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Abnormal skin barrier in the etiopathogenesis of atopic dermatitis

Elias, Peter M; Schmuth, Matthias

Current Opinion in Allergy and Clinical Immunology: October 2009 - Volume 9 - Issue 5 - p 437–446
doi: 10.1097/ACI.0b013e32832e7d36
Skin allergy: Edited by Torsten Zuberbier and Thomas Werfel

Purpose of review Many recent studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the pathogenesis of atopic dermatitis. Accordingly, current therapy has been largely directed towards ameliorating Th2-mediated inflammation and/or pruritus. We will review here emerging evidence that the inflammation in atopic dermatitis results from inherited and acquired insults to the barrier and the therapeutic implications of this new paradigm.

Recent findings Recent molecular genetic studies have shown a strong association between mutations in FILAGGRIN and atopic dermatitis, particularly in Northern Europeans. But additional acquired stressors to the barrier are required to initiate inflammation. Sustained hapten access through a defective barrier stimulates a Th1 → Th2 shift in immunophenotype, which in turn further aggravates the barrier. Secondary Staphylococcus aureus colonization not only amplifies inflammation but also further stresses the barrier in atopic dermatitis.

Summary These results suggest a new ‘outside-to-inside, back to outside’ paradigm for the pathogenesis of atopic dermatitis. This new concept is providing impetus for the development of new categories of ‘barrier repair’ therapy.

aDermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, California, USA

bDepartment of Dermatology, Innsbruck Medical University, Innsbruck, Austria

Correspondence to Peter M. Elias, MD, Dermatology Service (190), VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA Tel: +1 415 750 2091; fax: +1 415 750 2106; e-mail:

Copyright © 2009 Wolters Kluwer Health, Inc. All rights reserved.