Todd A. Meyer, DO, FAOCO, FAAOA

Todd A. Meyer, DO, FAOCO, FAAOA
None
vivianpaige.com
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Atopic
p Dermatitis
◦
◦
◦
◦
Epidemiology
Pathophysiology
Diagnosis
Management
http://s1 hubimg com/u/372124 f260 jpg
http://s1.hubimg.com/u/372124_f260.jpg
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2 year old female
New widespread rash on her face,
abdomen,
face arms,
arms abdomen
and behind both knees.
Rash has been present for the last two weeks and
seems to be getting worse.
Patient is scratching uncontrollably while sitting on
her mothers lap.
Mother states that this scratching
g is negatively
g
y
affecting her sleep.
Previous to this rash the child has been healthy, up to
date with immunizations and at the 50th percentile
ffor h
height
i ht and
d weight.
i ht Sh
She h
has a good
d appetite
tit and
d
has no gastrointestinal complaints.
There have been no sick contacts or recent travel.

y
Additional p
pertinent history:
◦ Mother has asthma and allergic rhinitis
(Major diagnostic criteria)
◦ No
N sun exposure, new soaps, detergents,
d
llotions,
i
clothing, bedding, etc.
◦ Patient has several p
potential infant triggers:
gg
 PMH:
Unremarkable
 PSH:
None
 Allergies:
NKDA

Family History:
Mother with asthma and allergic rhinitis
1. Foods such as eggs, milk, and soy in the diet.
2. The family has a dog
3. No smoke exposure
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Physical exam:
◦ The rash is particularly severe in the popliteal fossa.
generally
y has a fine p
papular
p
appearance
pp
with
◦ The rash g
some slight scaling and prominent erythema on the face,
arms abdomen, there is sparing of the diaper area.
◦ There are no crusts, pustules or exudates
HEENT: Positive for Dennie Morgan lines
lines,
periorbital darkening
Otherwise unremarkable exam with normal vitals

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Is made through
history and
appearance
Distribution
Di
t ib ti
off skin
ki
lesions!
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In 1980, Hanifin and Rajka developed criteria for the diagnosis of AD. They developed main
criteria and numerous minor criteria. Many articles have questioned the validity of the minor
g
g are the
criteria,, and the original
criteria have been modified on numerous occasions. Following
criteria for 2001.
◦
Essential features: These features must be present and, if complete, are sufficient for diagnosis.
 Pruritus
 Eczematous changes


◦
◦
◦
Typical and age-specific changes: Patterns include facial, neck, and extensor involvement in infants and
children current or prior flexural lesions in adults or persons of any age,
children,
age and sparing of the groin and axillary
regions.
Chronic and relapsing course
Important features (seen in most cases): These features are seen in most cases and add support to the
diagnosis
 Early age of onset
 Atopy (IgE reactivity)
 Xerosis
Associated features (clinical associations): These changes help in suggesting the diagnosis of AD but are too
nonspecific to be used for defining or detecting AD for research and epidemiologic studies.
 Keratosis pilaris/ichthyosis/palmar hyperlinearity
 Atypical vascular responses
 P
Perifollicular
if lli l changes
h
 Ocular/periorbital changes
 Perioral/periauricular lesions
Exclusions: Note that a firm diagnosis of AD depends on excluding conditions such as scabies, allergic
contact dermatitis, seborrheic dermatitis (SD), cutaneous lymphoma, ichthyosis, psoriasis, and other primary
disease entities.
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta
Derm Venereol (Stockh). 1980;92 (suppl):44-7.
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According to the criteria of Williams et al, proposed
diagnostic guidelines include the following:
◦ Patients must have an itchy skin condition (or parental
report of scratching or rubbing in children).
◦ Patients also must have 3 or more of the following:
 History of involvement of the skin creases, such as folds
of the elbows, behind the knees, fronts of the ankles, or
neck
 Personal history of asthma or hay fever or a history of
atopic disease in a first-degree relative in patients
younger than 4 years
 History of generally dry skin in the last year
 Visible flexural dermatitis or dermatitis involving the
cheeks or forehead and outer limbs in children younger
than 4 years
 Onset younger than age 2 years (not used if child is <4 y)

