PPARg ligands are potent inhibitors
of tumor-induced angiogenesis, and ligands such as fibrates and thiazolidinediones
may possibly have chemoprophylactic properties in high-risk patients. Recent
studies have also shown that fasting-induced adipose factor (FIAF) is highly
expressed in lung, breast, colon, ovarian, and prostate carcinoma, but no studies
have been performed so far on skin cancers. Hypoxia-induced factor (HIF) is thought
to mediate FIAF expression via a hypoxic mechanism.
Methods: The relative expression of PPARs, HIF, and FIAF in biopsy specimens of
squamous cell carcinoma (27 samples), its precursors (21 cases of actinic keratosis
and 20 cases of Bowen disease), and normal perilesional skin (27 samples) was
studied. The patients from which excision specimens were obtained were elderly
(average age, 74.4 yrs) and of Chinese descent. The tumors were predominantly in
sun-exposed sites and 25.9% of the patients had previous skin cancers or premalignant lesions. Total RNA was extracted from the tissues and underwent reverse
transcription to cDNA. The expression of each gene, namely PPARa, PPARb/d,
PPARg, HIF and FIAF were quantified by real-time PCR (QRT-PCR) and normalized to
b-actin expression.
Results: There was significantly decreased expression of PPARa in SCC compared to
Bowen disease (P ¼.001) and perilesional skin (P \.001). PPARb/d expression was
significantly decreased in SCC compared to Bowen disease (P ¼ .024), and PPARg
expression was significantly decreased in SCC compared to perilesional skin (P ¼
.014). These findings may reflect a downregulation of the PPARs as part of the
multistage pathogenesis of squamous cell carcinoma.
An increase in expression of FIAF and HIF was seen in tumor tissue compared to
perilesional skin and precursor lesions, reaching statistical significance for HIF in
SCC compared to Bowen disease (P ¼ .013), and FIAF in SCC compared to actinic
keratosis (P ¼.006). This finding of increased FIAF and HIF expression is similar to
previous studies on visceral tumors, and may represent an upregulation of both
factors in skin cancers.
PD05-ATOPIC DERMATITIS AND PEDIATRIC
DERMATOLOGY
P500
Transfer of atopic dermatitis in a case of allogeneic stem cell
transplantation
Juan Gabriel Vasquez, MD, University of Pittsburgh Medical Center Department
of Dermatology, Pittsburgh, PA, United States; Alexandra Zhang, MD, University
of Pittsburgh Medical Center Department of Dermatology, Pittsburgh, PA, United
States
A 26-year-old white female who had undergone a stem cell transplant 13 months
earlier for acute myelocytic leukemia was seen in our clinic for the evaluation of a
new, pruritic rash of 5months’ duration. Other than leukemia, her medical history
was unremarkable. The patient denied any rash before her transplant, and she did
not have any history of asthma, allergic rhinitis, or eczema. Her family history was
significant for longstanding, severe atopic dermatitis in her only sister, who was the
patient’s perfectly HLA-matched allogeneic bone marrow donor. To treat the rash,
the patient reported using her sister’s atopic dermatitis medications until they both
ran out and she presented for evaluation to receive her own medicines. On physical
examination, the patient had erythematous plaques in flexural surfaces with slight
scales and excoriations that was consistent with atopic dermatitis. She also had
erythematous lower lid edema with epiphora. She reported an otherwise uncomplicated posttransplant period with gradual and successful weaning of all immunosuppressants. Stem cell transplantation is an optimal treatment for acute myelocytic
leukemia and it results in the generation of select subset of donor-specific
immunologic cells. Although the immunopathogenesis of atopic dermatitis is not
known to be HLA-specific, it is reasonable to predict that it involves the development of an exuberant TH2-type response because of a specific cellular immunologic
milieu. Twin studies certainly support this assumption, because they have a very
high coincidence of atopic dermatitis. A literature review revealed other occurrences of stem cell transplantation associated with new-onset atopic dermatitis.
Similar phenomenon have also been noted in the ophthalmology literature in ocularpredominant, atopic disease. Moreover, the transfer of asthma and allergen-specific
allergies have also been reported. The converse also exists where latex allergies and
atopic dermatitis have resolved after transplantation. All together, this represents a
rare phenomenon that may be useful in the understanding of the pathogenesis of
atopic dermatitis with further investigation.
Conclusion: The PPARs, FIAF, and HIF may potentially be important biomarkers in
the pathogenesis of cutaneous squamous cell carcinoma. Validation of the results on
PCR analysis with tissue immunostaining is now underway.
P407
Sentinel node biopsy in patients with melanoma: Results after an 11-year
experience
Lidia Tomas Mallebrera, Hospital Universitario Dr. Peset, Valencia, Spain;
Caroline Martins Brand~ao, University of State of Pará, Belém, Pará, Brazil;
Marcella Coelho Mesquita, University of State of Pará, Belem, Pará, Brazil;
Rodolfo Costa Lobato, University of State of Pará, Belém, Pará, Brazil; Thais
Rodrigues Da Cunha Fischer, University of State of Pará, Belém, Pará, Brazil
Background: The sentinel node biopsy (SNB) procedure is now widely regarded as
the standard of care for staging patients with melanoma and breast cancer. It not
only allows accurate disease staging, but also provides a guide to prognosis and a
rational method of identifying patients most likely to benefit from adjuvant therapies
and those most appropriate for adjuvant therapy trials.
Methods: All patients with a diagnosis of melanoma who were studied with SNB in
Dr Peset Hospital from 1998 to 2008 were included in this epidemiologic study. A
total of 144 patients have been treated with this technique over 11 years. The mean
follow-up for every patient was 58.45 months.
Results: More than half (58.3%) of the patients included in the study were males, and
the mean 6 standard deviation age was 55.10 6 15.90 years. The most common site
of the primary melanoma was the trunk (54.2%), followed by the legs. Nodular
melanoma (45.1%) and superficial spreading melanoma (45.1%) were the most
frequent histologic types. The mean Breslow thickness was 2.160 6 1.660 mm. Most
of the melanomas had a Clark level III or IVof invasion. Ulceration was found in 60.4%
of patients. The SNB showed micrometastasis in 19.4% of the studied patients. Of
these patients, 17.9% with SNB positive had more affected lymphatic nodes a
complete lymphadenectomy was performed. Sex of the patient, phototype, and site
of melanoma were not statistically significant predictors of positive SNB. Nodular and
polypoid melanomas predicted a positive SNB. Positive SNB was more common in
patients with high Breslow thickness, and the number of patients with positive SNB
increased as Clark level invasion was higher. Ulceration was more common in
patients with positive SNB (85.7%) than in negative SNB, and the relative risk was 4.8.
Conclusions: None of the patients with Breslow thickness $ 1 mm had a positive
result in the SNB. Interestingly, we found that there is a trend toward a stage change
along few years in patients with positive SNB, because the estimated risk of stage
worsening in a patient with a positive SNB was 7-fold higher than in patients with
negative SNB. So we think a positive result in SNB helps to identify patients with
melanoma with Breslow thickness $ 1 mm who are at risk of progression of their
disease or death, because SNB has demonstrated its prognostic value in patients with
melanoma.
P501
A substituted trans-stilbene derivative as a novel topical treatment for atopic
dermatitis: Results from a randomized, placebo-controlled clinical trial
Robert Bissonnette, MD, Innoverdam Research, Montreal, Quebec, Canada;
Catherine Maari, Innovaderm Research, Montreal, Quebec, Canada; Chantal
Bolduc, MD, Innovaderm Research, Montreal, Quebec, Canada; Genhui Chen,
PhD, Welichem Biotech, Burnaby, British Columbia, Canada; Liren Tang, PhD,
Welichem Biotech, Burnaby, BC, Canada
Introduction: A novel synthetic natural compound, WBI-1001, was shown to inhibit
inflammatory cytokines, T-cell viability, and the skin infiltration processes in
preclinical studies. WBI-1001 is currently being developed as a topical treatment
for mild to moderate atopic dermatitis (AD). To evaluate the safety and efficacy of
topically applied WBI-1001 cream in the treatment of AD, a randomized, doubleblinded, vehicle-controlled study was conducted.
Methods: Thirty-seven patients aged 18 to 65 with chronic atopic dermatitis were
enrolled. Patients were randomized (1:1:1) to apply either WBI-1001 0.5%, 1.0%, or a
vehicle cream twice daily for 4 weeks with a follow-up visit 1 week later. Safety
assessments included adverse events and hematologic and biochemical parameters.
Efficacy assessments included eczema area severity index (EASI), scoring atopic
dermatitis severity index (SCORAD), investigator global assessment (IGA), body
surface area (BSA) affected, and pruritus.
Results: After 4 weeks of treatment, both 0.5% and 1.0% WBI-1001 showed
significant reduction in EASI score (59.3% and 54.9%, respectively, compared with
7.1% for vehicle; P \.05), SCORAD (56.2% and 50.1%, respectively, compared with
18.4% for vehicle; P \.05), IGA (38.9% and 45.8%, respectively, compared with
vehicle at 5.6%; P \.05), BSA (64.4% and 57.7%, respectively, compared with 1.08%
for vehicle; P \.05), and pruritus scores (74.0% and 56.0%, respectively, compared
with 25.0% for vehicle; P \.05 for the 0.5% arm). At week 4, 50.0% of subjects in
both active treatment arms were clear or almost clear compared with 16.7% for the
vehicle arm. Topical treatment with WBI-1001 creams at 0.5% or 1.0% for 4 weeks
was well tolerated. No treatment-related skin adverse events were observed.
Pharmacokinetics analysis showed that the active drug compound was minimally
absorbed into the blood system and no drug accumulation was reported.
Conclusion: WBI-1001 cream at 0.5% and 1.0% was well tolerated by patients with
mild to moderate AD, and both cream concentrations were more effective than
vehicle in improving atopic dermatitis.
Commercial support: This study was supported by Welichem Biotech, Burnaby,
Canada.
MARCH 2010
J AM ACAD DERMATOL
AB9
P502
P504
Assessing the long-term safety of tacrolimus ointment for the treatment of
atopic dermatitis: An update on a prospective pediatric longitudinal
evaluation study (APPLES)
Amy S. Paller, MD, Northwestern University, Chicago, IL, United States; M. Alex
Michaels, MD, Astellas Pharma US, Deerfield, IL, United States; Thomas Bieber,
MD, PhD, Friedrich-Wilhelms-University, Bonn, Germany
Objective: To assess the long-term safety of treatment with tacrolimus ointment
0.03% and 0.1% in pediatric patients with atopic dermatitis (AD) under actual use
conditions.
Methods: Enrollment of approximately 8000 patients is planned for this phase IV,
prospective, multinational, observational, cohort study. Patients treated for AD with
tacrolimus ointment before 16 years of age for a cumulative minimum of 6 weeks are
eligible. Each patient is followed for 10 years with yearly physical examinations,
biennial dermatologic examinations, and biannual follow-up calls to collect any
additional safety information. The study endpoints include systemic and cutaneous
malignancies. Interim data are presented.
Text messages as a reminder aid and educational tool in adolescents and
adults with atopic dermatitis: A pilot study
Venessa Pena-Robichaux, Partners Center for Connected Health, Massachusetts
General Hospital, Dermatology Department, Harvard Medical School, Boston,
MA, United States; Alice J. Watson, MPH, MBChB, Partners Center for Connected
Health, Massachusetts General Hospital, Dermatology Department, Harvard
Medical School, Boston, MA, United States; Joseph C. Kvedar, MD, Partners
Center for Connected Health, Massachusetts General Hospital, Dermatology
Department, Harvard Medical School, Boston, MA, United States
Results: Since May 2005, 3998 patients (51.5% female) have been enrolled (cutoff
date September 19, 2008). At enrollment: (1) the median age was 6 years; (2) 86.1%
of patients had mild to moderate AD with 9.8% reporting severe AD; (3) 73.5% of
patients were using tacrolimus ointment; and (4) 18.9% of patients were using
pimecrolimus cream. The median cumulative duration of time since initial application per patient was 2.4 years for tacrolimus ointment (range, 0.0-17.3 yrs) and
pimecrolimus cream (range, 0.0-28.6 yrs). Serious adverse events, irrespective of
causality, were reported in 4.9% of patients. The majority of these events were
asthma (38; 1%) or infections (72; 1.8%), including pneumonia, bronchitis, cellulitis,
gastroenteritis, tonsillitis, with each category constituting \1% of the enrolled
patients. Since study enrollment, there is one report of a peripheral glioneuronal
tumor. This observed rate in APPLES, compared to SEER pediatric data for overall
malignancy rates, is half that seen in the general US population.
Conclusions: The interim data confirm the established safety profile of tacrolimus
ointment for treatment of pediatric patients with AD.
Commercial support: Study was sponsored by Astellas.
Optimal management of atopic dermatitis (AD) requires patients to adhere to
medications and other behaviors, such as using emollients on a regular basis and
avoiding skin irritants. Evidence to date suggests that adherence to care plans is poor
amongst dermatology patients.1,2 Technologies, such as cell phones, have been
widely adopted in the United States and could potentially be used to promote
positive health behaviors. The use of cell phone technology in the care of AD
patients has not previously been studied. We conducted a pilot study with 20
adolescents and adults ages 14 years and older (mean, 29.6 yrs; SD, 13.6) with AD.
Daily text messages were sent for 6 weeks to participants with AD reminding them
to use their medication and providing educational information about AD. Our goals
were to: (1) assess the usability and satisfaction of the text message system and (2)
measure changes in pre- and posttest scores in medication adherence, maintenance
behaviors, and disease severity. Self-reported medication adherence and maintenance behaviors were assessed via surveys at the beginning and end of the 6-week
period. The poststudy survey also assessed usability and satisfaction of the text
message system. Disease severity was assessed before and after the text message
intervention by using the SCORing Atopic Dermatitis (SCORAD) index. Eighty-five
percent of participants found the text messages that reminded them to use their
medication helpful, and 90% reported that the AD educational information provided
to them via text message was helpful as well. Eighty percent of participants reported
that they would like to keep using the text message system, and 85% reported they
would recommend it to a friend. Eighty percent of participants reported an increase
in the number of days a week they were adherent to their medical treatment
(prestudy mean, 3.7 days, SD 2.4; poststudy mean, 6.1 days, SD 1.7). In addition, 95%
of participants reported an improvement of at least one health maintenance
behavior. Finally, the poststudy SCORAD score decreased in 70% of participants
(mean decrease, 7.3 points, SD 4.0), suggesting an improvement in disease severity.
Study participants were receptive to using text messages as a reminder aid and
educational tool. The positive trends observed with regard to various outcome
measures is promising and lays the ground work for further studies, which are
needed to elucidate the full potential of this simple and costeffective intervention.
REFERENCES
1. DiMatteo MR. Variations in patients’ adherence to medical recommendations: a
quantitative review of 50 years of research. Med Care 2004;42:200-9.
2. Renzi C, Picardi A, Abeni D, et al. Association of dissatisfaction with care and
psychiatric morbidity with poor treatment compliance. Arch Dermatol
2002;138:393-4.
P503
Treatment of moderate and severe atopic dermatitis in children with twice
weekly tacrolimus 0.03% ointment
Sakari Reitamo, MBChB, Hospital for Skin and Allergic Disease, Helsinki
University Central Hospital, Helsinki, Finland; Richard Allsopp, PhD, Astellas
Pharma Europe, Staines, Middlesex, United Kingdom; Shevani Naidoo, PharmD,
Astellas Pharma Europe, Staines, Middlesex, United Kingdom
Objectives: This abstract represents a post hoc analysis of the pediatric CONTROL
Study; twice-weekly tacrolimus 0.03% ointment maintenance therapy in mild to
severe atopic dermatitis (AD). The efficacy and tolerability of this treatment regimen
in moderate to severe AD are discussed here. Maintenance therapy with twice
weekly tacrolimus ointment (applied once daily) significantly reduced number of
flares and severity of AD symptoms, and prolonged the flare-free interval, compared
with a standard, reactive regimen with tacrolimus ointment.
Methods: After a screening period of 1 week, children (aged 2-15 yrs; n ¼ 166) with
active AD lesions were treated twice daily with tacrolimus 0.03% ointment for up to
6 weeks. Once patients achieved an Investigator’s Global Assessment (IGA) score of
# 2 (n ¼ 153), they were randomized to either twice-weekly double-blind
tacrolimus 0.03% ointment (n ¼ 78) or vehicle (n ¼ 75) for 12 months. Disease
exacerbations were treated with open-label twice-daily tacrolimus 0.03% ointment
for 1 to 6 weeks until resolution. The number of major flares (exacerbations
requiring tacrolimus ointment treatment for [7 days to treat an IGA of 3-5) during
the 12-month disease-control period was the primary endpoint.
P505
Increased risk of psychiatric disorders in a pediatric population with
psoriasis
Abbott Park, IL, United States; Shiraz Gupta, Abbott Laboratories, Abbott Park, IL,
United States
Objective: To compare the incidence of psychiatric disorders for pediatric patients
with versus without psoriasis.
Results: During the 12-month study, patients receiving maintenance therapy
experienced significantly fewer major flares than those receiving standard therapy
(P \.001). 46.2% of patients receiving maintenance therapy experienced no flares,
compared with 21.3% with the standard regimen. The number of days of disease
exacerbation treatment was also substantially lower in patients receiving maintenance therapy (42.3 vs 68.9 days), and time to first flare was significantly prolonged
(P \.001). Tolerability of tacrolimus ointment was similar with the two regimens.
Mean tacrolimus ointment use was 1.29 g/day with maintenance therapy versus
1.42 g/day with standard therapy (median, 1.00 vs 0.57 g/day; upper quartile, 1.70
g/day vs 1.49 g/day; 90th percentile, 2.78 g/day vs 3.87 g/day).
Conclusions: A treatment regimen with twice-weekly tacrolimus 0.03% ointment
was effective and well tolerated compared with a standard, reactive regimen in
children with moderate to severe AD.
Methods: Patients with psoriasis aged \18 years with continuous health plan
enrollment 6 months before and after the first psoriasis diagnosis date (index date)
were selected from the Thompson MarketScan database (2000-2006). Patients with
psoriasis were matched 1:5 on age and sex to psoriasis-free controls who were
attributed the same index date. Patients were followed from index date to the first
diagnosis of a psychiatric disorder (ie, alcohol or drug abuse, depression, anxiety
disorder, bipolar disorder, suicidal ideation, or eating disorder), end of data
availability, or disenrollment, whichever occurred first. Patients with psychiatric
diagnoses or any psychotropic medication use before the index date were excluded.
Cox proportional-hazards models controlling for age, sex, and comorbidities were
used to estimate the effect of psoriasis on the risks of developing psychiatric
disorders.
Results: The study included 2144 patients with psoriasis and 10,720 matched
controls. Mean (6SD) patient age was 11.4 (64.1) years. A significantly greater
percentage of patients with psoriasis had a psychiatric disorder compared with
controls (5.13% vs 4.07%; P ¼ .0001), especially depression (3.01% vs 2.42%; P ¼
.0036) and anxiety (1.81% vs 1.35%; P ¼.0048). The risk for developing a psychiatric
disorder was significantly greater for patients with psoriasis than for controls, with a
hazard ratio estimated at 1.25 (95% confidence interval, 1.11-1.40). Estimated hazard
ratios were 1.23 (1.06-1.43) for depression and 1.32 (1.09-1.61) for anxiety.
Conclusions: Pediatric patients with psoriasis were at increased risk of psychiatric
disorders, including depression and anxiety, compared with psoriasis-free patients.
Commercial support: Fully sponsored by Astellas Pharma Europe.
AB10
J AM ACAD DERMATOL
MARCH 2010
P506
Safety and efficacy of etanercept treatment in children and adolescents
with plaque psoriasis: 96-week results of open-label extension study
Amy Paller, MD, Children’s Memorial Hospital and Northwestern University
Medical School, Chicago, IL, United States; David Pariser, MD, Department of
Dermatology, Eastern Virginia Medical School and Virginia Clinical Research,
Norfolk, VA, United States; Elaine Siegfried, MD, Cardinal Glennon Children’s
Hospital and Saint Louis University, Saint Louis, MO, United States; Gregory
Kricorian, MD, Amgen, Thousand Oaks, CA, United States
In this open-label, multicenter, extension study to evaluate the long-term safety and
efficacy of etanercept in pediatric patients with moderate to severe plaque psoriasis,
patients received a once-weekly subcutaneous injection of 0.8 mg/kg etanercept (up
to a maximum of 50 mg) for a planned 264 weeks following completion of the
primary, randomized, double-blind, placebo-controlled study. Herein we report 96week results. Patients (4-17 yrs) were eligible if they completed the original 48-week
study or achieved PASI 50 or better on or after week 12 and did not have a serious or
clinically significant adverse event (AE) related to etanercept. The primary endpoint
was the incidence of AEs, including infectious episodes, serious AEs, and serious
infectious episodes. Further endpoints included efficacy response rates determined
by PASI 50, PASI 75, PASI 90 (relative to the baseline of the original study), and static
Physician’s Global Assessment (sPGA). Of 182 patients enrolled, 145 (80%) reported
at least one AE over the 96-week period. Upper respiratory tract infections,
nasopharyngitis, streptococcal pharyngitis, headache, and sinusitis were the most
common AEs, affecting 25%, 17%, 13%, 12%, and 11% of patients, respectively. Three
patients reported five serious AEs (all were noninfectious and considered not related
to study drug): anxiety (1 patient); intestinal obstruction (1 patient); and abdominal
pain, dehydration, and elective abortion (1 patient). Two AEs led to study
withdrawal (both considered not related to study drug): 1 case of Crohn disease
and 1 case of sinusitis. No malignancies, opportunistic infections, tuberculosis,
lymphomas, demyelinating events, or deaths were reported. A total of 140 (77%)
patients completed week 96 of the study when 123 of 138 (89%) achieved PASI 50,
84 of 138 (61%) achieved PASI 75, and 41 of 138 (30%) achieved PASI 90; and 66 of
139 (47%) patients achieved a sPGA of clear/almost clear (0, 1) (observed cases).
Extended etanercept therapy continued to be well tolerated overall for 96 weeks
after the initial 48-week trial in pediatric patients aged 4 to 17 years with moderate to
severe plaque psoriasis. In addition to a favorable safety profile, efficacy results were
maintained with continued etanercept therapy.
Commercial support: Funded by Immunex Corp, a wholly owned subsidiary of
Amgen, and by Wyeth.
PD06-BLISTERING AND SYSTEMIC DISEASES,
AND TELEDERMATOLOGY
P600
High-resolution, high-magnification capillary videomicroscopy imaging
as a useful adjunct in the assessment of pharmacological intervention
(tadalafil) for secondary Raynaud phenomenon due to scleroderma and
mixed connective tissue disease
Stephanie St. Pierre, MD, Northwestern University Department of Dermatology,
Chicago, IL, United States; Ana Ciurea, MD, MD Anderson Cancer Center,
Houston, TX, United States; Anne Laumann, MBChB, Northwestern University
Department of Dermatology, Chicago, IL, United States; Dennis West, PhD,
Northwestern University Department of Dermatology, Chicago, IL, United States;
Jenneé Rommel, MD, Northwestern University Department of Dermatology,
Chicago, IL, United States
Nailfold capillaroscopy has been used for years as a method of identifying
scleroderma-related capillary patterns in those with secondary Raynaud phenomenon. A capillaroscopy system with a CAM1 laser Doppler capillary anemometer
(CAM1 Capillary Anemometer CapiScope System, kk Technology, UK) noninvasively
measures average velocity and diameter of individual vessels. In addition to
measuring blood flow velocity in digital capillaries, the system also functions as a
video microscope that measures capillary diameter and density. This system is
suitable for use on capillaries parallel to the skin surface, such as at the nailfold. One
of the key features of this approach is the use of a near infrared laser (780 nm) that,
when backscattered by a column of red blood cells, can be used to calculate velocity
based on the Doppler shift. In order to enhance the contrast between blood and
nearby tissue when using this system, a green light at 525 nm is projected onto the
skin. Using this input, microscopy of the capillaries and the Doppler shift power
spectrum is determined and available as real-time video. As a result, images of the
nailfold capillaries have high resolution, and measurements of these structures are
reproducible. In this study, we obtained high-definition, high-resolution capillary
videomicroscopy before, during, and after treatment with tadalafil. We augmented
our study findings with the collection and analysis of digital blood pressures; the
global assessment by both subject and physician of Raynaud phenomenon; and the
completion, by the subject, of symptom-specific visual analog scales (VAS), Raynaud
Condition Scores, Arthritis Impact Measurement Scales (AIMS2) with mood and
tension subscales, and a health assessment questionnaire. Our findings show that
capillary videomicroscopy imaging may be a useful adjunct in quantifying response
to pharmacological interventions such as tadalafil in an approach to the treatment of
secondary Raynaud phenomenon.
Commercial support: Eli Lilly & Company provided 100% of the funding for this
project.
P601
Evaluation of store-and-forward teledermatology applications
April Armstrong, MD, University of California Davis, Sacramento, CA, United
States; Aron Farbstein, University of California Davis, Sacramento, CA, United
States; Christopher Sanders, University of California Davis, Sacramento, CA,
United States; George Wu, University of California Davis, Sacramento, CA, United
States
Q3
P507
Introduction: Despite the reported advantages of store-and-forward (S&F) teledermatology, wide implementation in the US has faced real-world challenges.
Among them, the lack of user-friendly, secure, and affordable S&F applications
presents a practical obstacle for dermatologists and referring physicians wanting to
start teledermatology programs. In this study, we developed evaluation criteria and
assessed major store-and-forward teledermatology applications in the United States.
Methods: We surveyed members of the AAD Telemedicine Task Force and the American
Telemedicine Association Teledermatology Special Interest Group to inquire about the
types of S&F applications currently used. Based on the survey results, we identified four
major S&F applications for evaluation. We developed criteria for comparative analysis of
these applications based on communication with thought leaders, high-volume
teledermatologists, and medical informatics experts. The four major S&F teledermatology applications were assessed by independent dermatologists, veteran teledermatologists, and information technologists using the evaluation criteria.
Results: The evaluation criteria for the S&F applications include system requirements,
HIPPA compliance and privacy, information sharing and storage, user interface,
compatibility scalability, billing, and cost. Our evaluation showed that the S&F
application used in Alaska was designed with touchscreen in mind with a simple to
navigate interface. The e-mailelike interface uses attachment for patient data
presentation; these features are user-friendly and easy to learn. The S&F application
used commonly in California requires local installation of software. The user interface
and data presentation are organized similar to traditional patient encounters. The
image viewer is versatile and allows users to annotate the images without altering
original images. Drawing upon teledermatology experiences from the military, the
third application offers an intuitive workflow for consultants. Important features
include assigning cases to trainees and assembled responses for common diagnoses.
Originally developed for radiology, the fourth application is a feature-rich application
that would require more time to learn than the other applications. This application has
extensive image handling options and dicom compatibility. Although teledermatologists desired integration of a billing component into the S&F application, none of the
application evaluated have a mature billing components.
Conclusion: The major S&F teledermatology applications have robust security
features, but they vary widely in referral data presentation, consultant data input,
and the length of time required for configuration and learning. Integration with
billing is a desired feature, but it is lacking from most current applications.
MARCH 2010
J AM ACAD DERMATOL
AB11
P602
P604
Teledermatology versus traditional in-office evaluation: A comparison of
per-visit and long-term billing trends at East Carolina University from
1996-2007
Charles Phillips, MD, Brody School of Medicine at East Carolina University,
Greenville, NC, United States; Jaclyn Beierlein, PhD, East Carolina University,
Greenville, NC, United States; Josh Porter, MD, Brody School of Medicine at East
Carolina University, Greenville, NC, United States; Robert Schosser, MD, Brody
School of Medicine at East Carolina University, Greenville, NC, United States;
William Burke, MD, Brody School of Medicine at East Carolina University,
Greenville, NC, United States
Susceptibility to experimental epidermolysis bullosa acquisita (EBA) is
correlated with expression of TH1 cytokines
Christoph Matthias Hammers, University of Luebeck, Institute of Anatomy,
Luebeck, SL-H, Germany; Detlef Zillikens, MD, University of Luebeck,
Department of Dermatology, Luebeck, SL-H, Germany; Juergen Westermann,
MD, University of Luebeck, Institute of Anatomy, Luebeck, SL-H, Germany; Katja
Bieber, PhD, University of Luebeck, Institute of Anatomy, Luebeck, SL-H,
Germany; Ralf Ludwig, MD, University of Luebeck, Department of
Dermatology, Luebeck, SL-H, Germany
Teledermatology is the delivery of dermatologic services using communication
technology (traditionally audio and video and still images). East Carolina University
(ECU) School of Medicine has provided telemedical services to eastern North
Carolina since 1992. The cost of the service is typically justified by indirect
economic measures such as a decreased driving distance and decreased time away
from work. We looked at the revenue generated from our teledermatology services.
Our study evaluated trends in single and total average lifetime charges for
teledermatology versus in-office dermatology services at ECU. We analyzed
116,398 patient encounters within the Division of Dermatology at ECU between
mid-1996 through 2007, of which 1501 encounters were listed under the teledermatology billing code. We looked at various billing centers: general dermatology
services, laser services, cutaneous surgery, and miscellaneous billing codes. The
general dermatology services code was our standard of measurement for all other
billing codes, because the majority of encounters at ECU fall under the general
services domain. Our data show that single teledermatology encounters yielded
average charges 6.3% higher than our baseline general dermatology encounters.
Over the study lifetime, however, patients initiating contact via teledermatology
generated 65.1% fewer billable services, 6.1% lower per visit charges, and 68.5%
lower net charges than the baseline general dermatology billing code. Fewer visits
coupled with lower average per-visit charges may explain our finding that patients
initiating contact via teledermatology do not appear to generate as much revenue as
general dermatology encounters at our institution. The benefit of telemedical
services is in keeping the patient closer to home communty and in the practice of
the referring physician. This may come at a cost benefit for the dermatologist of
following the patient over longer periods of time or for needed procedures. Periodic
adjunct live satellite clinics where teledermatologic services are provided may both
better serve the patient, keep the patient in their community and be an economic
benefit to the managing dermatologist.
The immune system recognizes and eliminates foreign antigens. Under certain
circumstances, B and T lymphocytes can also react to self-components and
initiate autoimmune diseases. One example is the generation of autoantibodies
against type VII collagen, which represents an integral part of the dermoepidermal junction (DEJ). These autoantibodies are deposited at the DEJ and induce
severe blistering of skin and mucous membranes, a disease which is also known
as epidermolysis bullosa acquisita (EBA). We have previously established an active
disease model of EBA by immunizing mice once with recombinant murine type
VII collagen. In this model, immunization of different mouse strains leads to
different disease activities. In the present study we show that susceptible mice of
the SJL strain feature an significant increase in T-cell proliferation and expression
of TH1-specific cytokines as IL-12, IFN-gamma, and TNF-alfa in the draining lymph
nodes of the skin. In contrast to this, resistant BALB/c mice show a lesser
expression of these cytokines, whereas IL-17 and IL-4 are increased significantly.
In line with these observations, we found significant higher levels of type VII
collagen-specific IgG2b in the serum of SJL mice, which has previously been
shown to be the most pathogenic antibody subclass in murine EBA because of its
complement-fixing abilities. Binding of IgG2b to the DEJ was also increased
significantly in SJL mice compared to BALB/c mice. Our results provide a basis for
new strategies to treat EBA (ie, by applying appropriate cytokines that shift the
autoimmune response to the production of nonpathogenic type VII collagen
antibodies).
P603
New molecular targets in the treatment of pemphigus vulgaris
Maider Pretel, MD, University Clinic of Navarra, Pamplona, Navarra, Spain;
Agustin España, MD, University Clinic of Navarra, Pamplona, Navarra, Spain;
Gorka Ruiz-Carrillo, MD, University Clinic of Navarra, Pamplona, Navarra, Spain;
Laura Marques, MD, University Clinic of Navarra, Pamplona, Navarra, Spain;
Maria Jesus Lopez-Zabalza, University of Navarra, Pamplona, Navarra, Spain
Introduction: Pemphigus vulgaris (PV) is a blistering autoimmune disease with
mucosal and cutaneous clinical manifestations. Treatment of PV is based on
corticosteroids and immunosuppressive drugs, causing several side effects.
Methods: This study was carried out by passive transfer mouse model of PV, using
sera of three PV patients (PV-IgG) and serum of one healthy patient (NHS-IgG).
Epidermal expression of several activated intracellular signaling molecules (HER,
Akt, Src, and mTOR) was analyzed by immunohistochemical procedures after PVIgG and NHS-IgG administration. The role of apoptosis in PV was analyzed by TUNEL
assay. In addition, mice were pretreated with inhibitors of these molecules in order
to analyze their effect on the PV manifestation of mice (erlotinib (HER inhibitor),
rapamycin (mTOR inhibitor), PP1 (Src inhibitor), and pan-caspase inhibitor).
Results: Elevated and significant expression of the three activated HER isoforms (pHER1, p-HER2, and p-HER3), p-mTOR, and p-Src on basal cell layer of epidermis after
PV-IgG administration was observed as compared with that observed after NHS-IgG
injection. p-Akt expression was not observed on basal cell layer. TUNEL assay
displayed a high number of apoptotic cells in the same localization as p-HER
isoforms, p-mTOR, and p-Src, and 3 hours before acantholytic cells were observed in
epidermis. Mice pretreated with all four inhibitors did not show clinical or histologic
manifestations of PV, and apoptotic cells were not found on basal cells of epidermis
by TUNEL assay.
Conclusions: Our work underlines three important findings. First, increased
expression of p-HER isoforms, p-mTOR, and p-Src was observed on basal cell layer
of epidermis in PV using a mouse model. Second, apoptotic mechanism was present
in PV before acantholysis developed. And finally, inhibition of apoptosis and
acantholysis observed in basal layer of epidermis by administration of inhibitors of pHER isoforms, p-Src, p-mTOR, and caspases in our model provide compelling
molecular evidence that these signaling molecules should be considered potential
therapeutic targets in PV therapy signaling.
AB12
P605
Molecular mechanisms involved in the initiation of solar lentigines
Connie B. Lin, PhD, MS, The Johnson & Johnson Skin Research Center, CPPW, a
unit of Johnson & Johnson Consumer Companies, Skillman, NJ, United States;
David Cassarino, MD, Pathology and Laboratory Medicine, University of
California, Los Angeles, CA, United States; Dianne Rossetti, The Johnson &
Johnson Skin Research Center, CPPW, a unit of Johnson & Johnson Consumer
Companies, Skillman, NJ, United States; Nannan Chen, PhD, The Johnson &
Johnson Skin Research Center, CPPW, a unit of Johnson & Johnson Consumer
Companies, Skillman, NJ, United States; Yaping Hu, PhD, The Johnson & Johnson
Skin Research Center, CPPW, a unit of Johnson & Johnson Consumer Companies,
Skillman, NJ, United States
Solar lentigines (SLs) are hyperpigmented lesions that are associated with sun
exposure and age. Here we showed the different progressive stages of SLs based on
melanin content and on the complexity of the elongated rete ridges. We found that
the protein levels of the proliferation and DNA synthesis markers Ki67 and CDC47,
keratinocyte growth factor (KGF) and its receptor (KGFR), stem cell factor (SCF)
and its receptor c-Kit, and protease-activated receptor-2 (PAR-2) were higher in the
early SL stages, as compared to the late stages. Tyrosinase (TYR) level was
significantly increased in all SL stages. The latest stage of SL exhibited significantly
lower levels of all proteins examined except TYR, suggesting keratinocyte dormancy with melanocyte activity. The possible involvement of KGF in the initiation of
SL formation was evaluated in vitro. We found that KGF is expressed in both
melanocytes and keratinocytes, and that its levels were upregulated by UVB or IL-1a.
Using pigmented epidermal equivalents and human skin explants, we showed that
KGF increases pigment deposition. In addition, the expression levels of several
pigmentary related genes were induced by KGF. We conclude that UVB-induced
KGF might have a key role in the initiation of hyperpigmentation and rete ridges
formation of SLs.
Commercial support: 100% is sponsored by Johnson & Johnson.
J AM ACAD DERMATOL
MARCH 2010
P606
Cardiovascular risk evaluation in psoriasis
Carolina Covalski, MD, Universidade Federal de Santa Catarina, Florianópolis,
Santa Catarina, Brazil; Daniel Holthausen Nunes, MD, Universidade Federal de
Santa Catarina, Florianópolis, Santa Catarina, Brazil; Marina Besen Guerini, MD,
Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil;
Naiana Bittencourt Sa, MD, Universidade Federal de Santa Catarina, Florianópolis,
Santa Catarina, Brazil
Introduction: Psoriasis is a relatively common skin condition that involves chronic
local and systemic inflammatory process. Currently, some studies seek to involve the
chronic inflammatory disease with increased risk for atherosclerosis, cardiovascular
events, and metabolic syndrome. Higher prevalences of diabetes, hypertension, and
abnormal lipid profile have been associated with psoriasis, which may indicate that
this disease can be a independent risk factor for cardiovascular events.
Objective: To evaluate the prevalence of cardiovascular risk factors in patients with
psoriasis, comparing them with a healthy control group without chronic inflammatory systemic diseases.
Methods: The project was approved by the ethics committee. Participants were
selected from a group of patients with psoriasis on treatment in the clinic of
dermatology and a healthy control group, matched by sex and age. All participants
were subjected to laboratory tests and interviews to complete the Protocol of
Cardiovascular Risk in Psoriasis. The variables analyzed were: gender, age, body
mass, height, calculation of body mass index (BMI) and waist circumference,
personal history of diabetes, smoking, hypertension, recent treatment with corticosteroids, use of hypolipidemic and antihypertensive drugs, individual history of
cardiovascular disease in first-degree relative, presence of first-degree relatives with
psoriasis, analysis of total cholesterol (TC) and high-density lipoprotein (HDL),
triglycerides, and uric acid. Were classified as bearer of dyslipidemia or not through
the parameters: TC [200 mg/dL, triglycerides [150 mg/dL, HDL \40 mg/dL, and
ratio TC/HDL [3.5. For uric acid, the cutoff was set at 7.0 mg/dL. For statistical
analysis, P \.05 was considered significant.
Results: There was a positive association between psoriasis and HDL \40 mg/dL (P
¼ .012), ratio TC/HDL-C [3.5 (P \0.001), triglycerides [150 mg/dL (P ¼ .0030),
and dyslipidemia (P \.001). History of heart attack and stroke (P ¼.021) and high
uric acid (P ¼.010) showed significant association with psoriasis. Family history of
psoriasis showed statistically proven relationship with the risk of developing this
disease (P \.001).
Conclusion: This sample shows that psoriasis is associated with higher prevalence of
alterations in lipid profile, dyslipidemia, hyperuricemia, and history of cardiovascular disease. In addition, significant association with the presence of first-degree
relatives with psoriasis was observed.
ACNE
P700
Human spermatogenesis is unaffected by 12 weeks of treatment with lowdose extended release minocycline
Larry Lipshultz, MD, Baylor College of Medicine, Houston, TX, United
StatesUnited StatesUnited States; Ira Lawrence, MD, Medicis Pharmaceutical
Corporation, Scottsdale, AZ, United States
Background: Reports have suggested that minocycline adversely affects human
spermatogenesis.
Objective: The primary objective was to investigate the effects of an extended
release (ER) minocycline on several parameters of spermatogenesis, including mean
changes in sperm count. Secondary objectives included assessing the effects of ER
minocycline on circulating follicle-stimulating hormone (FSH), serum testosterone
levels, and the proportion of subjects with $ 50% reduction in sperm motility and
with $ 20% reduction in normal sperm morphology.
Methods: This randomized, double-blind, placebo-controlled study enrolled healthy
men $ 18 years of age with clinically acceptable baseline sperm parameters, defined
as a total sperm concentration of [20 3 106/mL, of which [50% were motile and
[4.4% had normal morphology. The study drug was an ER minocycline (Medicis
Pharmaceutical, Scottsdale, AZ). One tablet (1 mg/kg) was taken daily for 12 weeks.
This treatment period corresponds to the approved ER minocycline product label
and exceeds the human 75-day spermatogenesis cycle. After the baseline evaluation,
blood and semen samples were collected after 12, 16, 20, and 24 weeks.
Results: Study subjects were randomized to receive treatment with ER minocycline
(N ¼ 92) or placebo (N ¼ 88); 146 subjects completed the study. At week 12, the
mean change in sperm concentration was 9.8% in the minocycline group versus
e1.3% in the placebo group (P ¼ not significant at all time points). At week 12, the
number of minocycline- and placebo-treated subjects with a 50% reduction in sperm
concentration was 11.1% and 11.0%, respectively; the number of subjects with a
50% reduction in motility was 0.0% and 1.4%, respectively, and the number of
subjects with a 20% reduction in normal morphology was 20.8% and 32.9%,
respectively (P ¼ not significant at all time points). At week 12, the mean FSH levels
in minocycline- and placebo-treated subjects were 3.2 and 3.1 IU/L, respectively, and
the mean testosterone levels were 465.1 and 476.9 ng/dL, respectively. At week 12,
the mean change in FSH levels in minocycline- and placebo-treated subjects were
e0.1 and 0.0 IU/L, respectively, and the mean change in testosterone levels were
e2.4 and 5.3 ng/dL, respectively (P ¼ not significant at all time points).
Conclusions: These results indicate that human spermatogenesis and circulating
levels of FSH and testosterone are unaffected by the administration of low-dose ER
minocycline for up to 12 weeks.
Commercial support: Medicis Pharmaceutical.
P701
P607
The molecular profile of psoriatic skin in responders to ustekinumab or
etanercept after 12 weeks of treatment: Results from the ACCEPT trial
James Krueger, MD, PhD, Rockefeller University, New York, NY, United States;
Carrie Brodmerkel, PhD, Centocor Research and Development, Malvern, PA,
United States; Katherine Li, PhD, Centocor Research and Development,
Horsham, PA, United States; Mayte Suarez-Farinas, Rockefeller University, New
York, NY, United States
Aims: To assess the impact of p40 cytokine (IL-12/IL-23) or TNF-alfa blockade on
resident and inflammatory cells and on the expression of gene circuits that may
drive chronic immune activation and inflammation in the skin.
Methods: In ACCEPT, a randomized, active-controlled study, the efficacy of
etanercept and ustekinumab were compared in 903 patients with moderate to
severe plaque psoriasis through week 12. Skin biopsies were performed in a subset
of patients at baseline, weeks 1 and 12. Microarray analyses (Affymetrix U133 1 2
array) comparing nonlesional skin (n ¼ 85) to lesional skin (n ¼ 85) at baseline
showed several thousand probe sets differentially expressed ([2-fold change FDR; P
\ .05) in lesional skin.
Results: Patients responding to each agent ( $ PASI 75, n ¼ 21 for etanercept, n ¼ 19
for ustekinumab) had significant changes in approximately 4000 transcripts compared to untreated lesions, indicating significant resolution of pathologic gene
circuits. A set of 2922 transcripts, which included S100 genes, keratins 6/16, and
innate defense products (cytokine-modulated genes in keratinocytes), were commonly regulated by ustekinumab or etanercept. The top 10 genes downregulated at
week 12 by ustekinumab overlap with nine of the top 10 genes down regulated by
etanercept at week 12; only two of the top 10 genes upregulated overlap (NTRK2,
THRSP) in this comparison. The genes upregulated by ustekinumab include a
number of keratin structural proteins indicating a unique effect of ustekinumab on
keratinocytes.
Conclusion: Elucidation of the common and unique effects of ustekinumab and
etanercept define critical pathways involved in psoriasis pathogenesis and a
successful therapeutic response. Broad genomic assessments provide an independent way to judge the extent to which disease pathology can be reversed by effective
therapeutics.
Commercial support: Centocor Research and Development, Inc.
Adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100
mg tablets compared to vehicle gel with doxycycline hyclate 100 mg
tablets in the treatment of severe acne vulgaris
Linda Stein Gold, MD, Henry Ford Health Systems, Bloomfield Hills, MI, United
States; Jean-Charles Dhuin, Medical and Marketing, Galderma, Sophia Antipolis,
Sophia Antipolis, France; Jerry Tan, Windsor Clinical Research, Windsor, Ontario,
Canada; Joseph Jorizzo, MD, Wake Forest University School of Medicine, Winston
Salem, NC, United States
A randomized, controlled, multicenter, double-blinded, parallel group study was
conducted to evaluate the efficacy and safety of adapalene 0.1%/benzoyl peroxide
2.5% gel with doxycycline hyclate 100 mg tablets, QD compared to vehicle gel with
doxycycline hyclate 100 mg tablets, QD in patients with severe acne vulgaris.
Patients used Cetaphil daily facial moisturizer with SPF 15 during the study. A total of
459 patients, aged 12 to 35 years with a minimum of 20 inflammatory lesions and
between 30 to120 noninflammatory lesions, were enrolled at 30 investigative sites
in the United States and five investigative sites in Canada. Patients were instructed to
apply the gel once daily in the evening and to take one tablet once daily in the
morning for 12 weeks. Study visits occurred at baseline and weeks 2, 4, 8, and 12.
A significant decrease in the median percent change from baseline in total lesion
count was observed in the patients treated with adapalene 0.1%/benzoyl peroxide
2.5% gel with doxycycline compared to those treated with vehicle and doxycycline
at all study visits (P\.001 for all time points; intent-to-treat population). At week 12,
a 64% decrease in the median percent change from baseline in total lesion count was
observed for the adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline
treatment group compared to a 41% decrease in the vehicle with doxycycline
treatment group (P \.001). This significant decrease from baseline in total lesion
count was seen as early as week 2 (e21% vs e13%; P \ .001) and continued
throughout the study. Treatment with adapalene 0.1%/benzoyl peroxide 2.5% gel
with doxycycline was also well tolerated and there were few cases (n ¼ 4, 1.7%) of
treatment-related dermatologic adverse events reported.
The results of this study demonstrated that adapalene 0.1%/benzoyl peroxide 2.5%
gel with doxycycline hyclate 100 mg tablets regimen was significantly superior to
vehicle gel with doxycycline hyclate 100 mg tablets in the treatment of severe acne
vulgaris.
Laboratories, L.P.
MARCH 2010
J AM ACAD DERMATOL
AB13
P702
P704
Trends in the treatment of acne vulgaris
Megan Kinney, WFU School of Medicine, Winston Salem, NC, United States; Alan
Fleischer, MD, WFU School of Medicine, Winston Salem, NC, United States; Brad
Yentzer, MD, WFU School of Medicine, Winston Salem, NC, United States; Steven
Feldman, MD, PhD, WFU School of Medicine, Winston Salem, NC, United States
Isotretinoin and association with depression
Victoria Chiu, MD, Saint Louis University Department of Dermatology, Saint
Louis, MO, United States; Amy Cheng, MD, Saint Louis University Department of
Dermatology, Saint Louis, MO, United States; Dana Oliver, MPH, Saint Louis
University Department of Dermatology, Saint Louis, MO, United States
Background: Acne vulgaris has been treated with long-term courses of antibiotics
since the 1960s. More than 20 years later, the problem of antibiotic resistance still
exists and practicing ecoresponsibility along with practicing medicine is the
responsibility of health care providers.
Background: Isotretinoin, a derivative of vitamin A, has been used to treat severe
cystic or recalcitrant acne since the early 1980s. Although the efficacy of isotretinoin
is well established in the treatment of acne vulgaris, its adverse side effect profile has
drawn attention from physicians and the public. Studies investigating the association between isotretinoin and depression have yielded mixed results. Much of the
evidence in support of an association between isotretinion and depression has been
in the form of case reports and adverse event reports sent to the FDA. More recent
evidence from prospective and retrospective reviews did not identify an association
between isotretinoin and depression. However, many of these studies have been
limited by their study design.
Purpose: The aim of this study was to assess current the current ecoresponsibility of
physicians treating acne vulgaris by looking at the trends in prescribing patterns
from 1997 to 2006.
Methods: The National Ambulatory Medical Care Survey (NAMCS) database was
analyzed for trends in prescriptions for acne vulgaris from 1997 to 2006. We
examined the recorded medications at all visits to the physician in which acne
vulgaris (ICD 9 code: 706.1) was the only diagnosis.
Results: Significant declines in the use of erythromycin and isotretinoin (both P \
.001) for acne were noted for all physicians. However, clindamycin, tetracyclines,
and benzoyl peroxide all had significant increases in prescription for acne (P \.001,
P ¼ .005, and P ¼ .020, respectively). Topical retinoids had significant increase in
utilization by dermatologists (P ¼ .032) but not by nondermatologists. The use of
topical retinoids by nondermatologists may even be on the decline (P ¼.067).
Conclusions: Antibiotic resistance is of paramount concern. We need to make other
specialties aware of retinoid use for acne therapy, use topical antibiotics in
combination with benzoyl peroxide to prevent resistance, and use oral antibiotics
for as short a time period as possible.
Objective: In this study, we examined an urban population of patients who are
taking isotretinoin for acne vulgaris and examined the rate of depression noted
during the treatment period. We especially focused on examining the subset of
patients who have a history or concurrent diagnosis of psychiatric illness before
being placed on isotretinoin therapy.
Methods: A retrospective chart review of the patients who were taking isotretinoin
from August 2005 to April 2009 from the outpatient clinics at Saint Louis University
Dermatology was performed for this study.
Results: A total of 163 medical records were reviewed for this study, of which 52.8%
(86) were male and 47.2% (77) were female. Most of the patients were white (89%)
and the subject ages ranged from 13 to 48 years old at the initiation of isotretinoin
therapy, with a mean age of 21 years. Eighteen (11%) patients were identified as
having a past or concurrent history of a psychiatric disorder. Of these 18 patients,
eight (44%) were diagnosed with attention deficit hyperactivity disorder, eight (44%)
with depression, one patient with Tourette syndrome, and one patient with bipolar
disorder. Six patients (4%) were noted to have mood changes during isotretinoin
therapy, and all presented with depressed mood. Only one of these patients had a
prexisting diagnosis of a psychiatric disorder before starting isotretinoin therapy,
and the diagnosis was attention deficit hyperactivity disorder. However, this patient
elected not to discontinue treatment and had resolution of his psychiatric
symptoms. Five of the patients reviewed (3%) were discontinued from isotretinoin
secondary to depression and none of these patients were identified with a
preexisting or concurrent psychiatric disorder prior to the start of therapy. In
addition, two out of these five patients were subsequently restarted on isotretinoin
by patient choice and did not report additional symptoms of depression. Most
patients (99%) experienced improvement of their acne while on isotretinoin, based
on clinician evaluation.
Conclusion: The association of isotretinoin and depression has been a controversial
topic for many years. In this limited review, we found that in our experience
isotretinoin use in patients with a history or concurrent diagnosis of a psychiatric
disease did not lead to the discontinuation of isotretinoin because of depressive
symptoms. Although it is important for clinicians to monitor for signs of depression
during the course of treatment, we hope to add to the evidence that there is not a
clear association between isotretinoin and depression.
P703
NB-003 activity against propionibacterium acnes in a pig skin model
Jessie Pannu, NanoBio, Ann Arbor, MI, United States; Alex Martin, NanoBio, Ann
Arbor, MI, United States; Ann McCarthy, NanoBio, Ann Arbor, MI, United States;
Joyce Sutcliffe, NanoBio, Ann Arbor, MI, United States; Susan Ciotti, NanoBio,
Ann Arbor, MI, United States
P705
Background: NB-003 is an antimicrobial oil-in-water emulsion in development for
the topical treatment of acne. NB-003 is formulated from materials included on the
US Food and Drug Administration’s list of inactive ingredients of approved drug
products. NB-003 contains nanometer-sized droplets that kill bacteria through lysis
of lipid membranes. NB-003 concentrates in the pilosebaceous unit and has potent
in vitro bactericidal activity against multidrug-resistant clinical isolates of P acnes.
NB-003 was evaluated in a pig skin model designed to mimic clinical studies that
measures the reduction of P acnes in human volunteers.
Methods: Full-thickness pig skin was obtained from a commercial source (Sinclair
Research Center) and stored at e70 8C until it was manually defatted before usage.
The surface was cleaned and a glass ring (2 cm in diameter) was attached to the skin
surface. The pig skin surface was inoculated with 106 to 107 cfu/cm2 of multidrugresistant P acnes and incubated under anaerobic conditions. One hour later, 50 L of
varying NB-003 concentrations, vehicle, or different commercial antiacne products
containing 2.5-5% benzoyl peroxide (BPO) were applied to the pig skin. After 1 or 24
hours of exposure to the test article, P acnes was collected from the swine skin using
two combined washes, and colony-forming units were then determined. Electron
microscopy was used to visualize killing of P acnes.
Results: A dose response in the reduction of surface P acnes on pig skin was
observed over the range of NB-003 concentrations tested (0.001% to 0.5% NB-003).
In 1 hour, 0.01% NB-003 reduced the P acnes colony counts by two logs and
concentrations $ 0.1% NB-003 resulted in $ 3.8-log reduction. BPO at 2.5%
(Proactiv repairing lotion) or 5% BPO (Clearasil cream) gave 2.5 to 2.6 log reduction
in P acnes (consistent with published data). Vehicle and 0.001% NB-003 had less
than a one-log reduction. For all treatment arms, no additional reduction was noted
in P acnes counts at 24 hours postapplication. Electron micrographs confirmed NB003 antimicrobial activity on pig skin.
Conclusions: NB-003 is more effective at reducing surface P acnes on pig skin than
commercial products containing BPO. NB-003 is currently being studied in a phase I
clinical trial to measure the reduction of facial P acnes.
Commercial support: NanoBio.
AB14
A 3-step acne system containing solubilized benzoyl peroxide versus
benzoyl peroxide-clindamycin in pediatric patients with acne
Lawrence Eichenfield, MD, Rady Children’s Hospital, San Diego, CA, United
States; Alan Shalita, MD, SUNY Downstate Medical Center, Brooklyn, NY, United
States; Diane Thiboutot, MD, Penn State University College of Medicine, Hershey,
PA, United States; Leonard Swinyer, MD, Dermatology Research Center, Salt Lake
City, UT, United States
Background: Solubility and stability challenges in formulating benzoyl peroxide
(BPO) may limit its bioavailability, follicular penetration, and antiacne efficacy.
Recently, a solubilized formulation of BPO has been developed which offers the
potential to help minimize these limitations. This solubilized BPO formulation is
available as part of a 3-step acne system for either normal to oily skin or normal to dry
skin.
Methods: In this pediatric subgroup analysis from a larger trial, 82 adolescents with
mild to moderate facial acne vulgaris were randomly assigned to receive 10 weeks of
treatment with one of the following: the 3-step acne system for normal to oily skin
(proprietary 2% salicylic acid cleanser twice daily, proprietary 2% salicylic acid toner
once daily, and solubilized 5% BPO gel twice daily) or control cleanser plus 5% BPO1% clindamycin gel twice daily.
Results: Compared with BPO-clindamycin, the 3-step acne system was significantly
more effective in reducing the number of noninflammatory lesions at weeks 2 and 4 (by
a mean of 32% vs 12%; P # .01 at week 4). The antibiotic-free 3-step acne system was
also comparably effective to BPO-clindamycin in reducing the number of inflammatory
lesions at all time points (by a mean of 40% vs 40%; NS at week 10). Both regimens were
generally well tolerated and mean levels of erythema, dryness, peeling, burning/stinging, and itching were less than mild at all time points in both groups.
Conclusions: The 3-step acne system is an effective and antibiotic-free treatment for
facial acne vulgaris. Compared with BPO-clindamycin, it can achieve significantly
greater reductions in the noninflammatory lesion count in the early weeks of
treatment, and comparable reductions in the inflammatory lesion count. It is likely
that these results can be attributable to the solubilization of the BPO enhancing its
bioavailability and follicular penetration.
Commercial support: Supported by OMP.
J AM ACAD DERMATOL
MARCH 2010
P706
P708
The aesthetic characteristics of a novel 6% benzoyl peroxide foaming
cloth may improve adherence to acne therapy
James Del Rosso, DO, Valley Hospital Medical Center, Las Vegas, NV, United
States
An open community-based trial with combination topical (1% salicylic
acid and 4% benzoyl peroxide/2% salicylic acid and 8% benzoyl peroxide)
and 5% tocopherol therapy for acne vulgaris
Todd Schlesinger, MD, Dermatology and Laser Center of Charleston, Charleston,
SC, United States; Otto H. Mills, Jr, PhD, UMDNJeRobert Wood Johnson Medical
Center, New Brunswick, NJ, United States; Rebecca Repaire, PA, Dermatology
and Laser Center of Charleston, Charleston, SC, United States
Salicylic acid and benzoyl peroxide have been mainstays of acne vulgaris therapy for
decades. Salicylic acid has a strong comedolytic effect that is produced by reducing
cellular adhesion and facilitates keratinocyte sloughing. Benzoyl peroxide exhibits
rapid antiproprionibacterial activity preventing any resistance making benzoyl
peroxide an effective long term therapy for acne vulgaris. Tocopherol is an
antioxidant and may reduce oxidative stress in the skin, thereby reducing inflammation. We conducted an 8-week open label trial in a private practice setting to
determine the efficacy of a combination therapeutic regimen involving these three
compounds. Subjects with mild to moderate facial acne vulgaris applied either 1%
salicylic acid with 4% benzoyl peroxide or 2% salicylic acid with 8% benzoyl
peroxide morning and evening, respectively, using a novel pad delivery system and
additionally applied 5% tocopherol supplied in a unique silicone capsule in the
morning post salicylic absorption. Subjects were evaluated at baseline and at weeks
2, 6, and 8. Efficacy endpoints included reduction in nominal and percent lesion
counts and Global Physician Evaluation Score. Local tolerability and safety were also
assessed. The results indicate that combination salicylic acid, benzoyl peroxide, and
5% tocopherol is an effective acne vulgaris therapy showing a reduction of
noninflammatory lesions (41%), inflammatory lesions (60%), and the Global
Physician’s Evaluation score (41%). Although there was an increase in the number
of macules, representing cleared inflammatory lesions, these were mildly erythemic. No treatment-related serious adverse effects were reported.
Background: With a prevalence of 70% to 85% among adolescents, acne vulgaris is
the most common skin disorder in the United States. Despite the widespread
availability of effective therapies, acne treatments fail in an estimated 10% to 15% of
patients because of noncompliance for reasons including dissatisfaction with drug
therapy products.
Objective: This study evaluated the aesthetic attributes of a novel benzoyl peroxide
(BPO) foaming cloth (Medicis Pharmaceutical, Scottsdale, AZ) and compared the
overall product satisfaction with two existing topical BPO acne products.
Methods: This randomized, single-blind study enrolled male and female subjects 17
to 30 years of age. Subjects initially cleansed their face with the BPO foaming cloth
and after 5 minutes were randomized to cleanse their face again using one of two
comparator BPO-containing cleansing products: a 6% BPO cleanser or a 4% BPO
wash. After washing with the BPO foaming cloth, subjects completed a 17-item
survey regarding various attributes of the product. After washing with a comparator
product, subjects completed an 11-item comparative survey. The survey results
were tabulated and a top two box analysis was performed. The study enrolled 69
male (36%) and 124 female (64%) subjects and most (73%) were 17 to 22 years old.
All subjects completed the study with no adverse events reported.
Results: The responses to 16 of 17 questions (94%) regarding the attributes of the
BPO foaming cloth attributes were positive (P # .05). The comparator survey
revealed that subjects found 11 of 11 (100%) attributes of the BPO foaming cloth
preferable to the 6% BPO cleanser and 10 of 11 (91%) attributes preferable to the 4%
BPO wash (for each, P # .05). Specifically, subjects consistently reported the
product cleansed well, washed off easily, and was more cosmetically elegant than
the other products. The BPO foaming cloth was also more convenient, portable, and
easier to use and aesthetically more appealing than the 4% BPO wash and 6% BPO
cleanser.
Conclusions: These results suggest that a novel BPO-containing foaming cloth has
several desirable attributes which make it superior to the available topical BPO acne
products tested. These attributes may increase patient satisfaction and improve
patient compliance with topical acne therapy.
In this open community-based efficacy trial, combination therapy with salicylic acid
1% pads, benzoyl peroxide 4% pads and tocopherol 5% capsules was effective in the
treatment of acne vulgaris with a favorable side effect and tolerability profile.
Commercial support: 50% JSJ Pharmaceuticals.
Commercial support: Sponsored by Medicis Pharmaceutical.
P709
Efficacy of a once-daily fixed combination clindamycin phosphate (1.2%)
and low concentration benzoyl peroxide (2.5%) aqueous gel across a
broad patient population with moderate to severe acne
Linda Stein-Gold, MD, Henry Ford Medical Center, Detroit, MI, United States;
Diana Chen, MD, Dow Pharmaceuticals, Redwood City, CA, United States; Fran
Cook-Bolden, MD, Department of Dermatology, New York, NY, United States;
Hilary Baldwin, MD, Department of Dermatology, Brooklyn, NY, United States
Background: The benefits of combination therapy for acne are well recognized.
Studies have shown that a fixed combination clindamycin phosphate 1.2%-BPO 2.5%
(clindamycin-BPO 2.5%) aqueous gel is an effective topical therapy for patients 12
years of age and older with moderate to severe inflammatory and noninflammatory
acne. The benefits also include once-daily application and excellent tolerability.
Objective: To evaluate the efficacy of clindamycin phosphate 1.2%-BPO 2.5% gel
across a broad patient population based on post hoc analyses by gender, ethnicity,
and race.
Methods: Two multicenter double-blind studies in 2813 subjects with moderate to
severe acne randomized 2:2:2:1 to receive clindamycin-BPO 2.5%, individual active
ingredients, or vehicle, once-daily for 12 weeks. Efficacy evaluations comprised
inflammatory, noninflammatory, and total lesion counts and evaluator global
severity score (EGSS) at baseline and weeks 4, 8, and 12. ‘‘Treatment success’’ was
based on at least a 2-grade improvement in EGSS.
P707
Topical retinoid flare analysis using the Weber-Fechner law
Norman Preston, PhD, Galderma Laboratories, Fort Worth, TX, United States;
Ronald W. Gottschalk, MD, Galderma Laboratories, Fort Worth, TX, United States
There is a belief that acne symptoms can flare during the early phase of topical
retinoid treatment, but the definition of a flare can be inconsistent among
physicians. Data from several phase II and phase III clinical trials were compiled
and compared to illustrate the inconsistency regarding the definition of flare. A flare
has been defined as an arbitrary 20% increase in inflammatory lesions from baseline.
The Weber-Fechner law can be used to measure clinical observations and states that
the magnitude of a sensation is proportional to the logarithm of the intensity of the
stimulus causing it. The Steven formula, which is based on the Weber-Fechner law,
demonstrates that a change is visually noticeable when log10R is at least 1 relative to
baseline lesion counts. Collectively, results from this analysis revealed that the 20%
change from baseline definition of flare may not match clinical observations in all
circumstances and that the Weber-Fechner law/Steven formula is a more reliable
analysis method which reduces the variability of lesion counting by approximately
five-fold.
Laboratories, L.P.
Results: At week 12, the median percent reduction in inflammatory lesion counts
relative to baseline in the female subpopulation (n ¼ 408) treated with clindamycinBPO 2.5% gel was 68.4% and 60.0% in males (n ¼ 389). This compared to 40.3% and
30.8%, respectively, in those treated with vehicle. The median percent reduction in
noninflammatory lesion counts was 50% (females) and 47.1% (males) compared to
34.1% and 23.5%, respectively, with vehicle. 37.7% of female and 31.9% of male
subjects treated with clindamycin-BPO 2.5% gel were considered ‘‘treatment
successes’’ at week 12 and 16.7% and 16.3%, respectively, with vehicle. In terms
of ethnicity, results showed treatment success with clindamycin-BPO 2.5% gel in
Hispanic/Latino subjects (n ¼ 124) was 38.7% at week 12 and 34.2% in the nonHispanic/Latino population (n ¼ 673). Rates for vehicle in the two groups (16.4%
and 16.5%) were similar. Treatment success with clindamycin-BPO 2.5% gel in white
subjects was 38.3% (n ¼ 618) and in black subjects was 27.3% (n ¼ 128). Rates for
vehicle were 16.1% and 19.1%, respectively.
Conclusions: Once-daily fixed combination clindamycin phosphate 1.2%-BPO 2.5%
aqueous gel is an effective topical therapy in patients 12 years of age and older with
moderate to severe inflammatory and noninflammatory acne. These post-hoc
analyses demonstrate effectiveness in a broad patient population.
Commercial support: 100% sponsored by Coria Laboratories.
MARCH 2010
J AM ACAD DERMATOL
AB15
P710
P712
Factors determining adherence to acne treatments: Results from an
international observational adherence study
Brigitte Dreno, MD, PhD, Department of Dermatology, Hotel Dieu, Nantes, France;
Alison Layton, Harrogate and District Foundation Trust, Harrogate, United
Kingdom; Andrew Y. Finlay, Cardiff University School of Medicine, Cardiff,
Wales, United Kingdom; James J. Leyden, MD, KGL, Malvern, PA, United States
Adapalene-benzoyl peroxide: A trans-Atlantic, randomized, double-blind,
controlled study in 1670 acne vulgaris patients
Harald P. M. Gollnick, Otto von Guericke Universität Magdeburg, Magdeburg,
Germany; Andrzej Kaszuba, DERMED Specjalistyczne Gabinety, Lodz, Poland; Les
Rosoph, North Bay Dermatology Centre, North Bay, Ontario, Canada; Zoe
Draelos, MD, Clinical Dermatology Center, High Point, NC, United States
The goals of this study were to measure adherence and identify major factors
influencing nonadherence to antiacne treatments in a cohort of patients treated
with topical and/or systemic treatments, using a validated questionnaire. This is a
cross-sectional survey of medical practices comprising a sample of dermatologists
and a cohort of acne patients returning to their dermatologist for a follow-up visit for
their acne. Evaluation criteria include level of nonadherence to current treatment
based on a validated adherence scale, sociodemographic criteria, acne characteristics, living habits, previous treatments, treatment underway at inclusion, clinical
improvement observed by the physician, patient’s level of understanding, satisfaction regarding acne and its treatments, and a patient quality of life questionnaire.
Results are presented for [3300 patients from 16 countries (United States, n ¼ 239;
Canada, n ¼ 89; Brazil, n ¼ 212; Chile, n ¼ 52; Colombia, n ¼ 39; Mexico, n ¼ 196;
Venezuela, n ¼ 125; Denmark, n ¼ 300; France, n ¼ 261; Norway, n ¼ 73; Spain, n ¼
428; Sweden, n ¼ 134; Hong Kong, n ¼ 22; India, n ¼ 778; Philippines, n ¼ 331;
Singapore, n ¼ 60). This cohort had an average age of 20.9 years (66.1), with 58%
female representation. Detected levels of nonadherence for each group within the
total cohort were: combination of topical 1 oral therapy (59%); topical monotherapy (39%); and oral isotretinoin monotherapy (46%). Factors with significant
(P # .05) correlation for nonadherence included: experience of at least one side
effect, presence of acne scars, poorer outcomes as assessed by the physician, and a
clinical decision to switch treatments. Higher patient DLQI scores (lower quality of
life) were associated with nonadherence (P \.001), as were poor perceptions of
self-knowledge about acne and/or the treatments, and low reported satisfaction
with the treatments. This is the first worldwide survey of adherence in acne. Levels
of detected nonadherence to treatment are high in all countries reported, but
surprisingly lowest with topical therapy. Finally, using multivariate analysis, patient
variables with an impact on adherence include age, satisfaction with treatment, and
knowledge about acne treatment and acne. Using comparative regional analyses, we
aim to identify country-specific differences that should be considered when trying
to improve adherence in acne patients. Further group analyses needs to be made at
the global and regional levels to understand specific differences.
The efficacy and safety of a once-daily, fixed-dose adapalene 0.1%-benzoyl peroxide
(BPO) 2.5% combination gel was evaluated when compared with the monads
(adapalene and BPO) and the vehicle, in the treatment of acne vulgaris for 12 weeks.
A North American and European multicenter, randomized, double-blind, parallel
group study was conducted in patients 12 years of age or older with moderate facial
acne vulgaris rated on the Investigator’s Global Assessment (IGA), 20 to 50
inflammatory lesions (IL), and 30 to 100 noninflammatory lesions (NIL). Efficacy
criteria included success rate (percent of patients with IGA rated clear or almost
clear) and percent change in IL, NIL, and total lesion counts. Safety evaluation
included assessment of local tolerability and adverse events. Of 1670 patients
enrolled, 87.4% completed the study. The mean age was 19 years and 56.2% of
patients were female. At the endpoint, success rate was significantly greater with
adapalene-BPO compared to adapalene, BPO or vehicle: 37.9%, 21.8%, 26.7%, and
17.9%, respectively (P \ .001). The net beneficial effect (active minus vehicle)
obtained from adapalene-BPO (20%) was greater than the sum of net benefits
obtained from the individual components (12.7%), indicating a synergistic therapeutic activity of these substances in a fixed-dose combination. The percent
reductions from baseline in IL, NL, and total lesions were significantly greater in the
adapalene-BPO group compared to the other arms (P \.001). Overall, slightly more
patients in the adapalene-BPO arm experienced local tolerability signs and symptoms compared to the other arms. However, these were transient and mostly mild or
moderate in severity. The unique and once daily fixed-dose combination of
adapalene and BPO provides significantly greater and synergistic efficacy in the
treatment of acne vulgaris combined with a good safety profile when compared to
the monotherapies and vehicle.
Laboratories, L.P.
Laboratories, L.P.
P711
A pivotal study comparing the efficacy and safety of the adapalenebenzoyl peroxide fixed-dose combination gel with each component and
the vehicle in 1668 patients with acne vulgaris
Linda Stein Gold, MD, Henry Ford Health Systems, Bloomfield Hills, MI, United
States; Jerry Tan, MD, Windsor Clinical Research, Windsor, Ontario, Canada; Kim
Papp, K. Papp Clinical Research, Waterloo, Waterloo, ON, Canada; Yves Poulin,
MD, Centre De Recherche Dermatologique Du Quebec Metropolitan, Quebec,
QC, Canada
International guidelines on acne management recommend the use of combinations
of agents with complementary mechanisms of action, because antiacne drugs when
used as monotherapy do not act against all of the major pathogenetic causes of acne.
A study was conducted to assess the efficacy and safety of a unique, once-daily, fixeddose combination gel containing adapalene 0.1% and benzoyl peroxide (BPO) 2.5%
in comparison to the monads (adapalene gel and BPO gel) and the vehicle in patients
with acne vulgaris for up to 12 weeks. In this multicenter, randomized, double-blind,
parallel group study, patients of either sex, 12 years and older with facial acne
vulgaris rated 3 (moderate) on Investigator’s Global Assessment (IGA) scale (ranging
from 0: clear to 4: severe), with 20 to 50 inflammatory lesions (IL), 30 to 100
noninflammatory lesions (NIL), no cysts and no more than 1 nodule were recruited.
Evaluations were performed at screening, baseline, and weeks 1, 2, 4, 8, and 12.
Primary efficacy criteria included success rate (percent of patients with IGA rated
clear or almost clear) and change in IL and NIL counts. Secondary criteria were
percent change in IL, NIL, and total lesion counts, change in IGA and patient’s
assessment of acne. Safety evaluation included assessment of local tolerability signs
and symptoms and adverse events monitoring. Other endpoints were Dermatology
Life Quality Index (DLQI) and treatment acceptability questionnaire. Of 1668
patients enrolled, 85.7% completed the study. Mean age was 18.2 years and 51.3% of
the patients were female. At endpoint, the success rate was significantly greater with
adapalene-BPO compared to adapalene, BPO or vehicle: 30.1%, 19.8%, 22.2%, and
11.3%, respectively (P # .006). Adapalene-BPO showed a greater mean reduction of
IL and NIL count compared to the three other treatment arms. A significant early
treatment effect of adapalene-BPO compared to the vehicle was observed as early as
week 1 (P \.001) for all lesion counts and week 4 (P # .004) for success rate, and
was sustained until the end of the study. The percent reductions from baseline in IL,
NL, and total lesions were significantly greater in the adapalene-BPO group
compared to the three other arms. All sensitivity analyses comparing adapaleneBPO to the three other arms were significant (P # .042). The results of the
questionnaires were similar among all treatment groups. Overall, more patients in
the adapalene-BPO arm experienced local tolerability signs and symptoms compared to the other arms. However, these were transient and mostly mild or moderate
in severity. The number of patients with a report of at least one adverse event was
similar across the all treatment groups. Adapalene-BPO gel is superior to the
individual components and gel vehicle in efficacy and has a rapid onset of
improvement. It provides the prescribing physician with a unique antibiotic-free
fixed-dose combination for the treatment of acne vulgaris.
Laboratories, L.P.
AB16
P713
Impact of acne vulgaris on the quality of life in patients from northern
Mexico
Alberto De La Fuente-Garcı́a, MD, Hospital Universitario ‘‘José E. González,’’
Servicio de Dermatologı́a, Monterrey, Nuevo León, Mexico; Jorge Garza-Gómez,
MD, Hospital Universitario ‘‘José E. González,’’ Servicio de Dermatologı́a,
Monterrey, Nuevo León, Mexico; Jorge Ocampo-Candiani, MD, Hospital
Universitario ‘‘José E. González,’’ Servicio de Dermatologı́a, Monterrey, Nuevo
León, Mexico; Minerva Gómez-Flores, MD, Hospital Universitario ‘‘José E.
González,’’ Servicio de Dermatologı́a, Monterrey, Nuevo León, Mexico
Introduction: Acne vulgaris (AV) is an inflammatory disorder of the pilosebaceous
unit affecting nearly 80% of individuals at some time in their lives. It is present in
almost all teenagers, affecting social and psychologic functioning. Patients often
show anxiety, depression, poor self-esteem, and report a poorer overall quality of life
(QOL). Although dermatologists have long recognized the impact of skin disease on
a patient’s life, it is only recently that QOL measures have been used as assessment
parameters in the management of chronic skin diseases. The Dermatology Life
Quality Index (DLQI) has been used in different skin conditions, including AV. It
consists of 10 questions concerning symptoms and feelings, daily activities, leisure,
work, school, personal relationships and treatment.
Objective: To determine the impact in the QOL from a Hispanic population with AV
and to compare the results with other studies.
Methods: Patients from both genders with AV who were attended by a dermatologist
for the first time were included. They were evaluated using the DLQI, giving a range
from 0 (no impairment of QOL) to 30 (maximum impairment). Patients with other
diseases or those with incomplete questionnaires were excluded. Acne severity was
classified according to the GLEA (Latin American Acne Study Group) classification.
Results: A total of 108 males and 126 females were evaluated, with mean ages of
20.78 and 19.55 years, respectively. The mean total score was 6.14 (SD 6 5.57).
Higher scores were associated with more severe acne in females and males, although
P values were not statistically significant in the latter. For both genders, the most
affected were those within the 31- to 35-year-old range and those with nodulocystic
and conglobata acne (P \.05). In general, the mean scores regarding symptoms and
feelings (2.12) had the greatest impact.
Conclusions: AV has a moderate effect on the QOL in Hispanics from Northern
Mexico, with variations compared with other studies. The impairment in QOL is
directly related with the severity of acne, especially in females, and in general with
aging. Our results highlight the importance of recognizing and managing the
psychologic burden in our acne patients, especially those regarding symptoms and
feelings.
J AM ACAD DERMATOL
MARCH 2010
P714
P716
An open-label study to assess efficacy and tolerability of tretinoin gel
microsphere 0.04% in a pump dispenser in early and preadolescents
Catalina Matiz, MD, Rady Children’s Hospital, San Diego, CA, United States; Ann
Funk, RN, Rady Children’s Hospital, San Diego, CA, United States; Lawrence
Eichenfield, MD, Rady Children’s Hospital, San Diego, CA, United States; Sara
Dill, MD, Rady Children’s Hospital, San Diego, CA, United States
Clinical morfology and ultrasound correlation in the assessment of acne
scars
Giuseppe Micali, MD, Dermatology Clinic University of Catania, Policlinico
‘‘Gaspare Rodolico,’’ Catania, Italy; Aurora Tedeschi, MD, PhD, Dermatology
Clinic University of Catania, Policlinico ‘‘Gaspare Rodolico,’’ Catania, Sicily, Italy;
Francesco Lacarrubba, MD, Dermatology Clinic University of Catania, Policlinico
‘‘Gaspare Rodolico,’’ Catania, Italy; Lidia Francesconi, MD, Dermatology Clinic
University of Catania, Policlinico ‘‘Gaspare Rodolico,’’ Catania, Italy
Acne scars (AS) are either the result of loss of or damage to tissue (atrophy) or
increased tissue formation (hypertrophy). Clinical manifestations and scarring
severity are generally related to the degree of inflammatory reaction, to tissue
damage, and to time lapsed since the onset of tissue inflammation. There have been
several attempts to standardize the classification of AS, however consensus
concerning nomenclature and classification is still a matter of debate. The
pleomorphic appearance of AS and the lack of an accepted assessment tool hamper
the development of new approaches to enhancement of standard clinical examination. The aim of this study is to correlate AS clinical and ultrasound appearance.
Twenty-six participants (16 males, 10 females; mean age, 27 years) affected by single
or multiple AS were evaluated. Based on the most common classification, AS were
distinguished as atrophic (icepick, boxcar, and rolling) or hypertrophic (hypertrophic and keloidal). Cross-sectional B-mode scans were obtained using a 22-MHz
ultrasound system allowing skin examination up to 12 mm in width and 8 mm in
depth. At ultrasound examination (UE) all atrophic scars (n ¼ 32) appeared as skin
invaginations of various shape and depth: icepick scars had a V-shaped appearance,
a narrow diameter at the surface (range, 2.0-2.3 mm; mean 2.16 mm) and a deep
vertical extension (range, 0.45-0.6 mm; mean 0.51 mm); boxcar scars had a
U-shaped appearance, a wide superficial diameter (range, 1.6-6 mm; mean 2.95
mm) and a variable vertical extension (range, 0.2-0.5 mm; mean, 0.32 mm); rolling
scars appeared as large (up to 5 mm), superficial, poorly demarcated skin
depressions; hypertrophic and keloidal scars (n ¼ 12) appeared as dome-shaped
localized increases in skin thickness. Our preliminary data show that rolling types
are relatively wider and more superficial AS. Boxcar and icepick AS are deeper with a
maximum depth of 0.5 and 0.6 mm, respectively. Of note, some boxcars and icepick
AS showed similar depth. These data suggest that UE may provide simple and
reproducible quantitative parameters that represent a promising tool for a more
accurate evaluation and classification of AS. Data derived from UE may also be
important for more focused therapeutic approach depending on lesion depth.
Further investigations in a larger subject population are in progress.
Background: While acne vulgaris is reported in[75% of children # age 12, there are
very few data assessing topical retinoid use in patients\12 years of age, even though
retinoids are often recommended as first-line therapy for acne.
Objective: The primary objectives of this study were to assess the degree of
improvement of facial acne vulgaris following treatment with TGM 0.04% in a pump
dispenser in patients 8 to 12 years of age, and to assess tolerability and safety of the
treatment in this population.
Methods: In this open-label study, patients 8 to 12 years of age with mild to moderate
acne vulgaris, defined by an Evaluator’s Global Severity Score (EGSS) between 2 and
3 (on a scale of 0-5), received TGM 0.04% in a pump dispenser for 12 weeks. Dosage
was two full pumps once daily at night (or as directed by the investigator) to the
affected facial areas. Patients were evaluated at baseline and at weeks 3, 6, and 12.
The primary efficacy endpoint was the change in the EGSS score at week 12; the
secondary efficacy endpoint was the Investigator’s Global Evaluation of treatment
response at week 12. Safety endpoints included cutaneous irritation as evidenced by
erythema, dryness, peeling, burning/stinging, and itching.
Results: A total of 40 patients were enrolled in this study and were included in the
ITT analysis. The mean age was 10.7 years; 33 patients were female and seven were
male. The majority were white (35%) or Hispanic (35%). Thirty-six patients
completed the study. While all patients experienced at least mild cutaneous
irritation that was more significant during the first 2 weeks of treatment, there
were no discontinuations related to adverse events. One patient was discontinued
because of a worsening of acne. The mean EGSS decreased significantly from
baseline to week 12 (2.1 vs 2.6; P\.001). The mean Investigator’s Global Evaluation
of treatment response for the 36 study completers was 3.39 at week 12, indicating
moderate improvement of acne.
Conclusion: TGM 0.04% in a pump dispenser was effective in the treatment of acne
vulgaris in this pediatric population, and the treatment was generally well tolerated.
Final data analysis will be presented at the meeting.
Commercial support: Ortho Dermatologics.
P715
Percutaneous collagen induction: A new treatment for acne scarring
Gabriella Fabbrocini, Department of Systematic Pathology, Division of
Dermatology, University of Naples ‘‘Federico II,’’ Naples, Italy; Anthony C. Chu,
Department of Dermatology, Hammersmith Hospital, London, Greater London,
United Kingdom; Benedetta Brazzini, Department of Dermatology, Hammersmith
Hospital, London, Greater London, United Kingdom; Maria Pia De Padova,
Ospedale Nigrisoli, Bologna, Italy
Background: Acne scars affect individuals of all races and ethnicities and are very
difficult to treat. Many treatments (ie, chemical peels, dermabrasion, invasive, and
noninvasive lasers, etc) are available and quite effective. However, these have a high
risk of side effects, especially for individuals with dark skin. Skin needling using
dermal rollers seems to be an effective and safe technique for the treatment of pitted
acne scarring in all skin types.
Aim: To confirm the efficacy and safety of skin needling in acne scarring in patients
with phototypes I to VI.
Methods: A total of 60 patients (36 females, 24 males; mean age, 27 years) were
included in this study: 10 were photoypes I to II (whites), 45 phototypes III to V
(Indians and Asians), and five phototypes VI (Afro-Caribbean). Each patient had
three treatments. Treatment was given every 4 to 12 weeks. In order to evaluate the
degree of improvement of the acne scars, digital photographs were taken. In
selective patients visioscan was used to directly measure the depth of the scars
before treatment, and 1 month after the third treatment. The aesthetic improvement
in each patient was evaluated by using the Global Aesthetic Improvement Scale
(GAIS). The photographic data have been analyzed by using the sign test statistic
(P \.05). Cutaneous casts’ data were analyzed by computerized image analysis (fast
Fourier transformation [FFT]).
P717
Efficacy, safety, and tolerability of two fixed-dose combination gels for the
treatment of acne vulgaris: results of the ‘‘DUETTA’’ study
Christos Zouboulis, MD, PhD, Dessau Medical Center, Dessau, Dessau, Germany;
Alessandra Alio, MD, Stiefel Research Institute, RTP, NC, United States
Objectives: Multiple pathophysiologic factors are associated with acne vulgaris.
Combination products have been developed to address several of these factors and
therefore to improve efficacy in the treatment of acne. This study was planned to
evaluate and compare the efficacy, safety, and tolerability of two marketed
combination products, namely a clindamycin phosphate 1%/benzoyl peroxide 5%
fixed-dose combination gel (BPO/C) and an adapalene 0.1%/BPO 2.5% fixed-dose
combination gel (adapalene-BPO) for the treatment of acne vulgaris.
Methods: Patients with mild to moderate facial acne were included in a multicenter,
investigator-blinded, parallel-group study and randomized (1:1) to BPO/C gel or
adapalene-BPO gel applied once daily in the evening for 12 weeks. The primary
efficacy outcome measure was the percent change in inflammatory lesion counts
from baseline to week 12. Additional key efficacy outcomes were the proportion of
subjects who achieved treatment success, defined as at least a 2-grade improvement
in Investigator’s Static Global Assessment (ISGA) score from baseline to week 12 and
the percent change in total and noninflammatory lesions counts from baseline to
week 12. Tolerability evaluations included investigator assessment of erythema,
drying, and peeling, and subject assessment of pruritus and burning/stinging. Safety
was evaluated by adverse event (AE) monitoring and withdrawals.
Results: Digital computerized analysis of patients’ photographs, supported by the
sign’s test, and irregularity degree analysis of surface microrelief, supported by FFT,
showed in most patients a reduction of the severity of the scars and an improvement
of the irregularity of skin texture. The aesthetic improvement was significant. No
side effects, such as hyper- or hypopigmentation have been observed.
Conclusions: This study shows that skin needling is a simple and safe modality for
acne scars. It improves skin appearance and quality without risk of hyper- or
hypopigmentation in patient with phototypes I to VI.
Acknowledgements: This study was conducted thanks to the contribution of Dr
Aikaterini Charakida, Professor A. Tosti, Professor G. Monfercola, and Mr Nunzio
Fardella.
Results: A total of 383 patients were enrolled. Greater reductions were observed in
inflammatory lesion counts in the BPO/C gel group than in the adapalene-BPO gel
group at week 12 (-76.1% vs -71.3%; P ¼ .076). Moreover, a significantly higher
proportion of subjects in the BPO/C gel group achieved ISGA treatment success
compared to the adapalene-BPO gel group (31% vs 22%; P \.05). Reductions in total
and noninflammatory lesion counts were similar between the treatment groups.
BPO/C gel showed a better tolerability profile, evidenced as early as week 1 and
maintained throughout the study. Application site related AEs were more frequent
for adapalene-BPO gel than BPO/C gel (78% vs 48%, respectively). In addition, severe
application-site related AEs were more frequent for adapalene-BPO gel as compared
to BPO/C gel (21% vs 5%, respectively).
Conclusions: The BPO/C fixed-dose combination gel was better tolerated and
provided greater overall improvement in the treatment of mild to moderate facial
acne vulgaris.
Commercial support: 100% is sponsored by Stiefel Laboratories.
MARCH 2010
J AM ACAD DERMATOL
AB17
P718
Time-release silica encapsulation in antiacne treatments
Avner Shemer, MD, Laniado Hospital, Netanya, Central, Israel; Daniela Mavor,
MBA, Sol Gel Technologies, Ness Ziona, Central, Israel; Eli Drori, MBBS, Sol Gel
Technologies, Ness Ziona, Central, Israel; Haim Barsimantov, Sol Gel
Technologies, Ness Ziona, Central, Israel; Ofer Toledano, PhD, Sol Gel
Technologies, Ness Ziona, Central, Israel
P720
The efficacy of benzoyl peroxide (BPO) for eradication of P acnes is well established.
Time-release encapsulation technologies in silica have been developed in order to
improve the efficacy, safety, and tolerability of BPO-based treatments.
Objective: This study compared efficacy, tolerability, and patients experience of two
antiacne treatment regimens (Kits) comparing Kits based on silica-encapsulated
BPO (Sol Gel Technologies [SGT], Israel) to commercially available Kits based on
nonencapsulated BPO (Guthy-Renker, Palm Desert, CA) (PRO) in mild to moderate
acne vulgaris patients.
Methods: The study was double-blind, controlled and randomized, 4-week, 4-arm
parallel groups. Seventy-eight eligible patients 16 to 35 years of age were randomized to receive one of the following Kits: SGT-7%BPO, SGT-4%BPO, PRO-7%BPO, or
PRO-2.5%BPO. Efficacy endpoints included nominal and percent reduction in lesion
counts (inflammatory, noninflammatory and total lesions, open and closed comedones) and dichotomized global severity assessment. Evaluation included both
superiority and noninferiority testing and analyzed in both intent-to-treat and perprotocol populations. Local tolerability and safety were assessed. Patients were
asked to complete a questionnaire after 1 and 4 weeks of treatment and indicate
their rating of treatment efficacy, tolerability and overall satisfaction. Evaluation was
based on a prospective cross-sectional survey.
Results: The group treated by SGT-7%BPO proved to be superior to PRO-7%BPO and
PRO-2.5%BPO by all efficacy parameters throughout the study (P ¼.047, P ¼.030).
Overall improvement by SGT-7%BPO reached 74.9% after 4 weeks. Tolerability
assessment indicated very high tolerability by all parameters for SGT-4%BPO
followed by SGT-7%BPO. Patient evaluations of efficacy and tolerability matched
closely those of the Principle Investigator. Satisfaction rates averaged 70.8% with
SGT-7%BPO and 76.5% with SGT-4%BPO after 1 week. At the end of treatment these
rates increased to an average 77.6% and 86.1%, respectively. The comparable
average satisfaction rates were 61.3% with PRO-7%BPO and 64.3% with PRO2.5%BPO, which decreased to an average 50.0% and 62.5% respectively.
Conclusions: Silica-encapsulated BPO-based treatment Kits tested in this study
improved their clinical outcome, tolerability, and patients’ satisfaction.
Commercial support: 100% is sponsored by Sol Gel Technologies.
AGING/GERIATRICS
P800
P719
Acneiform eruption in a newborn after steroid intravenous treatment
Ana Maria Mósca de Cerqueira, MD, Hospital Municipal Jesus, Rio de Janeiro,
Brazil; Ericka Andrade de Aguiar, MD, Policlinica Geral do Rio de Janeiro, Rio de
Janeiro, Brazil; Larissa Fernanda Campos Moreira, MD, Hospital Municipal Jesus,
Rio de Janeiro, Brazil; Soraya de S. Chantre Oliveira, MD, Hospital Municipal
Jesus, Rio de Janeiro, Brazil
Background: Acneiform eruption is much less common on young pediatric patients,
especially between 6 and 16 months of age; therefore, our knowledge about its
pathogenesis is limited, making it easy to diagnose but difficult to manage. The
patient’s age, the morphology of the injury, its distribution, and the presence of
itching are important factors for the differential diagnosis.
Methods: We present a 7-month-old male admitted with a case of pneumonia and
bronchiolitis showing no response with antibiotics and steroids intravenous
treatment. The patient was admitted on the Municipal Jesus Hospital and after the
third day, grouped vesicles on an erythematous base were disseminated throughout
the body. After examination, the conclusive diagnosis disseminated herpes simplex
infection. Systemic hypertension caused by acute adrenal insufficiency also
occurred. Fifteen days after the beginning of the treatment, he developed small
erythematous and itching folliculocentric papules on the cheeks and forehead, some
of then covered with hematic crusts; these also involved erythematous closed
comedones on the cheeks.
Results: The patient is being treated with benzoyl peroxide 2.5%, 2 hours a day,
showing satisfactory results.
Skin elasticity: Influence of age and regional body site
Stefanie Luebberding, University of Hamburg, Hamburg, Germany; Mareike
Oltmer, University of Hamburg, Hamburg, Germany; Martina Kerscher, MD,
PhD, University of Hamburg, Hamburg, Germany; Nils Krueger, MS, University of
Hamburg, Hamburg, Germany
Background: Skin elasticity is a very important function to protect skin against
mechanical effects and for the youthful appearance of the skin. The aim of this study
was to evaluate the influence of age and body site onto the biomechanical properties
of the skin in vivo.
Methods: One hundred twenty female subjects evenly distributed to four age groups
(I ¼ 18-29; II ¼ 30-39; III ¼ 40-49; and IV ¼ 50-65) were evaluated in vivo by suction
method (Cutometer MPA 580 with a 2-mm probe) on the cheeks, neck, cleavage,
volar forearm, and dorsal surfaces of the hands. While women in the age groups I to
III had to be in the follicular phase of their menstrual cycle, woman in age group IV
had to be postmenopausal. Hormone replacement therapies, treatments with
phytohormones, strong smoking habits, or extensive sun exposition were exclusion
criteria. All measurements were performed under standardized conditions at 20 8C
(688F) and 50% relative humidity.
Results: The data of 119 women aged 20 to 65 (Ø 39.6 6 12.4) were statistically
analyzed. The mean age in the four groups was 24.7 (group I), 33.1 (group II), 43.7
(group III), and 56.7 (group IV). The highest skin distensibility (Uf) was measured at
the neck. It showed a clear decrease at all sites from age group I to IV. While gross
elasticity (Ua/Uf) was high at neck, cleavage and forearm, pure elasticity (Ur/Ue) was
significant higher (P\ 0.001) at the neck than at all other sites. The loss in gross and
pure elasticity clearly correlated with age (r [ 0.4; P \.001).
Conclusions: The acneiform eruption is a side effect, widely known for the use of
corticosteroids, since the 1950s, but its occurrence in infants is rare. Discontinuing
the causative medication is the better therapy, if is possible. Treatment with benzoyl
peroxide 2.5% was effective in this case.
Conclusion: The results show a distinct influence of age and regional body site onto
the biomechanical properties of the skin in vivo. At all evaluated body sites skin
distensibility as well as gross and pure elasticity decreased significantly with age.
These data could be helpful to objectively show the effects of minimal invasive
procedures or cosmeceuticals influencing skin elasticity.
AB18
J AM ACAD DERMATOL
MARCH 2010
P801
P803
A single-blind pilot study of oral antioxidant supplementation on skin
aging parameters and age associated blood metabolites in female smokers
Anne Lynn Chang, MD, Redwood City, CA, United States; Claudia Munoz, MD,
MPH, Stanford University School of Medicine, Department of Dermatology,
Redwood City, CA, United States; Dale Kern, MS, Nuskin Enterprises, Provo, UT,
United States; Emily Gorell, Stanford University School of Medicine, Department
of Dermatology, Redwood City, CA, United States; Steve Wood, PhD, Nuskin
Enterprises, Provo, UT, United States
Background: Smoking has been associated with accelerated skin aging, thought to
be via several mechanisms including generation of oxygen free radicals leading to
changes in connective tissue production and breakdown.
Objective: To explore the effects of an oral supplement containing commonly
available antioxidants on clinical skin aging parameters and age-associated blood
metabolites in smokers versus nonsmokers.
Methods: Three-month, single-blind study of healthy female smokers (n ¼ 13) and
nonsmokers (n ¼ 17) 50 to 70 years of age with Fitzpatrick skin types I and II using a
daily oral supplement containing 2500 IU vitamin A, 500 mg vitamin C, 200 IU
vitamin E, 220 mg polyphenols, and 17.5 mg carotenoids. At baseline and 12 weeks,
all subjects were assessed for facial skin aging parameters via digital facial
photographs by a panel of 3 blinded dermatologists and by Visia scanning.
Elasticity was assessed by facial skin cutometry. Age-associated blood metabolites
were assessed using a commercially available biomarker platform.
Results: Smokers experienced significant improvements compared to nonsmokers
in a number of skin aging parameters. These include decrease in ultraviolet spots
and visible pores as assessed by Visia scanner (P ¼.031 and P ¼.030), and increase in
elasticity on cutometry (P ¼ .049). Overall, both smokers and nonsmokers had
increased glow as assessed by blinded dermatologists (P ¼.016). Blood levels of agerelated NADH oxidase (arNOX) were found to correlate with increased glow in
smokers (P ¼.024).
The effect of three topical treatments on desquamation rate using a
modified dansyl chloride fluorescence method
Margarita Yatskayer, L’Oréal Recherché, Clark, NJ, United States; Amanda Dahl,
L’Oréal Recherché, Clark, NJ, United States; Christian Oresajo, L’Oréal
Recherché, Clark, NJ, United States; Ronald Rizer, Thomas J. Stephens &
Associates, Colorado Springs, CO, United States
Conclusions: Oral supplementation with antioxidants may confer improved skin
appearance in individuals with metabolic stressors such as smoking. Additional
larger, well controlled studies are needed to confirm these findings.
Commercial support: This study was sponsored 100% by NuSkin International.
The shedding of stratum corneum cells (desquamation) represents a dynamic
process and is an integral aspect of epidermal physiology. Factors influencing
desquamation are complex, and are essential for the homeostasis of normal, healthy
skin barrier. Intrinsic factors contributing to desquamation rate include epidermal
basal cell replication and differentiation. Extrinsic factors contributing to desquamation rate include mechanical friction, exposure to contact irritants, and other
external stimuli. This study was designed to determine if topical experimental
treatments (lotions/creams) affect the stratum corneum replacement time in normal
human volunteers. We used the fluorescent reagent, dansyl chloride (5-dimethylamino-L-naphthalene-sulfonyl chloride), to stain the insoluble fibrous protein within
the keratin structure of the stratum corneum. A modified dansyl chloride fluorescence method was developed to enhance desquamation rate determination sensitivity, and complete a study in shorter time. Normally, the time when fluorescence
extinction occurs (process of desquamation of stained corneocytes) is directly
related to the rate of stratum corneum replacement. In this study, a new technique
was developed to establish stratum corneum replacement rate using ultraviolet (UV)
digital photography and determination of fluorescence saturation. The panel
consisted of 50 male and female subjects age 30 to 55 years of age. Subjects were
pretreated with the study products on the volar forearm for 1 week before dansyl
chloride patch application. UV photography was performed at approximately 4, 7,
9, and 11 days postpatch application. A Nikon D300 Digital SLR camera with a
Nikkor Micro AF 60 mm f/2.8D lens was used to image the test sites using UV light.
Subjects placed their arms into a proprietary device that eliminated all visible light
from the test areas. Digital photographs were analyzed for color saturation
(brightness).
Results of the study showed that establishing stratum corneum replacement time
using UV digital photography was effective in detecting the effect of topical
products on the desquamation rate. This new methodology has an advantage in that
it is able to determine stratum corneum replacement time in a shorter study period.
Using analysis of UV digital photographs enables us to improve desquamation rate
determination sensitivity, as well as removing the subjectivity of visual grading.
Commercial support: 100% is sponsored by L’Oreal.
P804
P802
A comparative study of the rheology and microstructure of hyaluronic
acid dermal fillers
Dave Stocks, Intertek MSG, Redcar, Cleveland, United Kingdom
Purpose: To compare the rheolologic properties of four commercially available
dermal fillers and predict product performance.
Introduction: The clinical performance (perceived feel and persistence) of
hyaluronic acid dermal fillers is believed to be dependant on its microstructure
and rheologic (flow) properties. An ideal rheologic profile for a dermal filler would
exhibit a high degree of elasticity (persistence and recovery) with yield like behavior
from a flat shear viscosity to a region where viscosity decreases with increasing
stress/shear rate. The material should also have the ability to resist permanent
destruction of the gel structure after being exposed to deformation such as injection
through a small-gauge needle.
Methods: This rheologic study was performed on controlled strain rate
(Rheometrics ARES) and controlled stress (Rheometrics SR5) rheometers with
parallel plate geometries at a test temperature of 24 8C. Parameters studied included
elastic modulus, complex viscosity, shear thinning profiles, stress relaxation
behaviour, strain amplitude dependency, and ‘‘recovery coefficients.’’
Results: Sample elasticity (gel performance and persistence)—the strain amplitude
dependence of the samples was performed at 24 8C and a fixed frequency (10
rads/s). The samples containing the hyaluronic acid in large particulate form
demonstrated a higher elasticity at low strain levels and a greater dependence of
elasticity on strain amplitude. Stress dependence/recovery profile (injectability and
gel strength)—the samples were compared on a controlled stress rheometer. Each
gel showed marked shear thinning behaviour indicating that these gels would be
able to be injected rapidly with minimum force. The recovery behavior of all four
samples was similar at lower temperatures but at higher temperatures the large
particulate samples showed superior performance. These samples also exhibited a
greater dependence of viscosity on both shear stress and rate.
Conclusion: Samples A and B are more elastic and hence form stronger gels. Stronger
gels enable more defined particles to be manufactured. The greater elasticity of large
particulate dermal filler would be expected to lead to better product performance
(ie, improved lift and persistence).
Commercial support: This research study was sponsored by Medicis
Pharmaceutical.
Topical turmeric extract in a moisturizing cream formula reduces the
appearance of facial spots and fine lines and wrinkles on human facial
skin
Cheri Swanson, PhD, The Procter and Gamble Company, Cincinnati, OH, United
States; Denny Deng, PhD, The Procter and Gamble Company Far East, Beijing,
Haidian District, China; Larry Robinson, PhD, The Procter and Gamble Company,
Cincinnati, OH, United States; Patricia Raleigh, The Procter and Gamble
Company, Cincinnati, OH, United States
Background: Turmeric (Curcuma longa) has a long history of use in Ayurvedic
medicine and is known for its potent antiinflammatory and antioxidant properties.
Despite reported efficacy, the use of turmeric in topical products has been limited
due to its bright yellow color, characteristic odor, and stability constraints. Here we
evaluate a stable, almost colorless turmeric extract in a moisturizing cream and
demonstrate its ability to provide facial appearance benefits.
Objective: Two separate clinical studies were performed to evaluate the efficacy of
turmeric extract in cream formulation on the appearance of facial hyperpigmentation and fine lines and wrinkles.
Methods: In the first clinical study, white women were subjected to a double-blind,
10-week, left-right randomized, split-face study that evaluated turmeric extract in
combination with niacinamide in cream formulation compared to a niacinamide
only control. The study entailed a 2-week washout followed by 8 weeks of twice
daily topical product application. The second clinical study was performed in
Beijing, China, and subjected Asian women to a double-blind, 9-week, left-right
randomized, split-face study to evaluate the effects of a cream formulation
containing only the turmeric extract. The study consisted of a 1-week washout
followed by 8 weeks of twice daily topical product application. Images of each
subject from both studies were captured at weeks 0 (baseline), 4, and 8 and were
analyzed for changes in spot area fraction (SAF) using REAL or NC2 image analysis,
and were also evaluated by expert graders for improvements in the appearance of
fine lines and wrinkles. All changes were calculated relative to baseline.
Results: In the study of white patients, the formulation containing the combination
of turmeric extract and niacinamide was significantly better at reducing the
appearance of fine lines and wrinkles than the formulation containing only
niacinamide at 4 weeks (P ¼ .004), directionally better at 8 weeks (P ¼ .125), and
significantly better overall (P ¼.009) as judged by expert graders. In the Asian study,
the formulation containing only turmeric extract reduced the appearance of
hyperpigmented spots by 14.16% (P \ .0001) at 4 weeks and by 14.91% (P \
.0001) at 8 weeks as measured by NC2-spot area fraction versus baseline.
Conclusion: Significant improvements in the appearance of fine lines and wrinkles
and the reduction of hyperpigmented spots were observed from moisturizing
creams containing turmeric extract.
Commercial support: This work was fully funded by P&G Beauty.
MARCH 2010
J AM ACAD DERMATOL
AB19
P807
P805
Comparison of a multiproduct cosmetic regimen versus 2% hydroquinone
for improving the appearance of facial hyperpigmentation in Chinese
subjects
Gang Deng, PhD, Procter & Gamble Technology Company, Beijing, China; Joseph
Kaczvinsky, PhD, The Procter and Gamble Company, Cincinnati, OH, United
States; Yan Wu, MD, Peking Unversity First Hospital, Beijing, China; Ziyi Wang,
Procter & Gamble Technology Company, Beijing, China
Background: Light and even facial skin tone is a key patient concern in China. There,
as elsewhere, hydroquinone is the treatment most prescribed by dermatologists to
improve the appearance of skin hyperpigmentation. However, the use of hydroquinone can cause irritation and other side effects in some patients. A cosmetic regimen
focused on improving hyperpigmentation was recently developed, including
products containing niacinamide, n-acetyl-glucosamine, hexamidine, and undecylenoyl phenylalanine. To assess its potential as an alternative treatment for
hyperpigmentation, the efficacy and tolerance of this regimen relative to hydroquinone was evaluated in Chinese subjects in Beijing.
Objective: To compare the efficacy of the cosmetic tone regimen (CTR) versus 2%
hydroquinone (HQ) treatment for reduction in thr appearance of hyperpigmented
facial spots and improvement in overall skin tone. A comparison of the relative skin
tolerance of the two treatments was a second objective.
Method: One hundred sixty-one Chinese female subjects with facial hyperpigmentation were treated for 12 weeks with either the four product CTR or 2% HQ. The
CTR consisted of two products used on the entire face in the morning and evening, a
daytime moisturizing sunscreen (SPF 30) and a targeted product used twice a day on
hyperpigmented facial spots. HQ was used on hyperpigmented facial spots in the
evening, with subjects using an SPF 30 moisturizing sunscreen in the morning.
Digital images of subjects were taken at baseline and after 2, 4, 8 and 12 weeks of
treatment. Cross-polarized and melanin-specific images were analyzed for changes in
area of hyperpigmented spots, L*a*b* values and melanin distribution. Treatment
tolerance was assessed via investigator irritation grading and by changes in skin
barrier function (trans-epidermal water loss [TEWL]).
