Review of Atopic Dermatitis
Review of Atopic Dermatitis
The author of a thorough review of atopic dermatitis (AD) in the New England Journal of Medicine discusses the epidemiology and clinical presentation of AD; the issue of pruritus; the contributions of genetics, allergens, disrupted barrier function, immunopathologic mechanisms, dendritic cells, T cells, Staphylococcus aureus, and immunoglobulin E (IgE) autoantibodies; and goals for prevention and therapy.
The hallmarks of AD include disrupted skin barrier resulting in dry skin; chronic, relapsing skin inflammation; pruritus; and increased IgE sensitization to food and environmental allergens. AD is a complex genetic disease that arises from gene–gene and gene–environment interactions. Mutations exist in two gene groups: those encoding epidermal or other epithelial structural proteins (e.g., filaggrin mutations) and those encoding major elements of the immune system (e.g., increased Th2 cytokine production).
Currently, two hypotheses attempt to explain the AD mechanism. The first proposes that an innate immunologic disturbance leads to IgE sensitization, which later results in disruption of the epithelial barrier. The second proposes that an intrinsic epithelial cell defect leads to barrier disruption and that the immunologic imbalance is an epiphenomenon.
AD is a biphasic T-cell–mediated disease. In acute AD, the Th2 profile predominates, with increases in interleukin (IL)-4, IL-5, and IL-13. In chronic AD, a Th1 dominance develops, with increases in IFN-γ, IL-12 and IL-5, and granulocyte-macrophage colony-stimulating factor. Even normal-appearing skin in AD patients may harbor a mild inflammatory infiltrate.
The innate immune system is impaired in AD. Decreased antimicrobial peptides result in increased S. aureus colonization. Scratching leads to increased S. aureus binding to the skin. Staph enterotoxins are proinflammatory, they inhibit regulatory T cells, and they increase the competing β-isoform of glucocorticoid receptors in mononuclear cells, leading to resistance to local corticosteroid treatment in lesional skin.
A triphasic natural history of AD was recently proposed. Phase I occurs in early infancy before IgE sensitization develops; 60% to 80% of affected infants (who are likely genetically predisposed) go on to develop IgE sensitization to food, environmental allergens, or both (phase II). Chronic scratching of severe AD sometimes leads to phase III, the development of IgE autoantibodies against proteins of keratinocytes and endothelial cells.
AD is as complex as it is commonplace. Proper treatment must include hydration of the skin, avoidance of triggers, decreased bacterial colonization or infection, and proper anti-inflammatory medications (topical steroids and calcineurin inhibitors). Aggressive management of acute flares is important. Minimization of staph colonization may improve local steroid responsiveness. Maintenance antimicrobial measures, such as dilute-bleach baths, are effective and safer than triclosan. Some patients may require maintenance topical anti-inflammatory medication between flares.