Initial presentation of stasis dermatitis mimicking solitary lesions: A previously unrecognized

Initial presentation of stasis dermatitis mimicking
solitary lesions: A previously unrecognized
clinical scenario
Joshua Weaver, MD,a and Steven D. Billings, MDa,b
Cleveland, Ohio
Background: Stasis dermatitis is a common skin condition secondary to chronic venous insufficiency.
Characteristic dermatologic changes in well-developed disease include bilateral erythematous, scaly, and
slightly discolored papules and plaques on the lower legs. Earlier signs, such as prominent superficial veins
and pitting ankle edema, are well known. Early recognition of signs and appropriate diagnosis can lead to
timely treatment that can prevent painful complications, such as leg ulcers which are at risk for
development of squamous cell carcinoma.
Objective: Herein we describe a yet unrecognized early sign of venous dermatitis—a solitary lesion, some
mimicking neoplastic processes.
Methods: Thirty-seven cases of stasis dermatitis submitted with the clinical diagnosis of a solitary lesion were
identified. Thirty-three had no clinical history of venous insufficiency. All cases of stasis dermatitis presenting
for the first time as a solitary lesion were reviewed retrospectively both clinically and pathologically.
Results: Squamous cell carcinoma was most commonly suspected (33%), followed by basal cell carcinoma
(24%), and a variety of other solitary lesions. The histopathology was characteristic of stasis dermatitis in all
cases with absent or mild spongiosis (82%), variable acanthosis and dermal fibrosis, and proliferation of
papillary dermal thick-walled vessels were prominent (2-3+) in nearly all cases ( $ 90%) along with
hemosiderin-laden macrophages and extravasated red blood cells ( $ 95%).
Limitations: The study is limited by its retrospective nature and absence of clinical images on all cases.
Conclusion: Stasis dermatitis may present as a solitary lesion mimicking a neoplasm. Early recognition of
stasis dermatitis can lead to appropriate treatment and possibly prevent further morbidity. ( J Am Acad
Dermatol 2009;61:1028-32.)
INTRODUCTION
S
tasis dermatitis is a cutaneous manifestation
and marker of increased venous pressure of
the lower extremities. It is a common condition affecting predominantly middle-aged to elderly
From the Departments of Anatomic Pathologya and Dermatology,b
Cleveland Clinic.
Funding sources: None.
Conflicts of interest: None declared.
A portion of this work was presented at the 45th Annual Meeting of
the American Society of Dermatopathology in San Francisco, CA.
Reprint requests: Steven D. Billings, MD, Department of Anatomic
Pathology/L25, The Cleveland Clinic. 9500 Euclid Ave, Cleveland,
OH 44195. E-mail: [email protected].
0190-9622/$36.00
ª 2009 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2009.04.025
1028
Abbreviations used:
H&E: hematoxylin-eosin (stain)
PAS: periodic acideSchiff
individuals that usually presents as erythematous,
slightly yellow to brown pigmented patches over the
bilateral lower legs with or without conspicuous
varicose veins. Most cases are caused by insufficient
deep venous system valves preventing proper return
of blood to the central circulation through the
muscular pumping action of the lower legs. Venous
valvular insufficiency can be caused by prior thrombophlebitis or congenital fragility. Pregnancy,
obesity, and other causes of increased abdominal
pressure can also lead to chronic venous
insufficiency.
Weaver and Billings 1029
J AM ACAD DERMATOL
VOLUME 61, NUMBER 6
Stasis dermatitis can be associated with signifisolitary lesion and in some cases mimicking a neocant complications. Long-standing stasis dermatitis
plastic process.
accounts for approximately half of chronic leg
ulcers.1 Chronic venous leg ulcers lead to significant
METHODS
decreases in the quality of these patients’ lives
A computerized search through the pathology
through physical pain, negative emotions, and
archives at the Cleveland Clinic was performed
monetary loss.2 Development of squamous cell
using the keywords ‘‘stasis dermatitis’’ in the diagcarcinoma in long-standing
nosis field between Jan 1,
chronic venous ulcers is
1992 (time when clinical
CAPSULE SUMMARY
another risk that patients
data from the pathology reqwith stasis dermatitis face.
uisition form were added to
Stasis dermatitis can commonly (7%)
Therefore diagnosis of stasis
the database) and March 25,
manifest early as a solitary lesion before
dermatitis early in the pro2008. All electronic and
more typical clinical diagnostic changes
cess is important as it may
physical clinical charts were
develop.
allow for earlier intervention
available for review docuThese solitary lesions most commonly
to potentially prevent these
menting at the initial visit:
clinically mimic neoplasms, including
complications.
presence or absence of a
SCC (33%) and BCC (24%).