Essential Features (3 of 4 Required)
◦ Pruritus
◦ Facial and extensor eczema in infants and young
children/Flexural eczema in older children and
adults
◦ Chronic or relapsing dermatitis
◦ Personal
P
l or family
f il history
hi
off atopic
i disease
di
allergyasthma.wordpress.com
skin-disease.org
travinka.ru
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Xerosis
Cutaneous infections
Cheilitis
Non specific dermatitis of hands and feet
Non-specific
Elevated serum IgE
Positive allergy
gy skin tests
Early age at onset
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta
Derm Venereol (Stockh). 1980;92 (suppl):44-7.
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Ichthyosis
jaskin.com
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Palmar Hyperlinearity
yp
y
medicaljournals.se
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Keratosis Pilaris
emedicine.medscape.com
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Pityriasis alba
lb
vitiligoarab.net
itili
b t

White dermatographism and delayed blanch
response
kmle.co.kr
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Anterior subcapsular cataracts, Keratoconus
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Dennie-Morgan infra-orbital folds
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Orbital Darkening
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Facial erythema or pallor
University of Iowa Dermatology 1997
medicine-article.com
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Prevalence
◦ 10-20% Children,
1-3% Adults
h ld
d l
◦ Higher in industrialized nations
 Higher in urban vs. rural regions

◦ More common in higher social class
Up to 85% develop symptoms before age 5
◦ Symptoms frequently
f
l present in early
l infancy
f
 45% before 6 months, 60% before age 1 year
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30% develop asthma
35% develop allergic rhinitis
Horii KA, Simon SD, Liu DY, Sharma V. Atopic dermatitis in children in the United States, 1997-2004: visit trends,
patient and provider characteristics,
characteristics and prescribing patterns.
patterns Pediatrics.
Pediatrics Sep 2007;120(3):e527-34.
2007;120(3):e527 34 [Medline].
[Medline]
Schultz-Larsen, Immunol Allergy Clin North Am 2002; 22: 1-24
Taylor, Lancet 1984; 2: 1255-57
Williams, Atopic Dermatitis, 2000: 41-59
Luoma, Allergy 1983; 38: 339-46
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Aberg (1995)
◦ Questionnaire study
d off Swedish
d h School
h l Children
h ld
(3000 7 year-olds) in 1979 and 1991
 Prevalence of AD more than doubled ((7% to 18%))
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Sugiura(1998)
◦ 7000 Japanese school children examined
 P
Prevalence
l
off AD in
i 9-12
9 12 year-olds
ld d
doubled
bl d compared
d
to 20 years earlier
 18 year-olds had a 5-fold increase in prevalence over
20 years
Aberg, Clin Exp Allergy 1995; 25: 815-819
Sugiura, Acta Derm Venereol 1998; 293-294
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Atopic Dermatitis
seems to
t be
b th
the
“Entry Point” for the
development
p
of
allergic disease
Bustos, Clin Exp Allergy 1995; 25: 568-73
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Should AD children be targeted for asthma
prevention? YES!
◦ Children with AD
AD, age 1-36 months
months, treated with
daily antihistamine (randomized, placebo
controlled)
 25% fewer diagnoses of asthma in the anti-histamine
group
◦ ETAC Study
 817 infants, age 1-2, treated with placebo or cetirizine
 50% developed asthma, but 25% less in cetirizine treated
patients who had specific
p
p
sensitizations to dust or g
grass
Bustos, Clin Exp Allergy 1995; 25: 568-73
Warner, ETAC Study Group, J Allergy Clin Immunol 2001; 108: 929-937
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60% of AD children are symptom
free by early adolescence
◦ 50% may recur in adulthood
Predictors of persistent disease course:
y onset,, severe early
y disease,, asthma and hay
y
◦ Early
fever, and family history
Evidence of food and inhalant allergy by age 2 also
predicts severe disease
Lammintausta, Int J Dermatol 1991; 30: 563-8
Illi, J Allergy Clin Immunol 2004; 113: 925-31
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Two types of atopic dermatitis
◦ Extrinsic
E t i i
 Associated with IgE-mediated sensitization
 70-80% of patients
p
◦ Intrinsic
 Absence of IgE-mediated sensitization
 20-30% of patients
Types of AD are identical clinically
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Infantile Phase – exudative, erythematous papules
and vesicles
◦ Face, trunk, extensor surfaces
Childhood Phase – lichenified papules and plaques
◦ Hands, feet, wrists, ankles, antecubital, popliteal
Adult Phase – dry, scaling, erythematous papules
and
a
dp
plaques
aques with
t large
a ge lichenified
c e
ed p
plaques
aques
◦ Flexural folds, face, neck, upper arms, back,
dorsa of hands, feet, fingers, and toes
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Most have peripheral blood eosinophilia and
increased
i
d serum IgE
I E
Increased allergen-specific Th2-cells
◦ IL
IL-4
4 and -13
13
 Isotype switching to IgE
 Induce expression of VCAM-1 (eosinophil infiltration)
 Downregulate
D
l t Th1 cytokines
t ki
◦ IL-5
 Development, activation, and survival of eosinophils
Hamid, J Clin Invest 1994; 94: 870-76
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Food allergy induces skin rash in 40% of children
with AD
Can be diagnosed with IPDFT, elim/challenge or
mRAST
◦ Most commonly
l – egg, milk,
lk wheat,
h
soy, and
d
peanut
T-cells specific
p
for foods have been cloned from
skin lesions
Sampson, J Allergy Clin Immunol 1999; 103: 717-28
Van Reijsen, J Allergy Clin Immunol 1998; 101: 207-09