Results: Treatment with either the CTR or HQ significantly (P \.05) reduced the
area of pigmented, melanin-related spots, lightened skin and improved skin tone
evenness relative to baseline over the entire study period. Skin yellowness was
significantly reduced by both treatments after 8 weeks. There were no significant
differences in improvement between the two treatments for any of these parameters. Irritation from the two treatments was similar and the CTR significantly
reduced facial skin TEWL relative to HQ after 4 weeks’ treatment (P \.05).
Conclusion: Overall, the observed efficacy and tolerance of the two treatments were
comparable.
Commercial support: Research was fully supported by the Procter and Gamble
Company.
P806
The use of topically dissolved oxygen as a pluripotent raw material
ingredient for medical aesthetic products
Lawrence Rheins, PhD, Aria Aesthetics, Scottsdale, AZ, United States
The second decade of the 21st century will continue to see the development of
innovative topical medical aesthetic products to address the growing older ‘‘baby
boomer’’ population. Continued optimization/innovation of minimal to moderate
invasive cosmetic procedures will continue, but for many aging patients comorbidities will limit the utility of these procedural technologies. As a result, safe and
efficacious topical approaches for cosmesis treatments will remain a mainstay of
aesthetic medicine. Patient desire for the incorporation of natural ingredients must
be considered in these development strategies. The utilization of topically dissolvable oxygen (TDO) meets the needs of both the patient and the health care provider.
There remains a growing interest in topical oxygen for a variety of common
dermatologic conditions, with antiinflammatory, antimicrobial, and extracelluar
matrix (ECM) as only a few reported experimental effects. TDO provides a
pluripotent mechanistic approach (eg, cellular energy, antiinflammationin, antimicrobial, protein turn-over effects, and cell to cell communication) to address
photodamage and other conditions associated with extrinsic aging. TDO is safe, and
is not associated with the other attendant issues of oxygen stability or release that
were associated with earlier perfluorcarbon oxygen technologies. Historically,
hyperbaric oxygen (HBO) has and continues to serve as a vital treatment modality in
chronic wound care but is impractical for cosmesis. The role of TDO in other
epicutaneous applications including cosmetic treatments will be discussed here. A
polyacrylate hydrophilic polymer impregnated with oxygen as a medical device
(FDA 510(k) clearance, 09/19/08) when applied in vitro to intermediate thickness
viable donor skin resulted in rapid oxygen penetration extending beyound 600
microns, a depth that had not previously been reported in the literature. When
compared to oxygen alone as a control under standard atmospheric pressure there
was an 32% increase in treatment vs control (P \.05). The oxygenation effect was
still evident at 90 minutes. In addition, in vitro dermal fibroblast cell cultures under
hypoxic conditions revealed long term (144-hour) protection of fibroblast metabolism, including cell viability and protein content with continuous oxygen
admistration. The TDO-treated group showed an increase in fibroblast viability
(92% greater than hypoxic cells and 28% greater than normoxic cells [P \.001]).
The enzymatic release of the TDO and desired epidermal/dermal penetration can be
controlled with this technology. This is important, when evaluating for example, the
Grenz zone as a microanatomic marker for changes in collagen synthesis associated
with cosmetic reparative approaches for aging skin. The reliability of the
H202/catalyst compartmentalization provides multiple/optimal approaches for
cosmetic products (eg, facial masks), with continuous oxygen release. The potential
mechanism(s) of action that are associated with continuous topical oxygen as a
micronutrient will be discussed.
Commercial support: 75% Aria Aesthetics Inc, 25% I-Flow Corporation.
AB20
P808
The activation of the ubiquitin-proteasome system protects significantly
from UV damage in vivo study
Claude Dal Farra, PhD, ISP Corporate Research Center, Wayne, NJ, United States;
Catherine Gondran, MBA, Vincience ISP Global Skin Research Center, Sophia
Antipolis, Alpes Maritimes, France; Gilles Oberto, MBA, Vincience ISP Global
Skin Research Center, Sophia Antipolis, Alpes Maritimes, France; Jean-Marie
Botto, PhD, Vincience ISP Global Skin Research Center, Sophia Antipolis, Alpes
Maritimes, France; Nouha Domloge, MD, Vincience ISP Global Skin Research
Center, Sophia Antipolis, Alpes Maritimes, France
The ubiquitin-proteasome system is an essential mechanism for maintaining cell
integrity because of its role in eliminating abnormal and damaged cell proteins.
Through aging, the synthesis and activity of this system decrease, leading to the
accumulation of damaged proteins that impair cell function, which accelerates
aging. In this study, we evaluated the beneficial effects of activating the ubiquitinproteasome system, using a previously described inducer (IV08.013). Twelve
volunteers participated in this double-blind study. They applied, twice a day, the
inducer-containing cream, or placebo, on a defined zone of the thigh for a week,
followed by full solar spectrum irradiation of 2 MED. Volunteers continued to apply
creams for 3 more weeks. Skin condition was evaluated by TEWL, in vivo confocal
microscopy (vivascope) assessment, and by clinical examination. From day 8 on the
induced side, TEWL studies revealed a significant decrease of TEWL measures (P ¼
.0323), indicating better barrier function. Interestingly, this effect was also seen after
UV stress. TEWL was significantly reduced on the irradiated-induced side (P ¼.0113)
at day 16 and (P ¼.0225) at day 23, suggesting significant UV protection of epidermal
functions and integrity on the ubiquitin-proteasome activated side. Vivascope study
revealed that UV damage was remarkably reduced on the induced side at all time
points, as revealed by stratum corneum thickness and stratum granulosum cell
shape and morphology. Observation and quantification of sunburn cells showed
significant reduction on the induced side, and similar results were obtained with
other signs of UV damage, such as vacuoles and edema, which were significantly
reduced. Clinical examination revealed a significant increase in the healthy appearance of the skin, and hydration and radiance, which were visible after 2 weeks of
study on 83% of volunteers. These results confirm the ubiquitin-proteasome
system’s key protective roles in skin biology and photoaging.
J AM ACAD DERMATOL
MARCH 2010
P809
P811
Aconitase plays a key role in reducing skin oxidative stress and damage
Jean-Marie Botto, PhD, Vincience ISP Global Skin Research Center, Sophia
Antipolis, Alpes Maritimes, France; Claude Dal Farra, PhD, ISP Corporate
Research Center, Wayne, NJ, United States; Eric Bauza, MBA, Vincience ISP
Global Skin Research Center, Sophia Antipolis, Alpes Maritimes, France; Gilles
Oberto, MBA, Vincience ISP Global Skin Research Center, Sophia Antipolis, Alpes
Maritimes, France; Nouha Domloge, MD, Vincience ISP Global Skin Research
Center, Sophia Antipolis, Alpes Maritimes, France
Oxidative stress generates mitochondrial DNA alterations and damage, therefore
compromising the cellular respiration process. In response to oxidant accumulation, cells have developed an ‘‘oxidative stress response’’ in which aconitase seems
to play an important role by triggering survival functions. We evaluated hydrogen
peroxide (H2O2) cytotoxicity on human skin fibroblasts in culture, grown for 48
hours with or without 1% of the IV08.001 compound, which has been previously
shown to enhance total cellular aconitase expression and activity. After 30 minutes
of 5 mM H2O2 treatment, fibroblasts were allowed to recover for 2 hours in medium
containing or not containing compound IV08.001. Free radical production was then
evaluated by dihydroxy-ethidium staining and subsequent analysis by flow cytometry. Aconitase-stimulated cells showed a significant reduction in the production of
free radicals when fibroblasts were pretreated for 48h before the application of
H2O2. In this study, the observed level of ROS production was less (-16%) than that of
the control condition. An 8-day in vivo study was also conducted with IV08.001
compound, versus placebo, on 12 healthy volunteers. In vivo confocal microscopy
(Vivascope) at days 0, 6, and 7 and 24 hours after UV (2 DEM of full spectrum solar
light), allowed comparison between placebo and aconitase-induced epidermis. At
days 6 and 7, we observed nice conserved structure with an improvement of
granular cell morphology on the aconitase-induced side, demonstrating skin with a
healthier appearance, compared to the placebo-treated side. Moreover, UV-generated damage, such as sunburn cells, vacuoles, and edema, was less apparent on the
aconitase-induced side. A Vivascope was used to quantify results and revealed a 61%
decrease of sunburn cells on the aconitase-induced side, which confirmed the
overall protective role of aconitase against UV damage.
Improving the appearance of wrinkling and puffiness of the eye area skin
using a pigmented foundation with SPF 20 and skin benefit agents
Kristine Schmalenberg, PhD, Johnson & Johnson, Skillman, NJ, United States;
Judith Nebus, Johnson & Johnson, Skillman, NJ, United States; Warren Wallo,
Johnson & Johnson, Skillman, NJ, United States; Yohini Appa, PhD, Neutrogena
Corporation, Los Angeles, CA, United States
Clinical evaluations, ophthalmologist evaluations, self-assessments, and digital
photography demonstrated skin benefits throughout the study. Clinical evaluations
indicated significant improvements (P \.05) in under-eye puffiness and wrinkles in
the crow’s feet area immediately after application of the eye foundation. Significant
improvements (P\.05) in the above parameters, with an additional improvement in
dark circles were observed through the 4-week time point even without the
foundation present. Patients perceived significant (P \ .05) improvements in
textural parameters and moisturization immediately after use, while improvements
in skin brightness, dark circles, and under-eye puffiness were noted as early as
1 week. Digital photographs also confirmed improvements in under eye puffiness.
In conclusion, this clinical study showed that an eye foundation containing a blend
of soy, yeast extract, and antioxidants was effective in reducing under-eye puffiness,
improving the look of dark circles, skin brightness. and fine wrinkling.
Commercial support: Johnson & Johnson.
With their busy schedules, women are looking for facial cosmetic products that not
only offer coverage but also conveniently deliver multiple skin benefits. A previous
clinical study in a serum form revealed that this unique blend of soy, yeast extracts,
and antioxidants has antiaging benefits. This optimal combination product adds sun
protection and pigments to even and enhance skin tone and provide natural-looking
coverage. With daily use, the skin enhancing ingredients help deliver antiaging
benefits, such as improving the appearance of fine lines, dark circles, and puffiness.
This clinical study evaluated the efficacy of an eye foundation with SPF 20 containing
a unique blend of skin enhancing ingredients on eye area skin. Forty healthy female
subjects between the ages of 18 and 44, with under eye puffiness, dark circles, and
moderate fine lines and wrinkles in the crow’s feet area completed this 4-week study.
Patients used the foundation once a day.
P810
Clinical evaluation of a novel eye cream containing b-C-xyloside, blueberry extract, and caffeine on under eye dark circles and puffiness
Margarita Yatskayer, L’Oréal Recherché, Clark, NJ, United States; Amanda Dahl,
L’Oréal Recherché, Clark, NJ, United States; Christian Oresajo, L’Oréal
Recherché, Clark, NJ, United States
The purpose of this study was to evaluate the efficacy and tolerance of an eye cream
containing 4% blueberry extract, 5% Pro-xylaneÔ (b-C-xyloside), and 0.2% caffeine
in improving the visible signs of aging, under-eye dark circles, and puffiness. A 12week, single center clinical study of 53 male and female subjects, age 41 to 65 years
old was conducted. The subjects recruited had Fitzpatrick skin classification I to IV,
and 50% of the study population had self-perceived sensitive skin. Subjects exhibited
mild to moderate periocular fine lines and wrinkles, mild to moderate under eye
dark circles caused by poor circulation, and mild to moderate under-eye puffiness.
The eye cream was used two times daily, in the morning and evening. Efficacy and
tolerance were assessed at baseline (pre- and posttreatment) and weeks 4, 8, and 12
posttreatment. The clinical study included clinical assessment, noninvasive bioinstrumental evaluation, digital imaging, and subject self-assessment questionnaires.
Clinical assessment included evaluation of the under eye area for dark circles,
puffiness, even skin tone, radiance, skin crepyness, tactile skin smoothness, tactile
firmness/elasticity, and periorbital fine lines and wrinkles, as well as overall
appearance of the eye area. Bioinstrumental evaluation included skin viscoelastic
properties, skin capacitance measurements, and blood flow mapping. Self-assessment questionnaires were administered to evaluate the perceived efficacy of the
product by the subjects. Statistically significant improvements compared to baseline
were observed for dark circles, puffiness, and tactile firmness/ elasticity after 4, 8,
and 12 weeks of product use. For under-eye radiance, skin tone, crepyness, and
tactile smoothness a statistically significant improvement compared to baseline was
observed immediately after a single application, and after 4, 8, and 12 weeks of
product use. In the periorbital area, statistically significant improvements compared
to baseline were observed for fine lines and wrinkles immediately after a single
application, and after 4, 8, and 12 weeks of product use. Objective and subjective
evaluations showed that the eye cream containing 4% blueberry extract, 5% ProxylaneÔ (b-C-xyloside), and 0.2% caffeine was well tolerated by the study panel.
Commercial support: 100% is sponsored by L’Oreal Research and Development.
P812
Glycolic acid peels and effective home care products rejuvenate skin and
complement the benefits of injectable fillers and botulinum toxin type A
in the treatment of photoaged skin
David Wrone, MD, Princeton Dermatology Associates, Princeton, NJ, United
States; Barbara Green, MS, NeoStrata Company, Princeton, NJ, United States;
Brenda Edison, NeoStrata Company, Princeton, NJ, United States; Colleen Crane,
NeoStrata Company, Princeton, NJ, United States
Treatment of skin aging in the dermatologist’s office frequently involves the
combination use of several different modalities to obtain the best results for
patients. Injectable therapies including fillers and botulinum toxin type A are
primarily used by physicians to improve rhytides. While injectable therapies
effectively address one major sign of aging, they do not address other important
signs, such as rough skin texture, mottled pigmentation, or reduced luminosity. Fine
lines present on the noninjected areas of the face become relatively more prominent
after localized therapy. Topical therapy has advanced greatly to safely address the
shortcomings of injectable therapies. For example, free acid glycolic peels, along
with citric acid booster peels produce profound desirable changes in the skin. They
exfoliate while stimulating cell renewal and dermal biosynthesis to provide
antiaging effects on skin. A series of free acid glycolic acid peels reduces skin
roughness while imparting a fresh luminous finish. Skin clarity is improved along
with a reduction in dyspigmentation. The peels act to soften the appearance of fine
lines and wrinkles. Combining injectable therapies with AHA peels in conjunction
with daily use of effective homecare products between treatments helps achieve
more complete skin rejuvenation and enhances patient satisfaction. This poster will
present cases involving combination therapy demonstrating compatibility of
superficial AHA peels when combined with injectables, as well as patient selfassessed improvements.
Commercial support: 100% is sponsored by NeoStrata Company, Inc.
MARCH 2010
J AM ACAD DERMATOL
AB21
P813
Fullerene is effective against wrinkles
Takahiro Fujimoto, MD, PhD, MBA, Clinic F, Chiyoda-ku, Tokyo, Japan; Hikaru
Taira, PhD, Vitamin C60 BioResearch Corporation, Chuo-Ku, Tokyo, Japan;
Masayuki Ito, Vitamin C60 BioResearch Corporation, Chuo-Ku, Tokyo, Japan;
Nobuhiko Miwa, PhD, Prefectural University of Hiroshima, Shobara, Hiroshima,
Japan; Yasukazu Saito, PhD, Prefectural University of Hiroshima, Shobara,
Hiroshima, Japan
Reactive oxygen species and lipid hydroperoxide, which are produced by ultraviolet
light, damage skin cells and collagen and elastic fibers in the dermis, leading to
wrinkle formation. Antioxidants such as vitamin E or C, LASER therapy, or botulinum
toxin are used for wrinkle therapy. Among these, antioxidant-containing cosmetics
are the easiest to use. Fullerene (C60), a carbon allotrope, has been reported to
exhibit antioxidant activity. Compared to other antioxidants, fullerene shows higher
thermostability, photostability, and antioxidant activity. Thus, fullerene may be
highly useful in preventing many skin problems related to oxidative stress. We
evaluated the potential of fullerene for protecting skin and preventing wrinkles by
conducting clinical tests. In addition, the combination of fullerene and LASER
therapy was assessed for wrinkle therapy. Fullerene was dissolved in squalane,
which is commonly used in cosmetics. To experimentally prove the effectiveness of
fullerene/squalane, an 8-week double-blind clinical test was conducted on 23 female
volunteers aged between 30 and 40 years according to the Japanese guidelines for
the evaluation of antiwrinkle creams. A test cream sample containing approximately
2 ppm fullerene in squalane was prepared. The percentage wrinkled area and
average wrinkle depth were measured by visual analysis. We found that the
percentage wrinkled area was significantly reduced in the fullerene/squalene
cream-treated area compared to the placebo-treated area. LASER therapy is a useful
anti-wrinkle therapy but may lead to the generation of free radicals from the
chemicals in the cream. We measured the free radicals generated by LASER
irradiation of squalane. Squalane or fullerene/squalane was introduced into a flatquartz cell, containing 10 L 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spintrapping agent. The sample was irradiated several times with an Affirm laser system
(1440 nm; Cynosure Inc; 3 J/cm2), which supposedly reduces wrinkles by fractional
technology. Then, the amount of free radicals was measured by electron paramagnetic resonance (EPR). LASER irradiation of squalane generated a significant amount
of hydrogen and methyl radicals, whereas that of fullerene/squalane suppressed free
radical generation under the same conditions. Thus, fullerene/squalane can be used
for antiwrinkle treatment, and fullerene may be useful for care after antiwrinkle
LASER treatment.
or medical association committees. Of the subset of 21 respondents that had
participated in the ADLP, 86% had current careers in academic dermatology. In
contrast, of the 80 respondents who had not participated in one of the programs,
14% served on an AAD committee, 1% chaired an AAD committee, 9% served on a
state, local dermatological society, or medical association committee, and 10%
chaired such a committee. Eighty-nine responded that aspects of participation in the
program had a direct impact on their involvement in a leadership role, while 12
reported it did not.
Conclusions: The goal of the AAD’s leadership program is to assist in developing
leadership skills. There is a high correlation between attendance at the conferences
and serving in a leadership role in dermatology, and a marked difference when
comparing this to the nonparticipants. A high correlation of ADLP participation
with current careers in academic dermatology is also evident. Additional data from
the survey demonstrated a large percentage of participants felt the course directly
impacted their involvement in a leadership role, rated value in the courses, and
reported relevance of the skills learned to their actual leadership roles. This data
supports the effectiveness of the AAD’s leadership programs in providing early
career leadership training and fostering leaders in the field of dermatology.
BASIC SCIENCE
ART, HISTORY, AND HUMANITIES OF
DERMATOLOGY
P900
Preliminary results on AAD formal leadership training programs for early
career dermatologists
L. Katie Morrison, MD, Wright State University, Dayton, OH, United States; David
Carr, MD, Wright State University, Dayton, OH, United States; Michael Heffernan,
MD, Wright State University, Dayton, OH, United States; Mary Maloney, MD,
University of Massachusetts, Boston, MA, United States; David Marks, MD,
Geisinger Medical Center, Danville, PA, United States
Background: In 2002, the American Academy of Dermatology (AAD) held the first of
its annual leadership training conferences, which through continued evolution has
come to be called the Leadership Forum (LF). This program was targeted toward
early career dermatologists to foster development of future leaders at the local, state
and national levels. In 2005, a year-long Academic Dermatology Leadership Program
(ADLP) was initiated. This program enabled a selected subset of the LF participants
who were in the first 8 years of an academic dermatology career to receive additional
mentoring and leadership training with a goal of promoting academic retention.
Objective: The purpose of this study was to analyze the effectiveness of the
leadership programs (LF and ADLP) at leadership development in early dermatology
careers and fostering careers in academic dermatology.
Methods: In 2007, a Web-based survey regarding current and previous roles in
leadership positions in dermatology, involvement in academia, and attitudes about
the AAD leadership programs was e-mailed to 302 previous ADLP and/or LF
participants, and randomly to 1000 AAD members, which yielded 182 usable
responses. We undertook analysis of this data to evaluate if there were correlations
between participation in the conferences with involvement in leadership positions,
current involvement in academic dermatology, and if there was a reported impact on
participant’s leadership roles.
Results: Of these respondents, 58% (103) had participated in one of the leadership
training conferences, and 42% (79) had not. Of those 103 participants group, 54%
were in academic dermatology positions. Fifty-five percent served on an AAD
committee, 17% chaired an AAD committee, 26% served on dermatologic societies
AB22
P1000
Hair follicle markers, expression and modulation: Studies on human scalp
skin grafts
Catherine Gondran, MBA, Vincience ISP Global Skin Research Center, Sophia
Antipolis, Alpes Maritimes, France; Armelle Perrin, MBA, Vincience ISP Global
Skin Research Center, Sophia Antipolis, Alpes Maritimes, France; Céline
Meyrignac, MBA, Vincience ISP Global Skin Research Center, Sophia Antipolis,
Alpes Maritimes, France; Claude Dal Farra, PhD, ISP Corporate Research Center,
Wayne, NJ, United States; Nouha Domloge, MD, Vincience ISP Global Skin
Research Center, Sophia Antipolis, Alpes Maritimes, France
Understanding the roles of different hair follicle components and the possibilities for
acting on them are key challenges in hair biology. Working with cells isolated from
the different compartments of the hair follicle fails to take into account the
complexity of the interactions which take place within it. For this reason, in the
present study, we used a model of human scalp skin grafts, placed in emersion on a
culture insert, and fed with a previously described serum-free medium. In order to
test the reactivity of this model, we applied two molecules; one activates cAMP, and
the other ATP, on the top of scalp biopsies for 48 hours. At the end of the incubation,
scalp grafts were paraffin-embedded or frozen in OCT, to perform immunohistochemical analyses. Our studies showed that stimulating cAMP in the samples
induced an increase in keratin 14, keratin 15, and keratin 16 in the outer root sheath
(ORS). This outcome could be relevant for hair growth and for the quality of the
anchoring of the hair. We also observed an increase in collagen IV and laminin-332,
indicating reinforcement of the basement membrane, and better communication
between the ORS and dermal sheath. A different set of markers, including beta1 integrin, fibronectin, Ki67, and P63, was modulated by ATP induction. These
results suggest an optimized cell matrix adhesion and enhanced cell signaling in the
hair follicle. Moreover, further study results on beta-1 integrin and p63 (identified as
potential markers for hair follicle stem cells) were in favor of a positive effect of hair
follicle ATP induction on hair renewal and growth cycle maintenance.
Consequently, this model of human scalp grafts seems appropriate to observe the
modulation of different hair follicle components, which could be essential for hair
vitality and regeneration.
J AM ACAD DERMATOL
MARCH 2010
P1001
P1003
Inhibition of Staphylococcus aureus abscess formation by nitric oxide
releasing nanoparticles
George Han, MS, Albert Einstein College of Medicine, Bronx, NY, United States;
Adam Friedman, MD, Albert Einstein College of Medicine, Bronx, NY, United
States; Luis Martinez, PhD, Albert Einstein College of Medicine, Bronx, NY,
United States
Cultured media from adipose-derived stem cells promotes fibroblasts
proliferation, migration, and matrix metalloproteinase expression
Kyu-Suk Lee, DO, Department of Dermatology, School of Medicine, Keimyung
University, Daegu, South Korea; Jae-We Cho, MD, PhD, Department of
Dermatology Keimyung University School of Medicine, Daegu, South Korea;
Jun-Il Kwon, MD, Department of Dermatology Keimyung University, School of
Medicine, Daegu, South Korea
Objective: To investigate the effects of cultured media (CM) of adipose-derived stem
cells (ADSCs) with or without transforming growth factor-beta (TGF-b) in biology of
cultured human skin fibroblasts, especially in the aspect of fibroblast proliferation,
migration, collagen synthesis, and matrix metalloproteinase (MMP) expression.
Methods: ADSCs were cultured with or without TGF-b and then CM were harvested.
The CM or TGF-betreated CM were added into fibroblats and the proliferation,
migration, collagen synthesis, and MMPs expressions were confirmed by proliferation, migration assay, Western blot, and RT-PCR analysis.
Results: The proliferation and migration rates were increased by CM-treated
fibroblasts and TGF-betreated-CM. There were no dramatic differences between
two conditions. The markedly increased expression of MMP-3 was observed in both
CM or TGF-betreated CM. However, the expression of type I collagen were not
markedly increased by CM or TGF-betreated CM.
Methicillin-resistant Staphylococcus aureus (MRSA) has drawn widespread attention as a major cause of both nosocomial and, more recently, community-acquired
cutaneous infections, such as impetigo, cellulitis, and abscess formation. With
respect to MRSA abscesses, treatment is difficult both because of poor clearance of
bacterial load secondary to limited drug penetration into the acidic wound site and
bacterial enzymes that interfere with antibiotic efficacy. As such, recurrences are
quite common, serving as a source of high morbidity and possibly even mortality.
Nitric oxide (NO), a critical component of innate host defense known to have broad
antimicrobial activity, has documented efficacy against MRSA. We previously
showed that a novel NO releasing nanoparticle system is efficacious against MRSA
infected excisional wounds. To further investigate the potential therapeutic role, the
effectiveness against MRSA induced abscesses was evaluated. In vitro anti-staphylococcal activity of NO releasing nanoparticles (NO-np) was confirmed both in
bacterial culture and in a fibroblast model. Reduction of abscess erythema, size, and
bacterial load was shown after the administration of NO-np 1 day after initial abscess
formation in vivo as compared to controls. To both further understand the
mechanism of action and to elucidate the physiologic role of NO in pathogen
response, we monitored cytokine levels in both treated and control MRSA abscess
murine models. TH1 cytokines IL-12, IFN-g, and TNF-a were all increased in the NOnp treated samples as compared to controls, while IL-10, a known TH2 cytokine
responsible for inhibition of a TH1 response, was decreased in this treatment group.
In addition, both pro-TH1 inflammatory mediators IL-1b and MCP-1 as well as TGF-b,
an important NO stimulated mediator in orchestrating the wound healing response,
were upregulated as compared to controls while IL-4, associated with a TH2
response, was unchanged. Together, these data suggest that not only does this NO
releasing platform offer new approach in the treatment of abscesses, but may serve
as a model through which we further characterize the regulatory mechanisms
involved in nitric oxide related wound repair and bacterial response.
Conclusion: Collectively, these data suggest that CM or TGF-betreated CM from
ADSCs promotes fibroblasts proliferation, migration, and MMP-3 expressions.
However the effect of collagen synthesis of CM or TGF-betreated CM still remains
to be elucidated. Our data indicate the CM or TGF-betreated CM from ADSCs will be
promising agent for wound healing.
P1002
Biomarker analysis confirms the antioxidant and antiinflammatory activity of a colorless turmeric extract in vitro
Cheri Swanson, PhD, The Procter and Gamble Company, Cincinnati, OH, United
States; Deborah Finlay, PhD, The Procter and Gamble Company, Cincinnati, OH,
United States; L. Timothy Laughlin, PhD, The Procter and Gamble Company,
Cincinnati, OH, United States; Michael Robinson, PhD, The Procter and Gamble
P1004
Results: Turmeric extract showed statistically significant antioxidant activity in both
the glutathione reductase and ARE assays (187% and 1060% vs control, respectively;
P \.02). Biomarker studies showed corresponding upregulation of 11 antioxidant
genes responsible for sensing and responding to oxidative stress or reducing
oxidative species. In parallel, a significant downregulation of genes involved in the
production of nitric oxide and other cellular markers of stress was observed.
Turmeric extract showed significant antiinflammatory activity in both the COX2
(74%; P \.01) and neutrophil elastase assays (IC50 ¼ 0.001%). Biomarker studies
revealed a corresponding upregulation of five antiinflammatory genes and a
corresponding downregulation in proinflammatory genes and inflammatory transcription factors and regulators.
In conclusion, antioxidant and antiinflammatory properties of turmeric extract
were confirmed and corresponding gene-related mechanisms of action for these
activities were identified.
Histologic differences in extracellular matrix protein expression in
photoprotected and photoexposed skin of Whites, East Asians, and
African Americans
Runa Sur, PhD, Johnson & Johnson Consumer Companies, Skillman, NJ, United
States; Anna Vorobyeva-Schiano, Johnson & Johnson Consumer Companies,
Skillman, NJ, United States; Jared Fantasia, Johnson & Johnson Consumer
Companies, Skillman, NJ, United States; Michael Southall, PhD, MS, Johnson &
Johnson Consumer Companies, Skillman, NJ, United States; Theresa Chen, PhD,
Johnson & Johnson Consumer Companies, Skillman, NJ, United States
While skin color is the most notable difference among ethnic skins, many other
differences exist in the structure and function of ethnic skins. Unfortunately, the
current knowledge of physiologic and pathologic properties of the skin is based
mainly on skin studies of white patients. Elucidating differences among ethnic skins
is not only of great biologic importance but is also of great interest in skin care
improvement. We therefore sought to evaluate the differences in extracellular
matrix protein expression and distribution in skin of white, East Asian, and African
American individuals. The study was conducted at Lynchburg, VA, on 35- to 45-yearold females from three different ethnic groups: whites, East Asians, and African
Americans (n ¼ 10 per ethnic group). A 2-mm punch biopsy specimen was obtained
from the inner upper arm (photoprotected site) and from the dorsal surface of the
forearm (photoexposed site) from individuals on a single visit. The histologic
endpoints assessed for comparison included elastin, tropoelastin, and collagen. The
findings from this study showed that in photoprotected skin of white subjects, the
expression of tropoelastin, which is the precursor to the elastin molecule, was
substantially less than in age-matched East Asian and African American skin.
Interestingly, in white skin there was a greater expression of tropoelastin in
photoexposed skin compared to photoprotected skin, and a greater expression of
tropoelastin in photoexposed white skin compared to photoexposed skin of East
Asian and African Americans. Expression of tropoelastin in photoexposed skin of
East Asian and African American subjects were similar to their photoprotected skin,
suggesting that in these ethnic subjects photoexposure did not effect tropoelastin
formation to the same extent as white subjects. In addition, the skin of East Asian and
African American subjects in this study had a greater level of elastin precursor than
age- and gender-matched white subjects. The levels of extracellular matrix protein,
such as elastin, have been shown to decrease with age resulting in a loss of elasticity
and sagging of the skin. The results suggest that East Asian and African American
subjects may have less age-dependent loss of elasticity than white subjects.
Commercial support: This work was funded entirely by P&G Beauty.
Commercial support: Supported by Johnson and Johnson.
Background: Turmeric (Curcuma longa) has a long history of use in Ayurvedic
medicine for its potent antioxidant and antiinflammatory properties. In vitro
evaluation of topically applied turmeric allows for mechanistic-specific analyses in
these pathways and gene expression analysis provides a further look into specific
genes linked to antioxidant and antiinflammatory activity.
Objective: Turmeric extract was evaluated in vitro for glutathione reductase
activation, antioxidant response element (ARE), cyclooxygenase 2 (COX2) inhibition, and neutrophil elastase inhibition. Biomarker analysis was used determine
corresponding gene expression activity.
Method: Glutathione reductase activation was measured by coupling the reduction
of glutathione with NADPH. ARE was measured by transfecting ARE-32 reporter
cells (CXR-Biosciences) with pGL8x-ARE and a luciferase reporter. COX 2 inhibition
was measured colorimetrically by monitoring the appearance of oxidized N, N, N’,
N’-tetramethyl-p-phenylenediamine (Cayman Chemical). Neutrophil elastase
(Biomol) was assayed using small peptide substrate and detecting release of paranitroanilide. Biomarker analysis was performed on reconstituted human epidermis
(SkinEthic, France) topically dosed with turmeric extract. RNA was isolated from
cultured cells and Affymetrix GeneChip technology was used to identify relevant
gene activity (P \.01 and fold change [2).
MARCH 2010
J AM ACAD DERMATOL
AB23
P1005
P1007
Sertaconazole nitrate mediates its antiitch activity by inducing PDG2 via
the p38 MAPK pathway
Simarna Kaur, PhD, Johnson & Johnson Consumer Products, Skillman, NJ, United
States; Frank Liebel, Johnson & Johnson Consumer Products, Skillman, NJ,
United States; Michael Southall, PhD, Johnson & Johnson Consumer Products,
Skillman, NJ, United States; Runa Sur, PhD, Johnson & Johnson Consumer
Products, Skillman, NJ, United States
Sertaconazole nitrate (STZ), a broad-spectrum antifungal agent, has recently been
shown to exhibit antiitch activity; however, the signaling pathways that mediate this
action are unknown. Therefore, to elucidate the cellular mechanism behind this
activity, the effects of sertaconazole nitrate were examined in vitro and in vivo. We
used compound 48/80, an agent known to induce itch and promote the release of
histamine, in RBL-2H3 mast cells to mimic a pruritic response, and observed that
sertaconazole nitrate induced PGD2 production. PGD2 is known to have antipruritic activity by suppressing histamine release. Similar results were obtained in the
macrophage cell line, RAW-264.7, when lipopolysaccharide (LPS)-stimulated PGD2
levels were further enhanced by sertaconazole. In order to dissect the pathway
involved in PGD2 production, an inhibitor of p38 MAPK, SB203580, was used along
with the aforementioned secretagogues. Blocking the p38 MAPK pathway eliminated PGD2 induction in both cell lines. Furthermore, using a murine model of
pruritus we showed that compound 48/80-induced scratching was successfully
reduced by the topical application of sertaconazole nitrate. This effect was reversed
by the addition of ibuprofen or a PGD2 receptor antagonist, confirming that
sertaconazole-induced PGD2 production was responsible for inhibiting the itch
response. Thus, the antipruritic activity of sertaconazole nitrate is mediated by the
induction of PGD2 through the p38 MAPK pathway.
Understanding sunscreens: The proposed FDA rule on UVA assessment
and labeling will drive US sunscreens towards a uniform UVB/UVA
protection profile
Uli Osterwalder, MS, Ciba, Basel, AL, United States; Bernd Herzog, PhD, Ciba,
Grenzach-Wyhlen, Baden-Würtenberg, Germany; Olga Dueva-Koganov, PhD,
Ciba, Tarrytown, NY, United States
Prevention of sunburn, photoaging, and eventually skin cancer is practiced in most
cultures by avoiding the sun and covering up (ie, solar radiation is reduced uniformly
without preference for either UVB or UVA). Consequently, the spectrum of solar
radiation to which the human skin has adapted to is essentially maintained. Yet with
the introduction of topical UV-sunscreens and more so with the sunburn protection
factor (SPF) relating mainly to UVB, this protection became biased towards UVB This
imbalance fostered ideas that extensive use of sunscreens may rather promote than
prevent skin cancer. As early as 1991, Diffey advocated for uniform UV protection as
the ideal sunscreen—this at a time when the importance of UVA in photoaging and
skin cancer was not yet of general consideration. In the meantime, the damaging
effect of UVA radiation has become generally accepted. In parallel, specific
procedures for UVA assessment are becoming international recognition.
Nonetheless, only few sunscreens provide uniform UV protection. The FDA
Proposed Rule, published in the Federal Register, 27 Aug 2007 would require US
sunscreen manufacturers to declare, in addition to the SPF, the degree of UVA
protection expressed in five categories; no, low, medium, high, and highest UVA
protection. Sunscreen fulfilling the ‘‘highest’’ UVA category (4 stars) is very close to a
uniform sun protection profile. Calculations of the sunscreen performance on the
skin (in silico) show that a four-star sunscreen transmits 10 times less UVA-I radiation
than a 1-star sunscreen. In silico simulations of typical US sunscreen compositions
show which UV filter combinations provide broad-spectrum UV protection. To date
it is mainly the content of the UVA filter avobenzone up to the maximum allowed
concentration 3 % that determines the degree of UVA protection of a US sunscreen.
Moreover simulations show that uniform sun protection cannot be achieved, at high
SPF, the highest UVA category with an in vitro ratio UVA-I/UV [ 0.95 cannot be
achieved with the UV filters available to date. In contrast modern European
sunscreens that can contain avobenzone (up to 5%) and broad-spectrum UV filters
such as bisoctrizole or bemotrizinol (both allowed up to 10%). If such sunscreens
fulfill the highest Boots UVA star rating criteria of 5 stars with a UVA/UVB ratio [ 0.9
that is used in Great Britain, they will putatively comply with the US highest (4 stars)
criterion. The rirst in vitro applications of the proposed FDA UVA method are in line
with our silico results.
Commercial support: Johnson & Johnson Consumer Products WW.
Commercial support: All authors are full-time employees of Ciba.
P1008
P1006
Novel follicular-targeted nanoemulsions for acne
Susan Ciotti, NanoBio, Ann Arbor, MI, United States; James R. Baker Jr, NanoBio,
Ann Arbor, MI, United States; Lyou-fu Ma, NanoBio, Ann Arbor, MI, United States;
Rone Eisma, NanoBio, Ann Arbor, MI, United States
Background: Acne vulgaris is a common condition caused by the blockage of
pilosebaceous units with proliferation of P acnes bacteria leading to unsightly,
inflamed lesions primarily on the face, neck, and back. The effectiveness of acne
treatments have been limited by the ability to permeate into the pilosebaceous unit.
A novel antibacterial nanoemulsion (NB-003) composed of nanometer-sized droplets that physically disrupt P acnes was investigated in the hamster ear model for its
ability to permeate the pilosebaceous unit.
Methods: In vitro skin permeation studies with several different NB-003 formulations (eg, lotions and gels) were performed using hamster ear as the skin model.
Nanoemulsions with entrapped fluorescein or green fluorescent protein were
assayed at various time points (4, 24, and 48 hours) under varying dosing conditions
(QD vs BID). Residual test article was removed by rinsing and swabbing. Hamster ear
skin was cryosectioned to 7-m sections and viewed under a fluorescent microscope. The permeation of NB-003 was assessed by measurement of a chemical
marker for the emulsion droplets, cetylpyridinium chloride (CPC), by HPLC
following dissection of sebaceous glands from hamster ears. The levels of NB-003
were analyzed in surrounding tissues (eg, epidermis dermis, dorsal ear) by
measurement of CPC content.
Results: Fluorescence micrographs showed permeation of NB-003 into the entire
pilosebaceous unit. All pilosebaceous units in the examined fields showed evidence
of NB-003 uptake. There was an increase in the delivery of CPC to the sebaceous
glands with increasing concentrations of NB-003 at 24 hours that appeared to
plateau at the 0.5% NB-003 concentration.
Muscle contractility reduction via the application of low temperatures
Michael Hsu, PhD, MyoScience, Redwood City, CA, United States; Francis R.
Palmer, MD, Beverly Hills International Center for Aesthetic Surgery, Beverly
Hills, CA, United States; Vic Narurkar, MD, Bay Area Laser Institute, San
Francisco, CA, United States; Wm. Philip Werschler, MD, Spokane Dermatology
Clinic, Spokane, WA, United States
Background: A novel, minimally invasive, percutaneous technology has been
developed to reduce muscle contractility with potential application in the reduction
of dynamic facial wrinkles. The device (MyoScience, Redwood City, CA) reduces
muscle activity by applying controlled low temperatures to targeted muscle groups
via needle-like probes. The thermal algorithm is designed to reduce the muscle fiber
count and weaken the muscle temporarily, without causing long-term chronic
changes in the tissue. Optimal treatment efficacy depends on the total volume of
affected tissue, which is determined by the temperature dosage delivered through
the device. These studies were undertaken to establish correlations between
treatment temperature and physiologic and histologic outcomes in a murine model.
Methods: Preclinical studies were conducted in Swiss-Webster white mice which
underwent treatment to the gastrocnemius muscle. Animals survived for up to 6
weeks posttreatment. Muscle function was assessed daily using the Digit Abduction
Scoring (DAS) assay, and tissue specimens were explanted for histologic evaluation
at weekly intervals.
Results: Treatment with the test device produced effective muscle weakening in the
murine model for approximately 3 weeks with gradual return to normal muscle
function. Adjustment to colder temperatures yielded an increase in efficacy and
duration of effect. Probe temperatures of -10 8C, -20 8C, and -30 8C created
progressively larger regions of affected tissue, and correlated to progressively more
profound muscle weakening (higher DAS scores) and a slower return to baseline
function. Myofiber regeneration leading to complete restoration of normal muscle
fiber size and density occurred within 5 to 6 weeks posttreatment for all temperatures studied. No systemic effects were observed at any point in any of the animals.
Conclusions: These data suggest that NB-003 specifically targets the pilosebaceous
unit achieving high concentrations where acne begins. The concentrations of NB003 are well above the MBC for P acnes, providing a potential acne therapy. NB-003
is currently being studied in a phase I clinical trial to measure the reduction of facial
P acnes.
Conclusions: These preclinical data demonstrate that the device is able to temporarily reduce muscle contractility by application of mild low temperatures, with an
inverse correlation between treatment temperature and degree and duration of
effect. Recovery of normal muscle function and morphology and the absence of any
systemic effects were observed for all temperatures studied.
Commercial support: 100% is sponsored by MyoScience, Inc.
AB24
J AM ACAD DERMATOL
MARCH 2010
P1009
P1011
Effect of topical antiaging products on stratum corneum thickness and
barrier integrity
Joseph Kaczvinsky, PhD, The Procter and Gamble Company, Cincinnati, OH,
United States; Jim Li, MS, The Procter and Gamble Company, Cincinnati, OH,
United States; Jonathan Crowther, PhD, The Procter and Gamble Company,
Egham, Surrey, United Kingdom; Sue Mirkovic, The Procter and Gamble
Company, Cincinnati, OH, United States; William Janson, MS, The Procter and
Gamble Company, Cincinnati, OH, United States
Background: Confocal Raman microspectrometry (CRM) has become an established
in vivo technique for determining stratum corneum (SC) thickness. This spectroscopic method can noninvasively determine the concentration of specific chemical
compounds in the skin as a function of depth. SC thickness is determined via the
shape and dimensions of the water concentration profile from the skin’s surface to
the point it becomes constant in the viable epidermis.
Retinyl rice branate: Epicutaneous and instrumental noninvasive assessment of irritation potential and efficacy profile
Joan Vilaplana, MD, PhD, Hospital Clı́nic de Barcelona, Barcelona, Spain; José
Ginestar, PharmD, Antonio Puig, S.A., Barcelona, Spain; Mar Recasens, PhD,
Antonio Puig, S.A., Barcelona, Spain
Objective: In this study, the effect of chronic treatment with each of three different
antiaging products on SC thickness was determined via CRM. Improvements in
barrier function accompanying changes in SC thickness were assessed using TEWL
measurements. The products tested included (1) a moisturizing cream containing
niacinamide and hexamidine, (2) a moisturizing serum containing niacinamide,
Lys’lastine, peptides and caffeine, and (3) a lotion containing alpha lipoic acid.
Method: Volar forearm sites on 36 female subjects were treated two times per day for
4 weeks. Subjects applied ;2 mg/cm2 of product to a randomized site (4 sites per
subject). One site per subject was left untreated as a control. CRM profiles and TEWL
measurements at each site were taken at baseline and after 4 weeks’ treatment and
changes in SC thickness and barrier function from baseline were determined.
Results: Four weeks’ treatment with each of the three products thickened the SC
relative to baseline. The niacinamide/hexamidine cream and niacinamide/Lys’lastine
serum both produced statistically significant (P \.05) plumping of the SC relative to
both no treatment and the lipoic acid cream. Thickening from the lipoic acid cream
was not statistically significant relative to no treatment. The niacinamide/Lys’lastine
serum plumped the SC the most (;8.6%) which was numerically, but not
significantly, greater than that from the niacinamide/hexamidine cream. All three
products also significantly (P \.05) reduced TEWL after 4 weeks treatment relative
to no treatment. Reductions from the two niacinamide containing products were
significantly better than that from the lipoic acid cream.
The aim of this study is to evaluate and to compare the in vivo irritation of retinoic
acid derivatives such as retinoic acid (0.2%), retinal (1%), retinol (1%), retinyl
palmitate (2%), and a proprietary mixture of retinyl esters (retinyl rice branate), and
to assess by in vitro methods the efficacy of the mildest ones. The irritation
capacities were measured by visual score in a 48-hour patch test on 25 volunteers
and by noninvasive bioengineering techniques including transepidermal water loss
(TEWL), stratum corneum hydration, cutaneous blood flow (CBF), and skin
erythema by a color measurement. Retinoic derivatives were incorporated in an
O/W emulsion and tested for their physico-chemical stability during the study. At the
studied concentrations, a weak irritation of retinoic acid, retinal, and retinol was
observed. Retinyl esters such as retinyl palmitate and retinyl rice branate did not
show any irritation potential. A further study was performed in order to evaluate
their in vitro efficacy. Cell renewal was evaluated on HaCaT culture cells after 72
hours of treatment with retinyl palmitate and retinyl rice branate at the same
concentration. Cell viability and procollagen type I synthesis were evaluated on
human dermal fibroblast after two radiations (5 J/cm2 UVA) over 2 consecutive days
followed by posttreatment with the same actives. In the HaCaT cells proliferation
study, the best results are achieved by the retinyl rice branate. In addition, this
treatment also produces the best human fibroblast restoration and the highest
procollagen type I synthesis after UVA irradiation. Retinyl rice branate promotes
HaCaT cell proliferation, human fibroblast cell renewal, and a procollagen type I
synthesis.
Commercial support: Antonio Puig, S.A.
Conclusion: CRM is an effective tool for differentiating product-induced thickening
of the SC. Products containing niacinamide and hexamidine or niacinamide and
Lys’lastine plumped the SC, and did so significantly better than a lipoic acid product.
Changes in SC thickness may be associated with improvement in barrier function.
Commercial support: Research was sponsored and funded by the Procter &
Gamble Company.
P1012
P1010
Ethnic patterns in response to retinol: An ex vivo study
Gaelle Bellemere, Johnson & Johnson Consumer France, Val De Reuil, Normandy,
France; Jared Fantasia, Johnson & Johnson Consumer Companies, Skillman, NJ,
United States; Theresa Chen, Johnson & Johnson Consumer Companies,
Skillman, NJ, United States; Thierry Oddos, Johnson & Johnson Consumer
France, Val De Reuil, Normandy, France
It is now well accepted that dark and white skins have different characteristics. For
instance, originally dark skin types (African type for example) that are more exposed
to sun and to UV light than whites, have developed a peculiar protection through an
increase in the synthesis of melanin, thus delaying skin aging onset in dark skin
when compared to white skin. Also, skin architecture, and more precisely the
epidermis, is different in dark African, Asian, and white skin. Vitamin A (Retinol) is a
key factor regulating epidermal homeostasis because it is known to influence
epidermal cell proliferation and cell differentiation. However, to our knowledge,
nothing is known on the capacity of different ethnicities, other than white skin, to
respond to retinol. The objective of our study was to compare the response of skin
from different ethnic groups to retinol. We have developed an ex vivo model based
on the in vitro maintenance of human skin explants from biopsies. The skin explants
are exposed to retinol for 24 and 48 hours and the expression of key markers of
retinol activity and irritation is evaluated by Real time quantitative PCR. This model
has been shown to mimic the in vivo response of white skin to retinoids in terms of
changes in gene expression. Key markers of retinoid activity such as cellular retinoic
acid binding protein II (CRABPII) and heparin binding epidermal growth factor (HBEGF) are upregulated while profillagrin or transglutaminase-1 genes are down
regulated. Also, in this model, retinol induces a clear increase in interleukin-8. Our
results revealed large variations in the magnitudes of retinol activated gene
expression among individuals, as much as 4- to 8-fold. In preliminary study, similar
gene expressions in response to retinol were observed between dark African and
white skin types but African skin appears to respond with somewhat greater change.
This early study result suggests potentially ethnicity-dependent patterns of skin
response to cosmetic ingredients. Further study is ongoing to confirm in both ethnic
groups, as well as in other ethnicities.
Commercial support: 100% sponsored by Johnson & Johnson Consumer
Companies, Inc.
The role of survivin and other chromosomal passenger complex proteins
in the regulation of adult epidermal stem cell differentiation
Nouha Domloge, MD, Vincience ISP Global Skin Research Center, Sophia
Antipolis, Alpes Maritimes, France; Catherine Gondran, MBA, Vincience ISP
Global Skin Research Center, Sophia Antipolis, Alpes Maritimes, France; Claude
Dal Farra, PhD, ISP Corporate Research Center, Wayne, NJ, United States; Florent
Labarrade, MBA, Vincience ISP Global Skin Research Center, Sophia Antipolis,
Alpes Maritimes, France; Jean-Marie Botto, PhD, Vincience ISP Global Skin
Research Center, Sophia Antipolis, Alpes Maritimes, France
The epidermis and the hair follicle need to continuously generate new cells through
proliferation of progenitor cells and subsequent differentiation. This renewal is
permitted by adult stem cells (ASCs) originating from the bulge region of follicles.
Under certain stimuli, ASCs are able to migrate towards interfollicular epidermal
regions and/or the hair follicle, in order to replenish the loss of terminally
differentiated cells (corneocytes and the hair shaft). This differentiation process is
tightly controlled and the underlying successive mitosis is strictly regulated,
particularly by the chromosomal passenger complex (CPC). The CPC is the key
regulatory complex which is responsible for the correct development of cellular
mitosis. The proteins survivin, borealin, aurora kinase B, and INCENP are the
interacting components of the CPC. Survivin is a member of the inhibitor of
apoptosis proteins (IAPs) family. In order to study the role of CPC proteins in adult
skin stem cell maintenance and protection from various stresses, we prepared
several fractions of primary cells from human epidermis, corresponding to cellular
enrichments at successive stages of differentiation (mainly transient amplifying and
differentiated adult epidermal stem cells). Cell morphology observation, RT-PCR
analysis, immunoblotting, as well as immunocytologic, histologic, and siRNAinduced knockdown expression studies, were all approaches used to further
evaluate and follow the implications of the four studied CPC components in correct
stem cell differentiation, their subcellular localization, as well as several relevant
markers (P63, beta-catenin, alpha-6 and beta-1 integrins, and KT15). In parallel, we
investigated whether an induced upregulation of survivin expression, or its
translocation into the nucleus, could have a protective role in the mitosis
phenomenon.
Together, these studies shed more light on the essential role and importance of ASC
protection.
MARCH 2010
J AM ACAD DERMATOL
AB25
CLINICAL DERMATOLOGY AND OTHER
CUTANEOUS DISORDERS
P1100
Livedoid vasculopathy with hyperhomocysteinemia: Therapeutic
approach
Paulo Morais, MD, Department of Dermatology and Venereology, Hospital S. Jo~ao
and Faculty of Medicine, Porto, Portugal; Alberto Mota, MD, PhD, Department of
Dermatology and Venereology, Hospital S. Jo~ao and Faculty of Medicine, Porto,
Portugal; Filomena Azevedo, MD, Department of Dermatology and Venereology,
Hospital S. Jo~ao and Faculty of Medicine, Porto, Portugal; Marta Almeida, MD,
Department of Dermatology and Venereology, Hospital S. Jo~ao and Faculty of
Medicine, Porto, Portugal
Case report: A 19-year-old nonsmoker and otherwise healthy white woman was
referred to our department because of a 4-year history of widespread livedo
reticularis (LR). There was a history of exacerbation in cold weather but without
pain or ulceration. The following investigations were normal or negative:
CBC/chemistry panel, coagulation study, autoimmune screening, cryoglobulins,
immune complexes, immunoglobulin levels, ASO titer and HBV serologies.
However, increased titers of anticardiolipin IgM antibodies were detected. Over
the following 2 years, her treatment included pentoxyfilline and aspirin. At this
moment, she started to experience symptoms of Raynaud syndrome (RS), and
nifedipine was initiated. However, follow-up was lost during 2 years. When she
returned to our clinic, she was on oral contraceptive and presented multiple painful
ulcers on the lower extremities, with inflammatory borders and surrounding
hyperpigmentation, small stellate areas of atrophie blanche, and telangiectasia.
Further investigation, including an extended coagulation and prothrombotic study,
revealed a heterozygous MTHFR mutation (C677T), and increased ESR, CRP and
homocysteine levels. The remaining blood panel and brain MRI scan were
unremarkable. A skin biopsy showed fibrinous occlusion of dermal blood vessels
without leukocytoclasis, associated with perivascular lymphocytic infiltrate. The
overall clinicopathologic features were suggestive of livedoid vasculopathy (LV).
Losartan was added to treatment regimen, with a positive control of RS, but without
improvement of skin ulcers. We decided to withdraw the oral contraceptive and
begin oral danazol (200 mg/day) and folic acid (5 mg/day). Within a month, there
was an almost complete healing of the ulcers, marked pain relief and normalization
of homocysteine levels. There were no signs of relapse at 6-month follow-up.
P1102
Cutaneous accumulation of cystine crystals in a cystinosis patient
Raj Patel, University of Alabama at Birmingham, Vestavia Hills, AL, United States;
Aleodor Andea, MD, University of Alabama at Birmingham, Birmingham, AL,
United States; Anca Croitoru, MD, University of Alabama at Birmingham,
Birmingham, AL, United States; Conway Huang, MD, University of Alabama at
Birmingham, Birmingham, AL, United States
Cystinosis is a rare autosomal recessive disorder in which there is a failure of carriermediated transport of the amino acid cystine across the lysosomal membrane. We
present here the second case reported in the literature of cutaneous accumulation of
cystine crystals in a patient with cystinosis. A 27-year-old white male with cystinosis
presented for evaluation of dry skin and multiple pruritic lesions on his face, chest,
and arms. He had a history of two renal transplants at an interval of 10 years. In
addition to Fanconi-like renal involvement, he had also ocular and neurologic
disease secondary to cystine crystal accumulation. The physical examination was
remarkable for short stature, premature aging, fair complexion and hair, and
scattered small erythematous hyperkeratotic macules and papules on sun-exposed
areas. Symptoms included pruritus, dry skin, and a sensation of ‘‘needle pricks’’ over
the skin. Microscopic evaluation of a shave biopsy specimen from the right temple
revealed actinic keratosis and a striking accumulation of rectangular cystine crystals
in the dermal fibroblasts and macrophages. Cystinosis is characterized by excessive
intracellular accumulation of cystine; however, plasma and intestinal absorption is
normal. Furthermore, urine cystine is normal, differentiating cystinosis from
cystinuria. Low solubility of cystine promotes precipitation of polygonal or
prismatic needle shape crystals at increasing concentrations in several tissues at
various rates. Elevated intracellular levels of cystine in these patients are known to
cause tissue damage most notably in renal, ocular, muscle, placenta, brain, and
gingival tissue. Early diagnosis is critical, and the best method involves measurement
of leukocyte cystine levels. Mainstay treatment is oral cysteamine therapy; however,
compliance is complicated by side effects, which include halitosis and GERD. The
findings in our case are unique because although cystinosis affects numerous organ
systems, there are very few reports of any cutaneous manifestations. Until recently,
the only known skin involvement by cystinosis consisted of slightly lighter color in
white patients and premature aging. Our case shows that it is possible for cystine
crystals to precipitate and accumulate in the dermis causing clinical manifestations.
Discussion: LV is an uncommon condition characterized by persistent LR and
recurrent painful ulcers, usually involving the lower extremity of young patients. LV
is considered to be a noninflammatory occlusive thrombotic process because of a
hypercoagulable state. Although heterozygous MTHFR mutations do not seem to
cause hyperhomocysteinemia, this was not the case of our patient. The therapy of LV
is usually difficult and unsatisfactory, but danazol is a good alternative in some cases.
Folic acid supplementation was found to reduce homocysteine levels, and can be
useful in patients with MTHFR mutation.
P1103
P1101
Adalimumab for the treatment of refractory cutaneous sarcoidosis
Jeffrey Crowley, University of California, Los Angeles, Los Angeles, CA, United
States
Objective: To describe the successful use of adalimumab therapy in a 48-year-old
white woman with an 8-year history of therapy-refractory cutaneous sarcoidosis.
Methods: Eroded plaques and nodules on the bilateral forearms, scalp, and trunk
were biopsied. A systemic evaluation included chest radiographs, pulmonary
function tests, a purified-protein derivative test, a comprehensive metabolic panel,
and coccidioidomycosis titers.
Results: Plaque and nodule biopsies revealed a granulomatous dermatitis consistent
with sarcoidosis. The patient was diagnosed with cutaneous sarcoidosis after
eliminating infectious disease and systemic sarcoidosis as possible etiologies. Initial
treatment with oral prednisone and high-potency topical corticosteroids resulted in
only minor improvement. After the patient received the initial treatment regimen for
4 months, hydroxychloroquine 200 mg twice daily was added. Two months later,
the patient improved. However, an attempt to taper the oral prednisone regimen
resulted in significant disease flares. Etanercept 50 mg twice weekly was added to
the prednisone, corticosteroid, and hydroxychloroquine treatment regimen.
Improvement during the 5-month period after etanercept initiation was minimal.
Etanercept was discontinued; 4 weeks later, adalimumab 40 mg every other week
was initiated. During the ensuing 5 months, the sarcoid lesions resolved; after 3
months, the patient discontinued oral prednisone and reduced the hydroxychloroquine dosage regimen to 200 mg once daily. The patient also discontinued topical
corticosteroids after the lesions resolved. The patient has been receiving adalimumab 40 mg every other week and hydroxychloroquine 200 mg once daily for 9
months and has no active sarcoid lesions.
Conclusion: Adalimumab therapy was associated with resolution of recalcitrant
cutaneous sarcoid lesions with discontinuation of oral prednisone and a reduction of
the daily hydroxychloroquine dose. Adalimumab may be an option for patients with
refractory cutaneous sarcoidosis. This case report may promote further evaluation
of adalimumab effectiveness and safety for patients with few therapeutic options for
treating this devastating disease.
Commercial support: Abbott provided editorial support for the abstract and
poster.
AB26
Clinical diagnostic sensitivity of clear cell acanthoma
L. Katie Morrison, MD, Wright State University, Dayton, OH, United States; H.
Nicholas Shamma, MD, Dermatopathology Laboratory of Central States, OH,
United States; Michael Duffey, MD, Wright State University, Dayton, OH, United
States
Objective: To evaluate the frequency that clear cell acanthoma (CCA) was listed in
the clinical differential diagnosis of histologically confirmed cases.
Design: A retrospective analysis.
Setting: Clinical biopsies sent to a regional dermatopathology laboratory for
histologic evaluation.
Methods: A regional dermatopathology lab database was evaluated between January
1998 and March 2008 for histologically confirmed cases of CCA. All biopsies were
read by board certified dermatopathologists. Clinical data that were submitted with
these cases, including differential diagnoses, was analyzed.
Results: During this period of review, 411 cases of CCA were identified. Eleven of
these cases had a clinical impression of CCA listed amongst the differential
diagnoses, resulting in an overall sensitivity in clinical diagnosis of 2.7%. The top
three differential clinical diagnoses were basal cell carcinoma (34%, n ¼ 140),
irritated seborrheic keratosis (25%, n ¼ 101), and squamous cell carcinoma (15%, n
¼ 63). The most common anatomic location was the leg (51%, n ¼ 211). Fifty-five
percent (n ¼ 226) of cases were in men, and 45% of cases (n ¼ 185) were in women.
The median age was 63 years. Ninety-eight percent (n ¼ 401) of subjects were above
the age of 40, 85% (n ¼ 348) were above the age of 50, and 62% (n ¼ 253) were
above the age of 60. The incidence in this study population was 0.03%, or 411 out of
1,489,818 dermatologic specimens received for evaluation at this dermatopathology
lab during the defined 9.25-year reference period.
Conclusion: This is the largest published collection of CCA cases to date. Our data
are in agreement with existing data of CCA being most commonly found on the
lower extremities of older patients, with nearly equal sex incidence. CCA was rarely
clinically suspected on biopsy proven specimens, yielding a low clinical diagnostic
sensitivity. This may be because of a hybrid clinical appearance of the lesion with
overlapping features of several neoplastic and inflammatory disorders making it
difficult to distinguish, or an entity that is rare and not frequently suspected.
Additional studies in conjunction with dermatoscopy may help further delineate the
factors that contribute to these results and improve clinical recognition of CCA.
J AM ACAD DERMATOL
MARCH 2010
ABS 5.0 DTD YMJD6693_6694_proof 17 January 2010 11:30 am
P1104
P1106
Umbilical cord blood transplantation can cure pruritic eczematous eruption in a hypohidrotic ectodermal dysplasia with immunodeficiency
patient
Satoko Minakawa, MD, PhD, Department of Dermatology, Hirosaki University
Graduate School of Medicine, Hirosaki, Aomori, Japan; Daisuke Sawamura, MD,
PhD, Department of Dermatology, Hirosaki University Graduate School of
Medicine, Hirosaki, Aomori, Japan; Eturou Ito, MD, PhD, Department of
Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori,
Japan; Hajime Nakano, MD, PhD, Department of Dermatology, Hirosaki
University Graduate School of Medicine, HIrosaki, Aomori, Japan; Hajime
Takeda, MD, PhD, Department of Dermatology, Hirosaki University Graduate
School of Medicine, Hirosaki, Aomori, Japan
Anhidrotic ectodermal dysplasia and immunodeficiency (EDA-ID) is an X-linked
recessive genodermatosis characterized by severe eczematous eruption, hypohidrosis, dental anomalies, alopecia, and immunodeficiency. A 4-month-old Japanese
boy with pruritic eruption on his entire body since birth was referred to our clinic.
Examination revealed diffuse erythema and reddish papules, with scratching
evident on most of the body, which was compatible with atopic dermatitis. A skin
biopsy specimen revealed spongiotic change in the epidermis and perivascular
lymphoid and eosinophilic infiltration in the superficial dermis. Results of appropriate laboratory tests confirmed deficient cellular immunity. A pathogenic mutation
c.1167insC was identified in the nuclear factor-kappaB (NF-kB) essential modulator
(NEMO) genes in both the patient and his mother. His mother had been diagnosed
with incontinentia pigmenti by skin biopsy a few months after her birth. His
maternal uncle died from a disorder of unknown etiology when he was 1 month old.
His maternal grandmother and grandmother’s sister were suspected to have had
incontinentia pigmenti from their histories. He was diagnosed as EDA-ID from
clinical features, family history, and mutation analysis of the NEMO gene. The patient
was treated with hydrocortisone cream and a moisturizing agent, which resulted in
minimal improvement of eczema and intense pruritus. When he was 3 years old, he
received an umbilical cord blood transplantation. After the transplantation, his itchy
eruption was gradually getting better. Nonpupuric erythema developed on the trunk
at day 135, and the biopsy specimen showed liquefaction in the dermoepidermal
interface with satellite cell necrosis, compatible with acute GVHD. His eczematous
eruption had almost disappeared, leaving slight xerosis a year after the transplantation. The responsible gene for EDA-ID is the NEMO gene, which is critical for the
activation of NF-kB signaling involved in inflammation, immune responses, and cell
survival.
Eruptive vellus hair cysts treated with lactic acid: Case report and review
of the literature
Bryant Tran, Wake Forest University School of Medicine, Winston Salem, NC,
United States; Andrew Lee, MD, Wake Forest University School of Medicine,
Winston Salem, NC, United States; Ashley Curtis, MD, Wake Forest University
School of Medicine, Winston Salem, NC, United States; Gil Yosipovitch, MD,
Wake Forest University School of Medicine, Winston Salem, NC, United States
Because eruptive vellus hair cysts were first identified 3 decades ago, treatment for
this condition remains unsatisfactory and time-consuming. We describe a 41-yearold African American female who presented with a 3-month history of a progressive,
pruritic eruption on her upper chest and neck that was characterized by multiple
dome-shaped, hyperpigmented papules. Skin biopsy of a lesion on her chest
revealed cysts lined by squamous epithelium and containing laminated keratin and
numerous vellus hair shafts. Oral antihistamines and topical corticosteroids did not
relieve her pruritus nor affect the appearance of the lesions. A trial of topical 12%
lactic acid resulted in modest improvement in the appearance of the lesions. Topical
lactic acid is an effective option for eruptive vellus hair cysts in richly pigmented
patients, because surgical options can produce scarring and dyspigmentation.
In male patients, the hypomorphic mutations, in which NEMO function is decreased
but not abolished, generally result in EDA-ID, while larger frameshift and deletion
mutations which completely impair NEMO function cause a lethal condition in male
fetuses. This family had one nucleotide insertion mutation of c.1167insC, which
might sustain some function of the NEMO gene, as previously reported.
P1107
P1105
Scleromyxedema with neurologic involvement: Therapy with intravenous
immunoglobulin
Filipa Ventura, Dermatology and Venereology Department, Hospital de S~ao
Marcos, Braga, Portugal; Celeste Brito, Dermatology and Venereology
Department, Hospital de S~ao Marcos, Braga, Portugal; Margarida Rodrigues,
Neurology Department, Hospital de S~ao Marcos, Braga, Portugal; Maria da Luz
Duarte, Dermatology and Venereology Department, Hospital de S~ao Marcos,
Braga, Portugal
Scleromyxedema is a rare idiopathic disorder characterized by dermal mucin
deposition with fibrosis associated with monoclonal gammopathy and systemic
manifestations. Despite some reports of success with numerous agents, there is not
a completely satisfactory therapeutic approach to the scleromyxedema. A 69-yearold male, previously healthy, presented in a coma without fever or meningeal signs
to the emergency department. He underwent a full neurologic workup and the EEG
showed slow and irregular background activity. The lumbar puncture, MRI and
laboratory studies were normal. He was prescribed valproate, cefotaxime, ampicilin,
acyclovir, and dexamethasone with a slow improvement. He was discharged
without complaints on the fourteenth day. Six months later, the patient presented
a widespread symmetric eruption of tiny waxy monomorphic papules predominating in the forehead, forearms, and hands. The physical examination also revealed a
diffuse erythema and induration of the skin, leading to decrease the motility
especially of the mouth and the hands. A skin biopsy specimen revealed a diffuse
mucin deposit in the dermis and a marked fibroblastic proliferation. The most
relevant results of the hematologic investigation were IgG monoclonal gammopathy
with l light chains and absence of thyroid disease. The diagnosis of scleromyxedema
was made. The patient was treated with thalidomide 100 mg/day. After 6 months,
there was a discrete improvement, but the treatment had to be stopped because of
neurologic complaints. In the meantime, he suddenly had a loss of consciousness
and he came back to the hospital in a comatose state. This episode was similar to the
previous one. A 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg/d)
was started and his encephalopathy improved steadily. After completing 6 cycles of
treatment, there was a dramatic skin lesions improvement. We present this case
because (apart of being rare) this case reports an encephalopathy associated with
scleromyxedema and the effectiveness of IVIG in treatment.
A retrospective review of the use of colchicine in chronic idiopathic
urticaria
Lana Pho, MD, University of Utah, Salt Lake City, UT, United States; Christopher
Hull, MD, University of Utah, Salt Lake City, UT, United States; Doug Powell, MD,
University of Utah, Salt Lake City, UT, United States; Mark Eliason, MD, University
of Utah, Salt Lake City, UT, United States; Michelle Regruto, MD, University of
Utah, Salt Lake City, UT, United States
Background: Chronic idiopathic urticaria (CIU) is a common condition that can be
debilitating, difficult to treat, and sometimes life-threatening. The disease is common
with a lifelong prevalence of 0.5% to 1%. Recent reports have shown that the
disability suffered by CIU patients is similar to that of patients with coronary artery
disease. The treatment of CIU patients can be frustrating, and for those who do not
respond to antihistaminic treatment, other treatment modalities are needed. In
many patients, immunosuppressant medications are required, but these have major
adverse effects, such as renal dysfunction, liver function abnormalities, and anemia.
A safer and more efficacious therapy is clearly needed for CIU.
Aims: To evaluate efficacy and side effects of colchicine in patients with CIU.
Methods: Chart review of patients with diagnosis of CIU based on history, physical
examination, and skin biopsy at the University of Utah between 2002 and 2007.
Results: A total of 36 patients who met criteria for CIU and were treated with
colchicine were identified. Twenty-eight (78%) were women and the mean 6 SD age
was 46 6 15 years. Mean 6 SD duration of the CIU was 41 6 63 months. Fifty-eight
percent had a history of angiedema. Maximum dose of colchicine achieved was 1.5
mg/day with the majority of patients taking 1.2 mg/day. Forty-seven percent were on
treatment for at least 1 month and 42% maintained treatment from [1 to 22 months.
Subjective clinical response to therapy reported as partial (n ¼ 5) or complete (n ¼
15) were found in 55% of patients. Although 39% (n ¼ 14) reported adverse effects
(diarrhea being the most common), only 11 patients (31%) stopped treatment. Of
the 15 patients who had complete clearance, eight patients continue to be
asymptomatic, two patients had recurrence after finishing treatment and switched
to other agents, three patients stopped treatment secondary to side effects, and two
patients had recurrence but responded to a second course of colchicine.
Conclusions: Colchicine is an effective treatment in 55% of our patients. In patients
who had complete response, eight (53%) patients remained clear after tapering of
colchicine. Side effects were mild. These results support the use of colchicine for
patients with CIU unresponsive to standard therapy. Larger, controlled trials will
further investigate colchicine for use in CIU patients.
MARCH 2010
J AM ACAD DERMATOL
AB27
P1108
P1110
Thrombotic nodules secondary to bevacizumab in a patient with glioblastoma multiforme
Christopher Burnett, MD, Henry Ford Hospital, Detroit, MI, United States; Dakara
Wright, MD, Henry Ford Hospital, Detroit, MI, United States; Ethan Nydorf, MD,
Henry Ford Hospital, Detroit, MI, United States; Pranita Vemulapalli, Henry Ford
Hospital, Detroit, MI, United States
Unusual self-inducted paraffinoma of the face in an old woman
Cristina Rodriguez-Garcia, MD, Hospital Universitario de Canarias, La Laguna,
Santa Cruz de Tenerife, Spain; Francisco Guimera, MD, PhD, Hospital
Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Maria-Jose
Gonzalez-de-Mesa, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz
de Tenerife, Spain; Nuria Perez-Robayna, MD, Hospital Universitario de Canarias,
La Laguna, Santa Cruz de Tenerife, Spain; Sorahaya Gonzalez-Hernandez, MD,
Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain
Dermatitis artefacta is an uncommon condition that is difficult to diagnose and treat.
Clinical presentation of the skin lesions does not conform to those of known
dermatoses and are located on easily reached parts of the skin. Typically, patients
deny having inflicted the lesions on themselves, and reports of self-introduction of
foreign material, such as feces, sand, oily materials, or silicone into the skin are rare.
We report 74-year-old woman with symmetric indurated periocular erythematous
plaques. Biopsy specimens taken had disclosed a granulomatous foreign-body
reaction, possibly related to silicone injection. The self-induced nature of the lesions
was not admitted when the patient was directly confronted with the biopsy results.
She was diagnosed as having a borderline personality disorder. Onset of dermatitis
artefacta may occur at any age, although the highest incidence of onset is in late
adolescence to early adult life. Most patients are young women who have a
personality disorder; borderline features are common and the patient’s denial of
psychologic distress makes management and treatment difficult.
Bevacizumab, a recombinant humanized monoclonal antibody directed against
vascular endothelial growth factor (VEGF), is currently FDA-approved in treatment
of several human malignancies. We present a case of a 75-year-old white male who
suffered recurrent glioblastoma multiforme following initial chemotherapy and
radiation. His oncologists began a second-line therapy of bevacizumab and
irinotectan. Ten weeks into this treatment course, he developed violaceous nodules
and tumors scattered over the upper and lower extremities. Shortly thereafter, he
developed pulmonary embolism and began treatment with enoxaparin with
subsequent worsening of the cutaneous eruption. Partial thromboplastin time,
prothrombin time, and platelets were within normal limits. A biopsy specimen
revealed focal vascular proliferation and red blood cell extravasation in the dermis. A
second, deeper saucerization biopsy demonstrated adherent blood clot on the
epidermal surface. The lesions improved with reduction of the bevacizumab dose.
Paradoxically, bevacizumab can simultaneously predispose to both thrombosis and
hemorrhage. These side effects are well described on a systemic level, but appear to
only rarely involve the skin, because only one previously reported case exists, in
which a patient on bevacizumab developed widespread ecchymoses. As bevacizumab becomes more popular in general oncology practice, it will be important for
dermatologists to be aware of potential cutaneous side effects. Moreover, in the
present case, the thrombotic cutaneous nodules preceded development of pulmonary embolism. Perhaps the development of cutaneous thrombosis or hemorrhage
may be an easily identifiable warning sign of impending systemic thrombosis or
hemorrhage.
P1109
A rare case of cutaneous and nasal extranodal RosaieDorfman disease
Suzanne Cheng, MBBS, Queen’s Medical Centre, Nottingham, United Kingdom;
Iain Leach, Queen’s Medical Centre, Nottingham, United Kingdom; William
Perkins, Queen’s Medical Centre, Nottingham, United Kingdom
RosaieDorfman disease (RDD) is a rare, usually benign systemic histiocytic disease
characterized by massive painless lymphadenopathy, particularly in the head and
neck region. Extranodal sites are involved simultaneously in 43% of cases, while
isolated extranodal RDD occurs in only 23% of cases. Common extranodal sites
include the skin (10%), paranasal sinuses, bone, eye, and soft tissues. RDD is most
common in adolescents and young adults. Typically RDD is associated with pyrexia,
anemia, leukocytosis, an elevated erythrocyte sedimentation rate, and hypergammaglobulinemia. We report a rare case presenting in middle age with extranodal
manifestations which made the diagnosis of RDD challenging. A 61-year-old white
male initially presented in 2004 with pigmentation around both ankles, bilateral
tender nonpitting leg edema, left inguinal lymphadenopathy, and profuse night
sweats. He underwent extensive investigations including magnetic resonance
imaging (MRI) of his legs which showed abnormal marrow signals in the left tibia
and a lymphoscintigraphy which showed functioning lymphatics in the left leg. No
definite diagnosis could be made, but parasitic infections, such as filiariasis or
leishmaniasis, low-grade chronic osteomyelitis, and cutaneous lymphoma, were
considered. His symptoms improved spontaneously. Three years later he developed
nasal symptoms. A large nasal septal mass with swelling of the right middle turbinate
was detected on MRI. This mass was excised and histology showed a heavy cellular
infiltrate rich in plasma cells with stromal scarring and bone erosion.
Immunohistochemistry showed the plasma cells to be polyclonal, indicating an
inflammatory infiltrate. At this stage, he was referred to dermatology with multiple
asymptomatic nodules on his posterior calves and thighs. An excision biopsy
showed sheets of large histiocytes with large vesicular nuclei, prominent nucleoli,
and abundant pale cytoplasm with focal emperipolesis and a peripheral mixed
inflammatory infiltrate with fibrosis. Immunohistochemistry showed positive staining of histiocytes with S100 protein but not CD1a, which is a characteristic of RDD.
The histology of the nasal septal mass was reviewed and showed similar features
consistent with nasal RDD. It is likely that his unexplained symptoms since 2004 are
all related to RDD. Because of the benign course of his disease so far, our patient
received no treatment. His skin lesions have improved spontaneously and his nasal
septum has healed well postsurgery.
AB28
P1111
Treatment of keratoacanthoma arising from hypertrophic lichen planus
Rachel Epstein, DO, HCA/Largo Medical/Sun Coast Hospital Osteopathic
Dermatology Residency Program, Largo, FL, United States
Hypertrophic lichen planus is a variant of lichen planus that has the potential to
undergo malignant transformation. We report an 86-year-old white female who
presented with multiple squamous cell carcinomas of the keratoacanthoma type
arising from hypertrophic lichen planus on the anterior shins. Because of the
numerous amount of lesions in this challenging anatomic location, a unique
treatment approach was attempted. Four weeks after her initial treatment, there
was marked clinical improvement of the squamous cell carcinomas, in addition to
the underlying hypertrophic lichen planus. An overall decline in new lesions was
also observed. Our findings suggest that intralesional triamcinolone acetonide is a
valuable treatment option for keratoacanthomas arising from hypertrophic lichen
planus on the lower extremities.
J AM ACAD DERMATOL
MARCH 2010
P1112
P1114
Cutaneous side effects of EGFR inhibitors: A study of 10 patients
Felicidade Santiago, MD, Dermatology Department, Coimbra, Portugal; Américo
Figueiredo, MD, PhD, Dermatology Department, Coimbra, Portugal; Margarida
Gonçalo, MD, Dermatology Department, Coimbra, Portugal
Introduction: Epidermal growth factor receptor (EGFR) inhibitors, both the monoclonal antibody—cetuximab—and the tyrosine kinase inhibitor—erlotinib—approved for patients with colorectal and lung cancer refractory or intolerant to
chemotherapy are associated with peculiar cutaneous side effects. A priori identification of patients who are more prone to develop skin toxicity is not yet available.
Erythema nodosum due to azothiaprine in a 13-year-old male with Crohn
disease
Risa Behar Ross, DO, Largo Medical Center, Largo, FL, United States; Richard
Miller, DO, Largo Medical Center, Largo, FL, United States
Objectives: Our aim was to describe the cutaneous side effects of EGFR inhibitors
and their management.
Methods: Between March 2006 and March 2009, our dermatology department
studied 10 patients (7 males and 3 females) with a mean age of 61.9 years (range, 5077), under therapy with cetuximab and erlotinib (5 cases each). The type of adverse
reaction, interval between introduction of EGFR inhibitor and skin symptoms,
treatment, and evolution were assessed.
Results: The most common side effect, observed in nine patients, was a papulopustular eruption, involving mainly the face, upper chest, and back. It appeared
within 1 to 6 weeks (mean, 15.6 days) after onset of EGFR inhibitor. All patients were
treated with oral antibiotic (minocycline or doxycycline) associated with a topical
treatment (metronidazole, benzoyl peroxide, or corticosteroids), with improvement
of the lesions in all patients and a very good response in six patients. One patient
presented paronychia with periungueal pyogenic granulomaelike lesions associated with erlotinib, which improved slightly on topical antibiotics and corticosteroids. Another patient had also asteatotic eczema, mainly in the trunk, 8 weeks after
initiation of erlotinib, with a good response to emollients. In the majority of patients,
the EGFR inhibitor was maintained in the same dose, except in two who reduced
erlotinib to 100 mg/day and in two other who suspended use of the drug because of
neoplastic disease progression.
Erythema nodosum is a well known form of panniculitis. It typically presents as
erythematous, subcutaneous, firm, tender, warm nodules on the lower extremities.
Many causes of erythema nodosum have been described, including infectious
etiologies, medications, and inflammatory bowel disease. Erythema nodosum often
gives clinical clues to systemic disease. The onset of erythema nodosum frequently
correlates with a flare of inflammatory bowel disease, a well reported association.
Certain medications, including oral contraceptives, sulfonamides, penicillin, bromides, and iodides, have all been repeatedly linked to erythema nodosum. We
present the case of a 13-year-old male with Crohn disease who developed an
eruption clinically consistent with erythema nodosum after initiating treatment
with azothiaprine for his inflammatory bowel disease. The development of his
erythema nodosum was not associated with a flare of his inflammatory bowel
disease and his gastrointestinal symptoms were well controlled at time of presentation. The eruption did resolve after discontinuation of the azothiaprine and did
reappear with rechallenge of the medication 4 weeks later. There are very few
reported cases of azothiaprine-induced erythema nodosum. Practioners prescribing
this medication should be aware of this potential side effect and recognize that
erythema nodosum may not be solely caused by underlying inflammatory bowel
disease.
Discussion: Although the number of patients treated is small, in our experience the
papulopustular eruption responded well to topical treatment and oral tetracycline,
whereas emollients improved skin xerosis. The expanding use of this new targeted
therapy requires that dermatologists became familiar with the associated cutaneous
reactions and promote an interdisciplinary approach with the oncology department
to ensure timely intervention and follow-up.
P1115
P1113
Multisystem Langerhans cell histiocytosis in an adult presenting with
vulvar lesions
Tiffany Brazeal, MD, Mayo Clinic, Scottsdale, AZ, United States; David DiCaudo,
MD, Mayo Clinic, Scottsdale, AZ, United States; Megan Weber, MD, Mayo Clinic,
Scottsdale, AZ, United States; Karen Warschaw, MD, Mayo Clinic, Scottsdale, AZ,
United States
A 65-year-old white female with a history of diabetes mellitus, obesity, and prior
tobacco abuse presented with a 1-year history of dysuria, frequent urinary tract
infections, and pruritic vulvar lesions. The vulvar rash had previously been treated as
a suspected yeast infection with several courses of antibiotics and antifungals. Over
time, the rash progressed to involve the inframammary folds, groin, axillae, and
scalp. Biopsy of the vulvar lesions revealed Langerhans cell histiocytosis (LCH) and
the patient was referred to our dermatology clinic. The skin examination revealed
numerous 3- to 5-mm indurated monomorphic red papules in the inframmamary
folds and groin. The postauricular scalp showed crusted pink papules extending
along the hairline. Biopsies from the vulva and inframmary fold revealed a dense
infiltrate of mononuclear cells with cleaved nuclei and scattered eosinophils. The
infiltrate strongly expressed S-100 and CD1a and were negative for CD68,
confirming the diagnosis of LCH. CT scan revealed numerous bilateral pulmonary
nodules. Pulmonary wedge biopsies were consistent with pulmonary LCH. Skeletal
survey and bone marrow biopsy were negative for evidence of involvement. The
occurrence of LCH in adults is exceedingly rare and the incidence may approach one
to two cases per million. The disease may affect the skin and other organs. Lung
involvement in children is rare, but is often the main manifestation of LCH in adults,
especially in those with a history of tobacco abuse. Although LCH in adults is rare, it
should be considered in the differential diagnosis when treating chronic and
refractory intertriginous lesions. In such cases, it is necessary to perform a biopsy,
rule out systemic involvement, and survey the patient over time.
Dermatology life quality index (DLQI) in HIV-associated lipodistrophy
patients
Patricia Contreras-Ferrer, MD, Hospital Universitario de Canarias, La Laguna,
Santa Cruz de Tenerife, Spain; Cristina Rodriguez-Garcia, MD, Hospital
Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Marta
Garcia-Bustinduy, MD, PhD, Hospital Universitario de Canarias, La Laguna, Santa
Cruz de Tenerife, Spain; Nuria Perez-Robayna, MD, Hospital Universitario de
Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Sorahaya GonzalezHernandez, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de
Tenerife, Spain
Introduction: HIV-associated lipodystrophy is a skin condition that is characterized
by the loss of subcutaneous fat. Although the exact mechanism of this is unknown, it
is believed that lipodystrophy in HIV patients is caused by antiretroviral medications. Patients often present with fat loss in the face, buttocks, arms, and legs. There
is also fat accumulation in various body parts, like fat deposits in their upper backs.
The breast sizes of patients (both male and female) tend to increase. In addition,
patients develop abdominal obesity. In this context, therapy-related body changes
gain in importance, in light of the psychological distress they cause and of their
association with adherence to treatment.
Methods: We have performed a cross-sectional observational study in 30 patients
affected with HIV-associated lipodystrophy. The presence of lipodystrophy was
defined by clinical criteria. The patients were evaluated with the Dermatology Life
Quality Index questionnaire (DLQI) using a like control group of 10 HIV patients
without lipodystrophy. In addition, dates of age and sex were registered.
Results: Eighty percent were male in both groups. The mean age of patients with
lipodystrophy was 44.7 years (male:female ratio, 44.5:44.8). Patients with lipodystrophy presented a low puntuation in DLQI (the mean punctuation was 2.7). On the
other hand, the control group (patients without lipodystrophy) obtained 2.3 points
in DLQI with a mean age of 34.7 years (male:female ratio, 29.5:36). These differences
were not statistically significant (P ¼.4).
Conclusion: We have observed a small effect on patients’ life in both groups (with
and without lypodystrophy). These data suggest that the impact of quality of life in
HIV-associated lipodystrophy depends on certain patients’ characteristics, rather
than on the presence of lipodystrophy itself. Nonetheless, our study is limited by the
small sample size.
MARCH 2010
J AM ACAD DERMATOL
AB29
P1116
P1118
Sweet syndrome following chemoradiation for tonsilar squamous cell
carcinoma
Jeffrey Williams, MD, West Virginia University, Morgantown, WV, United States;
Rodney Kovach, MD, West Virginia University, Morgantown, WV, United States
Eosinophilic cellulitis
Angela Bookout, DO, Largo Medical Center/Sun Coast Hospital, Largo, FL, United
States
Eosinophilic cellulitis is an uncommon recurrent granulomatous dermatitis with
predominant tissue eosinophilia. The etiology of this predominately sporadic
syndrome is unclear, but many precipitating factors, such as arthropod bites, fungal
infections, cutaneous viral and parasitic infections, atopic dermatitis, myeloproliferative disorders, leukemia, and hypersensitivity reactions to medications are
suggested. The typical clinical presentation is large, indurated plaques of edema
and erythema that resemble cellulitis and may be tender, pruritic, or have an
associated burning sensation. The plaques may gradually enlarge and resolve over
several weeks or may recur at intervals. Most cases have complete resolution
without scarring. We present a case of a 62-year-old white male with multiple,
slightly pruritic, erythematous, indurated nodules on his scalp that would enlarge
and spontaneously resolve over the course of 24 hours. A punch biopsy specimen of
his scalp revealed characteristic histopathologic findings consistent with eosinophilic cellulitis. Various treatment options for eosinophilic cellulitis include topical,
intralesional, and systemic corticosteroids, oral antihistamines, griseofulvin, dapsone, minocycline, and cyclosporine. Our patient was successfully treated with
cetirizine, diphenhydramine, systemic prednisone taper, and topical triamcinolone
and has been closely monitored for recurrence.
In 1964, Dr Robert Sweet first described an acute febrile illness with erythematous
plaques in women associated with a nonspecific infection. Based on his clinical and
histologic observations, he coined the term acute febrile neutrophilic dermatosis.
Subsequently, others reported similar cases and named it Sweet syndrome. The
pathogenesis of this uncommon condition remains unknown, but since the original
description, reported associations with malignancy, autoimmune disorders, and
medications suggest a hypersensitivity reaction. We report a case of Sweet syndrome
following concomitant chemoradiation for tonsilar squamous cell carcinoma.
P1119
We report a case of a 57-year-old white female with a longstanding history of chronic
plaque-type psoriasis, erythema elevatum diutinum diagnosed in 2007, and celiac
disease who presented with a new rash. Several weeks earlier, the patient developed
a painful, pruritic eruption on the buttocks, arms, and legs. A physical examination
revealed discrete infiltrated erythematous papules on the buttocks, bullae and tense
edematous plaques with overlying thick scale on the lateral aspects of the feet, and
blanchable erythematous arcuate patches and thin plaques on the proximal thighs
and upper arms. The patient also had psoriatic plaques on the elbows, knees, and
shins. A biopsy specimen from the right medial thigh showed neutrophilic
dermatitis. Direct immunofluorescence showed 31 continuous IgA granular staining at the basement membrance zone. The patient was started on dapsone to treat
her widespread neutrophilic dermatoses, with components of both erythema
elevatum diutinum and dermatitis herpetiformis. Neutrophilic dermatoses constitute a heterogeneous but intertwined spectrum of diseases, and as is the case with
our patient, several different types of lesions may present in the same patient.
A case of livedo reticularis from amantadine
Lisa Xu, MD, Henry Ford Hospital, Detroit, MI, United States; Holly Kerr, MD,
Henry Ford Hospital, Detroit, MI, United States
Livedo reticularis (LR) is a cutaneous physical finding consisting of a reticulated netlike vascular pattern. It is caused by factors that reduce blood flow to cutaneous
arterioles with secondary widespread dilatation of the dermal peripheral veins. LR
may be physiologic and primary or secondary to intravascular obstruction or vessel
wall disease. There are many causes of secondary LR, including medications.
Amantadine, a synthetic antiviral agent currently used in the treatment of Parkinson
disease and other neurologic disorders, is a cause of drug-induced LR. The reported
incidence of amantadine-induced LR is highly variable, ranging from 2% to 90%. We
report the case of a 70-year-old white male with a 2-month history of livedo
reticularis. He was started on amantadine 2 years ago for Parkinson disease. Workup
for LR was within normal limits and the patient was diagnosed with LR secondary to
amantadine. Because the lesions were asymptomatic and the medication benefited
his neurologic disorder, it was continued by his neurologist. This case serves as a
reminder that LR is a known side effect of amantadine and can occur months to years
after initiation of the medication. Lesions tend to resolve a few weeks after
discontinuation of amantadine; however, development of the lesions does not
necessarily warrant cessation of the medication if it is beneficial for the patient.
P1117
A woman with widespread neutrophilic dermatoses: A case report
Dina Elrashidy, MD, Henry Ford Hospital, Detroit, MI, United States; Holly Kerr,
Henry Ford Hospital, Detroit, MI, United States
AB30
J AM ACAD DERMATOL
MARCH 2010
P1120
P1122
Multiple seborrheic keratoses arising in previous surgical sites
Blair Clementson, MD, University of New Mexico Department of Dermatology,
Albuquerque, NM, United States; Barrett Zlotoff, MD, University of New Mexico
Department of Dermatology, Albuquerque, NM, United States; Nancy Joste, MD,
University of New Mexico Department of Pathology, Albuquerque, NM, United
States
Nail dystrophy and periungual discolorationas a presenting feature of
systemic sarcoidosis
Firas Al-Niaimi, Salford Royal Hospital, Manchester, Lancashire, United Kingdom,
John Ashworth, Salford Royal Hospital, Manchester, Lancashire, United Kingdom
A 43-year-old male was referred from general surgery for multiple dark brown
verrucous papules on his lower abdomen and scrotum that arose in incision sites of
previous hernia repairs. On history, the patient reported abdominal and inguinal
hernias for 13 years. He had undergone three previous surgical repairs and shortly
afterward he noticed a ring-like growth of wart-like papules around the incision
sites. He did not seek medical attention for these until January 2009 when he
presented to general surgery for evaluation for yet another hernia repair. He had
tried no prescription or over the counter treatment for the above mentioned lesions.
He had no other significant medical history and no HPV history to his knowledge.
Examination findings on presentation were significant for multiple hyperpigmented
verrucous papules with a velvety surface in an annular distribution on his lower
abdomen and scrotum. Each annular ring was present around previous surgical
repair sites. Although the lesions had the clinical appearance of seborrheic
keratoses, the apparent koebnerization made verrucae higher on the differential.
A biopsy with shave technique was performed with pathology indicative of common
seborrheic keratoses. HPV typing was then performed on these specimens and was
negative for both low and high risk HPV types. A diagnosis of koebnerizing
seborrheic keratoses was made and attempts were made to contact the patient to
discuss diagnosis and treatment options. He was lost to follow-up. Seborrheic
keratoses are quite common and are considered by some to be ubiquitous among
elderly individuals. Several types exist, but the most common clinical appearance is
a verrucous velvety papule or plaque in hair bearing areas. These lesions are not
known to demonstrate koebnerization, and to our knowledge this is the first report
of seborrheic keratoses arising around previous incision sites.
A 56-year-old Asian man with a 5-year history of periungual red-purplish discoloration associated with nail dystrophy of most of his digits presented to the
dermatology department. The digits were asymptomatic and felt warm to touch
with good peripheral pulses and normal sensation. Examination of his toes showed
evidence of red to purple discoloration in the nail folds with associated nail
dystrophy. Nail clippings did not reveal fungi and vascular assessment did not show
any abnormality. Examination of his entire skin did not show any other cutaneous
lesions. There were no stigmata to suggest connective tissue disease. Further history
revealed a chronic nonproductive cough and few episodes of arthralgia affecting his
small joints. A chest radiograph showed evidence of hilar lymphadenopathy and full
laboratory investigation showed a raised serum ACE level. Connective tissue screen
was negative. A bronchoscopy performed by the pulmonary physicians of a lymph
node showed evidence of noncessating granuloma consistent with sarcoidosis.
Although no skin or nail matrix biopsy was taken, the nail fold changes and
associated nail dystrophy were thought to be related to his sarcoidosis. Cutaneous
lesions may occur in around a quarter of patients with sarcoidosis and may consist of
papules, nodules, and plaques. Nail dystrophy in sarcoidosis is rare and is mainly
associated with lupus pernio of the adjacent digit or with sarcoidal dactylitis, but
they have been reported in patients without clinically apparent involvement of the
adjacent soft tissue. Bone cysts of the terminal phalanx is an uncommon feature in
sarcoidosis but is often associated with nail dystrophy and its presence may indicate
a chronic course of the disease. Our patient did have evidence of bone cysts on
radiologic examination of the fingers. Although no skin or nail biopsy was obtained
from our patient, it was felt that the affected proximal nail fold was continuous with
the nail dystrophy and therefore examination of the nail matrix biopsy was felt to be
unnecessary.
P1121
A retrospective review of the use of dapsone in urticarial vasculitis
Mark Eliason, MD, University of Utah, Salt Lake City, UT, United States;
Christopher Hull, MD, University of Utah, Salt Lake City, UT, United States;
Doug Powell, MD, University of Utah, Salt Lake City, UT, United States; Lana Pho,
MD, University of Utah, Salt Lake City, UT, United States; Michelle Regruto,
University of Utah, Salt Lake City, UT, United States
Background: Chronic idiopathic urticaria (CIU) has a lifelong prevalence of 0.5% to
1% and has been shown in some studies to be cause disability equal to that of
coronary artery disease. Urticarial vasculitis is a subset of chronic urticaria that
frequently fails to respond to first-line treatment with antihistamines and often
requires treatment with immunomodulatory agents. Dapsone has been used to treat
CIU; however, there is limited evidence in the literature investigating the potential
benefit of dapsone in the treatment of urticarial vasculitis.
Methods: We performed a retrospective medical chart review and identified patients
with biopsy-proven urticarial vasculitis that were treated with dapsone in the
department of dermatology at the University of Utah between 2002 and 2007. We
gathered demographic and clinical data to assess the efficacy of dapsone to treat
chronic urticarial vasculitis.
P1123
Dermoscopic features of nodular hidradenoma
Ana Moreira, MD, CHVNGai/Espinho, Vila Nova de Gaia, Portugal; Agostinho
Sanches, MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Armando
Baptista, MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Nuno Menezes,
MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Paulo Varela, MD,
CHVNGaia/Espinho, Vila Nova de Gaia, Portugal
Nodular hidradenoma is an uncommon benign, adnexal cutaneous neoplasm that
usually appears in adults, preferentially in women, most commonly on the scalp,
face, trunk, and abdomen.
Discussion: This retrospective case review provides evidence of dapsone as an
effective treatment for chronic urticarial vasculitis. In our cohort of patients, those
that did have a durable responses to dapsone usually responded quickly (within 4
weeks). Side effects, while frequent, were generally mild and resolved when therapy
was discontinued. Our work supports further investigation with controlled clinical
trials.
A 67-year-old woman was examined for an asymptomatic, slow growing, firm,
solitary, smooth-surfaced, whitish-pink, movable dermal nodule 1.2 3 0.8 cm in size
located above the upper lip. The lesion had been present for approximately 3 years
and had slowly increased in size during the last year. The physical examination did
not show any similar lesions or regional lymphadenopathy. We included in the
differential diagnosis basal and squamous cell carcinoma, eccrine poroma, dermal
nevus, amelanotic melanoma, and sebaceous hyperplasia. Dermoscopy analysis
revealed a reddish-pink lesion with a polymorphous vascular pattern with linear
irregular, dotted, and hairpin vessels at the periphery and a pink-white structureless
area at the center. A white scale was also observed. A complete surgical excision was
performed. Histopathologic examination showed a nodular, solid-cystic lesion in the
dermis. The tumor lobules were made up of two cell populations. The epithelial
component consisted of closely packed aggregations of round or polygonal cells and
the rare cystic spaces were often filled with mucin. The tumor was surrounded by a
fibrous capsule. These histopathologic findings allowed us to establish the diagnosis
of nodular hidradenoma. Because hidradenomas cannot be recognized clinically and
can mimic a variety of benign and malignant skin tumors, this case underscores the
importance of further dermoscopic characterization of nonmelanocytic amelanotic
lesions, such as nodular hidradenoma. To date, little is known about the
dermoscopic features of this condition, with just one case reported in the literature.
Results: We identified 58 continuous patients (44 female, 14 male) with biopsyproven urticarial vasculitis that were treated with dapsone. Their ages ranged from
21 to 81 years (average, 43.7). Their duration of urticaria ranged from 2 to 240
months with an average of 37.4 months. Thirty-two patients had a history of
angiedema. Thirty-eight patients had been treated previously with oral steroids. The
average duration of treatment with dapsone was 4.7 months. Their treatment dosage
ranged from 25 to 300 mg dapsone/day. Thirty patients (52%) had ‘‘excellenteclear’’
response. Fourteen patients (24%) had partial response. Seven patients (12%) had no
response and six patients (10%) worsened while on therapy. Twenty-three patients
(40%) that cleared on dapsone were successfully tapered off therapy and did not
require further systemic therapy. Side effects experienced by patients on dapsone
were generally mild and resolved upon cessation of dapsone. There were no serious
adverse events reported.
MARCH 2010
J AM ACAD DERMATOL
AB31
P1124
P1126
Successful long-term infliximab therapy in severe recalcitrant hidradenitis suppurativa
Ana Moreira, MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Armando
Baptista, MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Inês Leite, MD,
CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Rita Guedes, MD,
Extensive spontaneous keloidosis: A case report
Robert Sage, MD, Henry Ford Health System, Department of Dermatology,
Detroit, MI, United States; Jungho Kwon, MD, Henry Ford Health System,
Department of Dermatology, Detroit, MI, United States
Keloidosis is the deposition of excessive fibrous scar tissue composed of predominantly collagen types I and III at the sites of healed skin injuries. While most
commonly a result of trauma, keloid formation may result from systemic disease,
infection, tattoo placement or may be syndromic. More rarely keloids may erupt
spontaneously. We report the case of a 57-year-old African American man with a
history of spontaneous keloid formation since childhood. More than 20 years before
presentation to our department, he had surgeries to attempt removal. Since that
time, he developed gradually enlarging exophytic tumors with tissue breakdown
and secondary infection. Lesions were located diffusely on the shoulders, chest,
back, extremities, and inguinal region. Biopsies from abdominal and elbow lesions
revealed keloids with acute and chronic inflammation and multiple hairs embedded
within giant cells, similar to that seen in acne keloidalis nuchae. This case serves as a
reminder that keloids may occur spontaneously and develop unpredictably as
haphazard arrangements of collagen. Furthermore, this subtype of keloidosis is rare
and may be part of a follicular occlusion phenomenon. The literature on spontaneous keloidosis will be reviewed.
We report a case of a 41-year-old man who was referred to our department by the
gastroenterology department with a 5-year history of inflammatory nodules and
abscesses in the buttocks and perianal area. The lesions were very tender and
extremely painful. Over time, sinus tracts and hypertrophic scars developed,
accompanied by chronic drainage of purulent material with a foul smell. Bands of
scar tissue and bridging fibrosis developed later. A skin biopsy specimen showed
heavy mixed inflammatory cell infiltrate in the dermis, irregular acantosis, and
extensive fibrosis with the destruction of pilosebaceous follicles and sweat glands.
The laboratory evaluation revealed anemia, elevation of white blood cells, PCR, VS,
and other inflammatory markers. Colonoscopy was performed twice to exclude
Crohn disease. Pelvic TC and MR confirmed the diffuse involvement across the
perianal area with multiple interconnected sinus tracts and abscesses. The internal
organs were not involved. The diagnosis of stage III hidradenitis suppurativa was
established. Treatment with isotretinoin 1 mg/kg/day for 2 years had only very slight
impact. After contraindications exclusion, infliximab infusions (5 mg/kg) were
started. They were given at weeks 0, 2, 6, and 8. The patient has already completed
11 infusions, experiencing significant improvement with almost complete clearing
of the eruptions in the anogenital area with great improvement of quality of life
indexes. Hidradenitis suppurativa is one of the follicular occlusion diseases favoring
the flexural areas of the body. There is a need for effective medical antiinflammatory
therapy to control the disease and minimize the pathologic and socioeconomic
consequences. This case report supports the long-term use of infliximab in patients
with severe, longstanding hidradenitis suppurativa.
P1125
Giant polypoid clear cell acanthoma: New observations on dermatoscopy
Gloria Maria Garnacho Saucedo, Hospital Universitario Reina Sofı́a, Cordoba,
Spain; Antonio Velez Garcia Nieto, Hospital Universitario Reina Sofia, Cordoba,
Spain; Jose Carlos Moreno Gimenez, Hospital Universitario Reina Sofı́a, Cordoba,
Spain; Rafael Salido Vallejo, Hospital Universitario Reina Sofı́a, Córdoba, Spain
Introduction: Clear cell acanthoma (CCA) is a benign tumor of epidermal origin.
Although there are many publications about this entity, giant and polypoid clinical
variants are rare. We report a case of CCA clinically exceptional because it was giant
and polypoid and describe its particular dermoscopic pattern.
Case report: A 55-year-old man presented with a 10-year history of a slowly growing
lesion on the back of his right foot. The dermatologic examination revealed a red,
vascularized, cerebriform, and polypoid plaque with a diameter of 3.8 3 4.7 cm.
Dermoscopy disclosed rounded structures separated by septa white honeycomblike. Multiple homogeneous dotted vessels, arranged either in a linear, pearl-like
distribution or in a reticular pattern, were visible in each of these structures.
Systemic examination of the patient was normal and laboratory tests were within
normal limits. A skin biopsy specimen showed a well demarcated epidermal
hyperplasia with paled and strongly periodic acideSchiff (PAS) positive
keratinocytes.
P1127
Discussion: CCA is usually characterized by an asymptomatic red nodule located
over the lower extremities of adult patients. Dermatoscopic features of CCA are not
yet well established. Only six articles have been focused on the dermatoscopic
findings of CCA, and the common denominator of all these reports is the presence of
pinpoints-like/dotted vessels. In this poster, we describe new observations on the
dermoscopy of these unusual clinical variant.
Concordance between prescribed and dispensed topical corticosteroids
Brooke Shadel, MD, MPH, PhD, Saint Louis University Department of
Dermatology, Saint Louis, MO, United States; Dana Oliver, MPH, Saint Louis
University Department, Saint Louis, MO, United States; Samantha Hill, MD, Saint
Louis University Department of Dermatology, Saint Louis, MO, United States;
Sarah Jensen, MD, Saint Louis University Department of Dermatology, Saint Louis,
MO, United States
Topical corticosteroids are a frequently prescribed medication available in multiple
vehicle preparations, potencies, and quantities. Generic substitutions are often
made at the time of pharmacy dispensing. This study was a prospective survey of
patients of all ages in a general dermatology clinic who received a prescription for
topical corticosteroid medication. Differences between written prescriptions for
these medications and what was dispensed were evaluated. Fifty prescriptions were
recorded between November 2008 and March 2009, of which 43 were filled. Ninetytwo percent of the prescriptions allowed substitutions. Five substitutions were
made, one of which was written for dispense as written. The prescribed vehicle did
not match the dispensed vehicle for one prescription (a cream was dispensed for an
ointment). The written quantity matched what was dispensed in most encounters
(82%). Interestingly, one specific retail pharmacy was used by the majority of
patients (70%) even though the patients came from a wide referral base, making any
substitutions in dispensed medications somewhat standardized. The conclusions of
this study are somewhat limited by the small sample size; however, these data
suggest that substitutions are often allowed by providers and likely influenced by the
use of a common retail pharmacy type. Overall, prescriptions were filled as
prescribed.
AB32
J AM ACAD DERMATOL
MARCH 2010
P1128
P1130
Gold is skin deep: Multiple facial foreign body granuloma caused by
injection of gold acupuncture needle
Yu Jin Kim, MD, Department of Dermatology, School of Medicine, Chungnam
National University, Daejeon, South Korea; Dae Hoon Kim, MD, Department of
Dermatology, School of Medicine, Chungnam National University, Daejeon,
South Korea; Young Joon Seo, MD, Department of Dermatology, School of
Medicine, Chungnam National University, Daejeon, South Korea
Gold is generally considered to be an inert metal with low solubility, and gold allergy
has traditionally been regarded as a rare occurrence. But recent studies show that
gold allergy is more common than previously recognized. A 62-year-old woman
developed multiple palpable nodules on her face. The physical examination
revealed several erythematous papules and multiple subcutaneous nodules. Seven
months earlier, she had acupuncture on her face involving the injection of gold
needles to reduce wrinkles. An excisional biopsy of one lesion was performed, and
yellowish, thread-like metallic structures were found in the excised nodule.
