title: Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis.
abstract: Excessive Th2 cell signaling and IgE production play key roles in the pathogenesis of atopic dermatitis (AD). Yet, recent information suggests that the inflammation in AD instead is initiated by inherited insults to the barrier, including a strong association between mutations in FILAGGRIN and SPINK5 in Netherton syndrome, the latter of which provides an important clue that AD is provoked by excess serine protease activity. But acquired stressors to the barrier may also be required to initiate inflammation in AD, and in addition, microbial colonization by Staphylococcus aureus both amplifies inflammation, but also further stresses the barrier in AD. Therapeutic implications of these insights are as follows: While current therapy has been largely directed toward ameliorating Th2-mediated inflammation and/or pruritus, these therapies are fraught with short-term and potential long-term risks. In contrast, "barrier repair" therapy, with a ceramide-dominant triple-lipid mixture of stratum corneum lipids, is more logical, of proven efficacy, and it provides a far-improved safety profile.
authors.affiliation: Dermatology Service, Veterans Affairs Medical Center, San Francisco, CA 94121, USA. eliasp@derm.ucsf.edu
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Joan S
authors.initials: JS
authors.lastname: Wakefield
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D000091344:Filaggrin Proteins; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology; D013312:Stress, Physiological
chemical_list: D000893:Anti-Inflammatory Agents; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007166:Immunosuppressive Agents; D007381:Intermediate Filament Proteins