Ann Dermatol.  2010 Aug;22(3):245-254. 10.5021/ad.2010.22.3.245.

Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis

• Elias PM

• KMID: 2265356
• DOI: http://doi.org/10.5021/ad.2010.22.3.245

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.

Keyword

Antimicrobial peptides; Atopic dermatitis; Barrier function; Barrier repair

MeSH Terms

Dermatitis, Atopic
Glucocorticoids
Humidity
Hydrogen-Ion Concentration
Immunologic Factors
Inflammation
Intermediate Filament Proteins
Risk Assessment
Serine Proteases
Staphylococcus aureus
Stress, Psychological
Glucocorticoids
Immunologic Factors
Intermediate Filament Proteins
Serine Proteases

Figure

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  Fig. 1 Lamellar body secretion delivers key components of both permeability & antimicrobial barriers (modified from Elias11).

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  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.

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  Fig. 3 Pathogenesis of netherton syndrome. LEKTI 1: lymphoepithelial Kazal-type inhibitor 1, SCTE: stratum corneum tryptic enzyme, SCCE: stratum corneum chymotryptic enzyme.

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  Fig. 4 Relationship of ichthyosis vulgaris and netherton syndrome to atopic dermatitis.

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