Double-Blind, Placebo Controlled Oral Food
Challenges
◦ Food allergens caused increased symptoms
◦ Symptoms resolved when food was eliminated
Sicherer, J Allergy Clin Immunol 1999; 104
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Sensitization to aeroallergens correlates with
severity of AD
Inhalation challenge in sensitized individuals can
exacerbate pruritus and skin lesions
Proper “avoidance measures” in dust sensitive
patients has led to improvement in AD
Immunotherapy
py is not universally
y helpful
p
◦ Recent study showed improved AD when dust
allergy is treated with immunotherapy
Capristo, Allergy 2004; 59(suppl 78):53-60
Schafer, J Allergy Clin Immunol 1999; 104: 1280-1284
Scalabrin, J Allergy Clin Immunol 1999; 104: 1273-79
1273 79
Holm, Allergy 2001; 56: 152
152-58
58
Werfel, Allergy 2006; 61: 202-205
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Atopy Patch Testing
◦ Mostly used for research
 Occlusive patch testing with aeroallergens elicits
eczematoid reactions in 30-50% of AD patients
 Allergic patients without AD have no reaction to this
patch test
Wheatley in Leung, Allergic Skin Disease: A Multidisciplinary Approach 2000; 423
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Multipronged Approach
◦ Skin Care
◦ Identification and Elimination of Triggers
◦ Anti-pruritus Treatment
◦ Anti
Anti-inflammatory
inflammatory Treatment
Clinical Recommendation
Emollients
are the
off maintenance
therapy
for
E
lli
h mainstay
i
i
h
f
atopic dermatitis.
Topical corticosteroids should be first-line treatments for
patients with atopic dermatitis flare-ups.
Sedating antihistamines are indicated for the treatment of
atopic dermatitis when patients have sleep disturbances and
concomitant allergic conditions.
Antibiotics should be reserved for the treatment of acutely
y
infected lesions associated with atopic dermatitis.
Topical calcineurin inhibitors should be second-line
treatments for atopic dermatitis flare-ups and maintenance.
Evidence
Rating
B
A
A
A
A
References
3 , 4 , 10
3 4 11
11 13
4
25
A =consistent, good-quality patient-oriented evidence; B =inconsistent or limited-quality patient-oriented evidence; C
=consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT
evidence
id
rating
i system, see page 453 or http://www.aafp.org/afpsort.xml.
h //
f
/ f
l
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Liberal amounts of a lubricant or emollient cream
should be applied to the skin immediately after
bathing.
Emollients should be applied once or twice daily to
prevent skin dryness and irritation.
Patients generally prefer emollient creams over
ointments for daytime use because emollients have
a non g
greasy,
y, cosmetic appearance.
pp
Lubricating ointments may be preferred for
nighttime use because of their superior hydrating
properties.
Wearing cotton gloves or socks at night may
enhance these properties.
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Numerous studies have
evaluated a variety of dietary,
dietary
environmental, and alternative
approaches to the prevention
of atopic dermatitis flareups.[3] [4] [11]
“Scratch-itch-scratch” behavior
◦ Begins with habitual
scratching
◦ Perpetuates dry, irritated
skin
◦ Can be effectively modified
with psychological
treatment.[12
TABLE 2 -- Unproven Prevention and
Treatment Strategies for Atopic
Dermatitis
Information from reference 4 .
Chinese herbal therapy
Delayed
l
d introduction
d
off solid
l d ffoods
d in
infants
Dietary restrictions
Homeopathy
Massage therapy
Prolonged breastfeeding
Reduction of house mite dust
Salt baths
Use of different diaper
p materials

