New insights into atopic dermatitis

Abstract

Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.

Figure 1

Immunologic pathways in AD. Th2 cells circulating in the peripheral blood of AD patients result in elevated serum IgE and eosinophils. These T cells express the skin homing receptor, CLA, and recirculate through unaffected AD skin where they can engage allergen-triggered IgE⁺ LCs and mast cells (MCs) that contribute to Th2 cell development. Skin injury by environmental allergens, scratching, or microbial toxins activates keratinocytes to release proinflammatory cytokines and chemokines that induce the expression of adhesion molecules on vascular endothelium and facilitate the extravasation of inflammatory cells into the skin. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) and DC-derived IL-10 also enhance Th2 cell differentiation. AD inflammation is associated with increased Th2 cells in acute skin lesions, but chronic AD results in the infiltration of inflammatory IDECs, macrophages (Mφ), and eosinophils. IL-12 production by these various cell types results in the switch to a Th1-type cytokine milieu associated with increased IFN-γ expression. Figure modified with permission from The Journal of Allergy and Clinical Immunology (35).

Figure 2

Skin remodeling in AD. Van Gieson staining (original magnification, ×400) from acute AD (A) and chronic AD (B) showing extensive fibrosis in chronic, as compared to acute, AD lesions. Figures reproduced with permission from The Journal of Allergy and Clinical Immunology (8).

Figure 3

Role of chemokines in AD. (A) Chemokines activated in AD versus psoriasis. (B) Representative immunostaining for immunochemical staining of a chronic AD skin section using antibody to eotaxin (left panel; original magnification, ×400), in situ hybridization of chronic AD skin for MCP-4 using a complementary RNA radio-labeled probe. The image of mRNA-cRNA complex was developed with autoradiography. Dark field illustration shows positive signal in the epidermis of inflammatory cells (middle panel; original magnification, ×400). Immunostaining of psoriasis skin section with antibody to eotaxin shows weak staining (right panel; original magnification, ×400). TARC, thymus and activation–regulated cytokine; PARC, pulmonary and activation–regulated chemokine; GROβ, growth-related β.