Significance of Skin Barrier Dysfunction in Atopic Dermatitis

Abstract

The epidermis contains epithelial cells, immune cells, and microbes which provides a physical and functional barrier to the protection of human skin. It plays critical roles in preventing environmental allergen penetration into the human body and responsing to microbial pathogens. Atopic dermatitis (AD) is the most common, complex chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Multiple factors, including immune dysregulation, filaggrin mutations, deficiency of antimicrobial peptides, and skin dysbiosis contribute to skin barrier defects. In the initial phase of AD, treatment with moisturizers improves skin barrier function and prevents the development of AD. With the progression of AD, effective topical and systemic therapies are needed to reduce immune pathway activation and general inflammation. Targeted microbiome therapy is also being developed to correct skin dysbiosis associated with AD. Improved identification and characterization of AD phenotypes and endotypes are required to optimize the precision medicine approach to AD.

Current and emerging therapies for hand eczema

“…Skin barrier dysfunction in AD and HE is associated with reductions in ceramides (especially ceramides EOP and NP) in the stratum corneum, as well as the expression of enzymes involved in lipid metabolism, which leads to skin barrier defects (Belsito et al, ; Bieber, ; Di Nardo, Wertz, Giannetti, & Seidenari, ; Schmid‐Wendtner & Korting, ). Cytokines such as Type 2 helper T cells (Th2) and Th22 are overexpressed in the skin of AD patients, and function to alter lipid and protein content, down‐regulate tight junctions, and inhibit antimicrobial peptides (AMPs), all of which regulate the skin barrier (De Benedetto et al, ; Hamid, Boguniewicz, & Leung, ; Kim & Leung, ; Ong et al, ; Proksch, Brandner, & Jensen, ). Barrier dysfunction portends increased transepidermal water loss (TEWL) and cutaneous penetration of irritants, allergens, and microbial agents, such as Staphylococcus aureus (Boguniewicz & Leung, ; Kim & Leung, ; Proksch & Brasch, ; Proksch, Folster‐Holst, & Jensen, ).…”

“…Skin barrier dysfunction in AD and HE is associated with reductions in ceramides (especially ceramides EOP and NP) in the stratum corneum, as well as the expression of enzymes involved in lipid metabolism, which leads to skin barrier defects (Belsito et al, 2004;Bieber, 2008;Di Nardo, Wertz, Giannetti, & Seidenari, 1998;Schmid-Wendtner & Korting, 2006 Brandner, & Jensen, 2008). Barrier dysfunction portends increased transepidermal water loss (TEWL) and cutaneous penetration of irritants, allergens, and microbial agents, such as Staphylococcus aureus (Boguniewicz & Leung, 2011;Kim & Leung, 2018;Proksch & Brasch, 1997;Proksch, Folster-Holst, & Jensen, 2006).…”

The IL‐13–OVOL1–FLG axis in atopic dermatitis

“…Skin barrier function is disrupted in AD compared with that in normal controls . The epidermal barrier is formed by the coordinated and sequential cross‐linking of epidermal differentiation molecules such as FLG and intercellular lipids and corneocyte adhesion .…”

“…Skin barrier function is disrupted in AD compared with that in normal controls. [47][48][49] The epidermal barrier is formed by the coordinated and sequential cross-linking of epidermal differentiation molecules such as FLG and intercellular lipids and corneocyte adhesion. [47][48][49] The expression of FLG and the other differentiation molecules loricrin and involucrin is down-regulated or expressed prematurely in the lesional and non-lesional skin of AD compared with their expression in the normal skin of healthy individuals.…”

“…[47][48][49] The epidermal barrier is formed by the coordinated and sequential cross-linking of epidermal differentiation molecules such as FLG and intercellular lipids and corneocyte adhesion. [47][48][49] The expression of FLG and the other differentiation molecules loricrin and involucrin is down-regulated or expressed prematurely in the lesional and non-lesional skin of AD compared with their expression in the normal skin of healthy individuals. 7,50,51 As the daily application of moisturizer during the first 32 weeks of life reduces the risk of AD in infants, 52 skin barrier dysfunction is essential to the development of AD.…”