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Atopic Dermatitis:Atopic Dermatitis:
TherapeuticTherapeutic
ChallengesChallenges
PDA August 14, 2009
Jon Hanifin
OHSU, Portland
Dominant Concepts inDominant Concepts in
Atopic DermatitisAtopic Dermatitis
• Allergy / Immunology Era: 1915-2006
• The Epidermal Era: 2006----
� Barrier dysfunction
� KC / immunocyte interactions
� Innate immunity
1/5/82: It’s a
barrier problem!
Hydration protects!
The BarrierThe Barrier
ConceptConcept
Outside-in
Pathogenesis
IchthyosisIchthyosis
vulgarisvulgaris——FF
ilaggrinilaggrin
nullnull
mutationsmutationsPalmer, NaturePalmer, Nature
Genetics 2006Genetics 2006
Figure 1 Skin barrier function and allergic risk. An intact epithelial barrier (a) prevents
allergens from reaching antigen-presenting cells (APCs) in subepithelial tissues. Damage to
this barrier (b) allows allergens to penetrate into the subepidermal layer and interact with
APCs, leading to allergic sensitization and, secondarily, to allergic manifestations in the host.
Hudson TJ: Nat Gen 38(4):399-400, 2006
Treat the barrier--Treat the barrier--EarlyEarly
• The clinical presence of ichthyosis can
predict patients/families with:
� Allergic respiratory disease
� A more severe AD phenotype
� Early onset AD
AllergyAllergy
Atopic Dermatitis andAtopic Dermatitis and
AllergyAllergy
•AD is not an IgE-mediated
disease
•AD is not an allergic skin disease
•AD is a skin disease which
predisposes to allergies
Define Food AllergyDefine Food Allergy
• An adverse health effect that results from
stimulation of a specific immune response
• No immediate clinical reaction? Not
allergy!
• Eczema ups & downs diagnosed as
allergy are almost always wrong
Misdiagnosing Eczema asMisdiagnosing Eczema as
Food AllergyFood Allergy
• Positive allergy test— only a test!!!
• Allergy is an immediate clinical
reaction--by history or challenge
• Diet restriction--no challenge, no proof
• Skin care diverted to allergy search--
eczema continues
Allergy and AD:Allergy and AD:A more balanced perspective is needed forA more balanced perspective is needed for
parentsparents…… and pediatricians and pediatricians
• AD and ichthyosis promote IgE
production.
• Allergic reactivity is secondary
to barrier dysfunction.
•We now recognize the potential
to modulate / prevent allergic
diseases with barrier care.
AD in Teenagers AD in Teenagers
• “Rebelling out” is a way of life
• Non-compliance is assumed
• Magical thinking must be replaced
by reality
• Systematic care
� The teen’s lowest priority
� Negotiate to find room on a full
schedule
AD ManagementAD Management
Considerations in TeenagersConsiderations in Teenagers
• Sideline parents to consulting role
� Calls and appts initiate with teen
� Parent in room only at start and end
� Offer counseling
• Lower the threshold for considering
systemic therapy (e.g. CsA, MTX)
Adult Onset ADAdult Onset AD
• Rare in temperate climates
• Can follow move from tropics
• Might signal
� Allergic contact dermatitis
� Lymphoma
• Always consider biopsy
(JAAD 2005, 52: 579-82
BJD 2006, 155:557-60)
Adult-onset recalcitrantAdult-onset recalcitrant
eczema: A possible markereczema: A possible marker