Histopathologically, there was a dense, granulomatous lymphohistiocytic infiltration
of the mid- and reticular dermis and multinucleated giant cells. A subsequent
radiograph revealed numerous radiopaque curved or straight linear densities that
were consistent with the presence of gold acupuncture needles in her face. Based
on these findings, a diagnosis of foreign body granulomas caused by the injection of
gold needles was made. We report the development of multiple facial foreign body
granulomas at the site of gold needle injections. Our case shows that gold needle
injection to reduce wrinkles of the face can cause a delayed granulomatous reaction.
This side effect can be irreversible and therefore should be addressed in the
informed consent.
Bilateral multiple auricular pseudocyst of the auricle: A case report
Francisco Benavente, MD, Hospital Universitario ‘‘Virgen de las Nieves,’’ Granada,
Spain; Cesar Garcı́a-López, MD, Hospital Universitario ‘‘Virgen de las Nieves,’’
Granada, Spain; Valentı́n Garcı́a-Mellado, MD, PhD, Hospital Universitario
‘‘Virgen de las Nieves,’’ Granada, Spain
Pseudocyst of the auricle is a rare, asymptomatic cystic swelling of the auricle
resulting from accumulation of yellow viscous fluid. Although its etiology is
unknown, treatment is difficult and recurrence frequent. The lesion is usually
single and unilateral. An 84-year-old man was admitted in our department showing
bilateral, multiple auricular nodules, which were firm, tense, painless, and the skin
over it was erythematous, since several years. We considered a diagnosis of nodular
condrodermatitis helix or pseudocysts of the auricle. The lesion biopsied was
characterized by an intracartilaginous cavity that was lacking an epithelial lining,
with a mucoid content and market eosinophilic hyalinizing degeneration in the
auricle cartilage in a difuse distribution. The epidermis and dermis were normal, and
there was not an inflammatory infiltrate. The patient refused treatment. Auricle
pseudocyst was first described by Hartman in 1885, but the term auricular
pseudocyst was first used in 1966 by Engel. Auricular pseudocyst is a benign
process more frequent in males and from the fourth decade of life, often manifest as
an elastic, painless, swelling on the lateral or anterior surface of the auricle, usually
in the scaphoid or triangularis fossa. It contains straw-colored, sterile liquid. Most
published cases are single and unilateral, and there are very few multiple and
bilateral case reports. The etiology of pseudocyst is unknown, but two main theories
have been reported. The first theory suggests that a pseudocyst often results after
repeated minor low-grade trauma, such as rubbing, ear pulling, sleeping on hard
pillows, or earphones. The second theory hypothesized is that congenital
embryologic defect of the auricular cartilage is the predisposing factor in the
development of the pseudocyst. The characteristic histologic feature is an intracartilaginous cystic space with no epithelial lining. There is often some granulation
tissue and fibroblastic lining the cystic apace and inflammatory response indicated
by the presence of perivascular infiltration of leukocytes. The most accepted
treatment is to drain the cavity or surgical excision of the anterior cartilage and
pressure dressing. However, it is a highly recurrent injury.
P1129
P1131
A case of unusual idiopathic pseudoeKaposi sarcoma
Sang Hee Cha, MD, Sang Hee Cha, Bupyung-Gu, Inchon, South Korea; Eujin Cho,
MD, Eujin Cho, Bupyung-Gu, Inchon, South Korea; Jeong Deuk Lee, MD, Jeong
Deuk Lee, Bupyung-Gu, Inchon, South Korea; Sang Hyun Cho, MD, Sang Hyun
Cho, Bupyung-Gu, Inchon, South Korea; Young Bok Lee, MD, Young Bok Lee,
Bupyung-Gu, Inchon, South Korea
PseudoeKaposi sarcoma, a condition that is also known as acroangiodermatitis, is a
rare vasoproliferative disorder. It manifests usually as erythematous, violaceous, or
brown macules, patches, papules, or plaques on the extensor surfaces of the lower
extremities. There are two variants of pseudoeKaposi sarcoma: the Mali type,
associated with chronic venous insufficiency and commonly developing bilaterally
in elder patients, and the StewarteBluefarb type, associated with congenital
hemangioma, arteriovenous malformation, or arteriovenous fistula in younger
patients and often occurring unilaterally. Treatment of pseudoeKaposi sarcoma
involves correction of the underlying vascular condition. The mainstays of therapy
include pressure garments, such as compression stockings and compression pumps,
for venous stasis. Pulsed dye laser ablation may also be helpful. Although medical
therapies are limited, improvement with oral dapsone and oral erythromycin has
been reported. A 58-year-old man presented with a 20-year history of pruritic blueblack plaques on the dorsal surface of his right foot. The lesions were multiple,
grouped, hard, blue-black plaques. The lesion was initially a bluish macule, and the
number and the size gradually increased. The patient denied a history of a traumatic
event on the area. No notable findings were identified on either medical or family
history. On physical examination, localized heatness and edema of the involved foot
was prominent. Histopathologic examination of the lesion showed proliferative,
small sized capillaries forming lobules through the entire dermis with perivascular
lymphohistiocyte infiltration. Dilated vessels walls were thickened, endothelial cells
were plump, and vascular slits were absent. Cytologic atypia— which implies
Kaposi sarcoma—was not noted. The expression of the CD34 antigen was observed
only in the endothelial cells and not in the surrounding stroma. S-100 and HMB45
stained negative. The biopsy confirmed the diagnosis of pseudoeKaposi sarcoma,
and the patient was referred to a vascular surgeon. We report an unusual case of
pseudoeKaposi sarcoma that developed without associated diseases or preceding
trauma, and it is atypical in that it occurred unilaterally in an elderly age with
histologic findings throughout the dermis.
Elastosis perforans serpiginosa in a patient with Down syndrome treated
with imiquimod 5% cream
Birgitte Stausbøl-Grøn, MD, PhD, Department of Dermatology, Århus C, Region
MIDT, Denmark; Mette Ramsing, MD, Department of Pathology, Århus C, Region
MIDT, Denmark; Mette Sommerlund, MD, PhD, Department of Dermatology,
Århus C, Region MIDT, Denmark; Pernille Axel Gregersen, MD, Department of
Dermatology, Århus C, Region MIDT, Denmark
Elastosis perforans serpiginosa (EPS) is a rare skin disease characterized by
hyperkeratotic papules, transepidermal elimination of abnormal elastic fibers, and
focal dermal elastosis. After an inflammatory response, the abnormal elastic fibers
are eliminated through an epidermal perforation, a process varying from month to
years. The etiology is unknown. An association with underlying systemic disorders,
including Down syndrome, has been described, and in 2008 Espinosa et al
questioned whether EPS could be a marker for progression of cerebrovascular
occlusive disease in Down syndrome. Efficacy of treatments with cryotherapy,
curretage, CO2 laser treatment and isotretinoin are low. However, Kelly and Purcell
suggested treatment of idiopathic EPS with imiquimod 5% cream in 2006. In our
department, a 45-year-old man with Down syndrome presented with symmetrical
annular elements on his forearms and femurs. The elements were erythematous
with a centrifugal distribution and atrophic hypopigmented central healing.
Peripherally, infiltrated, keratotic papules with desquamation were seen. The
surrounding skin was normal. A punch biopsy specimen taken from the thigh
showed the classical histopathologic features of EPS. There were transepidermal and
transfollicular perforation canals containing inflammatory debris and degenerated
elastic fibers. In the surrounding dermis, the elastic fibers were thicker than normal
and partly degenerated. Examination of blood samples, blood pressure, echocardiogram, and echocardiography was normal. We initiated topical therapy with
imiquimod 5% cream once a day for 6 weeks followed by three times weekly for 4
weeks to a single element. As regression of EPS was observed and the patient
tolerated the therapy well, treatment of other lesions were commenced. In
conclusion, this abstract describes a patient with EPS and Down syndrome with
no clinical signs of cerebrovascular disease, treated with imiquimod 5% cream with a
promising result. The mechanism is unknown; however, imiquimod might accelerate the immune response to the abnormal elastic fibers, resulting in an accelerated
resolution.
MARCH 2010
J AM ACAD DERMATOL
AB33
P1132
P1134
Hyperpigmented spots modeling with the in vivo reflectance confocal
microscope (RCM)
Akiko Nakajima, MS, Kobe Technical Center, Procter & Gamble Japan, Kobe,
Hyogo, Japan; Tomohiro Hakozaki, PhD, Miami Valley Innovation Center, The
Procter & Gamble Company, Cincinnati, OH, United States
Sebaceous neoplasms in lung transplant patients with and without concomitant cyclosporine
John Vu, MD, PhD, University of Pittsburgh Medical Center, Department of
Dermatology, Pittsburgh, PA, United States; Alexandra Zhang, MD, University of
Pittsburgh Medical Center, Department of Dermatology, Pittsburgh, PA, United
States; Jonhan Ho, MD, University of Pittsburgh Physicians, Department of
Dermatology, Dermatopathology Unit, Pittsburgh, PA, United States
Background: Sebaceous neoplasms, such as sebaceous hyperplasia, are a common
occurrence in transplant patients who are immunosuppressed in particular by
cyclosporine. These neoplasms serve as a significant cosmetic problem and could be
harbingers to more destructive cutaneous nonmelanomatous skin cancers (NMSC).
Though the association between these tumors and NMSC has been well described in
renal transplant patients, we present such findings in association with lung
transplants.
Background: Facial hyperpigmented spot care has been one of the key benefits for
skin care products. Concerned consumers may have perceptions that certain
hyperpigmented spots seem to disappear by applying whitening products while
other spots do not, even with similar appearance. However, the differences of these
spots are not fully elucidated yet.
Objective: To classify cutaneous hyperpigmented spots regularly seen in healthy
Japanese females based on the pattern of inner skin structure by utilizing a
noninvasive technique.
Method: Forty-six healthy Japanese females (age, 33-59 years; average, 43.8 years)
who had either (1) moderate to severe freckles, (2) solar lentigo larger than 1 cm in
diameter, or (3) melasma participated in the study. Vivascope 1500 Plus, an in vivo
reflectance confocal microscope (RCM), was used to investigate the morphologic
features of cutaneous hyperpigmented spots on the face. The RCM technology
enables visualization of living human skin as deep as 200 m by 1-m increments in
depth. The pattern of dermoepidermal junction (DEJ), melanin amount, and
epidermal thickness were assessed visually. Konica-Minolta Chromameter (CR300)
was also used to evaluate the L* value of the pigmented areas.
Results: We found the facial spots could be divided into four unique types: (1) flat
DEJ, (2) flat DEJ with thicker epidermis, (3) flat DEJ and large melanosomes, and (4)
bumpy/wavy DEJ. In this study, more of the flat DEJ pattern was observed in freckles
and melasma panelists, and bumpy/wavy pattern was observed in large solar lentigo
spot panelists. The epidermis tended to be thicker in wavy DEJ type of pigmentation, suggesting a potential abnormality in keratinocyte proliferation, differentiation, turnover, et cetera, in this type of pigmentation. Interestingly, dendritic
melanocytes were dominant in flat DEJ patterns, especially more in melasma than in
freckles (melasma 46% vs freckles 23%). The visual grading score of RCM melanin
amount at the basal layer and Chromameter L* value had a significant negative
correlation (P \ .001). This confirms that the expert visual grading of the RCM
images reflected melanin amount correctly.
Conclusions: We were able to identify unique observations around facial hyperpigmentation and its internal structures. These new understandings of the internal
details of spots will help guide the development of efficacious compounds to aid in
reducing the appearance of hyperpigmented spots.
Case reports: We present two varying cases of sebaceous neoplasms. One patient
had eruptive development of facial sebaceous hyperplasia (SH) on cyclosporine
long-term with concomitant calcium channel blocker usage after single-lung
transplant secondary to Eisenmenger syndrome. Because of the extensive involvement of the face for this patient, he was elected to be placed on acitretin. During the
time of development of SH, he also developed multiple NMSCs, both squamous cell
carcinomas and basal cell carcinomas requiring excision. A second case is of a
patient with a single-lung transplant secondary to idiopathic pulmonary fibrosis on
mycophenolate mofetil and tacrolimus with spontaneous development of sebaceous adenoma and with normal expression of MLH-1 and MSH-2 by immunohistochemistry. Monitoring for new developing appendageal tumors was opted for this
patient.
Conclusions: The association between cyclosporine and the development of
appendageal tumors has been well described. Though the mechanism has not
been fully elucidated, it likely occurs independent of immunosuppression and can
possibly be caused by the imbalance of other molecular mediators, such as
overexpressed TGF-alfa, Smad7, c-myc, or underexpressed MLH-1, MSH-2, or higher
susceptibility to aging with reduced androgen or increased UV radiation damage
causing microsatellite instability or photoinduced DNA damage. Because of other
comorbidities in transplant patients, treatment of sebaceous neoplasms is often
limited to nonsystemic options, such as laser, photodynamic therapy, and chemical
peels, although systemic retinoids have been described. We present two unique
cases of sebaceous gland dysplasia in lung transplant patients.
Commercial support: 100% of this research was sponsored by Procter & Gamble
Japan K.K.
P1133
P1135
Chemotherapy-drug related symmetrical intertriginous dermatitis with
underlying eccrine squamous syringometaplasia: Clinicopathologic study
of 20 cases of a new drug reaction pattern
Antonio Martorell-Catayud, MD, Fundación Instituto Valenciano de Oncologı́a,
Valencia, Spain; Carlos Serra-Guillen, MD, Fundacion Instituto Valenciano de
Oncologia, Valencia, Spain; Onofre Sanmartı́n, MD, PhD, Fundación Instituto
Valenciano de Oncologı́a, Valencia, Spain; Rafael Botella-Estrada, MD, PhD,
Fundacion Instituto Valenciano de Oncologı́a, Valencia, Spain
Background: Eccrine squamous syringometaplasia is a histopathologic feature that is
characterized by a squamous metaplasia of the cuboidal epithelial cells of the
eccrine sweat ducts. This finding has been associated mostly with oncologic
patients receiving several chemotherapeutic regimens, but it has been described
with a great variety of conditions, mainly as single cases. The clinical pattern is
considered unspecific and includes erythematous macules, papules, plaques, or
vesicles that may be localized or generalized in rich eccrine gland areas. However,
there are some authors who suggest a characteristic clinical pattern affecting
predominantly the intertriginous areas, which appears specifically as a secondary
drug reaction to chemotherapeutic regimens.
A retrospective study of the demographics and clinical characteristics of
patients with hidradenitis suppurativa in an urban academic center
Katherine Flanagan, MD, Saint Louis University, Saint Louis, MO, United States;
Sarah Jensen, MD, Saint Louis University, Saint Louis, MO, United States
Background: Hidradenitis suppurativa (HS) can be a chronic and disabling disease.
Treatment response is variable, and there is no cure for patients with HS. Clinical
characteristics of patients with HS in the United States have not been well described,
and improved understanding of the clinical characteristics of these patients may
improve therapeutic options.
Methods: Our aim is to better define the features of this entity. For that purpose, we
are reporting the clinical and histopathologic characteristics of 20 patients under
cytostatic therapy who developed intertriginous lesions with the histopathologic
feature of eccrine squamous syringometaplasia.
Results: Patients with the intertriginous pattern were mostly men 48 to 60 years of
age. Clinically, the lesions presented as erythematous patches, papules, plaques, or
vesicles affecting symmetrically axillae, groins, and lateral aspects of the neck. With
lesser frequency, the lower eyelids and the palm of the hands were involved. The
lesions were characterized histologically by the transformation of the eccrine
cuboidal epithelium into two or more layers of squamous cells with intercellular
bridges. The onset of the eruption appeared within a range of 2 to 30 days after the
initiation of the cytostatic infusion. The eruption generally resolved within 10 days,
with desquamation and without scarring in any of the cases.The occurrence of this
characteristic pattern was mainly associated with patients receiving liposomal
doxorubicin and with those who were treated with the combined cytostatic
regimen used before the bone marrow autologous transplant, which included
cyclophosphamide, thiotepa and a third drug (carboplatinum, cisplatin, carmustine,
or etoposide).
Objective: To perform a study of clinical characteristics of patients treated for HS in
an urban academic center.
Methods: A retrospective chart review of patients $ 18 years old over the last 5
years was performed.
Results: One hundred eighty charts were identified with 115 of 180 patients (64%)
included in the study. Fifteen percent were male and 85% were female. More than
half (50.4%) were white and 41.7% were African American, with the remainder of
unknown ethnicity. Mean age was 33.36 years old. More than one quarter (26.1%)
had mild, 49.6% had moderate, and 24.3% had severe disease. The majority had
disease in the axillae and/or groin (54%) and the rest had disease in inframammary,
thigh, and buttock areas. Almost half (45.1%) had a history of acne vulgaris and 4.4%
had follicular occlusion triad. Eighty-eight percent received antibiotics, 90% were
treated with topical washes and 37% with topical antibiotics. Mild improvement
occurred in 28.7% of patients, and 40.3% had significant improvement with therapy.
Some patients (8.7%) were prescribed isotretinoin, but compliance varied and only
1.7% noted improvement. Few were treated with antietumor necrosis factor agents.
Thirty-one percent had surgical procedures for treatment of HS. Sixteen percent had
culture data, and 89% of cultures of lesions were negative or contaminant. Many
patients (26.8%) were described as overweight or obese. One quarter (25%) had
psychiatric disease with depression as the most common diagnosis. Some female
patients had a history of hyperandrogenism with PCOS and/or hirsutism (8.2%).
Conclusion: The intertriginous pattern with the typical histopathologic feature of
eccrine squamous syringometaplasia defines a distinctive subtype of chemotherapeutic drug reaction, related mainly with liposomal doxorubicin infusions and with
chemotherapeutic regimens used in the autologus bone marrow transplant.
Limitations: The retrospective design of this study allows for incomplete data
collection.
Conclusions: African Americans were overrepresented in our population. Therapy is
empiric, consisting of chronic courses of rotating antibiotics and variable response.
Many patients had diagnosed psychiatric disease, which may complicate their
treatment. Culture data often is negative, suggesting other inflammatory mechanisms besides bacterial superinfection. Women with HS may have a hyperandrogenic state and may benefit from antiandrogen therapy. Further prospective studies
are necessary in patients with HS.
AB34
J AM ACAD DERMATOL
MARCH 2010
P1136
P1138
Coexistence between actin granuloma and annulare granuloma in two
patients
Ana Rita Rodriguez de Valentiner, MD, Hospital Valle de los Pedroches,
Pozoblanco, Cordoba, Spain; Ada Cecilia Fiandesio, MD, Hospital Valle de los
Pedroches, Pozoblanco, Cordoba, Spain; Isabel Rosa Hidalgo Parra, MD, Hospital
Valle de los Pedroches, Pozoblanco, Cordoba, Spain
Methylaminolevulinate photodynamic therapy for granuloma annulare: A
case report
Joana Rocha, MD, Hospital S~ao Marcos, Braga, Minho, Portugal; Celeste Brito,
MD, Hospital S~ao Marcos, Braga, Minho, Portugal; Filipa Ventura, MD, Hospital
S~ao Marcos, Braga, Minho, Portugal; M.Luz Duarte, MD, Hospital S~ao Marcos,
Braga, Minho, Portugal
Actinic granuloma is an unusual disease. It has been defined as a disease localized in
chronically sun-damaged skin, with the presence of giant cells, degeneration and
phagocytosis of elastic fibers in the biopsy specimen, and low response to topical
corticosteroids. Actinic granuloma and annulare granuloma have been considered
either as separate entities or as features of the same disease. Herein, we report two
patients: a 48-year-old woman with a 15-year history of the disease and a 76-year-old
man with a 16-year history of the disease. Both of them had clinical and histopathologic diagnosis of actinic granuloma and annulare granuloma at different periods.
The lesions were mainly localized in sun-damaged skin with some lesions on the rest
of their bodies. Neither patient responded to topical corticosteroids. Several
biopsies were performed that confirmed the diagnoses of annular granuloma and
actinic granuloma in both patients. The existence of actinic granuloma as a
distinctive entity from annular granuloma is controversial. Our cases could suggest
that actinic granuloma, found in-sun exposed areas, are annulare granuloma
modified by sun radiation.
Granuloma annulare is a benign noninfectious granulomatous dermatosis characterised by a ring of asymptomatic skin-colored or erythematous papules, affecting
most frequently the upper and lower extremities. Generalized forms of the disease
have a later age of onset, a low tendency for spontaneous resolution, and a poorer
response to therapy. Although the etiology and pathogenesis of granuloma annulare
are not fully understood, many hypotheses have been postulated. Its association
with diabetes mellitus has not been completely clarified. We report the case of a 46year-old white diabetic woman who presented with a long-lasting history of multiple
disseminated granuloma annulare lesions. After failure of conventional topical
therapies, treatment with methylaminoelvulinate photodynamic therapy was tried.
There was significant improvement of the lesions with flattening and less erythema
after a few treatments. There were no major side effects. There are no large, well
designed, randomized controlled trials on the treatment of granuloma annulare.
Therapeutic modalities often remain unsatisfactory and can be accompanied by
potentially hazardous side effects. Encouraging case reports about the successful
effect of photodynamic therapy in generalized granuloma annulare have been
published, suggesting that it is a viable therapeutic option in these cases. The case
reported here is another one of these cases.
P1139
Conclusions: While several self-report measures of adherence have been validated in
chronic disease populations, their relevance in dermatology patients has not been
studied. A dermatology-specific instrument for the measurement of adherence
would contribute to improved outcomes; until such a tool exists, researchers and
clinicians should consider nonadherence as a possible factor in skin disease that is
not responsive to treatment.
HenocheSchönlein purpura of unusual location
Brazil; Fernando Mósca de Cerqueira, Hospital Municipal Jesus, Rio de Janeiro,
Brazil; Lorena Caselli, MD, Policlı́nica Geral do Rio de Janeiro, Rio de Janeiro,
Brazil; Marlene Albuquerque Sessim, MD, Policlı́nica Geral do Rio de Janeiro, Rio
de Janeiro, Brazil
Introduction: HenocheSchönlein purpura (PHS) is the most frequent small vessel
leukocytoclastic vasculitis in childhood. It is rare in adulthood and has a poorer
prognosis when it occurs in this age group. It is characterized by nonthrombocytopenic palpable purpura, arthritis and/or arthralgia, abdominal pain, gastrointestinal bleeding, and/or nephritis. In some cases, an allergic cause can be detected.
The skin lesions are present in 100% of cases either in the form of palpable purpura
or in other forms of rash, in most cases located predominantly in the lower limbs. In
general, the trunk is spared. The vasculitis may be associated with the presence of
infectious agents and the beta hemolytic streptococcus group A is the most common
of them. Other infectious agents involved are: parvovirus B19, Mycoplasma
pneumoniae, Yersinia spp., Campilobacter jejuni, and Helicobacter pylori.
Other triggers of the disease are contact with specific food allergens, such as dyes
and preservatives, drugs, and vaccines.
Reason for the communication: Report of a case with an unusual presentation and
location of lesions.
Case report: A 40-year-old white male who was born in Rio de Janeiro presented
with numerous purpuric erythematous papules on the palmar regions without
itching and systemic manifestations. The lesions appeared 1 day after the patient
ingested wine and Roquefort cheese. The histopathologic examination revealed
perivascular dermatitis with a predominantly lymphocytic infiltrate associated with
marked edema in the papillary and superficial reticular dermis and extravasation of
red blood cells. In addition, a mild lymphocytic exocytosis was observed in the
epidermis. Laboratory tests revealed a cell blood count and renal function tests that
were in the normal range.
Discussion: The diagnosis of PHS is essentially clinical, but biopsy and immunofluorescence can be used as complementary methods in the elucidation of this case,
revealing the presence of leukocytoclastic vasculitis and IgA in the wall of blood
vessels, respectively. The laboratory changes were nonspecific: moderate anemia,
changes in the urinary sediment, increased 24-hour urinary protein measurement,
and elevated levels of BUN and creatinine. The treatment duration was 1 week, and
it was performed with prednisone 60 mg per day initially, then the dose was reduced
to 40 mg per day.
P1137
Assessing adherence to dermatology treatments: A review of available selfreport measures
Sheila Greenlaw, MD, WFU School of Medicine, Winston Salem, NC, United
States; Brad Yentzer, MD, WFU School of Medicine, Winston Salem, NC, United
States; Rajesh Balkrishnan, PhD, Schools of Pharmacy and Public Health, Ann
Arbor, MI, United States; Steven Feldman, MD, PhD, WFU School of Medicine,
Winston Salem, NC, United States
Background: Nonadherence to prescribed medications is a common problem in
dermatology, and assessing adherence can be difficult. Electronic monitors are not
always practical, but self-report measures may be less reliable.
Purpose: To review the literature for self-report instruments used to measure
medication adherence in patients with chronic disease.
Methods: A PubMed literature search was conducted using the terms ‘‘scale,’’
‘‘measure,’’ ‘‘self-report,’’ and ‘‘medication adherence.’’ Relevant articles were
reviewed and selected if they addressed self-report measures of adherence in
chronic disease.
Results: Eleven self-report instruments for the measurement of adherence were
identified. Four were validated using electronic monitors. All produced an estimate
of adherence that correlated with actual behavior, though this correlation was not
strong for any of the measures. None of the scales was tested in patients who had
dermatologic disease and/or used topical medications.
MARCH 2010
J AM ACAD DERMATOL
AB35
P1140
P1142
Coinfection by herpes simplex virus and EpsteineBarr virus causing
erythema multiforme
Ana M. Mosca de Cerqueira, MD, Hospital Municipal Jesus, Rio de Janeiro, Brazil;
Fernando M. de Cerqueira, Universidade Gama Filho, Rio de Janeiro, Brazil;
Larissa Fernanda Campos Moreira, MD, Hospital Quinta D’Or, Rio de Janeiro,
Brazil; Soraya de S. C. Oliveira, MD, Hospital Municipal Jesus, Rio de Janeiro,
Brazil
Introduction: Erythema multiforme (EM) is a cutaneous reaction pattern precipitated by varied agents, notably herpes simplex virus (HSV) and drugs. It predominantly occurs in adolescents and young adults, but also can be seen at other ages.
While vaccination is rarely a precipitating factor for erythema multiforme, it may
occasionally be seen in infants and children. EM has been rarely reported in
EpsteineBarr virus (EBV)-associated diseases, which includes patients with chronic
fatigue syndrome. We report here a case of a 3-year-old child with EM with
involvement of oral mucous and abnormal antibody reactivity to EBV and HSV.
Case report: A 3-year-old female presented to our department with multiple annular
plaques on the acral parts of her body, bilaterally, with variable size and erythematous and violaceous depressed centers. It begins with no prodromal symptoms and
after a few days, target lesions appear typically on the palms, soles and extensor
aspect of extremities. Some have central blisters with a necrotic blister roof,
exulceration, without secondary infection. The pruritus was intense and mucous
oral membrane is involved. There is no hepatomegaly and lymphonodomegaly.
Laboratory findings included normal hepatic enzymes, negative monotest, enzymelinked immunosorbent assay with immunoglobulin M HSV antibody and EBV were
positives. Antibodies against other viruses, including enteroviruses, hepatitis A
virus, and cytomegalovirus were not found. Histopathologic study revealed perivascular mononuclear infiltrate, lichenoid interface dermatitis without bullae
formation consistent with EM. Treatment was made with antihistaminics and
systemic corticosteroids. After a few days, there was improvement of the skin
lesions and no complications were noted, so the patient was released on the
fifteenth day.
A unique case of cutaneous plasmacytosis
Carolin Penrose, MD, Mount Sinai School of Medicine, New York, NY, United
States; Claudia Vidal, MD, PhD, Mount Sinai School of Medicine, New York, NY,
United States
Plasma cell proliferations in the skin are found in a variety of disorders, including
extramedullary plasmacytoma, autoimmune diseases, and infections, such as
syphilis and Lyme disease. We report a case of 61-year-old Hispanic woman with
an isolated pruritic lesion on her right buttock for 7 months’ duration. The physical
examination revealed violaceous papules forming an annular plaque with mild
central atrophic changes and brown macules. A biopsy specimen from the edge of
the lesion showed a superficial and deep, perivascular and periadnexal inflammatory infiltrate composed mainly of mature polyclonal plasma cells. The patient did
not have known laboratory value abnormalities or immunoglobulin elevation. Also,
with an absence of lymphadenopathy and hepatosplenomegaly, this case differs
from other reported cases of cutaneous plasmacytosis in adults. Similar reported
cases have been found in children. To our knowledge, this is the first case of this type
reported in a Hispanic adult woman.
Discussion: This is a case of EM in which evidence of coinfection of HSV and EBV and
no association with chronic fatigue syndrome was found in a female child.
Corticosteroids have been used early in the course of illness, thereby shortening
convalescence time and preventing the development of serious complications.
P1141
Resource utilization in chronic pruritus
Scott Dunbar, Emory University School of Medicine, Department of Dermatology,
Atlanta, GA, United States; Ricardo Berrios, MD, Emory University School of
Medicine, Department of Dermatology, Atlanta, GA, United States; Sallyann
Coleman King, MD, Emory University School of Medicine, Department of
Dermatology, Atlanta, GA, United States; Suephy Chen, MD, Emory University
School of Medicine, Department of Dermatology, Atlanta, GA, United States
P1143
Chronic pruritus (CP), the sensation of itch for greater than 6 weeks, is an
understudied, often debilitating condition that has a negative impact on quality of
life. We performed a health care utilization study to better quantify the resource
consumption of CP. Patients completed a paper survey detailing demographics and
resource use over the preceding 3 months. From December 2006 to January 2009,
adult CP patients were enrolled from the Emory Dermatology Clinic and Atlanta VA.
Of 96 patients, 70.9% were male, 53.2% white, 64.6% had some college education,
and the mean age was 58.6 (13.4) years. Self-reported itch severity was as follows:
mild (16.5%), moderate (35.4%), and severe or very severe (48.1%). Prescription
medication use by category was as follows: nonsedating H1 antihistamines (16.7%),
sedating H1 antihistamines (22.9%), H2 antihistamines (19.8%), antileukotrienes
(10.4%), topical steroids (67.7%), oral steroids (12.5%), doxepin (9.4%), and
immunomodulators (9.4%). Over the counter, oral preparation use was 31.3% while
topical use was 50.0%; 50.0% used special soaps, shampoos, or detergents, 10.4%
required special clothing, and 19.8% used other treatments (acupuncture, bandages,
etc). Some (35.9%) subjects saw their primary care providers because of their CP at
least once, while 67.7% saw a specialist. While only 1.1% of subjects had been
hospitalized because of their itch, 8.2% had visited an emergency facility. Almost
one-tenth (9.9%) missed at least 1 day of work, 13.0% hired extra aid to cope with
their CP, and 60.5% of subjects spent more than 15 minutes treating their itch per
day. The need for several survey iterations limited some minor aspects of data
collection and analysis. Notwithstanding, our figures show that CP patients
consume a significant and varied spectrum of direct and indirect health care
utilities. More effective treatments for CP are needed to improve quality of life and
reduce disease burden.
Pyoderma gangrenosum in the setting of reconstructive breast surgery
Maria I. Hicks, MD, Geisinger Medical Center, Danville, PA, United States; Kyle J.
Garton, MD, PhD, Geisinger Medical Center, Danville, PA, United States; Thomas
J. Bitterly, MD, Geisinger Medical Center, Danville, PA, United States
Pyoderma gangrenosum in an uncommon ulcerative skin disease that can be
associated with a variety of underlying systemic conditions. In addition, lesions of
pyoderma gangrenosum can be precipitated or exacerbated by cutaneous trauma
including surgical procedures through a process termed pathergy. A diagnosis of
surgery-associated pyoderma gangrenosum is often delayed because the clinical
differential includes more common postoperative conditions, including necrotizing
soft tissue infections. We present the case of a 75-year-old woman with a remote
history of breast cancer who underwent surgical revision of a failed reconstructive
breast implant. During the postoperative period, she developed a rapidly expanding
inflammatory and ulcerative pyoderma, raising concern for a possible necrotizing
soft tissue infection. Multiple cultures failed to reveal an infectious etiology and the
ulcerations rapidly advanced despite broad spectrum antibiotic/antifungal coverage
and extensive surgical debridement. Multiple biopsy specimens revealed a dense
neutrophilic inflammatory infiltrate with dermal edema and focal necrosis without
evidence of organisms on special stains. There was no evidence of necrotizing
fasciitis. A presumptive diagnosis of pyoderma gangrenosum was made and the
patient was successfully treated with systemic steroids and cyclosporine leading to
rapid cessation of the advancing ulcerative disease. Laboratory investigations did not
show any evidence of an underlying systemic illness. Through this illustrative case,
we review the challenges associated with the diagnosis and management of surgeryassociated pyoderma gangrenosum and highlight the importance of including this
rare entity in the differential of progressive cutaneous ulcerations in the postoperative period.
AB36
J AM ACAD DERMATOL
MARCH 2010
P1144
P1146
Changes in rosacea comorbidities and drug utilization over time
Brad Yentzer, MD, WFU School of Medicine, Winston Salem, NC, United States;
Alan Fleischer, MD, WFU School of Medicine, Winston Salem, NC, United States
Background: Rosacea is a chronic skin condition, requiring lifelong treatment and
carrying significant morbidity. Given the rise in antibiotic resistant bacteria, many
physicians are reevaluating their use of antibiotics for long-term treatment of several
dermatoses.
Purpose: To examine trends in the treatment of rosacea and the comorbidities
associated with this skin condition.
Hyperhydrosis with symptoms of blue pigmented chromhidrosis and
bromhidrosis
Yitzy Fox, New Age Skin Research Foundation, Fresh Meadows, NY, United
States; Joshua Fox, MD, New Age Skin Research Foundation and Advanced
Dermatology PC, Fresh Meadows, NY, United States; Rao Saladi, MD, New Age
Skin Research Foundation, Fresh Meadows, NY, United States
Methods: The National Ambulatory Medical Care Survey was queried from 2002 to
2006 for drug mentions at visits for rosacea and coexisting diagnoses. Prescribing
patterns from dermatologists were compared to other physicians.
Results: Over the 5-year study period, 10 million visits made to physicians had the
diagnosis of rosacea. Seventy-four percent of rosacea visits were associated with
comorbidities, and 49% were dermatologic in nature. Metronidazole, tetracyclines,
azelaic acid, and sodium sulfacetamide accounted for the top four medications
mentioned at rosacea visits. When examining all physicians, there was an increase in
the prescribing of azelaic acid and a decrease in sodium sulfacetamide. Only
dermatologists showed a decrease in the prescribing of systemic medications for
rosacea.
Conclusions: Dermatologists are decreasing their use of systemic antibiotics for
rosacea and turning to therapies, such as azelaic acid, that do not induce bacterial
resistance and have other nonantimicrobial effects as well.
Commercial support: 100% is sponsored by Intendis.
Background: Chromhidrosis, a rare skin disorder characterized by colored sweat,
can be subcategorized based on its etiology from sweat producing apocrine or
eccrine glands. Bromhidrosis (by definition meaning ‘‘foul-smelling sweat’’), another
glandular condition, originates most commonly from apocrine glands and is
additionally linked to malodor.
Objective: We present a rare case of 63-year-old man with hyperhidrosis involving
eccrine pseudochromhidrosis and blue sweat with a coexisting presence of severe
bromhidrosis, a unique presentation that has not been reported in the dermatologic
literature.
Methods: In our further investigation for the culprit of the blue sweat from the
patient, we performed chemical analysis of the patient’s belongings.
Results: The patient noticed the discharge blue sweat for a period of 2 months before
he came to seek treatment. The patient’s medical and medication history is
noncontributory except that the patient was taking hypertensive drugs. The
conditions were ultimately treated with prescription antiperspirant Xerac-AC and
Drysol; they completely eliminated both the smell of bromhidrosis and the discharge
of chromhidrosis. This is the first time an antiperspirant deodorant was reported to
have significantly diminished both the smell and discharge of bromhidrosis and
chromhidrosis, respectively. The patient’s undergarments revealed excessive copper and zinc levels, which may be the cause for the blue color of the sweat. However,
the etiology is still unknown, and further research in patients with similar conditions
should be investigated.
P1145
Follicular mucinosis treated with tacrolimus
Ana Maria Mosca de Cerqueira, MD, Hospital Municipal Jesus, Rio de Janeiro,
Brazil; Camila Caberlon Cruz Oliveira, MD, Hospital Municipal Jesus, Rio de
Janeiro, Brazil; Claudia Fernanda Dias Souza, MD, Hospital Municipal Jesus, Rio
de Janeiro, Brazil; Cristiane Cassab Sasajima, MD, Hospital Municipal Jesus, Rio
de Janeiro, Brazil
Folicular mucinosis (FMu) is a relatively rare dermatosis characterized by deposits of
mucin in the skin or hairfollicles.There are two forms of the disease: an idiopathic or
primary form, and another symptomatic form associated to benign and malignant
processes. FMu does not have preference for sex and age, and the etiology is
unknown. The clinical manifestation generally presenting as squamous plaques
covered by porous pilosebaceous units, follicular papules, and alopecic areas. We
present a new and successfully case treated with tacrolimus, a possible effective
treatment for FMu.
Clinical synopsis: A 12-year-old female patient from Bom Jardim-Rio de Janeiro with
black skin, without personal or familiar antecedents, presented with cutaneous
lesions in her left side of the face, with tenuous scaling, centrifugal increase, and
asymptomatic. It was treated as face tinea for 15 days with topic antimycotic, but the
patient returned with intense scaling, hypopigmentation, and infiltration. Histologic
and immunohistochemical studies showed follicular mucinous. Finally, the patient
was treated with tacrolimus 0.1%, showing total lesion regression after 15 days of
treatment. A satisfactory evolution was observed in 9 months of follow-up.
Discussion: FMu belongs to the cutaneous mucinoses group and is a chronic
dermatosis involving the sebaceous glands and outer root sheaths. Recently, the FMu
classification was expanded as follows: (1) primary, short evolution; (2) primary,
prolonged course; and (3) secondary, associated with other processes. The first and
most common form is a benign condition that affects children and young adults; in
this condition, there are fewer lesions and those lesions are limited to the head and
neck. These cure spontaneously and generally do not recur. The histopathologic
findings are mucin degeneration in the external sheath of the hair follicle and
sebaceous gland. Generally, the presence of a high number of eosinophils in the
inflammatory infiltrate and marked mucinous alterations in the follicular epithelium
speak in favor of a benign form. FMu has been treated with steroids, dapsone,
indomethacin, interferons, isotretinoin, minocycline, and ultraviolet A, with variable success.
Reason for presentation: The use of tacrolimus has not been reported yet in the
treatment of FMu. We report a new and successfully case treated with tacrolimus in
children with FMu in her face.
P1147
Recalcitrant cutaneous sarcoidosis causing facial disfigurement: Failure to
respond to captopril and allopurinol
Anton Alexandroff, MD, PhD, Department of Dermatology, Leicester Royal
Infirmary, Leicester, United Kingdom; Karen Harman, MD, MBBCh, Department
of Dermatology, Leicester Royal Infirmary, Leicester, United Kingdom
Cutaneous sarcoidosis can be an extremely disfiguring and therefore distressing
condition. A 48-year-old patient has had pulmonary and cutaneous sarcoidosis for 12
years. The diagnosis was confirmed by skin biopsy, which showed typical
noncaseating granulomas, pulmonary function tests, and high-resolution chest
computed tomography. She had normal angiotensin-converting enzyme levels and a
normal chest radiograph and ECG. The pulmonary involvement was mild and easily
controlled by Pulmicort steroid inhalers (taken as required). However, widespread
cutaneous involvement with multiple purple indurated patches and plaques
(affecting the face, limbs, and body), although they were asymptomatic, proved
to be very distressing for our patient because of marked disfigurement; this affected
her social life. Over the years, she gained no benefit from or did not tolerate the
following treatments: potent and very potent topical corticosteroids with and
without occlusion, intralesional corticosteroids, topical tacrolimus, oral prednisolone alone or in combination with oral methotrexate, minocycline, acitretin,
hydroxychloroquine, azathioprine, and cyclosporin. In a few reports, it has been
suggested that angiotensin-converting enzyme inhibitors and allopurinol may be
beneficial in recalcitrant cases of cutaneous sarcoidosis. Our patient attempted
treatment with the ACE inhibitor captopril but had to stop it after 6 weeks because
of the side effects of a dry cough. She also received no benefit from a 4-month course
of allopurinol. Our patient is currently being treated with fumaric acid esters
(Fumaderm). No improvement has been noted so far following 6 months of
treatment despite developing lymphopenia (0.6 3 109/L) on the maximum dose of
Fumaderm (240 mg TDS). If the patient fails to respond to Fumaderm, we are
planning to attempt treatment with photodynamic therapy, which has been
reported successful in the treatment of three patients with cutaneous sarcoidosis.
Commercial support: ABA received P&G Beauty travel reimbursement.
MARCH 2010
J AM ACAD DERMATOL
AB37
P1148
P1150
Erythema nodosum in pregnancy: Etiology, fetal outcome, and therapeutic considerations
Julia Fruehauf, MD, Department of Dermatology, Medical University of Graz,
Graz, Austria; Christina M. Ambros-Rudolph, MD, Department of Dermatology,
Medical University of Graz, Graz, Austria; Heidrun Martini, MD, Department of
Dermatology, Medical University of Graz, Graz, Austria
Dermatologic secondary effects of the antimitotics: Incidence and risk
factors prospective study: 168 cases
Syrine Hamada, MD, Service of Dermatology and Venerology, Rabat, Morocco
Background: Erythema nodosum (EN) is a reactive inflammation of the subcutaneous fat, mediated by an immune mechanism in response to a variety of antigenic
stimuli. In pregnancy, it is often said to occur de novo but it is still debated whether
female hormones may directly cause EN or rather modulate the immune system to
make the individual more susceptible to other antigenic stimuli.
Objective: To evaluate etiology, clinical presentation, therapy, and fetal outcome of
patients (pts) with EN in pregnancy presenting to a specialized dermatologic
pregnancy clinic at a university-based hospital in Austria.
Methods: From 1999 and 2009, a total of 413 pregnant pts were seen for various skin
diseases of whom 68 (16.5%) presented with inflammatory conditions. Ten pts
(2.4%; median age, 31 years; range, 22-38 years) were diagnosed with EN based on
defined clinical parameters and/or histopathology. Patient records were retrospectively evaluated.
Results: On average, EN occurred at 18 weeks’ gestation (range, 5-39w). The median
duration of EN prior to the first visit was 17 days (range, 4-80 days). All pts presented
with ill-defined painful red nodular lesions on the legs; accompanying fever, malaise,
and arthralgias were noted in only one case. In six of 10 pts, skin lesions were
triggered by an infection (respiratory, 5; gastrointestinal, 1), whereas in the
remaining four no other underlying condition but pregnancy could be detected.
Besides of compression therapy and bed rest, the majority were treated with topical
corticosteroids and mild oral analgesics (paracetamol, 500 mg daily); two severe
cases further received oral cefalexine (1000 mg tid for 14 days) and prednisolone (25
mg daily in tapering doses for 14 days), respectively. This led to complete resolution
within 2 to 3 weeks without further sequelae in all pts. Recurrence of skin lesions in
a successive pregnancy was noted in only one idiopathic patient. In all cases,
pregnancy outcome was favorable with deliveries at term (mean, 40 weeks; range,
38-41 weeks) and healthy neonates (mean weight, 3240 g; range, 2815-4100 g).
Conclusions: EN appears to be a rare disease during pregnancy that generally runs an
uncomplicated course. Also in pregnancy, pts should be examined thoroughly for
commonly associated infections. Treatment consists in bed rest, compression,
topical corticosteroids, and oral paracetamol; if systemic antibiotics are required,
penicillins and cephalosporins should be the antimicrobial agents of choice and are
considered safe in pregnancy.
Background: The dermatologic side effects of antimitotics are various. The majority
of these molecules can be responsible for it. Nevertheless, the publications concern
essentially anecdotal cases of cutaneous toxicity or series of drug reaction due to a
single molecule of chemotherapies. The purpose of this work was to raise the
incidence of the main cutaneomucous side effects related to antimitotics the most
used in our context as well as to certain therapeutic targeted, to determine their
types, the different responsible molecules and the risk factors.
Methods: A prospective study was realized in the National Institute of Oncology of Rabat
over a period of month (from April 20 to May 20, 2009) and concerned the patients in
the service of medical oncology. The patients who were adults (more than 18 years old),
were treated by at least one of one of the following molecules: 5-fluouracil, taxanes,
capecitabine, and therapeutic targeted. The persons having a preexistent dermatosis
were excluded. The index card of exploitation enhanced the demographic data of the
patient, the medical antecedents, the treated cancer, the protocol of chemotherapy, the
used premedication, and the possible dermatologic side effects during the treatment.
The grading of the lesion was made from the scale of toxicity NCI-CTCAE version 3.0. A
comparative statistical study of the groups with and without drug eruption was then
realized with analytical univariate study to raise the quantitative risk factors (age, sex,
geographic origin, and phototype) and qualitative (sex and clinical examination) and
multivariate study to retain the independent factors. The results were exploited by the
software SPSS version 13.0. P \.05 was considered statistically significant.
Results: One hundred sixty-eight patients were examined (130 women and 38 men).
The average age was of 51 years (23-77 years). The cancers were gynecologic
(56.0%), digestive (31.5%), lungs (3.6%), superior air traffics (6.5%), hemopathy
(1.8%), and the other cancers (0.6%). Seventy-one patients were under taxanes
(42.3%), 66 patients under 5FU (39.3%), 19 cases under therapeutic targeted
(11.3%). The patients under capecitabine represented 7.1% (12 cases). The patients
were on average, at their fourth cure. Cutaneous lesions were found in 141 cases
(83.9%). Alopecia represented 108 cases (64.3%). The infringement interested 75 of
the patients (44.6%): melanonychia in 49 cases (36.7%) and onycholysis in 31cases
(23.2%). Other revealed nails were found in 20 cases (15%) made of pachyonychsis,
by bleeding undernail, leukonychsis and paronychsis. The pigmentary disorders
found in 50 cases (29.8%) included the hyperpigmentation of the bare zones
(23.8%), the serpiginous hyperpigmentation (4.2%), and the flagellate hyperpigmentation (3.6%). The cutaneous aridity was listed (counted) in 46 cases (27.4%).
The clinical examination had objectivized other revelations, such as facial eythema
(21.4%), edema of the face (11.3%), vasomotor drafts (12.5%), and folliculitis (3%).
The mucous infringement concerned 24 patients (14.3%). The risk factors held after
study united and multivariate were: female with a relative risk (RR) of 3.54 and the
molecule (taxanes): RR of 12.36.
Discussion: This study is original because in our knowledge it represents the first
one containing the dermatologics side effects of several molecules with a study of
the risk factors in these drug eruptions. As it is described in literature, the lesions
were dominated by the nails toxicity. The majority of the observed eruptions were
without gravity, they consequently required the stationary or the modification of the
protocol only in 1.7% of the cases. Being female and the taxanes represent the only
predictive factors of arisen of drug eruption in our study. This could have a
physiopathological explanation notably incriminating the hormonal factors. Other
studies would be nevertheless desirable to confirm their implication.
P1151
P1149
AntieTNF-alfa treatment in pyoderma gangrenosum: Thalidomide versus
etanercept
Rita Guedes, MD, Centro Hospitalar Vila Nova de Gaia - Serviço de Dermatologia,
Vila Nova de Gaia, Porto, Portugal; Ana Moreira, MD, Centro Hospitalar Vila Nova
de Gaia - Serviço de Dermatologia, Vila Nova de Gaia, Porto, Portugal; Armando
Baptista, MD, Centro Hospitalar Vila Nova de Gaia - Serviço de Dermatologia, Vila
Nova de Gaia, Porto, Portugal; Inês Leite, MD, Centro Hospitalar Vila Nova de
Gaia - Serviço de Dermatologia, Vila Nova de Gaia, Porto, Portugal; Paulo Varela,
MD, Centro Hospitalar Vila Nova de Gaia - Serviço de Dermatologia, Vila Nova de
Gaia, Porto, Portugal
TNF-alfa plays a central role in inflammation, and its blockade can be achieved by
using inhibitors of this cytokine. Etanercept is a soluble receptor of TNF-alfa
inhibiting its action and consequently inflammation. At this moment, etanercept is
approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing
spondylitis, juvenile idiopathic arthritis, and psoriasis. However, it has been used
with good results in other inflammatory dermatoses. The authors present the
clinical case of a 54-year-old man with the diagnosis of pyoderma gangrenosum. He
completed treatment with oral prednisolone with good clinical response, but with
recurrence after suspension of corticotherapy. We introduced thalidomide and at 2
months of treatment he presented total healing of the lesions. Later on he began
complaining of paresthesia and hypoesthesia in glove and sock, and thalidomide was
interrupted. Taking into account the favorable outcome with thalidomide and the
necessity of drug suspension, we choosed to introduce a therapy acting on the same
step in the inflammation cascade. In this regard, we started etanercept. The authors’
aim with this article is to present an alternative therapy in the treatment of refractory
pyoderma gangrenosum and to perform a review of the literature. To date only 15
cases of pyoderma gangrenosum treated with etanercept have been described.
AB38
The use of a shaving regimen for male facial shaving improves overall
skin condition
Angelika McDermott, PhD, The Procter & Gamble Company, Cincinnati, OH,
United States; Anne Westbrook, The Procter & Gamble Company, Cincinnati,
OH, United States; David Warnke, The Procter & Gamble Company, Cincinnati,
OH, United States; Helen Kemp, PhD, The Procter & Gamble Company,
Cincinnati, OH, United States; Tim Coffindaffer, PhD, The Procter & Gamble
Background: Millions of men around the world shave their facial hair regularly. The
quality of their shave experience depends on a myriad of factors, including their skin
and facial hair characteristics, their shaving technique, and the quality of their razor
and grooming products. This study investigates the impact of an advanced shave
care regimen, including a preshave wash of the face, a lubricating shave gel, the use
of a five-blade razor, and a postshave moisturizer on overall facial skin condition.
Objective: We assessed the impact of using a premium shaving regimen compared to
a more typical regimen on overall skin condition.
Methods: A 2-week split-face clinical study was conducted with the premium regimen
being used on one-half of the face and a more typical regimen (preshave wash of the
face, foaming shave preparation, and the use of a three-blade razor) on the other half (n
¼ approximately 40 subjects per treatment group). Skin hydration, barrier function,
microscopy, expert grading of erythema and dryness, and self-assessment were used to
quantify skin condition benefits delivered by the premium shaving regimen.
Results: The use of a premium shave care regimen improves skin condition after
shaving, relative to a more typical regimen. The use of the premium shaving regimen
provided significant increases in skin hydration, as assessed instrumentally and by
expert grader (P # .05). Self-assessment data showed significant improvement in
consumer-relevant parameters of shaving irritation with the premium shaving
regimen (P # .05). These results show the importance of using a premium shave
care regimen on skin health.
Commercial support: Procter & Gamble.
J AM ACAD DERMATOL
MARCH 2010
P1152
P1154
Pyoderma gangrenosum and hepatitis C virus infection: A case report
Rodrigo Carvalho, Dermatology and Venereology Department, Curry Cabral
Hospital, Lisboa, Portugal; Ana Afonso, Anatomopathology Department, Curry
Cabral Hospital, Lisbon, Portugal; Ana Rodrigues, Dermatology and Venereology
Department, Curry Cabral Hospital, Lisboa, Portugal; Daniela Cunha,
Dermatology and Venereology Department, Curry Cabral Hospital, Lisboa,
Portugal; Jorge Cardoso, Dermatology and Venereology Department, Curry
Cabral Hospital, Lisbon, Portugal
Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous condition of
uncertain etiology that can be associated with other medical conditions. The
diagnosis is clinical and is made by excluding other causes of similar appearing
ulcerations. The authors describe the case of a 39-year-old woman with chronic
hepatitis related to hepatitis C virus (HCV) infection and excessive alcohol intake
that presented an extensive bilateral ulcer on the lateral-dorsal aspect of her calf
with a violaceous border that overhangs the ulcer bed. This had begun 1 year
previously as a bulla leaving a rapidly enlarging ulcer. Examination also revealed
pustular lesions with violaceous halo on the dorsal aspect of the hands and temporal
region of the face with 3 days’ evolution. During this period, the patient maintained
excessive alcohol intake and did not performed any kind of medical therapy.
Investigations showed hepatic dysfunction with clinical and echographic ascitis.
Complementary tests performed included cryoglobulinaemia, arterial and venous
lower limb echo Doppler and colonoscopy and were all normal. The histologic
examination of the pustular lesions on her hands showed intense neutrophil
infiltrate with superficial and deep dermis leukocytoclasia. Histologic examination
of the edge of the leg lesion showed superficial and deep dermal leukocytoclastic
vasculitis with calcification foci. These results were consistent with PG diagnosis.
Diuretic therapy was instituted, and during the following months alcohol consumption abandon was achieved along with improvement of hepatic function.
Betamethasone dipropionate 0.5mg/g cream was instituted twice daily for hand
and face lesions with complete resolution after 8 weeks. For lower limb ulcers,
negative pressure dressing with vacuum-assisted closure was instituted with good
clinical response but without achievement of total wound closure. Pegylated
inferteron-alfa and ribavirin treatment were tried but suspended after 2 weeks for
behavioral disorders. Although association of PG and chronic liver disease is
frequently reported, only few cases of PG and HCV have been recorded in the
literature. The mainstay of therapy for PG is immunomodulatory and immunosuppressive therapy and management of the possible underlying associated disease, but
PG ulcers may take years to completely heal, even in patients with adequate therapy.
Moreover, HCV patients constitute a therapeutic challenge, where standard immunosuppressive therapies are not eligible.
Drug reaction with eosinophilia and systemic symptoms (DRESS) associated with acetaminophen and reactivation of HHV-6
Brooke Jeffy, MD, University of Louisville, Dermatology, Louisville, KY, United
States; Jeffrey P. Callen, MD, Department of Internal Medicine, Division of
Dermatology, University of Louisville School of Medicine, Louisville, KY, United
States; Mark Waldman, MD, University of Louisville, Dermatology, Louisville, KY,
United States
Background: DRESS is characterized by rash and multiorgan involvement. Altered
drug metabolism and immune mechanisms, particularly related to HHV-6, are
suggested etiologies. Acetaminophen has not been previously reported in association with DRESS.
Observation: A 48-year-old man with inflammatory bowel disease and hyperlipidema presented after four episodes of erythroderma and blistering of the trunk
and extremities over the past year. Recent medical history was significant for a
prolonged course of vancomycin and piperacillin/taxobactam following a bowel
perforation during which time he developed his first episode of erythroderma,
complicated by renal failure. He had no history of transfusion. Medications included
atorvastatin, pantoprazole, multivitamin and iron, and although these were stopped,
he continued to have episodes. Multiple biopsies showed confluent epidermal
necrosis. Initially a blistering disorder was suspected however immunofluorescence
was not supportive and IgG antidesmoglein-1 and -3 antibodies were not elevated.
HSV culture was negative. He did have elevated HHV-6 IgG titer and negative IgM
titers on two occasions subsequent to flare. During one of his first episodes he had a
peripheral eosinophilia and has had elevation of his liver enzymes during all flares.
Hepatitis serologies were negative. Each of his episodes was associated with the
ingestion of acetaminophen for myalgia or fever and responded rapidly to oral
corticosteroids. The patient was felt to have DRESS attributed to acetaminophen.
Comment: Our case illustrates what we believe to be the first report of DRESS in
association with acetaminophen and reactivation of HHV-6. This patient had
episodic erythroderma preceded by fever and myalgias that he treated with
acetaminophen. While acetaminophen may have caused his initial drug hypersensitivity, it is likely that subsequent episodes were triggered by HHV-6 reactivation,
which was possibly then exacerbated by further exposure to drug. Because the
characteristic findings in DRESS may mimic that of viral reactivation, demonstration
of reactivation of HHV-6 through the use of viral serologies is imperative for
diagnosis. Additionally, because there have been no clinical trials evaluating optimal
treatment for DRESS, we must rely on outcomes published as case reports. Each
episode in our patient responded rapidly to short, 9- to 15-day courses of oral
prednisone.
P1155
FoxeFordyce disease, also called apocrine milaria, is a rare, chronic disorder
characterized by pruritic follicular papules localized to apocrine glandebearing
areas such as the axillae, groin, pubic region, areola, and umbilicus. It is proposed
that a keratin plug in the follicle infundibulum obstructs the apocrine acrosyringium, thereby causing an apocrine anhidrosis, with eventual rupture of the apocrine
system and secondary dermal inflammatory changes. We present a 20-year-old
African American female who complained of diffuse, pruritic, confluent, hyperpigmented follicular based papules coalescing into plaques present for over 2 years in
her bilateral axillae. A shave biopsy was performed that revealed papillomatosis with
follicular plugging and secondary folliculitis. The patient was treated with a trial of
doxycycline and tretinoin but was noncompliant with medications. At last followup, doxycyline and tretinoin were discontinued and the patient was placed on a trial
of kenalog 0.1% cream daily for 1 month. The patient is currently awaiting follow-up
for treatment results. There have been reports of varying degrees of treatment
success with topical retinoids, topical steroids, antibiotics, hormonal therapy, UV
light, dermabrasion, and surgical excision. However, these treatments are not
curative and often only provide marginal cosmetic and symptomatic benefit to
patients with this refractory condition. The treatment of FoxeFordyce disease
continues to be a challenge and novel aprroaches are frequently attempted to
provide these patients with relief.
Multiple clear cell acanthomas in association with hepatitis C: A novel
presentation
Ranhy Bang, MD, PhD, Department of Dermatology, University of New Mexico,
Albuquerque, NM, United States; Lida Crooks, MD, Department of Pathology,
Veterans Affairs Administration Hospital, Albuquerque, NM, United States; Ran
Bang, MD, Department of Dermatology, University of New Mexico, Albuquerque,
NM, United States; Ruobing Xiao, MD, Department of Pathology, University of
New Mexico, Albuquerque, NM, United States
A 57-year-old man presented with a 6-month history of several grouped, asymptomatic, smooth, shiny red papules with collarettes of scale on his right anterior thigh.
The dermoscopic examination revealed highly ordered, orthogonally-branching,
linear arrays of dotted blood vessels. The patient’s medical history was significant for
squamous cell carcinoma of the skin, basal cell carcinoma, hypertension, hepatitis C
with undetectable virus by PCR but liver biopsy consistent with chronic hepatitis
type C, and condyloma acuminata. Clear cell acanthoma (CCA), or Dego acanthoma,
is a rare entity that usually presents during middle age on the lower extremities as a
lone pink or reddish-brown, glistening nodule, papule, or plaque, often with a
collarette of scale. The most notable histologic finding is sharply marginated
epidermal acanthosis and enlarged, clear, pale-staining keratinocytes overloaded
with glycogen. Multiple clear cell acanthomas are even rarer than the individual
instances, with fewer than 30 reported cases. Our case is the first, to our knowledge,
presenting in the context of hepatitis C infection. The etiology of CCA remains
controversial and is considered to be either neoplastic or reactive. The association
with hepatitis C in this case may offer one possible etiologic explanation. Hepatitis C
expresses the NS5A protein, which is known to modulate multiple host cell
processes, including cell growth, apoptosis, and interferon signaling. We postulate
that NS5A, derived from hepatitis C in our patient, may be driving epidermal
hyperplasia via blockage of apoptosis and keratinocyte growth and is responsible for
increasing keratinocyte glycogen content. The mechanism by which these processes occur may be deduced from the previously-described action of NS5A on
phosphoinositol-3 kinase-mediated survival pathways to result in inhibition of GSK3B through activation of AKT, resulting in loss of repression by GSK-3B on glycogen
synthase, as well as on B-catenin. These events result in glycogen synthesis, as well as
nuclear translocation of B-catenin to activate genes involved in cell survival.
P1153
Fox-Fordyce disease: A treatment challenge
Khongruk Wongkittiroch, DO, MS, Suncoast Hospital, Largo, FL, United States
MARCH 2010
J AM ACAD DERMATOL
AB39
P1156
P1158
Erythropoietic protoporphyria: An unusual skin presentation
Khadija Khadir, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Hakima Benchikhi,
Ibn Rochd UHC, Casablanca, Anfa, Morocco; Soumia el Mabady, Ibn Rochd UHC,
Casablanca, Anfa, Morocco
Introduction: Erythropoietic protoporphyria (EPP) is a rare genodermatosis that is
caused by decreased activity of the enzyme ferrochelatasis, the terminal enzyme of
the heme biosynthetic pathway. We report case of EPP where melanoderma was the
only evoking sign.
Observation: A 9-month-old girl of consanguines parents consulted in March 2008.
Her brother had similar disease at the age of 2 years and died at 3 years because of
deshydratation complicating chronic diarrhea. History begun at the age of 3 months.
Isolate melanoderma of the face and the upper and lower limb extension faces
appeared with no itching, nor transit disorders with no previous vesiculobullous
lesions, nor abdomen pains, nor neuropsychiatric syndrome. At examination,
melanoderma of sun-exposed areas were combined to a discrete edema of the
hand backs. No skin frailty was noticed, nor face dysmorphy signs, nor dental or
pilary anomalies. The diagnosis of suprarenal failure was evoked but rapidly
discarded due to the exclusive spread to sun exposed area of the melanoderma
and the negative hormone dosages (ACTHemorning cortisol). Allgrove syndrome
was also evoked but no alachrima was found nor any achalasia. The search for
malabsorption syndrome and avitaminosis leading to pellagra was negative (vitamin
PP normal). Porphyrin dosages showed the increase of the blood protoporphyrin
rate (130 g/L, normal,\0.01 g/L; or 1.14 g/gHb, normal,\0.80 g/gHb). Blood
coproporphyrin was normal as well as the urine dosages of the porphobilinogen of
the uroporphyrin and of the coproporphyrin. The patient presents microcytic
normochromia anemia with normal rates of transaminases. Thus, EPP diagnosis was
retained. As therapy, the patient underwent external photoprotection.
An analysis of efficacy data from five phase III studies of BoNT-A for the
treatment of glabellar lines
Leslie Baumann, MD, Cosmetic Medicine and Research Institute, Miami Beach,
FL, United States; Fredric Brandt, MD, Dermatology Research Institute, LLC,
Coral Gables, FL, United States; Michael Kane, MD, Kane Plastic Surgery, New
York, NY, United States
Discussion: The difficulty of the diagnosis in our patient is because of the isolated
melanoderma. Patients usually experience itching and burning, and develop
erythema even after brief exposure to bright light. EPP differs from other skin
porphyrias mainly by absence of increase of urinary porphyrin. This was the case of
our patient. The evolution is usually favorable with regression of thrusts at
adulthood. However, the hepatobiliary affection present in about 25% of the cases,
restrains the prognosis. The death of the brother could be retated to a non explored
hepatic affection. There is no therapeutic consensus. The only preventive measure
to take is sun eviction. The genic therapy can be a promise for definite treatment.
Background: A new US botulinum neurotoxin type A formulation (BoNT-A; Dysport
[abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) has recently been
approved by the US Food and Drug Administration for the treatment of moderate
to severe glabellar lines.
Objective: We describe the results of five phase III studies of BoNT-A for the
treatment of glabellar lines.
Methods: Three double-blind, multicenter, randomized, placebo-controlled studies
enrolled ethnically diverse healthy adults with glabellar lines of at least moderate
severity at maximum frown. In these studies, patients were followed for up to 180
days after treatment. The fixed-dose, single-treatment study randomized 158
patients to receive placebo or one dose of BoNT-A 50 U. The fixed-dose, repeattreatment study randomized 311 patients to assess treatment following the prior
BoNT-A treatment of 50 U. The variable-dose study randomized 816 patients to
receive placebo or a single variable dose (50-80 U, based on gender and assessment
of muscle mass). Clinical evaluations were performed on days 14 and 30 and
monthly thereafter. The primary endpoint was a response defined as a composite
21 grade improvement, at day 30 from baseline, on the wrinkle severity rating scale
(WSRS): from 2 to 0, or from 3 to 0 or 1 (where 3 ¼ severe wrinkles/severe, 2 ¼
moderate wrinkles/moderate, 1 ¼ mild wrinkles/mild, and 0 ¼ no wrinkles/none),
for both the blinded evaluator’s/blinded investigator’s and patient’s assessments.
Results: Patients (1116 total; 720 BoNT-A, 396 placebo) given BoNT-A received 50 to
80 U of treatment. The median duration of response was 85 days for fixed dosing and
109 days for variable dosing. Similar efficacy occurred at doses adjusted for gender
and muscle mass, although males required higher doses than females in the variabledose study. Responses appeared as early as 24 hours, with a median time to onset of
3 days. Extension studies evaluated 1200 patients for 13 months and 768 patients in
an interim analysis for 24 months. Maintenance of efficacy was seen after multiple
cycles, indicating a lack of tolerance.
Conclusions: BoNT-A significantly improved moderate to severe glabellar lines
compared with placebo, with onset seen as soon as 24 hours after treatment and a
median duration of effect of 85 or 109 days for fixed or variable dosing, respectively.
P1157
Imatinib-induced psoriasiform drug eruption: 2 cases
Samira Belyamani, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa,
Morocco; Hakima Benchikhi, Dermatology Department, Ibn Rochd UHC,
Casablanca, Anfa, Morocco; Samira Skali, Dermatology Department, Ibn Rochd
UHC, Casablanca, Anfa, Morocco; Sofia Azouzi, Pathology Department, Ibn
Rochd UHC, Casablanca, Anfa, Morocco
Introduction: Imatinib (Glivec*) is an inhibitor of tyrosine kinase, mainly used in the
treatment of chronic myeloid leukemia and some malignant stromal gastrointestinal
tumors. Currently, this molecule has several indications, and its cutaneous side effects are
becoming better known. We report two cases of psoriasiform drug-induced dermatitis.
Case reports: A 38-year-old woman presented in October 2008 for a malignant
stromal intestinal tumor; she was given imatinib (Glivec*) at a dose of 400 mg/day.
Three months later, she developed widespread psoriasiform itching erythematous
squamous lesions. Skin histology showed lichenoid vasculitis. All lesions disappeared after symptomatic treatment and Glivec* was maintained. Our second case
was a 37-year-old man who was treated for chronic myeloid leukemia with Glivec* at
the dose of 400 mg/day. Three months later, he presented with facial edema,
cheilitis, and generalized itching erythematous squamous lesions. The skin histology
showed an aspect of lichenoid drug-induced dermatitis. Imatinib was stopped for 6
months, with complete disappearance of skin lesions under symptomatic treatment.
The reintroduction of Glivec* was required, and the evolution was marked by the
recurrence of psoriasiform eruption after 3 months. The therapeutic decision was to
maintain Glivec* associated with symptomatic treatment (topical corticosteroids).
The evolution was marked by a complete skin bleaching.
Discussion: Imatinib has been imputed in our two patients; however, considering
the risk/benefit ratio, this drug has not been arrested in both cases. The cutaneous
side effects of this molecule are relatively common, occurring in 11% to 67% of
cases, and include mild to moderate itch, maculopapular exanthema, and facial
edema. However, more severe drug-induced dermatoses have been reported,
including DRESS syndrome, StevenseJohnson syndrome, acute generalized exanthematous pustulosis, and purpuric vasculitis. Recently, particular varieties were
also published, including bleeding under the nail, pigmentary disorders, drug
lymphoma, porphyria cutanea tarda, profuse cutaneous lichen, and oral erosive
lichen. Our cases are the first two observations of psoriasiform drug-induced
dermatitis which we classify as being of moderate severity. The time to onset of skin
reactions is variable, ranging from 20 days to 1 year. In our cases, this period was 3
months. The reccurence after reintroduction in the second patient was also 3
months. For many authors, these reactions result from a dose-dependent effect of
imatinib, they are more frequent and more severe with higher doses (600-800 mg/d),
and this suggests a pharmacologic effect rather than an immunologic one. However,
for our patients treated with doses of 400 mg/day, there is the question of an
immunologic effect. The resolution of drug-induced dermatitis despite the maintenance of Glivec* is another argument of immunologic effect.
Conclusion: Imatinib should be considered as a drug that induced severe cutaneous
reactions. Currently, its use in nonhematologic indications may increase the number
of serious drug-induced dermatitis.
AB40
P1159
Generalized perforating granuloma annulare
Nektarios Lountzis, MD, Geisinger Medical Center, Danville, PA, United States;
Dirk Elston, MD, Geisinger Medical Center, Danville, PA, United States; Tammie
Ferringer, MD, Geisinger Medical Center, Danville, PA, United States
Granuloma annulare (GA) is a benign dermatosis classically characterized by papules
assuming an annular configuration and histologically defined by degenerated
collagen surrounded by palisading histiocytes. It can be divided into several
subtypes, including a generalized perforating GA (GPGA) variant. Herein, we
present a case of an otherwise healthy 15-year-old white male with a several 3- to 7mm pink waxy umbilicated papules with central crusting that progressed over his
lower extremities in six months. Family history was significant for diabetes mellitus
in a maternal aunt. Histopathology revealed an interstitial infiltrate of histiocytes and
giant cells interlaced between collagen bundles and overlying a central epithelial
lined channel. In areas, there was a well developed palisade of histiocytes
surrounding a faint central mucinous deposition highlighted by colloidal iron. A
diagnosis of GPGA was rendered and 1 month of pentoxifylline 400 mg PO TID
resulted in no clinical change. The papules slowly progressed to the upper
extremities, and his medication was changed to clobetasol topically but the patient
was subsequently lost to follow-up. GPGA was first described in 1973 and since then
approximately 20 cases have been reported, including familial forms. In children, it
generally does not have an association with diabetes but the association is stronger
in the elderly, as seen in non-perforating generalized GA. Overall, GPGA represents
an interesting and rare variant of a common dermatosis.
J AM ACAD DERMATOL
MARCH 2010
P1160
P1162
Endemic African Kaposi sarcoma with lipodermatosclerosis-like
presentation
Dionne Louis, MD, The University of Oklahoma Health Sciences Center,
Oklahoma City, OK, United States; Pamela Allen, MD, The University of
Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Double-blind, double-dummy, randomized, placebo-controlled, fivearmed, multicenter phase II/III study to evaluate the efficacy and safety
of different concentrations of isotretinoin versus doxycycline in the
treatment of rosacea, subtype II and III
Harald Gollnick, University Magdeburg, Magdeburg, Sachsen-Anhalt, Germany;
Carmen Matthies, Almirall Hermal GmbH, Reinbek, Schleswig-Holstein,
Germany; Renate von der Weth, Almirall Hermal GmbH, Reinbek, SchleswigHolstein, Germany
Kaposi sarcoma (KS) is a malignant vascular neoplasm found in diverse clinical
settings with various presentations, epidemiology, and prognosis. The five clinical
subtypes are: (1) classic KS, seen chiefly in elderly men of Mediterranean and
Eastern European heritage, which follows a chronic and protracted course; (2)
African cutaneous KS, a locally aggressive but systemically indolent process
affecting middle-aged HIV seronegative Africans; (3) African lymphadenopathic
KS, an aggressive and rapidly fatal disease of prepubertal African children; (4)
Epidemic or AIDs-related in patients with advanced HIV infection; and (5) iatrogenic
immunosuppression-related after solid-organ transplantation or in patients receiving immunosuppressive therapy. We discuss an unusual KS presentation in a 50-yearold HIV-negative Nigerian patient with sclerotic hyperpigmented skin changes
typical of lipodermatosclerosis (LDS) on the left lower extremity. The initial biopsy
specimen was interpreted as chronic inflammation with fibrosis. The patient
subsequently developed violaceous nodules on the plantar surface of his left foot.
Repeat biopsy specimens of the sclerotic plaque and plantar nodules revealed
characteristic findings of KS. Immunohistochemistry staining of the tumor tissue
was positive for HHV-8. To our knowledge, LDS-like KS has not been reported in the
literature. The diagnosis of KS should be considered in patients with LDS who have
typical KS ethnicity or medical background.
A double-blind, randomized, placebo-controlled, five-armed, multicenter study
including 573 patients with rosacea subtypes II and III in 35 centers in Germany
was performed to evaluate the efficacy and safety of different concentrations of
isotretinoin in the treatment of rosacea. Patients were treated in a randomized
assignment either with one of three different doses of isotretinoin (0.1, 0.3, or 0.5
mg/kg body weight), with standard therapy with oral antibiotics (100 mg doxycycline daily for 14 days, then reduction to 50 mg daily), or with placebo. As the
primary objective, the reduction in the total sum of facial papules and pustules/noduli after a 12-week treatment was compared between the treatment groups. In an
interim analysis after about 45 patients per group had been treated, all three
isotretinoin doses showed a clearly higher reduction of lesions compared to
placebo, whereas treatment with 0.3 mg/kg showed the clearest reduction of
lesions with a statistically significant superiority versus placebo (P ¼ .005). In the
second part of the study, the efficacy of the most efficient isotretinoin dose (0.3
mg/kg) was compared to standard therapy with doxycycline, and the other arms of
the study were closed. Treatment with isotretinoin 0.3 mg/kg showed statistically
significant noninferiority versus treatment with doxycycline (P \ .001). With
isotretinoin 0.3 mg/kg, lesions were reduced for 90% compared to 83% with
doxycycline treatment. Physicians diagnosed complete remission in 24% and
marked improvement in further 57% of the patients with isotretinoin treatment,
versus remission in 14% and marked improvement in 55% of the patients treated
with doxycycline. Seventy-eight percent of the patients treated with isotretinoin
rated therapy success as ‘‘excellent’’ or ‘‘good,’’ compared to 64% of the patients
treated with doxycycline. Data on drug safety reveal a similar safety profile for the
treatment of rosacea with isotretinoin 0.3 mg/kg as with treatment of acne with
isotretinoin. No new, severe safety concerns were found; only an increase of
cholesterol occurred slightly more often (in 19% of patients) than in acne treatment.
Clinically relevant changes in blood count did not occur in any patient. Because of
the low dose, isotretinoin has a positive risk/benefit profile for the treatment of
rosacea. Isotretinoin 0.3 mg/kg is an efficient and well tolerated treatment for
rosacea subtypes II and III and can be used as an alternative to standard therapy with
oral antibiotics.
Commercial support: The study was sponsored by Laboratories Almirall, S.A.
P1161
Year 2 interim results of a 5-year open-label study for the correction of
human immunodeficiency virus: Related facial lipoatrophy with injectable poly-L-lactic acid
Marcus Conant, MD, Conant Medical Group, San Francisco, CA, United States; C.
William Hanke, MD, Laser and Skin Surgery Center of Indiana, Carmel, IN, United
States; Michael Gold, MD, Gold Skin Care Center, Nashville, TN, United States;
Tiffani Hamilton, MD, Atlanta Dermatology, Vein & Reseach Center, LLC,
Alpharetta, GA, United States
Background: Injectable poly-L-lactic acid (PLLA) is approved for the restoration
and/or correction of the signs of facial lipoatrophy in people with HIV.
Objective: Evaluate the long-term safety of injectable PLLA in subjects with HIVrelated facial lipoatrophy by Fitzpatrick skin type and gender.
Methods: This was a 2-year interim analysis of a 5-year, multicenter, open-label study.
Adult subjects with HIV-related facial lipoatrophy were targeted to receive up to six
treatment sessions (more were allowed for optimal correction if required) at 4- to 6week intervals. Yearly posttreatment evaluations included AEs, James scale clinical
evaluation of facial lipoatrophy, and completion of a Likert-based physician and
subject satisfaction questionnaire.
Results: A total of 290 subjects were treated with an average of 6.0 treatment
sessions (SD ¼ 2.46; median ¼ 6.0 [range, 1-18]). Overall, female and male subjects
with Fitzpatrick skin type IV to VI showed numerically lower rates of AEs. At year 2
interim, 71 (24.5%) subjects experienced AEs that were possibly injection
procedureerelated; 53 (18.3%) subjects had AEs that were possibly study
producterelated. The rate of injection site nodules was numerically lower for
female and male Fitzpatrick skin types IV to VI subjects (2.9% and 6.6%) than for
female and male Fitzpatrick skin types I to III (10.0% and 13.5%). Similarly, the rate of
injection site papules was numerically lower for female and male Fitzpatrick skin
type IV to VI subjects (5.7% and 6.6%) than for female and male Fitzpatrick skin type
I to III subjects (10.0% and 12.2%). No hypertrophic scars or keloids were reported.
The majority of AEs were mild or moderate in severity. The overall rate of SAEs was
16.2%; none were product-related. Significant improvement from baseline in James
scale lipoatrophy units was observed at the year 2 visit (-1.4 units overall; P \.001).
Overall physician and subject satisfaction with treatment was ‘‘very good’’ or
‘‘excellent’’ for 95.5% and 89.4%, and was comparable among all subject groups.
Conclusions: Overall, subjects with Fitzpatrick skin types IV to VI reported
numerically lower rates of AEs posttreatment. No treatment-emergent hypertrophic
scars, keloids, or product-related SAEs were observed. Significant improvements
from baseline in James scale facial lipoatrophy scores were reported across all
subject groups. High physician and subject satisfaction also was reported similarly
among all groups.
Commercial support: The study was funded by Dermik Laboratories, a business of
sanofi-aventis U.S.
P1163
Dermatologic manifestations of undernutrition
Brazil; Cristiane Cassab Sasajima, MD, Hospital Municipal Jesus, Rio de Janeiro,
Brazil; Joana Pimenta de Araujo Franco, MD, Hospital Municipal Jesus, Rio de
Janeiro, Brazil; Melissa Kühn, MD, Hospital Municipal Jesus, Rio de Janeiro, Brazil
Undernutrition, also known as protein-energy malnutrition (PEM), is characterized
by a multiple and progressive worsening of nutritional deficiencies. This is the most
common form of malnutrition in less developed countries, and it is caused by
diminished or inadequate ingestion of food. According to the World Health
Organization (WHO), 49% of the 10.4 million deaths occurring in children younger
than 5 years of age in developing countries are associated with PEM, and 5% of
Brazilian children under 5 years of age are in the state of undernutrition. Children
with marasmus usually have received a balanced diet, but the quantity was
insufficient, while children with kwashiorkor have received a high-calorie diet but
poor in proteins of animal origin. Dermatologic and other clinical changes are more
florid and characteristic in kwashiorkor than in marasmus. Xerodermia, atrophy,
edema, fissures, and diffuse dispygmentation may be present in both. In marasmus,
patients have a generalized absence of subcutaneous fat and the skin may become
thin, pale, lax, or wrinkled, and occasionally finely scaly and hyperpigmented.
Excess of lanugo-like hair are common. Loss of bucal fat pads results in wizened,
‘‘monkey facies’’ or an aged appearance. The hair is fine and brittle, and nails are thin
and fissured. Some develop angular cheilitis and a pale atrophic tongue and mucous
membranes. Growth deficiency and extreme muscular atrophy can be seen. In
kwashiorkor, skin lesions usually present lack of pigmentation, especially in areas of
friction, edema, and continuous pressure. The skin may be erythematous and shiny,
mainly in edematous regions. Areas of dryness, hyperkeratosis, and hyperpigmentation have a tendency to confluence. Large scales expose underlying tissues, which
are easily infected. Hair is sparse, dry, lusterless, and brittle, with a reddish tinge. The
flag sign (bands of light and dark coloration) reflect intermittent periods of
malnutrition. Nails are soft and thin. Mucosal alterations are cheilitis, xerophthalmia
and vulvovaginitis. The subcutaneous fat is present and serves as a parameter of the
level of calorie deficiency. Some muscular atrophy may occur. The treatment should
start with correcting fluid and electrolyte imbalances. Any infections should also be
treated appropriately. Food must be reintroduced slowly. Treatment given early in
the course of the disease generally produces a good recovery. Finally, the disease can
be fatal if it is not treated or when treatment is given too late.
MARCH 2010
J AM ACAD DERMATOL
AB41
P1164
P1166
Is topical 5% imiquimod cream effective in the treatment of capillary
malformation?
Margaret Song, MD, Department of Dermatology, School of Medicine, Pusan
National University, Busan, South Korea; Hyun-Chang Ko, MD, Department of
Dermatology, School of Medicine, Pusan National University, Busan, South Korea;
Hyun-Woo Chin, MD, Department of Dermatology, School of Medicine, Pusan
National University, Busan, South Korea; Moon-Bum Kim, PhD, Department of
Dermatology, School of Medicine, Pusan National University, Busan, South Korea;
Su-Han Kim, MD, Department of Dermatology, School of Medicine, Pusan
National University, Busan, South Korea
Capillary malformations, formerly known as port-wine stain, are low-flow vascular
malformations of the skin that occur in neonates. In adulthood, progressive
darkening and the development of nodular violaceous papules are common. The
majority of the capillary malformation can be significantly lightened with selective
photothermolysis with pulsed-dye laser, but the treatment of resistant capillary
malformation is challenging. Imiquimod, as a topical immune modifier, holds
indirect immunoregulatory effect and antiangiogenic property and its effectiveness
of antiangiogenic effect have been explored through the successful treatment of
infantile hemangioma and capillary malformation. Three patients with long-lasting
and refractory capillary malformation, including one patient with nodular change,
underwent trial of topical imiquimod therapy. Topical 5% imiquimod cream was
applied once daily, 5 days per week for 9 to 11 weeks. There was no clinical
improvement in two patients and only minimal improvement in one patient.
Application of 5% imiquimod cream may not be an effective alternative for the
treatment of capillary malformation.
P1167
P1165
A year at Stony Brook University Hospital
Daniel Lozeau, Stony Brook University Hospital, East Setauket, NY, United States;
Peter Klein, MD, Stony Brook University Hospital, East Setauket, NY, United
States
Stony Brook University Hospital is the only tertiary care medical center in Suffolk
County, NY. Throughout the year, during our clinical conferences and Grand
Rounds, fascinating patients are presented for diagnosis and/or treatment. Both
esoteric cases and atypical presentations of common conditions are sent to our
department of dermatology for consultation and interest. We present the best of
these cases.
AB42
J AM ACAD DERMATOL
MARCH 2010
P1168
P1201
An evaluation of neutralizing antibody induction during BoNT-A treatment
Ira Lawrence, MD, Medicis, Scottsdale, AZ, United States; Ronald Moy, MD, David
Geffen School of Medicine at UCLA, Los Angeles, CA, United States
Background: The induction of neutralizing antibodies during aesthetic application
of botulinum neurotoxin type A (BoNT-A) is rare, but of potential clinical concern.
Phase III studies of a new US BoNT-A preparation, Dysport (abobotulinumtoxinA;
Medicis Aesthetics, Scottsdale, AZ), have not identified any cases of neutralizing
antibody formation during the treatment of glabellar lines.
Objective: To provide an in-depth analysis of the potential for induction of
neutralizing antibodies in the study population enrolled in phase III trials of
BoNT-A in the treatment of glabellar lines.
Methods: First and last available serum samples from patients in the BoNT-A glabellar
lines development program were screened for BoNT-A antibodies with a radioimmunoprecipitation assay (RIPA), followed by a known confirmatory competitive
antibody assay (RIPA-C). Confirmed RIPA-Cepositive samples were further tested in
the mouse protection assay (MPA), a highly specific bioassay for neutralizing
antibodies. Safety and efficacy evaluations, including day 30 responder rate and
duration of response in the last treatment cycle, were conducted.
Results: Of 1554 patients who received at least one BoNT-A treatment (10 U at 5
injection points, for a total dose of 50 U per treatment; range, 1-9 treatments), five
(0.32%) were antibody positive on the RIPA-C assay—two at baseline and three at the
last treatment cycle. None of the RIPA-Cepositive samples tested positive in the
MPA. The RIPA-Cepositive group had a responder rate of 100% and a mean response
of 103.3 days, while the RIPA-Cenegative group had a responder rate of 90% and a
mean response of 89.4 days. The safety of BoNT-A did not appear to be altered in the
RIPA-Cepositive group.
ParryeRomberg syndrome
Daniel Hoffman, MD, Henry Ford Health System, Detroit, MI, United States; Holly
Kerr, MD, Henry Ford Health System, Detroit, MI, United States
A 32-year-old African American woman presented with a 1-year history of a linear
indentation extending along the left scalp to the eyebrow. She reported intermittent
episodes of vertigo and blurry vision lasting from a few seconds to a few minutes.
Upon examination, on the left side of the face, there was a linear depression that
extended from the left frontal scalp to the mid-left eyebrow associated with
alopecia. There was no induration or sclerosis. An MRI showed thinning of
subcutaneous tissue but not of bone or neural structures. A biopsy specimen
revealed a sclerotic dermis with mild lymphoplasmacellular inflammation at the
dermal/subcutaneous interface. A diagnosis of linear morphea (en coup de sabre)
was made. The patient was treated with methotrexate and pulsed intravenous
methylprednisolone at 1000 mg for 3 consecutive days a month for 6 months.
Methotrexate was started at 7.5 mg weekly and increased to 15 mg weekly with folic
acid. She reported mild improvement in the scalp alopecia, but not the eyebrow. She
also reported pain in the left eye and face and nose bleeds from the right nostril.
Repeat MRI at 6 months revealed no disease progression and no concerning
compression of optic or neurologic structures. Morphea en coup de sabre is a linear
morphea of the forehead. Hemifacial atrophy or ParryeRomberg syndrome is a
severe form characterized by atrophy of subcutaneous tissues including muscle,
bone, and brain and can present with neurologic symptoms. Our patient presented
with several neurological symptoms but no abnormalities on MRI. Thus,
ParryeRomberg was suspected but not confirmed. Linear morphea can be associated with high ANA titers, especially in children. The histopathology is identical to
plaque-type morphea. Phototherapy has been used to treat all types of morphea,
particularly bath PUVA and UVA1 therapy. Injection of corticosteroids at lesion
margins may help reduce progression. There are reports suggesting benefit from
topical calcipotriene or penicillamine injections. For severe morphea, systemic
treatments are indicated such as oral or intravenous corticosteroids combined with
methotrexate. The approach used for this patient was derived from a study by
Kreuter et al in which 1 g of methylprednisolone delivered 3 days a month was
combined with 15 mg of methotrexate per week. To date, the patient has been
stable without progression of her lesion or symptoms.
Conclusions: At the dose and treatment interval used in the correction of glabellar
lines, induction of neutralizing antibodies to BoNT-A is a rare event. None of the 5
RIPA-Cepositive samples tested positive in the definitive assay, the MPA. RIPACepositive status did not appear to correlate with reduced efficacy or an altered
safety profile, although the small number of RIPA-C-positive subjects prevents
definitive conclusions. These data suggest that the 5 samples represented false
positive results.
CONNECTIVE TISSUE DISEASE
P1200
Acquired cutis laxa and granuloma annulareelike lesions secondary to
multiple myeloma
Doug New, MD, University of Louisville Division of Dermatology, Louisville, KY,
United States; Jeffrey Callen, MD, University of Louisville Division of
Dermatology, Louisville, KY, United States
Background: Cutis laxa clinically presents as loose, redundant skin and may be
inherited or acquired. A lack of family history and later onset is associated with
acquired cases. A small number of cases of multiple myeloma associated with cutis
laxa exist in the literature. We describe a patient who developed lax, redundant skin
of the face, neck, upper trunk, and groin associated with granuloma annulareelike
lesions in the groin area, ultimately leading to a diagnosis of multiple myeloma.
Observation: A 48-year-old man who appeared older than his stated age was referred
for a 4-year history of an asymptomatic cutaneous eruption on the groin area
consisting of erythematous thin macules, papules, and plaques. He also had loose,
redundant skin on the face, upper trunk, and axillae without a history of previous
inflammation or primary skin lesions in these areas. He had a plasmacytoma of the
left axilla treated with surgery and postoperative radiation therapy 4 years before the
onset of cutaneous changes. He was considered disease free by oncology at the time
of referral to dermatology. Biopsy of the loose skin of the upper back revealed
middermal elastolysis and of the left hip revealed a scant histiocytic infiltrate with
middermal elastolysis. Stains were negative for amyloid. Immunofluorescent
electrofixation demonstrated the presence of monoclonal IgG-lambda paraproteinemia. The potential association of his cutaneous skin disease with an underlying
multiple myeloma prompted an evaluation, which revealed multiple bony lytic
lesions and a bone marrow with 10% plasma cells.
Comment: Acquired cutis laxa is a rare disorder and only a few reports have
associated its development with an underlying multiple myeloma. In addition to the
loose, redundant, lax skin changes on the upper body, he presented with granuloma
annulareelike plaques on his groin area associated with the development of
middermal elastolysis secondary to the inflammation. We felt the cutaneous changes
were related to an IgG-lambda paraproteinemia, which prompted a comprehensive
evaluation by his oncologist leading to a diagnosis of active multiple myeloma.
P1202
A case of nodular morphea and discussion
Roy Rindler, MD, University of Oklahoma, Oklahoma City, OK, United States;
Renee Grau, MD, Saint Anthony Hospital, Oklahoma City, OK, United States;
Todd Mollet, University of Oklahoma, Oklahoma City, OK, United States; Victor
Leal, MD, Universidad Anáhuac, Tabasco, Villahermosa, Mexico
We present an interesting case and discussion of nodular morphea in a 66-year-old
Hispanic woman. She presented with nodules widespread over the chest, abdomen,
back, shoulders, and arms. The lesions had been present for 18 to 24 months with
occasional spontaneous regression leaving hyperpigmented areas. The nodules
were largely asymptomatic except for transient mild pruritis, and she denied any
systemic symptoms. Physical examination revealed nodules that were smooth
topped, firm, flesh-colored, and measured 3 to 12 mm in diameter. Microscopic
findings showed a monomorphous appearance of the dermis with notable thickness
throughout the table of skin, and a unique pattern of fibrosis and banding of collagen
throughout with a patchy inflammatory infiltrate. There was preservation of the
adnexal structures with diminished periadenexal fat and a bound-down appearance
of the eccrine glands. Clinical presentation and examination of histology was
consistent with the diagnosis of nodular morphea. Nodular morphea is an uncommon form of scleroderma that can be found in both localized and systemic
scleroderma. It usually presents as rigid nodules in a localized, general, or linear
pattern on the neck, trunk, or proximal limbs. The nodular lesions can develop
before or after scleroderma is diagnosed. The cause of nodular morphea is unknown
with varying histologic presentations of sclerodermal, keloidal, or a combination of
the two. Treatment of nodular morphea has to date been disappointing and remains
a challenge for the clinician.
MARCH 2010
J AM ACAD DERMATOL
AB43
P1203
P1205
Does a pathogenic relationship exist between morphea and granuloma
annulare?
Rafael Jiménez-Puya, MD, University Hospital Reina Sofı́a, Córdoba, Spain; Gloria
Garnacho-Saucedo, University Hospital Reina Sofı́a, Córdoba, Spain; José MorenoGiménez, MD, PhD, University Hospital Reina Sofı́a, Córdoba, Spain; Maria
Alvarez-López, University Hospital Reina Sofı́a, Córdoba, Spain; Rafael SalidoVallejo, University Hospital Reina Sofı́a, Córdoba, Spain
Morphea and granuloma annulare are separate disorders according to the dermatologic literature. Only six cases of coexisting morphea and granuloma annulare
have been reported. Some authors suggested that a common etiologic link could
explain this association. Histologically, both diseases show a perivascular and
interstitial lymphohistiocytic infiltrate and collagen alterations. Moreover, an autoinmune etiology has been postulated for both morphea and granuloma annulare. It
remains unclear if a disregulation in the control of fibroblast function by Tcellederived cytokines could be the common event in the pathogenesis of both
diseases. We present a 68-year-old man who developed an annular asymptomatic
eruption over both sides of abdominal area that was clinically and histologically
characteristic of generalized granuloma annulare. He was treated first with oral
corticosteroids and later with sulfone, with good response. One year later, indurated
plaques appeared in the same localization and new lesions of granuloma annulare
were also noticed near them. Skin biopsy provided the diagnosis of morphoea.
Dermatomyositis associated with generalized subcutaneous edema and
Evans’ syndrome
Kyu-Dong Jung, MD, Samsung Medical Center, Seoul, GangNam-Gu, South Korea;
Hyun-Je Kim, MD, Samsung Medical Center, Seoul, GangNam Gu, South Korea; JiHye Park, MD, Samsung Medical Center, Seoul, GangNam-Gu, South Korea
Periorbital edema is a common manifestation of inflammatory myopathy. However,
generalized subcutaneous edema associated with dermatomyositis (DM) is extremely rare. The etiology and prognosis of DM with generalized subcutaneous
edema are still unknown. Evans syndrome is defined as the simultaneous or
sequential occurrence of Coombs positive hemolytic anemia and immune thrombocytopenia without underlying etiology. Evans syndrome with DM is very uncommon. We report the case of 52-year-old woman who presented generalized
subcutaneous edema, an erythematous skin rash, dysphagia, proximal muscle
weakness, and Evans syndrome. A 52-year-old Korean woman was admitted to our
hospital because of the erythematous skin eruptions, whole body swelling, and
progressive muscle weakness of 10 months’ duration. The skin examination showed
Gottron sign on the dorsal surface of her hand, a heliotropic rash on both eyelids,
and a ‘‘V’’ sign on her neck. A physical examination revealed generalized nonpitting
edema on the whole body. A neurologic examination showed decreased muscle
power in the extremities, shoulder, and pelvic girdles. We tentatively diagnosed her
as DM with generalized subcutaneous edema and performed the laboratory
evaluations. The muscle enzymes were elevated. Renal function test, thyroid
function test, and autoantibodies tests were performed to rule out other causes of
the generalized edema. However, those examinations were all unremarkable.
Computed tomographic scan, electromyographic examination, and muscle biopsy
of right rectus femoris were performed. All of these findings were compatible with
DM with generalized subcutaneous edema. The patients was treated with methylprednisolone (1 mg/kg/day IV), which resulted in rapid improvement in her muscle
weakness and edema within 10 days along with markedly decreased muscle
enzymes. The patient showed relatively good response to intravenous corticosteroids. After a brief improvement, she developed Evans syndrome and received
intravenous immunoglobuline and then oral corticosteroid and immunosuppressive
agents. After treatment, the patient’s laboratory condition was gradually improved.
Now she has been in good general condition over the follow-up period. In
conclusion, we experienced a extremely rare case of DM with generalized
subcutaneous edema and sequentially developed Evans syndrome. To the best of
our knowledge, it is the first case of DM with generalized edema and Evans syndrome
in the English literature.
P1204
Bilateral chondrodermatitis nodularis helicis associated with systemic
sclerosis
Eric Hossler, MD, Geisinger Medical Center, Department of Dermatology,
Danville, PA, United States; Michael Ramsey, MD, Geisinger Medical Center,
Department of Dermatologic Surgery, Danville, PA, United States
Systemic sclerosis (SSc) is an acquired multisystem disease of unknown origin that is
characterized by small vessel vasculopathy and fibrosis of the skin and internal
organs. Recurrent episodes of tissue ischemia and reperfusion can cause end organ
damage, such as skin ulceration. Digital ulcers are seen in 25% to 54% of patients
with SSc and can be a major cause of pain and disability. Chondrodermatitis
nodularis helicis (CNH) is characterized by a small tender nodule on the helix or
antihelix of the ear. The cause is felt to be localized ischemic necrosis of the skin
overlying the cartilage. Most cases are a consequence of excess external pressure,
such as sleeping on one side or extended telephone use. There have been four cases
of CNH occurring concomitantly with SSc. We present the fifth case, a 74-year-old
man with a history of SSc, esophageal cancer status postesophagectomy, and
pulmonary hypertension. He had symmetric painful lesions of the helices, having
developed 3 months ago on the left, and 6 weeks earlier on the right. He recalled
having similar lesions 30 years earlier that were treated surgically, and he has had no
problems until presentation. He sleeps mostly on his left side because of severe
coughing when lying on his right side. He is left-handed and does usually hold the
telephone on the left. He is an active fencer and notes that his mask may rub on the
affected areas. He was initially treated with a series of triamcinolone injections, with
minimal relief. Punch excisions into the cartilage provided rapid relief. His CNH
remains in remission at 24 months postexcision. Although the precise etiology of
CNH remains speculative, most sources suggest that local ischemia plays a major
role. The histologic changes are identical to those found in decubitus ulcers, with
crust, dermal fibrin, and granulation tissue. CNH has been reported only rarely in
association with SSc. There is also a single case of bilateral CNH in an 8-year-old girl
with dermatomyositis, another condition with prominent vascular dysfunction.
Ischemia and vascular changes may be the key pathologic changes in CNH and in
SSc. We agree with Bottomley et al that an association between these conditions may
be underreported.
P1206
AB44
Successful treatment of generalized morphea with methotrexate: A case
report
Shery Varghese, MD, PhD, University of Pittsburgh, Pittbsurgh, PA, United States;
Alexandra Zhang, MD, University of Pittsburgh Department of Dermatology,
Pittsburgh, PA, United States; Jonhan Ho, MD, University of Pittsburgh
Department of Dermatology, Pittsburgh, PA, United States
Generalized morphea is a cutaneous form of scleroderma with no systemic
involvement. There have been reports of chemically induced morphea. We report
a case of generalized morphea in a patient after exposure to cleaning chemicals with
significant decrease in functional status and a good treatment response with
methotrexate. A 41-year-old African American man with no significant medical
history was seen in our clinic with a complaint of chronic thickening and tightening
of skin on his bilateral upper extremities and chest. He reported that this had
occurred during his job in a cleaning business. He reported mixing two types of
cleaners and washing the floors and ovens without gloves. Over the year that he was
at this job, he noticed that his upper arms and chest, where he had contact with the
chemicals, were progressively ‘‘tightening’’ up and interfering with his ability to
work. The patient was incapable of making a fist, tying his shoelaces or raising his
arms above his head. Before presentation to our clinic, he had been unemployed for
a year without any noticeable improvement in his physical ability. He had no other
systemic symptoms. Blood work revealed that his ANA, Scl-70, anticentromere, SSA,
SSB, and ESR were negative and CBC, CMP, and LFTS were within normal limits. A
cutaneous biopsy showed a ‘‘square’’ punch biopsy with thickened and sclerotic
collagen bundles with a marked decrease in periadnexal fat. Overall, these findings
were consistent with morphea. This patient was treated with a weekly dose of 15 mg
of methotrexate with good response. After a treatment period of 7 months, the
patient regained most of his functional mobility. On physical examination, there was
more laxity of the affected skin. The patient was able to close his fist, tie his
shoelaces, and raise his arms over his head. In conclusion, this case shows the
physical complications that can arise from morphea and the importance in properly
recognizing and treating this disease. Furthermore, this case illustrates the efficacy
of methotrexate in treating morphea.
J AM ACAD DERMATOL
MARCH 2010
ABS 5.0 DTD YMJD6694_6697_proof 23 January 2010 7:25 pm
P1207
P1209
Reiter syndrome, beyond the classic triad: Presentation of two atypical
cases
Ruth Quiroz-Mejı́a, MD, Instituto Nacional de Ciencias Médicas y Nutrición
Salvador Zubiran, Tlalpan, Mexico City, Mexico; Ana Ruelas-Villavicencio, MD,
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Tlalpan,
Mexico City, Mexico; Carla Archer-Dubon, MD, Instituto Nacional de Ciencias
Médicas y Nutrición Salvador Zubiran, Tlalpan, Mexico City, Mexico; Rocio
Orozco-Topete, MD, Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Zubiran, Tlalpan, Mexico City, Mexico
High prevalence of vitamin D deficiency among patients with cutaneous
lupus erythemathosus
Eugenia Cutillas-Marco, MD, Department of Dermatology; Fundación Hospital de
Cieza, Cieza, Murcia, Spain; Amparo Fuertes-Prosper, MD, Department of
Dermatology; Hospital Universitario Doctor Peset, Valencia, Spain; Amparo
Marquina-Vila, MD, PhD, Department of Dermatology; Hospital Universitario
Doctor Peset, Valencia, Spain; Maria M. Morales Suarez-Varela, MD, PhD, Unit of
Public Health and Environmental Care, Department of Preventive Medicine,
University of Valencia, Burjasot, Valencia, Spain
Case presentation: We report the cases of two male peasant natives, 28 and 35 years
old, respectively, from the same geographic region, low socioeconomic status, and
who had no personal history of risky sexual behavior. One had a family history of
unclassified arthropathy. Both presented with a 2- to 4-year history of widespread
erythematous and scaly plaques mainly on head, legs, palms, and soles, as well as
pachyonichia. One of the patients had circinate balanitis and the other concomitant
erythematous and circinate oral plaques. They had a 1- to 10-year history of flares of
fever and polyarticular, asymmetric arthritis of large joints. By the time of diagnosis,
they had developed joint deformity and ankylosis with low functional class and
weight loss. No conjunctivitis was documented in either patient. Rheumatoid factor
and HIV were negative. One of the patients had positive determination for antigen
haplotype B27 and ureaplasma urealyticum was isolated from urethral discharge.
Radiographic studies of both patients showed chronic degenerative changes and
coxofemoral or tibial subluxation. Both skin biopsies showed a psoriasiform
dermatitis with spongiosis, intraepidermal microabscesses and a lymphocytic
infiltrate. Both patients were misdiagnosed elsewhere with psoriasis with seronegative arthropathy and had received prednisone and sulfasalazine for a short period of
time. They were admitted in our unit for septic shock and died despite antimicrobial
and supportive treatment.
Background: Vitamin D (vitD) is crucial for maintaining the body’s calcium
homeostasis. Its deficiency in progression of cancer and several autoimmune
diseases. It has been shown that the serum levels of vitD are significantly lower in
patients with systemic lupus erythematosus (SLE) compared with control groups.
We wanted to know whether these findings are limited to SLE or if vitD deficiency is
also observable in patients with chronic discoid lupus erythematosus or subacute
cutaneous lupus erythematosus.
Methods: We measured serum levels of 25-hydroxyvitamin D in 55 patients; 76.4%
were females, with an age (mean 6 SD) of 46.93 6 13.87 years and 49.69 6 11.82
years in males. A questionnaire was given to every patient at the time of being
including in the study, asking about medical history, current treatment, phototype,
tobacco, height, weight, use of sunscreens, sun exposure, duration of lupus, type of
lupus, and daily intake of vitD-rich food. A blood test was performed to measure
serum levels of 25-OH-vitamin D, calcium, phosphorus, and PTHi.
Discussion: Reiter syndrome is typically described as the triad of conjunctivitis,
urethritis, and arthritis; however, this clinical picture can be accompanied by
mucocutaneous manifestations such as circinate balanitis, oral lesions, nail changes,
and erythematous hyperkeratotic plaques (keratoderma blennorrhagicum) typically
on the palms and soles that can extend to other skin areas showing an atypical
clinical picture of this disease. We present these cases as two interesting examples of
the clinical spectrum of a longstanding, undiagnosed, and severe Reiter syndrome,
emphazising the relevance of the dermatologic manifestations as an important clue
for its diagnosis.
Results: The mean (SD) 25-OH-vitamin D level overall was 19.67 (770) ng/mL in men
and 20.17 (9.36) in women. Of the 55 tested patients, 52 (94.54%) had serum levels
of vitD less than 30 ng/mL, which is the range consistent with insufficiency,
including 6 patients (10.9%) with less than 10 ng/mL. In spite of the absence of
significant differences, we found that levels of vitD were higher in young people and
among people who received treatment with supplements of vitD. By contrast,
smokers and patients with shorter sun exposure presented lower levels of vitD.
Curiously, we found higher levels of vitD among patients with phototype IV, maybe
because of the longer sun exposure in patients with darker skin. VitD levels were
similar both in chronic and subacute cutaneous lupus, but decreased in patients
with a long history of lupus. Photosensitivity was found to be a predictor of
hypovitaminosis. Daily intake of higher vitD-rich food did not protect against
hypovitaminosis.