Use soft Clothing next
to the
h skin.
ki
◦ Cotton is comfortable
◦ Can be layered in the
winter.
◦ Wool products should be
avoided.

Clothes should be
washed in a mild
detergent with no
bleach or fabric
softener.

Cool temperatures,
particularly
i l l at night,
i h
are helpful
◦ Sweating causes irritation
and itch.

A humidifier (cool mist)
prevents excess drying
◦ Used in both winter, when the
heating dries the atmosphere,
and in the summer, when air
conditioning absorbs the
moisture from the air.

Food avoidance
http://emedicine.medscape.com/article/1049085-treatment
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Want to maintain moist
skin at all times
◦ Soak in clean, warm water
(bath, not shower)
◦ Avoid soap at every bath
 Use gentle non-drying soaps
(Aveeno, Dove, Basis,
Neutrogena) – minimal
defatting and neutral pH
◦ Avoid bath oils
◦ Avoid scrub brushes and
washcloths
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y after the bath
Pat dry
While skin is still moist, apply an emollient
(Aquaphor, Eucerin, Cetaphil, Neutrogena)
P t l
Petroleum
jelly,
j ll mineral
i
l oil,
il or C
Crisco
i
can b
be
used if xerosis is severe
realsimple.com
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When rash leads to open,
oozing
sores:
i
◦ Frequent baths
(4 per day) in clean,
warm water
◦ Add colloidal oatmeal to the
b th water
bath
t (3 tb
tbsp))
Avoid irritants!
omurtlak.bloguez.com
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Soaps and detergents
◦ Want
minimal
activity
W
i i l defatting
d f i
i i and
d neutrall pH
H
◦ Wash clothes in gentle, liquid detergent and
add extra rinse cycle
y
Heat and perspiration
Occlusive clothing
◦ Loose fitting cotton, silk, and cotton blends
are best
Sunburn

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Identify potential allergens through history and
skin testing or mRAST
Foods are very important and proper elimination /
rotation diets should be used
Immunotherapy for AD has not been proven to be
beneficial
◦ Reserve for patients with clear seasonal
exacerbations or other symptoms of allergic
disease

