Atopic Dermatitis: Therapeutic Challenges PDA August 14, 2009 Jon Hanifin OHSU, Portland Dominant Concepts in Atopic 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 Barrier Concept Outside-in Pathogenesis
Ichthyosis vulgaris F ilaggrin null mutations Palmer, Nature Genetics 2006 Hudson TJ: Nat Gen 38(4):399-400, 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.
Treat the barrier--early The clinical presence of ichthyosis can predict patients/families with: Allergic respiratory disease A more severe AD phenotype Early onset AD Allergy
Atopic Dermatitis and Allergy 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 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 as Food 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: A more balanced perspective is needed for parents 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 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 Management Considerations 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 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 recalcitrant eczema: A possible marker for lymphoma or leukemia Callen, JP, et.al. JAAD 2000, 43:207-10
Hand Eczema & Eyelid Dermatitis 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 Adult Onset 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 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/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 Regimen 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 Effective Management of AD Temerity (physician & patient) in using topical steroids Confusion and compliance issues Proper topical care diverted by allergy-seeking behavior
Common Glitches in Prescribing 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 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: 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 Steroid Products 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 Therapies used in AD Antihistamines Cromolyn Leukotriene inhibitors Allergy shots (aka immunotherapy ) Probiotics Borage/Evening Primrose oils Herbals Anti-IgE
Systemic 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 AD!Will they be effective for AD?!Are they safe?!which might show efficacy?!interferon-gamma!omalizumab and rituximab