Conclusion: We found a high prevalence of vitD insufficiency and deficiency among
patients with cutaneous lupus erythematosus. For that reason, we recommend
screening for deficiency of 25-OH-vitamin D in any person at risk, including all the
diseases where sun avoidance is recommended.
P1208
Hemicorporal morphea: Study of seven cases
Mercedes Lidia Hassan, MD, MPH, PhD, University of Buenos Aires-Ramos Mejia
Hospital, Buenos Aires, Argentina; Jesica Waiman, MD, Ramos Mejia Hospital,
Buenos Aires, Argentina; Maria Elena Melloni, MD, Ramos Mejia Hospital, Buenos
Aires, Argentina; Miriam Saposnik, MD, Ramos Mejia Hospital, Buenos Aires,
Argentina
Background: Hemicorporal morphea is an extremely infrequent disease. Its limits
and relations with facial hemiatrophy(ParryeRomberg disease) and linear morphea
remain under discussion.
Methods: Seven cases of patients ranging in age from 6 to 45 years were seen
between 2000 and 2009 in our department and were studied by reporting the
following: (1) the predominance of sclerosis or atrophy; (2) the age of consultation
and initiation of the disease; (3) the site of initiation; (4) ipsilateral or contralateral
involvement; (5) the presence of dystonia, muscular contractures of myoclonus; (6)
the loss or diminished visual function, including dry eyes; (7) neurologic examination and NMR and CRL findings and others; and (8) the laboratory findings.
DERMATITIS, ATOPIC
P1300
Results: Six females and one male with a disease from 1 month to 9 years’ duration of
disease. They reported starting at the upper or lower member in six, simultaneously
with the face in two. Sclerosis predominate in all but one, was ipsilateral in all seven,
and coexists with contralateral plaque of sclerosis in the face in one patient.
Dystonia (2) and muscular contractures (2) were prominent in four. Dry eyes (1),
mild queratitis (1), and diminished visual accuity (1) were found in three out of
seven. Laboratory findings: all cases exhibit at least one positive finding. High titer
FAN (Ho or Mo), RF, ACA, RR, diminished C4, or hypergammaglobulinemia. Scl70
tested positive in a 6-year-old girl with systemic sclerosis.
Complementary examinations: Oligoclonal bands in CRL (1 case) and multiple
hyperdense subcortical bifrontal and periventricular focus of demyelinization were
found in cerebral NMR.
Treatments: Ov methotrexate, UVA1 and PUVA, local calcipotriol, or corticosteroids
in cream. SC ceparin, aspirin, cilostazol in other with high-titer ACA and cutaneous
leg ulcer. Early treatment seemed to stop the rapid progression of sclerosis, but
information in the long-term follow-up was not available.
Conclusions: This particular form of morphea has a singular course and behavior
because of the rapid spreading, neurologic involvement, remarkable nonspecific
laboratory findings, and the site of initiation. Atrophy may be prominent, and early
treatment may stop, in the short-term, the progression of sclerosis.
MARCH 2010
J AM ACAD DERMATOL
AB45
P1301
P1303
Phototherapy for the treatment of atopic dermatitis in Asian children
Mark Koh, MBBS, Changi General Hospital, Singapore; Celene Hui, National Skin
Centre, Singapore; Wei-Sheng Chong, MBBS, National Skin Centre, Singapore
Objective: To review a cohort of Asian children with atopic dermatitis treated with
phototherapy at a tertiary dermatologic center in Singapore.
Adherence to topical tacrolimus 0.1% ointment in children with atopic
dermatitis
Brad Yentzer, MD, WFU School of Medicine, Winston Salem, NC, United States;
Adele Clark, PA, WFU School of Medicine, Winston Salem, NC, United States; Lisa
Williams, WFU School of Medicine, Winston Salem, NC, United States; Matthew
Sagransky, WFU School of Medicine, Winston Salem, NC, United States; Steven
Feldman, MD, PhD, WFU School of Medicine, Winston Salem, NC, United States
Background: Noncompliance with topical medications is responsible for many
treatment failures in dermatology.
Method: A retrospective analysis of Asian children with atopic dermatitis treated
with phototherapy at the National Skin Centre, Singapore, over a 5-year period from
2004 to 2008.
Results: Twenty-five patients were identified. Patients were aged between 7 and 15
years at time of undergoing phototherapy, and there was an equal number of boys
and girls. There were 22 Chinese, two Indian, and one Malay patient. Duration of
disease ranged from 2 to 14 years (mean, 9.7 years). Most patients had extensive
disease of more than 70% body surface area involvement. Apart from one patient
who had treatment with oral cyclosporin, all other patients were previously only on
topical treatments with intermittent oral corticosteroids and/or antibiotics. Fifteen
patients were treated with narrowband ultraviolet B (nbUVB) phototherapy, with 10
(66%) showing improvement of symptoms. Duration of therapy was from 3 to 30
months (mean, 11 monts) after a mean of 60 treatment sessions (range, 12-104).
Maximal doses reached ranged from 665 to 4598 mJ/cm2 (mean, 2351 mJ/cm2).
Three patients had poor response after 2 months of treatment, one patient had
worsening of symptoms, and one patient developed severe sunburn after the first
treatment. One patient developed eczema herpeticum that required cessation of
treatment. Nine patients were treated with combined ultraviolet A (UVA)/nbUVB
phototherapy. Five patients (55%) improved, with four having a good response and
one having mild improvement. Duration of therapy was from 1 to 6 months (mean,
3.6 months), after an average of 22 treatment sessions (range, 10-44). Maximal doses
reached was UVA 5.1 J/cm2 (mean, 2.5 mJ/cm2) and nbUVB 300 mJ/cm2 (mean, 300
mJ/cm2). Three patients had poor responses after 2 to 5 months of therapy, and one
patient had a worsening of symptoms. One patient developed eczema herpeticum
during treatment. The two patients who underwent combined UVA/broadband
ultraviolet B (bbUVB) phototherapy had a worsening of symptoms requiring
cessation of treatment. One of them subsequently had good response to
UVA/nbUVB.
Conclusion: Phototherapy is a useful adjunct in the treatment of moderate to severe
atopic dermatitis in children. From our study, the response rates of nbUVB and
combined UVA/nbUVB are comparable. However, the usefullness of combined
UVA/bbUVB requires further evaluation.
Purpose: We evaluated adherence and the impact of a return visit in children with
atopic dermatitis treated with topical tacrolimus 0.1% ointment. Methods: Thirty
subjects, ages 2 to 14 years, with moderate to severe atopic dermatitis were enrolled
in this prospective, double-blind clinical trial. Subjects or their parents were
instructed to apply the medication twice daily for 4 weeks. Half of the subjects were
scheduled an extra follow-up visit at week 1. Adherence was measured via electronic
monitors in the caps of the medication. Subjects were not informed about the
electronic monitoring until the end of the study. Assessments of disease severity
performed at each visit included Eczema Area Severity Index scores, Investigator
Global Assessments, and 100-mm Visual Analog Scales of Pruritus.
Results: Twenty-three subjects have completed the trial to date. Daily applications of
medication ranged from zero to six, with individual mean adherence ranging from
15% to 114%. Overall mean adherence to twice daily application over the 4 weeks
was better in the group with an extra return visit (77% vs 54%). The extra follow-up
group also had better improvement in disease severity as measured by mean percent
improvement in IGA, VAS, and EASI scores (42% vs 33%, 67% vs 38%, and 74% vs
51%, respectively).
Conclusions: These preliminary results support that better adherence to topical
medications can be achieved by an early return visit. In addition, there is some
evidence that better adherence to topical tacrolimus is associated with better
outcomes in disease severity.
Commercial support: 100% is sponsored by Astellas.
P1302
P1304
Daily application of fluocinonide 0.1% cream for the treatment of atopic
dermatitis
James Del Rosso, DO, Valley Hospital Medical Center, Las Vegas, NV, United
States
Improvement of skin conditions related to atopic eczema through the use
of a highly occlusive cationic emulsion
Lisa Adams, Kao Brands Co, Cincinnati, OH, United States; Andrea Schultz, Kao
Brands Company, Cincinnati, OH, United States; Monya Sigler, PhD, Stephens &
Associates, Carollton, TX, United States; Stacy Sherman, MS, Kao Brands
Introduction: Atopic dermatitis is a chronic disease affecting approximately 10% to
20% of children. The disease develops during the first 12 months of life in 75% of
affected children and completely clears at or shortly after puberty in 40% to 60%;
however, it may persist in more than 20% of adolescents. Fluocinonide cream 0.1%
(Medicis Pharmaceutical) is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in
patients 12 years of age or older. The following study was performed to assess the
efficacy and safety of topical fluocinonide 0.1% cream for the treatment of atopic
dermatitis.
Conclusion: Once or twice daily topical application of fluocinonide 0.1% cream for
14 days is effective for treating atopic dermatitis in adults. The efficacy of once daily
application was comparable to twice daily treatment while both application
frequencies were equally safe.
Atopic dermatitis is a disease of the skin and its symptoms include inflammation,
severe dryness, itching, and redness. Extreme heat, sweat, fabrics, or allergens can
trigger flare-ups and make the skin condition difficult to manage, especially among
children. Improving barrier function and increasing hydration through the use of a
highly occlusive cationic emulsion with high lipophilic and humectant properties is
a key mechanism for improving such skin conditions. The positive or cationic charge
of the emulsion is attracted to negatively charged dry skin and delivers the
moisturizing ingredients (ie, glycerin, ceramides, and lipophilic materials) to areas
of the skin where they are needed most, thereby improving the barrier function of
skin and reducing itch associated with atopic dermatitis. The efficacy of a cationic
emulsion on atopic and dry skin was shown in a series of clinical studies. One trial
was conducted on atopic and dry skin among men and women (18-58 years) and a
subsequent trial was run among children (6 months to 17 years). Dermatologist
evaluations (irritation: erythema, edema, and scaling) and self-assessments were
conducted at baseline and weeks 1, 2, and 4. More than half of the subjects had at
least one clinically confirmed lesion. Dermatologist evaluations indicated significant
improvement (P # .05) for erythema, edema, and scaling for both adults and
children within a week. The panelists perceived improvements (P # .05) in
dryness, redness, and itch as early as 1 week after use and 95% agreed it relieved their
dry itchy skin. No adverse reactions were received by the panelists. In a separate
study, digital photos were taken to visually capture these skin improvements. In
addition, a 1-week clinical regression study was conducted with very winter xerotic
skin. The moisturization benefits remained at a statistically significant level up to 3
days after the treatment was discontinued. In conclusion, this highly occlusive
cationic emulsion was shown to be safe and effective at improving dry skin, relieving
itch, and reducing redness on children and adults with atopy and/or very dry skin. It
provides better hydration than leading brands and helps to improve the skin
hydration. With continued use, the cationic emulsion prevents the reoccurrence of
dry skin and itching and provides an adjunct to prescription treatments for
management of atopic dermatitis.
Commercial support: Sponsored by Medicis Pharmaceutical.
Commercial support: 100% Supported by Kao Brands Co.
Methods: This double-blind, vehicle-controlled study enrolled patients 18 years of
age or older with atopic dermatitis affecting $ 2% but \10% of body surface area.
Patients were randomized to receive treatment with fluocinonide 0.1% cream
applied once (N ¼ 109) or twice daily (N ¼ 102) for 14 days or vehicle applied once
(N ¼ 50) or twice daily (N ¼ 52) for 14 days. Efficacy and safety measures included
lesion severity, pruritus, hypothalamic-pituitary-adrenal (HPA) axis suppression, and
reported adverse events.
Results: Fluocinonide 0.1% cream applied once or twice daily was more effective
than cream vehicle. Both fluocinonide regimens were similarly efficacious. At the
end of treatment, lesions were cleared or almost cleared in 59% of subjects treated
once daily and 57% of subjects treated twice daily with fluocinonide 0.1% cream;
however, considerable residual benefit remained after cessation of twice daily versus
once daily treatment. Skin safety evaluations showed that treatment with fluocinonide 0.1% cream did not cause significant signs or symptoms of skin atrophy.
Among subjects with a normal baseline serum cortisol response to the cosyntropin
stimulation test, HPA axis suppression following once and twicedaily treatment with
fluocinonide 0.1% cream was not significantly different than vehicle-treated subjects
Fluocinonide 0.1% cream was well-tolerated.
AB46
J AM ACAD DERMATOL
MARCH 2010
P1305
P1307
Airborne proteins and atopic dermatitis: A review
Sarah Hostetler, MD, Ohio State College of Medicine Division of Dermatology,
Columbus, OH, United States; Benjamin Kaffenberger, Ohio State University
College of Medicine, Columbus, OH, United States; Matthew Zirwas, MD, Ohio
State College of Medicine Division of Dermatology, Gahanna, OH, United States;
Todd Hostetler, MD, Ohio State College of Medicine Division of Allergy and
Immunology, Columbus, OH, United States
An open-label study to evaluate clobetasol propionate foam for the
treatment of chronic hand dermatitis
Leon Kircik, MD, Physicians Skin Care, Louisville, KY, United States
Atopic dermatitis is a common chronic skin condition with multifocal etiology. A
subset of patients exists in whom cutaneous exposure to common airborne proteins
exacerbates their disease. These reactions are medicated by multiple mechanisms,
including proteolytic activity of the proteins degrading the stratum corneum, direct
activation of PAR-2 itch receptors by the proteins, and IgE binding leading to mast
cell and dendritic cell activation. The most common airborne proteins that have
been shown to be significant in atopic dermatitis include the house dust mite, pet
dander, and multiple pollens. Patients likely to have airborne proteins contributing
to their disease typically have lesions on air-exposed surfaces including the face,
neck, décolletage, and arms along with relative sparing of covered areas; a history of
exacerbations during spring and/or summer; and/or very severe atopic dermatitis
resistant to conventional therapies. The literature on skin prick testing, specific-IgE,
and atopy patch testing is mixed, with greater support for the use of atopy patch test
results to identify this subset. The multiple mechanisms underlying aeroallergen
mediated atopic dermatitis and selection of affected patients predominantly by IgE
testing may be responsible for the contentious efficacy data of therapies such as
aeroallergen avoidance, frequent showering, topical and systemic barrier repair,
omalizumab, leukotriene inhibitors, and specific immunotherapy.
Objectives: Chronic hand dermatitis is a challenging disease to treat and a topical
product’s vehicle and excipients play a crucial role and can directly impact
treatment outcomes. The objective of this study was to assess the safety, efficacy,
and tolerability of clobetasol propionate 0.05% in a foam vehicle in subjects with
chronic hand dermatitis and to evaluate their preference and quality of life after
treatment.
Methods: A single-center, open-label pilot study assessed the safety, efficacy, and
tolerability of twice daily treatment with clobetasol propionate 0.05% foam for 2
weeks in 30 subjects with mild to moderate chronic hand dermatitis. The primary
efficacy endpoint was the change from baseline in Investigator’s Static Global
Assessment (ISGA). Additional evaluations included Hand Eczema Severity Index
(HESI), Subject’s Visual Analogue Assessment Scale, Work Productivity and Activity
Impairment (WPAI) Questionnaire, Dermatology Life Quality Index, and the Patient
Preference Product Post-Study Questionnaire. Adverse events (AEs) and concomitant medications were monitored for safety at each visit.
Results: The proportion of subjects who achieved a minimum 1-grade improvement
in ISGA score was 76.7% at day 8 and 96.7% at day 14 (P \.0001). After 2 weeks of
treatment with clobetasol propionate 0.05% foam, 80% of subjects achieved a score
of 0 (clear) or 1 (almost clear). In terms of patient preference, the majority of
subjects considered the clobetasol propionate 0.05% foam to be ‘‘better’’ or
‘‘superior’’ to other formulations used in the past. Overall, marked improvement
was observed in all secondary efficacy measures, including quality of life. Four
subjects experienced treatment-related AEs; however, no pattern of adverse event
occurrence or predisposition was found.
Conclusions: Clobetasol propionate foam was found to be well tolerated and
effective for the treatment of chronic hand dermatitis. Furthermore, improvement in
quality of life and a high degree of patient satisfaction were documented with the
twice-daily use of clobetasol propionate foam.
Commercial support: 100% is sponsored by Stiefel Laboratories, Inc.
P1306
Nutritional status and dietary patterns of children with atopic dermatitis
in Korea
Chun Wook Park, MD, PhD, Kangnam Sacred Heart Hospital, Seoul, South Korea;
Insu Ahn, MD, Kandnam Sacred Heart Hospital, Seoul, South Korea
Background: Atopic dermatitis (AD) is a disease characterized by itching and
eczema-like skin lesions, with a reduction of symptoms as the patient grows into
adulthood. Recently, the prevalence of AD has increased to range from adolescents
to adults. The prevalence of AD seems to increase in Korea related to Western
lifestyle and dietary patterns.
Objectives: The aim of this study was to evaluate the nutritional status and dietary
patterns of AD patients in Korea.
P1308
A unique complex of several amino acids can cure patients with atopic
dermatitis
Nishikori Koji, PhD, Laboratory of Aesthetic Immunology, NPO Japan Immune
and Beauty Association, Tokyo, Japan; Koyama Hideo, MPA, Laboratory of
Aesthetic Immunology, NPO Japan Immune and Beauty Association, Tokyo,
Japan; Shimano Takako, MS, Laboratory of Aesthetic Immunology, NPO Japan
Immune and Beauty Association, Tokyo, Japan
Conclusion: Our study indicates that the most deficient nutrients are folate and iron.
The study group tended to need vitamin A, vitamin C, calcium, and niacin as
determined by the nutritional status and food preference in AD patients. Essential
nutrients are more deficient in AD patients than healthy people. It is closely related
to AD severity. In addition, breastfeeding influences AD severity.
It has been elucidated that a unique complex of several amino acids (Parciastasis)
may have an extremely good therapeutic effect for the patients with atopic
dermatitis (AD). We have tried to cure AD patients with Parciastasis for more than
20 years, and the AD patients in this study group were comprised of more than 300
persons of varied ages and both genders. Application of Parciastasis to the skin of the
AD patients several times a day for 6 months to 1 year could cure them of AD almost
completely as far as it was not discontinued. Treatment of the AD patients with
steroids preceding Parciastasis tended to delay the complete cure of AD by
Parciastasis, since the treatment started by exclusion of steroids. Therefore, steroids
apparently seem to make AD deteriorate. Furthermore, approximately 65% of AD
patients exhibited elevation of serum LDH value and the rest was not. On the
contrary, the value of serum lymphocyte was significantly low. Very interestingly,
the high LDH values of the AD patients were lowered to the normal level
accompanying with the therapy of AD by Parciastasis. Assuming that high serum
LDH values might reflect an abnormal activation of skin cells due to AD, we consider
that the group with high serum LDH values may be true AD patients, and the group
with low LDH values may be pseudo-AD patients caused by other pathogenic
mechanisms. Because it is known that activation of Langerhans cells through nitric
oxide (NO) may play an important role for the therapeutic effect for AD, it is likely
that Parciastais may efficiently supply Arg to NO or NOS (NO synthase) activation.
Alternatively, Parciastasis may activate Langerhans cells directly by a different
mechanism. Because Parciastasis caused an apparent aggravation very often at
beginnings of the therapy, it is suggested that Parciastasis may induce apoptosis of
AD skin cells. Further studies of the mechanism by which Parciastasis can cure AD
patients of AD must be performed.
Methods: The study population consisted of 50 children with AD who visited the
department of dermatology in Kangnam Sacred Heart Hospital, Seoul, South Korea,
between May 2007 and May 2008. The physical condition of the patients and their
intake of calories were evaluated using the food-record questionnaire written by
subjects and the nutritional assessment program (Can-pro 3.0, Korean Nutrition
Society, 2005). This program is similar to Mosby’s Nutritrac nutirion analysis
software. We analyzed the dietary intake and the average requirements of three
major nutrients (carbohydrates, proteins, and lipids) and vitamins A, B, C, E, niacin,
folic acid, calcium, iron, phosphorus, and zinc.
Results: The intake of three macronutrients were investigated in all subjects and
were measured as follows: proteins, 18.02% (recommended dietary allowances
[RDA], 7;20%), carbohydrates, (RDA, 55;70%), and lipids (RDA 15;30%). The
most insufficient nutrients were folic acid, which was deficient in 31 subjects (62%),
and iron, which was deficient in 21 subjects (42%). When comparing preferences
between instant food and homemade cooking, patients preferred instant food (n ¼
34; 68%) to homemade cooking (n ¼ 16; 32%). There were 17 patients who had
been feed by breast milk among the 50 subjects.
MARCH 2010
J AM ACAD DERMATOL
AB47
P1309
P1311
Benefits of a novel moisturizing body lotion for patients with atopic
eczema
Jamie Regan, MS, Unilever R&D, Trumbull, CT, United States; Greg Nole, MS,
Unilever R&D, Trumbull, CT, United States
In vivo confocal microscopy reveals new skin moisturizing system that
hydrates all levels of stratum corneum more effectively than equivalent
dose of glycerol
Greg Nole, MS, Unilever R&D, Trumbull, CT, United States; Shuliang Zhang, PhD,
Unilever R&D, Trumbull, CT, United States; Vickie Foy, MS, Unilever R&D,
Trumbull, CT, United States
Water in the stratum corneum (SC) plays a key role in maintaining the suppleness,
health, and appearance of skin. However, the SC is often subjected to environmental
stresses that reduce its water retention and water holding capacity. Recent clinical
research has demonstrated significant differences in hydration through varying
depths of the SC between normal, healthy skin compared to atopic skin, using
Raman spectroscopy. Raman spectroscopy has recently become more widely used
for measuring hydration and NMF levels at varying depths within the SC. Glycerol is
recognized as one of the most effective moisturizing ingredients and is widely used
in skin care products for dry skin. We have recently discovered a proprietary new
humectant (glycerol quat) with physicochemical properties suggesting advantages
in hydration throughout the SC over glycerol alone. The objective of this research
was to confirm this hypothesis clinically, using Raman spectroscopy to quantify
differences in water content through varying depths of the SC. A series of 4-hour arm
moisturization studies using conductance and capacitance methods to assess skin
hydration showed that humectant systems containing the new glycerol quat
molecule were significantly more effective than equivalent moisturizing systems
based on glycerol alone. The superiority of the glycerol quat system was observed in
tests of both solutions and fully formulated skin care lotions. The efficacy of the
glycerol quat system was also significantly better compared to glycerol alone in
longer term moisturization studies. The advantage of glycerol quat was most evident
in the first few days of treatment. Faster recovery from dry skin is expected to be a
highly desired benefit for consumers. Using Raman spectroscopy, we have shown
that the greater moisturization of glycerol quat sytems reflects increased hydration
throughout all layers of the stratum corneum.
Atopic eczema is an intensely pruritic cutaneous inflammatory condition that affects
more than 15% of the population. Common clinical features of this disease include
erythema and pruritus. Glycerol quat (GQ) is a novel humectant that was developed
to provide enhanced moisturization concentrated on the outermost layers of the SC.
In a series of previous moisturization trials, GQ has been shown to deliver greater
moisture to the surface layers than glycerol alone. A novel moisturizing lotion using a
combination humectant system composed of glycerol, hydroxyethylurea and GQ
(GQ1gly) was found to be highly effective in a repeat daily-use study for the
treatment of dryness in a healthy skin population. It was therefore of interest to
evaluate the compatibility of this novel GQ1gly combination for compatibility with
eczema. A single-center, institutional review boardeapproved, double-blinded
randomized, monadic design clinical study in subjects diagnosed with mild to
moderate atopic eczema patients was conducted to evaluate potential benefits of
twice daily application of a GQ1gly moisturizing body lotion. Ten subjects were
enrolled into the test. Eczema severity was evaluated at baseline, week 2, and week 4
by a board-certified dermatologist using the standardized Eczema Area Severity
Index (EASI) score. In addition, transepidermal water loss (Dermalab) and hydration
(Skicon) were measured at the same time points. Photographs were taken at
baseline and week 4. This study was followed up by a full trial with 21 subjects at a
different test center. Results of both studies indicate that using the novel ingredient
containing body lotion twice daily showed the potential to deliver clinical benefits
to mild to moderate eczematous skin. Results of the dermatologic assessments
showed significant improvement versus baseline (P \ .05). Instrumental assessments showed improved hydration at all timepoints in the pilot study and at week 2
in the full trial. The results of the pilot study and the full trial verified that this
GQ1gly body lotion was compatible with mild to moderate atopic eczema. Both
studies showed the potential of this novel ingredient in a body lotion to deliver
genuine clinical benefits.
Commercial support: 100% is sponsored by Unilever R&D.
DERMATITIS, CONTACT AND ALLERGIC IRRITANTS
P1400
P1310
A novel, lipid-rich moisturizing body wash technology is suitable for
patients with eczema
Shuliang Zhang, PhD, Unilever R&D, Trumbull, CT, United States; Anthony
Geralis, Unilever R&D, Trumbull, CT, United States; K.P. Ananthapadmanabhan,
PhD, Unilever R&D, Trumbull, CT, United States; Vickie Foy, MS, Unilever R&D,
Cutaneous toxicity associated with tiotepa before autologous stem cell
transplant
Melissa Wise, MD, Geisinger Medical Center, Danville, PA, United States; Michele
Maroon, MD, Geisinger Medical Center, Danville, PA, United States; Nicole
Fussell, MD, Geisinger Medical Center, Danville, PA, United States
The traditional approach to minimize cleanser-induced stratum corneum protein
damage has been the use of a combination of anionic and amphoteric surfactants in a
liquid cleanser. In contrast, the lipid damage potential of liquid cleansers has not
received much emphasis in the past; however, recent research has highlighted the
importance of minimizing both protein and lipid damage potential with cleansing.
This insight led to the development of a new lipid-rich moisturizing body wash
(LRMBW) with fatty acids naturally found in skin and soybean oil as moisturizers,
combined with an ultramild surfactant. Previous research has shown that the
LRMBW technology shows a low potential for damage to both proteins and lipids in
vitro, and clinical efficacy to skin condition benefits in both normal and barriercompromised skin. It was therefore of interest to evaluate the compatibility of this
ultramild cleanser in eczema patients.
Subjects with mild to moderate eczema between 25 and 65 years of age were
enrolled to participate in this IRB-approved 4-week body wash compatibility study.
Subjects replaced their current cleanser with the LRMBW cleanser. Subjects were
evaluated by a dermatologist with the Eczema Area and Severity Index (EASI) and
completed self-perception questionnaires across several attributes. The LRMBW
was found to be suitable for these subjects, compatible with their treatments, and
was perceived to be mild, moisturizing, and appropriate for sensitive skin.
Chemotherapy regimens have been reported to cause a variety of mucocutaneous
side effects; the most common side effects include mucositis, acral erythema, and
hypersensitivity reactions. We report an interesting case that highlights the
cutaneous toxicity that can occur with chemotherapy and present the associated
histopathology. A 38-year-old white woman was diagnosed with amyopathic
dermatomyositis. Malignancy workup revealed that she had diffuse large B-cell
lymphoma of the cervix which later spread to the CNS. Her disease continued to
progress despite multiple cycles of chemotherapy and cranial radiation. She was
admitted to the hospital and received one dose of intrathecal methotrexate then 3
days of conditioning chemotherapy with thiotepa and etoposide, followed by
autologous stem cell transplant. Five days after her initial dose of thiotepa and
etoposide she was noted to have diffuse, deep red erythema with accentuation over
her back and flexural areas, such as antecubital fossa, axilla, around the waist, groin,
and knees. She complained of severe tenderness of her hands and feet and, on
examination, had palmar and plantar erythema, edema, and slight hyperkeratosis.
Desquamation occurred over the next several days and resolved with hyperpigmentation. A histologic examination of the affected area showed basket weave
orthokeratosis over a slightly acanthotic epidermis with slight thickening of the
granular layer and vacuolar interface change with minimal inflammatory infiltrate.
Thiotepa and etoposide have both been reported to cause hyperpigmentation of
occluded areas. However, this pattern of generalized erythema, desquamation, and
hyperpigmentation is most consistent with the characteristic thiotepa cutaneous
toxicity recently reported in a group of pediatric patients. We present this case to
highlight the clinical presentation of thiotepa induced cutaneous toxicity in an adult
and to characterize the histologic findings.
AB48
J AM ACAD DERMATOL
MARCH 2010
P1401
P1403
Common allergens in periorbital dermatitis
Lilla Landeck, MD, Department of Dermatology, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, United States; Ernesto Gonzalez, MD,
Department of Dermatology, Massachusetts General Hospital, Harvard Medical
School, Boston, MA, United States; Konrad Neumann, PhD, Department of
Biometry and Clinical Epidemiology, Charité- Universitätsmedizin Berlin, Berlin,
Germany; Lynn Baden, MD, MPH, Centre Dermatology and Aesthetic Medicine,
Newton Centre, MA, United States; Peter Schalock, MD, Department of
Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston,
MA, United States
Allergic contact cheilitis to toothpaste after pediatric liver transplantation:
A case series
Laura Proudfoot, MBChB, King’s College Hospital, London, Greater London,
United Kingdom; Anil Dhawan, King’s College Hospital, London, Greater
London, United Kingdom; Elisabeth Higgins, King’s College Hospital, London,
Greater London, United Kingdom; Mike Harrison, King’s College Hospital,
London, Greater London, United Kingdom
Cheilitis is an inflammatory reaction of the lips that may result from endogenous or
exogenous causes. Allergic contact cheilitis to toothpaste is uncommonly reported
despite the fact they contain a number of contact allergens, including flavorings and
preservatives. We report four pediatric cases of allergic contact cheilitis to the same
branded toothpaste that developed after liver transplantation in recipients maintained on low-dose tacrolimus and prednisolone. We believe these patients became
actively sensitised following transplantation despite immunosuppression. All cases
developed a persistent, treatment-resistant, fissured cheilitis involving both the
upper and lower lips 1 to 3 years posttransplant. In three cases, areas of secondary
impetiginisation had developed in the perioral region. The patients had all initially
been diagnosed with an irritant contact dermatitis secondary to lip-licking. All cases
tested negative for candidiasis and nutritional deficiencies. Patch testing to the
European standard series, fragrance series, and dental series was negative in all
cases. However, patch testing revealed persistent 21/31 contact sensitisation
reactions to their branded toothpaste and all patients had significant symptom
improvement on substitution for an alternative brand. To our knowledge, these are
the first reports of acquired allergic contact sensitivities to toothpaste in the
transplant population. This series highlights the potential of a branded toothpaste
ingredient to stimulate an acquired allergic dermal hypersensitivity reaction in
transplant recipients on low-dose immunosuppressive therapy. It may also reflect
underreporting of toothpaste allergic contact sensitivities in general. It is crucial to
recognise this phenomenon because it can be easily and successfully diagnosed and
treated with patch testing and by substitution for an alternative product. This poster
presents the four cases with discussion.
Background: Allergic contact dermatitis (ACD) of the periorbital area may result
from sensitization to cosmetics, topical drugs, nail preparations, and airborne
allergens.
Objective: The purpose of our study was to characterize general epidemiologic
findings and specific features of contact sensitization in patients tested with a
primary complaint of periorbital dermatitis. Results were compared to those tested
without periorbital dermatitis.
Methods: After obtaining approval from the institutional review board, data were
collected from charts reviewed for 266 patients with periorbital dermatitis undergoing patch testing to the standard and supplemental series at the MGH between
1990 and 2006. Results were compared to 981 patients tested for other than
periorbital dermatitis. Statistical analyses were carried out by the chi square test.
Results: Comparing periorbital patients (PP) and nonperiorbital patients (NPP) with
regard to gender and age distribution, significantly (P \.0005) more females were
found among PP (PP 87.6%, NPP 65.3%) while the age distribution was similar in
both groups. No difference (P ¼ .5) was seen in the number of patients with an
atopic background (PP 15.0%, NPP 13.5%) and in the percentage of sensitized (PP
57.5%, NPP 56.0%) in each group. Allergens commonly causing sensitization in
periorbital dermatitis consisted of fragrance mix, nickel, and cobalt. When
comparing sensitization to specific allergens between PP and NPP no statistically
significant difference was evaluated for most common allergens. Allergens with a
high clinical relevance ([85%) among PP were nickel, thimerosal, wool alcohols
and epoxy resin. Most frequent final diagnoses in both groups were ACD, followed
by atopic dermatitis.
Conclusion: Allergic contact sensitization in periorbital dermatitis more frequently
seen in females, most probably a result of increased use of cosmetic products. Most
common allergens are the same as in the NPP group. Therefore, in addition to
sensitization because of direct application of sensitizers to the periorbital area, one
must always consider the possibility of secondary transfer, such as from the hands.
Assessment of the relevance of positive results is important, because most common
allergens were not the most relevant. Because allergic contact dermatitis represents
a leading etiologic cause of periorbital dermatitis, patch testing should be a standard
diagnostic tool.
P1404
Granulomatous contact dermatitis secondary to ear piercing: A case report
Allyson Black, University of Oklahoma, Oklahoma City, OK, United States; James
Stewart, MD, Stewart & Collier, Oklahoma City, OK, United States; Miranda
Smith, MD, University of Oklahoma, Oklahoma City, OK, United States
Granulomatous contact dermatitis is a rare complication of ear piercing. Manifesting
as papules or nodules in locations of ornamental piercing, reports of patch
testepositive confirmation of allergy to associated piercing metals have been found.
We present a case in which lesions arose in areas where piercing occurred through
cartilage while sparing the earlobes. Biopsy showed a sarcoidal granuloma without
findings suggestive of a foreign body. Previous reports have shown mixed success
with intralesional steroid therapy. Ultimately, surgical excision was required for our
patient after intralesional therapy failed to provide improvement.
Occupational protein contact dermatitis caused by fish: Five case reports
Pablo Hernandez Bel, MD, Hospital General Universitario Valencia, Valencia,
Spain; Altea Esteve Martinez, Hospital General Universitario Valencia, Valencia,
Spain; Javier Lopez Davia, Hosptital General Universitario Valencia, Valencia,
Spain; Jesus De La Cuadra Oyanguren, Hospital General Universitario De
Valencia, Valencia, Spain; Victor Alegre De Miquel, Hospital General
Universitario Valencia, Valencia, Spain
Protein contact dermatitis is an allergic skin reaction induced principally by proteins
of either animal or plant origin. The clinical presentation is that of a chronic
dermatitis, and it is often difficult to differentiate between allergic contact dermatitis
and other eczematous dermatoses. One distinguishing clinical feature is that acute
flares of pruritus, urticaria, edema, or vesiculation are noted minutes after contact
with the causative substances. In addition, the patch test result is typically negative,
and the scratch or prick test result is positive. The pathogenesis of protein contact
dermatitis is unclear but may involve a type I IgE (immediate) hypersensitivity
reaction, type IV (cell-mediated delayed) hypersensitivity reaction, and/or a delayed
reaction caused by IgE-bearing Langerhans cells. Management involves avoidance of
the allergen. We present five cases of occupational protein contact dermatitis caused
by fish.
P1402
MARCH 2010
J AM ACAD DERMATOL
AB49
P1405
P1407
Alitretinoin is effective in clearing severe chronic hand eczema
Charles Lynde, MD, Lynderm Research, Markham, Ontario, Canada; Martin
Haarsch, Basilea Pharmaceutica International, Basel, Switzerland; Yves Poulin,
MD, Centre de Recherche Dermatologique, Ste Foy, Quebec, Canada
Aims: To summarize the efficacy of oral alitretinoin (9-cis retinoic acid) in the
treatment of severe chronic hand eczema (CHE) based on data from three clinical
trials.
Methods: Study A—A double-blind, randomized, placebo-controlled trial in 1032
patients who received alitretinoin 10 mg (n ¼ 418) or 30 mg (n ¼ 409) or placebo
(n ¼ 205) once-daily for up to 24 weeks. Study B—An open-label, single fixed dose
study in 249 patients who received oral alitretinoin 30 mg once daily for up to 24
weeks. Study C—A double-blind, placebo-controlled, randomized study of 117
patients who responded to treatment in study A and who subsequently relapsed
within 24 weeks. Patients were rerandomized to a second course of the same dose of
alitretinoin or placebo.
Results: Study A—Response (‘‘clear’’ or ‘‘almost clear’’ hands by Physician’s Global
Assessment) was achieved in up to 48% of patients treated with alitretinoin,
compared with 17% for placebo (P \.001), with up to 75% median reduction in
disease signs and symptoms. Time to achieve response was significantly shorter with
alitretinoin 30 mg compared with placebo (median time 85 days vs 141 days; P \
.001). Improvements were seen in all signs and symptoms of CHE. Study B—Fortyseven percent of patients achieved a response at the end of treatment. Median time
to response was 87 days and there was an 82% median reduction in disease signs and
symptoms. Study C—Amongst patients who were previously successfully treated
with alitretinoin, up to 80% responded to retreatment with the same dose of
alitretinoin compared with 8% to 10% who received placebo.
Clinical evaluation of a postshaving facial razor bump cream on pseudofolliculitis barbae
Margarita Yatskayer, MD, L’Oréal Recherché, Clark, NJ, United States; Christian
Oresajo, L’Oréal Recherché, Clark, NJ, United States; Susana Raab, L’Oréal
Recherché, Clark, NJ, United States
Conclusion: Oral alitretinoin taken once a day is highly effective in treating severe
CHE in patients unresponsive to potent topical corticosteroids and produces
improvements in all of the individual signs and symptoms of CHE. Patients who
relapse after initial treatment can be effectively retreated with alitretinoin.
African American men are prone to pseudofolliculitis barbae (PFB), a common and
distressing disorder in which growing hair shafts curve back into the skin,
producing a foreign body inflammatory reaction. The purpose of the study was to
assess the efficacy and tolerance of the postshaving facial razor bump cream for PFB.
A 72-hour, single-center clinical study of 35 African American men 21 to 65 years of
age with a self-perceived tendency toward razor bumps on the skin and the presence
of at least three razor bumps on the face and neck area were enrolled. Subjects
recruited were routine users of blade razors or electric shave. The cream containing
a blend of soothing/antiinflammatory botanical extracts was used once a day
immediately after shaving. Both efficacy and tolerance were assessed at baseline
(pretreatment) and at 30 minutes, 48 hours, and 72 hours posttreatment. This
included a clinical assessment, a noninvasive bioinstrumental evaluation, digital
photographs, and subject self-assessment questionnaires. The clinical assessment
included evaluation of skin roughness, skin tone (evenness), radiance, overall
appearance of razor bumps, and total lesion count. Bioinstrumental evaluation
included skin hydration and the visual assessment of razor bumps (color and size) via
D-Scope images. Digital photographs were taken of each of the face and neck area to
evaluate visual efficacy. Self-assessment questionnaires were administered to evaluate the perceived efficacy and tolerance by the subjects. The razor bump cream
showed efficacy in reducing the incidence and severity of PFB and improving all
clinical assessment parameters evaluated on the face and neck. Objective and
subjective evaluations showed that facial razor bump cream was well tolerated.
Commercial support: 100% is sponsored by L’Oreal.
Commercial support: Sponsored by Basilea Pharmaceutica International.
P1408
Chlorine and bromine compounds are inorganic agents used worldwide to prevent
the growth of microorganisms in the swimming pool water. Irritant contact
dermatitis by these products are seen in most cases; by contrast, allergic forms
are extremely rare. Because these substances are strong irritants, patch test
concentrations between 0.1% and 1% are recommended. We report the case of a
43-year-old Spanish man who worked in a public swimming pool. He was referred
because of a pruritic rash that had begun 1 and a half months earlier. The physical
examination revealed generalized eczematous lesions, predominantly in the feet,
legs, and hands, which were the most common contact regions with swimming pool
water. We performed patch testing directly with the chlorine compound (Q-Clor)
0.5% in aqueous solution. At the same time, the patch testing with the chlorine
compound was performed in 10 other persons. It resulted in strong positive only for
the patient and negative for the rest. The lesions disappeared completely avoiding
physical contact with chlorinated water and using gloves to apply the chlorinated
substances. Contact dermatitis to chlorine compounds constitutes a rare disease but
should be considered in individuals who work around or use swimming pools.
Lichenoid drug eruption induced by misoprostol
Maria Jo~ao Cruz, MD, Hospital de S~ao Jo~ao, Porto, Portugal; Ana Filipa Duarte,
MD, Hospital de S~ao Jo~ao, Porto, Portugal; Filomena Azevedo, MD, Hospital de
S~ao Jo~ao, Porto, Portugal; Teresa Baudrier, MD, Hospital de S~ao Jo~ao, Porto,
Portugal
Background: Lichenoid drug eruptions are common dermatoses that can closely
mimic idiopathic lichen planus (LP) and have been reported after inhalation,
contact, or systemic administration of several drugs. The list of drugs that can cause
them is long and steadily increases.
Case report: A 16-year-old healthy female received Cytotec (misoprostol) administered vaginally (800 g) to induce a first-trimester abortion. Two months after she
presented with scattered pruritic, violaceous, scaly papules with a symmetric
distribution over the thighs and legs, the papules progressed to the abdomen and
arms. There was no mucosal involvement. No previous skin or allergic diseases were
revealed and no other drugs were used. All laboratory findings were normal.
Histologic examination of skin lesions showed typically findings of lichenoid
dermatitis. A topical steroid (betametasone 0.1%) was started with partial improvement after 1 month. Patch tests were performed 3 months after the administration of
Cytotec with Standard European Series and misoprostol in commercialized form,
diluted at 0.01% in petrolatum, using Finn Chambers occluded for 2 days. She had a
weak positive (1) reaction to misoprostol. Four months later, a new patch test was
performed with the pure substance diluted at 1% in petrolatum and a positive
reaction (11) was observed after 48 hours and remained positive after 7 days. No
rechallenge with misoprostol was attempted. At that time, all skin lesions had
completely regressed, leaving a postinflammatory hyperpigmentation. After 1 year
of follow-up there was no recurrence of the lesions.
Conclusion: The authors report the present case because despite the great number
of drugs that can be implicated in the development of lichenoid eruptions, the
association of such dermatoses and misoprostol had never been described.
Misoprostol is currently used in the prevention and treatment of gastric ulcers
resulting from chronic administration of nonsteroidal antiinflammatory drugs.
Although it is not formally registered for use during pregnancy because of its
stimulating actions on uterus, it has been widely used in many obstetric and
gynecologic conditions. Nowadays, with the increasing number of countries in
which abortion may be legally performed, the use of this medication will probably
rise in an exponential manner and the cutaneous and noncutaneous reactions
associated with its use. When lichenoid drug eruptions are suspected, skin tests with
candidate drugs would be very useful before systemic challenge or could even
replace it in the identification of the causative agent.
P1406
Contact dermatitis to chlorine compounds
Rafael Rojo-Espana, Hospital Universitario Doctor Peset, Valencia, Spain; Amparo
Marquina, Hospital Universitario Doctor Peset, Valencia, Spain; Eugenia CutillasMarco, Hospital Universitario Doctor Peset, Valencia, Spain; Lidia TomasMallebrera, Hospital Universitario Doctor Peset, Valencia, Spain; Maria Neus
Coll-Puigserver, Hospital Universitario Doctor Peset, Valencia, Spain
AB50
J AM ACAD DERMATOL
MARCH 2010
P1409
P1501
Alitretinoin is well tolerated in the treatment of severe chronic hand
eczema
Robert Bissonnette, MD, Innovaderm, Montreal, Quebec, Canada; Jurgen Maares,
MD, Basilea Pharmaceutica International, Basel, Switzerland; Neil Shear, MD,
Sunnybrook & Women’s College Health Science Centre, Toronto, Ontario,
Canada
Acral dermatofibroma
Bijal Amin, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United
States; Jennifer DeFazio, MD, Memorial Sloan-Kettering Cancer Center,
Hauppauge, NY, United States; Klaus Busam, MD, Memorial Sloan-Kettering
Cancer Center, New York, NY, United States; Patricia Myskowski, MD, Memorial
Sloan-Kettering Cancer Center, New York, NY, United States; Philip Spencer, MD,
Memorial Sloan-Kettering Cancer Center, Hauppauge, NY, United States
Objective: To summarize the safety profile of oral alitretinoin (9-cis retinoic acid) in
the treatment of severe chronic hand eczema (CHE) based on data from three
clinical trials.
Methods: Study A—A double-blind, randomized, placebo-controlled trial in 1032
patients who received alitretinoin 10 mg (n ¼ 418) or 30 mg (n ¼ 409) or placebo (n
¼ 205) once daily for up to 24 weeks. Study B—An open-label, single study in 249
patients who received oral alitretinoin 30 mg once daily for up to 24 weeks. Study
C—A double-blind, placebo-controlled, randomized study that included 117 patients who responded to initial treatment in study A and who subsequently relapsed
within 24 weeks. These patients were rerandomized to a second course of the same
dose of alitretinoin or placebo.
Results: Studies A and B—Dose-dependent adverse events (AEs) were typical for the
retinoid class and comprised headache, flushing, erythema, and dry skin effects.
Headache was the most common AE in the alitretinoin 30 mg groups and the most
common AE leading to study withdrawal. Mucocutaneous effects (dry skin, dry eyes,
dry mouth, dry lips, and cheilitis) were seen less frequently than with other retinoids
and occurred in approximately 10% of patients receiving the 30 mg dose, compared
to 4% receiving placebo. Changes in triglyceride and cholesterol levels and
laboratory abnormalities in TSH/T4 were consistent with known retinoid effects.
Study C—No new safety signals were seen when patients who had initially received
alitretinoin were exposed to a second course of the drug.
Conclusions: Oral alitretinoin 10 to 30 mg taken once a day is well tolerated in the
treatment of severe CHE unresponsive to potent topical corticosteroids. Adverse
events are dose dependent, manageable, and consistent with retinoid class effects.
Following a second course of treatment, no late arising, cumulative toxicities were
observed.
Commercial support: Sponsored by Basilea Pharmaceutica International.
Introduction: Dermatofibromas are common cutaneous neoplasms; however,
occurrences on the palms and soles are extremely infrequently reported in the
literature. Here we report a series of three patients with acral dermatofibromas.
Case reports: The first patient is a 77-year-old man who presented with a 3- to 4month history of a painful, enlarging nodule on the plantar surface of his left foot.
The clinical differential diagnosis was poroma or other adnexal neoplasm. The
punch biopsy specimen revealed a cellular spindle cell tumor that was positive for
factor XIIIa and negative for smooth muscle actin (SMA), desmin, CD34, and S100,
consistent with a cellular fibrous dermatofibroma. The lesion was completely
resected, showing a cicatrix and residual dermatofibroma with a negative margin.
The second patient is a 54-year-old woman who presented with a 2-year history of an
asymptomatic nodule on the plantar surface of her left foot. She had lesions on her
right arm and leg clinically consistent with dermatofibromas and a firm, erythematous papule on the sole of her left foot; the clinical differential diagnosis again was
poroma. Histologically, the biopsy showed a spindled fibrohistiocytic neoplasm
with collagen wrapping diagnostic of a dermatofibroma. The third patient is a 54year-old man who presented with a 2-year history of a lump on his right fifth finger
near the distal interpharyngeal joint with an overlying cutaneous horn that had
recently developed a black eschar. He had a remote history of a fracture of that digit
and osteoarthritis of his hands. The clinical differential diagnosis was digital mucous
cyst, epidermal inclusion cyst, squamous cell carcinoma/keratoacanthoma, verruca,
and melanoma. He underwent excision. The pathology specimen showed a spindled
fibrohistiocytic tumor with collagen trapping, positive for factor XIIIa and negative
for CD34, SMA, and desmin, diagnostic of dermatofibroma, with positive margins.
No recurrence or progression has been reported in any of these cases.
Conclusions: We present these cases to highlight the possibility of acral locations for
dermatofibromas. These lesions may be symptomatic, and the clinical differential
diagnosis likely includes adnexal neoplasms, particularly poroma. In our series, the
behavior of acral dermatofibromas was the same as what would be expected of those
occurring on more common sites.
DERMATOPATHOLOGY
P1500
A case of tubular apocrine adenoma with syringocystadenoma
papilliferum
Mi Sun Kim, MD, Department of Dermatology, Eulji Medical Center, College of
Medicine, Eulji University, Seoul, Nowon-gu, South Korea; June Lee, MD,
Department of Dermatology, Eulji Medical Center, College of Medicine, Eulji
University, Seoul, Nowon-gu, South Korea; Kun Park, Department of
Dermatology, Eulji Medical Center, College of Medicine, Eulji University, Seoul,
Nowon-gu, South Korea; Sook-ja Son, MD, Department of Dermatology, Eulji
Medical Center, College of Medicine, Eulji University, Seoul, Nowon-gu, South
Korea
Background: Tubular apocrine adenoma (TAA) is a very rare sweat gland tumor.
Some authors suggest that TAA represents a variant of syringocystadenoma
papilliferum (SCAP). However, others have proposed that TAA is an independent
clinical entity consisting of a benign appendage tumor, of apocrine origin, often
associated with nevus sebaceous (NS). We report a case of TAA associated with SCAP
that developed in a NS on the scalp.
Case report: A 40-year-old woman presented with an asymptomatic nodule on the
scalp. The lesion first was recognized during childhood as a small papule that was
diagnosed as a nevus sebaceous; the lesion became elevated as the patient grew.
Dermatologic examination revealed a 2.5- 3 2.5-cm nontender, pedunculated
nodule. The surface was erythematous and lobulated. Histopathologic findings
showed two distinctly different zones. The upper portion of the tumor showed
cystic tubular structures with deep invaginations, from which emerged thick
papillomatous projections lined with two rows of epithelial cells. The lower portion
of the lesion consisted of variable sized tubular structures with two or more layers of
epithelial cells. The findings in the upper portion of the lesion were thought to be
representative of SCAP and those in the lower portion as TAA.
Immunohistochemical studies showed that the luminal layer reacted with antiepithelial membrane antigen antibodies and CAM5.2 in both the SCAP and TAA
sections. Staining for gross cystic disease fluid protein-15 (GCDFP-15) was strong in
the luminal cells of the TAA, but was negative in the luminal cells of the SCAP.
Staining for smooth muscle actin was strong in the peripheral layer of the TAA, but
was negative in of the SCAP. These findings might support that there are biologic
differences between the TAA and SCAP.
Discussion: Only seven cases of TAA-associated SCAP have been reported in the
medical literature. The histogenesis of the SCAP is unclear, while some investigators
have suggested that the tumor originates from eccrine or apocrine elements.
Apocrine differentiation has been shown in TAA, but both eccrine and apocrine
differentiation have also been shown to exist in TAA. These tumors might develop
from pleuripotent appendageal cells. We present an additional case of TAA
associated with SCAP developing in a NS.
P1502
Hobnail hemangioma in a child
Eduardo Calonje, MBChB, St John’s Institute of Dermatology, London, United
Kingdom; Emma Benton, MBChB, St John’s Institute of Dermatology, London,
United Kingdom; Rachael Morris-Jones, PhD, MBChB, King’s College Hospital,
London, United Kingdom
A 14-year-old previously well Colombian male presented with a 10-year history of a
lesion on the right thigh. The lesion had gradually grown in size over the years and
was tender to the touch. The physical examination revealed a firm nodule on the
right anterior thigh that measured 2 cm 3 2 cm. The nodule was well circumscribed
and red-brown in color with an obvious blue vascular component seen superficially.
A skin biopsy specimen revealed a wedge-shaped vascular lesion with irregular thin
walled vascular channels resembling lymphatics superficially and narrow angular
lumina with fibrous and hemosiderin deposition. The vascular channels were lined
with hobnail endothelial cells. Vascular markers were performed and highlighted
the endothelial nature of the cells. There was no association with HHV-8. These
features were consistent with a diagnosis of hobnail hemangioma (HH) or targetoid
hemosiderotic hemangioma (THH). THH is an uncommon benign vascular tumor
first described in 1988. The term HH, which emphasizes a constant special
histologic picture, was later proposed in 1999 because of the hobnail-like appearance of the endothelial cells. It is a benign lesion that is largely of diagnostic or
cosmetic concern. It typically affects young adults. It affects the trunk or extremities, especially the lower limb. Rare cases occur in the oral mucosa. The exact
pathogenesis of this condition is unknown, but some have postulated traumatic and
hormonal influences. Histologically, it is characterized by a biphasic vascular pattern
with dilated vessels lined by hobnail endothelial cells in the superficial reticular
dermis and narrow angular lumina appearing to dissect through collagen bundles in
the deeper dermis. Immunohistochemically, the dilated and slit-like vascular vessels
will be labelled by lymphatic endothelial markers and will be negative or only focally
positive for vascular endothelial markers and for actin. There is no association with
HHV-8. The main histologic differential is formed from the family of vascular tumors
characterized by hobnail endothelial cells. These include the Dabska tumor and
retiform hemangioendothelioma. It is clinically important to differentiate this
benign vascular lesion from its histologic mimics of low grade malignancy. Simple
excision is curative. Because it is benign, lesions are commonly removed for
diagnostic cosmetic or functional reasons.
MARCH 2010
J AM ACAD DERMATOL
AB51
P1503
P1505
Benign hypergranulotic keratosis with dyscornification
Lindsey Dohse, MD, Geisinger Medical Center, Danville, PA, United States; Dirk
Elston, MD, Geisinger Medical Center, Danville, PA, United States; Nektarios
Lountzis, MD, Geisinger Medical Center, Danville, PA, United States; Tammie
Ferringer, MD, Geisinger Medical Center, Danville, PA, United States
Clinical and histopathologic review on 28 cases of nodular fasciitis
Mira Choi, MD, Department of Dermatology, Seoul National University College of
Medicine, Seoul, South Korea; Chong Hyun Won, MD, PhD, Asan Medical Center,
Seoul, South Korea; In Ho Kwon, MD, Department of Dermatology, Seoul
National University College of Medicine, Seoul, South Korea; Soyun Cho, MD,
PhD, Department of Dermatology, Seoul National University Boramae Hospital,
Seoul, South Korea
Background: Benign hypergranulotic keratosis with dyscornification is a recently
defined keratosis demonstrating a unique pattern of epidermal maturation. Only
eight cases have been reported to date.
Case report: A 38-year-old woman presented with an enlarging and darkening
‘‘mole’’ of 2 years’ duration. She was otherwise healthy and the physical examination
revealed a 5-mm tan papule on her back. Shave biopsy showed a compact
hyperkeratotic stratum corneum with focal emanations of amorphous, homogenized, anucleate keratinocytes overlying papillated coarse hypergranulosis. No
atypia was seen in the epidermis that contained keratinocytes with focal intercellular basophilia. The findings were consistent with a benign hypergranulotic
keratosis with dyscornification.
Discussion: The term ‘‘benign hypergranulotic keratosis with dyscornification’’
accurately describes the histologic hallmarks of this rarely reported benign keratosis. It has distinct histologic features that include prominent hypergranulosis
contained within intact keratinocytes, scant intercellular pale basophilic material
within the upper spinous/granular/corneal layers, and large eosinophilic anucleate
keratinocytes forming homogenous orthokeratotic mounds over epidermal papillae.
Lesions are typically solitary and found on the trunk and extremities of adults 30 to
50 years of age. The current belief is that this finding represents an epithelial
maturation pattern that may be seen in benign keratoses, analogous to incidental
epidermolytic hyperkeratosis.
Background: Nodular fasciitis presents a solitary, slightly painful, rapidly growing
nodule. It is associated with a reactive, proliferative process of unknown cellular
origin and can be misdiagnosed as a sarcoma.
Objective: The study was designed to investigate the process and cellular origin of
the disease.
Methods: The clinical and histopathologic findings in 28 cases of nodular fasciitis
were reviewed. Additional various histochemical and immunohistochemical stainings were analyzed.
Results: (1) The mean age of onset was 29.8 years. A majority of the patients with
nodular fasciitis have the duration of symptom less than 6 months. The upper
extremity and face were most frequently involved. Most of the lesions had the
diameter of less than 2 cm. Total excisions were performed in 23 lesions, of which
three lesions recurred thereafter. (2) Histopathologically, the subcutaneous plane
was most frequently involved. The nodule consisted of numerous large, pleomorphic fibroblasts growing haphazardly in a vascular stroma containing varying
amounts of mucoid ground substance, which could be confirmed by histochemical
stains. (3) In the immunohistochemical stain, most lesions have positive finding for
smooth muscle actin (SMA), vimentin, and negative finding for CD34, except a few
cases. The stains for desmin and S-100 were negative in all cases.
Conclusions: It is suggested that nodular fasciitis could be associated with a reactive
proliferation of myofibroblasts rather than a sarcomatous process.
P1504
P1506
A case of gouty panniculitis developed on the extraarticular areas
Chang-Min Choi, MD, East-West Neomedical Center, Seoul, South Korea; BarkLynn Lew, MD, East-West Neomedical Center, Seoul, South Korea; Hee-Ryung
Cho, MD, East-West Neomedical Center, Seoul, South Korea, Woo-Young Sim,
MD, East-West Neomedical Center, Seoul, South Korea
Two new cases of dermatomyofibroma
Elisabeth Gomez Moyano, MHS, Carlos Haya Hospital, Malaga, Spain; Angel Vera
Casaño, MD, Carlos Haya Hospital, Malaga, Spain; Leandro Martinez Pilar, MEd,
Carlos Haya Hospital, Malaga, Spain; Silvestre Martinez Garcia, MD, Carlos Haya
Hospital, Malaga, Spain; Vicente Crespo Erchiga, MD, Carlos Haya Hospital,
Malaga, Spain
Introduction: Dermatomyofibroma is a rare but distinct benign cutaneous mesenchymal neoplasm of fibroblastic/myofibroblastic differentiation. It is more common
in adolescents and young adults, with a female predominance. In most cases, the
lesions are asymptomatic and small, measuring from 10 to 20 mm. Early and active
lesions tend to be actin positive.
Gout is a clinical syndrome that is characterized by recurrent, painful arthritis
caused by deposition of monosoduim urate. Urate deposit was usually detected in
synovial membrane, joint capsule, articular cartilage, and periarticular tissue and
rarely in extraarticular area. Gouty panniculitis is a relevant entity of the spectrum of
gout. It is characterized by widespread subcutaneous urate crystal depositions. A 47year-old man presented with multiple, various sized, oval to linear, firm, fixed,
subcutaneous nodules and plaques on the forehead, upper and lower extremities,
and both hands and feet joints. Histopathologic examination revealed the fine,
needle-shaped, radially oriented crystals surrounded by foreign bodyetype giant
cells and lymphohistiocytes at the level of subcutaneous fat layer. These crystals
were doubly refractile on polariscopic examination and stained black in silver stain.
On these histopathologic findings, he was diagnosed as gouty panniculitis.
Moreover, the crystals were also found in the bone marrow; however, the serum
level of uric acid was within normal limits. We report an interesting case of
generalized gouty panniculitis, rare variant of gout, showing characteristic depositions on the unusual sites.
AB52
Case reports: We present (1) a new case of dermatomyofibroma in an 11-month-old
male infant, the youngest case reported to date, and (2) the second reported case of a
giant annular dermatomyofibroma, measuring 10 cm 3 6 cm, in a 52-year-old
woman. In both cases, histologic examination showed a spindle cell proliferation
embedded among the collagen fibers of the dermis, arranged predominantly parallel
to the skin surface. In both cases, the spindle cells stained positive for smooth
muscle actin and the elastic fibers were increased and fragmented.
Conclusion: Dermatologists and pediatricians should be aware of this benign entity
in order to avoid unnecessary treatment.
J AM ACAD DERMATOL
MARCH 2010
P1507
P1509
Histopathologic features in skin biopsies of patients with drug hypersensitivity syndrome
Chia-Chun Ang, MD, Changi General Hospital, Department of Dermatology,
Singapore; Yi-Shi Wang, MD, Changi General Hospital, Department of
Dermatology, Singapore; Yong-Kwang Tay, MD, Changi General Hospital,
Department of Dermatology, Singapore
Clinicopathologic observation of hidradenitis suppurativa after treatment
with the long-pulsed Nd:YAG 1064-nm laser
Dakara Rucker Wright, MD, Henry Ford, Detroit, MI, United States; Bassel
Mahmoud-Abdallah, MD, Henry Ford Dermatology, Detroit, MI, United States;
David Mehregan, MD, Wayne State University, Dearborn, MI, United States; Iltefat
Hamzavi, MD, Henry Ford, Detroit, MI, United States; Lisa Xu, MD, Henry Ford,
Detroit, MI, United States
Hidradenitis suppurativa (HS) is part of the follicular occlusion tetrad and is a
chronic, painful, inflammatory condition that affects intertriginous areas. It can
involve the apocrine glands, but it is a disorder primarily of the hair follicles,
although the exact pathologic origin has been debated. Treatments are limited, with
radical surgical excision reported as the most effective treatement—but this results
in high levels of morbidity. Recently, our group has published data on the clinical
effectiveness of the long-pulsed Nd:YAG 1064-nm hair removal laser for the
treatment of HS. The primary goal of this study was to further examine the
histologic changes occurring after Nd:YAG laser treatment in 19 patients of various
skin types. The secondary goal was to clinically assess effects of the laser on HS. Two
Nd:YAG laser treatments were performed 30 days apart. Punch biopsy specimens
were obtained from an active lesion before laser treatment (day 0) and at days 1, 7,
and 60 in seven pilot patients. In an additional 12 patients, biopsy specimens of
active lesions were taken before laser and on days 7, 30, and 60. An active lesion
from an untreated site was biopsied as a control on day 60. All H&E slides were
reviewed by a dermatopathologist (D.M.). Total mean percent change using a
modified Hidradenitis Suppurativa Lesion, Area and Severity Index including patient
symptoms (based on the Sartorius scale) on all 19 patients from baseline to month
two was -31.6% (SD, 18.9; P \.001). Histologic findings varied by type of lesion
biopsied and time points. Histopathologic observations show follicular plugging,
follicular rupture, folliculocentric mixed inflammation with sparing of apocrine
glands when they were present in the sample, and folliculitis moving towards
fibrosis over the time points. In 11 of 19 patients (58%), the superficial inflammation
cleared after the second laser treatment and corresponded with a greater percent
decrease in HS-LASI scores. In a majority of tissue specimens, perifollicular
inflammation with sparing of the apocrine glands was noted. Histologic changes
specifically related to the Nd:YAG laser on HS lesions are suggested. This study
supports previous data that the Nd:YAG laser is effective in decreasing HS activity
per patient and physician assessment. We also have provided histologic evidence
that the condition is primarily folliculocentric and not centered around the apocrine
glands.
Drug hypersensitivity syndrome is a systemic adverse drug reaction presenting with
a rash, fever, and other organ involvement. Because of the varied clinical presentation, various authors have named the syndrome DRESS (drug rash, eosinophilia,
and systemic symptoms), DIDMOHS (drug-induced delayed multiorgan hypersensitivity syndrome), and DIHS (drug-induced hypersensitivity syndrome). We present
a review of the histopathologic features of patients with drug hypersensitivity
syndrome seen in our dermatology department from January 2003 to January 2008.
Twenty-seven patients were identified from case records. Sixteen patients (59.3%)
underwent a skin biopsy while the other 11 patients did not give their consent. The
most common histologic finding was a superficial perivascular dermatitis (14/16),
half of which had prominent eosinophils. Other accompanying changes that were
frequently seen include spongiosis, focal keratinocyte necrosis, and basal vacuolar
alteration. There were also two specimens that showed features of vasculitis
(nuclear dust, swollen endothelial cells, and red blood cell extravasate). Interface
dermatitis was seen in only one specimen. Histologic findings suggestive of
pseudolymphoma and erythema multiforme were not seen in our patients. There
is no consistent finding on histology that is unique and specific for a patient with
drug hypersensitivity syndrome in our case series. The diagnosis of drug hypersensitivity syndrome remains a clinical one.
P1508
Diffuse dermal angiomatosis versus microvenular hemangiomas
Oliver Perez, MD, UPMC Department of Dermatology, Pittsburgh, PA, United
States; Elissa Stern, UPMC Department of Dermatology, Pittsburgh, PA, United
States; Laura Ferris, MD, PhD, UPMC Department of Dermatology, Pittsburgh, PA,
United States
A 45-year-old white woman presented with a 1-month history of bilateral, inferior
breast ulcerations and tenderness with a medical history that was remarkable for
multiple cardiovascular accidents and subacute bacterial endocarditis resulting in
deep venous thromboses, pulmonary embolism, stroke, left hemiparesis, and
dysarthria. After these events, the patient was started on warfarin; however, no
known etiology for her apparent hypercoaguable state was identified. The inferior
aspect of bilateral pendulous breasts revealed superficial skin ulcerations and
violaceous plaques with a reticulated proliferation of superficial vessels. A skin
biopsy was performed. Microscopic findings were consistent with a multifocal
proliferation of endothelial cells at all levels of the dermis without pleomorphism. A
hypercoaguable work-up revealed laboratory findings consistent with elevated
homocysteine, polyclonal hypergammaglobulinemia, and a lupus anticoagulant
panel with positive dilute Russell viper venom test and an elevated silica clot time
ratio. Protein C and protein S levels were decreased, likely secondary to concomitant
warfarin therapy. Given her clinical, laboratory, and histopathology findings, a
diagnosis of diffuse dermal angiomatosis was made. Diffuse dermal angiomatosis
(DDA) is a rare skin disease involving dermal angiogenesis in response to tissue
hypoxia, and is considered to be a variant of reactive angioendotheliomatosis. Since
it was first reported, there have been 13 cases of DDA in the English literature.
Lesions of DDA usually occur on the extremities and trunk, but five cases have had
breast involvement. DDA is typically found in adults with atherosclerosis, peripheral
vascular disease, and other systemic illnesses such as chronic renal disease, insulindependent diabetes mellitus, and the antiphospholipid antibody syndrome.
Histopathologically, DDA is characterized by proliferation of endothelial cells
throughout the dermis, without evidence of pleomorphism, and it can be difficult
to differentiate from microvenular hemangioma without a clinical history. However,
MVH tend to occur in otherwise healthy young adults, with pregnancy, and in
patient with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changes) syndrome. When analyzed together, the patient’s
medical history, distribution of skin lesions, laboratory abnormalities, and histopathologic findings point to a diagnosis of DDA. Given the association of DDA with
an underlying hypercoagulable disorder, its prompt and accurate recognition with
institution of appropriate therapy may prevent future thromboembolic events. In
order to accurately differentiate DDA from MVH, it is essential to interpret
histopathologic findings in the context of the patient’s medical history and physical
examination findings.
Extramammary Paget disease with dermal invasion and metastasis
Jose Aneiros-Fernandez, MD, San Cecilio Clinical Hospital (Pathology), Granada,
Spain; Barbara Cancela-Diez, PharmD, Virgen de las Nieves Hospital, Granada,
Spain; Jose Aneiros-Cachaza, MD, PhD, San Cecilio Clinical Hospital (Pathology),
Granada, Spain; Marı́a Sierra Girón-Prieto, MD, Virgen de las Nieves Hospital,
Granada, Spain; Salvador Arias-Santiago, MD, San Cecilio Clinical Hospital
(Dermatology), Granada, Spain
Introduction: Extramammary Paget disease is generally a carcinoma in situ of skin of
uncertain origin.It is infrequent infiltrates the dermis (26%) and regional nodes
metastasized (13%).
Case report: A 67-year-old male presented within eczematous whitish areas on the
scrotum and groin of 3 years’ duration. Clinical suspicion of extramammary Paget
disease versus Bowen disease. The histopathologic study presents a cell proliferation within the epidermis with invasion of the dermis having intradermal location
with provision nests. The tumoral cells are arranged in nests rows and glandular
claster with a central lumen. Proliferating cells have moderate atypia irregularities
nuclei, slow mitotic activity, cytoplasm eosinophilic, and have PAS positive and
diastase resistant. There is also lymphatic invasion of vascular structures.
Inmuhistoquı́mico study in tumor cells shows positive for CK7, CEA, EMA,
GCDFP-15, Cerbb-2 and antimitochondrial, shows negative for CK20, Melan-A,
HMB45, P53, TTF-1, PSA, receptor androgens, RE, and RP. Ki67 \ 5%. The diagnosis
was of extramammary Paget disease infiltrating with changes oncocytic and
metastasis in inguinal adenopathy. The patient died 14 months after surgical
treatment and chemotherapy (cisplatin and 5-fluorouracil taxsotere) and herceptin.
Conclusions: The presence of tumor lymphatic invasion has been finding poor
prognosis. Differentiation apocrine (positive for GCDFP-15) is suggested.
Extramammary Paget disease and mammary Paget disease share a similar phenotype
but are differential primarily by RE and RP expression in the mammary localization.
The intense positivity for antibody antimitochondrial, in the proliferating cells with
broad and eosinophilic cytoplasm, both in tumors and metastases in the extramammary Paget disease, is indicative of oncocytic changes.
P1510
MARCH 2010
J AM ACAD DERMATOL
AB53
DERMATOPHARMACOLOGY/COSMECEUTICALS
P1600
Antioxidant property of fullerene is effective in skin whitening
Takahiro Fujimoto, MD, PhD, MBA, Clinic F, Chiyoda-ku, Tokyo, Japan; Hisae
Aoshima, Vitamin C60 BioResearch, Chuo-Ku, Tokyo, Japan; Ken Kokubo, PhD,
Osaka University, Suita, Osaka, Japan; Masayuki Ito, Vitamin C60 BioResearch,
Chuo-Ku, Tokyo, Japan; Nobuhiko Miwa, PhD, Prefectural University of
Hiroshima, Shobara, Hiroshima, Japan
Ultraviolet (UV) rays generate reactive oxygen species, which can cause a series of
biologic effects in human skin cells, resulting in cosmetic skin damage such as
pigmentation. Antioxidants have been reported to inhibit the progression of UVinduced skin damage. Fullerene, a carbon allotrope, is characterized as an antioxidant and is reported to react with various reactive chemical species, such as free
radicals. Because of certain properties of fullerene, such as poor water solubility and
stability, the cosmetic formulation of fullerene presents some technical and
formulating challenges. Therefore, we used polyvinylpyrrolidone (PVP), a water
soluble polymer commonly used in cosmetic products, as the physical trapping
material. PVP-wrapped fullerene was found to be a water soluble and very stable
cosmetic ingredient. In this investigation, we extensively evaluated the antioxidant
ability and whitening effects of PVPefullerene in vitro by testing its formulated
sample in our study subjects. We aimed to verify the performance of PVPefullerene
and to compare it with that of other major antioxidants; hence, we used a simple and
conventional method that employs beta-carotene as an indicator to assess antioxidant ability of fullerene. The results indicated that PVPefullerene can inhibit
radicals, such as liporadicals, hydroxyl radicals, and superoxide radicals. The ability
of PVPefullerene to inhibit ultraviolet A (UVA)-induced melanogenesis was tested in
human melanocytes. Cells were treated with or without PVPefullerene, arbutin, and
ascorbic acid for 3hours and irradiated by weak UVA rays for 24hours.
PVPefullerene significantly reduced UVA-induced melanogenesis in a dose dependent manner, and melanogenesis was reduced to a larger extent in PVPefullerenetreated cells than in ascorbic acide and arbutin-treated cells. To prove the practical
effectiveness of PVPefullerene, clinical tests were performed on 32 women
volunteers. A gel containing PVPefullerene (C60, 2ppm) was prepared and applied
on the face twice daily. Whitening efficiency was evaluated by L* value measurement. After 6 weeks of application, 94% subjects became fairer than before
treatment without any inflammation or irritation. These data suggest that
PVPefullerene has a whitening effect because of its ability to scavenge UV-induced
free radicals.
P1602
A new body wash provides all-day protection against UV light
Sergio Nacht, PhD, Riley-Nacht, Las Vegas, NV, United States; Clay J. Cockerell,
MD, Cockerell and Associates Dermatopathology, Dallas, TX, United States
Introduction: The incidence of skin cancer continues to increase and is reaching
epidemic proportions. In spite of knowing that UV exposure can lead to skin cancer,
most individuals either do not routinely apply sunscreens before sun exposure or
they do it deficiently. Skin cancers also pose a significant public health problem that
amounts to billions of dollars per year in the United States alone. An SPF 5 sunscreen
reduces UV exposure by 80%. The daily application of such a sunscreen starting at
age 10 could reduce the overall life UV exposure by 65% and, presumably, the
incidence of skin cancer by at least the same percentage.
Objective: To develop a body cleansing product to be incorporated in a daily routine
containing sunscreens in a formulation substantive to the skin to provide an SPF of at
least 8 following rinsing. The product contains zinc oxide, titanium dioxide,
octocrylene, and red petrolatum in a cleansing vehicle with natural melanin to
provide antioxidant and free radical quenching properties to further protect skin
cell structures. Two product forms were developed: a body lotion and an aerosol
‘‘mousse.’’
Methods: The SPF of all formulations was determined according to the guidelines in
the FDA OTC Tentative Final Monograph for sunscreen products. This document
does not provide a procedure for cleansing products; therefore, a suitable in vivo test
protocol was developed. Two 50cm2 areas were defined on the lower back of each
subject. The SPF as a sunscreen was determined on one site using a dosage of
2mg/cm2. The other site was wetted with plain water and the same amount of
product was applied. Product was rubbed in for 1minute followed by rinsing with
water at about 328C. The area was patted dry and SPF was determined. ‘‘Real life’’
studies were conducted by asking volunteers to use the product while they
showered daily.
Results: The lotion has an SPF 21 as a sunscreen and an SPF 19 as a wash while the
‘‘mousse’’ gave SPFs of 20 and 19, respectively. When used in the shower, the SPF
immediately after usage were 20 and 19 for the lotion and mousse and when retested
8hours later, the SPFs were 19 and 18 respectively. Finally, when the products were
used in the shower for 5 days, the SPF at day 5 was similar to those determined
without washing.
Conclusions: We developed a product that could be used as a daily shower cleanser
and provide significant long-lasting UV protection.
Commercial support: Riley-Nacht.
P1603
P1601
Antiitching properties of patented avocado peptides
Stephanie Bredif, Laboratoires Expanscience, Epernon, Eure Et Loir, France;
Caroline Baudouin, PhD, Laboratoires Expanscience, Epernon, Eure Et Loir,
France; Philippe Msika, PhD, Laboratoires Expanscience, Epernon, Eure Et Loir,
France
Objectives: Itch is defined as an unpleasant sensation evoking the desire to scratch.
Cross-talk between C neuron terminals and the spatially closely related dermal mast
cells seems to play an important part in the pruritus pathogenesis. Indeed, mast cell
mediators, such as histamine and tryptase (via proteinase-activated receptor 2
[PAR2]) are able to stimulate C neuron terminals, therefore inducing the sensation of
itch. Moreover, PAR2 is also expressed by keratinocytes, where its activation initiates
inflammatory response. Although the itch pathogenesis in dry skin is not fully
understood, the clinical association between itch and dry skin is well established. In
this study, we investigated the antiitching and moisturizing properties of a patented
natural extract, avocado peptides (AP).
Methods: Mast cells were treated with calcium ionophore or substance P in order to
induce the release of tryptase and histamine, respectively, measured according to
spectrophotometric and spectrofluorometric methods. Gene expression of PAR2
was analyzed in a reconstructed human epidermis model using DNA microarrays.
Epidermal lipid neosynthesis was followed in reconstructed human epidermis
thanks to lipids radiolabeling and thin layer chromatography analysis. Hyaluronic
acid release by normal human epidermal keratinocytes (NHEK) was measured by
ELISA. Glycosaminoglycans (GAGs) synthesis by NHEK was evaluated by measuring
incorporation of 35S-sulfate.
Results: Avocado peptides (AP) were able to significantly inhibit the release of
histamine (up to -53%; P \.01) and tryptase (-30%; P \.01) by mast cells. Epidermal
gene expression of PAR2 was reduced by 52% after treatment with AP. AP positively
affected epidermal ceramides and free fatty acid synthesis. Finally, AP significantly
enhanced NHEK production of hyaluronic acid and GAGs by 31% (P \.05) and 34%
(P \.05), respectively.
Effects of galactomyces ferment filtrate on epidermal barrier marker
caspase-14 in human skin cells
Kenji Hattori, PhD, MS, Keio University Faculty of Pharmacy, Tokyo, Japan; Akiko
Nakajima, MS, Procter & Gamble Japan, Kobe, Hougo, Japan; Akira Date, PhD,
MS, MPH, Procter & Gamble Japan, Kobe, Hyougo, Japan; Hiroomi Tamura, PhD,
MS, Keio University Faculty of Parmacy, Tokyo, Japan; Kyoko Ishida, MS, Procter
& Gamble Japan, Kobe, Hougo, Japan
Background: The stratum corneum of human epidermis is composed of terminally
differentiated keratinocytes serving as an essential barrier to environmental stresses,
such as UV-induced photodamage and water loss. The regulatory and proteolytic
events that coordinate barrier formation are tightly controlled. Caspase-14 belongs
to a conserved family of aspartate-specific proteases. Its epidermal expression is
restricted almost exclusively to the suprabasal layers, implicating this protease in
keratinocyte terminal differentiation and cornification. Therefore, caspase-14 is a
useful biomarker to monitor formation and homeostasis of the stratum corneum
barrier.
Objective: Determine the in vitro effects on barrier formation and hydration of
topically applied galactomyces ferment filtrate (GFF) via expression of epidermal
late differentiation biomarkers (caspase-14 and related genes).
Methods: In vitro human skin models, including skin keratinocytes and skin
equivalents (SE) with partially (EPI-201) or completely formed (EPI-200) stratified,
cornified epidermis were treated topically with GFF or dexamethasone (Dex).
Caspase-14 and related barrier biomarkers were assayed via enzyme activity
(caspase-14), mRNA expression by RT-PCR and protein levels by Western blot
analysis. Histologic evaluation was conducted also in the human SE models.
Results: GFF increased expression of caspase-14 and peptidylarginine deiminases
(PAD1, PAD3) in human SE cultures (EPI-200 and -201) and also increased the
expression of transglutaminase (TGM1) and involucrin in a human SE model of
earlier stage corneocyte differentiation (EPI-201). Dex increased only the expression
of caspase-14 in both human SE models. RU-486, a glucocorticoid receptor
antagonist, inhibited the effects of Dex but not GFF, suggesting independent
pathways such as MAPK may be involved.
Conclusion: The antiitching activities of these patented avocado peptides have been
shown on mast cells, which are at the heart of pruritus reaction. Moreover, its
moisturizing and relipidizing properties were suggested by in vitro assays. AP could
therefore be of particular interest in the management of cutaneous disorders
associated with itchy and dry skin.
Conclusions: These results indicate that GFF increases caspase-14 expression by
epidermal cells, specifically during late stage differentiation. The positive effect of
GFF on late differentiation biomarkers supports previous observations that GFFcontaining moisturizers help protect the skin against damage, such as dryness, from
environmental stress. These results provide a compelling reason to further understand the nature of GFF and its skin benefits.
AB54
J AM ACAD DERMATOL
MARCH 2010
P1604
P1606
Skin serum with human growth factors and cytokines for skin
rejuvenation
Joseph B. Bikowski, MD, Bikowski Skin Care Center, Sewickley, PA, United States
Skin benefits of a topical regimen containing retinol, total soy, and SPF
30 photostable sunscreen
Warren Wallo, MS, Johnson & Johnson Consumer and Personal Products
Worldwide, Skillman, NJ, United States; James J. Leyden, MD, University of
Pennsylvania, Philadelphia, PA, United States; Menas Kizoulis, Johnson &
Johnson Consumer and Personal Products Worldwide, Skillman, NJ, United
States; Yohini Appa, PhD, Johnson & Johnson Consumer and Personal Products
Worldwide, Skillman, NJ, United States
Patients are more likely to be compliant when given a simple yet effective regimen of
topical products to use daily. This can include a mild but effective cleanser coupled
with daily photoprotection and night moisturization. This approach provides the
patient with the opportunity to use multiple clinically proven antiaging technologies. For example, retinol has been shown in many studies to be an effective topical
treatment for fighting the visible signs of facial photodamage, including the
appearance of lines and wrinkles. Total soy contains specific nondenatured proteins
that influence the PAR-2 pathway, resulting in the evening out of skin pigmentation.
Current research supports the daily use of broad spectrum, photostable UVA/UVB
sunscreen as an essential tool in protecting the skin from future damage, and is
aligned with current dermatologic recommendations. With these factors in mind, a
new topical daily regimen combining stabilized retinol, total soy, and a patented
photostable sunscreen technology with SPF 30 was developed in order to effectively
reduce the visible signs of photodamage while protecting the skin against the
harmful effects of ongoing UV exposure. A 12-week, single-center, double-blind,
randomized study comparing the effects of daily topical usage of three different
antiaging treatment regimens was initiated to determine their clinical benefits on
photoaged skin. In each cell, 30 healthy female subjects between 30 and 61 years of
age who were exhibiting photodamage on the face—with moderate scores for fine
lines/wrinkles, mottled hyperpigmentation, and skin laxity—were enrolled.
Subjects applied the test products to their full face, including the eye area. In
clinical evaluations at weeks 2, 4, 8, and 12, the retinol, total soy, and photostable
sunscreen regimen demonstrated statistically significant improvements versus
baseline in the appearance of fine lines, mottled pigmentation, skin clarity, skin
tone, and overall photodamage. In addition, the retinol, total soy, and photostable
sunscreen regimen demonstrated statistical significance in numerous clinical
parameters when compared to the other regimens.
Growth factors are key regulators of wound healing, and their topical use for
cutaneous wound healing has been extensively studied. Because aged skin reveals
similar attributes related to growth factors than a chronic wound, the use of growth
factors for skin rejuvenation was suggested a few years ago. In the meantime, the
efficacy of growth factors for skin rejuvenation was shown in several clinical trials
including placebo studies. The present study investigated a serum comprising a
proprietary mixture of human growth factors in combination with specific skin care
actives to help address the signs of aging skin in a targeted and complementary
fashion. The growth factor mixture was obtained through a biotechnology process
using cultured human fetal skin cells that originated from a dedicated cell bank. The
serum contained four elemental amino acids and a stable form of ascorbic acid.
Glycine and proline are two indispensable building blocks in collagen because they
are mandatory for the formation of its unique triple helix. Arginine and glutamine are
other important amino acids involved in collagen biosynthesis. As cofactor of prolyl
and lysyl hydroxylases, which hydroxylate proline and lysine residues of procollagen
polypeptides, ascorbic acid is also needed for the formation of the triple helical
structure of collagen. In addition to the diverse roles of growth factors in collagen
formation, specific growth factors, such as platelet derived growth factor BB,
participate in the control of hyaluronic acid formation through stimulation of
hyaluronan synthase. The serum contained with N-acetyl-glucosamine a key
building block of hyaluronic acid. The serum was further supplemented with a
tripeptide that inhibits elastase and matrix metalloproteinase-1 in vitro. Under in use
conditions, 20 female subjects between 35 and 60 years of age were asked to apply
the serum twice daily over 4 weeks and report the perceived improvements (none,
slightly, moderately, or significantly) per questionnaire. After 1 week, 74% of the
subjects reported at least slight improvements in signs of periorbital wrinkles, and
63% of subjects for perioral wrinkles. After 4 weeks, 100% and 90% reported
improvements for periorbital and perioral wrinkles, respectively. Tone, overall look,
and feel were also assessed. This study confirmed that growth factors are emerging
as one of the most recent class of skin care actives for effective skin rejuvenation.
Commercial support: 100% sponsored by Neocutis.
Commercial support: The study was supported in full by Johnson & Johnson
Consumer Companies.
P1607
P1605
Ocular tolerance and fiber strengthening of a waterproof mascara with
rice protein
Judith Nebus, Johnson & Johnson, Skillman, NJ, United States; Warren Wallo,
Johson & Johnson, Skillman, NJ, United States
Mascaras need to be carefully formulated and tested for ocular tolerance because of
their use in such close proximity to the eye. Waterproof mascaras have additional
ingredients that aid in increasing resistance to external assault by water, and these
formulations may be prone to irritate those with sensitive eyes or may irritate
because of the need for more rigorous removal methods. This clinical study
evaluated the irritation potential of a waterproof mascara containing rice protein
used in conjunction with a two-phase silicone eye makeup remover. Rice proteins
are known for their gentleness and mildness while providing conditioning and
volumizing benefits to hair and eyelashes. Fifty healthy female subjects between 18
and 48 years of age who are regular mascara users (including a subset of contact lens
wearers and another subset of individuals with sensitive eyes) completed this 2week study. Comprehensive ophthalmologist evaluations and self-assessments
showed tolerance and benefits throughout the study. Instrumental analysis measured changes in strength and fatigue resistance of hair fibers coated with the
mascara. Ophthalmologist evaluations indicated no significant change in irritation
parameters (P \ .05) including edema, follicles, papillae, lacrimation, stinging,
burning, itching, and photophobia over the 2-week study. Patients perceive this
mascara to be well tolerated and provided significant benefits, including lashes
looking longer, and the mascara contributed to the healthy and natural look of their
lashes as well as leaving lashes soft to the touch after removal. In addition,
instrumental assessments documented a significant increase in the tensile strength
of the lashes.
Comparison of topical 5-fluorouracil formulations in the treatment of
actinic keratoses
Ravneet Ruby Kaur, MD, RN, University of California, Los Angeles-Olive View,
Sylmar, CA, United States; Ali Alialikhan, MD, University of California, Davis,
Sacramento, CA, United States; Howard Maibach, MD, University of California,
San Francisco, San Francisco, CA, United States
Background: Actinic keratoses (AKs) are common and may progress to squamous
cell carcinoma (SCC). While cryotherapy is the most commonly used treatment for
AKs, it is only suitable for treating a few lesions at a time. Topical medications such as
5-fluorouracil (5-FU) allow for more generalized treatment of AKs in the setting of
multiple lesions.
Objective: To evaluate and discuss clinical trials examining efficacy of 5-FU cream
formulations (0.5% and 5%), because 5% 5-FU has four times greater systemic
absorption.
Methods: We conducted PubMed and Embase searches (1965 to April 13, 2009) to
find studies evaluating the efficacy of 5-FU cream monotherapy (0.5% and 5%) in
treating multiple actinic keratoses of the face and scalp. We only included studies
employing standard treatment regimens (per the US FDA), with an endpoint of
complete clearance.
Results: Eleven studies met our criteria. At 4 weeks posttreatment, complete
clearance rates of 0.5% and 5% 5-FU ranged from 16.7% to 57.8% and 43% to 96%,
respectively. Because the various studies used different measurements of tolerability,
we were unable to pool these data. In the only split-face study comparing both
formulations, both treatments produced equivalent rates (43%) of complete
clearance, but 5% 5-FU had higher rates of adverse events.
Conclusions: Despite evidence suggesting the superior efficacy of 5% 5-FU to 0.5% 5FU, high-powered clinical trials comparing both treatments are lacking.
Furthermore, tolerability rates between formulations warrant further examination
given the possible enhanced systemic absorption of 5% 5-FU over 0.5% 5-FU. Such
studies will enable dermatologists to appropriately balance the risks and benefits of
each respective treatment to provide optimal solutions to patients with multiple
AKs.
MARCH 2010
J AM ACAD DERMATOL
AB55
P1608
P1610
Long-lasting relief for moderate to severe dry skin with a therapeutic
moisturizing cream
Michael Suero, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Dara Miller, Johnson & Johnson Consumer & Personal
Products Worldwide, Skillman, NJ, United States; Marilyne Candolives, Johnson &
Warren Wallo, MS, Johnson & Johnson Consumer & Personal Products
Worldwide, Skillman, NJ, United States
Patients suffering from dry skin are in constant search of an effective, long-lasting
solution. An effective moisturizer should be able to improve the visual signs of
dryness, the tactile roughness that accompanies this condition, and increase stratum
corneum water content and retard transepidermal water loss (TEWL). A dry leg
regression design allows for the assessment of a moisturizer’s efficacy in restoring
the skin to a hydrated state even after product application has stopped. A new
therapeutic moisturizing cream was evaluated for its ability to improve the overall
condition of dry skin. A randomized, controlled clinical study was conducted on 32
healthy volunteers 18 to 65 years of age with clinically evident moderate to severe
xerosis, to evaluate the efficacy of the moisturizer over a 7-day use period followed
by a 2-day regression period. Product application was performed on the lower lateral
legs by study personnel through day 7, with no product being applied on days 8 and
9. Product efficacy was determined via clinical grading of visual dryness and tactile
roughness, skin conductance measurements using two different instruments, TEWL
readings, and subject self-assessments at various time points over the 9-day study.
The immediate benefits of the therapeutic moisturizing cream were shown with
statistically significant increases in skin hydration levels and decreases in TEWL, as
measured instrumentally, and significant decreases in visual dryness and tactile
roughness after a single application through the 24-hour time point, as compared to
the untreated test site and its baseline scores. Twice daily applications produced
continued significant improvements in visual dryness and tactile roughness scores,
and skin conductance values from both instruments, versus the untreated site and
baseline scores throughout the 7-day treatment period. These significant improvements were maintained through the 48-hour regression period. Subjects also
perceived significant improvements in the itchiness, tightness and discomfort of
their dry skin at all the self-assessment time points. In conclusion, this new
therapeutic moisturizing cream has demonstrated its effectiveness in providing an
intensive and long-lasting relief for dry skin.
Micronized inorganic UV filter sunscreen use appears safe and efficacious
in babies and children
Alexandra Mccollum, MD, Rady Children’s Hospital & UCSD School of Medicine,
San Diego, CA, United States; Hao Ouyang, PhD, Neutrogena Corporation, Los
Angeles, CA, United States; Lawrence Eichenfield, MD, Rady Children’s Hospital
& UCSD School of Medicine, San Diego, CA, United States; Yohini Appa, PhD,
Neutrogena Corporation, Los Angeles, CA, United States
Although there is a large body of knowledge regarding sunscreen use in animals and
adults, clinical trials documenting the tolerability and efficacy of sunscreen in infants
and children are scarce. Infants and children possess a relatively higher body surface
to mass ratio than adults, and penetration, absorption, and irritation issues are of
higher concern in the younger population. Micronized inorganic UV filters are
chemically inert and do not penetrate into skin. Excellent and balanced UVA/UVB
protection can be provided in such products by combining titanium dioxide and
zinc oxide without additional chemical UV filters. A randomized, double-blinded,
crossover clinical study was conducted in infants and young children at Rady
Children’s Hospital in the summer of 2008 comparing the efficacy and tolerability of
a micronized inorganic filter sunscreen with a commercially available organic
sunscreen as benchmark. This is a real-world usage study. Thirty infants and children
from 6 months to 4 years of age were enrolled in the study. They were assigned
randomly to initially use one of the two sunscreens for 2 weeks; at the end of this
period they switched study products and used the other product for the following 2
weeks. Subjects were assessed by pediatric dermatologists at baseline and every 2
weeks for safety and tolerance and for product efficacy as measured by erythema
grading and photography. Sun exposure and sunscreen usage of the subjects were
recorded during the study period. Subjects reported an average of 28 hours in the
sun during the 2-week period as well as approximately 19 applications of sunscreen
totaling 34 to 39 g. The inorganic filter product showed statistically significant lack
of erythema on the body when compared to the benchmark sunscreen product;
however, there was no significant difference noted on the face between the two
sunscreens. Two adverse events were related to the use of the benchmark organic
sunscreen product while no adverse events were observed in association with the
use of the inorganic filter study sunscreen. This pilot study indicates that the
inorganic filter sunscreen tested is both gentle and efficacious when used on the
skin of infants and children.
Commercial support: Johnson and Johnson.
Commercial support: Sponsored by Johnson & Johnson Consumer & Personal
Products Worldwide.
P1609
The rapid and lasting efficacy of an oatmeal lotion in improving the
moisturization and skin barrier properties of extra dry, itchy skin
Judith Nebus, Johnson and Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Glenn Nystrand, Johnson & Johnson Consumer and
Personal Products Worldwide, Skillman, NJ, United States; Kristine
Schmalenberg, PhD, Johnson & Johnson Consumer & Personal Products
Worldwide, Skillman, NJ, United States; Warren Wallo, Johnson & Johnson
Consumer and Personal Products Worldwide, Skillman, NJ, United States
Daily routine skin moisturization is imperative to patients with compromised skin
and xerosis. Body moisturizers can be strategically formulated for these skin
conditions by utilizing benefit agents that help the skin to attract and retain
moisture, decrease irritation, and provide protection, which are all important in
helping to rebuild the skin barrier. Colloidal oatmeal has a long successful history of
use in skin care mainly because its skin protectant and antiirritant properties.
Colloidal oatmeal lotions with avenanthramides have been extremely beneficial to
patients with an array of compromised skin conditions, even demonstrating
tolerance and efficacy in babies and children with atopy. The purpose of this
clinical study was to demonstrate the efficacy of a colloidal oatmeal, skin protectant
lotion with avenanthramides in improving the skin condition of patients with
moderate itch and severely dry skin. Thirty patients between the ages of 18 and 55
completed the 9-day randomized, investigator blinded study. Patients used the lotion
twice a day for 7 days, followed by a 2-day regression period during which no lotion
was used. Efficacy was determined by clinical evaluations and instrumental
measures of moisturization and barrier function. Informed consent was obtained
from all study participants. Clinical evaluations showed a significant (P \ .05)
improvement in skin dryness after 1 day of using the colloidal oatmeal skin
protectant lotion. Skin moisturization conductance values on day 1, after a one-time
use of the lotion, nearly double compared to measurements obtained before the
study began. After 4 days of using the oatmeal skin protectant lotion, patients
reported a significant improvement in itching (P \.05). Transepidermal water loss
measurements demonstrated a significant improvement in skin barrier at this time
point. Improvements in skin condition continued throughout the 7-day treatment
phase of the study. In addition, these improvements were maintained during the 48hour regression phase of the study in which no product was used. In conclusion, this
colloidal oatmeal lotion with avenanthramides demonstrated the quick efficacy in
providing relief to patients with itchy, extra dry skin by providing moisturization,
relieving itching, and improving the skin barrier. In addition, this lotion was effective
in providing lasting skin benefits even after discontinuation of use for 2 days.
AB56
P1611
Efficacy and substantivity evaluation of a sunscreen formulation for
people conducting sporting activities in a high UV intensity locale
Darrell Rigel, MD, New York University Medical Center, New York, NY, United
States; Hao Ouyang, PhD, Neutrogena Corporation, Los Angeles, CA, United
States; Yohini Appa, PhD, Neutrogena Corporation, Los Angeles, CA, United
States
Background: It has been reported that when people conduct moderate physical
activities outdoors, sweat or heat can facilitate skin erythema reaction. Sunscreens
designed for people conducting sport activities should then provide higher
protection level to help compensate for the changes in skin physiology. In addition,
sweating or water immersion and rub-off can also compromise the performance of
the sport sunscreen, and a sport sunscreen needs to withstand these factors.
Methods: The performance of a SPF 701 sport sunscreen was tested under realworld conditions in a double-blinded, randomized clinical study conducted in the
summer of 2008 at Vail, CO (elevation 2500 meters above sea level) for people
playing golf (average exposure, 4.5hours). Subjects applied sunscreen themselves in
the study. To test the substantivity of the sunscreen, one subset of the subjects (21)
applied the SPF 701 sport sunscreen over the entire face at the baseline and
reapplied the sunscreen in the middle of the activities (about 2hours into the UV
exposure) to only one half of the face. To test the formulation’s efficacy, a second
subset of the subjects (22) in a split-face design applied the sport sunscreen on one
half of the face and a regular SPF 15 sunscreen on the other side at the baseline. Upon
completion of the sport activity, a dermatologic evaluation was conducted to
compare the lateral differences between the two sides of the face for both subsets.
Results: The UV condition during the study was monitored and was such that
virtually all of the participants would have been expected to sunburn in unprotected
skin areas. For the 21-subject reapplication group, none of the subjects could be
differentiated in terms of increased erythema on one side by clinical examination at
the end of the exposure. No postexposure sunburn was noted clinically, although
one subject had a slight increase in erythema. No subjects complained of symptoms
of early sunburning at the time of the final evaluation. Of the 22 subjects that had SPF
70 applied to one half of the face and SPF 15 applied of the other, seven had
noticeable increased erythema on one side associated with the SPF15 sunscreen (P
[ .001).
Conclusions: We found that the tested formulation is substantive to the skin and is
very effective in protecting skin from sunburns under extreme UV and real sporting
conditions.
J AM ACAD DERMATOL
MARCH 2010
P1612
P1614
Clinical evaluation of skin care product containing Thujopsis dolabrata
var. hondae extracts in the patients with dry skin
Satoko Minakawa, MD, PhD, Department of Dermatology, Hirosaki University
Graduate School of Medicine, Hirosaki, Aomori, Japan; Daisuke Swamura, MD,
PhD, Department of Dermatology, Hirosaki University Graduate School of
Medicine, Hirosaki, Aomori, Japan; Hajime Nakano, MD, PhD, Department of
Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki,
Aomori, Japan; Yasushi Matsuzaki, MD, PhD, Department of Dermatology,
Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
Evaluation of the clinical efficacy of onion extract cream in the treatment
of new stretch marks
Zoe Draelos, MD, Dermatology Consulting Services, High Point, NC, United
States; Bhushan Hardas, MD, MBA, Merz Pharmaceuticals, LLC, Greensboro, NC,
United States; Eric Pappert, MD, Merz Pharmaceuticals, LLC, Greensboro, NC,
United States; Mandeep Kaur, MD, Merz Pharmaceuticals, LLC, Greensboro, NC,
United States; Wendy Murray, Merz Pharmaceuticals, LLC, Greensboro, NC,
United States
Background: Stretch marks (striae distensae) are a common cosmetic problem
experienced by both genders but primarily women. Newly formed stretch marks
appear as wavy linear red scars aligned parallel to the limb and body. With time, the
stretch mark redness fades and the scars remain permanent.
Objective: To evaluate the effect of a new, proprietary formulation of onion extract
cream with centella asiatica (onion extract cream) in improving the overall
appearance of new stretch marks.
Methods: Female subjects (ages 18-45 years) with new bilateral outer thigh stretch
marks (striae rubra) were enrolled and randomized to apply a quarter-sized amount
of proprietary onion extract cream twice daily for 12 weeks to either the assigned
left or right side. Subjects were evaluated at weeks 2, 4, 8, and 12 for subject and
investigator assessments, photography, and skin elasticity measurements.
Assessments included color, texture, softness, and overall appearance of stretch
marks. The primary efficacy endpoint was the change from baseline to week 12 for
subject assessment of softness, texture, color, and overall appearance (5-point
ordinal scale: 0 ¼ no improvement, 1 ¼ minimal improvement, 2 ¼ mild
improvement, 3 ¼ moderate improvement, and 4 ¼ marked improvement). Safety
was assessed via adverse events (AEs). For all efficacy variables, paired 2-sided t tests
were performed.
Results: Of the 55 female subjects enrolled, 52 (94.5%) completed the study, while
three (5.5%) discontinued prematurely (lack of protocol compliance [1]; other
reasons [2]). The treated side revealed a statistically significant difference in the
mean change in subject evaluations of overall appearance (1.13 vs 0.20, respectively; P \.01), texture (1.06 vs 0.19, respectively; P \.01), color (0.70 vs 0.07,
respectively; P \.01), and softness (1.31 vs 0.15, respectively; P \.01) compared to
the untreated side. The blinded investigator assessment of the stretch marks
demonstrated similar results to the subject assessment. Although a trend toward
increased skin elasticity with treatment was observed compared to no treatment,
the difference was not significant (week 12 skin elasticity change from baseline:
-1.40 [treated] vs -0.10 [untreated]; P ¼.23). No AEs occurred during the study.
Background: The usefulness of moisturizers for maintenance in atopic dermatitis
(AD) is well known. We investigated the efficacy and safety of skin care moisturizer
containing Thujopsis dolabrata var. hondae extracts, which were obtained from
steam distillation of the woody portion of T dolabrata var. hondae.
Methods: Thirty-two patients with AD (n ¼ 6) and xeroderma (n ¼ 26) were
enrolled. That moisturizer was applied at right side of the arm and leg, while a
control moisturizer (consisting of same contents without T dolabrata var. hondae
extract) was painted on the left sides of the arm and leg for the comparison. They
were applied more than once a day for 2 weeks. Measurements were performed
concerning clinical findings (erythema, desquamation, xerosis, or scratch mark),
moisture level (uS) in the horny layer, morphologic shape of horny cells, and ratio of
IL-1 receptor antagonist (IL-1ra) to IL-1a in the stratum corneum (SC). Clinical
findings were scored from 0 (none) to 4 (severe). Morphologic shape of horny cells
was scored from 0 (severely damaged) to 4 (normal). The SC materials were obtained
with a noninvasive tape-stripping method. Soluble fraction of the IL-1ra and IL-1a
was analyzed by enzyme-linked immunosorbent assay. Statistical analysis was
performed using Wilcoxon signed rank between before and after administration
of moisturizer, and between T dolabrata var. hondae extracts and placebo
moisturizer.
Results: There was no side effect of both moisturizers. There was a significant
improvement in clinical findings and morphologic shape after using Thujopsis
dolabrata var. hondae extract and control moisturizer, while there was no
significant difference between the two moisturizers. Moisture level in the horny
layer was significantly increased after using two moisturizers, while there was no
significant difference between the two moisturizers. Although there was no
significant difference in IL-1ra/IL-1a ratio in both moisturizers, it was lower than
that of control after treatment with Thujopsis dolabrata var. hondae extracts
moisturizer (7.3 6 6.9 vs 9.9 6 8.6 in control).
Conclusions: The skin care moisturizer containing extracts of Thujopsis dolabrata
var. hondae was safe in clinical application for cutaneous manifestations of dry skin,
and it could improve skin conditions of atopic dermatitis and xeroderma.
Conclusions: Proprietary onion extract cream was well tolerated and improved the
overall appearance, softness, color, and texture of new stretch marks in female patients.
Commercial support: This research was funded by Merz Pharmaceuticals.
P1615
P1613
Global action of active ingredients in the management of stretch marks
Dalale Naaimi, Laboratoires Expanscience, Epernon, Eure Et Loir, France;
Caroline Baudouin, PhD, Laboratoires Expanscience, Epernon, Eure Et Loir,
France; Marisa Meloni, MD, Vitroscreen, Milano, Italy; Philippe Msika, PhD,
Laboratoires Expanscience, Epernon, Eure Et Loir, France
Objectives: Stretch marks, which are common during pregnancy (70-90% of
patients), are the result of many factors, including hormonal impact and mechanical
and physiologic stress. These lesions form an atrophied scar. Firstly, inflammatory
changes are significant with dermal edema and afterward, an epidermal atrophy and
thinning are observed. In this work, we have investigated the efficacy of a cream
specifically formulated to reduce stretch marks using a mimicking dermal injury
model. Previously, we have examined efficacy of the main patented ingredients
(lupeol, natural biopeptides, and arabinogalactane) to counteract tissue inflammation and to stimulate extracellular matrix (ECM) remodeling.
Methods: In fibroblast cultures, we analyzed ingredients’ effects on expression
regulation of collagens, elastin, and HSP47 by quantitative RT-PCR. Proteins
(collagens, elastin) or cytokine (Il1a) secretions were evaluated by ELISA or
immunolabelling (HSP47). A dermal injury model that mimics ECM changes as
they occur in the formation of stretch marks was conduced on in vitro reconstructed
full-thickness skin. Product application has been performed at the starting day after
injury and repeated at days 3 and 8. Collagen VII, elastin, integrin a1 gene
expression was analyzed different time after injury by QRT-PCR with Taqman assays.
Hyaluronic acid is superior to collagen in the correction of moderate to
severe nasolabial folds: Results from a randomized, blinded, controlled,
multicenter effectiveness and safety study
Rhoda Narins, MD, New York University School of Medicine, New York, NY,
United States; Corey Maas, MD, The Maas Clinic, San Francisco, CA, United
States; Derek Jones, MD, Skin Care and Laser Physicians of Beverly Hills, Los
Angeles, CA, United States; Gary Monheit, MD, Total Skin & Beauty Dermatology
Center, P.C., Birmingham, AL, United States; William Coleman III, MD, Tulane
University Health Sciences Center, New Orleans, LA, United States
Background: Dermal fillers are used to augment wrinkles and folds and a variety of
hyaluronic acid (HA)-based products are available. The HA in this trial was a
noneanimal sourced HA-based filler cross-linked in two consecutive steps and used
a cohesive polydensified matrix technology that contains a monophasic gel with
variable density (viscosity) zones for adaptation in the dermis (Merz).