Although most cases are
history of stasis dermatitis,
diagnosed clinically through
presence or absence of a
The histopathology of stasis dermatitis
history and physical findhistory of another concurconsists predominantly of dermal
ings, a biopsy is often emrent or metachronous eczechanges including lobular proliferation
ployed if there is no clear
matous process, evidence of
of thick-walled papillary dermal blood
history and physical findings
pedal edema on physical
vessels with evidence of dermal
are atypical. Histologically,
examination, symptoms of
hemorrhage. Epidermal changes are
stasis dermatitis demondependent ankle swelling
usually mild.
strates a lobular proliferation
during prolonged standing,
Early recognition of this clinical scenario
of thick-walled blood vesclinical presentation and deof stasis dermatitis initially presenting as
sels in the papillary dermis
scription of the lesion, age,
a solitary lesion can lead to appropriate
with a variable proportion of
sex, and the clinical differtreatment and prevent further morbidity.
other features including exential diagnosis. Available
travasated red blood cells,
follow-up
information
hemosiderin-laden macrophages, and dermal fibrothrough the electronic and physical clinical charts
sis.3 The variation of dermal changes is thought to
was reviewed to document the development of
be related to the age of the lesion with prominent
classic broader patches of stasis dermatitis. For
fibrosis and siderophages in long-standing disease.
inclusion in the study, the cases had to clinically
The distribution of siderophages can help distinpresent as a solitary lesion, and the patient could
guish stasis dermatitis from pigmented purpuric
not have an already established diagnosis of stasis
dermatosis, with the macrophages present throughdermatitis or chronic vascular insufficiency.
out the dermis in the former, but only in the upper
Cases meeting the selection criteria were reviewed
one third of the dermis in the latter.3 Variable
for histological changes including the degree of
changes of the epidermis occur as well, such as
acanthosis, spongiosis, parakeratosis, proliferation
spongiosis, parakeratosis, and development of a
of vessels, dermal fibrosis, presence of hemosiderincrust. The variation of these changes depend on
laden macrophages, thickness of vessels, and hemorwhether there is an overlying eczematous dermarhage based on a scale from +1 to +3 (mild, moderate,
titis thought to be caused by the oversensitive
or severe). Additionally, the presence or absence of
nature of the skin in stasis dermatitis—so-called
spongiotic vesicle and crust formation was noted. Any
‘‘autoeczematization’’.
available additional special stains (eg, Gomori methThe initial stage of venous insufficiency is cusenamine silver) and recuts were also reviewed. In
tomarily edema of the lower legs. However, we have
addition, two deeper hematoxylin-eosinestained
noted many cases of stasis dermatitis on skin biopsy
(H&E) sections were performed to rule out possible
specimens submitted with differential diagnoses
previously unrecognized preneoplastic/neoplastic
consistent with a solitary disease process. Herein
processes left in the paraffin block that could otherwe report a series of cases describing a previously
wise explain the presence of a solitary lesion.
undocumented phenomenon of stasis dermatitis
Furthermore, all cases with H&E findings of intraeppresenting in an initial evaluation clinically as a
idermal neutrophils, intraepidermal lymphocytes, or
d
d
d
d
1030 Weaver and Billings
J AM ACAD DERMATOL
DECEMBER 2009
Table I. Demographics, clinical features, and diagnosis
Patient No.
