Pathophysiology of atopic dermatitis: Clinical implications

Abstract

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Genetic predisposition, epidermal barrier disruption, and dysregulation of the immune system are some of the critical components of AD. An impaired skin barrier may be the initial step in the development of the atopic march as well as AD, which leads to further skin inflammation and allergic sensitization. Type 2 cytokines as well as interleukin 17 and interleukin 22 contribute to skin barrier dysfunction and the development of AD. New insights into the pathophysiology of AD have focused on epidermal lipid profiles, neuroimmune interactions, and microbial dysbiosis. Newer therapeutic strategies focus on improving skin barrier function and targeting polarized immune pathways found in AD. Further understanding of AD pathophysiology will allow us to achieve a more precision medicine approach to the prevention and the treatment of AD.

Figure 1.

Effects of cytokines on epidermis in AD. Disrupted epidermal barrier and environmental triggers stimulate keratinocytes to release IL-1β, IL-25, IL-33, MDC, TARC, and TSLP, which activate dendritic cells and Langerhans cells. Activated dendritic cells stimulate Th2 cells to produce IL-4, IL-5, IL-13, IL-31, and IL-33, which leads to barrier dysfunction, decreased AMP production, impaired keratinocyte differentiation, and itch symptoms. Chronic AD is characterized by recruitment of Th1, Th22, and Th17 subsets, which results in epidermal thickening and abnormal keratinocyte proliferation. AD = atopic dermatitis; AMP = antimicrobial peptide; DC = dendric cell; IFN = interferon; IL = interleukin; KC = keratinocyte; LC = Langerhans cell; MDC = macrophage-derived chemokine; S100A = S100 calcium-binding protein A; Th = T-helper type; TARC = thymus and activation-regulated chemokine; TSLP = thymic stromal lymphopoietin.

Figure 2.

Prevention and treatment of AD. Skin barrier defects are the initial steps in the development of AD. Moisturizer prevents skin barrier defects and inhibits Staphylococcus aureus colonization in the skin. Oral probiotics may prevent the development of AD and correct gut microbial dysbiosis. Various biologics, e.g., dupilumab, target immune dysregulation. Antibiotics, bleach batch, and skin microbiome transplantation inhibit S. aureus colonization and improve cutaneous dysbiosis. AD = atopic dermatitis; Th = T helper.