Objective: To determine the safety and effectiveness of HA compared to collagen
(COL; Allergan) in the correction of moderate to severe NLF in a split-face design.
Methods: Subjects randomly received HA in one NLF and COL in the contralateral
NLF in this blinded trial. The severity of NLF was measured using the Wrinkle
Severity Rating Scale (WSRS). The initial treatment was evaluated after 2 weeks and
an optional touch-up treatment was permitted. The primary effectiveness endpoint
was the mean change from baseline in the WSRS score (blinded evaluator) of each
NLF 12 weeks after the last injection. Safety was assessed via adverse events (AEs).
Conclusion: These results demonstrate the wound healing efficacy of the ingredients combination to counteract alteration at DEJ and ECM levels and to promote
tissue regeneration, supporting the cosmetic relevance of this cream for the
management of stretch marks.
Results: One hundred eighteen predominately white (97%) and female (92%)
subjects with a mean age of 52 years (range, 25-75 years) were treated, and 103
received a touch-up 2 weeks later. The mean baseline WSRS was 2.5. Approximately
90% of subjects completed this 24-week study. HA resulted in a significantly greater
reduction in the mean change of WSRS compared to COL at weeks 8 (1.38 vs 1.19,
respectively (R); P ¼.009), 12 (1.25 vs 0.98, R; P \.001), 16 (1.09 vs 0.66, R; P \
.001), and 24 (1.08 vs 0.50, R; P \.001). Overall, 116 of 118 (98%) subjects reported
AEs. There were no noteworthy differences in the proportion of AEs considered
related to the injection site procedure occurring in subjects on the side receiving HA
(92%) versus COL (93%). AEs considered related to device occurred in 59% of HA
and 65% of COL-treated sides. AEs that were most frequently reported to be related
to either HA or COL were general disorders and administration site conditions, such
as injection site nodules (33% vs 55%, R), injection site induration (34% vs 41%, R)
and injection site swelling (23% vs 22%, R). Most were mild to moderate in severity
with the majority of injection site responses lasting \7 days. All systemic AEs were
considered unrelated by investigators.
Conclusions: HA was well tolerated for the treatment of NLF, and its effectiveness
was superior to COL over 24 weeks. Local AEs attributed to either device or to the
injection site procedure were common but mild or moderate in severity.
Commercial support: This research was funded by Merz Pharmaceuticals.
Results: In fibroblasts, lupeol stimulated collagen I production (32 to 34.4) through
a targeted action on HSP47 that was increased at mRNA and protein level.
Arabinogalactane inhibited significantly the release of Il1a (-21%) and was able to
restore and stimulate collagen I expression in deleterious hormonal condition
(37%). Natural biopeptides induced significantly collagens and elastin neosynthesis
(60%, 34%). In skin injured model, from day 8, the cream topical treatment has
significantly upregulated elastin, collagen VII and integrin a1 (32.2, 33, and 31.7,
respectively). This effect has been extended and increased until day 16 for collagen
VII and integrin a1.
MARCH 2010
J AM ACAD DERMATOL
AB57
P1616
P1618
Quantifying the effect of makeup on facial attractiveness
Gabiella Cula, PhD, Johnson and Johnson Consumer Products Worldwide,
Skillman, NJ, United States; I-Ting Wu, MS, Neutrogena Coporation, Los
Angeles, CA, United States; Sylvia Barkovic, MS, Neutrogena Corporation, Los
Angeles, CA, United States; Yohini Appa, PhD, Neutrogena Corporation, Los
Angeles, CA, United States
Biomimetic electricity generated by an elemental bimineral complex
produce’s antiinflammatory activity
Peter Lyte, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Frank Liebel, Johnson & Johnson Consumer &
Personal Products Worldwide, Skillman, NJ, United States; Michael Southall, PhD,
Johnson & Johnson Consumer & Personal Products Worldwide, Skillman, NJ,
United States; Michelle Garay, MS, Johnson & Johnson Consumer & Personal
Products Worldwide, Skillman, NJ, United States; Runa Sur, PhD, Johnson &
Johnson Consumer & Personal Products Worldwide, Skillman, NJ, United States
Introduction: Research has shown that attractive faces draw more attention than
unattractive faces, and it is well known that facial attractiveness can be greatly
enhanced by using makeup. Facial beauty is typically assessed subjectively.
However, with the eye tracking technology, which uses the image processing of
an observer’s eyes to accurately measure the exact amount of time and the precise
location of focus, facial beauty can now be objectively quantified. In this study, we
have successfully used this technology to quantify the impact of make-up on facial
attractiveness.
Methods: Thirty-four female panelists 20 to 45 years of age looked at facial images of
14 females within the same age group. Panelists were shown a randomized sequence
of photographs on a computer screen. Each photograph consisted of two images of
the same face, before and after makeup application. The panelists were asked to
assess facial beauty by looking at the images, while the eye tracker recorded their
eye movements and reported the fixation length corresponding to each area of
interest within each image: face, eyes, nose, and mouth.
Results: Overall, faces with makeup attracted 32% longer attention time than faces
without makeup. Of the specific features of the face, the eyes attracted the most
attention. The eyes with makeup had 40% longer attention time than the eyes
without makeup. The nose and mouth showed an increase of 21% and 26% after
makeup application. Also, the data revealed that significant unevenness in faces
without makeup diverted attention away from the eyes. However, when makeup
was applied to the entire face, concealing the facial unevenness, the attention to the
eyes was increased by up to 80%.
Conclusion: The results in this study showed that the eye tracking technology is an
objective method of quantifying facial attractiveness, and that among all facial
features, the eyes were the focal point of interest when assessing facial attractiveness. The data also showed that application of makeup to the bare face resulted in
increased attention time by observers, suggesting enhanced attractiveness.
The human body has its own innate electrical system that regulates the body’s
functions via communications among organs through the well-known neural
system, and some less understood cellular activities, such as the bioelectricity
associated with tissue regeneration. The bioelectricity during wound healing has
been attributed the endogenous ‘‘skin battery’’ that pumps sodium ions using the
Na/K-ATPase located on epidermal cells and can generate a potential outward
electric current of about 10-100 aA/cm and an electric potential gradient about 60
mV/mm. While the effect of low-level electrical stimulation on wound repair has
been reported, few studies have examined the effect biomimetic electricity on
nonwounded skin. Physiologic levels of biomimetic electricity may be derived from
the unique combination of elemental zinc and copper. In the current study, we
developed an elemental zincecopper bimineral complex to determine the effect of
low-level electrical stimulation on skin physiology. Treatment with the bimineral
complex significantly reduced the release of proinflammatory cytokines from
activated human T cells and inhibited the release of cytokines from keratinocytes
and macrophages exposed to bacteria. Furthermore, topical application of a lotion
containing the bimineral complex reduced the UV-induced damage to human skin
equivalents. Taken together, these results indicate that biomimetic electricity
reduces inflammatory responses and therefore may protect skin from the numerous
external aggressions encountered daily by skin.
Commercial support: 100% is sponsored by Johnson & Johnson.
P1617
The relevance of high SPF products in the real world
Hao Ouyang, PhD, Neutrogena Corporation, Los Angeles, CA, United States; Curt
Cole, PhD, Johnson and Johnson Consumer Products Worldwide, Skillman, NJ,
United States; Nik Kollias, PhD, Johnson and Johnson Consumer Products
Worldwide, Skillman, NJ, United States; Yohini Appa, PhD, Neutrogena
Corporation, Los Angeles, CA, United States
Sun protection factor (SPF) is the globally recognized, in vivo measure of the
effectiveness of sunscreens in protecting skin from sunburn. SPF is calculated as the
minimal erythema dose (MED) of sunscreen protected skin over MED of unprotected skin. The higher the SPF, the longer the sunscreen can protect the skin with
the highly variable solar UV intensity. The biophysical and clinical aspects of the SPF
in the context of UV irradiance blocked, transmitted, and the accumulated damaging
dosage are key to understanding the relevance of high SPF protection. SPF is
measured in labs under controlled conditions with the application rate of 2 mg/cm2.
It has been well established that people significantly underapply sunscreen in real
life. The data show that SPF varies with the amount of sunscreen applied, and it is
important to understand the mismatch between label SPF and the actual sun
protection level achieved by the consumers when they underapply products.
Clinical data show that when people apply sunscreen themselves, as occurs in real
life, higher SPF sunscreens offer meaningful additional protection. UV exposure
dose is accumulated across one’s lifetime, and the risk of nonmelanoma skin cancers
is proportional to the dose of UV exposure. Suberythemal (as low as 1/10 of MED)
dose can still induce measurable biologic changes in skin. Modeling of that
relationship confirms that a slight increase in the amount of blocked UV intensity
can have significant impact to the long-term health of the skin. Lastly, SPF needs to
be measured accurately and reproducibly so that the label conveys a meaningful
indication about how well a sunscreen can perform relative to other products. A
multilaboratory study confirms that SPF to the level of SPF 100 can be measured with
accuracy and reproducibility. Sunscreens with high SPF can help compensate for
inadequate application and help slow the accumulation of chronic UV damages.
Sunscreens with higher SPF should be available and labeled as such for people who
need them.
AB58
P1619
increases extracellular matrix production in human skin explants
Nannan Chen, PhD, Johnson & Johnson Consumer & Personal Products
Worldwide, Skillman, NJ, United States; Connie Lin, PhD, Johnson & Johnson
Consumer & Personal Products Worldwide, Skillman, NJ, United States; Dianne
Rossetti, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Miri Seiberg, PhD, Johnson & Johnson Consumer &
Personal Products Worldwide, Skillman, NJ, United States; Yaping Hu, PhD,
Johnson & Johnson Consumer & Personal Products Worldwide, Skillman, NJ,
United States
Human skin generates an endogenous electric field that is known to affect wound
healing, inducing the directional migration of keratinocytes and melanocytes toward
the cathode. However, the effect of the endogenous electrical field on dermal cells
and on the dermal extracellular matrix (ECM) is not well studied. An elemental
bimineral complex that produces physiologic levels of electricity was evaluated for
its possible effects on dermal ECM. Human skin explants were topically treated with
this bimineral complex once daily for 7 days, and the effect on elastin and collagen
was evaluated. LUNA elastin staining showed that treatment with the bimineral
complex increased the elastin fiber network, as compared to untreated controls.
QPCR analysis documented an increase in elastin and collagen expression in the
bimineral complexetreated skin samples. Our results suggest that this bimineral
complex may be effective in restoring the integrity and functionality of dermal ECM,
and in particular of elastic fibers, suggesting its cosmetic use in aged skin.
J AM ACAD DERMATOL
MARCH 2010
P1620
P1622
Upregulation of elastogenesis in the skin and its potential for skin aging
benefits
Menas Kizoulis, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Christina Lee, Johnson & Johnson Consumer &
Personal Products Worldwide, Skillman, NJ, United States; Michael Southall, PhD,
Johnson & Johnson Consumer & Products Worldwide, Skillman, NJ, United
States; Samantha Tucker-Samaras, PhD, Johnson & Johnson Consumer &
Products Worldwide, Skillman, NJ, United States; Steve Cochran, MS, Johnson
& Johnson Consumer & Products Worldwide, Skillman, NJ, United States
Safety and tolerability of a topical bimineral complex that generates
biomimetic signals
Products Worldwide, Skillman, NJ, United States; Chong Jin Loy, PhD, Johnson
& Johnson Consumer & Personal Products Worldwide, Singapore; Michael
Southall, PhD, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; Timothy McCarthy, PhD, Johnson & Johnson
Consumer & Personal Products Worldwide, Skillman, NJ, United States; Ying
Sun, PhD, Johnson & Johnson Consumer & Personal Products Worldwide,
The elastin fiber network is responsible for the elasticity of our skin, allowing it to
resume its shape after stretching or contracting. In the dermal connective tissue, the
thin and sinuous elastin fibers represent approximately 5% of dermal compartment
by dry weight. Functional elastin fibers are made by properly linking many soluble
tropoelastin protein molecules, in a reaction catalyzed by lysyl oxidase, to make a
massive insoluble, cross-linked array. With aging, the elastic fibers progressively
degenerate and eventually disappear in the area just below the dermoepidermal
junction. In addition, an accumulation of nonfunctional elastin is observed, resulting
in an elastotic dermis. The skin progressively loses its elasticity while lines and
wrinkles start appearing. The creation of new, functional elastin requires a
comprehensive approach that targets all aspects of elastogenesis. Upregulating
the creation of the elastin fiber elements (tropoelastin, microfibrils, etc) while
simultaneously increasing the levels of the cross-linking enzymes can facilitate the
production of new elastin fibers in the dermis. We present two natural ingredients,
blackberry leaf and dill, which together work to enhance the skin’s elastin fiber
network. In vitro data shows that blackberry leaf inhibits the enzymes responsible
for the digestion of elastin while upregulating the production of tropoelastin, an
important elastin fiber building block. Dill extract has been shown to increase the
expression of LOXL1, a cross-linking enzyme that assembles elastin-related proteins
into functional fibers. In a 12-week, round-robin, double-blind, randomized study
comparing the effects of different formulations containing either blackberry leaf
alone, dill extract alone and the combination of both natural extracts, 49 healthy
premenopausal female subjects 35 to 50 years of age were enrolled. Subjects applied
products to the upper inner arm twice daily. Instrumental assessments were
conducted at baseline and week 12 of study. Two-millimeter skin biopsy specimens
were taken from each treatment site at the end of the study. Histologic analysis of the
skin biopsies and instrumental assessments on the treated skin suggest that the
combination of blackberry leaf and dill extracts upregulated the creation of new,
functional elastin fibers in the upper dermis. Therefore, the topical use of blackberry
leaf and dill extracts has the potential to provide long-term skin antiaging benefits.
A proprietary elemental bimineral complex that produces biomimetic signals has
demonstrated antiinflammatory activity, increases in extracellular matrix production in human skin explants, and inhibition of melanogenesis. This biomimetic
technology consisting of essential minerals zinc and copper was developed for use
in topical skin care compositions. To evaluate the safety and tolerability of this
technology in topical skin applications, several clinical and preclinical safety studies
were conducted. Clinical safety was assessed through Human Repeat Insult Patch
Tests (RIPT). Five RIPT studies were performed on topical compositions containing
various concentrations of the bimineral complex. Four RIPT studies were conducted
in a predominately white population in the United States, and one study was
conducted in an Asian population in Thailand. Together, more than 800 healthy
subjects completed the clinical safety studies. Results show that none of the topical
compositions induced dermal sensitization. In addition, a topical composition
containing the bimineral complex was evaluated versus placebo for its potential to
induce dermal and ocular irritation in a human skin model (EpiDerm) and human
corneal model (EpiOcular). The results show that the bimineral complex has low
potential for skin and eye irritation. Topical compositions containing the bimineral
complex have been evaluated for their tolerability and efficacy in reducing the signs
of facial and periorbital photoaging in more than eight clinical studies spanning
populations in three countries; the United States, France, and Singapore. The
bimineral compositions were shown to be mild and well tolerated in all populations
studied.
Personal Products Worldwide
Commercial support: The research was supported in full by Johnson & Johnson
Consumer Companies.
P1623
P1621
inhibits melanogenesis via suppressing tyrosinase expression
Nannan Chen, PhD, Johnson & Johnson Consumer & Personal Products
Worldwide, Skillman, NJ, United States; Chong Jin Loy, PhD, Johnson &
Johnson Consumer & Personal Products Worldwide, Singapore; Connie Lin,
PhD, Johnson & Johnson Consumer & Personal Products Worldwide, Skillman,
NJ, United States; Yaping Hu, PhD, Johnson & Johnson Consumer & Personal
Products Worldwide, Skillman, NJ, United States; Yen Kim Won, Johnson &
Johnson Consumer & Personal Products Worldwide, Singapore
The endogenous electric field of human skin plays an important role in many skin
functions. To examine the effect of electric field modulation on melanogenesis,
pigmented epidermal equivalents were topically treated with a proprietary elemental bimineral complex that produces biomimetic electricity once daily for 7 days.
F&M staining showed a significant decrease in melanin deposition in epidermal
equivalents treated with the bimineral complex, compared to untreated controls.
This reduction in melanin deposition was also observed in epidermal equivalents
treated with a cosmetic formula containing the bimineral complex. Exploring the
mechanism of this biomimetic electricity-induced depigmentation, we showed no
direct inhibitory activity against the phagocytic activity of keratinocytes.
Interestingly, the bimineral complex inhibited tyrosinase and tyrosinase related
protein 1 (TRP-1) expression using mouse melanoma B 16 cells, as analyzed by TYR
and TRP-1 promoter-luciferase reporter assays. Using cultured human skin explants,
we confirmed that melanin content and TYR mRNA are reduced by the exposure to
the bimineral complex. These data support the potential of using biomimetic
electricity generated by an elemental bimineral complex for skin lightening
applications.
A cosmetic product containing biomimetic signaling technology to improve the aging signs in the eye area
Marion Lanctin, Johnson & Johnson Consumer France, Issy les Moulineaux,
France; Alex Nkengne, PhD, Johnson & Johnson Consumer France, Issy les
Moulineaux, France; Christiane Bertin, MS, Johnson & Johnson Consumer
France, Issy les Moulineaux, France; Romain Roure, Johnson & Johnson
Consumer France, Issy les Moulineaux, France
It has been published that beauty is strongly linked to the appearance of the eyes.
Therefore, to fight against the signs of aging, particular attention needs to be paid to
the eye area. A new bimineral complex that consists of a proprietary blend of
elemental zinc and copper that generates biomimetic signals was recently developed to fight against multiple signs of aging. The objective of this study was to
investigate the efficacy of a composition using biomimetic signaling technology with
a special focus on the eye area. An open study was performed on 34 healthy white
women between 35 and 60 years of age with wrinkles and/or fine lines at the eye
contour area, dark circles, and puffiness. All volunteers signed an informed consent
form. The product was applied for 8 weeks, once a day, in the morning. Clinical
grading of the signs of aging was performed at baseline, immediately after the first
application, then after 1, 4, and 8 weeks of application. Wrinkles, tone, and sagging
were assessed by an expert grader around the eyes using visual analog scales. A
paired Student t test was performed versus baseline and the confidence level
considered was P \.05. Immediately after the first application, all the parameters
assessed were significantly improved versus baseline (P \ .05). The product
improved bags and dark circles (respectively 132.37% and 121.28%) as well as
wrinkles (crow’s feet, 124.06%; under eye, 122.47%), sagging (sloping eyelids,
120.29%; folds on the eyelids, 17.19%), and skin complexion (radiance, 117.38%;
yellowish complexion, 151.99%). Some changes were still increasing after 1 week
of application. The tested product containing the new biomimetic signaling
technology was shown to be efficacious from the first week of use and delivered
instant benefits to the eye area.
Commercial support: 100% is sponsored by Johnson & Johnson Consumer France
MARCH 2010
J AM ACAD DERMATOL
AB59
P1624
P1626
Biomimetic signaling technology generated by a bimineral complex
reduces signs of photoaging in the eye area
Products Worldwide, Skillman, NJ, United States; Elizabeth Bruning, Johnson &
Jue-Chen Liu, PhD, Johnson & Johnson Consumer & Personal Products
Worldwide, Skillman, NJ, United States; Ying Sun, PhD, Johnson & Johnson
Consumer & Personal Products Worldwide, Skillman, NJ, United States
The first signs of skin aging often occur in the delicate skin of the periorbital area.
Characteristic signs associated with chronological and photoaging in the eye area
include fine lines and wrinkles, dark circles and bags under the eye, and puffiness
and laxity in both the upper and lower eyelids. A bimineral complex that consists of
a proprietary coupling of elemental zinc and copper and is based on the latest
advances in biomimetic technology has demonstrated antiinflammatory activity and
extracellular matrix improvement, including collagen and elastin production. To
address the need for a targeted eye area product to treat periorbital photoaging, a
composition containing the bimineral complex was developed and evaluated for
immediate and continuous benefits. Two clinical studies were conducted to
evaluate the efficacy and tolerability in reducing signs of photoaging in the
periorbital area. The first study focused on immediate benefits after a single
application of the bimineral complex. Twenty-two females 25 to 45 years of age
completed this double-blind, benchmark controlled study. To enroll at baseline,
subjects must experience at least one of the following conditions of mild to
moderate severity based on expert grading: under-eye bags, puffiness, dark circles,
lines, and wrinkles. Clinical images and subject self-assessments were taken at
baseline, 20 to 30 minutes postapplication, and 3 hours postapplication. The results
show that the bimineral complex demonstrated visible improvement (P \.05) at 20
to 30 minutes postapplication and continued to show improvement at 3 hours in
parameters such as under-eye puffiness, bags, and fine lines. The second clinical
study was a placebo-controlled, double-blind study to evaluate the immediate and
continuous effects of the bimineral complex over an 8-week period. One hundred
twenty women 40 to 65 years of age with mild to moderate photoaging at baseline
completed this study. Clinical grading, clinical images, and subject self-assessments
were performed at baseline, immediately postapplication, and after 1, 2, 4, and 8
weeks of product use. Clinical grading immediately after the first product application shows that the treatments with the bimineral complex have significant (P\.05)
improvement versus placebo in under-eye dark circles, under-eye bags, skin
radiance, and overall photodamage. In both studies, the bimineral complex showed
immediate and lasting improvement versus baseline, and all compositions were well
tolerated.
Comparison of skin hydration levels among three ethnic populations in
the United States
Jared Fantasia, MS, Johnson & Johnson Consumer Companies, Skillman, NJ,
United States; Jue-Chen Liu, PhD, Johnson & Johnson Consumer Companies,
Skillman, NJ, United States; Theresa Chen, PhD, Johnson & Johnson Consumer
Companies, Skillman, NJ, United States
Skin hydration can have a significant impact on the health and appearance of the
skin. Baseline hydration level, that is, the hydration level in the skin before
application of any product, is a reflection of skin’s intrinsic moisture retention
(humectant) capability and is also associated with skin’s barrier function. The
objective of this study was to investigate the differences in facial skin hydration of
healthy adult women across three different ethnicities (white, African American,
and Asian Indian) living in the United States and gain important information about
variations in skin surface hydration. One hundred forty-one women 25 to 70 years of
age successfully completed this study. Specific ethnic breakdowns for white, African
American, and Asian Indian subjects in the study were: number of subjects, 46, 48,
and 47, respectively; mean age, 50 6 10, 46 6 11, and 45 6 11, respectively. All
panelists were subjected to a 1-week washout using only an assigned facial cleanser
and were instructed to discontinue use of all their current facial products prior to
any assessments being conducted. Instrumental measurements were conducted
after subjects had acclimatized for 30minutes under controlled temperature and
humidity conditions (71 6 38F; 30-35% relative humidity). Statistically significant
differences in facial skin hydration were observed between white and African
American as well as between African American and Asian Indian. No significant
differences were observed between whites and Asian Indians. The facial skin,
measured by conductance, of African Americans was on average 202 S (44%) and
167 S (36%) more hydrated than white and Asian Indian, respectively. When
analyzed across age brackets (25-34, 35-44, 45-54, and 55-70 years), a similar trend
was observed across all age groups. The findings from this study reveal a greater skin
hydration capacity of African American facial skin when compared to age-matched
white and Asian Indian skin.
Commercial support: 100% Sponsored by Johnson & Johnson Consumer
Companies.
P1627
Objective evaluation of skin color distribution in light and dark complexioned individuals
Gregory Payonk, PhD, Johnson & Johnson Consumer Companies, Skillman, NJ,
United States; Jared Fantasia, MS, Johnson & Johnson Consumer Companies,
Skillman, NJ, United States; Nikiforos Kollias, PhD, Johnson & Johnson Consumer
Companies, Skillman, NJ, United States; Theresa Chen, PhD, Johnson & Johnson
Consumer Companies, Skillman, NJ, United States
P1625
Facial moisturizer featuring biomimetic signaling technology from a
bimineral complex reduces skin laxity
Sidney Hornby, MS, Neutrogena Corporation, Los Angeles, CA, United States;
Dara Miller, Johnson & Johnson Consumer & Personal Products Worldwide,
Skillman, NJ, United States; James Herndon, MD, Thomas J. Stephens &
Associates, Carrollton, TX, United States; Monya Sigler, PhD, Thomas J.
Stephens & Associates, Carrollton, TX, United States; Yohini Appa, PhD,
Neutrogena Corporation, Los Angeles, CA, United States
Skin color has a wide range across geographic regions and ethnicities. Within
individuals, skin color can be noticeably affected by exposure, seasonal habits, or
contact with products. The changes come from chromaphoric reactions in the skin
that filter through and interact with the surface color(s). Visual detection and
assessment of the deeper color/hue changes by the naked eyes can be challenging.
Moreover, no two individuals see color exactly the same, which can lead to
ambiguity or uncertainty when describing or interpreting color, especially skin
color.
Several studies have shown that an electric potential gradient exists between
individual cells that may be involved in the regulation of cellular activities. During
wound healing, it has been reported that a potential develops, resulting in an
electric current of about 10 to 100 aA/cm. This biocurrent signals the reepithelialization and appears to be involved in the rehabilitation of the collagen matrix. In
the current study, we developed a bimineral complex that has been shown to
generate a physiologic level of biomimetic electricity. In preclinical studies, this
complex has demonstrated antiinflammatory activity and extracellular matrix
improvement, including collagen and elastin production. We have evaluated the
clinical efficacy of a facial treatment regimen consisting of this bimineral complex
plus a facial moisturizer in a 4-week double blinded controlled study. Thirty subjects
with mild to moderate signs of photodamage and moderate skin laxity completed
the study. The patients applied the regimen once per day in the morning. Clinical
evaluations, self-assessments and instrumental analysis demonstrated this twoproduct regimen’s multiple skin benefits throughout the study. The facial treatment
was particularly effective in improving skin firmness and laxity (P \.05), while also
providing significant improvements in overall photodamage. Patients also perceived
significant (P \.05) improvements in overall signs of photodamage and lifting. The
regimen was well tolerated.
The objective of this study was to develop a method to extract color information
from high-resolution digital facial images and objectively quantify differences across
three different ethnicities (whites, African Americans, and Asian Indians residing in
the United States) before and after treatment. One hundred forty-one women 25 to
70 years of age with Fitzpatrick skin types I to VI successfully completed this study.
Specific numerical breakdowns for whites, African Americans, and Asian Indians
were n ¼ 46, n ¼ 48, and n ¼ 47, respectively. All panelists were subjected to a 1week washout using only an assigned facial cleanser and were instructed to
discontinue use of all their current facial products prior to any assessments being
conducted. Visible and cross-polarized light digital facial images were acquired from
subjects of the three ethnicities. The analysis routines provided 3D-plots of L*a*b*
values of all pixels for each grouping variable (ethnicity, treatment), median L*a*b*
values, the ITA angles, and the median point of the data distribution. The median
L*a*b* values for the three population groups in the study were: white: L:54.5 a*:29.1
b*:35.3; African American: L:31.1 a*:33.1 b*:38.0; and Asian Indian: L:42.3 a*:32.1
b*:42.0. The study findings reveal that the image analysis routine can efficiently
separate color differences across ethnicities and between treatment groups.
Identifying differences for a particular combination of ethnicity and treatment
would have been nearly impossible by viewing only. This approach is flexible
allowing for rapid processing of large numbers of similar data sets and proven to be a
useful image analysis tool that removes the bias of human color perception in
evaluating skin color. This method is also capable of detecting the over- and
undertone color differences in the skin of light and dark individuals.
Commercial support: 100% Sponsored by Johnson & Johnson Consumer
Companies.
AB60
J AM ACAD DERMATOL
MARCH 2010
P1628
P1630
Skin penetration of calcipotriene from a new foam formulation
Jon Lenn, MS, Stiefel Laboratories, Palo Alto, CA, United States; Hans Hofland,
PhD, Stiefel Laboratories, Palo Alto, CA, United States; Kofi Nyam, Stiefel
Laboratories, Palo Alto, CA, United States; Mark Brown, Stiefel Laboratories,
Palo Alto, CA, United States
Bugrane, tetrahydroxypropyl ethylenediamine, and glycerin: Association
of three active ingredients to fight against facial sagging in a placebocontrolled study
Marion Lanctin, Johnson & Johnson Consumer France, Issy-Les-Moulineaux,
France; Alex Nkengne, Johnson & Johnson Consumer France, Issy-LesMoulineaux, Europe, France; Christiane Bertin, Johnson & Johnson Consumer
France, Issy-Les-Moulineaux, France; Romain Roure, Johnson & Johnson
Consumer France, Issy-Les-Moulineaux, France
Calcipotriene (or calcipotriol) a synthetic vitamin D analog for the topical treatment
of psoriasis is marketed in a cream, a solution, and an ointment, although the
ointment has been recently withdrawn from the US market. A new emollient
formulation of calcipotriene has been developed in a foam vehicle which might
improve patient compliance. This study was designed to compare the in vitro skin
penetration of calcipotriene from this foam. The assay uses freshly excised human
abdominal skin from elective surgeries. The subcutaneous fat is removed, and the
skin is dermatomed to a thickness of 0.25mm. The specimen, consisting of stratum
corneum, epidermis, and partial dermis, is mounted in flow-through diffusion cells,
which are temperature controlled to match real use (in vivo) conditions. Skin
distribution of calcipotriene after the foam was applied to the stratum corneum
surface was compared to distribution after application of a marketed cream and
ointment. At 2 and 6hours postapplication, the skin was washed, the stratum
corneum side was tape-stripped twice, and then the epidermis was separated from
the dermis using a heat block at 608C for 30 seconds. Each formulation was tested on
four separate donors (3-4 replicates each; n $ 12). Drug content was measured by
liquid chromatography-mass spectrometry (LC/MS/MS) with a lower limit of
quantitation of 50pg/mL. Calcipotriene foam was found to deliver 2- to 3-fold
more calcipotriene into the epidermis, which is the site of action, compared to the
ointment and cream. Equal amounts of calcipotriene were found in the dermis after
application of the foam, cream, and ointment, suggesting similar nontarget tissue
exposure. These findings suggest that the foam formulation may be more clinically
effective with a similar safety profile to the creams and ointments.
Commercial support: 100% sponsored by Stiefel Laboratories, Inc
In addition to normal skin changes associated with age, facial sagging affects the
overall shape of the face. Facial sagging potentially can decrease self-perception and
reduce the overall physiological quality of life. To reduce the effects of facial sagging,
we recently developed a new combination of bugrane, tetrahydroxypropyl ethylenediamine, and glycerin. The objective of this study was to investigate the efficacy
of a lifting technology to improve facial sagging with special focus on immediate and
lasting effects. A double-blind, randomized placebo-controlled study was performed
on 77 healthy white women ([45 years old). Thirty-nine volunteers applied the
active product and 38 the placebo product, once a day for 8 weeks. Clinical grading
of the aging signs was performed at baseline, immediately following, at 7 hours and 8
weeks after the first application. Ten sagging parameters were assessed by an expert
grader on the face and neck using visual analog scales. In addition, wrinkles and tone
parameters were evaluated. Skin replicas at the crow’s feet area were taken at
baseline and after 8 weeks of application. A paired Student t test was performed
versus baseline and between products with a confidence level of P \.05 considered
significant. Immediately after the first application, a significant improvement in the
lifting parameters, wrinkles/fine lines, and tone parameters was observed with the
active product versus baseline. These improvements were still significant 7 hours
after the first application and after 8 weeks of use. Moreover, the active product was
significantly more efficacious than the placebo in improving some sagging parameters. The analysis of skin replicas showed that the active product was significantly
more efficacious than the placebo after 8 weeks on the total number, total surface,
and total length of the wrinkles. The combination of the active ingredients bugrane,
tetrahydroxypropyl ethylenediamine, and glycerin used in this study were shown to
have an immediate and lasting (ie, 7 hours after application) effect on facial sagging.
Moreover, based on clinical assessment and skin replicas, the active product also
improved wrinkles and fine lines around the eye area.
P1629
Assessment of the effect of a topical treatment on early active stretch
marks in postpartum women: A simple blind, randomized, intraindividual
study
Nadege Lachmann, Laboratoires Expanscience, Epernon, Eure et Loir, France;
Jean Christophe Pittet, Orion Concept, Tours, Indre et Loire, France; Maud
Fischer, Pharmascan, Villeurbanne Cedex, Rhone, France; Philippe Msika, PhD,
Laboratoires Expanscience, Epernon, Eure et Loir, France
Background: Stretch marks are a well recognized, common skin condition that rarely
cause any significant medical problems but are often a significant source of distress
to those affected. The origins of stretch marks are poorly understood, but these
disfiguring lesions are usually caused by excessive stretching of skin, especially
observed during pregnancy.
Objective: We investigated the response of early, clinically active stretch marks
(stage 1 of the Deprez-Adatto classification) to topical application of a cream
specifically formulated to reduce stretch marks. This cream contains patented
ingredients (lupeol, natural biopeptides, and arabinogalactane) that counteract
tissue inflammation and stimulate extracellular matrix (ECM) remodeling.
P1631
Conclusion: These results demonstrate the efficacy of a topical cream on clinical
appearance of early, active stretch marks in postpartum women. We observed a
significant global improvement of the severity of stretch marks after 2 months. The
action of the cream was not limited to stretch marks. The cream proved to be
effective in improving global skin quality.
Determination of posaconazole nail levels in adults with onychomycosis
following oral treatment with four regimens of POS for 12 or 24 weeks
Gopal Krishna, Schering-Plough Research Institute, Kenilworth, NJ, United
States; Amir Tavakkol, Schering-Plough Research Institute, Kenilworth, NJ,
United States; Lei Ma, Schering-Plough Research Institute, Kenilworth, NJ,
United States; Monika Martinho, DMPK, Schering-Plough, Summit, NJ, United
States
This was a randomized, placebo- and active-controlled, parallel-group, multicenter,
investigator-blinded study in adults with onychomycosis of the great toenail.
Approximately 36 subjects were in each of the following groups: POS 100mg,
200mg, or 400mg QD for 24 weeks, 400mg QD for 12 weeks, terbinafine 250mg QD
for 12 weeks, and placebo. Subjects were asked to take the drug with their food.
After completing treatment, all subjects were followed to week 48. Samples from all
10 toenails as well as plasma samples were obtained at each visit. Plasma
pharmacokinetics (PK) and nail PK of POS in terms of time to reach steady state
and duration of persistence of POS in the nail after dosing discontinuation were
determined using a validated LC-MS/MS assay. Consistent with previous experience,
mean POS plasma concentration showed a dose-related increase and was characterized by a virtually flat plasma concentration profile. For the entire treatment
duration, the mean POS plasma concentration for all dose groups remained above
the MIC90 of 250 ng/mL for dermatophytes. In the toenail, POS was detected at the
first sampling time point of 2 weeks for all dose groups; the concentration was close
to the target MIC90 value by week 12. In general, the concentration of POS in the
great toenail exhibited a dose-related increase (100-400mg QD for 24 weeks) and
levels increased even after discontinuation of treatment; whereas, as expected, a
decline was seen in plasma level shortly after discontinuation of the treatment. POS
toenail levels continued to increase and remained substantially higher than the
MIC90 value for dermatophytes for 24 to 36 weeks after discontinuing treatment.
POS showed good toenail penetration with mean concentration ratio (nail to
plasma) of approximately 1 to 5 at the end of treatments. This ratio would be much
higher at week 48 since nail levels continued to increase. These findings demonstrate adequate nail penetration and have implications for treatment of mycotic nail
infections.
Commercial support: Funded by Schering-Plough
Methods: In a simple-blind, randomized, intraindividual comparative study, 16
postpartum women presenting with symmetrical and comparable stretch marks on
each of their thighs (or hips) at baseline applied the cream twice daily on one of their
thighs during 2 months. The other thigh served as the untreated control. Each thigh
was evaluated monthly by clinical examinations and by analysis of skin section of
stretch marks obtained by ultrasound imaging (35MHz) before and at the end of the
study. Viscoelastic properties and skin hydration were also measured at each kinetic
time. Cross-polarized photographs were taken to assess the inflammatory component of stretch marks.
Redults: After 1 and 2 months, we observed significant improvements on treated
stretch marks compared to the control. After 2 months, we observed a decrease in
mean length and width of 10% (P\.01) and 20% (P\.01), respectively, compared to
the untreated stretch marks. We also observed significant improvement on the
global quality of the skin around the stretch marks on the treated area compared to
the control: the relief of the skin and its roughness were significantly decreased,
respectively, by -11% (P ¼.019) and -18% (P ¼.038), the firmness and hydration were
significantly improved after 2 months. Ultrasound images and cross-polarized
photographs confirmed these clinical improvements.
MARCH 2010
J AM ACAD DERMATOL
AB61
P1632
P1634
A novel lipid-rich moisturizing body wash reduces clinical dryness and
improves self-perceived itch
Vickie Foy, MS, Unilever R&D, Trumbull, CT, United States; Amir Ashkenazi, PhD,
Unilever R&D, Trumbull, CT, United States; K. P. Ananthapadmanabhan, PhD,
Unilever R&D, Trumbull, CT, United States; Shuliang Zhang, PhD, Unilever R&D,
Onset of action of botulinum toxin type A in the treatment of glabellar
lines earlier by age and race
Charles Boyd, MD, private practice, Birmingham, MI, United States; Frederick
Beddingfield, MD, Allergan, Irvine, CA, United States; Kenneth Beer, MD, private
practice, West Palm Beach, FL, United States; Steven James, MD, Allergan, Irvine,
CA, United States
The traditional approach to minimize cleanser-induced stratum corneum protein
damage has been the use of a combination of anionic and amphoteric surfactants in a
liquid cleanser. In contrast, the lipid damage potential of liquid cleansers has not
received much emphasis in the past; however, recent research has highlighted the
importance of minimizing both protein and lipid damage potential with cleansing.
This insight led to the development of a new lipid-rich moisturizing body wash
(LRMBW) with fatty acids naturally found in skin and soybean oil as moisturizers. In
vitro, the LRMBW showed a low potential for both lipid and protein damage.
Background: Therapeutic benefit of botulinum toxin type A (BoNT-A) in the
treatment of glabellar lines has been shown in well controlled studies to have a
low rate of adverse events, a high treatment response rate, and a long duration of
effect. However, these studies did not assess onset of action, because the first followup visit did not occur until day 7. The current study investigated the physician- and
subject-evaluated onset of effect and subject satisfaction during the first 14 days
posttreatment.
In standard patch tests, the LRMBW showed significantly lower irritation compared
to typical anionic-amphoteric surfactant containing cleansers as well as to an
identical formulation with petrolatum as the moisturizer. Similarly, in-vivo clinical
studies under normal use conditions showed significant improvements in skin
hydration and dryness and provided perceivable appearance benefits, demonstrating that the LRMBW technology provided protection to both skin proteins and lipids
leading to healthy, hydrated skin. It was therefore of interest to investigate the effects
of the LRMBW in subjects with a compromised skin barrier, as the protection
benefits to both protein and lipids suggests the LRMBW may be relevant for this
group. Thirty female subjects 25 to 65 years years of age with a moderate degree of
visual dryness (as assessed by an expert clinical evaluator) and a moderate degree of
self-perceived itch provided informed consent to participate in this IRB-approved 4week home-use cleansing study, where subjects replaced their normal cleanser with
the cleanser provided. Expert clinical evaluation and self-perception assessments
were obtained at baseline and weeks 2 and 4. During this time, subjects refrained
from applying moisturizers to their legs. Visual dryness and self-perceived itch on
legs showed a significant improvement from baseline condition at all evaluation time
points. Together with our previous research, these results demonstrate that the
LRMBW technology provides skin condition benefits in both normal and barriercompromised skin.
Study design: In a multicenter, open-label, single-group, 14-day study, female, toxinna€ive subjects with moderate or severe glabellar lines at expression received 20 U
BoNT-A (Allergan) (4 U [0.1mL] at each of 5 sites). At days 2, 3, 4, 7, and 14,
physicians rated treatment effect (yes/no), and subjects completed a facial lines
outcome (FLO) and subject’s perception of age (SPA) treatment satisfaction
questionnaire. Subjects also completed a 14-day diary rating treatment effect
(yes/no) and whether an improvement or worsening. Physicians assessed adverse
events at follow-up visits.
Results: Of 45 subjects who enrolled, all completed the study (23 # 43.5 and 22 [
43.5 years old; 20 white and 25 nonwhites). Descriptively, younger or white subjects
reported earlier onset than older or nonwhite subjects. Reports of onset: day 1: half
of younger subjects (50%) versus 46% of older subjects; majority of white subjects
(58%) versus 40% of nonwhties; day 4L 100% of younger or white subjects; day 5:
100% of older or nonwhite subjects. Physician evaluations reflected similar onset
trends, as did FLO and SPA scores, which improved significantly (P # .008 and P #
.01, respectively) at every time point. No serious adverse events were reported. Two
subjects reported mild, transient headache.
Conclusions: This study shows a rapid onset of BoNT-A (Allergan) local effect as
nearly half of subjects noted onset and improved appearance on the 1st day after
treatment. Early onset was confirmed by physician evaluation and significant
treatment satisfaction. Onset was descriptively earlier in younger or white subjects
than in older or nonwhites.
Commercial support: This study was sponsored by Allergan.
P1635
P1633
Conclusions: The observed improvement of corneocyte maturity biomarkers
suggests that use of the cosmetic moisturizer containing known barrier enhancing
cosmetic ingredients promotes a more mature SC. This SC contains larger, more
hydrophobic corneocytes at the surface, providing greater tortuosity and better
covalent bonding of SC intercellular lipids to protect the skin and prevent water loss.
The use of hyaluronic acid in the treatment of moderate to severe
nasolabial folds: Results from an open-label extension trial
Rhoda Narins, MD, Dermatology Surgery & Laser Center, New York, NY, United
States; Corey Maas, MD, The Maas Clinic, San Francisco, CA, United States; Derek
Jones, MD, Skin Care & Laser Physicians of Beverly Hills, Los Angeles, CA, United
States; Gary Monheit, MD, Total Skin & Beauty Dermatology Center, Birmingham,
AL, United States; William Coleman III, MD, Tulane Unveristy Health Sciences
Center, New Orelans, LA, United States
Background: Dermal fillers are used to augment wrinkles and folds and a variety of
hyaluronic acid (HA)ebased products are available. The HA in this trial was a
noneanimal sourced HA-based filler cross-linked in two consecutive steps and used
a cohesive polydensified matrix technology that contains a monophasic gel with
variable density (viscosity) zones for adaptation in the dermis (Merz).
Objective: To determine the safety and effectiveness of HA for the treatment of NLF
over 96 weeks.
Methods: This report represents the optional OLEX of a double-blind (DB) trial in
which subjects had previously received HA in one NLF and collagen (COL; Allergan)
contralaterally. Results of the DB phase of the study are reported elsewhere. Subjects
were assessed at 24, 32, 48, 72, and 96 weeks after the last treatment in the DB phase
of the study. All subjects received injections into both NLF at week 24 with HA.
Touch-up treatments could be given at weeks 32, 48, 72, and 96 in both NLF, if WSRS
¼ 2 or 3. The severity of the NLF was measured using the Wrinkle Severity Rating
Scale (WSRS). Safety was assessed via adverse events (AEs).
Results: One hundred eighteen predominately white (97%) and female (92%)
subjects (mean age, 52 years) were enrolled in the DB trial. Ninety-five of 118
continued to the OLEX. At week 24, the mean volume was 0.71 and 1.04mL on the
sides previously injected with HA and COL, respectively. At week 32, eight subjects
received touch-up injections on the HA side (0.46mL) compared with 37 on the COL
side (0.73mL). The majority of subjects were reinjected at weeks 48 and 96. At week
24, the mean WSRS was ;2.5 on both sides. At all four timepoints, the severity of the
NLF showed a decrease from week 24 on both sides; however, the mean change was
greater on the side of the face that had been previously injected with HA than on the
contralateral side injected with COL. At every timepoint, more than 68% of the
subjects were assessed as having an improvement of at least 1 point on both sides of
the face. The mean change at week 96 was 1.13 on the side initially randomized to
HA and -0.96 on the side initially randomized to COL. All but two of the AEs,
injection site erythema and injection site bruising, were unrelated to study device
and most AEs were mild to moderate in severity.
Conclusions: HA is well tolerated and effective in the correction of moderate to
severe NLF when repeat injections are given over a 96-week period.
Commercial support: Procter & Gamble Beauty.
Commercial support: 100% sponsored by Merz Pharmaceuticals.
Use of a cosmetic moisturizer promotes corneocyte maturity
Bradley Jarrold, MS, Procter & Gamble Beauty, Cincinnati, OH, United States; Joe
Kaczvinsky, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States; Paul
Matts, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States; Rosemarie
Osborne, PhD, Procter & Gamble Beauty, Cincinnati, OH, United States; Shannon
Weitz, Procter & Gamble Beauty, Cincinnati, OH, United States
Background: The skin forms an effective barrier preventing invasion of pathogens,
fending off chemical and physical assaults and the loss of water. These barrier
functions are localized to the stratum corneum (SC), a two-component system of
corneocytes embedded in a lipid matrix. Corneocytes consist of a stabilized array of
keratin filaments contained within a covalently cross-linked cornified envelope.
Fully mature corneocytes located in the outer SC layers, are characterized by being
relatively large, very hydrophobic and highly cross-linked when compared to
immature corneocytes of deeper SC layers. Immature corneocytes in the outer SC
have been associated with poor barrier function.
Objective: In the current study we examined how a cosmetic moisturizer known to
improve skin barrier function affects biomarkers of cornoecyte maturity such as
size, hydrophobicity, and degree of cross-linking.
Method: Twenty female subjects (40-60 years of age) applied the test cosmetic
moisturizer containing known barrier enhancing cosmetic ingredients, including
niacinamide, hexamidine, and Pal-KT, to one side of their face twice daily for 4
weeks, with the other side serving as a nontreated control. D-Squame tapes were
collected at baseline and 4 weeks from an area just below the outside corner of the
eye on both the treated and nontreated sides. Corneocyte maturity was assessed
using a modification of the method of Hirao et al. Briefly, corneocytes were
extracted from the first tape and double stained with nile red and an antiinvolucrin
antibody to evaluate the degree of hydrophobicity and envelope cross-linking.
Corneocyte size (m2) and staining intensity were measured microscopically using
Image-Pro Plus.
Results: Compared to control, there was a significant 18% (P ¼.002) increase in the
percentage of nile red staining fully mature corneocytes as a proportion of the total
population of corneocytes. Concurrent with the higher number of mature corneocytes, there was also a significant 20% (P ¼.05) increase in the size of mature
corneocytes compared to control samples.
AB62
J AM ACAD DERMATOL
MARCH 2010
P1636
P1638
Beauty perception: A scientific evaluation of the importance of the eye
area across populations
Gabriela Oana Cula, PhD, Johnson & Johnson Consumer Companies, Skillman,
NJ, United States; Jared Fantasia, MS, Johnson & Johnson Consumer Companies,
Skillman, NJ, United States; Nikiforos Kollias, PhD, Johnson & Johnson Consumer
Companies, Skillman, NJ, United States; Theresa Chen, PhD, Johnson & Johnson
Consumer Companies, Skillman, NJ, United States
Eye movements are windows to human cognition. Traditionally, observations and
questionnaires are used to understand the beauty perception and treatment
performance from the clinician’s and subjects’ points of view. But those methods
fail to provide definitively what people notice and what they do not. Eye tracking
technology is a new and more precise way to determine what people really look at
when asked to perform a task such as evaluating the facial beauty of another person.
This study was conducted to explore the cognitive process involved when assessing
the facial beauty of different ethnicities, by means of eye tracking technology. The
attention given to different parts of the eyes, as a function of the ethnicities of the
observer and the stimulus (the observed), is quantified by measuring the eye
movements of observers visually stimulated by faces. Female panelists of three
different ethnicities: African American (n ¼ 48), Asian Indian (n ¼ 47), and white
(n ¼ 46), ages 25 to 70, were visually exposed to female faces of four different
ethnicities: African American, Asian Indian, white, and Northern Asian. For each of
the four ethnicities, we showed as stimuli three faces of different ages. Each of the
panelists was asked to assess the beauty of the faces shown on the screen, while the
eye tracker recorded the eye movements of the observers. The eye tracker reported
the length of the fixations detected within specific areas of interest on the face and
around the eyes. The results show that when an observer is asked to assess the facial
beauty of a person in an image, the main attention is on the eye area, independent of
the ethnicity of the observers and the observed. The attentions given to elements
within the eye area, on the other hand, show distinct ethnicity-dependent patterns.
The study results objectively demonstrate that the eye area is the most important
when assessing facial beauty.
Clinical improvements in facial photoaging with topical application of a
biomimetic mineral complex and naturals extract formulation
Dara Miller, Johnson & Johnson Consumer Companies, Skillman, NJ, United
States; Warren Wallo, MS, Johnson & Johnson Consumer Companies, Skillman,
NJ, United States; Yohini Appa, PhD, Johnson & Johnson Consumer Companies,
Commercial support: 100% sponsored by Johnson & Johnson Consumer
Companies.
Improving the signs of facial photoaging continues to be a primary dermatologic
concern for many patients, including reducing the appearance of lines and wrinkles,
improving skin texture, and evening pigmentation. An additional challenge is that
many patients wish to achieve these visible results but still desire products that are
mild to the skin and can be well tolerated with everyday, continued use. Natural
ingredients are increasingly being recognized for their skincare benefits as they
continue to be shown to have various in vitro and in vivo activities. Preclinical and
initial clinical data have shown the potential of a bimineral complex consisting of a
proprietary blend of elemental zinc and copper that generates biomimetic signals
for improving photoaging, and in vitro data has also suggested the antiaging benefits
of a combination of dill and blackberry leaf extract. A clinical study was performed
using a regimen of a bimineral complex gel and a dilleblackberry leaf extract lotion
with SPF 30 to evaluate its ability to rapidly improve multiple signs of facial
photoaging, while being mild to the skin. Thirty healthy female subjects between 30
and 55 years of age with moderate facial photoaging and who exhibited mottled
hyperpigmentation, skin roughness, laxity, and fine wrinkling completed this 4week study. Patients applied the two-product system once per day in the morning.
Clinical evaluations, self-assessments, and instrumental analysis demonstrated this
two-product regimen’s multiple skin benefits throughout the study. Clinical evaluations indicated significant improvements (P\.05) in facial skin clarity, smoothness,
and overall photoaging after 2 weeks of use. Significant improvements (P \.05) in
the appearance of mottled hyperpigmentation, firmness, and fine wrinkling were
observed by the 4-week time point. Patients also perceived significant (P \ .05)
improvements in skin tone, brightness, and textural parameters as early as after 2
weeks of use. Digital photographs also confirmed improvements in various overall
photoaging parameters. In conclusion, this clinical study demonstrated that a
regimen of a bimineral complex gel and a dilleblackberry leaf extract lotion with
SPF 30 was effective in improving the overall signs of facial photodamage, including
improvements in fine lines and wrinkles, tone, pigmentation, and texture, while
being mild and gentle to the skin.
Commercial support: 100% is sponsored by Johnson & Johnson Consumer
Companies.
P1637
Improvements in skin elasticity and cohesion from a petrolatum depositing bodywash
Susan Biehle, PhD, Procter & Gamble, Cincinnati, OH, United States; Amanda
Newman, Procter & Gamble, Cincinnati, OH, United States; Karl Wei, PhD,
Procter & Gamble, Cincinnati, OH, United States; Rolanda Johnson, PhD, Procter
& Gamble, Cincinnati, OH, United States
Background: Aging skin is frequently characterized by an increase in dryness and
subsequent flaking, as well as a general loss of elasticity. Daily activities such as
bathing can exacerbate some of these issues, particularly if skin drying products
such as soap are used. While moisturizing bodywashes are readily available in the
market, few purport to make improvements in skin condition beyond skin dryness.
Objective: In an effort to improve the overall condition, health, and viability of aging
skin, we have developed a petrolatum depositing bodywash that is aesthetically
pleasing to use and will deliver benefits beyond typical moisturization.
Method: Standard Leg Controlled-Application Test (LCAT) methodology was used.
Treatment was conducted over a 3-week period; women with dry leg skin had their
legs washed once daily with the randomly assigned body wash products and water
alone treatment as control (;50 per treatment). Typical moisturization measures
were taken, including expert dryness grading, corneometer, and TEWL. Elasticity
was measured using the cutometer. Furthermore, tape-strip analysis of biomarkers
was also conducted to gain insight into how our product affected the skin health and
integrity. Six successive D-Squame tapes were taken from virgin areas within each
treatment site at baseline and at the end of each treatment week. The strips were
then analyzed for total protein with a SquameScan 850 as a measure of stratum
corneum cohesiveness.
Results: The results indicate that the body wash delivers significant improvements in
all standard moisturization measures (dryness grades, corneometer hydration, and
TEWL), consistent with historical data. For the first time in the rinse-off context, the
results show significant improvement in skin elasticity as compared to the water
treatment control. The total protein results further reveal significant improvement
in stratum corneum cohesiveness. Taken together, these findings support the
conclusion that the petrolatum depositing bodywash improves the overall condition
of skin.
Commercial support: 100% sponsored by Procter & Gamble.
DIGITAL/ELECTRONIC TECHNOLOGY
P1700
More and better vessels: Optimal image processor conversions, layers, and
filters for vessel dermoscopy
Fernando Alfageme, Hospital Gregorio Marañon, Madrid, Spain; Cristina Ciudad,
Hospital Gregorio Marañon, Madrid, Spain; Jose Antonio Aviles, Hospital
Gregorio Marañon, Madrid, Spain; Pablo Lazaro, Hospital Gregorio Marañon,
Madrid, Spain
Vessel dermoscopy is day by day increasing in relevance in the diagnosis of
pigmented and nonpigmented lesions. On occasion, analysis of the shape and
distribution of vessels is the only way to diagnose amelanotic melanoma. Image
processing with professional or nonprofessional software is an available and useful
tool in working and everyday life. The application of filters, conversion to black and
white, and multiple layers are options available in most of these software applications; these allow the enhancement of certain elements with respect to others. The
ideal settings to outstand certain elements, such as vessels in dermoscopy, could be
of interest when studying a problematic lesion. We used Adobe Photoshop 6.0 as
image processor and tried to determine easy steps and reproducible combination for
most sensitive and optimal vessel visualization. We achieved better vessel visualization and definition through two different methods: conversion to RGB channel
and focus masks. We present some examples applied to the imporvement of vessel
visualization in malignant skin tumors both melanotic and nonmelanotic.
MARCH 2010
J AM ACAD DERMATOL
AB63
P1701
P1703
Digital measurement of melasma: Towards eliminating subjectivity from
treatment evaluation
Thaı́s Harumi Sakuma, MD, Federal University of the State of Rio de Janeiro HUGG - Unirio, Rio de Janeiro, Brazil; Bernard Kawa Kac, MD, Santa Casa da
Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil; Luna Azulay-Abulafia, MD,
PhD, Santa Casa da Misericórdia do Rio de Janeiro, University of the State of Rio
de Janeiro, Rio de Janeiro, Brazil; Ram Rajagopal, PhD, University of California,
Berkeley, CA, United States
Introduction: The most commonly used scoring system for the evaluation of
melasma treatment outcomes is the Melasma Area and Severity Index (MASI). Scores
are computed live by a doctor using a subjective scale that depends on affected area,
darkness, and homogeneity. Routine photographic procedures are not adequate to
capture the disease.
The evaluation of online tools in the recruitment of dermatology patients
for a research study
Venessa Pena-Robichaux, Partners Center for Connected Health, Massachusetts
General Hospital, Dermatology Department, Harvard Medical School, Boston,
MA, United States; Alice J. Watson, MPH, MBChB, Partners Center for Connected
Health, Massachusetts General Hospital, Dermatology Department, Harvard
Medical School, Boston, MA, United States; Joseph C. Kvedar, MD, Partners
Center for Connected Health, Massachusetts General Hospital, Dermatology
Department, Harvard Medical School, Boston, MA, United States
Objective: Digital measurement of melasma has considerable challenges: the skin
has strong reflective properties, the color of the disease differs depending on the
patient’s skin color, the disease commits the face, that is not in a plane. We describe a
system and method towards automatic measurement, addressing the first two
issues.
Method: To overcome skin reflectivity, we designed a digital imaging setup that uses
cross-polarization by incorporating polarizing filters in perpendicular directions in
the lighting and in the camera lens. The face of a patient is photographed in five
different positions: full frontal and 458 and 908 to the left and to the right. Next, a
computer-based treatment of the color image is performed. The method uses the
images as an input and requires two further calibration inputs from the user: a
selection of a small patch of affected and nonaffected area. For each full image, a
simple lighting compensation is performed and skin patches are identified using a
pixel filter. The user then selects an area for automatic evaluation. The method first
determines if each pixel is classified as melasma or not. The calibration patches are
used for this purpose together with a hidden Markov model based local threshold.
The percentage of pixels classified as disease is the affected area ratio. The disease
intensity is then calculated by subtracting the blue and green channels of affected
pixels from the average of the nonaffected pixels. Homogeneity is given by the
standard deviation of the affected pixels.
Results: We performed a preliminary validation of the method by manually
identifying disease areas for a single patient. The algorithm correctly detected
92% of the affected area and incorrectly detected 5% of the unaffected area as being
affected.
Conclusion: A fully automatic procedure requires incorporating more steps:
correlating the various patient views into a single patient face model, and
automatically detecting facial features. We also leave as future work evaluating the
procedure in a larger set of patients.
Traditionally, research subject recruiting has been done mainly through the use of
print media and the utilization of hospital resources. Our reliance on newspapers as
a source of subject recruitment is becoming a problem because of shrinking
readership over the last few years. We present here a preliminary analysis of the
utility of online tools in the recruitment of dermatology patients for a research study.
Advertisements for a research study recruiting adolescents and adults with atopic
dermatitis were placed in local print media sources (2 newspapers, 2 magazines),
flyers (posted at coffee shops, hospitals, and universities), and online media sources
(hospital website, Facebook [FB], Craigslist, Google Ad Words [GAW]). For each
mode of advertisement used, we collected: total cost of the ad, number of study
inquiries generated by the ad, and number of subjects enrolled as a result of the ad.
From these data, the cost per study inquiry and cost per subject enrollment were
calculated. In addition, qualitative observations were made with regard to the userfriendliness of the online applications and their potential to reach a targeted
population. Ads posted using online sources resulted in the greatest number of study
inquires and subjects enrolled (27 inquires, 16 enrolled), followed by flyers (10
inquires, 9 enrolled), and print media (5 inquires, 4 enrolled). The total cost per
inquiry and cost per enrollment were least expensive for flyers ($6.50 and $7.22,
respectively), followed by online media sources ($13.66, $23.05), and finally print
media ($312, $390). All online media sources used were found to be user-friendly
except for GAW, which required more effort to navigate. All online sources were
capable of targeting subjects within a general geographic region; however, FB was
the only application that was shown to target subjects based on specific demographics. In addition, ads on FB were easiest to view, because these ads appeared
near the profile of those being targeted by the ad and, unlike all other online media
sources used, did not require any actions (such as click-through) by users to view the
advertisement. These findings suggest that the use of online media sources to
advertise for research studies has great potential for recruitment and is cost
effective. While traditional paper flyers were the most cost effective mode of
recruitment in this study, as more people continue to favor the Internet over print
media online advertising may become the primary source used for research subject
recruitment. This is especially true for research studies targeting younger patient
populations, who are heavy users of communications technology.
P1702
The ProScope HR: A promising diagnostic tool
Adriana N. Schmidt, MD, Vanderbilt University Medical Center, Nashville, TN,
United States; Brent R. Taylor, MD, Vanderbilt University Medical Center,
Nashville, TN, United States; Lloyd E. King, MD, PhD, Vanderbilt University
Medical Center, Nashville, TN, United States; Stephen M. Tourjee, Vanderbilt
University Medical Center, Nashville, TN, United States
Background: Dermoscopy is increasingly being used to study hair loss and scalp
disorders. Several consistent findings have been described for alopecia areata and
androgenetic alopecia. In alopecia areata, these include yellow peripilar dots and
dystrophic and short, regrowing miniaturized hairs. In androgenetic alopecia, these
include brown peripilar dots and miniaturized hairs. Unlike currently used types of
dermoscopes, the ProScope HR (Bodelin Technologies, Lake Oswego, OR) has not
yet been used in dermatology practices but is widely used in science classrooms and
forensics. This handheld digital microscopic device connects to Windows-operated
or Apple computers via a USB cable to capture and save realtime digital images as
stills or videos. None of the ProScope HR lens options (0-103, 303, 503, 1003,
2003, 4003, and 10003 nonpolarized or 303 polarized) use immersion oil.
Methods: In the Vanderbilt Dermatology Hair Clinic, we used the ProScope HR to
photograph the scalps of 10 female patients with alopecia areata and 10 female
patients with androgenetic alopecia using the 303, 303 polarized, 503, and 1003
lenses. In alopecia areata, we found: (1) yellow dots (follicular hyperkeratototic
plugs); (2) black dots (cadaverized hairs—hairs broken below the follicular os); (3)
broken hairs (broken beyond the follicular os); (4) dystrophic hairs; (5) tapering
hairs (exclamation hairs); and (6) miniaturized hairs. These findings were seen at all
lens magnifications. The polarizing lens allowed for better visualization of dystrophic hairs beneath the follicular os and the vasculature. In androgenetic alopecia, we
found: (1) brown peripilar casts and (2) miniaturized hairs. The polarizing lens again
allowed for better visualization of the dermal vessels.
P1704
Importance of vascular patterns in the dermoscopy recognition of cutaneous tumors
Luis Dehesa, MD, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas
de Gran Canaria, Las Palmas, Spain; Gregorio Carretero, MD, PhD, Hospital
Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Las
Palmas, Spain; Jaime Vilar, MD, Hospital Universitario de Gran Canaria Dr. Negrin,
Las Palmas de Gran Canaria, Las Palmas, Spain; Nestor Santana, MD, Hospital
Palmas, Spain
Conclusions: The ProScope HR is easy to use, does not need immersion oil, uses low,
high power and polarizing lenses, and is affordable. Using the nonpolarizing lenses
and 303 polarizing lenses, the image quality is equivalent to that seen when using
other dermoscopes to examine alopecia areata and androgenetic alopecia. The
ProScope HR warrants further study as a type of dermoscope to evaluate hair loss,
scalp, and other skin conditions.
Dermoscopy is a diagnostic technique that is used worldwide in the identification
and diagnosis of numerous skin lesions. We present our experience on the use of
dermoscopy for the recognition of cutaneous tumors. We also highlight the
importance of the vascular pattern to distinguish between malignant and benign
tumors. You can see a selection of our most interesting cases in which the vascular
pattern suggests the diagnosis. Examples of comma vessels in dermal nevus, linear
dotted vessels in clear cell acanthomas, thick and branching blood vessels in basal
cell carcinomas, hairpin-shaped vessels in keratoacanthomas and irregular linear
vessels in malignant melanoma have been shown.
AB64
J AM ACAD DERMATOL
MARCH 2010
P1705
P1801
Use of in vivo confocal microscopy in the evaluation of a whitening agent
on pigmented skin lesions
Gopinathan Menon, MD, PhD, ISP Corporate Research Center, Wayne, NJ, United
States; Claude Dal Farra, PhD, ISP Corporate Research Center, Wayne, NJ, United
States; Gilles Oberto, MBA, Vincience ISP Global Skin Research Center, Sophia
Antipolis, Alpes Maritimes, France; Nouha Domloge, MD, Vincience ISP Global
Skin Research Center, Sophia Antipolis, Alpes Maritimes, France; Yolène Guerif,
MBA, Vincience ISP Global Skin Research Center, Sophia Antipolis, Alpes
Maritimes, France
Impact of sun safety education and skin cancer screening campaign on
attendees of national sporting events
Adam Perry, Emory, Atlanta, GA, United States; Cindy Bae, Boston University
School of Medicine, Boston, MA, United States; Lisa Nguyen, Boston University
School of Medicine, Boston, MA, United States
Through aging and skin color changes, the melanin repartition is less homogenous
and some age spots can appear. In this focus, we used an in vivo confocal microsopy
to evaluate the effect of a whitening agent on skin pigmentation. A 3-month study
was conducted on five volunteers. They applied the cream during 1 month on the
forearm. Two age spots were selected for the two zones (treated and untreated) to
be sure to evaluated the same lesion at each control visit. The change in melanin
content was appreciated by Mexameter, pictures, and in vivo confocal microscopy
(VivaScope) assessment and clinical examination; at the following times: D0, D28,
D59, and D89 (24hours and 1 and 2 months after the last application, respectively).
Already, at D28 we observed a decrease in melanin index on 70% of the pigmented
lesions, for the treated side, compared to the untreated side. This difference is
statistically significant (P ¼.03725). This decrease continued 1 month after the last
application (P ¼.03725) and the whitening effect remained 2 months after the end
of the application. In vivo confocal microscopy at D0, D28, D59, and D89 allowed
comparison of the melanin content in the basal layer for the untreated and
whitening- compound treated side at each time. For the treated side, we noticed a
decrease in melanin at D28, D59, and D89 compared to D0; whereas it was not the
case for the untreated zone. However the decrease in melanin was less important at
D89 than at the others times in accordance with the melanin index. These
observations were confirmed by the clinical exam and the volunteers’ evaluation.
All these results confirm the interest in using in vivo confocal microscopy in the
evaluation of skin pigmentation and whitening and tanning agents.
Objective: Spectators at outdoor sporting events are a little studied population at
risk of developing skin cancer. Our study examines sun protection methods and the
impact of sun damage assessments in this population.
Methods: Subjects were recruited from two golf tournaments on the Ladies
Professional Golf Association (LPGA) tour. They were given a short survey that
included questions about basic demographic information, perceived skin cancer
risk, and sun protection use, such as sunscreen use, hat use, and wearing a shirt with
sleeves that cover the shoulders. Each sun protection behavior was assessed using
an ordinal scale ranging from 1 (never or rarely) to 4 (always). Perceived skin cancer
risk was similarly assessed using an ordinal scale ranging from 1 (very low or low) to
4 (very high). Following the initial survey, all the participants underwent evaluation
with an ultraviolet reflectance unit. Once the subjects were aware of their
preexisting photodamage, they were asked to reanswer the same questions
regarding sun protection usage and perceived skin cancer risk.
Results: A total of 407 subjects were recruited for the study. They were primarily
middle-aged, white women. At baseline, the most popular method of sun protection
was wearing a shirt with sleeves that cover the shoulders. Wearing a hat was the least
popular method of sun protection. Following the intervention, the frequency of
intent to use sunscreen showed the greatest absolute increase of 0.808 (P \.0001).
The frequency of hat use increased by 0.553 (P \.0001). However, the frequency of
wearing a shirt with sleeves only increased by 0.293 (P \.0001). The perceived risk
of skin cancer was fairly stable. It only increased by 0.246 (P \.0001) after the
intervention.
Conclusion: Our subjects used inadequate sun protection at baseline according to
the US Department of Health and Human Service’s goal that at least 75% of adults will
use at least 1 method of sun protection by 2010. However, the intervention
effectively increased the level of intent to use sun protection by the subjects to a
level above that set by the HHS. Interestingly, the intervention had little effect on the
subject’s perceived risk of skin cancer. This low increase in perceived risk may be
related to the intention to increase levels of sun protection following the
intervention.
EDUCATION AND COMMUNITY SERVICE
P1802
Trends in types of dermatology books available over the last 10 years
Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Los Angeles,
CA, United States; Lisa Aquino, MD, Kaiser Permanente Los Angeles Medical
Center, Los Angeles, CA, United States
In recent years, a shift in interest toward cosmetic dermatology and surgical
dermatology and a shift away from medical dermatology has been observed. We
hypothesized that this trend would be reflected in the types of dermatology books
available for purchase that were published from between 1998 and 2008. Sentry
Surgical Supply, a Website providing access to more than 30,000 medical textbooks,
was searched for all dermatology publications. From the initial search, 591 one titles
were retrieved. Nonbook publications, books published before 1998, books not yet
published, and nondermatology books were excluded from the data set. After these
publications were excluded, 469 books remained. These were categorized into
medical, surgical, dermatopathology, pediatric, or cosmetic books. Basic science
books and books that were general in nature or covered many aspects of
dermatology were placed in the medical dermatology category. The
ManteleHaenszel chi-square test, which evaluates trend over time, was used to
analyze the association between category of book and year. The percentage of
medical books appears to be decreasing over time (1998: 82.4% to 2008: 50.0%; P \
.05). However, the percentage of surgical and cosmetic books appears to be
increasing over time (surgical [1998: 0% to 2008: 10.9%; P \.01]; cosmetic [1998:
11.8% to 2008: 32.6%; P \.05]). The ManteleHaenszel chi-square test confirmed
these trends. Counts were small for pediatrics and dermatopathology books, and no
obvious trends were seen. A limitation to our study is that only books currently
available through Sentry Surgical Supply could be analyzed. Therefore our numbers
do not necessarily reflect books published each year. Another limitation is that only
one medical textbook supplier was used in analysis. However, four other Websites
selling medical textbooks were reviewed, and the authors felt that Sentry Surgical
Supply had the widest selection of dermatology textbooks. Our study demonstrates
that the trend toward decreased interest in medical dermatology and increased
interest in surgical and cosmetic dermatology is reflected in the dermatology books
available through a major medical textbook supplier.
A national survey to determine an optimal fourth-year curriculum for
dermatology candidates
Ali Alikhan, MD, University of California Davis School of Medicine, Department
of Dermatology, Sacramento, CA, United States; April Armstrong, MD, University
of California Davis School of Medicine, Department of Dermatology, Sacramento,
CA, United States; Lynda Ledo, University of California Davis School of Medicine,
Department of Dermatology, Sacramento, CA, United States
Background: Application into dermatology programs is becoming increasingly
competitive, and senior medical students interested in dermatology frequently
inquire how to best structure their fourth-year curriculum.
Objective: To survey program directors (PDs) and chairs of US dermatology
programs as a primary step in determining an appropriate fourth-year framework
for students interested in dermatology, as well as the importance and number of
dermatology rotations away from their home institutions.
Methods: We e-mailed surveys to PDs and/or chairs from 106 US dermatology
programs, excluding military and overseas programs, and asked about the importance of away dermatology electives, how many such electives the students should
complete, and what nondermatology electives would be important to complete
during the senior year of medical school.
Results: Representatives from 67 programs responded. Twenty-eight respondents
(41%) considered away dermatology electives to be essential, and 11 who did not
consider away dermatology electives ‘‘essential’’ stated that they were still ‘‘important’’ in helping students match, especially if they had a particular location or
program in mind. Those who believed away dermatology electives essential for a
successful match reported a mean of 2.0 electives per student. Infectious disease,
internal medicine, rheumatology, pediatrics, and allergy were considered the three
most important nondermatology electives.
Conclusions: Our results revealed that most PDs and chairs did not find away
dermatology electives to be essential, and most of those who did felt one or two
were enough. Furthermore, the nondermatology electives most frequently chosen
seemed to overlap with dermatology, while still providing applicants a well rounded
medical education. In advising dermatology candidates, it may be important to
emphasize a diverse and well balanced curriculum, rather than ‘‘serial auditions,’’
which characterize the phenomenon known as ‘‘preresidency syndrome.’’
P1800
MARCH 2010
J AM ACAD DERMATOL
AB65
P1803
P1805
Comparison of sunscreen availability in Chicago area Hispanic and nonHispanic neighborhoods
Jesleen Ahuwalia, MD, University of Illinois at Chicago, Chicago, IL, United
States; Claudia Hernandez, MD, University of Illinois at Chicago, Chicago, IL,
United States; June Robinson, MD, Northwestern University, Chicago, IL, United
States; Robin Mermelstein, PhD, University of Illinois at Chicago, Chicago, IL,
United States
The incidence of melanoma is increasing faster than any other cancer in the United
States. Hispanic patients have been found to have poorer survival rates and greater
risk of functional impairment than their white counterparts. Potential reasons for
this growing health disparity are lack of knowledge regarding sun protection and
self-skin examination behaviors among Hispanics. The goal of this study was to
investigate a potential environmental influence on this disparity in terms of the
availability and promotion of sunscreen. Our hypothesis is that Hispanic neighborhoods have reduced availability of sun protection products versus predominately
white communities. Three noncontiguous Chicago neighborhoods were chosen for
inclusion based on similar median income, square mileage, and self-reported
ethnicity data from the 2000 US census. Pilsen, a predominately Hispanic neighborhood; Edgewater, a predominately white neighborhood; and Rogers Park, a
multiethnic neighborhood, were selected. To assess sunscreen availability, establishments that sold skin care products in each community were physically canvassed
during peak summer season. Pairs of trained surveyors determined whether
sunscreen was available, counted product varieties, sun protection factor range,
and measured shelf space allotted to sunscreens. Clear differences were found
between the number of stores carrying sun protection products between the three
neighborhoods. Approximately 30.77% of the stores in Pilsen carried sunscreen
versus 61.29% in Edgewater. On initial inspection, 30.95% of Rogers Park retail
stores carried sunscreen. However, when this multiethnic neighborhood was
divided into two adjacent sections, the predominately Hispanic area had only
13.33% of retail stores stocking sunscreen products versus 42.31% in the nonHispanic area. Differences in the variety of sunscreen products available in each area
were also noted. Retail ‘‘chain’’ Edgewater stores offered a greater variety of
sunscreen products (41.27 types) versus the non-‘‘chain’’ retail stores (5 types). In
contrast, there was a much smaller difference between the varieties of sunscreen
products available in chain stores versus nonchain stores (4.25 vs 3.75 types,
respectively) in Pilsen. Culturally and language appropriate in store product
promotion, such as displays, hang tags, and shelf advertisements, were not present
in Hispanic neighborhood retail stores. Our research shows the lack of availability of
sunscreen in Hispanic communities. In addition, visual reminders to purchase
sunscreen to customers were absent in retail stores serving the Hispanic community. These two important environmental deficiencies may contribute to a lack of
awareness of use of sun protection among Hispanics.
Educational needs assessment in psoriasis: Perspective from dermatologists, nurses, and patients
Martin Dupuis, Axdev Group, Brossard, Quebec, Canada; Gratton David, MD,
Montreal General Hospital, Montreal, Quebec, Canada; Karine Boulianne, Abbott
Laboratories, Saint-Laurent, Quebec, Canada
The purpose of this study was (1) to determine clinical care gaps and educational
needs of Canadian dermatologists and nurses specialized in dermatology and (2) to
assess the experience of patients diagnosed with/receiving care for psoriasis to
provide a broader perspective of healthcare professionals’ needs in this therapeutic
area. An IRB-reviewed mixed-method approach was employed. In phase one
(qualitative exploratory data collection), one discussion group with dermatologists
(n ¼ 6), five telephone interviews with nurses specialized in dermatology, and seven
telephone interviews with patients diagnosed with psoriasis were conducted. In
phase two (quantitative validation data collection), 50 dermatologists and 14 nurses
specialized in dermatology completed an online survey to validate the qualitative
findings. The total sample for this study was 82 participants. Purposive sampling was
used based on demographic criteria, level of specialization, and practice profile.
Findings revealed suboptimal collaboration and lack of clarity on the roles and
responsibilities of primary care physicians, dermatologists, and nurses caring for
patients with psoriasis. Dermatologists also reported lacking knowledge of how and
when to use biologic therapy and indicated concerns of potential negative long-term
effects. Furthermore, dermatologists and nurses reported being challenged to
objectively monitor response to therapy. They are sceptical about and lack training
in use of existing monitoring tools. Dermatologists and nurses also indicated
difficulty in dealing with patients’ beliefs, fears, and unrealistic goals, contributing to
inconsistent and incomplete patient education and emotional support. Finally,
results showed a public stigma of psoriasis because of the belief that psoriasis is
contagious, unimportant, and nonelife threatening. Identification of challenges
faced by professionals providing care for patients with psoriasis revealed perceived
as well as unperceived educational needs. Those findings are instrumental in
informing the design of targeted educational initiatives to address healthcare
professionals’ knowledge, confidence, skill, and performance gaps.
Commercial support: Funded by an unrestricted educational research grant from
Abbott Laboratories.
EPIDEMIOLOGY AND HEALTH SERVICES
ADMINISTRATION
P1804
Spanish-speaking patient health educational preferences
Claudia Hernandez, MD, University of Illinois at Chicago, Chicago, IL, United States;
June Robinson, MD, Northwestern University, Chicago, IL, United States; Robin
Mermelstein, PhD, University of Illinois at Chicago, Chicago, IL, United States
Background: Language and cultural barriers contribute to poor health outcomes.
Health educational resources focusing on English-speaking, literate individuals
marginalize non-English speaking Hispanic individuals. We hypothesized that
patients with the least education will prefer verbal presentation of health information with visual illustrations.
P1900
Discussion: The current recommended reading level for patient education materials
is that they should be written at the sixth-grade level. Our data suggest that even
materials at a sixth-grade reading level may be too difficult for approximately 30% of
the Hispanic patients we interviewed. The conundrum for health care delivery is
meeting the patient’s desire for communication of health education with in the
context of the clinical visit with the physician.
Vitamin D levels and oral supplementation in patients with skin cancer
Nikki Hill, Boston University School of Medicine, Boston, MA, United States;
Laura Delong, MD, MPH, Emory University School of Medicine, Atlanta, GA,
United States; Scott Dunbar, Emory University School of Medicine, Atlanta, GA,
United States; Suephy Chen, MD, Emory University School of Medicine, Atlanta,
GA, United States
Maintaining adequate vitamin D (vitD) levels is difficult to achieve with diet alone.
Given the increased risk of photodamage and skin cancers, dermatologists are
reluctant to recommend increased UV exposure, but can easily recommend daily
oral vitamin D supplementation (POvitD). We investigated the relationship between
vitD levels of patients diagnosed with skin cancer and POvitD while controlling for
photoprotection (PP). Seventy-eight subjects with skin cancer were recruited and
queried for skin cancer history, PP behavior, and oral vitD intake (both supplementation and diet). Adherence to PP was measured using the Glanz Sun Protection
Habits (SPH) instrument. We dichotomized the SPH scores using the median (2.80)
of our population, into adherent (\2.8) and nonadherent groups. Serum 25hydroxyvitaminD was determined using ELISA; insufficiency was defined as vitD
\32 ng/mL. The t test compared vitD levels between groups, and linear regression
determined predictors of vitD levels. P \.05 was considered statistically significant.
Of the 78 subjects, 62% were male, 98% were white, and 95% had completed
college. Mean (SD) age was 58 (14) years. Forty percent of subjects had a history of
melanoma; the remainder had nonmelanoma skin cancers. Sixty-five percent of
subjects were taking POvitD. VitD levels ranged from 11 to 73 ng/mL with a mean
(SD) of 31 (11) ng/mL. Mean (SD) values in the adherent (30 [11] ng/mL) and
nonadherent groups (32 [12] ng/mL) were not statistically significantly different.
Overall, 13% of subjects were vitD deficient and 42% were insufficient. Mean (SD)
vitD levels were higher and sufficient in the POvitD group compared to the group
not taking POvitD (33 [12] vs 27 [9] ng/mL; P ¼ .03). There was no statistically
significant difference in the dietary intake of vitD between groups. VitD levels (r ¼
0.25, P ¼.027) and age (r ¼ 0.34, P ¼.003) statistically significantly correlated with
POvitD. In a multivariate regression, POvitD was the only significant predictor of
vitD levels (P ¼ .009). Age, gender, education, melanoma history, skin type, SPH
score (P ¼.181), and hours outside/week were not significant predictors. We were
unable to demonstrate that PP adherence plays a significant role in vitD status, yet
our sample size is small. However a majority of subjects had vitD insufficiency.
Because POvitD significantly influenced vitD status, it is important that dermatologists identify patients at risk for vitD insufficiency and recommend oral supplements for overall patient health.
Methods: A convenience sample of 54 Spanish-speaking patients who presented for
care to the University of Illinois at Chicago Dermatology Clinic were interviewed to
determine their preferred communication method for learning how to perform a
complete skin self-examination for melanoma/skin cancer. Spanish-speaking
Hispanic adults over 18 years of age who requested an interpreter were eligible
for inclusion in the study. Subjects self-reported their demographic information and
preferences by completing a Spanish-language questionnaire collecting the following: highest school grade completed, reading skills, religious or cultural practices
that enhance or may be barriers to health education, use of communication aids, and
learning preferences. The Institutional Review Board of University of Illinois at
Chicago approved the research protocol. After reviewing the completed form, the
research assistant presented the following learning options: (1) self-education by
reading material with plain text or text and color pictures; (2) self-education by
listening to an audio explanation with or without accompanying pictures; (3) selfeducation using a DVD or by accessing the internet; or (4) reviewing the material
with a doctor or nurse. Patients were invited to suggest other means of communication. After the presentation, patients were asked if their original preference
remained the same or if they wished to change.
Results: Of the 54 adults interviewed, three never had formal education, 13 had a
maximum education level of grades 2 to 5, 20 an educational level between sixth and
eighth grade, and 18 reported a high school or college education. The majority of
Hispanics (53%) wanted to review the materials with their physician, not with
ancillary staff, and wanted to do it before completing the visit. Only 25% of patients
were comfortable reviewing written materials at a later time. All subjects, who were
amenable to reading materials presented to them by the physician, were educated to
at least the sixth-grade level.
AB66
J AM ACAD DERMATOL
MARCH 2010
P1901
P1903
Economic burden of comorbidities in patients with psoriasis
Alexa Kimball, Harvard Medical School, Boston, MA, United States; Eric Wu,
United States
Psoriasis is associated with increased mortality risk
Alexa Kimball, Harvard Medical School, Boston, MA, United States; Annie Guérin,
United States
Objective: To estimate the incremental economic burden associated with comorbidities in patients with psoriasis, accounting for psoriasis severity.
Methods: The Ingenix Impact National Managed Care Database (1999-2004) was
used. Adult patients with psoriasis who were continuously enrolled for $ 6 months
after a randomly selected psoriasis diagnosis date were included. Study comorbidities, identified during the 6-month study period, included psoriatic arthritis,
cardiovascular disease, depression, diabetes, hyperlipidemia, hypertension, obesity,
cerebrovascular disease, and peripheral vascular disease. Comparisons for resource
utilization and costs during the study period were made for patients with $ 1
comorbidity versus those with none and for patients with versus without a specified
comorbidity. Adjusted incidence rate ratios (IRRs) and odds ratios (ORs) were
estimated for resource utilization using negative binomial and logistic regression
models, respectively. Adjusted incremental costs associated with comorbidities
were reported using generalized linear models with log link and gamma distribution
or two-part models. All models controlled for age, sex, and psoriasis severity
(measured by type of treatment).
Results: A total of 114,512 patients were included; 51% had $ 1 studied comorbidity. Hyperlipidemia (27%) and hypertension (25%) were the most prevalent
comorbidities. Patients with comorbidities were more likely to experience urgent
care (OR [95% confidence interval], 1.58 [1.51-1.65]) than patients without a
comorbidity. They also had significantly greater rates of hospitalization (IRR, 2.27
[2.13-2.42]) and more frequent outpatient visits (IRR, 1.53 [1.52-1.55]). In particular, patients with cardiovascular disease had a rate of hospitalization more than four
times greater (IRR, 4.19 [3.90-4.50]) than patients without cardiovascular disease.
Compared with patients with no comorbidity, patients with comorbidities incurred
$2184 (P \.001) more in total costs. The incremental costs of comorbidities were
especially substantial for patients with cerebrovascular disease ($6191; P \.001).
Objective: To investigate psoriasis (Ps)-associated mortality risk for Medicare
beneficiaries in the United States.
Methods: This analysis used the 5% standard analytical file of the fee-for-service
portion of the Medicare database (1998-2006). Medicare patients (pts) aged $ 65
years who were continuously enrolled in Medicare Parts A and B for $ 6 months
were included. Pts with Ps were identified as those with $ 2 diagnoses of Ps (ICD-9CM: 696.1x) during the first 6 months of observed enrollment. Each pt with Ps was
matched to three control pts (free of Ps and psoriatic arthritis [ICD-9-CM, 696.0x])
based on age, sex, and race. Comorbidities recorded during the first 6-month period
were compared descriptively by cohort. Chi-square tests were used for categorical
variables and Wilcoxon rank-sum tests were used for continuous variables. Time
from enrollment to death was compared between pts with Ps and Ps-free controls
using Kaplan-Meier survival analysis. Results were reported as mortality rates and
differences between the 2 cohorts were evaluated using log-rank tests. Unadjusted
mortality risk was estimated using a Cox proportional-hazards model. In addition,
adjusted risk was estimated, controlling for age category and interaction terms
between age categories and cohort.
Conclusions: Other research has shown that psoriasis confers an increased risk of
cardiovascular disease and other comorbidities. This study demonstrates that
economic burden is increased for patients with psoriasis and comorbidities.
Results: A total of 5513 pts with Ps and 16,539 matched control pts were included in
the analysis. Mean 6 SD age was 71.3 6 6.8 years, 57.0% were women, and 91.6%
were white. The median follow-up time was 7.0 years. Pts with Ps had significantly
greater rates of comorbidities (eg, hypertension, diabetes, hyperlipidemia, cardiovascular disease, and anemia [all P \.001]). Over the observation period, 27.3% of
pts with Ps and 25.4% of controls died (P ¼.006). Overall, the mortality risk was 10%
greater for pts with Ps than for Ps-free pts (P ¼.002). Pts with Ps between the ages of
65 and 69 years experienced a 22.3% increased risk of mortality compared with
control pts without Ps (P ¼.002) in the same age category.
Conclusions: Pts with Ps have a significantly greater risk of mortality than pts who do
not have Ps. In this study, the Ps-associated mortality risk was greater for younger pts
compared with the full sample population.
P1904
P1902
Increased economic burden associated with moderate to severe psoriasis
compared with mild psoriasis
United States
Objective: To compare the economic burden and health care use by patients with
moderate to severe psoriasis (Ps) compared with those with mild Ps.
Methods: The Ingenix Impact National Managed Care database was used to identify
patients with Ps during the study period, defined as the 2003 calendar year. Patients
aged 18 to 65 years with continuous enrollment during the study period and $ 1
diagnoses of Ps before the end of study period were selected. Selected samples were
further stratified by Ps severity based on treatment patterns. Patients with moderate
to severe Ps were defined as those who received $ 1 systemic therapies. Outcomes
included total health care utilization and costs and their components (ie, prescription drug and medical costs including emergency department visits, hospitalizations, outpatient visits, and professional services). Multivariate logistic regression
models and two-part models were used to estimate the increased health care
utilization and incremental costs, respectively, among patients with moderate to
severe versus mild Ps. The models controlled for age, sex, and comorbidities during
the study period.
Results: A total of 56,528 patients with Ps met the inclusion criteria. Patients with
moderate to severe Ps (N ¼ 5248) had significantly greater total health care
utilization than did patients with mild Ps (N ¼ 51,280; adjusted odds ratio [AOR],
4.82), including greater medical (AOR, 1.19), hospitalization (AOR, 1.19), and
outpatient utilizations (AOR, 1.14; all P \.02). The adjusted incremental costs for
moderate to severe versus mild Ps were $7517 for total health care costs, including
$3886 for drug costs and $2814 for total medical costs.
Conclusions: Increased Ps severity is associated with greater resource utilization and
costs. Additional studies will be necessary to determine whether this increased
economic burden is driven by the disease itself and/or associated comorbidities.
Burden of illness in patients with hidradenitis suppurativa
Annie Guérin, Analysis Group, Boston, MA, United States; Parvez Mulani, Abbott
Laboratories, Abbott Park, IL, United States; Shiraz Gupta, Abbott Laboratories,
Abbott Park, IL, United States
Objective: Hidradenitis suppurativa (HS) is a chronic, inflammatory, relapsing
disease of the apocrine sweat glands of the skin. Patients present with nodules,
abscesses, or fistulas and substantial discomfort and/or itching. In the United States,
1% to 2% of the general population has HS. This study compared resource utilization
and incremental economic burden between HS patients and control patients
without HS.
Methods: The MarketScan claims database (2000-2006) was used to identify as HS
patients those with at least one diagnosis of HS (ICD-9-CM: 705.83). Adult patients
with HS continuously enrolled for $ 12 months after a randomly selected HS
diagnosis date (index date) were included in the analysis. Each patient with HS was
matched to 5 HS-free control patients by year of birth and sex. Comorbidity burden,
medication use, and resource utilization were compared between patients with HS
and HS-free controls during a 1-year follow-up period. Absolute and relative risks
(RRs) were estimated for comorbidities and adjusted incidence rate ratios (IRRs)
were estimated for resource utilization using negative binomial regression models.
All models controlled for age, sex, Charlson comorbidity index (CCI), and health
insurance plan type.
Results: The analysis included 20,652 patients with HS and 103,260 HS-free control
patients. The average patient age was 38.2 years; 73.9% were women. Patients with
HS had a greater comorbidity burden than HS-free patients (CCI, 0.401 vs 0.199; P [
.001). A significantly greater percentage of patients with HS were diagnosed with
depression compared with HS-free controls (7.5% vs 4.7%; P ¼ .0001). Compared
with HS-free patients, patients with HS had significantly greater risks (per 100
patients) of diabetes (11.2 vs 4.6; RR, 2.5) and asthma (5.4 vs 3.1; RR, 1.7; both P \
.001). The most commonly used drugs were antidepressants (18.8% vs 13.2%; P ¼
.001) and analgesics (37.6% vs 19.3%; P ¼ .001). Patients with HS had significantly
greater rates of emergency department visits (IRR, 2.49 [95% confidence interval,
2.35-2.63]), hospitalizations (2.47 [2.28-2.66]), and outpatient visits (2.31 [2.272.36]) compared with HS-free patients.
Conclusions: Patients with HS experience significant comorbidity and economic
burden compared with the HS-free population.
MARCH 2010
J AM ACAD DERMATOL
AB67
P1905
P1907
Knowledge gap in atypical mole syndrome patients with a history of
melanoma: Cancer worry about new primary versus recurrence
Sallyann King, MD, Emory University, Atlanta, GA, United States; Emir Veledar,
PhD, Emory University, Atlanta, GA, United States; Laura DeLong, MD, MPH,
Emory University, Atlanta, GA, United States; Suephy Chen, MD, PhD, Emory
University, Atlanta, GA, United States; Zakiya Rice, MD, Emory University,
Atlanta, GA, United States
Cancer worry is the emotional reaction to the threat of cancer. Moderate melanoma
(MM) cancer worry may be beneficial, leading to increased rates of cancer
screening. However, little is known about how a personal history of MM affects
the level of cancer worry in patients with atypical mole syndrome (AMS). Little is
also known about how AMS patients with a MM history view the occurrence of new
primary MM vs a recurrence of their disease. Between June 2005 and October 2009,
134 patients at Emory University with AMS who were scheduled for total body
digital photography were recruited to complete cancer worry surveys. Worry was
measured using the Revised Impact of Events Scale (RIES; range, 0-75) and the
Modified Breast Cancer Worry Scale (MWS; range, 4-16). The REIS allowed us to
compare the cancer worry for a new primary MM versus that of a recurrence.
Outcomes were compared using paired t tests with P # .05 considered significant.
Of the 134 AMS patients 38% were male, the mean age (SD) was 42 (11) years, 99%
were white, 48% had a history of MM, and 26% had a family history of MM. AMS
patients with a history of melanoma were found to be significantly more worried
then those without a history using both scales (RIES 15.4 6 14.1 vs 6.1 6 10.8; P \
.001; MWS 9.4 6 3.3 vs 7.4 6 2.7; P ¼ .0004). However, AMS patients with a MM
history were not significantly more worried about a new primary vs a recurrence of
their disease (15.4 6 14.1 vs 14.8 6 15.6, correlation coefficient ¼ 0.88). Not
surprisingly, patients with AMS are worried about developing MM; with those with a
MM history have a significantly higher level of worry. Interestingly, those AMS
patients with a MM history seem to experience similar levels of worry about a new
primary MM versus a recurrence of their disease. This may represent a knowledge
gap in our melanoma patients. Therefore more attention may need to be spent
educating patients regarding the prognostic difference between recurrent and new
primary MM.
Economic burden of severe chronic hand eczema/dermatitis in Canadian
adults
Charles Piwko, PhD, MS, PIVINA Consulting, Thornhill, Ontario, Canada; Arima
Ventin, MBA, Basilea Pharmaceuticals, Toronto, Ontario, Canada; Basil Bereza,
PIVINA Consulting, Thornhill, Ontario, Canada; Colin Vicente, MS, PIVINA
Consulting, Thornhill, Ontario, Canada; David Wortzman, MD, Basilea
Pharmaceuticals, Toronto, Ontario, Canada
Background: Severe chronic hand eczema (CHE) or chronic hand dermatitis (CHD)
is characterized by thick scaly skin causing painful fissures, erythema, itching,
blistering, and edema. Severe CHE/CHD is often unresponsive to conventional
topical corticosteroids and results in substantial occupational, personal, and
psychological disability. There is currently a lack of information regarding the
economic burden of CHE/CHD in Canada.
Methods: A dynamic Excel model was developed to estimate the cost of treating
adults with severe CHE in Canada. Epidemiologic/clinical data were derived from
systematic literature searches. A Delphi panel of dermatologists provided estimates
of resource utilization and validated epidemiological/clinical rates. Given the impact
on lost productivity, a pseudosocietal perspective was chosen; out of pocket
expenses (travel and nonprescription pharmacotherapies) were excluded from the
analysis. Unit costs were derived from Ontario standard lists and reported as 2009
Canadian dollars.
Results: In 2009, the estimated adult population was ;26 million. From the
literature, it was determined that ;0.67% of adults may have severe CHE/CHD.
Assuming 50% of these patients do not adequately respond to topical corticosteroids, an estimated ;87,200 Canadians have severe CHE being refractory to topicals.
Treatment cost, including lost productivity, was calculated to be ;$737 million per
annum. Even in an optimistic scenario, which included current second-line
treatment market shares, but assumed treatments were 100% effective, the cost of
severe CHE was estimated to be $390 million per annum.
Conclusion: This study estimated that the cost of severe CHE/CHD unresponsive to
topical corticosteroids in Canada ranges from $390 million to $737 million per
annum. The majority of cost comes from lost productivity because of disease, cost
associated with a lack of treatment efficacy, and the cost of accessing treatment.
Commercial support: Printing costs were funded by Basilea Pharmaceuticals.
P1908
P1906
Recent literature has documented the presence of coronary artery disease (CAD) in
moderate/severe psoriasis, usually defined as the usage of systemic medications. The
correlation has intimated a common inflammatory pathway. However, limited data
have explored the paradigm of a dose-response relationship between psoriasis
severity and CAD severity. We sought to explore how clinical measures of psoriasis
severity would relate to degree of cardiovascular disease risk. Psoriasis severity was
measured in two ways: (1) percentage body surface area involvement (BSA) and (2)
by physician placement of study subject on systemic therapy (systemic use) in
addition to or in lieu of topical therapy. A retrospective chart review was performed
of 233 psoriasis patients seen at the Emory Dermatology Clinic between June 2007
and June 2008. BSA was determined from the clinic visits, which documented
initiation of treatment. We also obtained data regarding medication (systemic vs
topical therapy alone), age, gender, LDL level, HDL level, presence of diabetes
and/or hypertension, and smoking status. The cardiovascular risk factors were used
to gauge CAD risk scores via the online University of Maryland Heart Disease Risk
Calculator. These CAD Risk scores provide the likelihood that subjects will
experience coronary heart disease within the next 10 years and are based upon
data derived from the Framingham Heart Study. Overall, 49.8% of our subjects were
male, 77.6% white, 36.6% were on systemic therapy, and the mean age was 54.4
years (SD, 15.6 years). Mean CAD Risk was 11.69 (SD, 10.14) while mean BSA was
12.52% (SD, 14.14). Systemic use was not found to correlate with CAD risk (P ¼
.495). However, there was a trend towards significance in the correlation between
BSA and CAD Risk (r ¼ 0.148; P ¼.095). We have shown that increased severity of
psoriasis as measured by BSA is a better dose-response predictor for CAD Risk than
use of systemic therapy. Future studies should employ BSA measures when
evaluating the relationship between psoriasis severity and CAD Risk. Study limitations included inability to include erythema severity or Psoriasis Area and Severity
Index scores as a measure of psoriasis severity secondary to the retrospective nature
of the study.
Banding and the clinical interpretation of Skindex-29 scores using an
anchor based technique
Scott Dunbar, Emory University School of Medicine, Department of Dermatology,
Atlanta, GA, United States; Kathy McCombs, MD, Emory University School of
Medicine, Department of Dermatology, Atlanta, GA, United States; Laura DeLong,
MD, Emory University School of Medicine, Department of Dermatology, Atlanta,
GA, United States; Melissa Alexander, Emory University School of Medicine,
Atlanta, GA, United States
Dermatologic disease has been shown to have a profound impact on a patients’
health-related quality of life (HRQL). The objective of this study is to use an anchorbased technique to assign clinical significance to the raw score of the Skindex-29, a
dermatology-specific HRQL measurement. From 2006 to 2008, adult subjects with
nonselected skin disease were recruited prospectively from Emory and Grady
general dermatology clinics. Each patient provided demographic information,
completed the Skindex-29, and answered a global question (GQ) measuring the
overall HRQL impairment caused by their skin disease. The Spearman rank
correlation coefficient was used to examine the correlation between the Skindex29 scores and the GQ scores. The mean, median, and mode of the GQ scores for each
5-point interval of Skindex scores were used to delineate separate groupings, or
bands, of the Skindex scores and the kappa coefficient of agreement was calculated
for each set. A P \.05 was considered statistically significant. Of 378 subjects, the
mean 6 SD age was 47 6 16 years and 34% were male. The overall mean 6 SD
Skindex score was 34 6 24 (range, 0-100), with a higher score signifying greater
HRQL impairment. The mean 6 SD emotional, symptomatic, and functional
Skindex subscores were 42 6 28, 39 6 24, and 24 6 26, respectively. The overall
mean 6 SD GQ score was 3.0 6 1.4 (range, 0-5). The Spearman rank correlation
coefficient showed a statistically significant correlation between the Skindex scores
and the GQ scores (r ¼ 0.62). The mean, median, and mode of the GQ scores for
each 5-point interval of Skindex scores was used to create a series of bands with the
highest kappa coefficient (0.293). The calculated bands of Skindex scores were: 010, 11-25, 26-50, 51-70, and 71-100, which correspond to the following degrees of
impairment respectively: none, mild, moderate, severe, and very severe. The
primary limitation of this study is small sample size, and further investigation into
the clinical grouping of these scores is warranted. The banding of Skindex-29 scores
will allow clinicians to use this measure of dermatologic HRQL to more effectively
understand and manage their patients’ skin diseases.
Body surface area as a measure of psoriasis-associated cardiovascular
disease risk
Loebat Kamalpour, MD, Emory University, Atlanta, GA, United States; Adam
Perry, Emory University, Atlanta, GA, United States; Heather Leslie, Emory
University, Atlanta, GA, United States; Nikki Hill, Emory University, Atlanta, GA,
United States
AB68
J AM ACAD DERMATOL
MARCH 2010
P1909
P1911
The epidemiologic and clinical presentation of syphilis in Paris: A cohort
study of 284 consecutive cases over the period 2000 to 2007
Nada Zizi, Department of Dermatology, Rabat, Morocco; David Farhi,
Department of Dermatology and Venereology, Paris, France; Marie-Françoise
Avril, Department of Dermatology and Venereology, Paris, France; Nadjet
Benhaddou, Department of Bacteriology, Paris, France; Nicolas Dupin,
Department of Dermatology and Venereology, Paris, France
Background: Since 2000, the incidence of syphilis increased 10-fold in France.
Accurate knowledge of the epidemiologic and clinical presentation is essential for
early diagnosis and treatment.
Objectives: To appraise the clinical and epidemiologic presentation of syphilis in
Paris, France.
A Web system survey about awareness, attitudes, and behavior of teenagers to sunlight in Andalusia (south of Spain)
Salvador Arias-Santiago, MD, San Cecilio Hospital, Granada, Spain; Agustı́n
Buendı́a-Eisman, MD, Medicine Faculty, Granada, Spain; Andrés Cabrera-León,
MD, Escuela de Salud Publica, Granada, Spain; José Carlos Moreno-Gimenez, MD,
Hospital Reina Sofia, Cordoba, Spain; Leonor Prieto, MD, Medicine Faculty,
Granada, Spain
Introduction: The use of the Internet and new technologies is widespread in
children and adolescents, and that is why a school program to evaluate healthy
habits before sun exposure has been designed through a Web system aimed at
teenagers. It must be kept in mind that sunlight exposure is the main changeable risk
factor for skin cancer and that this exposure is most significant in childhood and
adolescence.
Study design: Retrospective monocentric descriptive study.
Setting: Venereal disease center in an academic public hospital in Paris.
Subjects: A cohort of 284 consecutive cases of syphilis diagnosed over the period
2000 to 2007.
Methods: Systematic collection of epidemiologic, clinical, and microbiologic data
using standardized medical forms.
Results: Overall, 95% of the cases occurred in men (271/284), 83% in men having sex
with men (MSM; 231/278), 58% in patients having more than 10 partners/year
(138/240), and 19% in patients who never use condom (49/253). At least one
sexually transmitted disease has been diagnosed in 79% (220/279) and 26% (72/279)
of the cases, respectively, previous and concomitantly. In 50% of the cases
(141/281), HIV serology was positive (median CD4 cell count: 475/mm3; median
HIV RNA level: 299 copies/mL). Most patients had a symptomatic syphilis (216/279,
77%), at primary (82/279, 29%) or secondary (125/279, 45%) stages. The most
frequent physical signs in primary and secondary syphilis were, respectively, a
genital chancre (63/82, 77%) and a diffuse exanthema (108/125, 86%).
Conclusion: Most syphilis are diagnosed at early stages, and tertiary syphilis is
seldom. Syphilis occurs chiefly in MSM, often in HIV-positive patients, and in onefifth of patients who never use condoms. The knowledge of these data should
support oriented information and screening national campaigns.
Methods: We determine levels of awareness and the behavior of students with
respect to sunlight through a Web-based system. A total of 2170 students from
randomly selected schools in Andalusia participated in the present study. The
questions were regarding about the relationship between sun and skin, sun and
environment, sun and health, and the evaluation of attitudes and behavior.
Results: Most pupils had a high (26.3%), very high (22.4%), or excellent knowledge
(16.5%) about the risks of sun exposure, although this knowledge does not translate
into healthy habits, as high sun exposure occurred in 65% of student and nonsolar
prevention in 35.3% . Sunburns during the previous summer were found in 48.4%.
Most of the students (77.4%) do not use any photoprotection methods in cloudy
days. Participant satisfaction was very high, valued primarily using the computer,
and 99.6% of students would participate in a new campaign with similar
characteristics.
Conclusion: Prevention campaigns for students are definitely necessary and could
be designed through a Web system. Intervention to change behavior patterns should
be the main goal of primary prevention programs, because high levels of awareness
does not translate into healthy sun habits.
P1912
P1910
Lifestyle factors and comorbidities in individuals with psoriasis and
mental illness: A descriptive study
Ruby Kaur, MD, RN, David Geffen School of Medicine, Los Angeles, CA, United
States; Abrar Qureshi, MD, MPH, Brigham & Women’s Hospital, Boston, MA,
United States; Patrick Dominguez, MD, Brigham & Women’s Hospital, Boston,
MA, United States; Sandeep Kumar, MD, Brigham & Women’s Hospital, Boston,
MA, United States
It is known that patients with psoriasis (Pso) are more likely to suffer from mental
illness compared to the general population. Recently there has been much
discussion regarding lifestyle factors and comorbidities associated with both Pso
and mental illness. Ascertainment of life style factors and comorbidities that are
prevalent among individuals with both Pso and mental illness may help identify and
address the needs of this unique population. In this study, we examine the
demographic profile and prevalence of comorbidities and lifestyle factors in a
population of psoriatic individuals with mental illness. We retrospectively reviewed
data from the Pso and Psoriatic Arthritis Follow-up Study (PAFS), a longitudinal trial
at Brigham & Women’s Hospital in Boston, MA. All data were collected on
participants who self-reported a diagnosis of depression and/or mental illness.
