Significance of Skin Barrier Dysfunction in Atopic Dermatitis

Atopic dermatitis (AD) is the most common chronic skin disease worldwide. It affects about 20% of children and 5% of adults. Patients with persistent or severe AD suffer from profound impairment of their quality of life. Additionally, AD places a heavy economic burden on patients and their family. AD is strongly associated with the development of food allergy, bronchial asthma, and allergic rhinitis, commonly referred to as the Atopic March. The epidermis provides a physical and functional barrier to the human body, and skin barrier defects are the most important pathologic findings in AD skin. Skin barrier defects have been considered an initial step in developing AD. Recently, investigators have demonstrated that multiple factors, including immune dysregulation, defects in terminal epithelial differentiation such as lack of filaggrin (FLG), deficiency of antimicrobial peptides (AMPs), altered composition of stratum corneum intercellular lipids, and altered skin microbiome may affect skin barrier function (Fig. 1). These factors interact with each other and may modify skin barrier function. In this review, we discuss normal skin barrier and pathogenesis of skin barrier defects associated with the development of AD skin disease. Additionally, we review the role of emollients, anti-inflammatory agents, sodium hypochlorite, probiotics, and microbiome in the treatment and prevention of AD development. Moreover, various types of immune-directed targets for biologic therapy are reviewed. Normal skin barrier The skin barrier plays a critical role in preventing allergen and microbial penetration into the human body. The epidermis consists of a 15to 30-nm-thick layer of proteins and lipids, and provides a physical and functional barrier to the human body. The physical skin barrier is mainly localized to the uppermost area of the epidermis which is the cornified layer (stratum corneum). The epidermis is continuously regenerated by terminally differentiating keratinocytes, which is known as cornification or keratinization. Cornification begins with the migration of keratinocytes from the basal to upper layers, and ends with the formation of the cornified layer. During epidermal differentiation, lipids are produced by keratinocytes and extruded into the extracellular space to form extracellular lipid-enriched layers. Omega-hydroxy-ceramides are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids, and cholesterol in the cornified layer. The epidermis undergoes complete turnover every 28 days. Cell proliferation, differentiation, and death occur sequentialReview Allergy Asthma Immunol Res. 2018 Forthcoming. Posted online 2018 pISSN 2092-7355 • eISSN 2092-7363