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Proper bathing and emollients may be enough
Add antihistamine if needed
◦ Cetirizine, loratadine, desloratadine, fexofenadine,
diphenhydramine, hydroxyzine
Try non-sedating in morning and sedating at night to
help with sleep
Topical Doxepin works well, but is sedating
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Increased colonies of S aureus in 90% of AD skin
lesions
l i
Improved response to therapy when anti-staph
antibiotics
a
t b ot cs a
are
e included
c uded
Superantigen production is the likely mechanism
Leyden, Br J Dermatol 1977; 96: 179-87
Breuer, Allergy 2000; 55: 551-55
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Scratching enhances binding
◦ Exposes extracellular
ll l matrix adhesins
dh
Th2 inflammatory responses promote binding
◦ IL
IL-4
4 induces fibronectin expression
AD skin is deficient in antimicrobial peptides (βdefensins)
Cho, J Invest Dermatol 2001; 116: 658-63
Ong, N Engl J Med 2002; 347: 1151-60
Cho, J Allergy Clin Immunol 2001; 108: 269-74
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Topical mupirocin (Bactroban) works well when
Staph
is
always)
S h colonization
l i
i
i present (almost
( l
l
)
◦ Treat the nose, too!
Watch for super-imposed HSV infection
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Reduce inflammation and pruritus in acute and
chronic
h
i AD
Goal is to use the lowest strength possible to
control
co
t o sy
symptoms
pto s
Ointments are generally preferred over cream / gel
◦ More occlusive and fewer additives
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Thinning skin
Telangiectasias
Bruising
Hypopigmentation
Acne
Striae
Face and intertriginous areas are more
tibl tto th
t
susceptible
these events
◦ Low Potency formulations only!
Elidel and Protopic for the Treatment of Eczema, Black Box Warning on Elidel and Protopic by Daniel More, MD,
About.com Guide Updated September 08, 2011
Acta Derm Venereol Suppl (Stockh). 1989;151:26-30; discussion 47-52.
Adverse effects of topical corticosteroids. Piérard GE, Piérard-Franchimont C, Ben Mosbah T, Arrese Estrada J.
Department of Dermatopathology, University of Liège, Belgium

Least Potent to Most Potent
◦ Group 7
 Hydrocortisone (Hytone) 1 and
2.5% oint/cream
◦ Group 6
 Desonide (DesOwen) .05%
oint/cream/lotion
 Alclometasone (Aclovate) .05%
oint/cream
◦ Group 5
 Fluocinolone (Synalar) .025%
cream
 Hydrocortisone valerate
(Westcort) .2% oint
◦ Group 4
 Mometasone (Elocon) .1% cream
 Fluocinolone (Synalar) .025% oint
 Triamcinolone (Kenalog) .1%
oint/cream
◦ Group 3
 Fluticasone (Cutivate) .005%
oint
 Halcinonide
H l i
id (Halog)
(H l ) .1%
1% oint
i
 Betamethasone (Valisone) .1%
oint
◦ Group 2
 M
Mometasone (Elocon)
(El
) .1%
1% oint
i
 Halcinonide (Halog) .1% cream
 Fluocinonide (Lidex) .05%
oint/cream
 Desoximetasone
D
i
(T i
(Topicort)
)
.25% oint/cream
◦ Group 1
 Betamethasone (Diprolene)
05% (ointment
.05%
(ointment, gel)
 Clobetasol (Temovate) .05%
oint/cream
Hengge, U, Ruzicka, T, Schwartz, R, and Cork, M. ÒAdverse Effects of Topical Glucocorticosteroids,
Journal of the American Academy of Dermatology January 2006. Vol. 54, No. 1, P 4
http://www.psoriasis.org/page.aspx?pid=469
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BID dosing for most, QD for Fluticasone and
Mometasone
30g is needed to cover the entire body of an
average
a
e age adu
adultt
Instruct patients in the FTU (Finger Tip Unit)
◦ Medication extends from tip to the first joint of
the
h index
i d fi
finger
◦ 1 FTU = Hand or groin, 2 FTU’s = face or foot, 3
U = arm,, 6 FTU’s
U = leg,
g, 14 FTU’s
U = trunk
FTU’s
http://www.patient.co.uk/health/Fingertip-Units-for-Topical-Steroids.htm

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Start with a higher potency steroid for moderate to
severe AD
When improved after 2 weeks or so – step down to
a lower potency before stopping
◦ Iff not tapered,
d AD fl
flares can develop
d
l
Steroid therapy may be discontinued when
inflammation has resolved
◦ Continue hydration and emollients
◦ Consider twice weekly steroid maintenance
Van Der Meer, Br J Dermatol 1999; 140: 1114-1121


Tacrolimus (Protopic) and Pimecrolimus (Elidel)
Bind to intracellular immunophilins in T-cells
◦ Inhibits calcineurin – a calcium-ion-calmodulin
dependent protein phosphatase necessary for
signal transduction
◦ Cytokine gene transcription cannot occur
Boguniewicz, J Allergy Clin Immunol 2003; 112: S140-50