Self-reports were validated by medical record review. Of the 402 Pso participants in
the PAFS study, 43 (11%) self-reported a diagnosis of mental illness. Of these 43 selfreports we were able to validate 37 cases. Of these 37 cases, 84% had depression, 8%
had anxiety disorders, and 8% had bipolar disorder. Women (60%) and whites (81%),
constituted the majority of the group. Participants’ ages ranged from 21 to 75 years
with a median age of 56 years, 47% had incomes less than $20,000/year, 62% were
divorced, widowed, or never married, 62% were either current or past smokers, and
49% consumed alcohol. DLQI scores ranged from 0 to 26 with a median of 7. The
prevalence of comorbidities was as follows: psoriatic arthritis (38%), obesity (32%),
hypertension (27%), diabetes (19%), inflammatory bowel disease (19%), cardiovascular disease (11%), hyperlipidemia (11%), and alcoholism (5%). Participants
received either topical (57%) or systemic therapy (43%) including phototherapy
for their Pso and/or psoriatic arthritis. In conclusion, we found that the prevalence
of mental illness, especially depression, was higher in older white women with Pso.
Lower income and single status were also prevalent among psoriatic individuals
with mental illness, and a significant percentage also had one or more comorbidities.
Psoriatic patients with mental illness may benefit from a multidisciplinary approach
for optimum medical management.
A novel measure to assess eyelash patient-reported outcomes: Psychometric validation and determination of the minimal important difference for
the eyelash satisfaction questionnaire
John Walt, MBA, Allergan, Irvine, CA, United States; Frederick Beddingfield, MD,
PhD, Allergan, Irvine, CA, United States; Geoffery Hammond, PhD, QualityMetric
Health Outcome Solutions, Lincoln, RI, United States; Jan Hansen, PhD, Allergan,
Irvine, CA, United States; Somali Burgess, PhD, Allergan, Irvine, CA, United States
Aims: The Eyelash Satisfaction Questionnaire (ESQ) was developed to provide a selfreported measure of the physical attributes of eyelashes, subjective eyelash
characteristics, and impact of one’s eyelash routine on daily life.
Methods: Patient and physician focus groups were convened to develop appropriate
wording for questionnaire items and the conceptual framework underlying the ESQ.
Validation was performed on a large sample (n ¼ 970) of respondents from an
internet convenience sample (n ¼ 909) and a sample given a paper version (n ¼ 61).
Psychometric investigation was used to examine the relationship between the ESQ
domains and other health-related quality of life (HRQoL) measures assessing general
health and body image. The 12-Item Short Form Health Survey (SF-12) and Body
Image Quality of Life Inventory (BIQLI) were used. Calculations were made of how
much change on each of the questionnaire domains is needed for a minimal
important difference (MID). MID was ascertained using a clinical trial sample
receiving bimatoprost ophthalmic solution 0.03%, an FDA-approved treatment that
increases length, thickness, and darkness of eyelashes (n ¼ 278).
Results: Results of the qualitative research identified three related domains: (1)
length, fullness, and overall satisfaction with eyelashes; (2) confidence, attractiveness, and professionalism from eyelash appearance; and (3) impact on daily routine.
These domains were supported by factor analysis. The three domains were found to
have moderate correlations with the BIQLI (convergent validity, 0.20-0.65) and
appropriate lower correlations with a more general measure (SF-12: 0.02-0.16). The
measure also had high levels of convergent and overall structural validity, with high
levels of Cronbach’s alfa for all three domains (domains 1 and 2: 0.97 each, domain 3:
0.92). In all domains, distribution-based MID calculations showed a change of 1 to 2
points on a 15-point scale. Assessing MID longitudinally (associating changes in scale
scores to a 15-point anchor) showed a larger MID estimate of 2 to 4 points,
dependent on scale. Results indicated that a 2-point change in each of the three
domains is the optimal definition of MID.
Conclusions: The ESQ was developed using both qualitative and quantitative
techniques to measure the patient- and physician-recommended domains of eyelash
patient reported outcomes. A change of 2 points in any of the three ESQ domains
provides evidence of a clinically meaningful change.
Commercial support: 100% is sponsored by Allergan.
MARCH 2010
J AM ACAD DERMATOL
AB69
GENODERMATOSES
P2000
Germline and somatic mutations in the CYLD and PTCH genes in patients
with multiple familial trichoepitheliomas: Is there a third gene implicated
in the pathogenesis of the disease?
Dmitry V. Kazakov, MD, PhD, Sikl’s Department of Pathology, Charles University,
Medical Faculty Hospital, Pilsen, Czech Republic; Denisa Kacerovska, MD, PhD,
Multiple familial trichoepitheliomas (MFT) constitute an autosomally inherited
syndrome possibly related to BrookeeSpiegler syndrome (BSS) though the relationship between MFT and BSS is unclear. Whereas some early studies suggested a role of
the PCTH gene on chromosome 9 in the etiopathogenesis of MFT, recent studies of
occasional patients with the MFT clinical phenotype identified mutations in the
CYLD gene on chromosome 16, a gene responsible for BSS. Systemic investigations
of MTF patients for PTCH and CYLD mutations have never been performed; ergo,
our objective was to study a series of such patients. The study group included 14
individuals (6 men, 8 women; age range, 11-63 years), all of whom presented with
multiple trichoepitheliomas preferentially located in the nasolabial folds. In all
patients, the diagnosis was confirmed histologically; many had multiple skin
biopsies and in no case was there another adnexal tumor. Family histories disclosed
similar lesions involving relatives of all but one patient. Relatives of two patients, in
addition to trichoepitheliomas, presented with other cutaneous adnexal neoplasms
of the BSS spectrum. Analysis of germline mutations of CYLD (12 cases) and PTCH (9
cases) was performed using either peripheral blood or nontumorous tissue. Somatic
mutations were studied using formalin-fixed, paraffin-embedded material. In none of
the nine patients tested was a germline mutation of the PTCH gene identified.
Germline CYLD mutations were detected in five patients, whereas the remaining
seven individuals showed wild-type allele. Two patients with wild-type CYLD
showed however a somatic mutation in the gene, which represented either a
duplication or substitution mutation. Five patients demonstrated a germline
mutation in neither CYLD nor PTCH. It is concluded that the PTCH gene is rarely
involved in the pathogenesis of MFT. Absence of a germline mutation of the CYLD
gene in cases wherein a somatic mutation was identified may be explained by large
deletions in the gene, a mutation in intronic sequences or in the promoter region.
Another possibility would be methylation of the promoter regions resulting in gene
inactivation. Considering our five patients with no mutation in either gene, the final
possibility is that another, as yet undescribed gene (neither CYLD nor PTCH) is
implicated in the pathogenesis of some MTF patients.
P2002
The relation of port wine stain with pneumosinus dilatans: A controlled
study
Bilal Dogan, MD, GATA Teaching Hospital, Department of Dermatology, Istanbul,
Kadikoy, Turkey; Cinar Basekim, MD, GATA Teaching Hospital, Department of
Radiology, Istanbul, Kadikoy, Turkey; Ozlem Karabudak, MD, GATA Teaching
Hospital, Department of Dermatology, Istanbul, Kadikoy, Turkey
Port wine stain (PWS) is the most common type of vascular malformation. It is
characterized pathologically by ectasia of superficial dermal capillaries and clinically
by persistent macular erythema. Pneumosinus dilatans (PSD) is a term used to
describe a localized abnormal dilatation of one or more paranasal sinuses without
radiologic evidence localized bone destruction, hyperostosis, or mucous membrane
thickening. This study was planned to investigate if the association of PWS and PSD
is coincidental. Twenty-three patients with PWS (22 males, 1 female; mean age,
25.74 years) and 20 controls (20 males; mean age, 20.9 years) were included in the
study. The difference of having PSD and the severity of PSD between patients and
controls were statistically significant (P ¼ .001 and P ¼ .00001, respectively). In
conclusion, this study showed that the coexistance of PWS and PSD was not
coincidental, although the number of patients was small. This association may help
to determine the possible causes of PSD.
Commercial support: Supported in part by the Internal Grant Agency (IGA) of the
Ministry of Health of the Czech Republic (NS 9734-4).
P2001
Juvenile/adult galactosialidosis in a Peruvian family
Mercedes Lidia Hassan, MD, PhD, MPH, Department of Dermatology-Ramos Mejia
Hospital-University of Buenos Aires, Buenos Aires, Argentina; Alexander Moreno
Figueredo, MD, Department of Dermatology-Ramos Mejia Hospital-University of
Buenos Aires, Buenos Aires, Argentina, Mercedes Lidia Hassan, PhD, MPH, MD,
Department of Dermatology-Ramos Mejia Hospital-University of Buenos Aires, Buenos
Aires, Argentina; Paula Luna, MD, Ramos Mejia Hospital, Buenos Aires, Argentina;
Ruben Laguens, MD, MPH, PhD, Rene Favaloro University, Buenos Aires, Argentina
Background: Galactosialidosis is an infrequent recessive-autosomal disease caused
by the combined deficit of two lysosomal enzimes, neuraminidase and B-galactosidase, because of a deficit of a protective protein similar to cathepsin A, its gene
encoded in chromosome 20q13.
Case report: A 26-year-old Peruvian woman consulted for dystonia and mental
retardation. The physical examination revealed gargoyle face, short stature, cutaneous puntiform angiokeratomas, palmar and labial telangiectasias, three plantar
nevi in lineal arrangement, and hirsutism were seen. No visceromegaly or osseous
anomalies were found. One sister showed a few angiokeratomas, and short stature as
well as her mother. Laboratory examinations: In addition to routine laboratory tests,
beta galactosidase(3.1 NV:14.0), alfa fucosidase (71 NV:15.0), and alfa-N-acetilgalactosaminidase (9.5 NV:4.6-21.0) were determined by fluorimetric method in units
mole/l. Beta mannosidase and carnitine (total 53.90 NV:46-70, free 44.40 VN41-58,%
free 82.00 VN:80-90) were determined in peripheral blood by radioenzimatic
method, and urinary levels of sialic acid (350.7). Blood oligosaccharides determination were undergone on filter-paper chromatography (abnormal profile similar to
what was described in galactosialidosis).
Complementary examinations: The ophtalmologic examination failed to demonstrate the retinal ‘‘cherry red spot,’’ and the neurologic examination confirmed the
presence of myoclonus and mental retardation. Cutaneous biopsies were performed
for light and electron microscopic studies. Confirming the diagnosis, characteristic
cytoplasmic vacuoles in endothelial cells, fibroblasts, pigmented nevus cells, and
scarce keratinocytes were observed. Enzymatic determinations and light and
electron mycroscopic study of healthy skin and angiokeratomas of the sister and
the mother are at present being undergone.
Treatment: The patient was put under a regimen of o.v. valproic acid and periodic
control.
Conclusions: We present the findings of laboratory determinations and light and
electron mycroscopy of a case of juvenile/adult form of galactosialidosis characterized by a long survival and absence of visceromegaly and osseous abnormalities.
Other apparently healthy members of the family are at present being studied.
AB70
P2003
BrookeeSpiegler syndrome: Evidence of diverse somatic mutations in the
same patient regardless of tumor type: A clinicopathologic and molecular
biologic study, including eight novel germline mutations in the CYLD gene
Denisa Kacerovska, MD, PhD, Sikl’s Department of Pathology, Charles University,
Medical Faculty Hospital, Pilsen, Czech Republic; Dmitry V. Kazakov, MD, PhD,
BrookeeSpiegler syndrome (BSS) is an inherited autosomal dominant disease
characterized by the development of multiple adnexal cutaneous neoplasms
including spiradenoma, cylindroma, spiradenocylindroma and trichoepithelioma.
BSS patients have various mutations in the CYLD gene, a tumor suppressor gene
located on chromosome 16q. To date, 52 germline CYLD mutations have been
reported. Somatic CYLD mutations have rarely been investigated. We studied 10 BSS
patients from eight families, including eight women and two men ranging in age
from 22 to 66 years. All individuals presented with multiple, variably sized papules
and nodules with a predilection for the scalp. Analysis of germline mutations of the
CYLD gene was performed using either peripheral blood or nontumorous tissue. In
addition, 19 formalin-fixed, paraffin-embedded tumor samples were analyzed for
somatic mutations, including loss of heterozygosity (LOH) studies, for which short
tandem repeat markers D16S304, D16S308, D16S419, D16S476, and D16S541
located on chromosome arm 16q and D16S407 located on chromosome arm 16p
were used. A total of 38 tumors were available for histopathologic review. These
consisted of 16 cylindromas, 11 spiradenomas, seven spiradenocylindromas, and
four trichoepitheliomas. We have identified eight novel germline mutations, all of
which consisted of substitutions, deletions, and insertions/duplications; all except
one led to premature stop codons. In four cases, there were diverse somatic
mutations in the same patient regardless of tumor type. In one case, each of the
three spiradenocylindromas had a different somatic mutation including LOH, one
showed a duplication mutation, and the last had a substitution mutation. In another
individual, one spiradenocylindroma demonstrated LOH and the other a duplication
mutation. In one patient with two cylindromas, one neoplasm harbored a substitution mutation, whereas a second cylindroma revealed an insertion mutation.
Lastly, in the remaining case, two of three cylindromas showed LOH, whereas the
third neoplasm demonstrated a substitution mutation. In all of these cases, the
sequence somatic mutations resulted in a truncated protein. We demonstrate for the
first time that somatic events, LOH or sequence mutations, may differ among
multiple neoplasms even of the same histologic type, occurring in the same patient.
Commercial support: Supported in part by the Internal Grant Agency (IGA) of the
Ministry of Health of the Czech Republic (NS 9734-4).
J AM ACAD DERMATOL
MARCH 2010
P2004
P2006
Netherton syndrome
Curt Mafra Treu, MD, Policlinica Geral do Rio de Janeiro, Rio de Janeiro, Brazil;
Luana Boeira Rocha, MD, Policlinica Geral do Rio de Janeiro, Rio de Janeiro,
Brazil; Manuela Boleira Sieiro Guimaraes, MD, Policlinica Geral do Rio de Janeiro,
Rio de Janeiro, Brazil; Paula Periquito Cosenza, MD, Policlı́nica Geral do Rio de
Janeiro, Rio de Janeiro, Brazil
Treatment of erythrokeratoderma variabilis with isotretinoin
Lyubov Avshalumova, DO, SunCoast Hospital/Largo Medical Center, Largo, FL,
United States; Matthew Mahoney, MD, Mahoney Dermatology Specialists, Largo,
FL, United States
Erythrokeratoderma variabilis (EKV), also known as Mendes da Costa syndrome, is a
rare, autosomal dominantly inherited disorder of keratinization. It has been shown
to be associated with mutations in genes for gap junction proteins GJB3 (encoding
connexin 31) and GJB4 (encoding connexin 30.3). EKV usually presents within the
first year of life, and has a chronic course. It is characterized by coexistent
hyperkeratotic plaques and transient erythematous patches. Patients are otherwise
healthy with normal life expectancy. However, the psychosocial impact on life can
be tremendous in affected individuals. We describe a 12-year-old boy presenting
with generalized yellow-brown, thick, hyperkeratotic plaques. He also exhibited
sharply demarcated, arcuate and spiral-shaped erythematous and hypopigmented
patches with fine scale, along with confluent palmar and plantar keratoderma.
According to his mother, scaly red patches first appeared at 6 months of age, which
subsequently evolved into thick plaques with geographic shapes at 5 years of age.
The clinical picture was suggestive of EKV. The patient’s father had similar lesions in
childhood; however, his skin disease improved around the end of adolescence and
he now has less erythematous, pink hyperkeratotic plaques present over the knees
and elbows. Treatment with multiple topical agents, including urea and lactic acid
creams as well as tazarotene, was attempted without success. Patient was started on
a course of isotretinoin at 20mg/day with some improvement noted within months
of therapy. Tapering to 10mg/day, however, did not sustain the benefit and dose of
isotretinoin was again increased to 20mg/day. Monthly monitoring of the laboratory
values has not revealed any changes after 6 months of therapy, and the patient has
denied side effects other than dry lips. The efficacy of systemic retinoids in disorders
of keratinization is well documented in the literature. However, their use in children
is limited because of concerns of serious adverse effects on musculoskeletal,
neurologic, and gastrointestinal systems with chronic use. Low doses are often
effective in EKV. Patient education and close follow-up are essential to reduce the
risk of potential complications. When used appropriately, systemic retinoids are safe
and effective in pediatric population. They can minimize discomfort and significantly improve quality of life and social interactions in affected children.
Background: Netherton syndrome is an autosomal recessive genodermatosis (5q32)
of unknown cause. In its complete form is characterized by erythroderma, linear
circumflex ichthyosis, trichorrhexis invaginata, atopic diathesis, and
hypodevelopment.
Case report: A 42-year-old man reported the appearance of erythematous papules
with centrifugal growth, forming arciform lesions, some circinate with peel edges,
various sizes, in the upper extremities, lower extremities, buttocks, palms, and
soles. The lesions were migratory, involuted spontaneously, and reemerged elsewhere over a period of approximately 2 to 3 months with eventual itching. He had
no comorbidities, denied smoking, the regular use of alcohol or drugs, and atopy. He
had 19 previous nonspecific biopsies. He has a brother, also male, with similar
clinical appearance, since 12 years of age. He had a previous treatment with topical
keratolytics with partial resolution of his symptoms and oral acitretin without
improvement. VDRL, serology for HIV 1 and 2, also for HTLV-1, ANA and serum IgE
were negative. Diagnostic hypotheses: poroceratose, symmetric progressive erythrokeratodermia, linear circumflex ichthyosis, and erythrokeratodermia variabilis. A
new histologic examination was consistent with linear circumflex ichthyosis.
Discussion: In 1958, Netherton described a girl with generalized dermatitis peel and
deformities of nodular fragile hair shaft, which he called trichorrhexis nodosa
(bamboo hair). This was later renamed appropriately as trichorrhexis invaginated, a
deformity of the hair shaft of the ball and socket type, suggested by Wilkinson et al.
Netherton syndrome is an autosomal recessive genodermatosis (5q32) of unknown
cause. In its complete form, it is characterized by erythroderma inflammatory
changes; trichorrhexis invaginated (bamboo hair); linear circumflex ichthyosis;
atopic diathesis; and hypodevelopment—the development returns to normal after 2
years. Netherton syndrome has been described in all races, but is more common in
females. Its frequency is still unknown, probably because of the diagnostic difficulty.
The most common complications are skin and systemic infections. The diagnosis is
clinical and laboratory, the histologic finds are nonspecific. The response to
treatment is unsatisfactory. Possible complications need to be treat with appropriate
and effective therapeutic regimens. Emollients, keratolytics, and antibiotics are the
cornerstones of treatment.
P2005
A novel mutation in the GJB2 (connexin 26) gene in a child with clinical
and histologic features of keratitis-ichthyosis-deafness syndrome
Uffe Koppelhus MD, MD, PhD, Department of Dermatology, Aarhus University
Hospital, Aarhus C, Denmark; Gitte Esberg, MD, Department of Pediatrics, Skejby
Hospital, Aarhus University Hospital, Aarhus N, Denmark; Lisbeth Tranebjaerg,
MD, PhD, Department of Audiology, Bispebjerg Hospital, Copenhagen NV,
Denmark; Mette Ramsing, MD, PhD, Department of Pathology, Aarhus
University Hospital, Aarhus, Denmark; Mette Sommerlund, MD, PhD,
Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark
Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder that is characterized by the presence of an atypical ichthyosiform erythroderma
associated with congenital sensorineural deafness and vascularizing keratitis. KID
was first described in 1915 and fewer than 100 cases have been reported so far. The
syndrome is caused by a heterozygous missense mutation in GJB2 encoding the gap
junction protein connexin 26 (Cx26). The most frequent mutation is the p.D50N
mutation, but a few other mutations have been described. The mutations are mainly
sporadic, but familial cases (approximately 30 %) have also been reported. When
inherited, the mutation seems to follow an autosomal dominant pattern. We here,
describe a new mutation p.A88V of the Cx26 gene, leading to KID syndrome. A
different missense mutation (p.A88S) has been described in heterozygosity in a deaf
child, whose mother was also heterozygous carrier, but had normal hearing ability.
The diagnosis KID syndrome was suspected from the clinical findings: hearing loss,
ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar keratoderma, and alopecia of the scalp and eyelashes. At birth, a thick vernix caseosa like
covering of the scalp was observed. Histologic analysis showed the characteristic
pattern for KID syndrome with acanthosis and papillomatosis of the epidermis with
basket-weave hyperkeratosis. The boy was born prematurely (33 1 4), weighed
3000g (ie, as large for his gestational age), and had Apgar scores 1/1, 5/3, and 9/10.
He had intraventricular hemorrhage grade 1 to 2 and intracerebral bleeding and
developed hydrocephalus. The skin symptoms were treated successfully with
acitretin (0.5mg/kg) in combination with intensive skin care resulting in a significant
improvement of the severe hyperkeratotic lesions within 4 to 5 days. However, the
child’s condition was further complicated by septicemia and meningeal infection
with extended-spectrum beta-lactamase producing Klebsiella pneumoniae followed by severe respiratory impairment and death at 46 weeks of gestational age (13
weeks postnatally).
P2007
Mutations in TRPS1 gene in tricho-rhino-phalangeal syndrome type I
Li-Hsuan Chen, MD, Department of Dermatology, National Cheng-Kung
University Hospital, Tainan, Taiwan; Sheau-Chiou Chao, MD, Department of
Dermatology, National Cheng-Kung University Hospital, Tainan, Taiwan
Background: The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) are
autosomal dominant disorders characterized by craniofacial and skeletal abnormalities. They share common features, such as sparse and slow-growing scalp hair,
laterally sparse eyebrows, bulbous pear-shaped nose, elongated and flat philtrum,
thin upper lip, and protruding ears. Various skeletal abnormalities are also observed,
including short stature, shortening of the phalanges and metacarpals, cone-shaped
epiphyses, and Perthes-like change of the hips. The TRPS1 gene was first identified
in 2000 and mapped to 8q24.1. The gene encodes a zinc-finger transcription factor
and the mutations in it are responsible for TRPS.
Objectives: To examine clinically suspected cases of TRPS I for mutations in the
TRPS1 gene.
Methods: Blood specimens were obtained from seven patients of TRPS I. DNA
purification, PCR amplification, heteroduplex scanning by conformation-sensitive
gel electrophoresis (CSGE), and automated nucleotide sequencing were performed.
Then verification of the mutations was performed.
Results: Seven patients with the typical phenotype of TRPS I were included. Two
cases showed familial inheritance, and the others were sporadic. Three nonsense
mutations, including C2113T (Q705X), G2179T (E727X), and C1591T (R531X), and
two frame shift mutations,1184delG and C1140TA, resulting in premature stop
codons were identified in five of the patients. We were not able to detect the
mutations in the rest two patients one of whom had familial inheritance.
Conclusions: If clinicians are aware of the disease, TRPS is readily recognizable from
the clinical and radiologic features. Molecular analysis of the mutations underlying
TRPS is a viable and accessible means for diagnosis and future gene therapy. Further
study will be needed to find out if there is another gene contributing to TRPS to
explain the absence of mutations in the two patients in the series.
MARCH 2010
J AM ACAD DERMATOL
AB71
P2008
P2010
Trichorhinophalangeal syndrome: Diagnostic pearls
Marı́a Magdalena Nájera-Garcı́a, MD, Hospital Universitario ‘‘Dr José Eleuterio
González,’’ Monterrey, Nuevo León, Mexico; Carmen Liy-Wong, MD, Hospital
Universitario ‘‘Dr José Eleuterio González,’’ Monterrey, Nuevo León, Mexico; Dan
Rolando López-Garcı́a, MD, Hospital Universitario ‘‘Dr José Eleuterio González,’’
Monterrey, Nuevo León, Mexico; Diana Patricia Garza-Salazar, MD, Hospital
Universitario ‘‘Dr José Eleuterio González,’’ Monterey, Nuevo León, Mexico; Jorge
Ocampo-Candiani, MD, Hospital Universitario ‘‘Dr José Eleuterio González,’’
Monterrey, Nuevo León, Mexico
Trichorhinophalangeal syndrome (TRPS) is an autosomic genetic disorder of
variable penetrance. In 1966, Giedon associated the clinic and radiologic findings.
Its clinical manifestations are quite heterogeneous. Although three variants have
been described, they share the classic triad: hair, skeletal, and craniofacial anomalies. An 18-year-old patient came to the dermatology service with a history of
avascular necrosis of the right femoral head in childhood, who complains of
onychodystrophy and alopecia. Dermatologic exploration: dermatosis disseminated
to handnails, characterized by xantonychia, distal onycolysis, and thinning of the
ungueal plate. Furthermore he presents alopecia with a Hamilton III to IV pattern.
Physical findings: hand and feet brachydactylia, oval face, high frontal and occipital
hair implantation, olympic forehead, piriform nose, long nasal filtrum, micrognatia,
thin upper lip, winged scapulas, short height; fragile, striated, wide, and short nails,
and Trendelenburg gait. He denoted that he shares the same phenotype as his
mother and an uncle. The hand radiography reveals short phalanges with piriform
epiphyses. A mycologic examination was negative. With all the above, the diagnosis
of trichorhinophalangeal syndrome type I was made. The alopecia was managed
with minoxydil 5% spray with good results. The patient was referred to the genetics
department where he was studied, and genetic counseling was given. The TRPS type
I is associated to a mutation in 8q24.1, characterized by hipotrichosis, high frontal
and occipital hair implantation, protruyent ears, long nasal filtrum, separated and
coarse eyebrows, piriform nose, brachidactylia, and onychodystrophy. Skeletal
findings include piriform epiphyses, predominating on middle phalanges in hands,
premature ossification of epiphyses, younger skeletal age as chronologic, coxa
plana, magna or vara, and late dentition. Considering that onychodystrophy and
alopecia are common dermatologic complains, early identification of TRPS type I is
important for patients and their families, in order to receive genetic counseling and
other interventions addressing growth, orthopedic, and cosmetic issues.
Becker nevus and plexiform neurofibroma in a child with neurofibromatosis type 1: Case report
Brazil; Cı́ntia Botelho Silveira, MD, Policlı́nica Geral do Rio de Janeiro, Rio de
Janeiro, Brazil; Ludimila Nolêto de Rezende, MD, Policlinica Geral do Rio de
Janeiro, Rio de Janeiro, Brazil; Mariana Rodrigues Zangrando, MD, Policlı́nica
Geral do Rio de Janeiro, Rio de Janeiro, Brazil
Introduction: Neurofibromatosis is a group of different autosomal dominant genetic
disorders, with several aspects in common. The principal are the von
Recklinghausen disease or neurofibromatosis type 1 (NF-1), the most common,
and neurofibromatosis type 2 or acoustic bilateral. The disease occurs at any age,
sex, and race and has been observed in all parts of the world, with high incidence in
the population. The NF-1 presents cutaneous manifestations characterized by caféau-lait macules, freckle-like lesions in vaults and multiple peripheral neurofibromas;
furthermore, may affect other organs with congenital anomalies, tumors and
hamartomas. Plexiform neurofibromas (PN), lesions that practically define the
diagnosis of NF-1, are benign tumors involving multiple issues nervous. They are
nonmetastatic, vascularized, slow growing and locally invasive tumors. Their most
common site is the trunk, followed by head, neck and extremities. Reason for the
communication: uncommon association of NF-1 with Becker nevus.
Case report: The patient is a 4-year-old white male, born in Rio de Janeiro, who
presented with sessile tumor of soft consistency, skin color, on right dorsal region.
He also presents numerous café-au-lait macules on the trunk and unilateral
hyperpigmented lesion with hypertrichosis, at the right arm and shoulder. The
tumor was approached by neurosurgery.
Discussion: PN manifestations are relatively common in NF1 patients and may be
cause of increased morbidity among this group. Diagnosis is confirmed by biopsy of
one of subcutaneous nodules, but the presence of six or more macules that exceed
5mm, as occurred in this case, associated with cutaneous nodules, is sufficient to
clinical diagnosis, even in the absence of familial history. PN can be treated
surgically, although the results are often unsatisfactory, with risk of recurrence in
cases of age less than 10 years in initial surgery, presence of tumor after the initial
surgery, and tumor site (head and neck). The relationship of NF-1 with nevus of
Becker is not well established. It has been suggested that Becker nevus could be an
organoid hamartoma accompanied by variable proliferation of dermal and epidermal structures. Cases of Becker nevus associated with neurofibromas might be
another evidence supporting that suggestion.
P2009
Lack of correlation between extent of cutaneous findings and end-organ
involvement in a patient with Cowden syndrome
Erin Reese, MD, Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich, MD,
Mayo Clinic, Jacksonville, FL, United States
A 59-year-old white female presented for evaluation of new onset, asymptomatic,
slowly expanding lesions on the left lower lip and left thigh. Examination revealed a
cutaneous horn, a smooth, skin colored papule, and multiple, palmoplantar
hyperkeratotic pits. Histopathologic examination of the left lower lip lesion revealed
an endophytic epithelial neoplasm with focal clear cell change and squamatization
characteristic of inverted follicular keratosis; while the left thigh lesion demonstrated an unencapsulated dermal neoplasm comprised of finely laminated, arrayed
collagen fibers characteristic of storiform collagenoma. The presence of these
hamartomas simultaneously in a single patient was suggestive of Cowden syndrome.
On subsequent medical history review, the patient was noted to have a spinal
arteriovenous malformation, a LhermitteeDuclos lesion of the right cerebellum,
endometrial carcinoma, multinodular thyroid goiter, and numerous colon polyps.
With this constellation of findings, the patient met diagnostic criteria for Cowden
syndrome as per the National Comprehensive Cancer Network. Defects in PTEN
gene expression are well established as the cause of Cowden syndrome. This
patient’s skin findings were minimal in number and extent, while other end-organ
involvement was severe. The discrepancy between cutaneous and extracutaneous
findings is reflective of the differential effect of a given PTEN mutation on a specific
end-organ system.
This case highlights that minimal cutaneous findings in Cowden syndrome neither
predict the degree of systemic involvement nor obviate the need for multidisciplinary investigations.
P2011
AB72
Collodian baby with a prolonged membrane resulting in constrictive
bands of the fingers
Jennifer Roberts, MD, The University of Oklahoma Department of Dermatology,
Oklahoma City, OK, United States; David Adelson, MD, The University of
Oklahoma Department of Dermatology, Oklahoma City, OK, United States
A 2-month-old female born at 37 weeks with a collodion membrane presented to the
dermatology clinic with a 2-week history of the left fourth digit and left third digit
constrictive bands of prolonged membrane at the distal interphalangeal joints with
severe erythema and edema. Physical examination was notable for total ichthyosis
but sparing the genital region. The infant exhibited ectropion and residual collodion
membrane on the scalp, as well as the extensor surfaces of the legs and arms and
fingers. The marked edema, erythema, and pain of the fingers suggested substantial
risk for autoamputation. Using a no. 11 blade, the constrictive bands were cut on the
palmar aspect. Immediately following the release of the constrictive bands, the
fingers improved with less erythema and edema. At a 1-week follow up appointment, the left fourth digit and right third digit were indistinguishable from the other
fingers. Differential diagnosis for a collodion baby with a prolonged collodion
membrane primarily includes loricrin deficiency (Vohwinkel syndrome with
icthyosis), lamellar icthyosis, and congenital ichthyosiform erythroderma. These
findings prompted a pediatric genetics consult and labs including connexin 26,
connexin 30, and loricrin gene analysis. The test results are currently pending. We
report an unusual complication of a prolonged membrane creating a constrictive
band on the fingers of a collodion baby and propose a prompt treatment to release
the constrictive bands. We suggest the importance of following infants born with
collodion membranes until the membrane has fully desquamated.
J AM ACAD DERMATOL
MARCH 2010
P2012
P2014
Conradi-Hünermann-Happle: A diagnostic challenge
Cristina Susana Cantu Salinas, MD, Hospital Universitario ‘‘Dr Jose E. Gonzalez,’’
Monterrey, Nuevo Leon, Mexico; Carmen liy-Wong, MD, Hospital Universitario
‘‘Dr Jose E. Gonzalez,’’ Monterrey, Nuevo Leon, Mexico; Jorge Ocampo-Candiani,
MD, Hospital Universitario ‘‘Dr Jose E. Gonzalez,’’ Monterrey, Nuevo Leon,
Mexico; Maria Magdalena Najera Garcı́a, MD, Hospital Universitario ‘‘Dr Jose E.
Gonzalez,’’ Monterrey, Nuevo Leon, Mexico; Minerva Gomez Flores, MD, Hospital
Universitario ‘‘Dr Jose E. Gonzalez,’’ Monterrey, Nuevo Leon, Mexico
Introduction: Conradi-Hünermann-Happle syndrome is a rare genodermatosis
characterized by skeletal dysplasia, stippled epiphyses, cataracts, transient ichthyosis, and residual atrophic plaques. Mutations in the gene encoding the emopamilbinding protein (EBP) have been identified as an underlying cause.
Case report: A 1-year-old female came for evaluation with ill defined patches of
alopecia that had been present since birth. On physical examination, patches of
scarring alopecia that followed the line of Blaschko were observed; the remaining
hair appeared sparse, fine, and dry. The left hemibody clearly showed confluent,
hypochromic, and atrophic plaques following the same pattern. She also had left eye
cataract and an evident craniofacial asymmetry caused by left hemifacial hypoplasy
and short stature. Relevant clinical history: at birth, she presented on her scalp
alopecic plaques in a linear pattern and a generalized dermatosis, suggestive of
ichthyosis, therefore she was referred to the genetics department. She was referred
for evaluation to genetics and ophtalmology departments to confirm the diagnosis.
Radiologic studies revealed punctiform calcifications in axial skeleton, larynx
cartilage, ribs, and long bones epiphysis. Genetic tests were positive to EBP,
establishing polymorphism confirming the diagnosis of CHH.
Discussion: CHH is characterized by skeletal abnormalities like short stature,
asymmetric rhizomelic shortening of the limbs, and strippled epiphyseal and
craniofacial defects. Skin abnormalities are characterized by striated hyperkeratosis
and pigmentary defects patterns following the lines of Blaschko. Cataracts could be
present and the hair is coarse and lusterless with alopecic areas. Mutation in the
gene encoding the EBP, mapped in Xp11.22-p11.23, and increased levels of 8dehidrocholesterol and 8(9)-cholestenol have been implicated. These patients can
be managed with emollients and orthopedic and ophthalmologic treatments to
prevent premature arthritis and visual defects respectively.
Conclusion: It is important to diagnose CHH at an early stage to avoid complications
and to offer parents genetic advice for further offspring. Despite the efforts to treat
the patient’s main complain, it becomes a challenge to find an adequate management. It is imperative to offer a realistic panorama for the dermatologic manifestations of this syndrome.
Familial dyskeratotic comedones: Management dilemmas and social
stigma
Rashmi Mittal, MD, MBBS, Kokilaben Dhirubhai Ambani Hospital & Research
Institute, Mumbai, Maharashtra, India
Introduction: Familial dyskeratotic comedones is a rare, asymptomatic, autosomal
dominant condition with characteristic clinical and histopathologic features. The
preliminary case report was by Rodin et al in 1967. Ever since, only 17 patients from
eight families have been reported in the literature. Only two families have been
reported so far in India with this rare disorder.
Case report: A 42-year-old woman presented with a 20-year history of multiple
asymptomatic, widespread hyperpigmented keratotic papules, comedones, pitted
scars, sinuses, and freckles on all areas of body except the mucosa, legs, palms, and
soles. The keratotic papules on the trunk presented as painful, inflamed swellings. A
family history of similar lesions starting at puberty was noted in her mother,
daughter, son, siblings, maternal uncle, and maternal aunts. Her 19-year-old
daughter also presented with similar keratotic papules and multiple pits on the
face of a short duration of 4 months. In addition, she developed multiple sebaceous
cysts on the shoulder. Systemic examination was normal in both patients. All
laboratory parameters were within normal limits. Skin biopsy from the keratotic
papule revealed a crater-like invagination filled with lamellar keratinous material and
few foci of dyskeratosis.
Discussion: Familial dyskeratotic comedones is an entity described with few
characteristic findings: clinical resemblance to comedones, familial occurrence,
dyskeratotic changes on histology. It should be considered as a differential diagnosis
in conditions like Kyrle disease, reactive perforating collagenosis, nevus comedonicus, Darier disease, perforating folliculitis, and keratosis pilaris. Treatment has
largely been unrewarding. The above patients have shown minimal improvement
with isotretinoin. This case is being presented for its rarity and challenging medical
management dilemmas and attached social stigma to the entire clan. Managing these
heritable disorders is difficult both from practical and psychological standpoint. The
severity of the disease and its inheritance through generations has a severe impact
on family life.
P2015
Botulinum toxin type A as an adjuvant therapeutic option for axillary
HaileyeHailey disease
Nuria Pérez-Robayna, MD, Hospital Universitario de Canarias, La Laguna, Santa
Cruz de Tenerife, Spain; Cristina Rodrı́guez-Garcı́a, MD, Hospital Universitario de
Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Francisco Guimerá Martı́nNeda, PhD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife,
Spain; Rosalba Sánchez-González, PhD, Hospital Universitario de Canarias, La
Laguna, Santa Cruz de Tenerife, Spain; Sorahaya González-Hernández, MD,
P2013
Dystrophic epidermolysis bullosa modulated in the setting of compound
heterozygous type VII collagen mutations
Eric Harlan, MD, Mayo Clinic, Jacksonville, FL, United States; Erin Reese, MD,
Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich, MD, Mayo Clinic,
Jacksonville, FL, United States
Introduction: HaileyeHailey disease (benign familial pemphigus) is an uncommon
autosomal dominant acantholytic disorder, mainly affecting the intertriginous areas
of the body, with recurrent blisters and erosions, even smelly. These lesions are
exacerbated by heat, sweat, and rubbing, and may interfere with the daily life of
patients. At present, most medical and surgical treatments are not able to keep these
patients free of disease for a long time.
Clinical case: A 59-year-old woman with personal history of obesity had been
followed in our deparment since 1990 with the diagnosis of HaileyeHailey disease,
histologically confirmed. Since then, she has presented with significant erosive,
smelly lesions in the axillae, groins, and inframammary folds, so they interfere with
her daily life. She has made various topical and systemic therapies with occasional
slight improvement. Given that cutaneous lesions worsened by heat and sweat of
the intertriginous areas, we decided to treat the patient with botulinum toxin type A,
2.5 U distributed over 20 injection sites in each axilla, so we could observe a
significant improvement at 2 weeks of treatment. We also want to emphasize that we
did not observe any adverse effect on our patient.
We report a case of a 34-year-old woman with life-long intertriginous blisters and
extensive mucosal erosions complicated by esophageal strictures requiring esophagectomy. Her father and paternal grandmother had mild predominantly acral
blistering but completely lacked mucosal involvement. Her mother was unaffected.
Given the patient’s severe phenotype relative to her father, the patient underwent
under COL7A1 gene sequencing before conceiving a child. The patient was found to
have a paternally inherited COL7A1 splice mutation at exon 79 associated with
dominant dystrophic epidermolysis bullosa (EB), and a maternally inherited COL7A1
point mutation in exon 74 reported in recessive dystrophic EB. Clinically, her
phenotype was of intermediate severity between recessive and dominant EB forms,
as reflected by intertriginous blistering, extensive oral and esophageal involvement,
and the absence of acral scarring. This case represents a unique phenotypic example
of molecular heterogeneity characterized by dominant and recessive COL7A1
mutations in a patient with dystrophic EB.
Discussion: Botulinum toxin is used successfully in the treatment of hyperhidrosis
because it has been shown to inhibit cholinergic transmission in postganglionic
sympathetic fibers of the sweat glands, so a temporal anhidrotic effect is generated.
Improvement of the lesions in HaileyeHailey disease after treatment with botulinum
toxin might be related to a decrease in sweat production, which is usually increased
in the intertriginous areas and exacerbate the cutaneous lesions. Furthermore, by
reducing the sweating, bacterial and fungal colonization of these areas is also
reduced, which also contributes to the development of skin lesions. In conclusion,
botulinum toxin seems to be a safe and effective adjuvant therapeutic option in the
treatment of HaileyeHailey disease.
MARCH 2010
J AM ACAD DERMATOL
AB73
P2016
Ichtyosiform nevus in a 22-year-old woman
Nayra Merino de Paz, MD, Hospital Universitario de Canarias, La Laguna, Santa
Cruz de Tenerife, Spain; Antonio Martı́n-Herrera, MD, PhD, Hospital Universitario
de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Antonio Noda Cabrera,
MD, PhD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife,
Virgin Islands, United States; Eduardo Salido-Ruiz, MD, PhD, Hospital
Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Marina
Rodrı́guez-Martı́n, MD, PhD, Hospital Universitario de Canarias, La Laguna, Santa
Cruz de Tenerife, Spain
Introduction: Congenital hemidysplasia with ichthyosiform nevus and limb defects
(CHILD) syndrome is an X-linked dominant disorder. A lost of function of an enzyme
in cholesterol biosynthesis located in NSDHL gene is involved (3beta-hydroxysterol
dehydrogenase). There are fewer than 50 cases described so far. It is usually lethal in
males. This condition is included in epidermal nevus syndromes (the association of
epidermal nevi and extracutaneous abnormalities).
Clinic case: A 22-year-old Hispanic woman with a hip malformation was referred to
our department to evaluate a linear lesion located on the dorsal surface of the right
hand, forearm, and elbow since she 5 years of age. It began on the medial dorsal
surface of the hand and later it extended to the fingers and the forearm following the
lines of Blaschko. She was treated in Colombia with cryotherapy once a week from
2007 to the last year. Physical examination revealed a linear verrucous plaque with
erhytematous-yellowsish scales over an erythematous surface, 15cm long and 1cm
wide.
Results: Blood test, EKG, thoracic radiography, kidney ecography, and a cutaneous
biopsy were performed. The biopsy showed hyperkeratosis, parakeratosis, acanthosis, perivascular lymphohistiocytic infiltrate, and foamy histiocytes in dermal
papillae. The ME study showed abnormal membranes fusion and rare lysosomes
with amorphous lamellar bodies inside them.
Discussion: Some authors propose the term CHILD nevus to define this linear
verrucous lesion, but others have suggested that both NEVIL and CHILD nevus are
the same entity. They described NEVIL as an incomplete form of CHILD syndrome.
For genetic counseling, the diagnosis of mild cases is very important.
HAIR AND NAIL DISORDERS
P2100
Ischemic onycholysis of the hands
Miguel Cabanillas, MD, Complejo Hospitalario Arquitecto Marcide-Novoa Santos,
Ferrol, A Coruña, Spain; Benigno Monteagudo, MD, Complejo Hospitalario
Arquitecto Marcide-Novoa Santos, Ferrol, A Coruña, Spain; Cristina de las
Heras, MD, Complejo Hospitalario Arquitecto Marcide-Novoa Santos, Ferrol, A
Coruña, Spain; Oscar Suárez-Amor, MD, Complejo Hospitalario Arquitecto
Marcide-Novoa Santos, Ferrol, A Coruña, Spain
Introduction: Onycholysis is the distal and/or lateral separation of the nail from the
bed nail. Although it can be idiopathic, there are several factors associated with the
development of this condition. Ischemia is recognized as one of these possible
causes, but this relationship has been poorly described in the literature.
Case report: A 70-year-old woman with a personal history of ischemic cardiomiopathy and carpal tunnel syndrome was referred to our clinic with 6-year history of
onycholisis confined to the third, fourth, and fifth fingers of both hands, with no
improvement with hardening nail polish or protective measures. Traumatic etiology
was considered as she had been sewing for 20 years, but this hypothesis did not
explain the distribution of the lesions. Suspecting an ischemic origin of the lesions,
an angio-MRI of both hands was performed, that showed a severe and diffuse
vascular impairment with predominance of blood flow in radial vessels. In the right
hand, there were stenotic areas in the deep palmar arch. Daily injection of illoprost
for 1 month was proposed to the patient, but she rejected the treatment until now.
Discussion: There are many causes of onycholysis, which is one of the most common
nail signs. Although ischemia is also a recognized etipathogenic factor of onycholisis,
a search in PubMed crossing the terms of ‘‘ischemia’’ and ‘‘onycholysis’’ did not
return any result. The role of vascular hypoperfusion in the delopment of nail lesions
in our patient seems likely, because distribution of the lesions fit with the arterial
impairment showed in angio-MRI, and no other factor that explained the localization
of the nail disease could be identified. Chronic ischemia could be responsible in our
patient of the abnormal nail growth with progressive separation of the nail and the
bed nail. Intravenous iloprost, effective in the treatment of Raynaud phenomenon
secondary to scleroderma and digital ulcers, could be an useful therapeutic tool in
the treatment of vascular onycholysis, especially in those cases associated to other
ischemic manifestations.
P2017
Surgical approach of ectropion in lamellar ichthyosis
Brazil; Camila Caberlon Cruz, MD, Hospital Municipal Jesus, Rio de Janeiro,
Brazil; Joanna Pimenta de Araujo Franco, MD, Hospital Municipal Jesus, Rio de
Janeiro, Brazil; Melissa Kuhn, MD, Hospital Municipal Jesus, Rio de Janeiro, Brazil
Lamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin
disease caused by mutations involving multiple genetic loci. Type 1 maps to band
14q11.2 and is caused by mutations in the gene for keratinocyte transglutaminase 1,
an enzyme responsible for the assembly of the keratinized envelope. Type 2, which
is clinically indistinguishable from type 1, maps to band 2q33-q35. In classic lamellar
ichthyosis, children with the disease are referred to as collodion babies and are
covered at birth by a thickened membrane that subsequently is shed. The scaling of
the skin involves the whole body with no sparing of the flexural creases.
Approximately one third of children affected with this disorder develop bilateral
ectropion of the cicatricial type that appears to result from excessive dryness of the
skin and subsequent contracture. The ectropion exposes the cornea and may cause
abrasion due to friction with the epithelium squamous keratinized. The continued
aggression to cornea may lead to loss of vision, requiring the eyelid reconstruction.
In the reconstruction, two aspects should be considered: the functional aspect and
the aesthetic. Such procedure requires three basic elements: skin, mucosa, and a
structure of support. Several techniques for reconstruction of eyelid in patients, in
most cases after tumor resection, were described, including the use of skin flaps, lip
and oral mucosa, palate mucoperiosteum, aorta, composite graft of opposite
elements of the eyelid, and nasal and ear cartilage. The reconstruction of the eyelid
in patients with lamellar ichthyosis is more difficult. One of the limitations to correct
ectropion in these patients is the lack of viable skin over the entire body surface. We
present the case of a male infant showing a very important ectropion, with ulcer of
cornea. Even using occlusive dressings, the ulcer did not improve. Plastic surgery
was performed with suture of the eyelids with gaps for the child to remain with
stimuli of light. The result was very satisfactory, because the corneal ulcer was
corrected and there was substantial regression of ectropion. Currently, the patient is
8 year of age with reasonable ophthalmic conditions.
The role of mimicking growth factors to control anagen phase: Evaluation
in vitro and in vivo
Fabio Rinaldi, MD, International Hair Research Foundation, Milano, Italy;
Elisabetta Sorbellini, MD, International Hair Research Foundation, Milano, Italy;
Mauro Castiglioni, PhD, International Hair Research Foundation, Milano, Italy;
Paola Bezzola, MD, International Hair Research Foundation, Milano, Italy
The hair follicle has a very complex biologic structure, regulated by specific growth
cycles. The mature follicle undergoes successive transformation from anagen (active
hair shaft production) to catagen (apoptosis-driven regression) to telogen (resting
phase with the involution of hair follicle), and the role of apoptosis (by the pathway
of caspasis cascade) in well known in determining the passage from anagen to
catagen. Many growth factors play a fundamental role in life-long cyclic transformation of the hair follicle, functioning as a biologic switch that are turned on and off
in the different phases, controlling the active phase and promoting apoptosis to
induce catagen and telogen. The main growth factors involved in the establishment
of hair follicle are vascular endothelial growth factor (VEGF), epidermal growth
factor (EGF), and insulin 1elike growth factor (IGF-1). We studied the effect of a
pool of selected mimicking growth factors (MGFs; polypeptides) on hair bulb. We
made an evaluation in vitro (Philpott method) with single MGF and with the pool of
all of MGF, and a double-blind, randomized clinical trial on 40 women affected by
chronic telogen effluvium to evaluate the clinical effect of a mimicking growth
factors topical solution (IGF 10%, EGF10%) during 18 months. Our goal was to show
if MGFs solution could prevent dermal papilla apoptosis, prolong anagen phase
delaying catagen and telogen, and to evaluate if this effects in vivo could reduce
diffuse hair loss in chronic telogen effluvium. Our data confirm this hypothesis, and
show that a specific solution of MGFs have a significant effect on hair bulb in vitro
and in vivo used as a topical treatment, without side effects during the treatment
period and after 12 months from the end of treatment.
AB74
P2101
J AM ACAD DERMATOL
MARCH 2010
P2102
P2104
Profile of alopecia areata in 655 Chinese patients
SiSi Qi, MD, Department of Dermatology, Huashan Hospital, Fudan University,
Shanghai, China; Feng Xu, MD, Department of Dermatology, Huashan Hospital,
Fudan University, Shanghai, China; QinPing Yang, MD, Department of
Dermatology, Huashan Hospital, Fudan University, Shanghai, China; WeiWei
Dai, DO, Texas College of Osteopathic Medicine, University of North Texas
Health Science Center, Fort Worth, TX, United States
Alopecia areata and primary sclerosing cholangitis
Baptista, MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Paulo Varela, MD,
CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Rita Guedes, MD,
CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Rolando Pinho, MD,
Background: Alopecia areata (AA) is an autoimmune disorder requiring both genetic
and environmental factors for manifestation. The native Chinese population may
differ from other ethnicities in both factors, contributing to clinical variability. The
clinical profile of AA in the Chinese population has not been adequately studied.
Objective: To investigate the demographic features, clinical characteristics, and
quality of life (QoL) of AA in Chinese patients.
Methods: Six hundred fifty-five patients (320 men and 335 women) newly diagnosed
with AA were recruited as part of a prospective study between January 2006 and
May 2008 at Huashan Hospital, Shanghai, China. Demographic data, medical history,
and family history were collected. Patients were categorized by disease subtype.
Each patient was evaluated for disease onset, duration, severity, and relapse.
Psychological impact of AA was assessed by a validated Chinese version of
Dermatology Life Quality Index (DLQI) questionnaires.
Results: Three clinical subtypes of alopecia were observed in this study: patchy
alopecia, alopecia totalis (AT), and alopecia universalis (AU). Overall mean age of
onset was 35.2 years with a mean duration of 14.79 months. Patchy alopecia was
observed in the majority (86.6%) of patients while a minority (13.4%) exhibited
alopecia totalis or universalis (AT/AU). However, AT/AU patients exhibited earlier
age of onset (29.4 vs 36.1 years; P ¼.001) and longer disease duration (43.1 vs 10.3
months; P \.001) than patchy AA. Disease relapse was present in 29.8% of patients.
Patients with recurrent versus primary disease also exhibited an earlier age of onset
(28.6 vs 38.0 years; P \.001) and longer disease duration (32.5 vs 7.8 months; P \
.001). Females demonstrated a higher rate of relapse (P ¼ .004). Positive family
history was observed in 12.6% of patients, with a higher frequency in females (P ¼
.007). A medical history of at least one atopic disorder was observed in 9.9% of
patients. Atopy was found to be associated with an earlier age of onset (P ¼.026) and
more extensive disease (P ¼.022). QoL, demonstrated by DLQI scores, ranged from
0 to 29 with a mean 6 SD of 5.4 6 5.5. Mean scores of patients with AT/AU were
higher compared to patchy AA (8.0 vs 5.1; P \.001). Patients with recurrent versus
primary disease also exhibited higher scores (6.8 vs 4.9; P \.001).
Conclusion: In this study, patients with AT/AU had earlier age of onset, longer
disease duration, and quality of life was more severely impacted than patients with
patchy AA. Similar observations were made for patients with recurrent disease. In
addition, history of atopy was associated with greater disease severity.
We present a 33-year-old man with a 2-year history of extensive alopecia areata with
patchy, confluent hair loss of the scalp. The remaining dermatologic examination
was normal. He was referred by the gastroenterology consultation with the
diagnosis of small duct primary sclerosing cholangitis. He presented chronic
cholestasis with persistent high levels of alkaline phosphatase (AlkP), g-glutamyl
transpeptidase (GGT), alanine aminotranferase (ALT), and bilirubin discrete elevation. The patient had no symptoms and these alterations were noticed in a routine
serum analyses. The peripheral antineutrophil cytoplasmic antibody (P-ANCA) was
positive (1/160). The hepatic histology was consistent with primary sclerosing
cholangitis showing intrahepatic bile duct inflammation and fibrosis but with
normal findings on magnetic resonance cholangiography. A normal colonoscopy
and upper endoscopy excluded the hypothesis of inflammatory bowel disease. Drug
history, viral serologies, a1 antitrypsin, and ceruloplasmin were negative. The renal
and thyroid functions were normal as well as the remaining immunologic study.
Improvement of alopecia areata has been difficult despite treatment with oral
cyclosporine (4mg/kg/day), topical, intralesional, and systemic glucocorticoids, and
PUVA. Control of hepatic disease parallels alopecia areata although ingestion of
ursodeoxycholic acid (12mg/kg/day). There is an increased incidence of autoimmune diseases in patients with alopecia areata, particularly thyroid-related disease.
Its pathogenesis is still obscure, although most authors tend to classify alopecia
areata as an autoimmune disease. To our knowledge, this is the third case that
reports the association between alopecia areata and primary sclerosing cholangitis.
P2105
Incidence and risk factors for neonatal occipital alopecia: A retrospective
study
Bong Seok Shin, MD, Department of Dermatology, School of Medicine, Chosun
University, Gwangju, South Korea; Chan Ho Na, MD, Department of
Dermatology, School of Medicine, Chosun University, Gwangju, South Korea
Background: For many years, the etiology of neonatal occipital alopecia (NOA)
ocurring on the occiput during the early months of life has been thought to be
friction caused by the neonate’s sleeping position. It is recently clear that NOA has
no relationship with the sleep position but with the physiologic shedding of hair in
early neonatal life. However, very few studies have focused on epidemiology and
etiology of NOA.
Objective: We sought to evaluate the incidence and risk factors for NOA.
Discussion: The diagnosis of LAHS is essentially clinical and is confirmed by firmly
pulling locks of hair and microscopically examination of typical loose anagen hairs.
With the present case report, the authors highlight that even though hair loss in
children raises a considerable concern, LAHS is of cosmetic importance only and
improvement occurs with aging. Diagnostic tests, other than trichogram and hair
microscopic examination, and unnecessary treatments should be avoided.
Methods: Medical records of 240 postpartum patients delivered in the obstetrics
department at Chosun University Hospital between January 2006 and June 2007
were reviewed to obtain data on gravid females and their neonatal baseline
characteristics. Telephone interviews with 193 respondents among them were
conducted to investigate the actual conditions of babies’ NOA. Along with record
reviews, the related clinical data including the presence of NOA, initial occurrence
and restoration time of NOA, baby’s sleeping position, hair volume at birth, and the
presence of maternal postpartum telogen effluvium were asked to assess maternal
correlation and fetal risk factors of NOA.
Results: Among 193 respondents, the presence of NOA was in 39 babies (20.2%).
Bivariate analyses showed that NOA was not significantly associated with sleeping
position, hair volume at birth, birth weight, gender of baby, and parity and
postpartum telogen effluvium of mother, but was significantly associated with
gestational age, maternal age, and delivery method (P \.05). In multivariate logistic
regression analyses, the maternal risk of NOA was higher in subjects delivered after
38 weeks’ gestational age (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.229.79), in subjects younger than 36 years of parturition age (OR, 3.80; 95% CI, 1.0613.65), and in subjects not undergoing a Caesarean section (OR, 2.38; 95% CI, 1.065.33).
Conclusion: The fetus-related factors (eg, the baby’s sleeping position, etc) are not
associated with NOA, while the maternal pregnancy-related factore, such as mature
gestational age, younger gravida (\36 years old), and nonsurgical delivery are
associated with babies’ NOA in this study population. This finding raises possibility
that NOA is a physiologic condition resulting from synchronised shedding of telogen
hairs initiated in utero, because it is more affected by usual pregnant state than by
unusual pregnant state in our study.
P2103
Loose anagen hair syndrome: An unusual cause of alopecia in a child
Felicidade Santiago, MD, Dermatology Department, Coimbra, Portugal; Américo
Figueiredo, MD, PhD, Dermatology Department, Coimbra, Portugal; Ricardo
Vieira, MD, Dermatology Department, Coimbra, Portugal
Introduction: Loose anagen hair syndrome (LAHS) is characterized by the ability to
easily and painlessly extract unsheathed anagen hairs from the scalp with only a
gentle hair pull. This is an unusual benign hair disorder of childhood that is
considered to be underdiagnosed, with no more than 100 patients previously
reported in the literature.
Case report: A 5 year-old girl was referred to our clinic because of a 5-month history
of diffuse hair loss. Her hair was blond and dull with evident patches of alopecia.
There were no signs of scalp inflammation or scarring. The condition did not affect
the eyebrows or eyelashes. The girl was in good health and had no abnormalities of
her nails, teeth, skin, or eyes. A hair pull test revealed multiple hairs, easily and
painlessly extracted. Light microscopic examination and trichogram were consistent with loose anagen hair syndrome.
MARCH 2010
J AM ACAD DERMATOL
AB75
P2106
P2108
A randomized, placebo- and active-controlled, parallel-group, multicenter,
investigator-blinded study of four treatment regimens of posaconazole in
adults with toenail onychomycosis
Boni Elewski, MD, University of Alabama at Birmingham, Birmingham, AL, United
States; Amir Tavakkol, Schering-Plough Research Institute, Kenilworth, NJ,
United States; Richard Pollak, Endeavor Clinical Trials, PA, San Antonio, TX,
United States; Scott Ashton, Ashton Podiatry Associates, Dallas, TX, United States
Onychomycosis, a fungal infection of the nails, accounts for up to 50% of all
onychopathies. Although oral terbinafine (TERB) is effective and well tolerated,
approximately two in three patients do not attain complete cure with treatment.
The search for a more effective drug has proven elusive. A total of 218 subjects (1875 years of age) were randomized across six treatment arms with approximately 36
subjects in each arm. Subjects with a clinical diagnosis of moderate to severe distal
subungual onychomycosis of at least one great toenail were enrolled after confirmation of positive KOH and culture for dermatophytes. Subjects with bilirubin and
transaminases [1.5 3 ULN or on drugs that interact with azoles were excluded.
Subjects received POS oral suspension 100, 200, or 400mg QD for 24 weeks, 400mg
QD for 12 weeks, TERB 250-mg tablets QD for 12 weeks, or placebo for 24 weeks.
Treatment was given with food. Subjects were followed to week 48 after completing
therapy. The primary efficacy endpoint was complete cure at week 48, defined as
negative mycology (negative culture and KOH) and 0% nail involvement.
Frequencies of adverse events (AEs) and clinically significant abnormalities in liver
function tests (LFTs) and electrocardiograms (ECGs) were also assessed. Complete
cure rates at week 48 were significantly higher than placebo in all POS and TERB
regimens (P \.05); 22.9% on POS 100mg/24 weeks, 54.1% on 200mg/24 weeks,
45.5% on 400mg/24 weeks, and 20% on 400mg/12 weeks vs 0% on placebo.
TERB/12-week complete cure rates were 37.1%, close to the 38% shown in the TERB
PI. The overall pattern of AEs did not differ significantly among treatment arms, and
most AEs were mild to moderate. The most common reason for discontinuation was
transient increases in LFTs, which returned to within normal range on discontinuation of treatment. A total of 12 (6%) subjects discontinued the study for AEs.
Reasons for discontinuation included increases in GGT (n ¼ 5), ALT (n ¼ 3), and
others (n ¼ 4). The percent of subjects with AST/ALT [2.5 3 ULN was 0%/3% on
POS 100mg/24 weeks, 3%/3% on 200mg/24 weeks, 0%/9% on 400mg/24 weeks,
0%/3% on 400mg/12 weeks, 3%/3% on TERB, and 0%/0% on placebo. There were no
treatment-related serious AEs, life-threatening AEs, or death. There was no clinically
significant difference between treatment arms in laboratory values or ECG parameters evaluated. The results suggest that POS warrants further consideration as a
new treatment for onychomycosis.
Efficacy of topical nanoemulsion (NB-002) for the treatment of distal
subungual onychomycosis: A randomized, double-blind, vehicle-controlled trial
Marian Ijzerman, PhD, NanoBio, Ann Arbor, MI, United States; James Baker Jr,
MD, NanoBio, Ann Arbor, MI, United States; Mary Flack, MD, NanoBio, Ann
Arbor, MI, United States; Paula Robinson, MS, NanoBio, Ann Arbor, MI, United
States
Background: More effective topical therapies for distal subungual onychomycosis
(DSO) are needed. A novel antifungal emulsion (NB-002) with nanometer-sized
droplets that mechanically destabilize fungal hyphae and spores was recently tested
in a phase IIA study in 432 subjects with DSO where the baseline disease
involvement ranged from 13% to 84%. We performed a post-hoc analysis of the
subset of subjects from this trial with # 50% disease involvement at baseline to
assess the posttreatment mycologic cure and effective treatment rates of a 42-week
treatment regimen of NB-002 compared to vehicle.
Methods: Two hundred twenty-seven subjects aged 18 to 75 with # 50% disease
involvement at baseline were randomized to receive NB-002 (0.25% BID, 0.5% QD,
or 0.5% BID) or vehicle (BID or QD). Two-mL treatments were applied to all 10
toenails and 5mm of adjacent skin for 42 weeks. At 4 and 8 weeks posttreatment, the
mycologic cure rates (negative dermatophyte culture and KOH microscopy) and the
effective treatment rates (mycologic cure plus # 10% disease involvement or
$ 5mm of new nail growth determined by planimetry) were determined.
Results: All 227 subjects included in the analysis had a confirmed positive
dermatophyte culture and KOH at baseline. Four or 8 weeks posttreatment, the
mycologic cure rates in the three NB-002 treatment groups ranged from 25.0% to
31.7% versus 8.8% in the vehicle group. The effective treatment rates in the three
NB-002 treatment groups ranged from 4.2% to 16.9% in the NB-002 treatment groups
versus 5.3% in the vehicle group.
Conclusions: In subjects with DSO and # 50% nail involvement at baseline, NB-002
showed clear antifungal activity with clinically significant nail clearing. NB-002
represents a novel topical antifungal agent with an excellent safety profile for the
treatment of mild to moderate DSO.
Commercial support: Funded by Schering-Plough.
P2107
Hair care practices in different populations: What makes a difference?
Jeaneen Chappell, MD, Saint Louis University Department of Dermatology, Saint
Louis, MO, United States; Dana Oliver, MPH, Saint Louis University Cancer
Center, Saint Louis, MO, United States; Eric Armbrecht, PhD, Saint Louis
University Center for Outcomes Research, Saint Louis, MO, United States;
Sarah Jensen, MD, Saint Louis University Department of Dermatology, Saint
Louis, MO, United States
Background: A better understanding of factors influencing various hair care
practices is important for the management of hair and scalp disorders. Our review
of the literature suggests that no studies have attempted to assess what differences
(sociodemographic and/or hair attributes) are most associated with different hair
care practices.
Objectives: This study examines whether sociodemographic (SD) factors and/or hair
attributes (HA) are predictive of hair wash frequency (WF).
Methods: Ninety-six patients were recruited from the general dermatology outpatient clinic to complete an 18-item questionnaire by self-report. The questionnaire
measured SD factors, HA, and hair care practices including but not limited to
number of washes per week. Three linear regression models were constructed and
compared to determine whether SD, HA, or a combination of factors were the best
predictors of hair wash frequency. The SD group of factors included race (black/white), gender, and age group (18-30, 31-40, 41-50, and [51 years of age). The HA
group of factors included hair type (curly, straight, or wavy), texture (fine or coarse),
length (short, medium, or long), and scalp type (dry or oily).
Results: Eighty-one females and 15 males between the ages of 18 and 75 completed
the survey. Thirty-seven were African American and 59 were white. The average age
was 42.7 years. There were no statistically significant differences in age group or
gender distributions by race. The best model for predicting WF contained only SD
factors (adjusted R2 ¼ 0.59), with all factors being statistically significant: race (P \
.001), gender (P ¼ .02), and age group (P ¼ .03). The HA only model yielded an
adjusted R2 of 0.25 with the only significant variable being curly (P \.001). The
model which combined HA and SD factors yielded an adjusted R2 of 0.58, with the
only significant variables being race (P \.001) and age group (P ¼ .03).
P2109
Evaluation of the activity of laser light doses compared to an inactive
control dose on ex vivo hair growth
Matt Leavitt, DO, Medical Hair Restoration, Maitland, FL, United States
Background: Low-level laser therapy (LLLT) has been demonstrated in a commercially available device (*) to stimulate the growth of hair in males with certain classes
of androgenetic alopecia at 660nm in the clinical setting. However, to date no
studies have been conducted to ascertain the effect of other doses of lower level
laser energy on hair growth ex vivo.
Objectives: To ascertain the effect on hair growth ex vivo between two different
wavelengths of laser energy alone, a combination of the two doses together, and an
inactive control.
Methods: The four-arm study used laser wavelengths of 635nm, 660nm, a combination of concurrently administered doses of 635nm and 660nm, and a control. The
test material was gathered by scalpplasty on a 58-year-old man. Hairs were placed in
classical cell culture condition (ie, Philpott medium at 378C in a 5% CO2
atmosphere). On the day the hairs were isolated, each hair was cut approximately
1mm above the infundibulum and photographed. The length of each individual hair
was measured from the bulb to the hair tip using the measurement module of the
Olympus Cell software at baseline and days 3, 7, and 10. At baseline, hairs with a
diameter between 200 and 700m were selected for active laser exposure and then
randomized and distributed into four batches of 10 hairs. For the control, 10 hairs
with a diameter of between 400 and 900m were selected. For the control and the
635-nm and 660-nm wavelength groups, exposure was 4minutes per day. For the
combination wavelength group, exposure was 2minutes of the 635-nm wavelength
followed by 2minutes of the 660-nm for a total of 4minutes of exposure per day. For
sampling purposes, hairs exposed to the control batch were collected at baseline
and hairs exposed to the three active wavelengths were collected on day 10 and
frozen at -808C.
Conclusion: Sociodemographic variables (race, gender, and age group) are better
predictors of hair wash frequency than hair attributes (hair type, texture, length, and
scalp type). These data suggests that wash frequency, and possibly other hair care
practices, are dependent on social or cultural norms rather than attributes of the hair
itself.
Results: Mean growth for the hairs exposed to control were 38m on day 3, 255m
on day 7, and 432m on day 10. For the hairs exposed to the 635-nm wavelength,
mean growth was 327m on day 3, 602m on day 7, and 697m on day 10. For the
hairs exposed to the 660-nm wavelength, mean growth was 200m on day 3, 347m
on day 7, and 533m on day 10. For the combined wavelengths given concurrently,
hairs exposed demonstrated a mean growth of 134m on day 3, 355m on day 7,
and 533m on day 10.
Conclusions: The results of this study reveal a significant increase in the rate of
growth of ex vivo hair follicles exposed to LLLT as compared to a control group.
Commercial support: Lexington International.
Limitations: Results were limited by patient recall of WF and failure to measure other
factors that may influence WF. The sample may not be representative of the general
population and results should not be generalized widely.
AB76
J AM ACAD DERMATOL
MARCH 2010
P2110
P2112
Restoring dry, damaged hair with a novel natural wheat protein and wheat
germ oile containing shampoo and conditioner line
Judith Nebus, Johnson & Johnson, Skillman, NJ, United States; Saurabh Desai,
Johnson & Johnson, Skillman, NJ, United States; Warren Wallo, Johnson &
Johnson, Skillman, NJ, United States
Forty-twoeweek safety study of topical nanoemulsion (NB-002) for the
treatment of mild to moderate distal subungual onychomycosis: A randomized, double-blind, vehicle-controlled trial
Marian Ijzerman, PhD, NanoBio, Ann Arbor, MI, United States; James Baker Jr, MD,
NanoBio, Ann Arbor, MI, United States; Mary Flack, MD, NanoBio, Ann Arbor, MI,
United States; Paula Robinson, MS, NanoBio, Ann Arbor, MI, United States
Background: Current topical therapies for the treatment of distal subungual
onychomycosis (DSO) are largely ineffective, and oral therapies carry significant
safety risks. NB-002 is an oil-in-water emulsion made with pharmaceutically
approved ingredients to produce droplets with an average diameter of 180nm.
The size and composition of these droplets allows selective uptake into the
epidermis and dermis via hair follicles and skin pores without skin irritation. The
nanoemulsion is applied to the skin surrounding the nail and the droplets then
penetrate into the skin and diffuse laterally to the site of infection in the nail bed
where they physically disrupt and kill dermatophytes. We assessed the safety and
tolerability of a 42-week treatment regimen of NB-002 compared to vehicle.
Methods: Four hundred forty-three subjects aged 18 to 75 with a clinical diagnosis of
mild to moderate DSO of the toenails were randomized to receive NB-002 (0.25%
BID, 0.5% QD, or 0.5% BID) or vehicle (BID or QD). Two-mL treatments were applied
to all 10 toenails and 5mm of adjacent skin for 42 weeks. Safety including dermal
irritation was evaluated by AE query at weeks 1, 3, 6, 12, 18, 24, 32 42, 46, and 50.
Patients often present problems they are experiencing with their hair to their
dermatologist. Damage to hair can be caused by a multitude of factors, including the
use of harsh surfactants and excessive heat styling. Efficacious natural ingredients
have been used for many years in skin care products, but have only recently been
recognized for their benefits in hair care formulations. While many shampoos and
conditioners contain chemically modified hydrolyzed wheat proteins, these formulations have been specially designed to include whole native wheat proteins and
wheat germ oil. Wheat proteins are substantive to hair and provide lubricity to help
protect hair from styling damage. A dermatologist and professional stylist helped in
developing formulations, clinical study design, and evaluations. This clinical study
evaluated the efficacy and tolerance of three shampoo and conditioner combinations on individuals with dry damaged hair. Seventy-four female subjects between
the age of 18 and 50 with dry damaged hair were separated into three groups (thin,
normal, and thick) depending on their hair type finished the 1-week study. Subjects
used the selected shampoo and conditioner combination once daily after a 2-day
washout with a nonconditioning shampoo. Trained evaluator/clinical assessments,
self-assessments, and instrumental testing demonstrated hair benefits after three
uses. Clinical evaluation demonstrated that after three uses, the wheat protein and
wheat germ oilecontaining shampoo and conditioner regimen was well tolerated
with no significant (P\.05) increases in scalp itching, dryness, or tightness. Trained
evaluator assessments showed significant (P \.05) improvements in visual breakage, softness, and shine after just three uses of the shampoo/conditioner combination. Instrumental analysis further verified these findings. After three uses of the
wheat protein and wheat germ oilecontaining shampoo and conditioner regimen
on hair tresses, significant improvements (P \.05) were seen in strength against
breakage and hair smoothness, along with highly significant improvements in shine.
Results: Four hundred forty-three subjects started treatment and were included in the
safety population. The mean age was 52 years and subjects were generally white
(94%) and male (84%) with 49% mean nail involvement of the target great toenail at
baseline. In the three NB-002 treatment groups, the reported AEs were generally mild
to moderate in severity and as expected for this population. There were no treatmentrelated serious AEs and no subjects withdrew from the study because of treatmentrelated AEs in any of the three NB-002 groups. The most commonly reported
treatment-related AE was nail discoloration (5 subjects in the 0.25% BID group, 2
subjects in the 0.5% QD group, and 3 subjects in the 0.5% BID group); all of these
cases were mild and the majority resolved before the last study observation. Overall,
the active treatments were well tolerated with seven treatment-related application
site reactions (1 case of paraesthesia in each group; 1 case of anaesthesia, dermatitis,
and pain in the 0.25% BID group; and 1 case of irritation in the 0.5% QD group).
Conclusions: Topical application of NB-002 for 42 weeks was safe and well tolerated
in subjects with DSO. The safety and novel mechanism of antifungal action make NB002 a candidate for further investigation in the treatment of onychomycosis.
IMMUNODERMATOLOGY AND
BLISTERING DISORDERS
P2200
P2111
Bullous phemphigoid associated with hypereosinophilic syndrome and
GuillaineBarré syndrome
Badr Eddine Hassam, Department of Dermatology, University Hospital Ibn Sina,
Rabat, Rabat Salé Zemmour Zaer, Morocco; Karima Senouci, Department of
Dermatology, University Hospital Ibn-Sina, Rabat, Rabat Salé Zemmour Zaer,
Morocco; Leila Benzekri, Department of Dermatology, University Hospital IbnSina, Rabat, Rabat Salé Zemmour Zaer, Morocco; Nada Srifi, Department of
Dermatology, University Hospital Ibn-Sina, Rabat, Rabat Salé Zemmou Zaer,
Morocco; Nadia Ismaili, Department of Dermatology, University Hospital Ibn
Sina, Rabat, Rabat Salé Zemmour Zaer, Morocco
Introduction: Bullous pemphigoid (BP) is a frequent autoimmune blistering dermatosis. We describe a patient with coexistence of hypereosinophilic syndrome and
bullous pemphigoid and Guillain-Barré syndrome.
Case report: A 31-year-old woman presented in October 2007, at the time of her eighth
month of pregnancy, with a generalized bullous eruption. Cutaneous biopsies had
been carried out yet could not help decide between a bullous pemphigoid and a
dermatitis herpetiform. The patient did not improve under corticoid therapy at
1mg/kg/day and disulones at 150mg/day. In October 2008, the patient had been
admitted to the service of neurology for a syndrome of Guillain-Barré, with a good
reaction to the treatment except sequelae of fingers flexion. In January 2009, she had
been hospitalized at the service of dermatology. The diagnosis of a bullous pemphigoid
had finally been kept on data of the immunoblot. Otherwise, the patient presented
with a 7-month history of a massive hypereosinophilia that reached over 7000
elms/mm3; parasitic causes had been eliminated with the absence of Taeniasis, ascaris,
ankylostomes, and anguillules in the stools, and with the negative serologies of
toxocariasis, distomatosis, schistosomiasis, and hydatidosis. The rate of the IgEs was
increased to four times the normal, a osteomedullar biopsy had revealed a proliferation
of myeloid type, the dosage tumor markers were negative, rates of folates and the
vitamin B12 were normal. The retained diagnosis was the one of hypereosinophilic
syndrome of myeloproliferative type. A research of transcribes of fusion PDGFRaFIP1L1 was negative. A treatment with interferon-alfa and hydroxyurea is foreseen.
Discussion: Hypereosinophilic syndrome (HES) is a myeloproliferative disorder
defined by unexplained, persistent hypereosinophilia with cutaneous or systemic
involvement. HES and BP are rare disorders; four cases of BP with coexisting HES
have been reported in the literature. The fact that two rare disorders coexist may
relate to the similar cellular and molecular background of both diseases. The
association of a PB to a SGB has been described only once in the literature within the
framework of a multiple autoimmune syndrome. To our knowledge, the association
of a bullous pemphigoid to an HES and Guillain-Barré syndrome has never been
described in the literature.
MARCH 2010
J AM ACAD DERMATOL
AB77
P2201
P2203
Different bullous dermatoses in two patients with the same systemic
lymphoma: What makes the difference?
Marisa C. André, Clı́nica Universitária de Dermatologia, Lisbon, Portugal; Joana
Antunes, Clı́nica Universitária de Dermatologia, Lisbon, Portugal; L. M. Soares de
Almeida, Clı́nica Universitária de Dermatologia, Lisbon, Portugal; Paulo Filipe,
Clı́nica Universitária de Dermatologia, Lisbon, Portugal
We present two cases with similar clinical presentations of distinct bullous diseases
associated with the same type of systemic non-Hodgkin lymphoma (NHL) but with a
different diagnosis, treatment approach, and prognosis. A 59-year-old man with
tense pruriginous bullae on erythematous base on the trunk, arms, forearms, thighs,
and legs, painful erosions on his tongue, difficulty in swallowing, voluminous
ascites, and generalized adenopathies. Lymph node aspirate diagnosed NHL, Bfollicular type, stage 1, positive for CD20, CD10, and Bcl2 and negative for CD5 and
cyclin D1. Perilesional skin evidentiated suprabasal acantholysis. Direct immunofluorescence (DIF) showed intercellular deposition of IgG in the epidermis; indirect
immunofluorescence (IIF) detected intercellular IgG antibodies on monkey esophagus (1/400) and on rat bladder (1/200) but were absent on normal human skin. He
had generalized lymphadenopathies and small left pleural effusion.
Cyclophosfamide, doxorubicin, vyncristin, and prednisolone with rituximab with
rapid cutaneous response. Unfortunately, after three cycles, the patient died from
respiratory failure. A 62-year-old man was diagnosed with systemic follicular B-cell
lymphoma. He underwent autologous bone marrow transplantation after remission.
Six months later, he developed disseminated pruriginous bullae on erythematous
base with hemorrhagic filling on the feet and wrists. Suprabasal acantholysis was
seen on perilesional skin. DIF showed intercellular deposition of IgA and to a lesser
extent C3 in the epidermis; IIF evidentiated intercellular IgG antibodies on normal
human skin (1/1600) and on monkey esophagus (1/1600) but were negative on rat
bladder. He began prednisolone and intravenous immunoglobulin treatment with
significant cutaneous improvement after the first cycle; 2 weeks later he had
additional lesions on the oral mucosa and lips and reported swolling disability; after
the second combined therapy cycle the cutaneous lesions improved but the oral
lesions remained. After the ninth therapeutic cycle, he has no mucosal involvement
and reports small bullae on the ankles few days before the immunoglobulin infusion.
He is still dependent of periodic platelet and haemoglobin transfusions but has no
evidence of lymphoma recurrence. These two cases illustrate the variable presentations of pemphigus associated with systemic lymphomas, their evolution, and
different responses to treatment, which ultimately determine distinct prognosis.
P2202
Usefulness of new skin imaging techniques as accessory tools in diagnosing pemphigus vulgaris and pemphigus foliaceus
Malgorzata Olszewska, MD, PhD, Department of Dermatology, Warsaw Medical
University, Warsaw, Mazowieckie, Poland; Lidia Rudnicka, MD, PhD, Department
of Dermatology, CSK MSWiA, Warsaw, Mazowieckie, Poland; Marta Kurzeja, MD,
Department of Dermatology, CSK MSWiA, Warsaw, Mazowieckie, Poland
In pemphigus vulgaris (PV) and pemphigus foliaceus (PF), histology shows
intraepidermal acantholytic blisers. The aim of the study was to evaluate whether
new skin imaging techniques, dermoscopy, and in vivo reflectance confocal
microscopy may be used to visualize acantholytic blisters. A total of 15 lesions in
five patients with immunologically confirmed pemphigus (9 lesions in 3 patients
with PV and 6 lesions in 2 with PF) were evaluated. Dermoscopy was performed at a
20-fold and 70-fold magnification with the use of Fotofinder2 videodermoscope.
Reflectance confocal microscopy was performed with the use Vivascope 1500. Both
examinations were performed in the middle portion of the lesion and in the
adjacent, healthy appearing skin. Dermoscopy of all skin lesions in patients with PF
showed nonspecific crusting with scattered hemorrhagic inclusions. In PV,
dermoscopy showed whitish areas corresponding most probably to subclinical
epidermal detachment. In the proximity of all lesions, in both patient groups,
dermoscopy showed multiple irregular elongated blood vessels. In reflectance
confocal microscopy skin lesions of patients with both types of pemphigus showed
superficial crusts and normal or slightly disarranged basal and suprabasal layer. In
two of six (33%) lesions of patients with PF and in five of nine (55%) of lesions in
patients with PV, an intact stratum corneum was visible. In some cases a blister was
mechanically disrupted by the pressure of the camera. In all patients with PV,
confocal microscopy of skin in the close proximity to pemphigus lesions showed a
homogenous granular layer (8/9, 88%), blisters with acantholytic cells (8/9, 88%),
intraepidermal fissures in hair follicles (3/4, 75%), and enlarged blood vessels (7/9,
77%). Confocal images of adjacent skin in PF showed a less specific picture of
superficial blisters with acantholytic cells in two of six (33%) of evaluated locations
and enlarged blood vessels with vigorous blood flow in four of six (66%) lesions. In
conclusion, most reproducible findings were: irregular elongated blood vessels in
the proximity of lesions in dermoscopy and intraepidermal blisters with acantholytic cells and enlarged blood vessels in close proximity to skin lesions in in vivo
reflectance confocal microscopy. These data show that both dermoscopy and in
vivo reflectance confocal microscopy may be of some value as fast, accessory
screening tools for patients suspected of pemphigus and may be useful for
monitoring slow healing pemphigus lesions.
AB78
P2204
Hyper IgE syndrome: Cutaneous manifestations of 17 cases
Khadija Khadir, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Hakima Benchikhi,
Ibn Rochd UHC, Casablanca, Anfa, Morocco; Meriem Chrifi Alaoui, Ibn Rochd
UHC, Casablanca, Anfa, Morocco
Bagkround: Hyper-IgE syndrome (HIES) is a complex primary immunodeficiency
characterized by high serum IgE, chronic eczematoid dermatitis, and recurrent
extracellular bacterial infections. Two types of HIES have been reported: types 1 and
2. Type 1 displays abnormalities in multiple systems, including the skeletal, dental,
and immune systems, whereas type 2 shows abnormalities confined to the immune
system. The dermatitis in HIES has been described in many ways. Buckley et al
reported a generalized dermatitis that was similar to, but atypical for, atopic
dermatitis. We describe cutaneous manifestations in patients with a clinical and
biological diagnosis of HIES.
Methods: Retrospective evaluation of children who had a clinical diagnosis of HIES
and seen in our dermatology department of Ibn rochd UHC of Casablanca between
January 2000 and December 2008. Inclusion criteria were the beginning of desease
in young childhood; recurrent infections: cutaneous, bronchial/lung, or of ENT
sphere; cutaneous injury (eczematoid or not); and an IgE rate [2000 UI/mL.
Results: Seventeen patients were collected (2.08 % of patients followed for atopic
dermatitis during the same period). Average age of patients in the first consultation
was 4.82 years (14 months-16 years) with a feminine predominance (sex ratio, 1:1).
Average age in the beginning of disease was 8 months (4 days-5 years). Parental
consanguinity was found in 7 cases. In family history, we noted an atopic ground in
eight cases, recurrent pyodermite at the sister in one case, multiple sclerosis at the
mother in one case, death of a brother after purulente meningitis in one case, and a
similar symptomatology at the brother in two other cases. In personal history, we
found pharyngitis, purulente otitis, or severe pleuropneumopathy in 10 patients,
meningitis in one case, asthma in one case, chronic diarrhea in one case, cutaneous
abscesses in six cases, and eczematoid lesions of the face and members treated as
atopic dermatitis in seven cases. Cutaneous injuries were represented by cutaneous
xerosis and diffuse eczematoid plaque in 16 cases (94%), multiple pyodermite of
legs in three cases, cutaneous abscesses in four cases, impetigo in four cases, and
ichthyosis in two cases. A 4-year-old female presented with recurrent acropustulosis
associated with an oral aphtosis. Another 7-year-old patient had multiple verruca of
hands and face, erythematous papule of cheeks with varioliform healing, scalp
folliculitis, and nodular lesion of knees which histologic examination revealed
rheumatoid nodule. Recurrent arthritis of elbows was noted in this patient. A facial
dysmorphy was noted in three cases with dental defect in one case. Bacteriological
study of cutaneous lesion isolated Staphylococcus aureus in six cases. A blood
hypereosinophilia was found in 10 cases. Average IgE rate was 2438 UI/mL; other
immunoglobulin assays revealed no defects. An antistaphylococcal antibiotic was
recommended in all patients, as well as topical corticosteroids and emollients.
Evolution was able to be appreciated in only seven cases, noting an improvement
interrupted with flares of secondary infection (herpetic and bacterial).
Discussion: The particularity of our series lives in the polymorphism of cutaneous
signs. Indeed we found eczematoid lesion, already reported in the literature, in 94 % of
cases, but also other signs which are not common in HIES, such as oral aphtosis,
acropustulosis, and rheumatoid nodule. Chamlin et al described eight children with
HIES who had papulopustular eruption on the face and scalp in the first year of life.
Skin biopsy specimens showed spongiosis and perivascular dermatitis and/or
folliculitis with a predominance of eosinophils. Erdos et al reported an association
of HIES with necrotising fasciitis in 19-year-old female. The dermatitis in HIES
resembles classic atopic dermatitis but may have distinctive features. Recently, studies
were identified hypomorphic mutations in the signal transducer and activator of
transcription 3 in type 1 HIES, accompanied by susceptibility to intracellular bacteria
in type 2 HIES. Analyses of cytokine responses in both types of HIES revealed that
severe defects in the signal transduction for multiple cytokines, including interleukins-6 and -23, are leading to impaired T-helper type 17. However, the pathogenesis of
the many varied features including cutaneous remains poorly understood.
J AM ACAD DERMATOL
MARCH 2010
P2205
P2207
Rowell syndrome: Two cases of lupus erythematosus associated with
erythema multiforme
Virginia Taylor, MD, East Carolina University, Brody School of Medicine,
Greenville, NC, United States; Charles Phillips, MD, East Carolina University
Brody School of Medicine, Greenville, NC, United States; Robert Schosser, MD,
East Carolina University Brody School of Medicine, Greenville, NC, United States
Endemic pemphigus folicaceus: Laboratorial profile of patients and family
members from Juquitiba, State of S~
ao Paulo, Brazil
Valeria Aoki, MD, Department of Dermatology, University of S~ao Paulo Medical
School, S~ao Paulo, Brazil; Celina Wakisaka Maruta, MD, Department of
Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Claudia
Giuli Santi, MD, Department of Dermatology, University of S~ao Paulo Medical
School, S~ao Paulo, Brazil; Ligia Maria Fukumori Ichii, MS, Department of
Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Maria
Fernanda Longo Borsato, MS, Department of Dermatology, University of S~ao
Paulo Medical School, S~ao Paulo, Brazil
Objectives: To describe the clinical, pathologic, and serologic findings of two
patients with Rowell syndrome and to review the current literature on this rare
condition, its proposed diagnostic criteria, and management.
Case 1: A 73-year-old woman with a 1-month history of progressive rash. On
examination, she had infiltrative plaques on her face, oral erosions, and multiple
bullae on her body. There were no medications found to be associated with her rash
onset. She had a positive ANA titer of 1:640 with a speckled pattern. Her anti-SSA and
anti-RNP were positive with a negative SSB, Smith, and dsDNA. Her skin biopsy
specimen showed epidermal necrosis with acute inflammation consistent with
erythema multiforme (EM). Direct immunofluorescence was negative. She was
started on prednisone with good resolution of her skin disease and slowly tapered
off.
Case 2: A 47-year-old woman who presented with an acute onset of a pruritic rash.
She had oval erythematous patches on her trunk and extremities associated with
malar erythema. Her skin biopsy specimen showed interface dermatitis with
satellite cell necrosis felt to be most consistent with EM. She was started on
prednisone, but then began to flare as the dose was tapered. At that time, she
developed bullous lesions on her skin with surrounding erythema, as well as
mucosal erosions on her hard palate. She had a weakly positive ANA at 1:80 with a
homogenous pattern. Her anti-dsDNA, anti-Smith, and anti-RNP were negative. Her
anti-SSA antibody was positive and an anti-SSB was equivocal. She was again placed
on prednisone with a very slow taper. Unfortunately, her rash again worsened as the
dosage was lowered. A repeat biopsy showed interface dermatitis consistent with
EM. Complement levels, urinalysis, liver function tests, and serum creatinine were
all normal. Her prednisone dose was increased, and the patient was started on
mycophenolate mofetil with resolution of her symptoms. The prednisone was
eventually discontinued with no recurrence of her rash.
Summary: The rare association of lupus erythematosus and EM with specific
immunologic laboratory changes is referred to as Rowell syndrome. Since its initial
description in 1963, there have been multiple case reports in the literature and
attempts have been made to further define diagnostic criteria for the disorder. We
will review the current literature on this rare condition and present two cases who
we feel meet the criteria for diagnosis.
Background: Pemphigus foliaceus is an autoimmune blistering disease, characterized by IgG antibodies against desmoglein 1, leading to acantholysis. Endemic
pemphigus foliaceus (EPF) occurs in Brazil, especially in the states of Mato Grosso,
Mato Grosso do Sul, Goias, Minas Gerais, Parana, and S~
ao Paulo. EPF differs from
classical pemphigus foliaceus by early age of appearance, familial cases, and
inhabitants of endemic areas.
Methods: We hereby describe eight patients of EPF and eight healthy family
members from Juquitiba, state of S~
ao Paulo, Brazil, followed at the Department of
Dermatology, University of S~
ao Paulo Medical School, between 2002 and 2009.
Results: Age of the eight patients varied from 11 to 56 years of age. The diagnosis of
the eight EPF patients was confirmed by histopathologic findings, which showed
subcorneal blisters with acantholysis. Direct immunofluorescence (DIF) from the
eight patients demonstrated intercellular anti-IgG deposits. Indirect immunofluorescence (IIF) of the eight patients showed intecellular anti-IgG, titers variyng from
1:40 to 1:5120. ELISA-Dsg1 from the eight patients showed positive titers, varying
from 39 to 278 (cutoff [ 20). All eight healthy family members showed negative IIF.
Seven of out eight healthy family members showed negative ELISA-Dsg1. One of the
eight healthy family members showed positive ELISA-Dsg1 titer of 24 (cutoff [20).
Conclusion: EPF is a cutaneous blistering disease characterized by IgG antibodies
against desmoglein 1, a glicoprotein of 160kDa of the desmossome. Clinical findings
of EPF include flacid vesicles and blisters, initially on the face and scalp, with
progression to trunk and limbs. Mucosal lesions are absent. Histopathologic findings
of subcorneal acantholysis and intercellular deposits of anti-IgG in DIF and IIF are
diagnostic for the disease. ELISA-Dsg1 is positive in 98% EPF patients, indicating
active disease. Our findings confirmed the diagnosis of EPF in eight patients. Six out
eight EPF patients were blood-related. Seven out eight healthy family members
showed negative results for ELISA-Dsg1. However, one out eight healthy family
members showed positive ELISA-Dsg1, titer of 24 (cutoff [ 20). Therefore, this
healthy family member should be under clinical and immunologic surveillance for
EPF.
P2206
Umbilical involvement in pemphigus vulgaris
Valeria Aoki, MD, Department of Dermatology, University of S~ao Paulo Medical
School, S~ao Paulo, Brazil; Celina Maruta, MD, Department of Dermatology,
University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Claudia Santi, MD,
Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo,
Brazil; Felipe Sanders, MS, Department of Dermatology, University of S~ao Paulo
Medical School, S~ao Paulo, Brazil; Jose Vitor Oliveira Jr, MD, Department of
Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil
Background: Pemphigus are autoimmune bullous disorders characterized by acantholysis as a consequence of auto antibodies directed to desmosomal glycoproteins,
desmogleins 1 and 3 (Dsg1 and Dsg3). Two main forms, pemphigus vulgaris (PV)
and pemphigus foliaceus (PF), are described.
P2208
Methods: This retrospective study enrolled three patients with the diagnosis of
pemphigus with umbilical manifestation from the University of S~
ao Paulo Medical
School, Brazil. The diagnosis of pemphigus was based on clinical findings, histologic
features (HE), and direct and indirect immunofluorescence (DIF and IIF). Biopsy
from the umbilical site was taken for HE and DIF. Serum samples were collected by
the time umbilical lesions were observed.
Results: Patient 1—A 59-year-old woman with refractory mucocutaneous PV since
1994. Systemic treatment included prednisone, azathioprine, dapsone, and plasmapheresis. Umbilical lesions with crusts and vegetation appeared when PV started to
remit. Biopsy from the umbilical lesion revealed suprabasilar cleavage. DIF showed a
moderate intercellular staining. IgG circulating antibodies (1:640) were detected by
IIF. Patient 2—A 24-year-old woman with mucocutaneous PV since 2006 was treated
with prednisone (1mg/kg/day). Umbilical manifestation initiated when patient
started PV remission. HE from umbilical region revealed suprabasilar acantholysis.
DIF showed intercellular intraepithelial staining. IIF titers were 1:320. Patient 3—A
69-year-old woman with mucocutaneous PV since 2004 was treated with prednisone 1mg/kg/day. A vegetating plaque in the umbilicus was seen when PV lesions
remitted. HE revealed suprabasilar acantholysis. DIF showed intercellular intraepithelial staining, and IgG titers were 1:2560.
Conclusion: Umbilical lesions as a clinical manifestation of PV have not been
reported so far. Recognition of this presentation is relevant, once the differential
diagnosis should be made with pyogenic granuloma, Saint Joseph nodule, or
intestinal fistulae. Possible explanations for this phenomenon include expression of
altered antigens, linked with embrionary structures such as umbilical cord that
would stimulate IgG against desmogleins. Moreover, a role of the inflammatory
response related with HLA-G antigens may also be involved in autoimmune
conditions, such as pemphigus.
Evolution of signs. . .rethink. . .rebiopsy
Kashif Ahmad, MBBS, Limerick Regional Hospital, Limerick, Ireland; Bart Ramsay,
MD, Limerick Regional Hospital, Limerick, Ireland
A 55-year-old woman presented with a 6-month history of nonitchy rash on her
trunk and face. There were no aggravating factors. Before the referral she had been
treated with and had no response to potent topical steroids and two short courses of
oral prednisolone. Her medical history was not significant. On physical examination, she had an erythematous rash on her face especially around her eyes, upper
neck, and upper back. Distribution was strikingly photoexposed. A clinical
diagnosis of cutaneous lupus was made and a skin biopsy specimen was consistent
with lupus. However, routine laboratory blood values including ESR and ANA were
all normal or negative. Over the next 2 weeks, she developed transient bullae on her
lower back. A diagnosis of bullous lupus was considered and she was started on
hydroxychloroquine and prednisolone 0.5mg/kg. Three weeks later, her condition
got worse and she developed thick scaly psoriasisform plaques. Her diagnosis was
revised to psoriasis and her medication was stopped and she was started on
cyclosporin 4mg/kg. Two weeks later, her condition deteriorated with impetiginised plaques on her trunk and limbs. She was admitted and showed signs of
improvement on flucloxacillin. Three weeks later, she became erythrodermic.
Because of lack of response to cyclosporin, methotrexate was started but she did not
show any sign of improvement on this. A review diagnosis of pitryiasis rubra pilaris
was considered and acitretin was commenced. In the meantime, she developed a
few areas of erosions on her trunk. An autoimmune blistering condition was
considered and a repeat biopsy showed changes consistent with pemphigus
foliceous and direct IF showed intraepidermal deposition of IgG. She was started
on prednisolone 1mg/kg and first time in 3 months her condition improved.
Azathioprine was also added and prednisolone was tapered. We are presenting this
case to illustrate the striking staccato like evolution of her rash over many weeks.
This case confirms the need to revisit ones diagnostic hypothesis as signs change,
the importance of repeating histology and expert dermatopathology review. Two
years later, she remains clinically clear and well on low-dose azathioprine.
MARCH 2010
J AM ACAD DERMATOL
AB79
P2209
Pemphigus foliaceus in an American adolescent female
Crystal Brooks, MD, MPH, Henry Ford Medical Center, Detroit, MI, United States;
Ethan Nydorf, MD, Henry Ford Medical Center, Detroit, MI, United States
This is a case report detailing the diagnosis of pemphigus foliaceus in an African
American adolescent. The patient is a 16-year-old African American female who
presented to our dermatology clinic with a 2-month history of a pruritic, pustular
eruption of the scalp, face, and torso. She also has a history of atopic dermatitis and
epilepsy, the latter which had been well controlled on topiramate. Biopsy revealed
superficial pemphigus with 3 1 IgG staining in a desmosomal pattern. Indirect
immunoflourescence was strongly positive as was the ELISA for desmoglein 1.
Patient was placed on prednisone 40mg daily for 1 month and then transitioned to
twice daily application of fluocinonide 0.05% ointment to all erythematous, crusted
areas on the body and fluocinolone 0.01% oil to the scalp. Patient had a good initial
response to recommended therapies but was lost to follow-up. Nonendemic
pemphigus foliaceus is an uncommon phenomenon in pediatric populations, but
case reports do exist. Standard management is systemic corticosteroids. However,
adjunct therapy with topical and intralesional corticosteroids as well as dapsone
have been cited. Alternative medications described in the literature include
hydroxychloroquine, erythromycin, chloroquine, azathioprine, sulfapyridine, methotrexate, and adrenocorticotropic hormone. Although cited as a relatively benign
disease course, sporadic pemphigus foliaceus of childhood can be quite distressing
for both the affected patients and their families. As such, early recognition of disease
and initiation of appropriate therapy is important in minimizing patient morbidity.
INFECTION (BACTERIAL & PARASITIC)
P2300
Cutaneous tuberculosis inoculation after tattoing
Francisco Guimera-Martin-Neda, MD, PhD, Hospital Universitario de Canarias, La
Laguna, Santa Cruz de Tenerife, Spain; Cristina Rodriguez-Garcı́a, PhD, Hospital
Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Nuria PerezRobayna, PhD, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Santa
Cruz de Tenerife, Spain; Rosalba Sanchez-Gonzalez, MD, PhD, Hospital
Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Sorahaya
Gonzalez, PhD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de
Tenerife, Spain
Inoculation cutaneous tuberculosis after tattooing is quite rare. The skin is supposed
to be one of the organs most resistant to tuberculous infection an some cutaneous
injury is therefore necessary for inoculation of Mycobacterium tuberculosis.
Although with the appearance of professional tattoo studios, the risk of infectious
complications has been reduced, there are also many allergic reactions, granulomas,
and tumors as complications of a tattoo. We report a 27-year-old woman with
multiple erythematous papules on her left ankle over a decorative tattoo which was
created about 6 months earlier by a tattoo artist who was not authorized by the
Department of Health. No sensory loss, nerve thickening, adenopathy, or other skin
lesions were found. The Mantoux test was positive. A chest radiograph and blood
counts were normal. The skin biopsy specimen showed mild hyperkeratosis and
irregular acanthosis, with multiple compact granulomas in papillary and mid-dermis,
composed of epitheloid cells, lymphocytes, and Langhans giant cells, along with
caseation necrosis and clumps of blackish tattoo. No acid-fast bacilli were demonstrated on ZiehleNeelsen staining and culture on LowensteineJensen medium.
Polymerase chain reaction (PCR) showed positivity to Mycobacterium tuberculosis.
The patient was put on antitubercular therapy for 6 months and the lesion
completely regressed. It is likely that the shared tattoo equipment, saliva, or the
topical preparations applied after the procedure might harbor Mycobacteria,
resulting in cutaneous tuberculosis. Diagnosis is based in history, clinical features,
histology, culture, and the Mantoux test, but it is preferible to perform PCR to
identify the DNA of Mycobacterium tuberculosis in the tissues. Atypical
Mycobacterial infections, sarcoidosis, leprosy, and foreign body granulomas should
be considered in the differential diagnosis. It would be desirable to confirm the
origin of infection and culture the causative organism from the tattooing equipment
or the tattoo artist.
P2210
P2301
Bullous pemphigoid induced by radiotherapy: A case report and literature
review
Nadia Ismaili, University Hospital Ibn Sina, Rabat, Rabat Salé Zemmour Zeir,
Morocco; Badreddine Hassam, University Hospital Ibn Sina, Rabat, Rabat Salé
Zemmour Zeir, Morocco; Nada Srifi, University Hospital Ibn Sina, Rabat, Rabat
Salé Zemmou Zeir, Morocco; Noha Ezzaghba, National Institute of Oncology,
Rabat, Rabat Salé Zemmour Zeir, Morocco; Sophia Benomar, University Hospital
Ibn Sina, Rabat, Rabat Salé Zemmour Zeir, Morocco
Background: Radiotherapy (RT) may cause a range of acute and late side effects of
the skin within the irradiated area. In rare cases, radiotherapy can cause bullous
pemphigoid. Only 28 cases of bullous pemphigoid have been described in the
literature. We bring back a case of radioinduced bullous pemphigoid in a patient
treated for a squamous cell carcinoma of the vulva.
Case report: A 48-year-old patient presented in June 2008 with a vulvar ulceration.
The biopsy specimen revelated a squamous cell carcinoma. After vulvectomy and
lymph node dissection, radiotherapy was begun. Three months later (32Gy) she had
developed an erythema at the irradiated area. After 2 months (46Gy), she had
presented bullous lesions in the vulvar region that became widespread after 4 days.
The radiotherapy had been stopped. The diagnosis of a bullous pemphigoid was
confirmed at the cutaneous biopsy, the direct and indirect immunofluorescence.
The patient had evolved well under general corticotherapy.
Discussion: Bullous pemphigoid (PB) is a very common pruritic bullous skin disease,
but is rarely reported after RT. In the 28 cases described, PB complicated 22 cases of
cancer of the breast, a cancer of the cervix, a cancer of the vulva, a cancer of lung, a
cancer of the esophagus, a non-Hodgkin lymphoma, and a case of ganglionar
metastasis of a squamous cell carcinoma were identified. The PB had occurred after a
minimal dose of 20Gy. In eight patients, lesions were localized at the radiated area
and became generalized. Our patient is the second described after irradiation for a
cancer of the vulva. The triggering mechanisms remain unclear, one theory is that
RT itself changes antigenic properties and induces autoantibody formation through
the very alteration of the basal membrane with unmasking of the antigen. New
biologic agents like anti-CD25, anti-CD20 medication to reduce the production of
autoantibodies may play a role in treating BP.
Leprosy: Its different faces across time in the centro Dermatológico Dr
Ladislao de la Pascua, México
Claudia Aquino-Pérez, MD, Centro Dermatológico Dr Ladislao de la Pascua,
Mexico City, Distrito Federal, Mexico; Fermı́n Jurado-Santa Cruz, MD, Centro
Dermatológico Dr Ladislao de la Pascua, Mexico City, Mexico City, Mexico; Myrna
Rodrı́guez-Acar, MD, Centro Dermatológico Dr Ladislao de la Pascua, Mexico City,
Distrito Federal, Mexico; Obdulia Rodrı́guez-Rodrı́guez, MD, Centro
Dermatológico Dr Ladislao de la Pascua, Mexico City, Distrito Federal, Mexico
The Centro Dermatológico Dr Ladislao de la Pascua (CDP) was founded in January
1937 as a leprosy clinic; nowadays, it is the most important dermatologic referral
center in Mexico. The CDP has treated more than 7465 patients with leprosy or
Hansen disease, an infectious and chronic disease that is characterized by its low
virulence and low infectivity but serious affection with many social implications. It
does not only affect skin but it has systemic involvement, because the clinical signs
of leprosy are due related to the degree of infection but to the immunologic status of
the host. The most frequent type of the disease in the CDP is nodular lepromatous
leprosy, with 65% of our patients sharing this diagnosis, the remaining 35% account
for tuberculoid leprosy and indeterminate and borderline cases. Although its
existence has been underestimated, leprosy continues to be an important health
issue, and new cases are diagnosed every year in our center. Since it was founded,
150 patients per year were seen for the first time and diagnosed with leprosy. At
present, five to seven patients per year arrive; this reduction correlates with the
actual prevalence of 0.06% and incidence of 0.02% of leprosy in our country. In
2008, there were 650 patients with confirmed diagnosis and 223 new cases
detected, 165 of them were multibacillary and 93 were women. With the advent of
antileprotic sulphonic drugs (Promin), then dapsone and finally multidrug therapy
(MDT), infection can be treated, individuals made noninfectious, and the pool of
infection in the community reduced. It also changed the way leprosy manifested
itself clinically: from the destructive and disfiguring images of lepromatous leprosy,
the permanent sequelae and disability results we were used to see; to a more
discrete picture with fewer lesions and lesser consequences, making the diagnosis
more challenging every day. Our objective is to compare between the different types
and cases of leprosy we saw in the CDP before MDT and nowadays and to illustrate
its differences.
