Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis
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Vol. 22, No. 3, 2010 245Received April 13, 2010, Revised June 18, 2010, Accepted for publication June 21, 2010*This work was supported by NIH grants R01-AR019098 and R01-AI059311, DOD grant W81XWH-05-2-0094, and the Medical Research Service, Department of Veterans Affairs. Dr. Matthias Schmuth, Chairman, Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria provided multiple insights that substantially improved the content of this manuscript. Joan Wakefield provided superb editorial assistance. Corresponding author: Peter M. Elias, M.D., 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:eliasp@derm.ucsf.edu Ann Dermatol Vol. 22, No. 3, 2010 DOI: 10.5021/ad.2010.22.3.245REVIEW ARTICLE Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis Peter M. Elias, M.D. Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, CA,USA 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. (Ann Dermatol 22(3) 245∼254, 2010)
Abstract
Vol. 22, No. 3, 2010 245Received April 13, 2010, Revised June 18, 2010, Accepted for publication June 21, 2010*This work was supported by NIH grants R01-AR019098 and R01-AI059311, DOD grant W81XWH-05-2-0094, and the Medical Research Service, Department of Veterans Affairs. Dr. Matthias Schmuth, Chairman, Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria provided multiple insights that substantially improved the content of this manuscript. Joan Wakefield provided superb editorial assistance. Corresponding author: Peter M. Elias, M.D., 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:eliasp@derm.ucsf.edu Ann Dermatol Vol. 22, No. 3, 2010 DOI: 10.5021/ad.2010.22.3.245REVIEW ARTICLE Therapeutic Implications of a Barrier-based Pathogenesis of Atopic Dermatitis Peter M. Elias, M.D. Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, CA,USA 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. (Ann Dermatol 22(3) 245∼254, 2010)
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