Tacrolimus
.03%
T
li
03% BID -- Moderate
M d
t to
t severe AD,
AD
over the age of 2, unresponsive to, or intolerant of,
steroids
Tacrolimus .1% BID -- As above, over the age of 16
Pimecrolimus 1% BID -- Mild to Moderate AD, over
the age of 2, unresponsive to steroids
http://www.astellas.us/therapeutic/product/prograf.html
http://www.novartis.com
/
A 2006 black box warning has been issued in the United
States based on research that has shown an increase in
malignancy in association with the calcineurin inhibitors.
 While these claims are being investigated further, the
medication should likely only be used as indicated (ie, for
atopic dermatitis in persons older than 2 y and only when
first-line therapy has failed).
 Primate study with oral pimecrolimus demonstrated
development of lymphoma
◦ 30x the maximum recommended human dose
 2005 ACAAI and AAAAI Calcineurin Inhibitor Task Force
◦ Recommend no change in current usage patterns

Black Box Warning, Safety of Allergy and Asthma Medicines by Daniel More, MD, About.com Guide Updated July 27, 2007
Elidel and Protopic for the Treatment of Eczema, Black Box Warning on Elidel and Protopic by Daniel More, MD,
About.com Guide Updated September 08, 2011
FDA Approves Updated Labeling with Boxed Warning and Medication Guide for Two Eczema Drugs, Elidel and Protopic,
January 19, 2006
Fonacier, J Allergy Clin Immunol 2005; 115(6): 1249-53

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Phototherapy – sunlight in small doses, UV-A, UVB,
B a combination of both,
both psoralen plus UV-A
UV A
(PUVA), or UV-B1 (narrow-band UV-B) therapy may
be used. Long-term adverse effects of skin
malignancies in fair-skinned
fair skinned individuals should be
weighed against the benefits.
Systemic steroids – Avoid as much as possible
(di
(discontinuing
i i
usually
ll associated
i d with
i h fl
flares))
Interferon Gamma – Downregulate Th2 function
Cyclosporin
y
p
– systemic
y
calcineurin inhibitor can
improve symptoms, but side effects (renal
impairment and HTN) limit its use
http://emedicine.medscape.com/article/1049085-treatment
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Antimetabolites – Mycophenolate, Methotrexate, Azathioprine
Psychological Treatment–Emotional stressors exacerbate
disease
di
Probiotics
◦ The rationale for their use is that bacterial products may
induce an immune response of the Th 1 series instead of Th
2 and could therefore inhibit the development of allergic
IgE antibody production.
◦ Some report
p
limited benefit in p
preventive/therapeutic
/
p
roles.
◦ This research has yet to be proven.
◦ 56 infants with mod-severe AD, randomized to
lactobacillus or placebo – significant improvemnet in
b
f
8 weeks
k
probiotic
group after
Tar Preparations – coal tar is anti-pruritic and antiinflammatory, may induce folliculitis and photosensitivity, use
restricted to chronic lesions
Michail S. The role of Probiotics in allergic diseases. Allergy Asthma Clin Immunol. Oct 22 2009;5(1):5.7
Weston, Arch Dis Child 2005; 90: 892-89

Omalizumab

Efalizumab
f l
b

◦ IgG humanized antibody to binding site on IgE
◦ Approved in mod-severe asthma
◦ 2 small case series in AD – one shows benefit, one shows
none
◦ Humanized monoclonal antibody to CD11a
◦ Blocks T-cells ability to bind to ICAM-1 on antigen
presenting cells
◦ Approved in mod-severe chronic plaque psoriasis
TNF-α Inhibitors (etanercept, infliximab,
adalimumab))
◦ Blocks migration of T-cells, blocks attraction of TH-2 cells,
blocks eosinophil and basophil recruitment
◦ Approved in psoriasis and rheumatoid arthritis
Lane, J Am Acad Dermatol 2006; 54: 68-72
Krathen,, J Am Acad Dermatol 2005; 53: 338-340
Connor, Curr All Asthma Rep 2006; 6: 275-281