AB80
J AM ACAD DERMATOL
MARCH 2010
P2302
P2304
Regional cutaneous BCGosis in a host with normal interferon gamma
cellular responses
Rishika Sinha, MBBCh, University College Hospital, London, United Kingdom;
Emma Edmonds, MBBS, Department Of Dermatology, London, United Kingdom;
Francisco Vega-Lopez, MD, MBBS, PhD, Department Of Dermatology, London,
United Kingdom; Patricia Gorak-Stolinkska, MBBS, Immunology Unit, London,
United Kingdom
It has been estimated that approximately one third of the worldwide population is
infected with Mycobacterium tuberculosis. From this pool, nine million cases of
active tuberculosis emerge every year resulting in approximately two million deaths
per year. Early last century, researchers developed the Bacillus-Calmette-Guérin
vaccine (BCG) from a weakened strain of M bovis. This vaccine confers variable
degrees of protection against tuberculosis and other mycobacterial infections.
Eventhough vaccination with BCG can be frequently associated with local cutaneous reactions, disseminated BCG infection following vaccination is rare and largely
seen in patients with inherited or acquired immunodeficiency syndromes. In the
context of effective cell mediated immunity, interferon gamma (IFN-g) is a pivotal
cytokine in the protective response to M tuberculosis via macrophage activation. A
16-year-old patient was referred to the dermatology department for assessment of
three nonhealing nodular lesions on her left upper arm that had persisted following
a BCG vaccination at that site 4 years earlier. Routine serologic markers and a chest
radiograph were normal. Microscopic appearances of an incisional skin biopsy
taken from the scar site and adjacent nodule were consistent with a BCG vaccination
granuloma and scar. Special stains for acid-fast bacilli, fungi and bacteria failed to
detect microorganisms. Bacterial culture of biopsy tissue revealed no growth.
Investigations were carried out to assess her cytokine profile before and during
therapeutic intervention. An enzyme-linked immunosorbant assay (ELISA) demonstrated an appropriate decrease in the number of spot forming cells during
treatment. A cytokine release assay was performed showing a reduction in the
magnitude of response to BCG antigen both before and during treatment. A
functional assay confirmed our patient’s ability to produce tumor necrosis
factorealfa in response to stimulation with recombinant IFN-g and lipopolysaccharide. On the basis of the clinical presentation and positive ELISA testing, the patient
was treated for local and regional cutaneous BCGosis and commenced on rifampicin, isoniazid, and ethambutol. Pyrizinamide was not offered as chemotherapy
because of the known resistance of BCG to this drug. Clinical and immunologic
resolution of the infection was seen after completion of triple therapy.
Actinomycetoma of the head—a clinical and therapeutic challenge
Amelia Morales-Toquero, MD, Hospital Universitario Dr Jose Eleuterio Gonzalez,
Monterrey, Nuevo Leon, Mexico; Jorge Ocampo Candiani, MD, Hospital
Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico;
Lucio Vera-Cabrera, DDSc, Hospital Universitario Dr Jose Eleuterio Gonzalez,
Monterrey, Nuevo Leon, Mexico; Minerva Gomez-Flores, MD, Hospital
Universitario Dr Jose Eleuterio Gonzalez, Monterrey, Nuevo Leon, Mexico;
Oliverio Welsh, MD, DDSc, Hospital Universitario Dr Jose Eleuterio Gonzalez,
Monterrey, Nuevo Leon, Mexico
Treatment of cranial actinomycetoma is difficult. It requires rapid diagnosis and
effective treatment to prevent spreading to the brain. We report a case of a 44-yearold woman with diabetes with actinomycetoma of the head cured with a combination of trimethroprim-sulfamethoxazole (SXT) and amikacin. She had an automobile accident 7 years earlier that caused multiple injuries of the head and face that
were surgically repaired. Six months before presenting at our service, a neoformation of the left temporoparietal region appeared. A plastic surgeon performed a fineneedle biopsy before that showed a lymphohystiocytotic infiltrate. Imaging studies
did not reveal bone affection. She was referred to our department for evaluation
before surgery. On physical examination, we observed a 6- 3 5-cm red friable
granulomatous vascular tumor on the left temporoparietal region with 10cm of
perilesional swelling and a 5-mm nodule on the external cantus of the left eye. Direct
mycologic examination showed multiple granules of Nocardia. Biopsy and culture
confirmed the diagnosis of actinomycetoma caused by N brasiliensis. Antibodies
were positive for N brasiliensis with an initial absorbance titer of 0.8935. After
normal renal and audiometric study, she was treated with amikacin 15mg/kg/day IM
for 12 weeks together with oral SXT 8/40mg/kg/day (8 months). After therapy, there
was total remission of the lesion. Antinocardia antibodies returned to normal levels
(0.317). Actinomycetoma of the head is rare presentation. This case represents a
diagnostic challenge because it mimics a vascular neoplasm, sarcoma, and other
tumors as well as fungal and mycobacterial infection. In cases with a risk of
spreading infection to underlying organs or in those unresponsive to previous
treatment, amikacin together with SXT can be used until cure is achieved. Treatment
can be changed if antimicrobial resistance or side effects develop. N brasiliensis is
the most frequent agent causing actinomycetoma in Mexico and generally responds
well to SXT. In a case such as this, SXT-amikacin is the best choice because it achieves
a rapid cure and prevents dissemination.
P2303
P2305
Reactive arthritis with psoriasiform skin lesions and the importance of
using DNA amplification tests for not missing Chlamydia trachomatis
genital infections: Report of a case
Joao Costa, Serviço de Dermatologia do Hospital de Santa Maria, Lisboa, Portugal;
Filomena Martins, Unidade de DST do Instituto de Higiene e Medicina Tropical,
Lisboa, Portugal; Luı́s Soares de Almeida, Serviço de Dermatologia do Hospital de
Santa Maria, Lisboa, Portugal; Manuel Marques Gomes, Serviço de Dermatologia
do Hospital de Santa Maria, Lisboa, Portugal
Reactive arthritis, also known as Reiter syndrome, is defined by the classical triad of
arthritis, urethritis, and conjunctivitis following a gastrointestinal or a nongonococcal genitourinary infection. We describe a 23-year-old man with recurrent episodes,
after engagement in new relationships, of mucous urethral discharge and dysuria
usually followed 3 weeks later by a mild bilateral conjunctivitis, severe joint pain,
and articular swelling in an asymmetrical distribution, cutaneous lesions of keratoderma blennorrhagicum, balanitis circinata, and nail dystrophy. An etiologic agent
was never found, and after this admittance he developed also psoriasiform skin
lesions in a disseminated pattern. Besides elevation of the laboratory parameters of
inflammation he had a positive a skin biopsy compatible with psoriasis and tested
positive for HLA-B27. Serology for HIV and syphilis was negative as also were the
laboratory tests for autoimmunity and antirheumatoid factor. We treated him and his
asymptomatic female partner with 1g per os of azithromycin after collection of urine
and exsudates for testing with a polymerase chain reaction for Chlamydia
trachomatis with a technique targeting the cryptic plasmid of these bacteria. The
patient and his partner had both positive reactions to C trachomatis with the
visualization of a 241 pb band in the gel electrophoresis. As recommend by the
Center of Disease Control and also with epidemiologic purpose, the tests were
repeated with a different target in the genome of C trachomatis. These tests were
also positive and the bacteria had genotype E in both the patient and his partner. The
patient was then informed of the association of C trachomatis infection with his
reactive arthritis, the absence of protective immunity to new infections with this
bacteria and the use of condoms was promoted. The genitourinary complaints
remitted with the antibiotic but control and regression of skin lesions and articular
complains were only achieved after the initiation of IM methotrexate.
Mycobacterium chelonae: A rare but important cause of leg ulceration
Kusuma R Narayana, MBBS, Addenbrooke’s Hospital, Cambridge,
Cambridgeshire, United Kingdom; Jane Sterling, MBBCh, Addenbrooke’s
Hospital, Cambridge, cambridgeshire, United Kingdom; Jonathan Batchelor,
MBBS, Addenbrooke’s Hospital, Cambridge, Cambridgeshire, United Kingdom
Mycobacterium chelonae is a rare pathogen that causes infection among humans. It
has been reported among both immunocompetent and immunosuppressed patients. We describe a case of leg ulcers caused by M chelonae. A 86-year-old man
presented with painful red areas on his legs, which appeared spontaneously. These
rapidly changed to multiple, shallow, superficial ulcerated areas of erythema with
overlying eschar. There was no history of trauma or vascular disease. He had been on
long term oral corticosteroids for polymyalgia rheumatica and had a long-term
indwelling catheter for urethral stricture related to bladder carcinoma. A skin biopsy
specimen revealed a normal epidermis with multiple microabscesses and faintly
granulomatous inflammation in the dermis. There were vacuoles containing
elongated and rod-shaped organisms, which stained strongly positive with both
Zeil-Neilson (ZN) and modified ZN stain, suggesting atypical mycobacteria. Liquid
culture and subcultures identified M chelonae. The patient was treated with
clarithromycin and moxifloxacin but discontinued treatment because of side
effects. Topical fucibet and regular dressings has made significant improvement.
M chelonae is a Gram-positive, opportunistic, fast growing atypical mycobacterium,
which is rarely pathogenic. The organism is found in sewage, soil, and is especially
common in tap water. Infection with M chelonae can be caused by trauma to the
skin, cosmetic procedures (eg, pedicure, Botox injections) and invasive procedures
(eg, central venous catheters, implants, and subcutaneous injections). The infection
is more frequent in males, the elderly, and those with autoimmune disorders. More
than 90% of cases occur in patients on long-term corticosteroids. There is no
evidence of human-to-human transmission. M chelonae can also cause serious lung
disease, osteomyelitis, corneal ulceration, and keratitis. Local wound care and
antibiotics are reported to be the mainstay of medical management. Surgical
debridement is required for extensive lesions. Standard antituberculous drugs have
been shown to have no role in treatment. Dermatologists should be aware that M
chelonae is a rare but important cause of skin ulceration.
MARCH 2010
J AM ACAD DERMATOL
AB81
P2306
P2308
Generalized Tunga penetrans infestation: Brazilian case report and review
of the literature
Marina Besen Guerini, MD, Universidade Federal de Santa Catarina, Florianopolis,
Santa Catarina, Brazil; Claudio Kern Nogueira, MD, Universidade Federal de Santa
Catarina, Florianopolis, Santa Catarina, Brazil; Daniel Holthausen Nunes, MD,
Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brazil;
Naiana Bittencourt Sa, MD, Universidade Federal de Santa Catarina, Florianopolis,
Santa Catarina, Brazil
Introduction: Tungiasis is an ectoparasitic infection caused by the penetration of the
sand flea Tunga penetrans into the skin of the host. Flea infestation is associated
with poverty. In Brazil, it is widespread in urban squatter settlements, villages in the
rural hinterland, and in traditional fishing communities along the coast. Standard
therapy for tungiasis consists of removing the embedded flea with a sterile needle.
We describe a case of severe infestation treated with surgical extraction and oral
ivermectin.
Case report: A 73-year-old man presented with multiple papular eruptions and
pruritus on the feet, hands, and legs. He was an alcoholic who lived in precarious
housing conditions with a dog. On examination, the patient had multiples
papulonodules, some brownish with a central black dot, some crusted necrotic
papules, and other hyperkeratotic nodules, involving mainly the feet but also the
hands and knees. There were no lesions on the area covered by his usual sandal. He
was admitted at the University Hospital and the severe infestation was treated with
daily surgical removal of the fleas and oral ivermectin (300g/kg/wk) over the
course of 2 weeks. Antibiotic and antitetanic immunizations were also performed. At
the end of therapy, he was sent to an alcoholism rehab center.
Discussion: Tungiasis is an endemic dermatosis in Brazil. The flea is indigenous to
the West Indies/Caribbean/Central America region, but it has spread to Africa, India,
Pakistan, and South America. Typically, it affects the periungual area of the toes,
heels, and soles of the feet. However, in severe cases, other ectopic sites of infection
have also been reported, including the hands, elbows, thighs, and the gluteal region.
Generalized infestation is common in alcoholics, mental illness patients, and the
homeless. Although tungiasis is a self-limited infection, severe complication such as
deformation or loss of toenail, secondary infections, or tetanus are common in
endemic areas. Surgical extraction of the flea with a sterile needle remains the
appropriate treatment. In generalized infestation, the pharmacology therapy was
controversial, but there are reports of use of niridazole (30mg/kg), thiabendazol (2550mg/kg/day), and oral ivermectin (200-300g/kg/wk). The patient reported
presented improvement after hospitalization, being treated with ivermectin
(300g/kg/wk), and surgical removal. The treatment and the evacuation of his
poor environment contributed to the positive results.
Imported leprosy in Spain
Antonio Alcaide-Martı́n, Virgen de la Victoria University Hospital, Málaga, Spain;
Enrique Herrera, Virgen de la Victoria University Hospital, Málaga, Spain;
Francisco Vı́lchez, Virgen de la Victoria University Hospital, Málaga, Spain;
Guillermo Ruiz del Portal, Virgen de la Victoria University Hospital, Málaga,
Spain; Ricardo Bosch, Virgen de la Victoria University Hospital, Málaga, Spain
Introduction: Leprosy is a chronic granulomatous disease principally affecting the
skin and peripheral nervous system. It is caused by infection with Mycobacterium
leprae. Although much improved in the last 25 years, knowledge of the pathogenesis, course, treatment, and prevention of the disease continues to evolve. The
worldwide prevalence of leprosy is reported to be just less than 1 case per 10000.
Most affected persons live in the tropics and subtropics. Six major countries in Asia,
Africa, and South America have not achieved the goal of elimination (\1 case per
10000 population). Approximately 77% of reported cases are found in eight
countries: Brazil, the Democratic Republic of the Congo, India, Indonesia,
Madagascar, Mozambique, Nepal, and the United Republic of Tanzania. We present
six cases of imported leprosy newly diagnosed in our hospital.
Case reports: Four women and two men between the ages of 26 and 80 years old.
The infection occurred in four cases in south American countries (Colombia,
Venezuela, and two in Brazil), an in two cases in Africa, one in Mali, and the other in
Nigeria. Three patients were diagnosed with an indeterminate type of leprosy, two
cases of borderline tuberculoid leprosy, and one of tuberculoid leprosy. All the
patients were treated and diagnosed in our hospital with a good outcome of their
infection.
Discussion: Although Spain is one of the historic hotbeds of leprosy, the diagnosis of
new cases among natives is very rare. On the other hand, recently with the
immigration and the increased mobility of people, the detection of imported cases of
this disease has raised. Approximately 95% of these patients acquired their disease in
developing countries. We present these cases in order to remark the importance to
think in this patology in patients coming from endemic countries. Clinical forms of
the disease are frequently different from those we used to see in our country, which
together with the wide variety of clinical leprosy often makes the diagnosis difficult.
P2307
P2309
Uncomon presentation of secondary syphilis in an HIV-positive patient
Rita Guedes, MD, Centro Hospitalar Vila Nova de Gaia, Porto, Portugal; Ana
Moreira, MD, Centro Hospitalar Vila Nova de Gaia, Porto, Portugal; Armando
Baptista, MD, Centro Hospitalar Vila Nova de Gaia, Porto, Portugal; Eduarda
Ferreira, MD, Centro Hspitalar Vila Nova de Gaia, Porto, Portugal
Secondary syphilis can have protean clinical manifestations and may present with
unusual lesions, which may go unrecognized. Often referred to as the ‘‘great
imitator,’’ the disease poses diagnostic dilemmas when it produces unusual skin
lesions. Recognizing these unusual manifestations becomes especially important in
the era of HIV infection. We describe the clinical case of a 34-year-old man who
presented with an asymptomatic eruption on the face, chest, and extremities. He
reported the appearance of the first lesion 4 weeks before, first on the dorsal surface
of his hand, spreading over the next several weeks. He had no constitutional
complains. He referred a history of syphilis (10 years earlier) that had apparently
been successfully treated. Clinically he presented with multiple, widespread, fleshcolored to red-brown nodules, of which several had a crusted surface. Findings of
the physical examination were otherwise unremarkable. VDRL and TPHA were
positive, as was an HIV test. The histologic evaluation supported the clinical
diagnosis of syphilis, and PCR evaluation for Treponema pallidum was positive and
confirmed the secondary phenomenon. The lesions healed slowly after treatment
with penicillin, first with attenuation of their infiltrative pattern, and later with a
postinflammatory pigmentation. Nodular lesions of syphilis seem to be uncommon
but are periodically reported in the literature. Although these nodules are said to be
more common in tertiary syphilis, most recent reports have diagnosed them as a
manifestation of secondary syphilis. These nodular lesions have been referred as
framboesiform or raspberry-like. Some authors have suggested that the nodular form
of syphilis represents a reaction of specific hypersensitivity to treponemal infections, while others believe the nodular lesions should be correlated with the
duration of the disease, representing a transition to a tertiary phase. The authors’
aim with this poster is to emphasize the many clinical forms of syphilis and point out
that this variability is even more marked when HIV infection is present. Nodular
syphilis is an uncommon manifestation of secondary syphilis and may go unrecognized. However, a high degree of clinical suspicion and a careful sexual history,
followed by serologic, histologic and, in some cases, molecular tests, permits
accurate diagnosis, thus facilitating prompt treatment of these cases.
Atypical presentation of lues maligna in an HIV patient
S. Priya Sivanesan, MD, University of Pittsburgh, Pittsburgh, PA, United States;
Alexandra Zhang, MD, University of Pittsburgh, Pittsburgh, PA, United States;
John Ho, MD, University of Pittsburgh, Pittsburgh, PA, United States
Lues maligna is a rare noduloulcerative variant of syphilis. Several cases of lues
maligna as the initial presentation of HIV have been reported, but this remains a rare
entity. Here we report a dramatic presentation of lues maligna as the initial
presentation of HIV. A previously healthy 52-year-old white man presented to our
clinic complaining of painful skin lesions that developed after starting amoxicillin
for ‘‘welts’’ on his chest 6 months before his visit to our office. He also reported an
unintentional weight loss of 50 lbs in 2 months that was associated with decreased
appetite, chills, persistent diarrhea, drainage from the eyes, generalized pain,
peeling of his hands, and weakness of all extremities. An IM steroid injection and
diphenhydramine resolved the rash in a few days, but it returned a month before his
visit to our clinic. The physical examination revealed a cachectic male with
significant weakness requiring assistance during the examination. He was disoriented to time. There were diffuse ulcerations and erosions with yellow exudates and
hemorrhagic crusting over scalp, face (including eyes, nose, and lips), trunk, upper
extremities, and lower extremities. There were erythematous, scaly thin plaques
over the scrotum and penis and desquamation of the palms and soles with
erythematous macules on bilateral palms. Bacterial and viral cultures, DFA for
HSV/VZV, pan CT scan, and Clostridium dificile cultures were negative. The skin
biopsy specimen showed a florid mixed infiltrate of lymphocytes, neutrophils, and
numerous plasma cells that was consistent with syphilis. DIF was negative. RPR and
FT-ABS were positive. Additional tests revealed a positive HIV with CD4 of 224,
positive hepatitis B, and positive CMV. Treatment with IV penicillin after desensitization led to rapid improvement in both skin and neurologic status. The patient
was eventually discharged home with no assistance and had complete resolution of
his skin lesions. HIV and low CD4 counts make the presentation of syphilis more
dramatic in cases of lues maligna; however, the presentation of this patient is unique
with extensive ulcerations with hemorrhagic crusting and profuse exudates. In
addition, the mucosal involvement was reminiscent of a paraneoplastic or
immunobullous process. This atypical presentation of lues maligna is a reminder
that syphilis can have various presentations and should be considered in any unusual
case.
AB82
J AM ACAD DERMATOL
MARCH 2010
P2310
P2312
Use of operating microscope to visualize eggs of Tunga penetrans
Karen Powers, MD, Virginia Commonwealth University Medical Center,
Richmond, VA, United States; Michael Edmond, MD, MPH, MPA, Virginia
Commonwealth University Medical Center, Richmond, VA, United States;
Steven Montante, MD, Virginia Commonwealth University Medical Center,
Richmond, VA, United States
Secondary syphilis: Case report
Clarissa Caramez, Policlinica Geral do Rio de Janeiro, Rio de Janeiro, Brazil;
Camila Alves, Fiocruz, Rio de Janeiro, Brazil; José Augusto Nery, PhD, Fiocruz, Rio
de Janeiro, Brazil; Laeciana Godin Sampaio, Fiocruz, Rio de Janeiro, Brazil
Background: Syphilis is an infectious disease caused by etiologic agent Treponema
pallidum. Tegumentary lesions determined polymorphism, able to mimic various
dermatoses.
Purpose: Demonstrate a case of secondary syphilis exuberant in spouses.
Background: Tunga penetrans is a sand flea that burrows into human skin, causing
an ectoparasitic public health disease endemic to South America, Africa, and the
Caribbean. Although tungiasis is not endemic to the United States, patients may
present with this disease upon return from tropical locations. Usually tungiasis is
acquired by walking barefoot in sand contaminated by feces of sylvatic and domestic
animals, the preferred hosts of T penetrans. The female parasite penetrates the
epidermis of its host and hypertrophies before expelling hundreds of eggs and dying
in situ. While such infestation is self-limited, the sequelae of tungiasis include
cellulitis and gangrene.
Methods: Four days after returning from a 4-week trip to Gabon, a 49 year-old
biologist noted a central 3-mm brown lesion with a 5-mm white halo near her right
great toenail. Plastic surgery was consulted for wide local excision of the painful
lesion, which included the lateral nail fold and perionychium to ensure that no flea
remnants remained in the wound. After excision in the operating room, the lesion
was examined using a Carl Zeiss surgical operating microscope.
Results: In situ the lesion most closely resembled stage 3b/4a according to the
Fortaleza classification system. A convex white halo surrounded a central dark
periungual protrusion. After excisional biopsy, microscopic examination of the
lesional dermis revealed inflammation, vascular dilatation, and at least a dozen
Tunga eggs. The Tunga eggs were shining white ovoids that measured approximately 0.5mm in length and 0.3mm in width. No arthropod carcass was readily
identified grossly, microscopically, or when the specimen was sent to pathology. An
infestation with the flea T penetrans was confirmed by gross and microscopic
analysis by surgical pathology.
Conclusions: Descriptions of the lesions caused by female flea T penetrans and its
eggs using histology, scanning electron microscopy, and dermoscopy have been
described in the literature. We used a surgical operating microscope to visualize the
Tunga eggs and the dermal host inflammatory findings in an excisional biopsy from a
periungual lesion. This modality may prove useful for clinical and basic science
research into tungiasis.
Presentation: A 38-year-old woman who was born and lived in Rio de Janeiro sought
various health services showing nodules, erythematous maculopapular spread by
skin, and cervical lymph node. Presented, the typical clinical examination, VDRL
1:64, TPHA-positive and biopsy of skin compatible with secondary syphilis. She
contacted her husband who had alopecia in light and scattered erythematous
papules on the trunk. Both were treated with benzathine penicillin 2.4 million in
two doses in the week, with significant improvement of lesions and reduction of the
titration. The tests recommended by the Health Ministry on Sexually Transmitted
Diseases had been made with negative results.
Discussion: It is important to emphasize early diagnosis by health professionals in
order to interrupt the chain of transmission of the disease, which interferes with the
occurrence of new cases, including other sexually transmitted diseases. Syphilis
continues as a bigger public health problems today, although the treatment is
inexpensive and highly effective.
INFECTION (FUNGAL)
P2400
P2311
Diagnostic difficulties before a case of lymphogranuloma venereum
exuberant
Clarissa Caramez, Policlinica Geral do Rio de Janeiro, Rio de Janeiro, Brazil; José
Augusto Nery, PhD, Fiocruz, Rio de Janeiro, Brazil; Roberta Lemos, Fiocruz, Rio
de Janeiro, Brazil; Thatiana Hadlich, Policlinica Geral do Rio de Janeiro, Rio de
Janeiro, Brazil
The lymphogranuloma venereum (LGV) is a disease primarily of sexual transmission,
caused by Chlamydia trachomatis, characterized by the presence of an inguinal
bubo. Although the prevalence of LGV is not significant between sexually
transmitted diseases (STDs), some cases have been reported and have increased
the occurrence of cases of disease exuberant. A 53-year-old man from Rio de Janeiro
had several health issues like condilomatosa lesion that are shown in the glans and in
the inguinal lymph node. After going through various departments of dermatology,
he was referred to our clinic for evaluation and diagnosis. Some tests were requested
(culture for mycobacteria, VDRL, FTA-Abs and serology for viral hepatitis) with
negative results. We confirm lymphogranuloma venereum through a complement
fixation test with titre more than 1:64. The patient was subjected to the treatment of
the National Program for Sexually Transmitted Diseases of the Health Department,
standardized for our country, doxaciclina, 200mg per day for 7 days, developed with
healing of the lesion. The LGV is a disease that often is not noticed in the initial lesion
by the patient and is rarely observed by doctor. After 1 to 3 weeks of the initial
apearence, there are signs of inflammatory acute in the inguinal and femoral nodes,
comprising the secondary stage and may be accompanied by fever, general malaise,
myalgia, headache and generalized lymphadenopathy, usually subacute, painful,
unilateral (in 70% of cases) and becoming the main cause of lymphogranuloma
venereum consulta. Confirmed up through the test setting completion of titres with
more than 1:64. This test is the most often used, with a high sensitivity and low
specificity. Becomes positive after 1 to 3 weeks after onset of disease and an increase
of four times in the titles of antibodies is indicative of active disease. O test is positive
in 80% to 90% of cases of LGV. Although the prevalence of LGV is not significant
between STIs, it is important to consider the cases of LGV that still exist, even in a
lush, and in many cases it can be identified by the dermatologist is difficult.
Oral manifestations of disseminated sporotrichosis in a patient with AIDS
André Luiz da Rocha Azevedo, MD, DDS, Federal University of the State of Rio de
Janeiro - HUGG - Unirio, Municipal Hospital of Petrópolis - HMNSE, Rio de
Janeiro, Brazil; Carlos José Martins, MD, Federal University of the State of Rio de
Janeiro - HUGG - Unirio, Rio de Janeiro, Brazil; Ricardo Barbosa Lima, MD, Federal
University of the State of Rio de Janeiro - HUGG - Unirio, Rio de Janeiro, Brazil;
Thaı́s Harumi Sakuma, MD, Federal University of the State of Rio de Janeiro HUGG - Unirio, Rio de Janeiro, Brazil
Background: Sporotrichosis is a deep fungal infection, with a worldwide distribution, caused by the dimorphic fungus Sporothrix schenckii. Besides the conventional route of inoculation through wood splinters, thorns, and contaminated
organic material, there is an epidemic of cat-transmitted sporotrichosis in Rio de
Janeiro, Brazil. Humans can be contaminated by cat’s scratch or bite and even by
contamination of previously injured skin. S schenckii disseminated infection is
unusual, but it has been reported in immunodeficient individuals, such as HIVpositive patients. It results from the hematogenic dissemination of the fungus
starting from an inoculation focus. We report a case of cutaneous disseminated
sporotrichosis with oral lesions in an HIV-infected patient, who developed the
disease after a scratch from his cat.
Case report: A 45-year-old HIV-positive black man with a CD4 count of 13 cells/mm3
presented with a 3-week history of multiple cutaneous lesions accompanied of pain
in the oral cavity. The physical examination revealed ulcerated lesions on the palate,
the dorsal surface of the tongue, and the left nare. He also presented with
variceliform pustules and crustued nodules on the face, ears, and limbs. He reported
a scratch from his diseased cat on his right hand 2 weeks before the start of
symptoms. The cytology of the scrape of oral lesions showed periodic acideSchiff
positive spherical or elongated (cigar bodies) spore forms. The biopsy of a crusted
nodule on the dorsal surface of the hand revealed necrosis and a granulomatous
infiltrate and the culture for fungus demonstrated colonies of S schenckii.
Amphotericin B was introduced but the patient developed impairment of renal
function. The drug was changed to itraconazol, with initially good response, but
then the patient followed with worsening of the disease and death.
Conclusions: Sporotrichosis most often represents a localized infection of the skin
and lymphatics, and spontaneous remission may occur in some cases. However,
immunosupressed patients may develop a severe form of the disease that can be
disseminated and associated to unusual clinical forms, such as involvement of the
oral cavity.
MARCH 2010
J AM ACAD DERMATOL
AB83
P2401
Tinea incognito masquerading as a polymorphous eruption in a patient on
antieTNF-alfa therapy
Alison Adams, MD, Mayo Clinic AZ, Scottsdale, AZ, United States; Charles Chia,
MD, Mayo Clinic AZ, Scottsdale, AZ, United States; Karen Warschaw, MD, Mayo
Clinic AZ, Scottsdale, AZ, United States
A 46-year-old man was referred to our institution for a rash present for 6 months. He
had a history of psoriasis and was initially started on etanercept and methotrexate.
Approximately 3 weeks after starting these medications, he developed a papular,
tender, scaly eruption on his arms, legs, and face. The appearance and symptoms of
the eruption were different from those of his psoriasis. He discontinued methotrexate
and remained on etanercept with continued progression of his eruption. In addition,
he was treated with multiple high-potency topical steroids as well as several courses
of prednisone without relief. Eventually, etanercept was discontinued and adalimumab treatment was started. An outside biopsy was reported as acute ruptured
folliculitis and psoriasiform dermatitis. Direct immunoflorescence was nondiagnostic. The patient was subsequently referred to our institution for potential photopatch
testing with the suspicion of chronic actinic dermatitis. A full skin examination
revealed a polymorphic eruption with multiple perifollicular pustules on red plaques
scattered over the bilateral upper extremities and even extending to the right cheek.
On his trunk there were multiple annular red lesions with scale. Genital skin had
several well demarcated, pink, flat-topped papules. Oral mucosa was within normal
limits. KOH preparation from the right shoulder demonstrated multiple hyphae.
Fungal and bacterial cultures were negative. Complete blood count revealed a
continued mild WBC elevation, normal LFTs, and negative serologies for coccidiomycoses, ENA, ANA, HIV, SS-A, and SS-B. More biopsies were obtained and they revealed
orthohyperkeratosis with fungal hyphae present. One biopsy was notable for a
follicular pustule containing hyphae. The patient was treated with oral terbinafine
250mg daily and experienced clearing of his skin eruption. Tinea incognito, as per its
name, is often mistaken for other skin eruptions. Although this patient’s fungal
culture was negative, histology showed numerous hyphae and the KOH preparation
was densely positive. In addition, the patient’s improvement on antifungal therapy is
characteristic of this disease. The patient’s protracted course before correct diagnosis
and treatment demonstrates the importance of a broad differential with special
attention to infectious causes in patients on anti-TNF-alfa therapy.
P2402
Cutaneous histoplasmosis mimicking cutaneous malignancy
Melissa Reyes Merin, MD, MPH, University of California, Davis, Sacramento, CA, United
States; Daniel Eisen, MD, University of California, Davis, Sacramento, CA, United States
Cutaneous histoplasmosis is a rare skin disorder that typically presents to otolaryngologists as the lesions most commonly present as oral ulcers. The authors describe a
case of cutaneous histoplasmosis that presented in the eyelid tissue mimicking basal
cell carcinoma. Biopsy and staining demonstrated histopathologic changes consistent
with histoplasmosis and was confirmed by fungal culture and DNA probe. To the
authors’ knowledge, this presentation has not been previously reported in the
dermatologic literature. A 79-year-old Mexican immigrant with a history of esophageal
cancer presented to ophthalmology with a 3-month history of a solitary ulcerated
papule on the medial left lower eyelid causing a mechanical ectropion. The patient
reported it started as a ‘‘red bump’’ that slowly increased in size. Further investigation
into his history revealed that the onset of the lesion occurred after returning from a 6month stay in Jalisco, Mexico. He lived on a ranch where he was exposed to sheep,
chickens, and cows. His past medical history was notable for a ‘‘liver cyst,’’ asthma, a
recent diagnosis of hepatitis C, and a positive HIV screening test with negative Western
blot. Review of systems revealed he had lost 20 lbs in the last several months. He
denied smoking, alcohol, and drug use. The physical examination revealed a 1-cm
ulcer on the medial left lower lid margin involving the palpebral conjunctiva. The ulcer
had raised, pearly margins with central ulceration and madarosis. Because there was a
concern for malignancy, the patient was referred to dermatology and a biopsy was
performed. Histopathology revealed dense neutrophilic infiltrate in a granulomatous
pattern with small, ovoid yeast-like organisms within macrophages. The differential
diagnosis included leishmaniasis (parasitized organisms on mucocutaneous tissues),
Penicillium marneffei, Trypanosoma, Candida, and Histoplasma. GMS and immunohistochemical staining confirmed a diagnosis of Histoplasma capsulatum. Fungal
cultures confirmed with a DNA probe were also positive for H capsulatum. His blood
and urine were negative for H capsulatum immunoglobulins. Oral itraconazole was
started, but the patient was never seen in follow-up because he passed away 1 month
after presentation. H capsulatum is a dimorphic soil fungus found worldwide in river
valleys in North and Central America, and temperate climates. Most commonly,
infection occurs via inhalation of spores and primary affected the pulmonary system.
Most who are affected are asymptomatic or suffer a flu-like self-limited illness. It is
those patients who are immunocompromised that develop clinical manifestations.
Cutaneous histoplasmosis usually manifests from disseminated disease and is uncommon and nonspecific in appearance. Most cutaneous manifestations occur as oral or
AB84
hard palate ulcers and thus present in otolaryngology rather than dermatology clinic.
Other reported cutaneous manifestations include molluscum-type papules, pustules,
subcutaneous nodules, papulosquamous lesions, and erythema multiforme. There are
few reports of cutaneous histoplasmosis secondary to traumatic inoculation. To our
knowledge, there have been only two previous reports of primary cutaneous
histoplasmosis masquerading as a cutaneous malignancy, and neither was on the
eyelid. One report in 1991, reported from India, was a 58-year-old man with a ulcerated
nodule of the right ala. The second (2008) was out of Missouri of an 86-year-old man
with an ulcerated plaque of the left temple. Because there are no reported cases of
disseminated or primary cutaneous histoplasmosis involving the eyelid and palpebral
conjunctiva, this case demonstrates that histoplasmosis should be included in the
differential diagnosis for mucucutaneous, nonhealing ulcers in individuals with risk
factors such as immunosuppression and exposure to endemic areas.
P2403
Fatal strongyloidiasis as a cause of purpuric rash in a patient treated with
systemic steroids
Jacqueline Russo, MD, University of Florida College of Medicine, Department of
Pathology & Laboratory Medicine, Gainesville, FL, United States; Kenneth Rand,
MD, University of Florida College of Medicine, Departments of Infectious Disease
and Pathology & Laboratory Medicine, Gainesville, FL, United States; Ronald
Rusiecki, MD, University of Florida College of Medicine, Department of
Infectious Disease, Gainesville, FL, United States; Vladimir Vincek, MD, PhD,
University of Florida College of Medicine, Department of Pathology & Laboratory
Medicine, Gainesville, FL, United States
A 58-year-old white woman presented with Escherichia coli bacteremia, vancomycin-resistant Enterococcus faecium (VRE) meningitis, and septic shock. Before this
admission, she received systemic corticosteroids on three separate occasions at
another hospital for COPD exacerbations secondary to alfa-1-antitrypsin disease.
The physical examination showed an extensive purpuric rash on her abdomen and
anterior thighs. Unfortunately, the patient soon died. Microscopic sections from her
skin taken at autopsy showed epidermal bullae formation with underlying basophilic parasitic organisms located in the superficial dermis and subcutaneous fat.
Notably, no inflammatory response or granuloma formation is seen. Organisms were
also present in the brain, lungs, and gastrointestinal tract. The nematodes are
consistent with Strongyloides stercoralis and the diagnosis is disseminated strongyloidiasis. Strongyloides is endemic in the United States, particularly in the
Southeast and Appalachia regions. Typically, the worm penetrates the foot from
contaminated soil and enters the blood circulation. Then, they travel to the lungs,
invade through the capillary walls, and enter alveolar spaces. Next, they migrate up
the trachea, are coughed up, and then swallowed where they attach to the small
intestines and produce rhabditiform larvae. Now, one of two things can happen:
rhabditiform larvae get excreted back into soil and complete a free-living cycle, or
rhabditiform larvae transformation into infectious filariform larvae within the host,
penetrate the intestinal mucosa and/or perianal tissue, reenter blood circulation,
and reinfect its host. This is called ‘‘autoinfection’’ and is unique to S stercoralis.
Autoinfection results in chronic infection that typically persists in the host for
decades causing no symptoms until the host becomes immunocompromised, most
commonly by systemic steroids. Once immunosuppressed, disseminated disease
ensues potentially affecting any organ in the body causing hyperinfection.
Furthermore, these parasites carry enteric organisms with them as they infiltrate
the tissues causing superinfections like bacteremia, meningitis, and endocarditis.
Forty-five percent of patients with dissemination develop superinfections and bear a
mortality rate approaching 80%. Patients present with nonspecific GI and/or
respiratory symptoms depending on the extent of involvement. Eosinophilia is
frequently present in patients with uncomplicated infection and should raise
suspicion; however, eosinopenia is more common in patients treated with steroids
and is a poor prognostic factor. Stool sampling for ova and parasites is the most cost
effective diagnostic tool. One stool examination has only 30% sensitivity; therefore,
three stool samples are recommended to increase sensitivity to 50%. Additional
diagnostic studies include sputum samples, bronchial washings, CSF analysis, tissue
biopsy, and serologic studies (available only in commercial laboratories). There are
two skin manifestations associated with Strongyloides. Larva currens, present in
immunocompetent patients, is considered by some to be pathogneumonic for
strongyloidiasis. It is a serpiginous, erythematous rash caused by larval migration
through the skin that rapidly migrates 5 to 15cm/hour. The second, associated with
immunocompromised patients, involves a purpuric eruption that occurs on the
abdomen and thighs (presented above) because of vessel destruction from the
invasive organism. These rashes can strikingly resemble a drug eruption; therefore,
recognizing disseminated strongyloidiasis as a cause of purpuric rash in immunocompromised patients may be life-saving.
J AM ACAD DERMATOL
MARCH 2010
P2404
P2406
Current and emerging tests for diagnosis of cutaneous blastomycosis
William B. Adams, MD, University of Louisville, Department of Dermatology,
Louisville, KY, United States; Andrew H. Kalajian, MD, University of Louisville,
Department of Dermatology, Louisville, KY, United States; Jeffrey P. Callen, MD,
University of Louisville, Department of Dermatology, Louisville, KY, United States
Potassium hydroxide examination in superficial fungal infection of the
skin: The experience-based procedure
Sumanas Bunyaratavej, MD, Department of Dermatology, Faculty of Medicine
Siriraj Hospital, Mahidol University, Bangkok, Thailand
Background: Blastomyces dermatitidis is a dimorphic fungus classically located in
the southeastern United States. A unique feature of this pathogen is its ability to
cause significant disease in immunocompetent patients. Cutaneous blastomycosis
most commonly arises via hematogenous spread following primary pulmonary
infection although direct cutaneous inoculation does rarely occur. Diagnosis can be
very difficult given the variety of presentations and difficulty in isolation of the
organism. Herein we describe a case of cutaneous blastomycosis and discuss current
and future diagnostic tests that may aide in the identification of this pathogen.
Observation: A 41-year-old African American woman presented with a firm violaceous to erythematous verrucous plaque with pustules on the upper cutaneous lip.
Upon further questioning, she related a 3-month history of fever, chest congestion,
arthralgias, and myalgias that preceded her first cutaneous lesion. Shortly thereafter,
she developed pustular plaques on the dorsal surface of her left hand and left
shoulder, followed by the development of a similar lesion in her left conchal bowl,
which was excised. Histologic examination showed pseudoepitheliomatous hyperplasia overlying suppurative granulomas, but no organisms were found with special
stains or cultures. Tissue culture from the upper lip plaque revealed no growth at 6
weeks. A chest CT showed a left-sided lobar consolidation, and bronchoscopy with
tissue sampling was performed. Subsequently, histologic evaluation of a newly
developed nodular plaque on her chest revealed broad based budding yeast on
Grocott methenamine silver stain consistent with B dermatitidis. All cultures from
pulmonary and cutaneous sources remained negative. The patient was started on
fluconazole 200mg twice daily for 1 month and was then switched to itraconazole
400mg daily, resulting in dramatic resolution of all cutaneous lesions over the
following 3 months.
Comment: The isolation of B dermatitidis can be extremely difficult. Differential
diagnosis includes sarcoidosis, pyoderma gangrenosum, squamous cell carcinoma,
halogenodermas, or other cutaneous infections. Given the prevalence of this fungus
and its ability to cause marked morbidity in immunocompetent people, significant
search has been undertaken for nonculture diagnostic modalities. Some of the
newer ideas to arise are a polymerase chain reaction (PCR) for the DNA of B
dermatitidis and measurement of a urinary antigen.
Background: Potassium hydroxide (KOH) examination is commonly used in
dermatologic practice. The experience in specimen collection, preparation, and
interpretation is very important, despite its simplicity, rapidity, and minimal
invasiveness. This study determined the ability in interpretation of KOH preparation
of six technicians with different levels of experience within the department of
dermatology ranging from the least to the most.
Methods: Six volunteer technicians who know basic KOH examination have had
different levels of practical experience defined as specimens per week (SPW),
ranging from\0.05 to 250 SPW. Each technician examined the 10 unknown slides of
skin scraping in the first session, 10minutes/slide. Next, all six technicians were
paired in three groups (2 per each). Each of them was asked to exchange the set of
10 slides to the other member for slide interpretation in the second session, 3 to
5minutes per slide. Results of this examination, based on fungal culture and clinical
features, were classified as correct, false negative, false positive, and
misinterpretation.
Results: This study shows that experienced technicians can interpret more correct
answers than the fairly experienced group in both sessions, especially in the second
session which had more limited time for specimen interpretation. Noticeably, there
was positive correlation (r ¼ 1.0, Spearman rank; P ¼ .01) between SPW and the
correct answers. Furthermore, there was negative correlation (r ¼ -1.0, Spearman
rank; P \ .01) between SPW and misinterpretation, exclusively in the second
session.
Conclusion: Experience of slide examination per week and time exposure were
significant factors for accurate interpretation of KOH examination. Positive correlation between experience and the correct answers and also negative correlation
between experience and misinterpretation were identified particularly in limited
examination time.
P2405
Severe nail candidiasis in a diabetic patient
Baptista, MD, CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Inês Leite, MD,
CHVNGaia/Espinho, Vila Nova de Gaia, Portugal; Virgı́nia Lopes, MD, Centro
Hospitalar do Porto, Porto, Vila Nova de Gaia, Portugal
We report the case of a 79-year-old woman who consulted our department with a
severe deformation of the distal phalange of the third finger of the left hand, with a
yellowish, opaque, rough, exuberant hyperkeratosis that destructed the entire nail
plate. She had diabetes, peripheral arterial disease with amputation of the right leg,
cardiac stroke, and left foot ulceration history. A nail surgical avulsion was
performed. Biopsy of the nail bed showed an acute inflammatory process with
epidermal and dermal involvement and numerous spores were detected by PAS
staining. There was no sign of malignancy. KOH-prepared direct microscopy
revealed the presence of numerous spores and pseudohyphae. Candida albicans
was isolated and identified by cultivation. Routine serum analyses were normal
except for elevated fasting glucose levels and hemoglobin A1c. The Rx of the left
hand revealed clinodactyly of the fingers and severe osteopenia. The distal phalange
of the third left finger did not reveal osteolytic or sclerotic changes. Imidazoles
(fluconazole, itraconazole) were administered and after 4 years of intermittent
treatment her clinical findings had substantially improved. C albicans and C
parapsilosis are the species identified more frequently from nails, particularly
from fingernails. Because they could be resident flora of the skin, cultures should be
interpreted according to clinical data, direct microscopic observation of clinical
samples, and quantification of colonies.
Onychomycosis has the potential to cause severe complications in diabetics and
should be treated promptly. The existence of comorbid conditions and potential for
drug interactions complicates the selection of an appropriate treatment regimen.
The role of Candida in onychomycosis may be of increased significance in the
diabetic population due to an underlying vulnerability to this organism. The
exuberance of the cutaneous lesion and the slow answer to the administered
treatment make, in our opinion, a particularly interest example of the impact of
diabetes on C albicans infection of the nails.
P2407
Naftifine: A topical antifungal agent reevaluated
Lawrence Charles Parish, MD, Jefferson Medical College, Philadelphia, PA, United
States; Hirak B. Routh, MBBS, Paddington Testing Company, Philadelphia, PA,
United States; Jennifer L. Parish, MD, Jefferson Medical College, Philadelphia, PA,
United States
Naftifine, the first of two available allylamine antifungal agents, was originally
synthesized in 1974. Initial screens showed this agent to be fungicidal against
dermatophytes and fungistatic against yeasts. It also was shown to have both
antibacterial and antiinflammatory activity. Its mechanism of action against fungi
involves the inhibition of squalene epoxidase and of ergosterol. The increased
squalene formation and decreased ergosterol formation of the cell walls interfere
with intake of nutrients by the fungi. Clinically, naftifine penetrates the skin
transdermally, and in vivo, a 1% cream formulation maintained epidermal pentration
for 5 to 10 days after application, providing concentrations up to five times higher
than the miniumum inhibitory concentration (MIC) for pathogens such as
Trichophyton mentagraphytes. This is the basis for the recommendation of a
once-a-day regimen. A trial in the treatment of a 1% cream formulation showed
superior clinical and mycological efficacy over a fungistatic azole, oxiconazole, at
the end of 2 weeks. In a comparision with another azole, econzaole, naftifine had
favorable results at 4 weeks in the treatment of tinea cruris and tinea corporis. The
currently available gel and cream formulations have had minimal side effects, which
have been limited to occasional minor irritation and one instance of contact
dermatitis. Dermatophyte resistance to the allylamines has been extremely rare.
Commercial support: 90% supported by MerzUSA.
MARCH 2010
J AM ACAD DERMATOL
AB85
P2408
P2410
Disseminated trichosporonosis in a patient with relapsed acute myeloid
leukemia
Megan Kinney, Wake Forest University School of Medicine, Winston Salem, NC,
United States; Andrew Lee, MD, Wake Forest University School of Medicine,
Winston Salem, NC, United States; Rita Pichardo, MD, Wake Forest University
School of Medicine, Winston Salem, NC, United States
Cutaneous alternariosis in renal transplant recipient
Almudena Mateu-Puchades, MD, Department of Dermatology, Hospital
Universitario Doctor Peset, Valencia, Spain; Amparo Marquina-Vila, PhD,
Department of Dermatology; Hospital Universitario Doctor Peset, Valencia,
Spain; Francisco Ferrando-Roca, MD, Department of Dermatology; Hospital
Universitario Doctor Peset, Valencia, Spain; Maria Neus Coll-Puigserver, MD,
Department of Dermatology. Hospital Universitario Doctor Peset, Valencia, Spain
Disseminated trichosporonosis is an emerging opportunistic fungal infection
associated with immunocompromised patients. We describe an 18-year-old patient
admitted for relapsed acute myeloid leukemia. Six weeks into his hospital course,
after receiving high-dose cytosine arabinoside and etoposide, he developed a
neutropenic fever and a morbilliform eruption on his trunk, and a skin biopsy
specimen revealed sparse dermatitis. Blood cultures were negative at that time,
although the patient was on prophylactic antibiotics. One week after his first skin
biopsy, the patient became hypotensive and tachypneic, requiring intubation and
admission to the ICU. At this time, purpuric nodules on the extremities were
observed, and a skin biopsy specimen revealed a dermal invasion of fungal elements,
at which point aggressive antifungal therapy was initiated. Subsequent blood
cultures and tracheal aspirates were positive for Trichosporon beigelii.
Dermatologists may play a key role in the early diagnosis of disseminated
trichosporonosis among immunocompromised patients.
Background: Alternaria is a genus of dematiaceous fungi that is ubiquitous in the
environment. Alternariosis is rare, but increasingly prevalent among immunosuppresed population. We report a case of cutaneous alternariosis in a renal transplant
recipient with good response to combined surgical and medical therapy.
Case report: A 60-year-old man who suffered two chronic rejections of two previous
renal transplant underwent the last renal transplant 6 months before attending our
clinic. Since then, he had been treated with prednisolone, tacrolimus, and
mycofenolate mofetil. Four months after transplant, he developed a 2-cm solitary,
ulcerated, violaceus nodule on his right arm. The lesion was asymptomatic and there
was no history of trauma. The nodule was completely excised and the biopsy
speciemen showed a granulomatous infiltrate in the dermis with round shaped
fungus spores, and hyphae stained positive with periodic acid-Schiff. The biopsy
specimen was cultured in Sabouraud dextrose agar and Alternaria alternata was
identified. Itraconazole 200mg bid for 4 weeks was added after surgical treatment.
Tacrolimus levels were controlled along medical treatment without any complications. The patient has been free of lesions after 1 year of follow-up.
Discussion: Alternaria produces a wide range of infections, from noninvasive
colonization to severe systemic involvement. Cutaneous infection is the most
common presentation. It usually produces a solitary lesion, but multiple lesions with
sprotrichoid spread have been observed. Because Alternaria is frequently found in
the environment and on normal human skin, it could be difficult to establish
whether it is a contaminant or not. Therefore, the diagnosis requires tissue culture
and histologic evidence of dermal granuloma with hyphae. The optimal treatment
for cutaneous alternariosis is controversial. Surgical excision, when possible, seems
to be the best therapeutical option. Alternaria species are sensitive to oral
itraconazole, amphotericin B, fluconazole, micoazole, and ketoconazole, and are
resistant to griseofulvin and flucytosine. Some authors recommend to combine
surgery and oral itraconazole, but doses and duration of treatment are not fully
established and we have to take care because simultaneous administration of
tacrolimus and itraconazole may result in tacrolimus toxicity if the dosage of
tacrolimus is not adjusted and serum levels monitored. Follow-up is essential,
because relapse has been shown to occur frequently.
P2409
Tinea pedis in an immunocompetent patient caused by Fusarium spp.
Maria Encarnacion Gimenez-Cortes, MD, Hospital Fundacion de Cieza, Cieza,
Murcia, Spain; Eugenia Cutillas-Marco, MD, Hospital Fundacion de Cieza, Cieza,
Murcia, Spain; Silvina Gaglio de Grecco, MD, Hospital Fundación de Cieza, Cieza,
Murcia, Spain
P2411
Onychomycosis therapy: Room for improvement
Aditya Gupta, MD, PhD, MBA, Mediprobe Research, London, Ontario, Canada
Case report: A 64-year-old man presented with a 3-month history of an exudative
plaque affecting the dorsal surface of the feet.The patient lived in a rural area in the
south of Spain and medical history was unremarkable except for hypercholesterolemia, hyperuricemia, and trasplant of cornea. Before being referred to our clinic,
he had been on treatment with prednisone and ciprofloxacin, with partial response.
On physical examination, he had an erythematous plaque in his left foot with both
exudative and hyperkeratotic areas, affecting the dorsum, and interdigital skin, and
spreading to the sole. He presented a yellowish opacification of hyperkeratotic
mails. Lesions were scraped for culture, which was positive for Fusarium spp. After a
3-week treatment with terbinafine all the skin lesion disappeared, although he was
advised to continue the treatment because of nail infection.
Discussion: Most of the cutaneous infections caused by Fusarium spp. occur in
immunocompromised hosts, especially solid organ transplant patients or those with
hematologic neoplasia. The most common cutaneous manifestation of an infection
by Fusarium spp. is onycomycosis, which is the only skin manifestation in
immunocompetent hosts. Nevertheless, a disseminated infection is possible in
immunocompromised patients. When Fusarium spp. produces an onychomycosis
in an immunosupressed host, it can spread rapidly to paronychia and a disseminated
infection, causing the death of the patient. In contrast, infections in immunocompetent hosts spread slowly and have a good response to treatment. After clinical
examination, confirmation of an infection by Fusarium spp. requires a positive
culture and the absence of concurrent isolation of a dermatophyte, because
Fusarium can be a contaminant.
Effective onychomycosis therapy has historically required oral antifungal use.
Despite being the criterion standard for onychomycosis, the typically moderate
efficacy rates of oral therapies leave much room for improvement. These therapies
are also costly, and can pose potentially significant risk to patients. To date, only two
topical therapies have been approved for onychomycosis, one of which is not
available in North America. The efficacy of the topical therapies is typically not as
high as for oral antifungals, and their use is restricted to less severe cases of infection.
Though some new azole antifungal medications are being developed, new research
is exploring many other avenues of onychomycosis therapy. Two novel classes of
antifungals, oxaboroles and arylguandines, are being tested. AN2690, an oxaborole
nail solution, provided an efficacy of 45% to 50% after 6 months of daily application,
and therefore appears to have potential in onychomycosis therapy. Other new ideas
being explored seek to improve nail penetration using penetration enhancers,
nanoemulsions, drug implants, and iontophoresis. Testing of light therapy devices
and lasers is also progressing, to determine if these modalities can sufficiently
penetrate the nail plate and provide effective treatment of onychomycosis.
Aminolevulinic acid photodynamic therapy has provided high rates of efficacy in
small scale trials. A pilot trial of a new patented laser device (200 mJ; 100 msec pulse
duration with 10 pulses per spot in 0.5 sec) showed that the percent of patients with
75% to 100% involvement pretreatment declined from 85.7% to 14.3% at 6 months
posttreatment. Laser and light devices not requiring drug activators are particularly
exciting because they may avoid potential drug interaction and renal/liver toxicity
provided by drug therapies, while also potentially reducing issues of patient
compliance that operate with drug regimens. There is no shortage of ideas for
improving onychomycosis therapy, with most testing being in the phase II stage of
research. In conjunction with molecular diagnosis techniques, it is hoped that many
of these new modalities will help provide new avenues of effective treatment for
onychomycosis, while maintaining or improving the safety profile of antifungal
therapy.
Background: Fusarium spp. are nondermatophyte molds that are present all over the
world. They can cause both localized or disseminated infections, commonly from
pulmonar focus. Localized infections usually present as onychomycosis.
AB86
J AM ACAD DERMATOL
MARCH 2010
P2412
P2414
Uncertainty in onychomycosis assessment
Aditya Gupta, MD, PhD, MBA, Mediprobe Research, London, Ontario, Canada;
Elizabeth Cooper, Mediprobe Research, London, Ontario, Canada
There are several issues in onychomycosis assessment that provide uncertainty in
trials. Determination of efficacy typically relies on clinical observation of infected
area, and mycologic assessment of the presence or absence of fungal organisms. To
provide consistent and comparable data when determining efficacy, clinical evaluations need to be accurate and replicable between observers, while laboratory
testing for organisms needs to provide conclusive infection status. Without
replicable conclusive assessment, the accuracy of efficacy must also remain in
question. There will always remain some subjectivity between individuals where
clinical evaluation is done by visual methods, but trials can improve standardization
by providing investigators with photos of infection limits/presentations acceptable
for enrollment and to be considered ‘‘effective cure.’’ Trial design should involve
onychomycosis experts when deciding upon entry and cure criteria standards. To
further improve clinical assessment, objective evaluation is obtained using computerized nail planimetry. Digital photography is now widespread. Digital photographs can be sent anywhere in the world for assessment; widespread experts could
provide secondary visual evaluation to ensure enrollment/cure criteria is met.
Computerized planimetry also provides an exact measure of proportion of affected
area, which may be under- or overestimated by subjective visual assessment. Review
of efficacy based on visual assessment compared to planimetry in a recent large-scale
study showed that where effective cure was declared by visual assessment, more
than 20% of subjects at week 84 and over 50% of subjects at week 48 would not be
considered to have EC using planimetry data. New technology is also aiding
mycologic assessment. Fungal organisms are being found at significantly higher rates
with molecular biology compared to the standard microscopy/culture methods. It
has long been known that mycologic detection of dermatophytes has a high rate of
false negatives. The impact of this detection problem is currently unassessed. Only
with the development of improved clinical and mycological methods will we be able
to determine treatment efficacy rates with better reliability, and better modify
treatment to improve cure rates.
A novel itraconazole tablet for the treatment of onychomycosis
Steven Kempers, MD, Minnesota Clinical Study Center, Fridley, MN, United
States; John Quiring, PhD, QST Consultations, Allendale, MI, United States; Lynne
Bulger, Stiefel Laboratories, Montreal, Quebec, Canada; Richard Scher, MD,
University of North Carolina at Chapel Hill, Chapel Hill, NC, United States;
Robert Bissonnette, MD, Innovaderm Research, Montreal, QB, Canada
Objectives: Itraconazole is approved for the treatment of onychomycosis as a 12week, once-daily (QD) regimen of two 100-mg itraconazole capsules. In order to
provide a more convenient, one tablet per day dosing regimen, a novel 200-mg
itraconazole tablet has been developed using the proprietary Meltrex technology.
This phase III study evaluates this new dosage form for treating onychomycosis.
Methods: This randomized, multicenter, parallel group, placebo-controlled, evaluator-blinded study was designed to compare the efficacy of itraconazole given as one
200-mg tablet QD with itraconazole given in two 100-mg capsules QD for 12 weeks
of treatment and 40 weeks of follow-up. In addition, this study evaluated the
superiority of 1 itraconazole 200-mg tablet to 1 placebo tablet. Noninferiority and
superiority were evaluated using the proportion of subjects with complete cure of
the great toenail at week 52. Complete cure was defined as clinical cure (an
Investigator’s Global Assessment score of 0) plus mycologic cure (a negative
potassium hydroxide [KOH] examination and a negative culture for dermatophytes).
Results: A total of 1381 subjects were randomized (3:3:1) to treatment and received
study drug. The proportions of subjects (intent to treat population) with complete
cure at week 52 were greater in the active treatment groups (22.3% in the
itraconazole 200-mg tablet group and 21.7% in the itraconazole 100-mg capsule
group) compared with the placebo group (1.0%). In addition to demonstrating
superiority to QD dosing with 1 placebo tablet (P \.001), QD dosing with one
itraconazole 200-mg tablet demonstrated noninferiority to QD dosing with two
itraconazole 100-mg capsules (lower limits of the 97.5% CI, -4.3%). Overall, no safety
signals or trends associated with abnormal changes in clinical laboratory findings,
ECG outcomes, or audiology evaluations were observed following intake of
itraconazole 200-mg tablets. Furthermore, the AE profile of subjects treated with
one itraconazole 200-mg tablet was comparable to that of subjects treated with two
itraconazole 100-mg capsules or placebo tablet.
Conclusions: This novel itraconazole 200-mg tablet is well tolerated and effective in
the treatment of onychomycosis. The convenience of a one tablet per day dosing
regimen may improve patient compliance.
Commercial support: 100% is sponsored by Stiefel Laboratories.
P2415
An open-label study of the safety and efficacy of sertaconazole nitrate in
the treatment of seborrheic dermatitis
Boni E. Elewski, MD, University of Alabama, Birmingham, AL, United States
P2413
Disseminated cutaneous cryptococcus infection with neurocryptococcus
presenting as cellulitis in a liver transplant patient
William Camp, MD, MPH, University of Pittsburgh, Pittsburgh, PA, United States;
Arash Radfar, MD, PhD, University of Pittsburgh, Pittsburgh, PA, United States;
Timothy Patton, DO, University of Pittsburgh, Pittsburgh, PA, United States
Cryptococcosis is the infection caused by the encapsulated yeast Cryptococcus
neoformans, a dimorphic fungus. Although the primary site of infection is most
often the lungs, the disease frequently manifests with signs of extrapulmonary
dissemination, involving the skin in approximately 10% to 15% of cases. We report a
55-year-old man with hepatitis C and multifocal hepatocellular carcinoma who
underwent an orthotopic liver transplantation and was admitted to the hospital
because of worsening encephalopathy. He was also found to have a new-onset left
facial droop, recurrent fevers, and an erythema on his left medial thigh. The initial
physical examination showed a 4- 3 6-cm erythematous patch on the left inner thigh
with surrounding mottled and reticulated diffuse erythema descending down the
right leg with fine scale that was tender to palpation and slightly warm to touch. A 6mm punch biopsy was performed within the erythematous patch on the left thigh,
which revealed psuedoepitheliomatous hyperplasia of the epidermis and granulomatous infiltrates in the dermis, within which aggregates of spores was revealed.
Mucicarmine, colloidal iron, FontanaeMasson, GMS, and PAS stains were consistant
with cryptococcus infection. Laboratory studies revealed a serum cryptococcal
antigen titer of 1:256 and a CSF cryptococcal antigen titer of 1:512. Despite
treatment with multiple antifungal agents for disseminated cryptococcal infection,
the patient developed sepsis with multiorgan failure and died. Cellulitis is the rarest
skin finding associated with cryptococcosis; it is most commonly encountered in
transplantation patients. The characteristic clinical presentation, differential diagnosis, and treatment reviewed in this case is helpful in promoting early recognition
and appropriate management of this potentially life threatening disease.
Introduction: Seborrheic dermatitis is a common recurrent dermatosis characterized by redness and scaling, with occasional papule and plaque formation and
variable pruritus. Diagnosis is based chiefly on clinical findings, with dermatopathology helpful only occasionally. Malassezia globosa and M restricta are believed
to play a role in its pathogenesis, although their presence is not definitive of disease
because both yeasts are among the normal flora found in large numbers in the
sebaceous regions. Treatment usually involves antifungal agents such as ketoconazole, alone or in combination therapy, topical corticosteroids, or other topical
agents including shampoos, many of which are available over the counter.
Corticosteroid therapy has been associated with frequent recurrence of disease
and adverse events, however, and the need for safe, effective nonsteroidal therapy
for seborrheic dermatitis has long been established. Sertaconazole nitrate has a long
history of successful use in Europe in seborrheic dermatitis, which indicates that it
may well be a useful agent in the United States as well.
Objective: To demonstrate the efficacy and evaluate the safety of sertaconazole
nitrate 2% cream in the treatment of seborrheic dermatitis.
Methods: A single-center, open-label study of 30 male and female patients 19 years of
age or older with seborrheic dermatitis of the face was conducted. Subjects applied
sertaconazole cream twice daily for 4 weeks and were clinically evaluated at baseline
and at the end of weeks 1, 2, and 4. Efficacy measures included the 5-point
Investigator’s Static Global Assessment (ISGA) as well as clinical assessment of target
symptoms including pruritus, erythema, and scaling. Primary endpoint is the
proportion of subjects who achieved ISGA scores of 0 or 1 by week 4. Secondary
endpoints included percent change in sum of individual scores of signs of disease at
target lesion by end of treatment. Safety assessment is by vital signs and reports of
adverse events.
Conclusion: Sertaconazole nitrate cream, 2% proved to be effective for the treatment
of seborrheic dermatitis, although some patients experienced minor irritation.
Commercial support: Support provided by Ortho Dermatologics, a division of
Ortho-McNeil-Janssen Pharmaceuticals.
MARCH 2010
J AM ACAD DERMATOL
AB87
P2416
Deep mycoses in Morocco: Clinical and epidemiologic studies of 42 cases
Hayat Skali, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa,
Morocco; Hakima Benchikhi, Dermatology Department, Ibn Rochd UHC,
Casablanca, Anfa, Morocco; Leila Merzoug, Dermatology Department, Ibn Rochd
UHC, Casablanca, Anfa, Morocco; Maha Soussi, Parasitology Department, UHC Ibn
Rochd, Casablanca, Anfa, Morocco; Soumia Chiheb, Dermatology Department, Ibn
Rochd UHC, Casablanca, Anfa, Morocco
Introduction: Deep mycoses are rare and chronic diseases. Because of its geographic
situation, Morocco is subject to various climatic influences (Mediterranean, Atlantic,
subtropical) with a tendency towards the development of deep mycoses. The aim of
our study is to assess the epidemiologic and clinical characteristics of deep mycoses
observed in the dermatology departement in the University Hospital of Casablanca.
Methods: All the deep mycoses cases admitted to the dermatology department from
January 1981to December 2008 were subject to clinical and epidemiologic analysis .
For each patient, we specified the following data: age, sex, geographic origin,
clinical aspect, duration of evolution, mycologic examination, histopathology study,
radiologic assessment, treatment, and evolution.
Results: Forty-two cases of deep mycoses were collected over a period of 28 years.
The average age was 45 years with a male predominance (sex ratio, 1.3).
Development duration ranged from 2 months to 16 years with an average of 7
years. The lesions intersed the lower limbs in 25 cases. Polyfistulised slabs form was
found in 18 cases. Verrucosa form in 12 cases and gummy form in 11cas. Mycologic
examination was performed in 34 cases and was positive in 25 cases. The study
allowed a histologic diagnosis in 18 cases. The diagnosis of chromomycosis was
raised in 13 patients, mycetoma in 20 cases, and sporotrichosis in nine cases.
Treatment with terbinafine was introduced in 11 patients, G penicillines in six cases,
and surgery was indicated in five patients.
Discussion: Mycetomas are common in rural areas; in a dermatologic study of Ibn
Rushd Hospital, 38 cases of mycetoma were recorded between 1961 and 2006.
Deep mycoses are chronic conditions represented in our country mainly by the
fungal mycetoma actinomycosis, chromomycosis, and sporotrichosis. This unexceptional disease in Morocco causes enormous problems in treatment.
INFECTION (VIRAL)
P2500
Treatment of generalized molluscum contagiosum in an HIV patient with
diphencyprone
Leena Chularojanamontri, MD, Faculty of Medicine Siriraj Hospital Mahidol
University, Bangkok, Thailand; Kanokvalai Kulthanan, MD, Faculty of Medicine
Siriraj Hospital, Mahidol University, Bangkok, Thailand; Papapit Tuchinda, MD,
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;
Woraphong Manuskiatti, MD, Faculty of Medicine Siriraj Hospital, Mahidol
University, Bangkok, Thailand
Background: Diphencyprone (DPC) is a universal contact immunotherapy. The
mechanism of action is based on an induction of the delayed-type hypersensitivity.
DPC has been used in various forms for treatments of recalcitrant and facial warts,
and alopecia areata. However, this treatment modality has not been generally used in
immunocompromised patients. The present report demonstrated the efficacy of
DPC immunotherapy on the treatment of generalized molluscum contagiosum in an
HIV patient.
Methods: A 32-year-old HIV patient presented with widespread genital and extragenital molluscum contagiosum for 7 months. The lesions did not improve when the
patient was on the antiretroviral medications. The molluscum lesions were spread
on the eyelids, trunk, and genital areas. Because of the widespread nature of the
lesions, we decided to treat this patient with DPC. The patient was sensitized with
DPC 2% and was later started treating with a concentration of 0.001%. Ten percent
of the lesions were applied with DPC on each follow-up visit. The concentrations of
DPC were gradually increased from 0.001% to 2.0%, depending on the patient’s
tolerability. The frequency of DPC application was 1- to 2-week intervals.
Result: All of the lesions on the eyelids cleared within 2 months of treatment. The
other lesions on the trunk and the genitalia gradually decreased in size and resolved
with consecutive applications of DPC. Minimal and transient side effects including
pruritus, postinflammatory hyperpigmentation and irritation were noted.
Conclusion: DPC contact immunotherapy appears to be a challenging treatment of
molluscum contagiosum in immunocompromised patients.
P2417
Efficacy of once-daily treatment of interdigital tinea pedis with sertaconazole 2% cream
Jeffrey M. Weinberg, MD, St. Luke’s-Roosevelt Hospital Center and Beth Israel
Medical Center, New York, NY, United States; Evelyn K. Koestenblatt, MS, St.
Luke’s-Roosevelt Hospital and Beth Israel Medical Center, New York, NY, United
States
Introduction: Tinea infections of the foot, usually caused by Trichophyton spp., are
increasingly prevalent owing to a large aging population, increased numbers of
immunocompromised patients, growing use of gyms and swimming pools, wearing
of occlusive footwear, and drug-resistant organisms. Treatment typically involves the
use of topical antifungal agents, usually azoles. Efficacy depends on each agent’s
mechanism of action and pharmacokinetic profile, as well as on duration of therapy,
but also on patients’ willingness to use topical creams as prescribed without early
discontinuation. Sertaconazole is a broad-spectrum antifungal agent with antifungal,
antibacterial, and antiinflammatory activity known to be effective against dermatophytes, yeasts, and opportunistic filamentous fungi. Its favorable pharmacokinetics
include absorption levels in the skin lasting 48hours postdose and a half-life for
clearance of 60hours, supporting once-daily dosing and thus likely to promote
patients’ adherence to treatment.
Objective: To demonstrate that sertaconazole 2% cream dosed once daily for 4
weeks is at least as effective in the treatment of interdigital tinea pedis as twice-daily
dosing for 4 weeks.
Methods: This was a 6-week, nonrandomized, open-label, active control, singlegroup assignment efficacy study of 30 male and female patients 18 years of age or
older with a clinical diagnosis of interdigital tinea pedis confirmed by KOH and
fungal culture. Subjects applied sertaconazole 2% cream once daily for 4 weeks and
were examined at baseline, days 7, 14, and 28, and 2 weeks posttreatment. Primary
efficacy variable was the proportion of patients demonstrating successful treatment
outcomes after once-daily treatment with sertaconazole 2% cream. Successful
treatment outcomes at 6 weeks were defined as either complete cure (resolution of
all signs and symptoms plus negative KOH and fungal culture), or effective
treatment (marked improvement in signs and symptoms plus negative KOH and
fungal culture).
Conclusions: It is anticipated that this study will demonstrate that once-daily
application of sertaconazole 2% cream for 4 weeks provides adequate therapy for
treatment of interdigital tinea pedis. Such a regimen is associated with improved
patient adherence, contributing to a higher mycological cure rate and better clinical
outcome, while diminishing the risk of premature discontinuation of treatment.
Commercial support: Support provided by Ortho Dermatologics, a division of
Ortho-McNeil-Janssen Pharmaceuticals.
AB88
P2501
Recalcitrant verruca plana responding to human papillomavirus quadrivalent (types 6,11,16, and 18) vaccine, recombinant
Alisa Funke, MD, University of Louisville, Louisville, KY, United States; Joseph
Fowler, MD, University of Louisville, Louisville, KY, United States
Background: Verruca plana (VP), typically caused by human papillomaviruses (HPV)
3, 10, 28, and 41, most commonly present as grouped erythematous to light brown
flat-topped papules on the face, neck, or extremities. Despite a high rate of
spontaneous remission they can occasionally be resistant to treatment. Commonly
used treatments include destructive methods such as cryotherapy, podophyllin,
tazarotene, laser treatment, and photodynamic therapy and immunotherapy with
imiquimod cream, squaric acid, dinitrochlorobenzene, and cimetidine. The quadrivalent HPV vaccine is indicated to prevent malignancies caused by HPV 16 and 18,
and condyloma acuminata caused by HPV 6 and 11. Although not indicated to treat
cutaneous warts, we elected to try vaccination in a man with resistant facial VP.
Observation: A 62-year-old immunocompenent man presented with VP on his face
and neck. Despite treatment with numerous rounds of cryotherapy, podofilox gel,
imiquimod cream 5%, cimetidine, and tretinoin 0.4% gel in various combinations
and durations he continued to develop more lesions. Eleven months after initial
presentation he was frustrated and seeking alternate treatment options. We elected
to try the HPV quadrivalent vaccine series consisting of three injections administered at 0, 2, and 6 months in an attempt to illicit an immune response. One month
after his first injection, he had a decrease in the size of his lesions. He continued to
use his topical treatments and received cryotherapy at monthly office visits. After his
second injection, he had only a few residual warts and after the final vaccine had
only one remaining lesion that has resolved. He has continued to be clear several
weeks after completing the HPV vaccine series.
Conclusion: VP often spontaneously remit, but they can be recalcitrant and cause
significant distress. Although different HPV types are targeted by the quadrivalent
vaccine than those responsible for flat warts, we felt that some immunity may be
stimulated because of the high degree of homology among numerous HPV strains.
After nearly a year of poor response to a number of treatments, our patient
experienced impressive improvement while receiving the HPV quadrivalent
vaccine series. Although the placebo effect or spontaneous remission could account
for the effect, we feel that this is an interesting case and may represent a new option
to treat recalcitrant warts and should be further investigated.
J AM ACAD DERMATOL
MARCH 2010
P2502
P2504
Infective dermatitis associated with HTLV-II: A case report
Marilia Brasil Xavier, University of State of Pará, Belém, Pará, Brazil; Alena
Margareth Darwich Mendes, University of State of Pará, Belém, Pará, Brazil; Ana
Clara Yamada, Federal University of Pará, Belém, Pará, Brazil; Antonio Valinoto,
Federal University of Pará, Belém, Pará, Brazil; Francisca Regina Oliveira
Carneiro, University of State of Pará, Belém, Pará, Brazil
Kaposi varicelliform eruption
Tiago Torres, MD, Serviço de Dermatologia Hospital Santo António, Porto,
Portugal; Aristoteles Rosmaninho, MD, Serviço de Dermatologia Hospital de
Santo António, Porto, Portugal; Madalena Sanches, MD, Serviço de Dermatologia
Hospital Santo António, Porto, Portugal; Manuela Selores, MD, Serviço de
Dermatologia Hospital Santo António, Porto, Portugal
Introduction: Human T-cell lymphotropic virus (HTLV) types I and II are endemic in
the Amazon region. The main known transmission routes are sexual contact,
exposure to contaminated blood components, and vertical transmission. Type I is
associated both with a group of hematologic disorders known as adult T-cell
leukemia/lymphoma (ATLL) and a group of neurologic conditions known altogether
as the HTLV-1 neurologic complex, of which the most common is the HTLV1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-II is still not
clearly associated with any disease, although recently some authors had proposed
the relationship with a neurologic disease similar to peripheral neuropathy.
Kaposi varicelliform eruption is a potentially fatal widespread cutaneous infection
caused by herpes simplex and certain other virus that arises in preexisting skin
conditions, most commonly atopic dermatitis. We report a case of a 1-year-old male
with atopic dermatitis who presented with extensive vesicular eruption affecting
the face and trunk, associated with fever, malaise, and irritability. The diagnosis of
Kaposi varicelliform eruption was made based on clinical features, tzanck smear
examination and polymerase chain reaction assay of the vesicle content. The patient
responded adequately to oral acyclovir therapy without any complications. Kaposi
varicelliform eruption is a rare condition and severity varies from mild transient
disease to a fulminating fatal disorder involving the visceral organs. Mortality ranges
from 1% to 9%, with reported rates as high as 75% before the advent of effective
antiviral drugs. Antiviral treatment is very effective and should be instituted without
delay to avoid significant morbidity and mortality. Therefore, a high clinical
suspicion for Kaposi varicelliform eruption should be maintained in children with
atopic dermatitis who have a vesicular eruption.
Case report: A 13-year-old female with a history since she was 6 months old of
erythematous scamous plaque predominantly in the scalp, face, retroauricular fold
without pruritus had been observed. During her whole childhood, many respiratory
infections were related, all of them treated with antibiotic with good response.
Actually, the same lesions are observed including abdominal lesions. An ELISA test to
HTLVI/II was performed which resulted positive. PCR test confirmed the presence
of HTLV-II.
Conclusion: Until now no other case of infective dermatitis was related associated
with HTLV-II so this can be the first description of this relation.
P2505
P2503
Age-adjusted incidence of anogenital warts in Qatar in the year 2003
Sharifa Aldosari, MD, MBBS, Hamad Medical, Doha, Qatar; Hassan Riad, MD,
MBBCh, Hamad Medical, Doha, Qatar
Atypical pityriasis rosea in a pregnant woman in the setting of herpes
simplex virus type 2 reactivation
Maria Jo~ao Cruz, MD, Hospital de S~ao Jo~ao, Dermatology and Venereology
Department, Porto, Portugal; Ana Luisa Cunha, MD, Hospital de S~ao Jo~ao,
Pathology Department, Porto, Portugal; Filomena Azevedo, MD, Hospital de S~ao
Jo~ao, Dermatology and Venereology Department, Porto, Portugal; Teresa Baudrier,
MD, Hospital de S~ao Jo~ao, Dermatology and Venereology Department, Porto,
Portugal
Background: Pityriasis rosea (PR) is a relatively common skin disorder of still
unknown cause, but many epidemiologic, clinical, and experimental features
suggest an infectious etiology. The search for a microorganism continues and
most speculations now centers on a viral etiology. In its typical form it is easily
recognizable, however, atypical forms are found in a considerable proportion of
patients (20%) and can pose diagnostic problems.
Conclusion: We concluded that the incidence of genital warts in Qatar is lower than
the majority of the announced figures for other countries in the region as well as
countries with increased incidence of sexually transmitted diseases. We need to
continue reporting and registering patients with genital warts and to update
calculations for incidence. We recommend adoption of a new policy of vaccination
against oncogenic HPV for the population at risk.
Case report: A 28-year-old pregnant woman in the last trimester came to our
department because of the appearance of grouped pruriginous papulovesicles on an
erythematous base located in the right side of the hip. Swab specimens from vesicles
revealed HSV type 2 DNA by polymerase chain reaction (PCR). Serology for that
virus was positive only for IgG antibodies in the beginning of pregnancy, and was
positive for both IgM and IgG antibodies at our first examination. Laboratory
evaluation was otherwise unremarkable. Two days after, a well demarcated
erythematous round asymptomatic patch, 3 cm in diameter, and a fine central
scaliest collarette aroused in her left thigh, right next to the knee. In the following
days, identical but smaller lesions blossomed in both thighs. At that time, the
herpetic lesion was clearly in a healing process. She was otherwise healthy and
denied similar eruptions before. Two skin biopsies were performed in the first
patch: PCR analysis demonstrated HSV type 2 and histologic examination was
compatible with PR. No treatment was prescribed and the eruption completely
subsided within approximately 8 weeks. Delivery was uneventful and the baby was
perfectly healthy.
Conclusion: This case emphasizes the theory proposed by Kempf et al that
herpesvirus closely related to alfa-herpesviruses (such as HSV or VZV) may be the
causative agent of PR. The spectrum of varying and contradictory data regarding an
infectious etiology may represent the nature of PR (ie, it is probably a multifactorial
disease that can be induced by various infectious agents). To our knowledge there
are no reports in medical literature of PR associated with HSV reactivation. High
level of suspicion and histologic examination are important and helpful for the
diagnosis of atypical cases as the one reported.
Background: Genital HPV infection is the fastest spreading sexually transmitted
infection; it is also a major cause of cervical carcinoma of females after an incubation
period of 10 to 20 years. Epidemiologic studies from the gulf region are sluggish. The
aim of this study is to detect the age adjusted incidence of genital warts in Qatar in
the year 2003.
Methods: The study was done in the dermatology OPD of Hamad Medical (the major
hospital in Doha). All patients with genital warts in the year 2003 were registered.
Detailed history and thorough examination was done for each case. Biopsies were
performed to confirm the diagnosis in selected cases. Descriptive statistics was done
using Statistical Package for Social Sciences version 10. The crude incidence equals
the number of patient with genital wart reported divided by the total number of
population in Qatar in 2003. Age-adjusted incidence equals the crude incidence
multiplied by the population weight.
Results: The calculated crude incidence was 9.54 per 100000 per year and the
calculated age adjusted incidence was 9.706 per 100000 per year.
MARCH 2010
J AM ACAD DERMATOL
AB89
P2506
P2508
Atypical clinical manifestation of acyclovir-resistant HSV in an AIDS
patient: Case report and review of the literature
Denise Woo, MD, Henry Ford Hospital, Detroit, MI, United States; Margaret
Douglass, MD, Henry Ford Hospital, Detroit, MI, United States
Varicella zoster myelitis
Maulina Sharma, MD, MBBS, Department of Dermatology, Queen’s Medical
Centre, Nottingham, Nottinghamshire, United Kingdom; Catherine Roberts, MD,
MBBS, Department of Dermatology, Queen’s Medical Centre, Nottingham,
Nottinghamshire, United Kingdom; Jan Bong, MD, MBBS, Department of
Dermatology, Queen’s Medical Centre, Nottingham, Nottinghamshire, United
Kingdom
Background: In immunocompromised patients, HSV frequently presents with
atypical clinical morphology.
Case report: We report the case of a 45-year-old man with AIDS, a CD4 count of
129/uL, on HAART therapy who presented with a 2-month history of an asymptomatic lesion on his lower lip. Of note, the patient also had a long history of
marijuana smoking. The physical examination revealed an approximately 4- 3 3-cm
exophytic white stuck-on soft plaque with a smooth surface, located on the lower lip
extending from the oral mucosa to the vermilion border and lateral commissures. A
shave biopsy specimen revealed herpes cytopathic changes, and a viral culture grew
herpes simplex. The lesion did not respond to several courses of oral acyclovir,
including an increased dose of 800mg five times daily for 14 days. The patient is
currently undergoing treatment with topical trifluridine three times daily.
Conclusions: Atypical HSV presentations often occur in HIV patients, especially in
advanced disease. These include hyperkeratotic verrucous lesions, exophytic
plaques, and nodular lesions, which may appear in nontraditional locations, such
as the tongue and endobronchial tube. This case serves as a reminder that HSV
should be considered in the differential diagnosis of chronic exophytic plaques in
HIV positive patients, and that atypical presentations of HSV infection should
prompt screening for underlying associated immunodeficiency. The location on the
lower lip has not been reported previously, and suggests a possible contributory role
of local burn injury in the pathogenesis given our patient’s history of marijuana
smoking. Of note, the majority of these atypical cases are resistant to acyclovir as in
our patient, but may respond to higher-bioavailability valacyclovir, topical trifluridine, topical imiquimod, and both topical or intravenous cidofovir or foscarnet.
Varicella zoster can have significant neurologic complications. We present a case of
varicella zoster myelitis. A 66-year-old man presented to the accident and emergency
department with rapid onset of spreading saddle anesthesia, difficulty passing urine,
constipation, and difficulty walking. He had a 1-week history of prodromal
symptoms of headache, bodyache, and tiredness. He had noticed an asymptomatic
rash over his buttock 2 weeks before these symptoms. Examination revealed a
sensory deficit at S2-S4 sacral levels with decreased anal tone. Examination of skin
revealed a cluster of papular eruption on right buttock with central necrosis. A
diagnosis of zoster associated with polyradiculopathy was made. Viral skin swab was
positive for varicella zoster. PCR of cerebrospinal fluid was also positive for varicella
zoster. MRI of the spine showed subtle signal change and enhancement in the cord,
conus and cauda equine. Other infectious causes and vasculitis were excluded.
Neurology, dermatology, and microbiology teams were involved in his joint care.
The patient made a remarkable recovery on IV acyclovir 10mg/kg three times daily
for 2 weeks. Varicella zoster virus (VZV) is a double-stranded DNA in a single
molecule. Primary infection causes chicken pox (varicella). Following this, it
establishes latency and can subsequently reactivate to cause herpes zoster. Central
nervous system (CNS) complications can follow both primary infection and
reactivation of VZV. The more serious manifestations arise when the virus invades
the spinal cord or cerebral arteries after reactivation of the virus, causing diseases
such as myelitis and focal vasculopathy. Many of the recently reported cases have
been associated with a diagnosis of HIV, and this should always be considered in this
context. Although herpes zoster myelitis generally carries a good prognosis, early
diagnosis is important, as aggressive antiviral treatment can be effective in
preventing complications.
P2509
P2507
Flavokine, a novel topical antiviral for use against molluscum contagiosum in children and adults
Arnold R. Oppenheim, MD, Virginia Beach Dermatology, Virginia Beach, VA,
United States; Abigail Pekoe, Dalos BioPharma, Virginia Beach, VA, United States;
Amanda K. Houck-Miller, MS, Dalos BioPharma, Virginia Beach, VA, United States;
Gary Pekoe, PhD, Dalos BioPharma, Virginia Beach, VA, United States; M. Kirby
Query, MS, Dalos BioPharma, Virginia Beach, VA, United States
Vesiculobullous Chikungunya fever with a severe and atypical clinical
course
Hazel H. Oon, MD, National Skin Centre, Singapore; Mark B. Y. Tang, MBBS,
National Skin Centre, Singapore; Shiu Ming Pang, MBBS, Singapore General
Hospital, Singapore; T. Thirumoorthy, MBBS, Singapore General Hospital,
Singapore
Flavokine (Dalos BioPharma) is a novel complex botanical entity containing more
than 270 flavonoids and other components. Different fractions of flavokine have
been associated with antiviral, antibacterial, antitumor, antiinflammatory, and
enhanced wound healing activity. Mechanisms of action include direct activity
against viruses and bacteria including MRSA, as well as stimulation of factors and
cells within the skin through a variety of biologic pathways.
Chikungunya is an alfavirus transmitted by the Aedes mosquito. Severe atypical
cases, defined as requiring the maintenance of at least one vital function or demise
during the course of the disease, are now increasingly recognized since the
2005/2006 outbreak in Reunion. Vesiculobullous Chikungunya is rarely described
in adults and is associated with a poor clinical prognosis. We report a case of severe
Chikungunya in an adult with an extensive blistering dermatosis who progressed to
develop septic shock, rhabdomyolysis, and Guillain-Barré syndrome. Initial laboratory investigations revealed mild leukocytosis, a low normal platelet count of
143000/L (normal range, 140-440 3 109/L), markedly elevated creatinine kinase,
and creatinine. Histologic examination revealed a subepidermal blister with a few
mononuclear cells and some fibrin strands. Direct immunofluorescence of perilesional skin was negative. The serum Chikungunya reverse transcription real-time
polymerase chain reaction (RT-PCR) serology for Chikungunya IgG and IgM were
positive; dengue PCR was negative. Blister fluid and paraffin block section of the
blister for chikungunya RT-PCR were positive. While little is known about
vesiculobullous Chikungunya, this entity may herald a more severe clinical course
of illness and mortality. Our patient featured an array of rare manifestations of
Chikungunya, including blistering dermatoses, rhabdomyolysis, acute renal failure,
hypotension, autonomic neuropathy of the bladder, and Guillain-Barré syndrome.
Clinicians should have a high index of suspicion for this entity in epidemic, endemic
areas and in the returning traveler.
Molluscum contagiosum (MC) is a common infection worldwide, accounting for
about 1% of all diagnosed skin disorders in the US. Children, most commonly under 5
years old, become infected through direct skin-to-skin contact or by touching MCcontaminated objects. In adults, MC can be a sexually transmitted disease. It is
estimated that 5% of children and up to 20% of AIDS patients have MC. In healthy
children and adults, the MC rash will eventually clear, but it can last 18 months or
longer, and is bothersome for parents and children because of its appearance and
contagiousness. MC causes a characteristic lesion/rash with one or more round,
dome-shaped pink, waxy papules, with a small central indentation. They are usually
2.5 mm in diameter but can be as large as 1cm in diameter. Current treatments for
MC include curettage, cautery, cryotherapy, or blistering agents. Eighty-two patients
aged 18 months to 62 years who had used flavokine twice daily for MC were
evaluated for their response to the agent. The mean time of application was 6 weeks.
Thirty-seven patients (45%) had complete clearing of their lesions. Twenty-four
patients (30%) experienced partial clearing of their lesions. Twenty-one patients
(25%) had no clearing of their lesions. Two patients reported mild skin irritation that
may or may not have been related to flavokine. A partial or complete response rate of
75% of MC to flavokine is very positive, as no other topical antiviral agent
demonstrates this response in this troublesome albeit benign skin disease.
Flavokine may have potential across a broad range of topical conditions because
of its complex nature and biologic activity.
Commercial support: 100% is sponsored by Dalos BioPharma.
AB90
J AM ACAD DERMATOL
MARCH 2010
INTERNAL MEDICINE DERMATOLOGY
P2600
Atrophying scamous papulous dermatitis (Degos disease): Nine years of
follow-up
José Luis Iribas, MD, Hospital Dr. José M. Cullen, Santa Fe, Argentina; Adriana
Albertengo, MD, Hospital J. B. Iturraspe, Santa Fe, Argentina; José Gabriel Casas,
MD, Hospital Britanico, Ciudad Autonoma de Buenos Aires, Buenos Aires,
Argentina
Background: Degos disease was described in 1942 as atrophying scamous papulous
dermatitis. It is a rare disease which, in most of the cases, starts as a cutaneous
manifestation; it hardly ever begins with gastrointestinal or neurologic symptoms.
Skin manifestation can occur only in 4% to 15% of the cases. The main cause of death
is the involvement of gastrointestinal organs and the second is the neurologic as
well. Its etiology is unknown, its thrombotic patogenia is possible. Nowadays, for
some authors, it is considered within the lupus erythematouss (LE) spectrum and
also it was described during the evolution of the systemic scleroderm, dermatomyositis, AIDS, and antiphospholipid antibody syndrome. Panniculitis lesions were
described during its evolution.
Case report: We present a 36-year-old woman after 9 years of evolution. Her disease
started as a panniculitis in buttocks and thigs areas, and its histopathology was
compatible with LE. After these lesions, she started with clinical typical Degos
lesions disease, with thrombotic findings in a histopathology and dermal necrosis.
During her evolution she developed polymyositis with a positive response to the
steroid treatment. The last years she presented new typical lessons above right knee
and bilateral involvement of ankles that developed in deep ulcers without any
general symptoms. She has extensive calcinosis cutis and lipodystrophy. The patient
was pregnant twice during her evolution, without any problems for her and for her
children. She has been taking antiplatelet, antipaludic drugs, and pentoxifiline (a
TNF inhibitor), except during her pregnancy. She is currently under medical control
without any systemic complications.
P2602
Graft versus host diseaseelike: A new paraneoplastic syndrome
Diana Garza-Salazar, MD, Hospital Universitario ‘‘Dr José E. González,’’ Monterrey,
Nuevo León, Mexico; Alberto De la Fuente-Garcı́a, MD, Hospital Universitario
‘‘Dr José E. González,’’ Monterrey, Nuevo León, Mexico; Ivett Miranda-Maldonado,
MD, Hospital Universitario, Monterrey, Nuevo León, Mexico; Jorge OcampoCandiani, MD, Hospital Universitario, Monterrey, Nuevo León, Mexico; Minerva
Gómez-Flores, MD, Hospital Universitario, Monterrey, Nuevo León, Mexico
Introduction: Thymoma is the most frequent thymic malignancy; it is associated
with various neoplasic syndromes, being myasthenia gravis the most frequent. In
medical literature, it has been reported only seven cases of thymoma associated with
acute graft versus host disease like.
Case report: A 39-year-old Hispanic woman diagnosed with myasthenia gravis 10
years ago was managed with pyridostigmine. Soon after, a thymoma was diagnosed
and thymectomy was performed without complications. She presented 2 years ago
at another dermatology clinic with erythematous scaling patches and pruritus
which was first confined to her legs an that later progressed to erythrodermia. A
diagnosis of psoriasis was established and treatment was initiated with antihystaminics and topical steroid, with poor response to treatment. Later on, her plaques
developed hyperpigmentation and sclerodermoid changes. Six months before her
first visit to our department, she suffered from generalized hair loss, oral mucous
ulcerations, and episodes of self-limited diarrhea. Laboratory tests evidenced
normocitic normocromic anemia, elevated levels of alkaline phosphatase and also
lactose dehydrogenase. A skin biopsy specimen was taken and showed typical
changes of chronic graft versus host disease. Based on her background history,
clinical presentation, and histopathology, a diagnosis of thymoma associated with
chronic graft versus host diseaseelike was established.
Discussion: Thymoma tumors have an incidence of 0.15 cases per 100000 people,
predominantly affecting males between their fourth and sixth decades of life. Graft
versus host disease presents in patients with bone marrow transplant. There are
many cell populations responsible for this disease, being T-lymphocytes the most
relevant. The presence of autoimmunity in patients with thymoma should be
considered because this organ plays a major role in T-lymphocytes maturation.
There have been only seven case reports of graft versus host disease associated with
thymoma, which presented with acute cutaneous and gastrointestinal symptoms.
Recently AIRE (autoimmune regulator gene) has been described and could help in
understanding the scenario of these autoimmune diseases. In this case, the
presentation was a chronic form of graft versus host disease. To our knowledge,
this is the first case described of a chronic presentation.
P2603
Results: AGA patients showed significant higher systolic BP values (139.43 vs
107.80mm Hg; P\.0001), diastolic BP values (87.65 vs 67.48mm Hg; P\.0001) and
aldosterone levels (249.55 vs 155.14pg/mL; P ¼.002) versus controls, respectively.
A positive relationship was observed between blood pressure and higher aldosterone values in women with AGA (r ¼ 0.337, P ¼.033 for systolic blood pressure and r
¼ 0.210, P ¼ .194 for diastolic BP).
Conclusion: A higher prevalence of hypertension in women with AGA has been
found. The elevated aldosterone values in these patients may contribute, alongside
other mechanisms, to the development of AGA and may also explain the higher
prevalence of hypertension. Aldosterone antagonists, have been used for a long time
for female AGA and may exert a dual beneficial effect in hypertensive AGA patients,
controlling BP and preventing alopecia progression, especially if taken in early
stages.
Nephrogenic systemic fibrosis: Report of two cases
Yann Charli-Joseph, MD, Instituto Nacional de Ciencias Médicas y Nutrición
Salvador Zubirán, Mexico City, Distrito Federal, Mexico; Ana RuelasVillavicencio, MD, Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Zubirán, Mexico City, Distrito Federal, Mexico; Linda Garcı́a-Hidalgo, MD,
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
City, Distrito Federal, Mexico; Rocı́o Orozco-Topete, MD, Instituto Nacional de
Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Distrito Federal,
Mexico
Nephrogenic systemic fibrosis (NSF) is an emerging disorder exclusive of patients
with renal disease, but its precise etiology is yet unknown. So far, only 315 cases
have been reported. Thickening of the skin coincides with progressive multisystemic tissue collagen deposition. There is no effective standard treatment, but
correction of glomerular function can alleviate the disease. Recently, a clear
epidemiologic association with gadolinium chelateebased contrast agents (GdCA) has been reported. We describe the features of two patients recently diagnosed
with NSF: patient A is a 38-year-old woman with end-stage renal disease (ESRD)
secondary to eclampsia, renal transplantation failure, and currently on hemodialysis.
She acquired primary cutaneous cryptococcosis and was submitted to MRI in order
to rule out osteomielitis. Ten days later, she developed confluent thickened
erythematous patches in distal limbs. A biopsy specimen revealed septal granulomatose paniculitis, extensive dermal fibrosis, and an increased number of CD341
spindle cells, consistent with NSF. Patient B is a 50-year-old man with ESRD with
associated hyperparathyroidism and cardiomiopathy secondary to hypertension
under treatment with peritoneal dialysis, erythropoietin, calcium and iron. Two
weeks after a cardiac MRI performed to study progressive dyspnea he developed
symmetric, indurated, edematose yellowish patches in both arms and legs. A punch
biopsy specimen was consistent with NSF. The clinicopathologic characteristics of
these patients are consistent with literature reports on NSF. Both cases reaffirm the
association with Gd-CA, which in the presence of ESRD have an increased half-life,
and are thought to transmetallate (free gadolinium ion is released from the chelate in
exchange for endogenous metals) with subsecuent binding of gadolinium to human
tissue and promotion of fibrosis. Furthermore, our findings support the requirement
of co-factors to generate a suitable environment for fibrosis (erythropoietin,
proinflammatory conditions such as infection, or metals that facilitate transmetallation). Finally, the importance of recognizing this disease and avoiding GdCA in patients with ESRD cannot be overemphasized.
P2601
Blood pressure levels in women with androgenetic alopecia
Salvador Arias-Santiago, MD, San Cecilio Clinical Hospital, Granada, Spain;
Husein Husein-El-Ahmed, MD, San Cecilio Clinical Hospital, Granada, Spain;
Jose Aneiros-Fernández, MD, San Cecilio Hospital, Granada, Spain; Marı́a Teresa
Gutiérrez-Salmerón, MD, San Cecilio Hospitai, Granada, Spain; Ramón NaranjoSintes, MD, San Cecilio Hospital, Granada, Spain
Introduction: Androgenic alopecia (AGA) is the most common type of alopecia both
in men and in women, but its prevalence and pathogenic mechanisms have been
mainly investigated in men. Few studies have analyzed the relationship between
AGA in women and cardiovascular disease. There is reported to be an elevated
prevalence of hypertension among men with AGA, and it has been proposed that
both phenomena may be explained by the presence of hyperaldosteronism.
However, no data on blood pressure (BP) and aldosterone levels in women with
AGA have been published to date. The objective of this study was to evaluate
aldosterone levels and the presence of systolic and diastolic hypertension in women
with early-onset AGA and in healthy controls.
Methods: This case-control study included 40 women with AGA and 40 healthy
controls from the Dermatology Department of San Cecilio Hospital, Granada
(Spain).
MARCH 2010
J AM ACAD DERMATOL
AB91
P2604
P2606
Nodular cutaneous amyloidosis: A rare case and review of amyloidosis
classification
Jessica Flowers, DO, Largo Medical Center/Sun Coast Hospital, Largo, FL, United
States; Richard Miller, DO, Bay Dermatology/LMC/Sun Coast Hospital, Largo, FL,
United States
Porphyria cutanea tarda as the presenting sign of hereditary
hemochromatosis
Morgan Wilson, MD, Geisinger Medical Center Department of Dermatology,
Danville, PA, United States; Tammie Ferringer, MD, Geisinger Medical Center
Department of Dermatology, Danville, PA, United States
A 56-year-old white man presented with a mildly pruritic, waxy, pink, cobblestonelike plaque on his right shoulder that developed over several weeks. A shave biopsy
revealed findings consistent with nodular cutaneous amyloidosis of the amyloid light
(termed AL)-type with kappa light chain positivity. Amyloidosis is generally classified
as systemic or cutaneous with both primary and secondary forms. There are also
heredofamilial and hemodialysis-associated varieties of amyloidosis, all with specific
amyloid fibril derivatives. Nodular cutaneous amyloidosis is the most rare form of
primary cutaneous amyloidosis. Lesions typically present as a crusted nodule on the
face, extremities or acral sites. The amyloid fibrils are immunoglobulin derived,
either kappa or lambda light chains. Systemic involvement is dependent upon
plasma cell amyloid protein deposition. Lesions may otherwise be classified as a
local plasma cell clone or cutaneous plasmacytoma. Recent reports state there is
\10% risk of systemic progression. Workup should be performed and include at
least a full history and physical, serum protein electrophoresis (S-PEP) and urine
protein electrophoresis (U-PEP), and gingival, rectal or abdominal fat pad biopsies to
rule out presence of extracutaneous amyloid deposition. Management is very
challenging because there is no consistently effective treatment and local recurrence is common.
Porphyria cutanea tarda (PCT) is a bullous disorder of sun-exposed sites that is
associated with a reduction in the activity of uroporphyrinogen decarboxylase.
Acquired cases may be associated with systemic illnesses such as hepatitis C, HIV, or
hereditary hemochromatosis. We report the case of a 35-year-old woman who
presented with a 3-month history of blisters and erosions on the bilateral dorsal
surfaces of her hands and forearms. Family history was positive for an uncle with
hemochromatosis. Urine porphyrin levels and skin biopsy findings confirmed a
diagnosis of PCT. Genetic testing revealed homozygous C282Y mutations in the
hemochromatosis (HFE) gene, and liver biopsy showed iron overload, but no
fibrosis. Aggressive phlebotomy led to gradual resolution of bullae and skin fragility.
Evaluation of PCT patients for hemochromatosis may aid in early diagnosis and
institution of therapeutic iron reduction before irreversible organ damage.
P2607
Ear helix necrosis caused by cryoglobulinemic cutaneous occlusive
vasculopathy
Antoni Bennàssar-Vicens, MD, Hospital Clı́nic, Barcelona, Spain; Antonio
Guilabert, MD, Hospital Clı́nic, Barcelona, Spain; Irene Fuertes-de Vega, MD,
Hospital Clı́nic, Barcelona, Spain; Jose Manuel Mascaró, MD, PhD, Hospital
Clı́nic, Barcelona, Spain
Background: Multiple myeloma (MM) is a blood dyscrasia characterized by clonal
proliferation of plasma cells in the bone marrow that produces a monoclonal protein
rarely involving the skin. Nevertheless, there are several cutaneous manifestations of
monoclonal gammopathies that may occur in the setting of MM.
Elephantiasis nostras verrucosa: A case report
Carlos Gomez-Meade, DO, Nova Southeastern University College of Osteopathic
Medicine/Broward General Medical Center, Fort Lauderdale, FL, United States;
Angela Combs, DO, Nova Southeastern University College of Osteopathic
Jerry Obed, DO, Nova Southeastern University College of Osteopathic
Stanley Skopit, DO, Nova Southeastern University College of Osteopathic
Medicine/Broward General Medical Center, Fort Lauderdale, FL, United States
Elephantiasis nostras verrucosa is a rare, chronically deforming multifactorial
disease that presents as a nonfilarial lymphedema. Causative factors include obesity,
congestive heart failure, venous stasis, neoplastic obstruction, and radiation injury
to name a few. Patients with this disease are susceptible to frequent episodes of
cellulitis which leads to worsening fibrotic changes and inflammation. This is
represented clinically as chronic lichenification, nonpitting edema, limb deformation, cobblestone-like papules and nodules with a woody induration of the affected
limbs. Histologically, there is parakeratosis, hyperkeratosis of the epidermis with
dilated lymphatic channels. This debilitating condition requires close monitoring
and appropriate management of both the edematous and infectious states. A case of
a patient with a history of progressive chronic indurated lymphedema with frequent
hospitalizations for cellulitis to the lower extremities is presented in the following
case report.
Case report: We present a 62-year-old woman who was referred to our outpatient
clinic with a large necrosis of both ear helixes. She stated that the lesions had
appeared every winter within the last 4 years. They self-healed in summer. The
pathologic study revealed necrosis throughout the skin and cartilague. An eosinophil, PAS-positive material was occluding the blood vessels, but the features of
vasculitis were absent. Serum cryoglobulins were positive and a monoclonal IgMkappa gammopathy was detected by serum electrophoresis. A bone marrow biopsy
was then performed showing a monoclonal plasma cell neoplasm. Therefore, the
diagnosis of cryoglobulinemic cutaneous occlusive vasculopathy (type I cryoglobulinemia) was made. Furthermore, our patient had inactive hepatitis C virus
infection. However, she presented without features of vasculitis as patients with
mixed cryoglobulinemia usually do.
Discussion: MM is a plasma cell dyscrasia where plasma cells proliferate and release
monoclonal immunoglobulins. There are many cutaneous eruptions that have been
associated with MM. On one hand, there are skin disorders that are the result of skin
infiltration by the malignant cells (plasmocitoma) or a product they produce
(amyloidosis, monoclonal cryoglobulinemia or type I). In addition, many skin
disorders have been associated with MM in a paraneoplastic manner (POEMS
syndrome, normolipemic plane xantoma, scleredema, scleromyxedema, necrobiotic xantogranuloma, Sweet syndrome, pyoderma gangrenosum, erythema elevatum diutinum, etc) or as a result of MM treatment (graft versus host disease). Type I
cryoglobulinemia or cryoglobulinemic cutaneous occlusive vasculopathy (CCOV) is
composed of monoclonal immunoglobulins that may cryoprecipitate within the
blood vessels producing thrombosis, necrosis and ulceration in acral sites of cold
exposure. CCOV vessel deposit is composed of only monoclonal IgG or IgM (and less
frequently IgA) cryoglobulins and is usually related with an underlying plasma cell
dyscrasia or lymphoproliferative disorder. All patients diagnosed of CCOV should
undergo monoclonal gammopathy screening. Treatment is primarily directed at
minimizing cold exposure and controling the underlying disorder.
