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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
for lymphoma or leukemiafor lymphoma or leukemia
Callen, JP, et.al. JAAD 2000,
43:207-10
Hand Eczema & EyelidHand Eczema & Eyelid
DermatitisDermatitis
• ACD or AD?—AD much more
frequent cause
• Treat first; patch tests if
recalcitrant
• Calcineurin inhibitors crucial for
control of AD eyelid problems
Case Finding for AdultCase Finding for Adult
Onset ADOnset AD
• Sensitive skin?
• Infant or early childhood eczema?
� Adult can’t recall mild/mod disease� Maybe only manifest in winter� Parents needed for history� ?Food allergy
• Mime the itch—scratch antecubitals/popliteals
NACDG Patch Test tray negative
30 yo Asian/American man30 yo Asian/American man
• Flaring of chronic AD with lichenification,
pigmentation and itch—using only Cetaphil cr
• Similar presentation 3 yrs ago; responded
well to topicals steroids and CI’s
• Stopped all medications because of warnings
� Hesitant to restart� Especially concerned about steroid near eyes� Hates ointments
Discussion/NegotiationDiscussion/Negotiation
• Why flaring? Winter?, out of meds?
?depressed
• Options
� Topicals safer than systemics� Potent steroids needed for lichenified lesions
• No danger from short-term, aggressive use
• Evaluate each week—phone or clinic
RegimenRegimen
• Betamethasone ung (1#) b.i.d after
20 minute tub bath for 1 week
• Only 3-4 days on face, then TCI
• Call 1 wk—plan taper to qd x 1 wk,
then qod, then goal: twice weekly
Obstacles to EffectiveObstacles to Effective
Management of ADManagement of AD
• Temerity (physician & patient) in
using topical steroids
•Confusion and compliance issues
•Proper topical care diverted by
allergy-seeking behavior
Common Glitches inCommon Glitches in
Prescribing Topical SteroidsPrescribing Topical Steroids
• Confusing when more than one steroid prescribed
initially (triamcinolone 0.1% safe on face bid x 3d;
then biw)
• Failing to hydrate before topical medication
• Dilution (mixing steroid + emollient or TCI) reduces
drug effect
• Vehicle—creams can’t compete
• Size matters!!! Small tubes cause recurrent flares
Impact of Topical Calcineurin InhibitorsImpact of Topical Calcineurin Inhibitors
• Effective anti-inflammatory to follow
corticosteroids
• Safe (hopefully long-term) maintenance
for prolonged therapy
• More efficient management of AD
patients:
� Increased optimism with good control� Reduced concern about allergy� Potential to reduce later allergy
Barrier Maintenance Devices:Barrier Maintenance Devices:
Atopiclair, Epiceram, MimyX Atopiclair, Epiceram, MimyX
• For maintenance over co-existing
skin cancer areas
• For steroid over-indulgers
•Recurrent infection sites
• For steroidophobics
• For the well-insured
Newer Topical SteroidNewer Topical Steroid
ProductsProducts
• Desonate—0.05% desonide in hydrocolloid gel *
• Verdeso--0.05% desonide foam *
• Olux-E—0.05%clobetasol in emollient foam
• Cutivate—0.05% fluticasone lotion
• Vanos--0.1% cream
*These and fluticasone cream approved for infants
as young as 3 months
Unsupported TherapiesUnsupported Therapies
used in ADused in AD
• Antihistamines
• Cromolyn
• Leukotriene inhibitors
• “Allergy shots” (aka “immunotherapy”)
• Probiotics
• Borage/Evening Primrose oils
• Herbals
• Anti-IgE
Systemic Therapy of ADSystemic Therapy of AD
• Cyclosporin A
• Antibiotics
• Gamma interferon
• Methotrexate*
• Azathioprene
• Mycophenolate
mofetil*
• Systemic steroids
• IVIg*
• Leukotriene inhibitors**
• Antihistamines**
• Anti-IgE (Xolair)**
• Thalidomide*
* No Randomized Clinical Trials
** RCT’S show no benefit
Biologic agents for ADBiologic agents for AD
!Will they be effective for AD?
!Are they safe?
!Which might show efficacy?
!Interferon-gamma
!Omalizumab and rituximab
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