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. 2010 Aug;22(3):245-54.
doi: 10.5021/ad.2010.22.3.245. Epub 2010 Aug 5.

Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis

Peter M Elias  1
Affiliations

Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis

Peter M Elias. Ann Dermatol. 2010 Aug.

Abstract

In this review, I first provide relevant background information about normal epidermal barrier structure and function. I then update recent information about how inherited defects in either filaggrin and/or in the serine protease inhibitor, lymphoepithelial Kazal-type inhibitor 1, converge to stimulate the development of atopic dermatitis (AD). Next I explain the multiple mechanisms whereby a primary barrier abnormality in AD can lead to inflammation. Furthermore, I explore how certain acquired stressors, such as a reduced external humidity, high pH soaps/surfactants, psychological stress, as well as secondary Staphylococcus aureus infections initiate or further aggravate AD. Finally, and most importantly, I compare various therapeutic paradigms for AD, highlighting the risks and benefits of glucocorticoids and immunomodulators vs. corrective, lipid replacement therapy.

Keywords: Antimicrobial peptides; Atopic dermatitis; Barrier function; Barrier repair.

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Conflict of interest statement

Dr. Elias is a co-inventor of the optimal ratio, ceramide-dominant, triple-lipid therapy for atopic dermatitis. He also is a consultant for Promius Pharma, LLC and Pediapharm, Inc., which market EpiCeram® in the United States and Canada, respectively.

Figures

Fig. 1
Fig. 1
Lamellar body secretion delivers key components of both permeability & antimicrobial barriers (modified from Elias11).
Fig. 2
Fig. 2
Mechanisms whereby filaggrin deficiency could predispose to the development of atopic dermatitis. CD: corneodesmosomes, FLG: filaggrin, LB: lamellar body, SC: stratum corneum, TSLP: thymic stromal lymphopoietin.
Fig. 3
Fig. 3
Pathogenesis of netherton syndrome. LEKTI 1: lymphoepithelial Kazal-type inhibitor 1, SCTE: stratum corneum tryptic enzyme, SCCE: stratum corneum chymotryptic enzyme.
Fig. 4
Fig. 4
Relationship of ichthyosis vulgaris and netherton syndrome to atopic dermatitis.
See this image and copyright information in PMC

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