P2605
AB92
J AM ACAD DERMATOL
MARCH 2010
P2608
P2610
A case of blue toe syndrome in a patient with lupus anticoagulant and
proteus mirabilis septicemia
Lana McKinley, DO, Largo Medical Center / Nova Southeastern College of
Osteopathic Medicine, Largo, FL, United States
Langerhans cell histiocytosis presenting in a 79-year-old man
Andrea Musel, MD, University of Oklahoma Department of Dermatology,
Oklahoma City, OK, United States; Pamela Allen, MD, University of Oklahoma
Department of Dermatology, Oklahoma City, OK, United States; Yaohan Adrienne
Li, University of Oklahoma Department of Dermatology, Oklahoma City, OK,
United States
Lupus anticoagulant and antiphospholipid antibody syndrome are prothrombotic
disorders characterized by either venous or arterial occlusion and/or fetal morbidity.
These disorders are often triggered by underlying exacerbations of autoimmune
disease, infection (including bacteremia), drugs, or genetic predisposition. The
cutaneous manifestations of these disorders can be variable, including painful
purpura and ischemia most often affecting the distal lower extremity. We describe
the case of a 27-year-old woman admitted for an obstructed renal calculus
complicated by Proteus mirabilis urosepticemia. The patient gradually developed
severely painful, violaceous, nonblanching patches that progressed into bullae
encompassing her bilateral feet with involvement of all 10 toes. Skin biopsy of these
lesions revealed evidence of a thrombotic vasculopathy. Coagulopathy workup was
consistent with the presence of a lupus anticoagulant. The patient improved after 3
days of plasmapheresis and anticoagulation therapy.
A 79-year-old white man presented to the OU Department of Dermatology in April of
2009 with a 6-year history of a worsening rash present throughout the body. The
rash was mainly erosive with copious exudates in the body fold areas, including
behind the ears, in the groin, gluteal cleft, axillae, and under the breasts. He also had
scattered red papules over the trunk and extremities. His face had confluent
background erythema, with some scale, and several ulcerated, pearly papules which
were suspicious for basal cell carcinoma. Both conchal bowls were scaly and had
exudate, which was interfering with the use of his hearing aids. When the patient
was referred to us, his working diagnosis was fungal or candidal intertrigo. Outside
skin biopsies performed on December 31, 2008 were taken from the groin and were
reported as psoriasiform dermatitis, negative for stainable organisms. In addition,
there was a bacterial culture from the groin on 2/7/09, which grew normal skin
flora. KOH from the same day was negative for fungal elements.
In the 6 years since the patient’s disease started, various therapies were prescribed
including topical and oral antifungals, topical and oral antibiotics, topical steroids,
and a water-based emulsion used to treat skin wounds. We elected to perform
several biopsies including one on the bridge of the nose, which appeared clinically
to be a basal cell carcinoma, an ulcerated lesion in the posterior sulcus of the left ear
and from the erosion in the right groin. The groin biopsy was read as lichenoid
dermatitis. The biopsies from the nose and the posterior sulcus of the ear showed a
dense infiltrate of large, atypical cells, with oval to reniform nuclei. There were
scattered mitoses. The atypical cells stained positively with S100 and CD1a. They
were negative for CD20, CD30, and CD 3. The histopathologic diagnosis was
Langerhans cell histiocytosis (LCH). We referred the patient to oncology for work-up
and staging, because LCH can have visceral involvement. Typically LCH occurs in
very young children. This is a rare case of LCH appearing in an elderly male.
P2609
P2611
Cutaneous metastasis occurring only within an irradiated field
Jessica Liggett, MD, Henry Ford Hospital Department of Dermatology, Detroit,
MI, United States; Henry Lim, MD, Henry Ford Hospital Department of
Dermatology, Detroit, MI, United States
We present a case of cutanesous metastasis confined to a field of previous radiation.
The patient was a 60-year-old white man with a history of poorly differentiated
adenocarcionma admitted with a 2- to 3-week history of a new eruption on the right
axilla, arm, chest and back. Two weeks before the eruption began, the patient had
completed radiation therapy to the right axilla, arm, chest, and back. The lesions
were firm, erythematous papules in a background of bronzed erythema. There were
no lesions seen outside of the irradiated field. The skin biopsy confirmed poorly
differentiated adenocarcinoma and immunohistochemical stains, suggested lung
origin. Cutaneous metastases confined to a previously irradiated field are rare, but a
few cases have been reported in patients with breast cancer, squamous cell
carcinoma of the nasopharynx, and gastric cancer. The mechanism behind this
phenomenon is yet to be fully elucidated.
Inflammation of actinic keratoses secondary to systemic chemothrapy.
Jessica Ghaferi, MD, Henry Ford Hospital, Detroit, MI, United States; Margaret
Douglass, MD, Henry Ford Hospital, Detroit, MI, United States
We present the case of a 68-year-old white man undergoing chemotherapy for B-cell
lymphoma that presented with a 1-week history of a pruritic eruption. He
completed three cycles of his chemotherapeutic regimen: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). The patient’s history
was significant for colon cancer and ulcerative colitis. The physical examination
revealed several hyperkaratotic, scaly macules and plaques with surrounding
erythema scattered throughout the sun-exposed areas of the body. These were
clinically consistent with inflamed actinic keratoses. The reaction resolved entirely
upon completion of chemotherapy. Inflammation of preexisting and subclinical
actinic keratoses has previously been described in patients undergoing chemotherapy with several different agents including doxorubicin, systemic 5-fluorouracil, and
capecitabine. The mechanism remains unknown, but the reaction resolves with the
discontinuation or completion of chemotherapeutic agents.
MARCH 2010
J AM ACAD DERMATOL
AB93
P2612
P2614
Cutaneous metastases from internal malignancies: Experience from a
Mexican university hospital
Alberto De La Fuente-Garcı́a, MD, Hospital Universitario ‘‘José E. González,’’
Servicio de Dermatologı́a, Monterrey, Nuevo León, Mexico; Ivette MirandaMaldonado, MD, Hospital Universitario ‘‘José E. González,’’ Servicio de
Dermatologı́a, Monterrey, Nuevo León, Mexico; Jorge Ocampo-Candiani, MD,
Hospital Universitario ‘‘José E. González,’’ Servicio de Dermatologı́a, Monterrey,
Nuevo León, Mexico; Minerva Gómez-Flores, MD, Hospital Universitario ‘‘José E.
González,’’ Servicio de Dermatologı́a, Monterrey, Nuevo León, Mexico; Oralia
Barboza-Quintana, MD, Hospital Universitario ‘‘José E. González’’ U.A.N.L,
Servicio de Anatomı́a Patológica, Monterrey, Nuevo León, Mexico
Diffuse idiopathic skeletal hyperostosis associated with bexarotene
Courtney Schadt, MD, Vanderbilt University Medical Center Division of
Dermatology, Nashville, TN, United States; Howard Fuchs, MD, Vanderbilt
University Medical Center Division of Rheumatology, Nashville, TN, United
States; John Zic, MD, Vanderbilt University Medical Center Division of
Dermatology, Nashville, TN, United States
Introduction: Internal malignancies rarely spread to the skin with the exception of
breast carcinoma. Cutaneous involvement has been estimated to occur in 0.7% to 9%
of patients. Metastases may help to identify and locate an occult malignancy, and
may also constitute the first manifestation of a relapse.
Objective: To determine the rates of cutaneous metastases from internal cancers,
ages at presentation, locations, histologic types, and the time from diagnosis of the
primary malignancy until the detection of metastases.
Methods: This was a retrospective study (1994-2008) in which pathologic records
and biopsy specimens from all cases of cutaneous metastases were evaluated.
Metastases were defined as cancer spreading through the bloodstream, lymphatic
system, direct extension or iatrogenic implantation that involved the skin. Primary
blood and skin cancers were excluded.
Results: Twenty-seven skin specimens were evaluated in 6 males (mean, 60.5 years;
SD 6 13.2) and 21 females (mean, 56.63 years; SD 6 16.62). The most common
locations for metastases were the chest (70.3%), as well as head and neck (18.5%).
The mean time until the diagnosis of cutaneous metastasis was 29 months; 7.5
months for males (SD 6 4.43) and 35.41 months (SD 6 60.7) for females. Breast
cancer was the most frequent metastatic tumor (59.25%), with a mean age at
presentation of 60.8 years (SD 6 13.18), and a mean time until the diagnosis of
cutaneous metastasis of 39.28 months; being its most common site of metastases the
chest (93.75%). Other tumors were: from unknown origin (2 cases), lung, kidney,
pancreas, stomach, testis, prostate, thyroid, parotid and choriocarcinoma. By
histologic type, adenocarcinoma (24 cases) was the most frequent (88.8%).
Conclusions: Females develop metastases at younger ages but tend to metastasize
later than males. Although we confirm that the most common metastatic tumor to
skin is breast cancer, by histologic type adenocarcinomas, and that the most
common location of metastases is the chest, we found higher rates of breast cancer
metastases, chest involvement and adenocarcinomas than previous studies. Recent
data suggest that only 5% to 10% of breast cancers in Mexico are detected at initial
stages as compared to 50% in the United States. Given that breast cancer mortality is
increasing in Mexico, and that it affects adult women from all ages and conditions,
these may be reasonable explanations for the higher rates of breast cancer
metastases in our study.
Background: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by
ossification of ligaments and entheses, particularly in the spine. The use of the
retinoids etretinate, isotretinoin, and acitretin have been associated with the
development of DISH. We present a patient who developed DISH while taking
bexarotene, a retinoid approved by the US Food and Drug Administration for the
treatment of cutaneous T-cell lymphoma in 1999.
Case report: A 71-year-old man was seen at the Nashville Campus of the Tennessee
Valley Healthcare System, Department of Veterans Affairs Medical Center. In 2001,
he was diagnosed with cutaneous T-cell lymphoma stage IIB with transformation.
Bexarotene was started in May 2002, and the eventual chronic stable dose was
600mg/day. In April 2005, he was seen with a 2-year history of increasing back pain
and proximal muscle dysfunction related to pain. He had limited mobility with a
Shober maneuver elongating from 10cm to 12cm, neck rotation of 608, and lateral
neck flexion of 158. Radiographs of the lumbosacral spine revealed spinal
osteophytes consistent with DISH. Naproxen was prescribed initially with significant improvement of his back pain, but dysphagia developed and cervical spine
radiographs demonstrated large anterior osteophytes. The bexarotene dose was
reduced, but because of continued difficulties with pain and activities of daily living,
bexarotene was discontinued in November 2005. In January 2006, the spinal pain
had resolved, but he continued to have limited chest expansion, a Shober maneuver
of 10cm to 13cm, neck rotation of 608, and lateral neck flexion of 158. Cervical and
lumbar spine radiographs were unchanged in September 2008. A physical examination in April 2009 showed reduced neck lateral flexion of 108, lateral rotation of
458 to the left, and 608 to the right. He continues to be managed medically for his
pain.
Discussion: While numerous cases in the literature report DISH associated with
etretinate, isotretinoin, and acitretin, this is the first case showing the development
of DISH in a patient taking bexarotene, a newer retinoid. More studies are needed to
examine the etiology of DISH in patients on retinoids. Furthermore, dermatologists
should consider performing a simple three-stage screening on physical examination
at baseline that includes evaluating rotation and lateral flexion of the neck, chest
wall expansion with deep breath, and the Shober maneuver.
P2613
Atypical clinical presentations of myxedema in thyroid diseases: Case
series
Silvia Méndez-Flores, MD, Instituto Nacional de Ciencias Médicas y Nutrición
Salvador Zubirán, Mexico City, Distrito Federal, Mexico; Carla Archer-Dubon,
MD, Intituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico
City, Distrito Federal, Mexico; Linda Garcı́a-Hidalgo, MD, Intituto Nacional de
Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Distrito Federal,
Mexico; Rocı́o Orozco-Topete, MD, Instituto Nacional de Ciencias Médicas y
Nutrición Salvador Zubirán, Mexico City, Distrito Federal, Mexico
Typical thyroid dermopathy (TD) or myxedema commonly begins with raised,
indurated, skin-colored or yellowish brown waxy plaques in the pretibial area.
Because hair follicles are prominent, the lesions resemble, in appearance and
texture, an orange peel (peau d’orange) or pigskin. Diagnosis is based on these
typical pretibial skin lesions in association with a history of Graves hyperthyroidism
and ophthalmopathy. However, in our experience, myxedema or thyroid dermopathy may may have diverse clinical presentations, such as lesions in the upper parts
of the body exposed to trauma. The aim of this series is to report the diverse clinical
manifestations of TD in our patients with thyroid diseases. We reviewed the charts of
patients diagnosed with myxedema. Seventeen patients were identified; 55%
presented as diffuse nonpitting edema of the legs, 27% as typical plaques and 18%
as sharply circumscribed tubular or nodular lesions. In conclusion, although the
literature reports that the most common area of involvement is pretibial skin, we did
not corroborate this finding in our patients. Our findings suggest that a diffuse
edema of the legs in patients with thyroid disease may be an early feature of
myxedema which requires clinical suspicion. Most cases of thyroid dermopathy are
asymptomatic and do not require specific therapy.
AB94
P2615
Cutaneous presentation of familial dyslipidemia
Rola Gharib, MD, West Virginia University School of Medicine, Section of
Dermatology, Morgantown, WV, United States; Angela Kovach, MD, West
Virginia University, Department of Medicine, Morgantown, WV, United States;
Rodney Kovach, MD, West Virginia University School of Medicine, Section of
Dermatology, Morgantown, West Virginia, United States
Type III hyperlipidemia is an autosomal recessive disorder of lipid metabolism
characterized by both hypercholesterolemia and hypertriglyceridemia. Cutaneous
manifestations include xanthomas, which are lipid deposits in the skin and
subcutaneous tissue. The classic xanthoma striata palmaris of type III hyperlipidemia presents clinically as yellowish lesions in the creases of the palms. We present a
case of a patient who was referred to our clinic for further evaluation of yelloworange plaques in the creases of both palms of her hands.
J AM ACAD DERMATOL
MARCH 2010
LYMPHOMA, CUTANEOUS/MYCOSIS FUNGOIDES
P2700
Large cell transformation in mycosis fungoides: Clinicopathologic study
in nine patients
Cristina Eguren, Hospital Universitario de La Princesa, Madrid, Spain; Amaro
Garcı́a-Diez, Hospital Universitario de La Princesa, Madrid, Spain; Javier Fraga,
Hospital Universitario de La Princesa, Madrid, Spain; Sara Ibañes, Hospital
Universitario de La Princesa, Madrid, Spain; Silvia Pérez-Gala, Hospital
Universitario de La Princesa, Madrid, Spain
Background: The occurrence of large cell transformation (LCT) in mycosis
fungoides (MF), although rare, has been well described. The diagnosis of LCT relies
on the presence of more than 25% large cells on the lymphoid infiltrate throughout
or forming microscopic nodules. We describe clinicopathological features and
prognosis of nine patients with transformated MF of our cutaneous lymphoma
database.
Case reports: LCT was diagnosed in nine patients (2 men and 7 women), seven with
classical MF and two with follicular MF. The median age at diagnosis of transformation was 58 years (range, 43-82). The median time from first MF symptoms to
transformation was 8 years (range, 6 months to 49 years). At the time of diagnosis of
transformation, one patient had plaque lesions and eight patients had tumor lesions
(1 patient was in stage IB, 6 were in stage IIB, and 2 in stage IVA). In seven patients,
the disease progressed to higher states but only one of them died 9 months after
transformation. All patients received several treatments with topical and oral
corticosteroids, PUVA, topical carmustine, alfa-interferon, oral retinoids, radiotherapy, and chemotherapy. Two patients needed peripheral blood stem cell transplants.
Conclusion: Our results differ from other studies in several points: in our group
there are more women than men (77.8 % women and 22.2% men). The median
survival from initial diagnosis of MF has been reported as 37 months for patients with
LCT. In our group, only one patient died 9 months after transformation. To date, the
median time survival from initial diagnosis of MF is of 138 months and 60 months
from diagnosis of transformation. As in other studies, LCT is diagnosed on tumor
stage in most cases (8/9 patients).
P2702
Age-adjusted incidence and types of mycosis fungoides in Qatar
Samya Abou Shaikha, MD, MBBCh, Hamad Medical, Doha, Qatar; Hassan Riad,
MD, MBBCh, Hamad Medical, Doha, Qatar
Background: Mycosis fungoides (MF) is a lymphoma of low-grade malignancy with
prolonged survival. The progression from the clinical stage of patches to those
characterized by plaques, tumors, and extracutaneous spread usually takes place
over many years or decades. One of the problems in describing this disease is that it
does not look the same for all patients. Patches, plaques, and tumors are the clinical
names of the different presentations. Patches are usually flat, possibly scaly. Patches
are often mistaken for eczema, psoriasis or ‘‘nonspecific’’ dermatitis until an exact
diagnosis of MF is made. The aim of this study is to find the incidence and types of MF
in Qatar in the year 2003.
Methods: The study was conducted in the dermatology OPD of Hamad Medical. All
patients with MF in the year 2003 were registered. Detailed history and thorough
examination was done for each case. Biopsies were performed to confirm the
diagnosis in all cases, stained by H&E and immunophenotyping. Descriptive
statistics was done using Statistical Package for Social Sciences version 16. The
crude incidence equals the number of patient with MF reported divided by the total
population of Qatar in 2003. Age-adjusted incidence equals the crude incidence
multiplied by the population weight.
Results: The calculated crude incidence of MF was 1.1 per 100000 per year and the
calculated age adjusted incidence was 1.236 per 100000 per year.
Conclusion: The incidence of MF in Qatar is high; most of the patients are young
expatriates. They presented in nonearly stages. The types of MF also were mostly
rare variants. On both clinical and laboratory levels, we need more insight to
increase the sensitivity of early detection of the disease.
P2701
Follicular mucinosis associated with adult T-cell leukemia/lymphoma
Akira Kawada, MD, PhD, Department of Dermatology, Kinki University Scool of
Medicine, Osaka, Japan; Ayaka Hirao, MD, Department of Dermatology, Kinki
University School of Medicine, Osaka, Japan; Naoki Oiso, MD, PhD, Department
of Dermatology, Kinki University School of Medicine, Osaka, Japan; Shigeru
Kawara, MD, PhD, Department of Dermatology, Kinki University School of
Medicine, Osaka, Japan; Tamae Wada, MD, Department of Dermatology, Kinki
University School of Medicine, Osaka, Japan
CD41/CD561/TdT1 hematodermic neoplasm (previously called blastic
natural killer cell lymphoma) in a patient with chronic HTLV-1 infection
Johnny Gurgen, DO, Largo Medical/Nova Southeastern University, Largo, FL,
United States; Daniel Hogan, MD, Largo Medical/Nova Southeastern University,
Largo, FL, United States
Follicular mucinosis (alopecia mucinosa) is frequently associated with malignancies
including mycosis fungoides and Sézary syndrome. However, the association of
follicular mucinosis and adult T-cell leukemia/lymphoma (ATLL) has not been
reported. We report a 49-year-old man who had pruritic follicular papules and
erythemas clinically and follicular and perifollicular infiltrates and follicular mucin
deposition histopathologically. The patient showed 11% of flower-shaped atypical
lymphocytes in blood examination and positive human T-cell leukemia virus type I
antibody in serology, consistent with acute type of ATLL. This case seems to be a
very rare association of follicular mucinosis and acute ATLL, suggesting that
malignant T cells may have a feature of folliculotropism and epidermotropism.
CD41/CD561 hematodermic neoplasm—formally known as blastic natural killer
(NK) cell lymphoma—is a rare and aggressive neoplasm with a median survival time
of 14 months. The previously reported cases did not demonstrate a relationship with
HTLV-1 infection. HTLV-1 infection is well documented in other lymphomas, such as
adult T-cell leukemia/lymphoma. We report a case of CD41/CD561 hematodermic
neoplasm that was associated with chronic HTLV-1 infection. We propose that
screening should be done to further correlate the relationship between HTLV1 infection and CD41/CD561 hematodermic neoplasm. Close follow-up of patients
with chronic HTLV-1 infection may lead to earlier recognition and treatment of this
aggressive tumor.
P2703
MARCH 2010
J AM ACAD DERMATOL
AB95
P2704
P2706
Generalized subcutaneous panniculitis-like T-cell lymphoma following
rituximab for hemolytic anemia in a patient with chronic lymphocytic
leukemia
Matthew Hall, MD, Mayo Clinic, Jacksonville, FL, United States; Jason Sluzevich,
MD, Mayo Clinic, Jacksonville, FL, United States; John Snow, MD, Mayo Clinic,
Jacksonville, FL, United States
A 76-year-old man with a decade long history of chronic lymphocytic leukemia,
recently complicated by Coombs-positive hemolytic anemia, was treated with four
monthly infusions of rituximab (375mg/m2) in combination with cyclophosphamide (750mg/m2). The anemia resolved, but 2 months later the patient developed
rapidly progressive, generalized, asymptomatic, red-brown indurated cutaneous
nodules and plaques. Histopathology revealed infiltration of the subcutaneous fat
with atypical lymphocytes that rimmed adipocytes, as well as zonal lobular fat
necrosis. Immunohistochemical studies were positive for CD3, CD8, granzyme B,
and beta F1, and negative for CD4, CD30, and CD56. In situ hybridization studies for
Epstein-Barr virus were negative. T cell gene rearrangement studies by polymerase
chain reaction revealed monoclonality. A diagnosis of subcutaneous panniculitis-like
T-cell lymphoma (SPTCL) was rendered. The development of B-cell lymphoproliferative disorders in the setting of iatrogenic immunosuppression is well recognized.
This case represents the unique development of a clonal cutaneous T-cell lymphoma
in the setting of an immunosuppressive milieu characterized by systemic B cell
depletion. To our knowledge, this is the first reported case of SPTCL associated with
previous treatment with rituximab.
Topical carmustine in the treatment of mycosis fungoides: Efficacy and
side effects
Diana Santiago-et-Sánchez-Mateos, PhD, Hospital Universitario de La Princesa,
Department of Dermatology, Madrid, Spain; África Juárez, PhD, Hospital
Universitario de La Princesa, Department of Dermatology, Madrid, Spain;
Amaro Garcı́a-Diez, MD, Hospital Universitario de La Princesa, Department of
Dermatology, Madrid, Spain; Maximiliano Aragüés, PhD, Hospital Universitario
de La Princesa, Madrid, Spain; Rebeca Goiriz, PhD, Hospital Universitario de La
Princesa, Department of Dermatology, Madrid, Spain
Results: This study includes 19 patients ranging in age from 40 to 83 years. The time
from diagnosis to start of treatment ranged from \1 to 17 years. Fourteen patients
were in initial stages (3 in IA, 10 in IB, and 1 in IIA) and five were in advanced stages
of the disease (1 in IIB, 1 in III, and 3 in IVA). The patients in IVA stage were receiving
other systemic treatments. They were followed up for 7 to 142 months. Eighteen
patients responded (94.7%): 13 patients achieved CR (72.2%) and five patients got
PR (27.7%). Only in one case this treatment was withdrawn for the acute cutaneous
side effects. The CR was reached after a period of treatment from 2 to 10 months.
Two patients have maintained the CR. The time of freedom from relapse ranged
from 3 to 130 months. Although the majority of patients have suffered from relapses
of the disease, they most have maintained a stable stage. Four patients have
experienced progression of the disease. We have observed frequent cutaneous side
effects, such as erythema after application and persistent poikilodermatous changes
with striking telangiectasias. Neither hematologic side effects nor skin cancer were
observed.
Conclusions: Topical BCNU is an effective treatment for MF in initial stages and even
in advanced stages when used as a coadjuvant therapy. It is a remarkable safe
modality of treatment because the side effects observed are usually cutaneous
without secondary malignancy.
Introduction: Carmustine (BCNU) is a nitrosourea alkilating agent topically used for
mycosis fungoides (MF) for more than 3 decades. According to the EORTC
consensus recommendations, it is included in the skin-directed therapy as a firstline recommendation for stages IA, IB, IIA, and III.
Methods: Retrospective study of the patients diagnosed clinically and histologically
with MF who have ever received topical BCNU at the Derpartment of Dermatology
in Hospital Universitario de La Princesa from January of 1982 to February of 2009. It
was used in alcoholic solution (2mg/mL) diluted in water once daily on involved
areas, or undiluted if \3% of the body surface area was involved. Definitions of
response are as follows: complete response (CR), disappearance of all clinical
evidence of disease; partial response (PR), 50% or more improvement, both for at
least 4 weeks; no response (NR), less than 50% of improvement. We have analyzed
response, time of treatment to get CR, time of freedom from relapse, evolution and
side effects.
P2705
Sarcoid-like granulomatous mycosis fungoides presenting with markedly
hyperpigmented plaques
Steven Nelson, MD, Mayo Clinic, Scottsdale, AZ, United States; David DiCaudo,
MD, Mayo Clinic, Scottsdale, AZ, United States; Jennifer Ray, MD, Mayo Clinic,
Scottsdale, AZ, United States
A 69-year-old white woman presented with a 10-year history of asymptomatic,
enlarging, hyperpigmented plaques on the lower extremities, upper extremities,
and trunk. Cutaneous sarcoidosis was diagnosed 2 years earlier based on skin biopsy
findings, and hydroxychloroquine was started shortly after receiving the diagnosis.
Minocycline was used for a 2-month period during the treatment course. Physical
examination revealed multiple, large, well marginated, black patches and indurated
plaques bilaterally on the lower legs. On the buttocks, trunk, and arms were
violaceous plaques with overlying laxity and wrinkling of the skin. No skin changes
were present in the axillae or groin. Incisional biopsy showed dense dermal and
subcutaneous infiltrate composed of small lymphocytes admixed with numerous
histiocytes and large multinucleate giant cells. The infiltrate expressed CD2, CD3,
CD4, and CD5, with diminished expression of CD7, and absent expression of CD30
and CD56. Throughout the infiltrate, numerous intracellular and extracellular
pigment granules stained positively with the Fontana and iron stains. Clonal T-cell
receptor gene rearrangement was detected by PCR analysis. The patient has
discontinued the hydroxychloroquine and is scheduled to be seen in hematology
to discuss treatment options. Sarcoid-like granulomas are present in approximately
2% of primary cutaneous lymphomas; granulomatous mycosis fungoides (GMF) is
the most common lymphoma to demonstrate this feature. Sarcoidosis has been
reported to precede the diagnosis of GMF. Many of these cases have been shown
actually to be early GMF masked by the sarcoid-like reactions. The black hyperpigmentation makes this patient’s presentation unique. The hydroxychloroquine is
suspected to have contributed to the impressive amount of both melanin and iron
deposition. Although several of the plaques have overlying wrinkled, lax skin, the
term granulomatous slack skin (GSS) is reserved for similar changes in the axillae and
groin. GSS and GMF are differentiated by clinical features because they cannot
reliably be distinguished histopathologically. Recent studies suggest that the
prognosis of GMF is worse than that of classic mycosis fungoides.
AB96
P2707
Sézary syndrome and lung cancer association: Case report
Ana Rita Travassos, Clı́nica Universitária de Dermatologia, Hospital de Santa
Maria, Lisboa, Portugal; Luı́s Soares de Almeida, Clı́nica Universitária de
Dermatologia, Hospital de Santa Maria, Lisboa, Portugal; Marisa André, Clı́nica
Universitária de Dermatologia, Hospital de Santa Maria, Lisboa, Portugal; Paulo
Leal Filipe, Clı́nica Universitária de Dermatologia, Hospital de Santa Maria,
Lisboa, Portugal
Background: Cutaneous T-cell lymphoma (CTCL) has been associated with increased risk for secondary malignancies, namely other lymphomas and lung cancer.
Sézary syndrome (SS) is a leukemic variant of CTCL and is classically defined by the
triad of erythroderma, lymphadenopathy, and the presence of Sézary cells in the
skin, lymph nodes, and peripheral blood.
Case report: A 66-year-old white man, a heavy smoker, with a dermatosis characterized by erythematous patches and plaques confined to the lower limbs for 7 years,
which were devalued. The patient was subsequently diagnosed of squamous cell
carcinoma of the left lung (4 years later), and underwent neoadjuvant chemotherapy
and lobectomy followed by chemotherapy. During this lung-guided treatment
period, there was also a significant improvement of the skin lesions. Thereafter,
there was a progressive worsening of the dermatosis and the patient came to our
outpatient unit with erythroderma and generalized pruritus. Laboratory examinations showed peripheral leukocytosis with the presence of circulating Sézary cells
(4600 cells/L); an expanded CD41 population and T-cell receptor (TCR) gene
rearrangement was detected on peripheral blood and bone marrow aspirate. Skin
punch biopsies were compatible with mycosis fungoides/CTCL. Computed tomography scan of chest, abdomen and pelvis revealed small bilateral axillary and inguinal
enlarged lymph nodes. On the basis of these clinical, histopathologic, and molecular
biologic findings, the patient fulfilled the WHO-EORTC criteria for SS.
Conclusion: This clinical case reports the association of SS and lung cancer of the
squamous cell carcinoma type. Although we do not know why there is an increased
risk of lung cancer in CTCL patients, an appropriate monitoring for the early
detection of second cancers might be warranted in patients with CTCL.
J AM ACAD DERMATOL
MARCH 2010
P2708
P2710
A case of WoringereKolopp disease
Un Ha Lee, MD, Department of Dermatology, Sanggye Paik Hospital, Seoul, South
Korea; Hyun Su Park, MD, Department of Dermatology, Sanggye Paik Hospital,
Seoul, South Korea; Sang Hoon Park, MD, Department of Dermatology, Sanggye
Paik Hospital, Seoul, South Korea
Cutaneous involvement by extranodal NK/T-cell lymphoma of the colon,
histologically mimicking mycosis fungoides: A case report
Panitta Sitthinamsuwan, MD, Department of Pathology, Faculty of Medicine,
Siriraj Hospital, Mahidol University, Bangkok, Thailand
WoringereKolopp disease is a rare variant of mycosis fungoides and also known
localized pagetoid reticulosis. It presents solitary, usually localized hyperkeratotic
patches or plaques on the extremities with a slowly progressive course. Clinical
features may mimic other skin dermatoses including contact dermatitis, fungal
infection, localized psoriasis resulting in misdiagnosis and inappropriate treatment.
A 51-year-old woman presented with a 6-year history of well defined erythematous
annular patch 7cm in diameter with brown-colored indurate border on the left leg.
The lesion was asymptomatic and has been gradually enlarged. She had no history of
internal disease, any preceding eruption, inflammation, or injury to the area. Her
family had no history of skin abnormalities. Laboratory studies including complete
blood cell count, peripheral blood smear, and liver and renal function tests were
normal. A skin biopsy speciment revealed hyperkeratosis, acanthotic epidermis, and
epidermotrophic infiltration of atypical pagetoid cells with pleomorphic nuclei and
peripheral halo and band-like infiltration of lymphocyte in the papillary dermis. The
atypical cells were positive for CD3, CD8, and negative for CD4 in immunohistochemical stain that revealed cytotoxic T-cell phenotype. We report herein a case of
WoringereKolopp disease showing typical clinical features with a review of
literature.
We report a 51-year-old woman with cutaneous involvement by extranodal NK/Tcell lymphoma of the colon, histologically mimicking mycosis fungoides. She had
history of fever of unknown origin for 2 months and then developed multiple
erythematous papules on the extremities. A skin biopsy specimen revealed
superficial perivascular infiltration by atypical small- to medium-sized lymphocytes
with epidermotropism and Pautrier microabscesses. Immunohistochemical studies
showed positivity of CD3 and TIA-1 with double negative CD4 and CD8. Initially, we
reported mycosis fungoides, cytotoxic variant. Thereafter, a colonic mass was
incidentally found in abdominal CT scan. A colonic biopsy revealed abnormal diffuse
lymphoid infiltration with same morphology and immunophenotype as those found
in the skin. In addition, TCR-d gene rearrangement was rearranged. CD56 and EBER
in situ hybridization were diffusely positive. Extranodal NK/T-cell lymphoma was
diagnosed. Finally, the patient died within 2 months after the diagnosis.
P2709
Complete remission of lymphocytoma cutis with short-course anti-CD20
monoclonal antibody (rituximab)
Maria Navedo, MD, Clinica Universitaria de Navarra, Pamplona, Navarra, Spain;
Agustin España, MD, PhD, Clinica Universitaria de Navarra, Pamplona, Navarra,
Spain; Carlos Panizo, MD, PhD, Clinica Universitaria de Navarra, Pamplona,
Navarra, Spain; Gorka Ruiz-Carrillo, MD, Clinica Universitaria de Navarra,
Pamplona, Navarra, Spain; Laura Marques, MD, Clinica Universitaria de
Navarra, Pamplona, Navarra, Spain
Introduction: Cutaneous pseudolymphoma refers to a heterogeneous group of
nonneoplastic T- or B-cell lymphoproliferative processes. Localized forms (72%) are
the most frequent clinical presentation. It is usually seen as a single skin-colored to
red-purple asymptomatic soft or firm nodule although lesions may be aggregated in
small clusters. We report two cases of lymphocytoma cutis treated with anti-CD20
antibody (rituximab) with good results.
Methods: A 69-year-old man was admitted to further investigation of an asymptomatic 3-cm red tumor on the back that had arisen 5 months earlier and had been
increasing in size in the last weeks. Similar lesions had been observed during the last
year. The second case is a 53-year-old man with a clinical history of several redbrown indurated papules in the left forearm for several months. Thoracic and
abdominal CT were performed in both patients to exclude systemic presentation.
Both patients were treated with four doses of rituximab (375mg/m2 every week). In
both cases skin biopsy was performed for histopathologic and immunohistochemical studies on paraffin-embedded tissue sections for CD3, CD4, CD5, CD20, CD7,
CD8, bcl-2 and both k and l immunoglobulin light chains. A genetic analysis for
clonality in the IgH gene was also performed.
Results: In both patients pathologic studies were compatible with lymphocytoma
cutis and clonal IgH gene rearrangement was detected by PCR without systemic
manifestations. They had complete response following treatment with rituximab.
The postreatment course was uneventful and the patients had experienced no signs
of recurrence after 1 year of follow-up.
Conclusion: Although cutaneous pseudolymphoma is a nonneoplastic reactive
condition, the presence of a clonal population is a marker of progression to
lymphoma. The question remains whether clonal cutaneous pseudolymphoma is
early cutaneous lymphoma or it represents true cutaneous pseudolymphoma that
later undergoes lymphomatous transformation. This uncertainty emphasizes the
importance of long-term follow-up. Usually treatment for this pathology is conservative, as spontaneous resolution is a frequent evolution. In our cases, the presence
of a monoclonal B-cell population indicating neoplastic transformation led us to
treat more aggressively these patients. Therapy results are promising in this
pathology in which further investigation is needed to throw light on its biology
and clinical course.
P2711
Primary plasmacytoma of the penis associated with chronic lymphocytic
leukemia
Salvador Arias-Santiago, MD, San Cecilio Clinical Hospital, Granada, Spain; José
Aneiros-Fernández, MD, San Cecilio Clinical Hospital, Granada, Spain; Marı́a
Sierra Girón-Prieto, MD, San Cecilio Clinical Hospital, Granada, Spain; Mercedes
Gomez-Morales, MD, San Cecilio Clinical Hospital, Granada, Spain; Miguel Angel
Arrabal-Polo, MD, San Cecilio Clinical Hospital, Granada, Spain
Introduction: Primary cutaneous plasmacytoma is a rare entity characterized by a
monoclonal proliferation of mature plasma cells in the skin in the absence of
myeloma. The evolution to systemic disease has been described primarily in bone
plasmacytomas, but may also occur in others extramedullary forms.
Case report: A 79-year-old patient presented with a 3-month history of an asymptomatic penile lesion. A physical examination revealed a violaceus plaque of 3 3
2cm, slightly infiltrated on palpation, located on the dorsal surface of the penis. A
biopsy of the lesion was performed showing infiltration by plasma cells at various
stages of maturation with positivity for CD38, EMA, and IgG kappa chain. The bone
marrow aspirate presented infiltration by chronic myeloproliferative syndrome type
chronic lymphocytic leukemia. Treatment with chlorambucil and prednisone was
prescribed.
Discussion: The primary extramedullary plasmacytoma of the skin without bone
involvement is extremely rare and is characterized by the presence of atypical
multinucleated and binucleated plasma cells. It is important to establish a differential diagnosis from other granulomatous entities. Its evolution to multiple myeloma
is controversial and the presence or absence of M component may be useful in the
evolution of the disease. Various treatments such as radiotherapy, surgery, or
chemotherapy have been applied with variable success. In the present case, we
want to highlights its location on the penis and the association with a chronic
lymphocytic leukemia.
MARCH 2010
J AM ACAD DERMATOL
AB97
P2712
P2714
Clinicopathologic features and T-cell receptor gene rearrangement findings of mycosis fungoides in patients younger 20 years of age
Kee Suck Suh, MD, Department of Dermatology, Kosin University College of
Medicine, Busan, South Korea; Jae Woo Baek, MD, Department of Dermatology,
Kosin University College of Medicine, Busan, South Korea; Sang Tae Kim, MD,
Department of Dermatology, Kosin University College of Medicine, Busan, South
Korea; Tae Kwon Kim, MD, Department of Dermatology, Kosin University
College of Medicine, Busan, South Korea; Young Seung Jeon, MD, Department
of Dermatology, Kosin University College of Medicine, Busan, South Korea
Clinical and pathologic features of skin involvement by angioimmunoblastic T-cell lymphoma: Report of the University of Iowa experience and
review of the literature
Vincent Liu, MD, University of Iowa Carver College of Medicine, Iowa City, IA,
United States; Brian Link, MD, University of Iowa Carver College of Medicine,
Iowa City, IA, United States; Ryan Hegg, University of Iowa Carver College of
Medicine, Iowa City, IA, United States
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive malignancy classified
as a peripheral T-cell lymphoma. Most commonly seen in middle-aged or elderly
patients who present with constitutional symptoms, AITL has been reported in the
literature to exhibit varied cutaneous manifestations. Similarly, the dermatopathologic features of AITL have been variously described. Herein we report two patients
with cutaneous involvement by AITL seen at the University of Iowa Hospitals and
Clinics over the past 10 years, and review the literature. Specifically, we highlight a
68-year-old woman with a history of AITL who presented with intensely pruritic
erythroderma with histopathology demonstrating a mycosis fungoideselike appearance, and thereby expand our understanding of the clinicopathologic spectrum of
AITL.
Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma
that usually arises in middle age or older people. The incidence of childhood MF is
low, but studies in childhood MF suggests that the incidence is rising. The number of
studies in childhood MF is few, and there are currently no studies about childhood
MF in Asians. We investigated the clinicopathologic features, T-cell receptor (TCR)
gene rearrangement findings, treatment, and follow-up in childhood MF. This
retrospective study was performed on a population consisting of 23 MF patients
aged from 4 to 19 years. The duration of the disease ranged from 1 month to 10 years
(mean, 2.7 years). In TNM classifications, all cases were confined to stage IA or IB.
Histopathologic findings revealed epidermotropism and perivascular infiltrates,
epidermotropism in the infundibulum, Pautrier microabscesses, haloed lymphocytes, epidermal lymphocytes larger than dermal lymphocytes, atypical cells with
hyperchromatic nuclei, and wiry bundle of collagen. TCRg gene rearrangement was
performed except for 4 patients, and monoclonality was detected in 16 of 19 cases
(84%). Treatment was performed with psoralen plus ultraviolet A light phototherapy, UVA1, narrowband UVB, topical steroid, retinoic acid and calcipotriol. Most
patients showed a good response. At a mean follow-up of 90.4 months, no patient
had either an exacerbation of the disease or extracutaneous involvement. Compared
with adult-onset MF, MF in children may show a variety of clinical features. Its
prognosis is considered to be good. Moreover, histopathologic study and TCR gene
rearrangement study can help in the diagnosis of MF in children.
P2713
The World Health OrganizationeEuropean Organization for Research and
Treatment of Cancer classification of cutaneous lymphomas in Korea
Ji-Hye Park, MD, Department of Dermatology, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, South Korea; Dong Youn
Lee, PhD, Department of Dermatology, Sungkyunkwan University School of
Medicine, Samsung Medical Center, Seoul, South Korea; Hae Young Park, MD,
Department of Dermatology, Department of Dermatology, Sungkyunkwan
University School of Medicine, Seoul, South Korea; Ji Yeon Byun, MD,
University School of Medicine, Seoul, South Korea; Kyu Dong Jung, MD,
University School of Medicine, Seoul, South Korea
Background: The relative frequency and the clinocopathologic characteristics of
lymphomas vary according to geography and ethnicity. Data about the features of
cutaneous lymphoma presented according to the WHO-EORTC classification (2005)
in Korea are limited.
Objective: The aim of this study is to determine the relative frequency of cutaneous
lymphoma in Korea and to present clinical relevance of cutaneous lymphomas,
based on the WHO-EORTC classification.
Methods: The cases diagnosed as cutaneous lymphoma over a 15-year period were
collected in an institution-based dermatologic setting in Korea. These clinical
records and pathology slides were reviewed retrospectively.
Results: One hundred forty cases of 79 primary and 61 secondary cutaneous
lymphomas were reclassified. The group of primary cutaneous lymphomas
contained 81% T- and NK-cell lymphomas, 16.5% B-cell lymphomas, and 2.6%
immature hematopoietic malignancies. The relative frequency of the major diagnostic group resulted as follows: mycosis fungoides, 20 cases (25.3%); extranodal
NK/T-cell lymphoma, nasal type, 14 cases (17.7%); primary cutaneous anaplastic
large cell lymphoma, 10 cases (12.5%); cutaneous marginal zone B-cell lymphoma
(MALT-type), 9 cases (11.4%); subcutaneous panniculitis-like T-cell lymphoma, 8
cases (10.1%).
Conclusion: Korea presents a higher rate of T-cell and NK/T-cell lymphoma and a
lower rate of cutaneous B-cell lymphoma than the Western countries. Whereas,
compared to previous Korea reports (2003), the rate of mycosis fungoides was lower
and the rate of nasal and nasal-type NK/T cell lymphomas was higher than before.
Because the relative frequency of lymphomas differs according to geography and
ethnicity, there is a need to collect more data to describe the epidemiologic
characteristics in the Far East.
Neurofibromatosis associated with malignant melanoma in familial atypical melanoma syndrome(FAMM) affecting three generations
Wen Lyn Ho, MD, Department of Dermatology, Limerick, Ireland; Bartholomew
Ramsay, MD, Departmentof Dermatology, Limerick, Ireland; Nicola Daly, MD,
MBBCh, Department of Dermatology, Limerick, Ireland
A 46-year-old woman was referred for evaluation of her pigmented lesions in
September 2004 after the removal of an in situ malignant melanoma from her
abdomen the previous year. She had multiple irregular large and atypical nevi but
also a 10- 3 10-cm area of fleshy lesions on her right lower chest wall consistent
clinically with segmental neurofibromatosis that was confirmed histologically. In
March 2006, a dysplastic nevus was excised from her back. In May 2007, a malignant
melanoma (Clarke level 3, Breslow thickness ¼ 0.7mm) was removed from her left
thigh with negative sentinel node biopsy. Her mother died at 56 years of age of
metastatic melanoma and her brother had a malignant melanoma removed in 2004.
In summer 2008, her 8-year-old daughter developed a squint which was subsequently found to be caused by ocular malignant melanoma. This was removed in the
Royal Liverpool Hospital, UK. Neurofibromatosis type 1 (NF1) is the commonest
inherited neurocutaneous condition and results from mutations of NF1 gene which
codes for the protein neurofibromin—the regulator for a ras-dependant pathway.
There is a four-fold increase in neoplasia, especially neural crest derived tumors, in
NF1. In NF1 associated with malignant melanoma, there seems to be a female
predilection, a higher thickness of melanoma, and a frequent association with a
second neoplasm. A somatic deletion of the NF1 gene in NF1 associated with
malignant melanoma has been demonstrated by digital PCR. There is an increased
incidence of uveal nevi and malignant melanoma in NF1. This paper further
demonstrates the emerging link being recognised between NF1 and malignant
melanoma.
AB98
MELANOMA AND PIGMENTED LESIONS
P2800
J AM ACAD DERMATOL
MARCH 2010
P2801
P2803
Agminated atypical spitzoid neoplasm
Christine Cole, MD, Mayo Clinic, Scottsdale, CA, United States; David Swanson,
MD, Mayo Clinic, Scottsdale, AZ, United States; David Dicaudo, MD, Mayo Clinic,
Scottsdale, AZ, United States; Karen Warschaw, MD, Mayo Clinic, Scottsdale, AZ,
United States
Digital necrosis and severe Raynaud syndrome induced by alfa-interferon
in metastasic melanoma patient
Husein Husein-ElAhmed, MD, Hospital Universitario San Cecilio, Granada, Spain;
Jose-Luis Callejas-Rubio, MD, Hospital Universitario San Cecilio, Granada, Spain;
Norberto Ortego-Centeno, MD, Hospital Universitario San Cecilio, Granada,
Spain; Raquel Rios-Fernández, MD, Hospital Universitario San Cecilio, Granada,
Spain; Salvador Arias-Santiago, MD, Hospital Universitario San Cecilio, Granada,
Spain
IFN-alfa is the best adjuvant treatment for patients with melanoma in stage II and III.
We highlight the IFN-alfa potential serious toxicity by describing a patient who
developed severe Raynaud syndrome and a later digital necrosis during treatment for
melanoma with IFN-alfa. A 47-year-old woman underwent to surgery for ulcerated
nodular melanoma with Breslow thickness of 5mm and IV level of infiltration.
Surgery margins were free of disease. To stage melanoma, a positron emitting
tomography was performed and showed captation in pelvis lymph nodes. After
lymphadenectomy, histology confirmed metastasic melanoma, and subsequently
adjuvant therapy with 10 millions U/m2/dose of IFN-alfa, three times per week, was
started. Five months later, she attended to our hospital urgencies reporting painful
and cianotic digits of the left hand (the second and third digits). In anamnesis,
patient reported: Raynaud syndrome for several years which got worse in last 3
months, hand skin changes in last 12 months, and pyrosis with regurgitation.
Physical examination showed telangiectasias in the face, acrosclerosis, and digital
necrosis in fingers two and three of the left hand. Avascular areas and splinter
hemorrhages were observed in capilloscopy. Baryum swallow confirmed gastroesophageal reflux and severe esophageal hypomotility. Antinuclear antibody with
nucleolar form and anti-SLC-70 were positive. IFN-alfa has to be discontinued and
intravenous prostaglandin infusion was iniciated. After 1 week, necrosis disappeared and skin recovered completely. The preexisting Raynaud syndrome in our
patient was probably aggravated by IFN-alfa leading to digital necrosis. Association
between Raynaud syndrome and IFN-alfa is rare. In patients with mild attacks,
therapy has been continued, without aggravation of symptoms. In more severe
cases, as our patient, IFN-alfa was discontinued and treatment with calcium
antogonists or prostaglandins was initiated. Dermatologists and oncologists should
be aware that IFN-alfa may cause peripheral vascular toxicity manifested by the
development of Raynaud syndrome.
A 21-year-old healthy man with Fitzpatrick type III skin presented to dermatology
clinic for an asymptomatic, enlarging lesion on his left medial thigh. He had first
noticed it when he was 14, but it had since doubled in size. Family history was
negative for melanoma. Physical examination of the left medial thigh revealed an 8 3
10.2cm area containing hundreds of agminated, 2- to 4-mm, red-brown to gray to
black, well circumscribed macules and papules. Under dermoscopy, different
patterns were seen, including reticular, reticuloglobular, globular, and starburst
patterns. There were borderline atypical pigment networks and polymorphous
globules varying in size and color. Initially four 3-mm punch biopsies were
performed of representative macules. On histology, three of the four biopsies
were consistent with atypical junctional Spitzoid neoplasms with moderate to
severe atypia, and one junctional nevus with mild cytologic atypia. With clinicopathologic correlation, we made a diagnosis of agminated atypical Spitzoid
neoplasm. The patient underwent a staged reexcision. The first reexcision showed
residual severely atypical, agminated compound Spitzoid neoplasm. Scattered along
the dermoepidermal junction were small, nested, melanocytic proliferations composed of atypical Spitzoid melanocytes. Some of the melanocytic nests extended
superficially into the papillary dermis to a depth of 0.3mm. The term ‘‘atypical
Spitzoid neoplasm’’ is used to describe lesions that deviate from the typical
appearance of Spitz nevi and which have an uncertain biologic significance and
prognosis. There is a broad continuum from the benign Spitz nevus to the Spitzoid
melanoma, with atypical Spitz tumor in between. The clinical management of these
lesions is complex and controversial. Many prefer aggressive treatment, as it may
represent a potentially lethal lesion, with wide local excision and consideration of
sentinel lymph node biopsy if the depth is [0.75mm. There are more than 70 case
reports of agminated Spitz nevi. Our case is unique in that the agminated nevus was
composed of numerous atypical Spitz tumors that were difficult to discern from
frank melanoma on histology alone. In addition to complete reexcision, we intend to
follow the patient closely.
P2802
Wood light utility in the surgical treatment of pigmentary tumors and
vitiligo
Gorka Ruiz-Carrillo, MD, Department of Dermatology. University Clinic of
Navarra, Pamplona, Navarra, Spain; Laura Marques, MD, Department of
Dermatology. University Clinic of Navarra, Pamplona, Navarra, Spain; Maider
Pretel, MD, Department of Dermatology. University Clinic of Navarra, Pamplona,
Navarra, Spain; Maria Navedo, MD, Department of Dermatology. University Clinic
of Navarra, Pamplona, Navarra, Spain; Pedro Redondo, MD, PhD, Department of
Dermatology. University Clinic of Navarra, Pamplona, Navarra, Spain
Introduction: Wood lamp emits long-wave UV radiation between 320 and 400nm
with a peak at 365nm. Melanin absorbs wavelength of radiation between 350 and
1200nm, especially in the UV range. UV radiation penetrates superficially in the skin,
making superficial pigmentary lesions darker by contrast to the surrounding normal
skin. UV radiation is not absorbed but rather reflected off the epidermis and dermis
in the absence of melanin. Collagen, elastin, and other components of the dermis
have a faint autofluorescence with UV radiation. Hypopigmentary and amelanotic
lesions appears bright blue-white under Wood light because there is a window
through which induced autofluorescence can be seen and because of UV radiation
reflection. It allows delimiting them sharply.
P2804
Malignant melanomas in a dermatology department: A 5-year review
Pedro Andrade, Department of Dermatology and Venereology - Coimbra
University Hospital, Coimbra, Portugal; Américo Figueiredo, Department of
Dermatology and Venereology - Coimbra University Hospital, Coimbra, Portugal;
Maria Brites, Department of Dermatology and Venereology - Coimbra University
Hospital, Coimbra, Portugal; Oscar Tellechea, Department of Dermatology and
Venereology - Coimbra University Hospital, Coimbra, Portugal
Background: Epidemiologic characterization of malignant melanoma (MM) patients
observed in a dermatology department during 5 consecutive years.
Results: The Wood light assisted our group in determining the clinical borders of
three relapsing lentigo maligna melanomas and of one acral lentiginous melanoma
with important regression areas, before the surgery treatment. The Wood light
examination was also useful in evaluating the efficacy of autologous transplantation
of cultured pure melanocytes. We observed partial or total repigmentation in all of
the six patients treated.
Conclusion: The Wood light enhances the exploration of superficial pigmentary
tumors; it has a potential role in reducing the number of excisions in Mohs surgery.
Wood light and UV photography can be very helpful to physicians evaluating clinical
borders of vitiligo and monitoring response to treatment. Transplantation of pure
melanocytes may be a good therapeutic option for stable vitiligo. The Wood light’s
unique photointeractions with melanin makes the Wood light ideal for the
evaluation of pigmented and hypopigmented lesions. It is a simple, noninvasive,
cheap, and accessible device for the dermatologist.
Methods: A retrospective and descriptive analysis was conducted evaluating all
patients with histopathologic diagnosis of MM in a 5-year period (2004-2008) in a
dermatology department. Skin biopsies showing recurrence or persistence of
previously diagnosed MM were excluded. Patients were characterized according to
several criteria: sex, age at diagnosis, and neoplasm location.
Results: A total of 224MM were diagnosed in our department between 2004 and
2008, representing 6.4% of all diagnosed malignant neoplasms in the same period. A
tendency for MM absolute frequency increase was reported each year, with no
significant changes in its relative frequency among all malignant neoplasms. A clear
and statistically significant (P\.05) female predominance was reported in the group
(60.3%). Most patients were over 60 years old (66.5%), with a mean age at diagnosis
of 66.9 years (616.3). A statistically significant association (P \.001) was reported
between MM and higher age groups (over 60 years old). MM in situ represented
34.9% of all diagnosed MM—the mean age within this group was 66.5 years (619.0
years). The lower limbs were the most affected body area, with 33.9% of all
diagnosed MM—they represented 27.7% of all lower limb malignant neoplasms. MM
was reported as the most common malignant neoplasm for that location, after
squamous cell carcinoma. In addition, 24.1% of all MM were located on the face
(representing 2.8% of all facial malignant neoplasms)—the malar eminence was the
most affected area, representing 40.7% of the facial MM. The remaining MM were
diagnosed on the torso (24.6%), upper limb (9.3%), pelvic and genital areas (2.2%),
scalp (2.2%), and neck (0.9%). Interestingly, the majority (53.6%) of all limb MM
were located on the extremities (acromelanomas). Approximately 29.5% of all MM
were diagnosed on sun-exposed skin, representing only 3.0% of all malignant
neoplasms on those locations.
Conclusions: MM is a relevant health care problem. An efficient preventive and
therapeutic approach demands a regular review of clinical and epidemiologic data.
Methods: We present a series of 10 patients with hypo- and hyperpigmentary
lesions, selected based on their Wood light findings. Three patients with lentigo
maligna melanoma and one with acral lentiginous melanoma were treated with
Mohs micrographic surgery. Six patients with stable focal vitiligo were treated with
autologous transplantation of cultured pure melanocytes using amniotic membrane
as a carrier. Photographic documentation was undertaken using an UV camera
(Clear-stone UV-DA; DigiMed Systems, Madrid, Spain).
MARCH 2010
J AM ACAD DERMATOL
AB99
P2805
P2807
Melanoma, daily erythematic dose and place of residence in the southeast
of Spain
Pedro Aceituno, MD, Faculty of Medicine, University of Granada, Granada, Spain;
Amparo Marquina Vila, Hospital Universitario Dr Peset, Valencia, Spain; Eugenia
Cutillas Marco, Hospital Universitario Dr Peset, Valencia, Spain; Rafael Rojo
España, Hospital Universitario Dr Peset, Valencia, Spain
An innovative approach to enhancement of medical student dermatology
clinical assessment skills in the early detection of melanoma
Kachiu Lee, Northwestern University, Chicago, IL, United States; Juan J. Moreno,
Hospital Clı́nico San Cecilio de Granada, Granada, Spain; Ramón Naranjo,
Hospital Clı́nico San Cecilio de Granada, Granada, Spain; Salvio Serrano,
Facultad de Medicina, Granada, Spain
Background: The incidence of melanoma rate has increased in Spain over the past
few decades. Ultraviolet (UV) radiation is the main variable environmental risk factor
for development of cutaneous melanoma. Many populations in our province live at
high altitudes and receive high doses of UVB radiation. Our objectives were to
examine a possible association between melanoma and altitude and to measure the
daily erythematic dose at different altitudes.
Methods: An ecologic study was performed to determine relationships among
melanoma prevalence, altitude, and daily erythematic dose. The study period was
the past 25 years (1982-2007). The melanoma prevalence was based on the number
of residents of Granada province clinically and histologically diagnosed with
melanoma at the San Cecilio University Hospital. Melanoma prevalences at different
altitudes (100-m intervals) were calculated, and pyranometers were used to record
UVB radiation at altitudes of 0, 680, 1200, 2100, and 3398m.
Results: The highest prevalence of melanoma was 2.36 per 1000 inhabitants at the
highest altitude interval with population centers (1400-1499m above sea level; 95%
CI, 0.64-6.03). Above 700m above sea level, the daily erythematic dose increased
exponentially with altitude.
Conclusions: In Granada province, melanoma prevalence tends to increase with
altitude and is more intense above 700m above sea level.
Background: Exposure to dermatology is limited in medical schools, with an average
of 10hours over 4 years. These experiences may represent the only opportunity for
training in detecting skin cancer among those pursuing nondermatology fields. This
study assessed the effectiveness at finding an incidental melanoma in a group of
second-year medical students.
Methods: Medical students were recruited at the end of their second preclinical year.
Demographic characteristics, such as interest in dermatology and related educational experiences, were self-reported. Groups of three to five students were asked
to evaluate nine patients (Fitzpatrick skin phototypes I-V) with dermatologic
conditions such as psoriasis or severe eczema. Two patients (white, phototype II;
African American, phototype V) wore a prosthesis (moulage) simulating melanoma
at the dorsal web space of the first and second toe. The remaining seven patients did
not have any nevi suggestive of melanoma. Two dermatology faculty members
monitored studentepatient interactions. In groups that identified the moulage,
faculty recorded whether melanoma was on the differential diagnoses offered by
students. Statistical methods used for analysis were chi-square and t tests.
Results: Fifty-eight medical students volunteered for this study; 48 (83%) had
previous experience in dermatology in the form of didactic lectures and small group
discussions; seven (12%) had previously observed a dermatologist for a half-day
clinical session. Thirteen (22%) students intended to pursue dermatology, and nine
(16%) intended to pursue primary care. Nine (16%) students noticed the ‘‘melanoma’’ lesion. Students interested in dermatology were more likely to notice the
‘‘melanoma’’ (P ¼.035). Students correctly identifying the lesion were more likely to
offer melanoma as a possible diagnosis in the white patient than those identifying
the same lesion in the African American patient (P ¼ .03).
Conclusions: We present a novel method for evaluating students’ clinical dermatologic skills. We detected differences in clinical skills correlating with clinical
experiences and interests, suggesting that this tool may be used as part of an
evaluation and measurement tool in dermatologic education. We highlight the
importance of education on the risks of melanoma in ethnic skin, as students were
less likely to offer melanoma as a diagnosis in dark skin types.
P2808
P2806
Description of cost on the diagnosis and treatment of cutaneous melanoma stages
Francisco M. Almazán, Hospital Clı́nico San Cecilio de Granada, Granada, Spain;
Agustı́n Buendı́a, MD, Faculty of Medicine. University of Granada, Granada,
Spain; Francisco José Olmo, PhD, Faculty of Science. University of Granada,
Granada, Spain; Salvio Serrano, MD, Faculty of medicine. University of Granada,
Granada, Spain
Background: Health expenditure in Spain is growing every year, and with it the
resources for the treatment of cancer. Cutaneous melanoma is the skin cancer that
causes more morbidity.
Objective: To know the total costs (direct and indirect) about the process of
diagnosis and treatment in the different stages of cutaneous melanoma.
Methods: First, we conducted a survey description of costs, based on a theoretical
model of diagnosis and treatment. We have used as a source the Control Program for
Management of Andalusian Hospital ‘‘COAN hyd’’ and ‘‘COAN Module of Total
Costs’’ for the year 2007, applied to the protocol that we follow in the Melanoma
Unit of our hospital. Secondly, we calculate the total costs at the different stages.
Results: Stage 0 (Tis, N0, M0): 592.22V; stage IA (T1a, N0, M0): 1038.53V; stage IB
(T1b-T2a, N0, M0): 1746.55V; stage IIA (T2b-T3a, N0, M0): 1746.55V; stage IIB
(T3b-T4a, N0, M0): 1481.36-1746.55V; stage IIC (T4b, N0, M0): 1481.36-1746.55V;
stage III (Tx, Nx, M0), with 1 cycle of INF: 7938.46-9231.80V; stage IV (Tx, Nx, M1)
have many possibilities.
The impact of dermoscopy on the biopsy rate of pigmented lesions by a
general dermatologist
Melanie Warycha, MD, NYU Langone Medical Center, New York, NY, United
States; Claudia Hernandez, MD, University of Illinois Chicago, Chicago, IL, United
States; June Robinson, MD, Northwestern University, Chicago, IL, United States;
Nikki Kim, Northwestern University, Chicago, IL, United States; Peter Lio, MD,
Northwestern University, Chicago, IL, United States
Background: Noninvasive imaging technology, such as dermoscopy, has been shown
to improve the benign to malignant ratio of biopsied pigmented lesions.
Nevertheless, dermoscopy remains underused by many US dermatologists. This
may be attributed in part to a lack of publications supporting its use in nonspecialist
general dermatology practices. Many of the studies that highlighted the benefits of
dermoscopy have been conducted by pigmented lesion specialists who inherently
see a large number of melanocytic lesions, and may have a different threshold for
pursuing biopsies. The objective of our study was to assess the impact of
dermoscopy on the management of pigmented lesions by a general dermatologist
and compare the findings to a pigmented lesion specialist (PLS).
Conclusions: Patients with advanced melanomas that have a poorer prognosis
consume more health care costs. Although the cost prognostic relation is directly
proportional, it does not progress gradually. The diagnosis and treatment that are
done by dermatologists who use appropriate surgical techniques and complementary tests by themselves is the best way to lessen costs.
Methods: A chart review of all patient visits (n ¼ 23104) and skin biopsies (n ¼ 2337)
conducted by a general medical dermatologist and PLS at the NYU Langone Medical
Center Dermatology Faculty Group Practice was performed over 4 years. Period
1 was defined as the 2-year period preceding the introduction of dermoscopy into
the general dermatologist’s practice. Period 2 was defined as the 2-year period after
dermoscopy use was initiated. The PLS had been using dermoscopy for 9 years,
including the 4-year study period. The main outcome measure included a benign-tomalignant ratio for biopsy-proven pigmented lesions.
Results: The proportion of pigmented lesions biopsied by the general dermatologist
decreased by 37.7% in the second year of dermoscopy use compared to the first
(94/428 vs 62/453; P ¼ .006; Fisher exact test). During the same time period, the
general dermatologist biopsied 40% fewer dysplastic nevi (65 vs 39) and the benignto-malignant ratio decreased from 22.5:1 to 7.9:1. The total number of melanomas
diagnosed in periods 1 and 2 were 12 and 11, respectively. There were no significant
changes in these measures for the PLS.
Conclusions: The implementation of dermoscopy by a general dermatologist can
lead to a decrease in the biopsy of benign skin lesions without negatively impacting
melanoma detection.
AB100
J AM ACAD DERMATOL
MARCH 2010
P2809
P2811
Multiple epidermotropic cutaneous melanoma metastases
Marisol Contreras, Virgen de la Victoria University Hospital, Málaga, Spain; Alfred
Kopf, MD, NYU Langone Medical Center, New York, NY, United States; David
Cohen, MD, MPH, NYU Langone Medical Center, New York, NY, United States;
David Polsky, MD, PhD, NYU Langone Medical Center, New York, NY, United
States; Vitaly Terushkin, NYU Langone Medical Center, New York, NY, United
States
Malignant melanoma arising as a Marjolin ulcer
Mary Guo, MD, MSN, MS, Saint Louis University Hospital, Department of
Dermatology, Saint Louis, MO, United States; Enrique Herrera, Virgen de la
Victoria University Hospital, Málaga, Spain; Matilde Mendiola, Virgen de la
Victoria University Hospital, Málaga, Spain; Norberto Lopez, Virgen de la Victoria
University Hospital, Málaga, Spain; Rosa Castillo, Virgen de la Victoria University
Hospital, Málaga, Spain
Introduction: Epidermotropic metastases of malignant melanoma are very rare and
there are few published cases. The presence or absence of junctional activity has
always been considered to be the histologic feature to distinguish primary and
metastatic lesions, but in many cases there are overlapping features that make them
difficult to differentiate. Therapeutic management will be different in the case of a
primary malignant melanoma and a metastatic lesion of melanoma.
Case report: A 41-year-old man consulted for a pigmented lesion of 2 years’ evolution
and 3cm in size located on the left shoulder blade. The lesion has been growing
slowly but in the last 3 months has presented with a sudden eruption of more than
300 pigmented lesions. Her sister was operated of a extension superficial melanoma
20 years ago and is currently free of disease. The extension study showed the
presence of supraclavicular, mediastinic, and hiliar lymph nodes in the computerized tomography scan. Before referring the patient to the oncology service, we
removed the primary lesion and multiple pigmented lesions also suggestive of
melanomas. The histopathology study of the larger lesion shows an extension
superficial melanoma, Clark level IV and Breslow index 2.5mm. The multiple lesions
suggestive of melanomas showed thinning of the epidermis by aggregates of atypical
melanocytes within the dermis and melanocytes sometimes in the vascular lumen in
the upper part of the dermis. They were diagnosed as metastases of malignant
melanoma.
A 61-year-old white woman with a history of diabetes, hypertension, and chronic
venous stasis presented to her podiatrist with a nonhealing ulcer on the left medial
ankle for 5 months. The ulcer base was biopsied and showed malignant melanoma,
nodular type, Breslow depth 3.7mm, Clark level IV with ulceration. Patient was
referred to our facility for treatment. On physical examiantion, she had a 1.0- 3 0.9cm crusted red papule on her left medial ankle and changes of lipodermatosclerosis.
There was left inguinal lymphadenopathy. Further work-up revealed multiple
nonhemorrhagic lesions on brain MRI. Full body PET/CT showed lymphadenopathy
in the left lower extremity, abdomen, and pelvis consistent with metastatic
melanoma. The patient’s disease progressed in spite of interleukin-2 immunotherapy. She passed away a few months after the diagnosis of melanoma. A Marjolin ulcer
is a cutaneous malignancy occurring in the setting of chronic ulcers, sinuses, or longstanding scars of various etiologies. These malignancies include squamous cell
carcinoma, basal cell carcinoma, and melanoma. Melanomas arising as Marjolin
ulcers pose diagnostic and treatment challenges. Review of the literature identified
eight cases of malignant melanoma arising at sites of chronic ulceration. Seven of the
eight cases involved ulcers of the foot and five patients had metastases at diagnosis.
This highlights the aggressive nature of melanoma arising as a Marjolin ulcer. Delay
of diagnosis often accounts for thicker Breslow depth and poor prognosis.
Discussion: The development of multiple primary cutaneous malignant melanomas
in a single individual is an unusual but recognized phenomenon. It is only in the case
of familial melanoma that the rate of multiple primary melanomas becomes
disproportionately higher. There are a variety of criteria in the literature on how
to distinguish multiple primary melanomas from cutaneous metastases of melanoma. It is important to learn components of the patient history that can aid in the
correct diagnosis, to describe histologic characteristics of primary and metastatic
malignant melanoma lesions, and to emphasize the need to distinguish between
primary and malignant processes relative to therapy. To clarify this problem,
Kornberg et al tried to further define the histologic differences between primary and
epidermotropic malignant melanomas, even though there vas a significant overlapping of the histologic features.
P2810
Pigmented mammary Paget disease mimicking cutaneous melanoma
Teresa Meyer, Virgen de la Victoria University Hospital, Málaga, Spain; Blanca
Moyano, Virgen de la Victoria University Hospital, Málaga, Spain; Enrique
Herrera, Virgen de la Victoria University Hospital, Málaga, Spain; Enrique
Herrera-Acosta, Virgen de la Victoria Univeristy Hospital, Málaga, Spain; Maria
Angustias Gallardo, Virgen de la Victoria University Hospital, Málaga, Spain
Introduction: Paget disease of the breast nipple and areola complex represents a
cutaneous manifestation of an underlying breast malignancy. The typical clinical
presentation is that of an itching, excoriated nipple with associated erythema and
nipple drainage. Pigmented mammary Paget disease is a rare clinicopathologic
variant of mammary Paget disease that may clinically, dermoscopically, and histopathologically mimic malignant melanoma.
Case report: We report a case of a 55-year-old Spanish woman who was referred to
our department regarding a 3-year history of asymptomatic progressively enlarging
pigmented lesion on her left mammary nipple and areola. Physical examination
revealed a 4.5 3 3cm, dark brown, well defined plaque involving 80% of the areola;
the nipple had disappeared. On dermoscopy, the lighter portion of the lesion
corresponded to a whitish-pink area with irregular linear vessels resembling an area
of regression, whereas the darker portion was characterized by dark brown diffuse
pigmentation with irregular black dots and small grey-white structures. There was
no palpable breast masses, and no supraclavicular or axillary lymphadenopathy.
Suspecting a melanocytic lesion, we decided to take a punch biopsy specimen of the
pigmented area. Histologic evaluation integrated with immunohistochemical staining showed pigmented mammary Paget disease, therapeutic excision was performed, showing an in situ ductal breast carcinoma.
Discussion: Paget disease of the breast usually presents as an erythematous patch,
typically eczematous in appearance. The pigmented variant is rare. Dermoscopic
results that showed a nonspecific pattern with irregularly diffuse pigmentation and
regression like structures suggesting a diagnosis of melanoma have been previously
reported. This case shows that the diagnosis of pigmented mammary Paget disease
cannot be determined by clinical examination and dermoscopy alone. Detailed
pathologic evaluation, including immunohistochemical staining, is essential for
making the correct diagnosis.
P2812
Dermoscopic features of amelanotic melanoma
Luis Dehesa, MD, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas
de Gran Canaria, Las Palmas, Spain; Joel Crockett, MD, Saint Louis University,
School of Medicine, Saint Louis, MO, United States; Nicole Burkemper, MD, Saint
Louis University, Dept of Dermatology, Saint Louis, MO, United States; Scott
Fosko, MD, Saint Louis University, Dept of Dermatology, Saint Louis, MO, United
States
Dermoscopy is an in vivo technique that enables the clinician to visualize hundreds
of different features in pigmented and nonpigmented skin lesions. It is useful to be
able to recognize specific features that are indicative of early melanoma, but it can
still be very difficult. That is the case of amelanotic melanoma. We present three
cases of amelanotic melanoma in which the dermoscopy helped us strongly to
suspect the diagnosis. In our opinion, it is very important to perform a thorough
examination of the lesions in order to find the diagnostic clue. The presence of some
globules grouped in the periphery of the amelanotic tumor was the clue in our three
patients.
MARCH 2010
J AM ACAD DERMATOL
AB101
P2813
P2901
Melanoma simulating acantholysis: An unusual diagnostic pitfall
Jose Aneiros-Fernández, MD, San Cecilio Clinical Hospital (Pathology), Granada,
Spain; Gregorio Carretero, MD, PhD, Hospital Universitario de Gran Canaria Dr.
Negrin, Las Palmas de Gran Canaria, Las Palmas, Spain; Jaime Vilar, MD, Hospital
Palmas, Spain; Pedro Valeron, MD, Hospital Universitario de Gran Canaria Dr.
Negrin, Las Palmas de Gran Canaria, Las Palmas, Spain
Synergistic enhancement of death ligandeinduced apoptosis in cutaneous
SCC cells by treatment with diclophenac/hyaluronic acid correlates with
downregulation of CFLIP
Lothar Fecker, PhD, Skin Cancer Center Charité, Berlin, Germany
Introduction: Architectural variations in malignant melanoma include nesting,
trabeculation, whirling, fasciculation, pseudoglandular, pseudopapillary, pseudofollicular, pseudorosette, and angiocentric patterns. The term discohesive MM was
recently proposed for entities with discohesive pattern mimicking acantholysis. We
report the case of a little-known histologic variant with an acantholytic-like pattern
on the abdomen of a 61-year-old man and discuss possible pathogenetic mechanisms
and the differential diagnosis.
Case report: A 61-year-old man was referred with a 2-month history of a pruriginous
lesion on the abdomen. Physical examination showed a raised, nonulcerated tumor
of 2.6 3 2.2cm with irregular limits and homogeneous pigmentation. Digital
dermoscopy showed a multicomponent pattern with central pigmented spot,
irregular dots, globules and streaks at the periphery of the tumor with a blue-white
veil, as well as an irregular and broken pigmented network in some areas.
Microscopy revealed intraepidermal bullous spaces covered by keratinized epidermis that were filled with loose, rounded tumor cells, lymphocytes, and a proteinaceous fluid. The base of the lesion showed blunt dermal papillae lined with a
nonstratified columnar cell component. Cords and nests invaded both papillary
and reticular dermis beneath the bullous lesion and were surrounded by a stroma
with moderate lymphocytic infiltrate. The Breslow thickness was 2.1 mm.
Immunohistochemistry revealed positivity for vimentin, Melan-A, HMB-45, E-cadherin, and b-catenin.
Discussion: The recognition of this new pattern of MM is important to avoid
erroneous diagnoses of amelanotic MM, acantholytic squamous cell carcinoma,
acantholytic acantoma, acantholytic actinic keratosis, acantholytic seborrheic
keratosis, acantholytic dyskeratotic epidermal nevus, or acantholytic dermatosis.
The pathogenetic mechanisms are unknown. It has been proposed that the
disruption of adhesion receptors and downregulation of desmoglein 1 explains
the pattern of discohesive melanoma. We consider that the detection of loose,
noncohesive, acantholytic-like cells may be partly explained by the presence of
abundant inflammation-related extracellular fluid, which may contribute to separating weakened intercellular bonds (punctate adherens junction).
Objectives: Actinic keratosis (AK) occurs on sun-exposed skin and may progress into
squamous cell carcinoma (SCC). Diclofenac/hyaluronic acid has been approved for
topical treatment of AK. As a nonsteroidal antiinflammatory drug, it is expected to
exert inhibitory activities on cyclooxygenase-2 (COX-2), which is rate limiting for
the synthesis of tumor promoting prostaglandins. Increased COX-2 activities have
been found in epithelial tumors; however, the mechanism of diclofenac/HA in AK is
largely unknown.
Methods: In the present study, the effects of diclofenac/HA on the regulation of
apoptosis in cutaneous SCC cells were investigated. For comparison, the proapoptotic effects of death ligands (TNF-alpha, TRAIL and agonistic CD95 stimulation)
were also investigated and combinations were performed.
Results: Enhanced apoptosis was seen in all SCC cells by death ligands. Moderate
induction of apoptosis was also seen in three of four cell lines after treatment with
diclofenac/HA. Apoptosis was associated with caspase-8 activation and with an
increased sub-G1 cell population. Interestingly, combined treatment with
diclofenac/HA and death ligands resulted in synergistic enhancement of apoptosis.
Also in caspase inhibition experiments diclofenac/HA and death ligand-induced
apoptosis were blocked by the same caspase inhibitors, indicating related pathways.
The effects were largely independent of upregulation of death receptors, however
strong downregulation of c-FLIP isoforms were obtained after Diclofenac/HA
treatment.
Conclusions: HA was without direct effect on SCC cell apoptosis but may be related
to an activation of immune cells in the clinical situation. In contrast, induction of
apoptosis was highly characteristic for the mode of action of diclofenac in
diclofenac/HA, and the therapeutic effect may result from sensitization of neoplastic
keratinocytes for an immune response driven by death ligands.
P2902
NONMELANOMA SKIN CANCER
P2900
Trichilemmal carcinoma: A study of five cases
Todd Nelson, MD, East Carolina University Brody School of Medicine, Greenville,
NC, United States; Charles Phillips, MD, East Carolina University Brody School of
Medicine, Greenville, NC, United States; Robert Schosser, MD, East Carolina
University Brody School of Medicine, Greenville, NC, United States; Virginia
Taylor, MD, East Carolina University Brody School of Medicine, Greenville, NC,
United States; William Burke, MD, East Carolina University Brody School of
Medicine, Greenville, NC, United States
Background: Trichilemmal carcinoma (TLC) is an uncommon cutaneous adnexal
neoplasm found primarily on the sun-exposed skin of elderly individuals. It is
thought to arise from the external root sheath of the hair follicle. We report five cases
of TLC in an effort to analyze the clinical and histopathologic features of this
malignant lesion.
Penile squamous cell carcinoma: A case report
Francisca Regina Oliveira Carneiro, PhD, University of State of Pará, Belém, Pará,
Brazil; Francisco Nogales-Fernández, PhD, San Cecilio Clinical Hospital
(Pathology), Granada, Saint Barthélemy; Francisco Valle-Ravassa, PhD, San
Cecilio Clinical Hospital (Pathology), Granada, Spain; Jose Aneiros-Cachaza,
PhD, San Cecilio Clinical Hospital (Pathology), Granada, Spain; Salvador AriasSantiago, MPH, San Cecilio Clinical Hospital (Dermatology), Granada, Spain
Introduction: Penile carcinoma is a rare neoplasm with low incidence in developed
countries like the United States. In underdeveloped countries, its frequency reaches
high levels. The main risk factors are fimosis, lack of personal hygiene, local chronic
irritation, and HPV types 16 and 1, and the most comon carcinoma type is squamous
cell carcinoma.
Case report: A 50-year-old man came to the dermatologist with a history of a painful
penile lesion with 1 year of evolution. On physical examination, an erythematous
infiltrated plaque on the shaft of penis and a verrucous lesion on the glans were
observed. A biposy with histologic examination revealed a squamous cell carcinoma
with moderated differiation.The patient was submitted to a total penile amputation.
Case report: The mean age of the patients was 69 years (range, 52-80 years). All were
white males. Every patient but one had a personal history of previous nonmelanomatous skin cancer at the time of presentation. The average lesion size was
7.5mm (range, 3-12mm). In each case, lesions were limited to the head and neck.
Two patients developed these neoplasms on postauricular skin, while the three
remaining patients had lesions on the cheek, neck, and nasal ala, respectively. In all
but one case, the lesions had been present for less than 6 months (3-year duration
reported by 1 patient). On clinical examination, solitary erythematous papules and
nodules were observed, some keratotic and others with overlying superficial
ulceration. Squamous cell carcinoma was included in the differential diagnosis for
all cases at the time of biopsy, in addition to basal cell carcinoma in two cases and
Bowen disease in two other cases. Histologically, invasive lobular proliferations of
prominent atypical clear cells were noted emanating from follicular epithelia and the
epidermis. One case in particular appeared to arise from a previously existent
trichilemmoma. These polygonal clear cells exhibited pleomorphic nuclei, mitotic
figures, and PAS-positive cytoplasmic staining. Foci of trichilemmal keratinization
were identified in the majority of cases. Three of the patients were treated with
electrodessication and curettage, while one patient each underwent excision and
Mohs micrographic surgery, respectively.
Discussion: Penile cancer is an aggressive and mutilating disease that is more
frequent in the fifth and sixth decades of life, with a strong association between the
presence of the prepuce and the development of the disease. The risk is 3.2 times
higher in men that had never been circumcised than in those that were circumcised
at birth and 3 times higher than the men who were circumcised during the neonatal
period. Among with phimosis or excess prepuce, low socioeconomic level, and
poor personal hygiene were the most important risk factors for the disease. The
authors related a case of penile cancer in a man that was not circumcised and alert to
the importance of an early diagnosis of penile cancer to avoid total penile
amputation.
Discussion: TLC is a rare adnexal tumor that usually occurs as a single lesion on sunexposed skin and is more common in the elderly. It is the malignant counterpart of
trichilemmoma. These neoplasms lack distinguishing clinical features and are often
mistaken for squamous cell carcinoma, basal cell carcinoma, or keratoacanthoma.
Histologically, lobular proliferations of cytologically malignant clear cells (PASpositive, diastase-sensitive) with trichilemmal keratinization are characteristic.
Despite its cytologically aggressive appearance, TLC is usually an indolent tumor
that follows a relatively benign course and carries a good clinical prognosis with
treatment. This series of cases illustrates many of the common clinical and
histopathologic features of this disease.
AB102
J AM ACAD DERMATOL
MARCH 2010
P2903
P2905
Zosteriform pattern of cutaneous metastases in two patients
Sorahaya Gonzalez-Hernandez, MD, Hospital Universitario de Canarias, La
Laguna, Santa Cruz de Tenerife, Spain; Cristina Rodriguez-Garcia, MD, Hospital
Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Francisco
Guimera, MD, PhD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de
Tenerife, Spain; Nuria Perez-Robayna, MD, Hospital Universitario de Canarias, La
Laguna, Santa Cruz de Tenerife, Spain; Rosalba Sanchez-Gonzalez, MD, PhD,
Introduction: Cutaneous metastases from internal malignancies have been reported
with a variable frequency of 0.7% to 0.8%, and a zosteriform pattern is very
uncommon. Segmental metastases were first reported in 1933 in a patient with
breast cancer.
Case report: We report two patients with zosteriform metastases. Case 1—A 78-yearold man with a 3-month duration of multiple indurated nodules on the left side of his
flank. He had been previously affected with herpes zoster and had had a nonHodgkin lymphoma. Case 2—A 72-year-old woman with zosteriform eruption
consisted in multiple eritematous indurated papules on the left side in her chest. She
had been previously diagnosed as herpes zoster at this site and had been treated with
acyclovir. The skin biopsy permitted the diagnosis of cutaneous metastases in our
two patients.
Discussion: Zosteriform metastases are rare and it is important to include cutaneous
metastases within the differential diagnosis of zosteriform eruptions. The most
frequent site of skin metastases is the chest wall. A skin biopsy is necessary to
confirm the diagnosis. The mechanism of zosteriform distribution in skin cancer is
still speculative. It has been suggested that it might be due to accidental surgical
implantation, Koebner-like reaction at the site of a prior herpes zoster infection or
perineural lymphatic or neural lymphatic spread.
Large nodular plaque on the leg in the setting of chronic lymphedema
Hyland Cronin, MD, Geisinger Health System, Danville, PA, United States;
Christen Mowad, MD, Geisinger Health System, Danville, PA, United States
Introduction: Angiosarcoma is a rare malignant endothelial neoplasm that represents less than 1% of all sarcomas. It is most commonly found in the elderly affecting
the head and neck, but has also been found in areas of chronic lymphedema or
postradiation. The association between chronic lymphedema and angiosarcoma
remains unknown. One theory is the idea that there may be unknown carcinogens
within the lymph fluid that undergo neoplastic change. A second theory is that these
areas of chronic lymphedema lose their afferent lymphatic connection making them
safe from attack by the immune system.
Case report: A 29-year-old man with chronic left lower extremity lymphedema for 8
years presented with an enlarging and ulcerated nodular plaque on his left leg. The
lesion had started out as a bruise, then progressively enlarged and ulcerated over 4
months. He went to many physicians during this time at which he was tested and/or
treated for possible infection, deep venous thrombosis, vasculitis, and a torn muscle.
The patient’s family history was remarkable in that mother and sister both have
chronic bilateral lymphedema. Physical examination of his left leg revealed a 20-cm
blue and black hemorrhagic nodular plaque with a large central eschar and a few
smaller satellite bluish nodules. An open incisional biopsy of the lesion was
obtained. Pathology revealed a deep infiltration through the dermis and subcutis by
spindle cells with atypical features and a high mitotic rate. The proliferation was
associated with prominent hemorrhage. In some areas, the cells form vascular
structures with slit-like spaces. Focally anastomosing irregular blood channels were
present. The neoplastic cells were positive for CD31, CD34, factor VIII, and FLI1 and were negative for HHV-8, AE1/AE3, CD45, CD20, CD3, and S-100 supporting a
diagnosis of angiosarcoma. CT scans showed some nonspecific mediastinal, axillary,
and retroperitoneal nodes. MRI of the leg showed patchy infiltration in the
subcutaneous fat circumferentially throughout the thigh to the level of the
femoroacetabular joint. Enhancement was minimal making it difficult to separate
lymphedema from tumor. Bilateral inguinal lymph nodes were noted and suspicious
for metastatic disease. Fine-needle aspiration of the left inguinal node was negative.
The patient then went to the operating room for possible amputation. The left groin
node was dissected and on frozen section was negative. In view of this, the patient
underwent the amputation. Postoperatively, the final pathology of the left groin
node was positive for metastasis. Radiation therapy was planned. He subsequently
developed a recurrent lesion in his surgical incision that was biopsied and consistent
with angiosarcoma. He completed radiation therapy, but his follow up CT scan
showed tumorous nodules in the lung, a mass in the right lobe of the liver, and left
inguinal adenopathy. Given his poor prognosis and limited treatment options, he is
enrolling in a clinical trial.
Discussion: Angiosarcoma typically presents as firm violaceous nodules or plaques
superimposed on a background of brawny, nonpitting edema. Lymphedema
following mastectomy and lymph node dissection (Stewart-Treves syndrome)
comprises more than 90% of all lymphedema associated angiosarcomas. Other
forms of chronic lymphedema are linked with angiosarcoma, including congenital,
filarial, traumatic, and idiopathic. Our patient’s lymphedema was undiagnosed upon
presentation but was by family history. Histologically, anaplastic pleomorphic
endothelial cells are present with nodular and interstitial vascularity. The pattern
most commonly seen is hyperchromatic nuclei dissecting through the collagen,
producing the appearance of cracks between the collagen bundles.
Immunohistochemical staining for endothelial markers such as CD31, CD34, factor
VIII, and Ulex europeus lectin aids in the diagnosis.2Treatment consists of surgical
excision with wide margins. The recurrence rate and chance of metastasis is still
very high despite negative margins by histology as portrayed in our patient. Adjuvant
radiotherapy has been shown to be of clinical benefit. The role of chemotherapy is
still unclear. However, some studies have shown that in a minority of patients with
advanced disease, there can be dramatic responses with chemotherapy.
Doxorubicin based chemotherapy regimens produce a modest response rate.
Paclitaxel and interferon have shown some response especially for scalp and facial
angiosarcomas. More recently, a clinical trial has shown efficacy of weekly paclitaxel
as a treatment for metastatic or locally advanced angiosarcoma. There have also been
isolated case reports of success with docetaxel and thalidomide. Unfortunately,
these current treatments are not very successful with an overall estimated 5-year
survival rate of 15%.
P2904
Using photodynamic therapy in morpheaform basal cell carcinoma to
ease surgical treatment
Tiago Torres, MD, Serviço de Dermatologia Hospital Santo Antonio, Porto,
Portugal; Manuela Selores, Serviço de Dermatologia Hospital Santo Antonio,
Porto, Portugal; Virgilio Costa, MD, Serviço de Dermatologia Hospital Santo
Antonio, Porto, Portugal
Introduction: Topical photodynamic therapy is currently approved to treat nonmelanoma skin cancers, such as actinic keratoses, Bowen disease, and basal cell
carcinoma (superficial and nodular). Because of its excellent cosmetic results it has
also been used, with good results, in ‘‘difficult to treat’’ basal cell carcinomas (large
lesions, multifocal, or midface localized), lesions that would otherwise require
extensive surgical procedures. Morpheaform basal cell carcinoma is an uncommon
variant in which tumor cells induce a proliferation of fibroblasts within the dermis
and an increased collagen deposition (sclerosis) that clinically resembles a scar.
Because the tumor infiltrates in thin strands between collagen fibers, treatment is
difficult, and the clinical margins are difficult to distinguish.
Methods: To evaluate the possible use in morpheaform basal cell carcinoma of
topical photodynamic therapy (MAL-PDT) as an adjuvant therapy, to reduce tumor
size, and to ease surgical treatment. Four histologically confirmed morpheaform
basal cell carcinomas were carefully selected: tumors that would require an
extensive surgical procedure with a possible negative cosmetic outcome and
patients with comorbidities that would make surgical treatment more difficult.
Localization of the tumors: two on the face, one on the back, and one on the leg.
Results: After two treatments with MAL-PDT, the size of all the tumors was
significantly reduced. The performed surgical excision (with histologic free
margins) was less extensive that the one that would be necessary initially. After
16 months, all the patients remained without any evidence of recurrence and with a
better cosmetic outcome than the one that would have resulted if a more extensive
surgical treatment had been performed.
Conclusion: Several physicians did not consider the possibility of a malignancy in
this patient and thus, diagnosis was delayed. This case report should prompt us that
although rare, we should not forget about the possibility of angiosarcoma in the
setting of familial lymphedema. We also should not be reluctant to biopsy an
edematous nonhealing leg, because the diagnosis was readily made after a biopsy
was obtained.
Discussion: Although no reports can be found in literature concerning the use of
topical photodynamic therapy in the treatment of morpheaform basal cell carcinoma and despite the reduced number of patients taken in consideration, we have
found that PDT may be an option as an adjuvant therapy to surgery.
MARCH 2010
J AM ACAD DERMATOL
AB103
P2906
P2908
Clinical development of GDC-0449, a hedgehog pathway inhibitor, for the
treatment of advanced basal cell carcinoma
Ivor Caro, Genentech, South San Francisco, CA, United States; Daniel D. Von
Hoff, Translational Genomics Research Institute and Scottsdale Healthcare,
Phoenix, AZ, United States; Howard Mackey, Genentech, South San Francisco,
CA, United States; Josina C. Reddy, Genentech, South San Francisco, CA, United
States; Robert L. Yauch, Genentech, South San Francisco, CA, United States
Hereditary and sporadic forms of basal cell carcinoma (BCC) are associated with
mutations in the Hedgehog (Hh) pathway genes Patched (PTCH1) and Smoothened
(SMO). GDC-0449 is an orally available small molecule Hedgehog pathway inhibitor
(HPI) that binds to SMO, which is being developed for the treatment of locallyadvanced (la) or metastatic (m) BCC. The safety, preliminary efficacy, and pharmacokinetics of GDC-0449 were assessed in a phase I trial for patients with solid tumors
refractory to therapy, including an expansion cohort for patients with laBCC or
mBCC. Thirty-three patients with mBCC or laBCC received GDC- 0449 orally.
Preliminary phase I data were previously presented: six of 11 evaluable patients had
partial responses (2 by RECIST, 4 by physical examination), four patients had stable
disease, and one had progressive disease as best response. GDC-0449 was generally
well tolerated, with three reversible grade III events (2 fatigue, 1 hyponatremia) and
no grade $ 4 events assessed to be related to study drug. Updated phase I data for 33
patients will be presented. Because of the encouraging tolerability and efficacy data
observed in the phase I study, a phase II, open-label, single-arm global trial of GDC0449 in advanced BCC is currently enrolling patients. Patients are enrolled into one
of two cohorts (laBCC or mBCC) and are treated with GDC-0449 at 150mg daily,
until disease progression, toxicity or withdrawal. Further details of phase II
development in advanced BCC will be presented.
Giant condylomatous cell carcinoma of the penis associated to HPV with
multiple metastases
Salvador Arias-Santiago, MD, San Cecilio Clinical, Granada, Spain; Antonio
Jimenez-Pacheco, MD, San Cecilio Clinical Hospital, Granada, Spain; José
Aneiros-Fernández, MD, San Cecilio Clinical Hospital, Granada, Spain; Miguel
Angel Arrabal-Polo, MD, San Cecilio Clinical Hospital, Granda, Spain; Ramón
Naranjo-Sintes, MD, San Cecilio Clinical Hospital, Granada, Spain
A 67-year-old man complained of an excrescent lesion in the penis and difficulty in
passing urine for 5 months. Abdomen-pelvis CT showed retroperitoneal adenopathies, a 1-cm nodule in hepatic segment III, and hypoattenuating nodules in spleen,
and a right adrenal nodule; all these conditions were identified as compatible with
metastasis. A thoracic radiograph showed a metastatic nodule localized in right lung
base. The patient required total penectomy and perineal urethrostomy. The patient
developed dysarthria and vertiginous syndrome; cerebral CT showed multiple
nodules compatible with metastases. The histologic study of the sample reported a
condylomatous variety of squamous cell carcinoma which showed antigen positivity
for HPV, type 16 (T3N2M1). Palliative treatment was established, although the
patient died on the twentieth day after the operation. The incidence of penile cancer
in Spain varies between 2.81 and 4.86 cases per 100,000 male patients per year. It
roughly represents 0.5% of all tumors in Europe and the United States; however, this
tumor represents 10% of cancers in some countries in Africa, Asia, or South America.
It has been related to diverse risk factors, such as smegma retention associated with
a poor personal hygiene favored by the presence of phimosis, some inflammatory
diseases, PUVA treatment in psoriasis patients, tobacco abuse, sexually transmitted
diseases, genital warts, and human papillomavirus infection, especially HPV type 16.
In most cases, they are keratinocyte-derived squamous cell carcinomas. Metastases
associated with penile cancer have been described in the brain, lungs, heart, and
skin. However, literature does not describe metastases to the spleen. According to
the therapeutic protocol for the management of penile cancers, conventional
surgery, Mohs surgery, topical route of imiquimod, cryotherapy, and photodynamic
therapy are different options that can be employed when tumors do not infiltrate
into the cavernous bodies. The presence of palpable ganglia is the main prognosis
factor. As for advanced stages, combined treatments based on methotrexate,
bleomycin, vincristine, cisplatin, and 5-fluoroucil have proven to be useful and
can be added to surgery and radiotherapy techniques. Circumcision, an adequate
genital hygiene, tobacco withdrawal, and the use of preservatives are preventive
strategies that must be borne in mind; also the arrival of vaccines against the human
papillomavirus serotypes 16 and 18 seems to be useful for the prevention of this
tumor, and could potentially reduce by one-third the incidence of squamous cell
cancer of the penis.
Commercial support: 100% is sponsored by Genentech.
P2907
Cutaneous metastases from visceral not hematologic tumors: A review of
six cases
Rafael Salido Vallejo, Hospital Universitario Reina Sofı́a, Córdoba, Spain; Gloria
Maria Garnacho Saucedo, Hospital Universitario Reina Sofia, Cordoba, Spain; Jose
Carlos Moreno Gimenez, Hospital Universitario Reina Sofia, Cordoba, Spain;
Manuel Galan Gutierrez, Hospital Universitario Reina Sofı́a, Córdoba, Spain
Introduction: Cutaneous metastases of a primary internal malignancy are an
uncommon phenomenon, occurring in only 1% to 2% of patients with metastases.
Several revisions have determined that skin lesions are the first clinical sign of the
disease in 0.8% of patients with systemic cancer.
Case reports: We report six patients with cutaneous metastases from primary
visceral not hematologic tumors: two women suffering from high-grade urothelial
carcinoma and breast carcinoma, and four males suffering from colon adenocarcinoma, renal clear cell carcinoma, squamous cell carcinoma of the lung and
bronchogenic squamous cell carcinoma of the tonsil. The skin lesions were the
first sign of the disease in four patients. Clinical, epidemiologic, and therapeutic
considerations in each case are explained.
P2909
Discussion: Cutaneous metastases are perceived as a sign of advanced disease and
are regarded as a grave prognostic indicator. Cutaneous involvement by cancer can
occur by several different routes: hematogenous, lymphatic, direct contiguous
tissue invasion, and iatrogenic implantation. Internal malignancy most frequently
associated with the development of skin metastases is breast cancer followed by
squamous cell carcinomas of head and neck. If we take into account the sex, skin
metastases originate from lung, colon, oral cavity, larynx, and kidney are more
frequent in men, and breast and ovary carcinomas are the most frequent in women.
The highest incidence is observed between the fifth and seventh decades of life.
They usually present as firm, skin-colored growths initially but then remained at the
time. Some lesions can mimic benign entities as epidermoid cysts, lipomas, or
vascular lesions. Another form of clinical presentation is inflammatory patches,
mimicking cellulitis, or erysipelas. Treatment may be surgery, chemotherapy, or
radiotherapy depending on several factors, but the prognosis is poor.
Primary cutaneous extraskeletal osteosarcoma occurring on operation
scar
Chan Ho Na, MD, Department of Dermatology, School of Medicine, Chosun
University, Gwangju, South Korea; Bong Seok Shin, MD, Department of
Dermatology, School of Medicine, Chosun University, Gwangju, South Korea
Extraskeletal osteosarcoma (ESOS) is a malignant tumor of mesenchymal origin,
with greater rarity than that of osteosarcoma arising primarily in bone. Skin as a
primary site has seldom been reported. A 56-year-old man presented to our
institution on June 10, 2008 with a 3-month history of a painful, solitary, slowly
growing, exophytic, brown colored, and 1.5- 3 0.8-cm nodular lesion with firm
consistency located on linear scar of right iliac crest region. Ten years ago, he had
undergone the partial amputation of left tibia because of osteosarcoma occurring on
left foot and the bone graft from right iliac crest bone to amputation site. At his first
visit, the nodule was completely excised with a clinical diagnosis of dermatofibroma. Microscopically, the tumor was confined to the dermis without connection
to epidermis and underlying fascia. Pleomorphic osteoblastic cells showing frequent
mitoses and osteoclast-like giant cells were observed with coarse, lacelike pattern of
osteoid matrix. Immnunohistochemical stains showed the tumor cells were positive
for vimentin but negative for S-100 protein, desmin, and cytokeratin. Upon
histopathologic examination, laboratory tests and PET-CT were carried out and no
other bone lesions were found. The final diagnosis was primary cutaneous
osteoblastic ESOS, which had primarily developed from previous traumatized
skin, that is, operation scar. In our case the possibilities for the metastasis from
the past osteosarcoma or the seeding of tumor cells during bone graft operation
could be excluded by no evidence of tumor on other sites (eg, left tibia, right iliac
crest) and by presence of the long remission duration over 10 years. He did not
receive any more treatment and has been being well without relapse to date. Herein,
we report a patient with primary cutaneous ESOS occurring on an operation scar.
AB104
J AM ACAD DERMATOL
MARCH 2010
P2910
P2912
Demographic, clinical, and histologic factors in basal cell carcinomas: A
prospective study
Husein Husein-ElAhmed, MD, Hospital Universitario San Cecilio, Granada, Spain;
Jose Aneiros Fernandez, MD, Hospital Universitario San Cecilio, Granada, Spain;
Maria Teresa Gutierrez Salmeron, MD, Hospital Universitario San Cecilio,
Granada, Spain; Ramón Naranjo Sintes, MD, Hospital Universitario San Cecilio,
Granada, Spain; Salvador Arias-Santiago, MD, Hospital Universitario San Cecilio,
Granada, Spain
Background: Basal cell carcinoma (BCC) is the most common skin cancer and its
incidence is increasing. While ultraviolet radiation is recognized as the main
etiologic factor, the relationship between exposure and BCC development remains
unclear. Burns in infancy and intermittent sun exposure may have an important role.
Objectives: Our purpose was to describe sun exposure habits and dermographic,
clinical, and histologic factors of patient with BCC excised in a public hospital.
Methods: We evaluated 120 BCC excised in our hospital in 2009. For each case, data
regarding age, sex, hair and eye color, phototype, and sun exposure at work, history
of burns in infancy and adult age, type of burn, previous case of BCC, close relative
diagnosed with BCC, tumor location, clinical type, histologic type, solar elastosis,
ulcer, peritumoral inflammation, necrosis, and positive surgical margins were
collected.
Violaceous nodule within sclerotic plaque of inguinal region: An unusual
case of dermatofibrosarcoma protuberans
Emily Archbald, MD, University Of Oklahoma, Department Of Dermatology,
Oklahoma City, OK, United States; Michael John, MD, Edmond Dermatology
Clinic, Edmond, OK, United States
Results: The mean age of the patients was 74.55 with slight prevalence of men
(1.3/1). Blonde and brown hair was found in 37% and 62% and blue/green and
brown eyes in 82% and 18% respectively. The most frequent phototype was II (45%),
followed by I (30%), III (20%), and IV (5%). Sun exposure at work was reported by
59% of the patients. Forty-eight percent of patients reported sunburns in childhood,
although the percentage increases to 72% to sunburns in adult life. There was only
34% of patients with previous BCC, and none of them reporting close relative with
BBC. The location most common was nose (25%) followed by eyelid (23%), cheek
(17%), forehead (15%), trunk (12%), upper limb (5%), and scalp (3%). Seventy-three
percent of patients had nodular variant of BBC;14%, superficial; 11%, infiltrative; and
2%, pigmented. Histologic subtypes were solid-cystic (68%), superficial (17%),
micronodular (8%), and infiltrative (7%). Histology study showed 74% had solar
elastosis: 22% grade I, 43% grade II, and 35% grade III. Most of BBC showed
inflammation (93%) with predominance of lymphocytes. Necrosis and ulceration
were found in 37% and 18% respectively.The percentage of incomplete excision was
11.6%.
Conclusions: These data emphasize the importance of sunlight, sunburn as a child or
adolescent, and skin response to sunlight as determinants of BBC.
This report documents the case of a 23-year-old woman with a 5-year history of a
slow growing, slightly tender sclerotic plaque of the left inguinal region.
Dermatologic examination revealed a 7-cm violaceous and sclerotic plaque, with
an inferiorly located 2-cm tender, soft nodule at the left inguinal region. No inguinal
lymphadenopathy or limb defects were detected on examination. Punch biopsy
specimens were obtained from both the underlying plaque and the neighboring
nodule. Histopathology demonstrated a spindle cell neoplasm comprised of
irregular, interwoven, CD341 spindle cells filling the reticular dermis and percolating into the subcutis. Although the two specimens differed slightly in morphology,
both demonstrated features consistent with dermatofibrosarcoma protuberans
(DFSP). Recent MRI revealed tumor invasion near the femoral artery, and this
patient was sent for further surgical evaluation. DFSP typically begins as an
indurated pink, red, or flesh-colored plaque or patch that gradually becomes
more protuberant and fixed to underlying subcutaneous tissue and fascial planes.
DFSP occurs most commonly on the trunk, followed by the proximal extremities of
middle-aged adults, with a slight male preponderance. Although DFSP is considered
to be a low-grade malignancy, these tumors can demonstrate locally aggressive
behavior, associated with recurrences and distant metastasis. Optimal therapeutic
options include wide local excision with margins of 3cm or Mohs surgery. More
recently, it has been shown that imatinib may decrease the size of these tumors if
associated with the t(17;22) translocation, via inhibition of platelet-derived growth
factor B chain (PDGFB). This case of DFSP is important as it illustrates the young age
of the patient at onset, the uncharacteristic location of this tumor, the clinical
appearance of a tumor with both a sclerotic plaque and a neighboring soft nodule,
and the aggressiveness of the tumor into the surrounding tissue, which further
complicates surgical resection.
P2913
Bowen disease, or squamous cell carcinoma in situ, is an intraepidermal carcinoma
that is most commonly seen in elderly white persons within actinically damaged
skin. This neoplasm is typically indolent with progression to invasive squamous cell
carcinoma occurring in less than 5% of cases. The risk of metastases is even lower
and virtually zero if the neoplasm remains intraepidermal. Bowen disease typically
presents as an erythematous, scaly plaque; however, other rarer presentations, such
as pigmented or verrucous lesions, have been reported. Bowen disease in African
Americans, like other skin cancers, is rare and may present in an atypical fashion. We
report a case of a 78-year-old African American man who was noted incidentally
during an inpatient admission to have a lesion on his right wrist. Review of his
electronic medical record showed that the patient had been biopsied 6 years earlier
from the same area, pathology showing squamous cell carcinoma in situ, but did not
follow-up for treatment. Examination during inpatient admission revealed a 9- 3 9cm exophytic, hyperkeratotic fungating plaque with several large cutaneous horns
on the right volar wrist. No lymphadenopathy was found on examination. CT scans
of the chest, abdomen, and pelvis showed no metastases. Wide local excision with
full-thickness skin grafting was performed by plastic surgery. Pathology still showed
Bowen disease, with negative margins. We present this case of verrucous Bowen
disease in an African American man which, despite the lack of treatment for many
years, did not progress to become invasive.
Multicenter, randomized, double-blind, vehicle-controlled, dose-ranging
study to evaluate the efficacy and safety of PEP005 (ingenol mebutate) gel
0.005%, 0.01%, and 0.015% when used to treat actinic keratoses on the
head
James Spencer, MD, Spencer Dermatology and Skin Surgery Center, Saint
Petersburg, FL, United States
A vehicle-controlled, dose-ranging study was conducted to evaluate the safety and
efficacy of PEP005 (ingenol mebutate) gel 0.005%, 0.01%, or 0.015% applied once
daily for two or three consecutive days to a 25-cm2 contiguous area for treatment of
AK on the face or scalp. The primary safety variables were the incidence of adverse
events, incidence and severity of local skin responses, pigmentation, scarring, and
compliance. T

68th Annual Meeting, Miami Beach, Fla., March 5

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