Clinical Reviews in Allergy & Immunology

, Volume 41, Issue 3, pp 282–295

Therapeutic Implications of a Barrier-Based Pathogenesis of Atopic Dermatitis

Authors

    • Dermatology Service (190)Veterans Affairs Medical Center
    • Department of DermatologyUniversity of California
  • Joan S. Wakefield
    • Dermatology Service (190)Veterans Affairs Medical Center
    • Department of DermatologyUniversity of California
Article

DOI: 10.1007/s12016-010-8231-1

Cite this article as:
Elias, P.M. & Wakefield, J.S. Clinic Rev Allerg Immunol (2011) 41: 282. doi:10.1007/s12016-010-8231-1

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.

Keywords

Antimicrobial peptides Atopic dermatitis Barrier function Barrier repair

Abbreviations

AD

Atopic dermatitis

AMP

Antimicrobial peptides

Cer

Ceramides

FLG

Filaggrin

FFA

Free fatty acids

hBD

Human β-defensins

hCAP

Human cathelicidin

IV

Ichthyosis vulgaris

LB

Lamellar bodies

LEKTI

Lymphoepithelial Kazal-type inhibitor

NS

Netherton syndrome

PAR2

Plasminogen activator type 2 receptor

SP

Serine protease

SC

Stratum corneum

t-UCA

Trans-urocanic acid

Copyright information

© Springer Science+Business Media, LLC 2010