Sex
Age (y)
Clinical morphologic description (if available)
1
2
3
4
5
6
F
F
F
F
M
F
59
42
49
67
61
59
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
M
M
M
F
F
F
F
F
F
M
F
M
F
F
F
M
F
M
F
F
F
F
M
F
M
M
M
64
79
76
52
64
82
89
77
60
57
53
87
75
57
66
64
78
74
84
68
79
66
46
76
56
61
65
15-mm scaly plaque w/ central erosion on R lower leg
12-mm scaly nummular patch on L pretibial area
7-mm scaly erythematous papule on L pretibial area
9-mm erythematous atrophic plaque w/ smooth surface on R medial malleolus
Erythematous red firm papule on L lower leg
2-cm erythematous atrophic plaque w/ minimal circumferential scale w/
adjacent hypopigmented scar on R pretibial leg
7-mm erythematous scaly patch on L medial lower leg
Small flesh-colored flat plaque on R leg
Thick keratotic area on lower leg
8-mm erythematous scaly papule on R mid anterior pretibial leg
6-cm ulcer with surrounding mild erythema on R lower anterior leg
Not available
L posterior leg ulcer
Erythematous papule on R lower leg
8-mm erythematous scaly irregular plaque on R lateral calf
1-cm lesion w/ central erosion on L leg
2-cm, somewhat eczematous, erythematous irregular patch on L pretibial area
Erythematous plaque w/ ulceration on R lower leg
13-mm erythematous shallow plaque on L pretibial leg
Not available
3-cm shiny atrophic plaque, slightly hypopigmented on L pretibial leg
Not available
Erythematous scaly plaque on L lateral calf
Not available
2.3-cm violaceous crusted plaque on L medial ankle
Not available
Not available
2-cm erythematous plaque w/ scale on R lower leg
Erythematous plaque with central ulceration and crust on R lower leg
Not available
Not available
5-mm papule on L ankle
18-mm firm erythematous scaly nodule on L lower leg
Clinical diagnosis
ISK
SCC
BCC
ISK
GA
Scar
ISK
BCC
SCC
BCC
PG
GA
SCC
SCC
SCC
Nevus
BCC
SCC
GA
BCC
Scar
Kaposi sarcoma
BCC
AK
SCC
BCC
SCC
BCC
PG
SCC
Scar
SCC
SCC
AK, Actinic keratosis; BCC, basal cell carcinoma; F, female; GA, granuloma annulare; ISK, irritated seborrheic keratosis; L, left; M, male; PG,
pyoderma gangrenosum; R, right; SCC, squamous cell carcinoma.
impetiginized serum crust were evaluated with a
periodic acideSchiff stain, if fungal stains were not
performed during initial evaluation, in order to rule
out the possibility of superficial dermatophytosis.
The study was approved by the institutional
review board of the Cleveland Clinic.
RESULTS
The initial query identified 483 cases with the
primary diagnosis of stasis dermatitis. Of the initial
483 cases, 37 patients presented with a clinical
diagnosis of a solitary lesion. Four patients with a
history of chronic venous insufficiency were excluded from the study, leaving 33 cases for the study,
representing 7% of all cases of stasis dermatitis (Table
I). None of the remaining 33 patients had history of a
previously diagnosed nummular eczema or irritant
dermatitis prior to the biopsy of the lower leg solitary
lesion.
Demographically, this under-recognized event
occurred in the usual setting for stasis dermatitis:
the lower extremities of older adults (average age, 66
years-old), with a female predominance (female:male, 1.8). Eleven cases (33%) had evidence of pedal
edema on initial physical examination; however,
only 3 patients (9%) were elicited to describe symptoms of ankle swelling after prolonged standing.
Detailed clinical descriptions were available on a
subset of cases (n = 29). The most common presentation was a single erythematous plaque on the lower
portion of the leg, affecting either lower extremity
with equal frequency (right:left, 0.8) (Fig 1). The
exact location of the lesions on the lower legs could
not be ascertained in the majority of cases due to the
J AM ACAD DERMATOL
Weaver and Billings 1031
VOLUME 61, NUMBER 6
Fig 1. The most common clinical presentation of stasis
dermatitis mimicking a solitary lesion was a single erythematous plaque on the lower portion of either leg.
lack of additional detail provided in the clinical notes
during the retrospective chart reviews. Only 3 cases
were specifically mentioned to have occurred on the
medial malleolus, which is the classic location of the
initial onset of stasis dermatitis; however, this number is likely an underestimation because of the
limitations of this retrospective study. The average
size of the lesion was 1.6 cm. Out of a total of 21 cases
described as a papule, plaque, nodule, or patch; the
most common presentation was a plaque (57%),
followed by papule (24%), patch (14%), and nodule
(5%). Fifty-six percent of cases presented with some
erythema, 40% described scaling, while only 24%
were eroded.
The most common clinical diagnosis was squamous cell carcinoma (33%) followed by basal cell
carcinoma (24%). Another 3 (9%) cases were thought
clinically to be consistent with a granuloma annulare
and another 3, irritated seborrheic keratosis. Other
clinical differential diagnoses included scars, pyoderma gangrenosum, actinic keratosis, Kaposi’s sarcoma, nevus, and a neoplasm, not otherwise
specified.
The histopathology of all the cases demonstrated
the classical morphologic picture of stasis dermatitis
with variable acanthosis and mild spongiosis of the
epidermis and underlying proliferation of thickwalled blood vessels in the papillary dermis with
deposition of hemosiderin and extravasation of red
blood cells (Fig 2). Spongiotic change in the epidermis was absent or mild (0 or 1+) in 27 cases (82%),
and spongiotic vesicles were never demonstrated.
Parakeratosis was present in roughly half of the cases
(58%), which correlated with the clinical impression
of a scale also approximately half of the time. A
serum crust was only identified in 5 cases (15%). The
characteristic lobular proliferation of thick-walled
Fig 2. A, Skin biopsies of all cases demonstrated classical
morphologic picture of stasis dermatitis with mild acanthosis and spongiosis of the epidermis and underlying
proliferation of thick-walled blood vessels in papillary
dermis. B, Evidence of hemorrhage including extravasated
erythrocytes, hemosiderin deposition, and siderophages
were essentially always present. (A and B, Hematoxylineosin stain; original magnifications: A, 3100; B, 3400.)
blood vessels in the papillary dermis was always
present; in the vast majority of the cases ([90%), this
finding was moderate to marked (2-3+). Evidence of
hemorrhage including extravasated erythrocytes,
hemosiderin deposition, and siderophages were
essentially always present ([95%). Some dermal
fibrosis was present in all cases, but in variable
proportions.
All recuts or levels performed at the time of
original diagnosis (n = 6; 18%) and all subsequent
deeper levels performed (n = 33; 100%) showed
similar histologic findings as the original H&E slides
with no evidence of an additional process that could
explain a localized lesion. Special stains (Gomori
methenamine silver, PAS, Steiner, Gram, and
Twort’s) for microorganisms were performed during
the initial evaluation on 9 of the cases (27%). All were
negative for fungal or bacterial organisms. Six cases
required additional PAS stain for the histopathologic
findings of intraepidermal neutrophils, intraepidermal lymphocytes, or impetiginized serum crust to
rule out dermatophyte infection. None of the cases
showed evidence of fungal forms on PAS stain. Only
1032 Weaver and Billings
J AM ACAD DERMATOL
DECEMBER 2009
one case had an iron stain performed, which was
positive for hemosiderin within macrophages.
Follow-up clinical data were available for 31 of 33
patients (94%) and demonstrated that 64% (14/22) of
patients undergoing biopsy during 2004 and earlier
developed classic broader patches of stasis dermatitis, whereas only 11% (1/9) of patients undergoing
biopsy during 2005 and since have currently developed classic findings of stasis dermatitis.
DISCUSSION
Stasis dermatitis caused by chronic venous insufficiency is a common condition that affects older
individuals. The diagnosis is typically straightforward and made on routine history and physical
examination by identifying the usual dermatologic
manifestations—pruritic bilateral scaly erythematous
papules and plaques located on the lower third of
the legs. Hyperpigmentation and hair loss may also
be associated with the above findings. The hyperpigmentation is usually a yellow-brown discoloration thought to be secondary to the hemosiderin
deposition from extravasated red blood cells which
is then engulfed by dermal macrophages. In a
minority of cases melanin in the form of dermal
melanophages and melanocytes have been implicated in contributing to the hyperpigmentation of
stasis dermatitis.4 The pigment incontinence may be
explained by resolution of a concurrent eczematous
process; so-called autoeczematization which has
been described in this population. Initial signs before
the characteristic lower leg skin changes include
congestion and dilation of the saphenous vein with
fibrosis and pitting edema of the medial aspect of the
ankle and lower shins.5
Early diagnosis and appropriate treatment with
compression therapy in combination with patient
education can help prevent the development of
painful and difficult-to-treat venous stasis ulcers
and therefore decreases the risk of development of
an ulcer-associated malignancy.6-9
Herein we have demonstrated the rare occurrence
of stasis dermatitis presenting as a solitary lesion as
an initial manifestation before more typical clinically
diagnostic changes. This early manifestation of stasis
dermatitis accounts for 7% of all cases of stasis
dermatitis in our clinical material. Importantly, the
patients had no history of chronic venous insufficiency; therefore the solitary lesion frequently mimicking a neoplasm was the initial presenting sign of
disease. Interestingly, 64% of patients (14/22) with
follow-up longer than 4 years had already progressed to a more definitive clinical picture with
the development of classic broad patches of stasis
dermatitis, whereas only 11% of patients (1/9) with
less extensive follow-up had undergone the same
process. These findings suggest that a relatively long
(4 years) period of time is required for the solitary
patch of stasis dermatitis to progress to a more
definitive clinical picture. The remaining 8 patients
without significant progression of their stasis dermatitis are most likely still at risk of developing a classic
clinical picture of stasis dermatitis down the line.
Therefore the evidence supports the findings that
stasis dermatitis can initially present as a solitary
lesion with or without other classic signs or symptoms of chronic venous insufficiency; furthermore a
significant subset of these patients go on to develop
more classic broad patches of typical stasis changes
on their legs.
As it is well-known that patients with a longstanding history of stasis dermatitis with associated
ulcers are at risk of developing squamous cell
carcinoma and rarely basal cell carcinoma,7-9 dermatologists and dermatopathologists should also be
aware that stasis dermatitis may clinically mimic
neoplasms. Furthermore, the histopathology of
stasis dermatitis has not been extensively described
in the literature. This series emphasizes that the
dermal changes including the lobular proliferation
of thick-walled papillary dermal blood vessels and
evidence of dermal hemorrhage are the essential
findings in stasis dermatitis. Epidermal changes are
usually mild in the lesions clinically mimicking
neoplasms.
REFERENCES
1. James WD, Berger TG, Elston DM. Andrews’ Diseases of the skin
clinical dermatology. 10th ed. Philadelphia: Saunders Elsevier;
2006. p. 845-7.
2. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of
leg ulcers on quality of life: financial, social, and psychologic
implications. J Am Acad Dermatol 1994;31:49-53.
3. Weeden D. Skin pathology. 2nd ed. Edinburgh: Churchill
Livingstone; 2002. p. 112.
4. Kim D, Kang WH. Role of dermal melanocytes in cutaneous
pigmentation of stasis dermatitis: a histopathological study of
20 cases. J Korean Med Sci 2002;17:648-54.
5. Worley CA. ‘It hurts when I walk:’ venous stasis disease—differential diagnosis and treatment. Dermatol Nurs 2006;18:582-3.
6. Erickson CA, Lanza DJ, Karp DL, Edwards JW, Seabrook GR,
Cambria RA, et al. Healing of venous ulcers in an ambulatory
care program: the roles of chronic venous insufficiency and
patient compliance. J Vasc Surg 1995;22:629-36.
7. Baldursson B, Sigurgeirsson B, Lindelof B. Leg ulcers and
squamous cell carcinoma. An epidemiological study and a
review of the literature. Acta Derm Venereol 1993;73:171-4.
8. Baldursson BT, Hedblad MA, Beitner H, Lindelof B. Squamous
cell carcinoma complicating chronic venous leg ulceration: a
study of the histopathology, course and survival in 25 patients.
Br J Dermatol 1999;140:1148-52.
9. Combemale P, Bousquet M, Kanitakis J, Bernard P. Malignant
transformation of leg ulcers: a retrospective study of 85 cases.
J Eur Acad Dermatol Venereol 2007;21:935-41.