The etiology of atopic dermatitis is not fully known. Food and airborne allergens, entering through mucosal surfaces or breaks in the skin, may exacerbate eczematous lesions after reaching cutaneous mast cells, monocytes, and Langerhans cells (antigen-presenting cells) by way of the circulation. The interaction of allergens with allergen-specific IgE on the surface of mast cells and Langerhans cells leads to the release of a variety of inflammatory mediators. Mast cells release histamine, leukotriene C₄ (LTC₄), platelet-activating factor, tryptase, cytokines (IL-4 and IL-13 promote IgE synthesis, upregulation of FcεI receptors on mast cells and antigen-presenting cells, and vascular cell adhesion molecule 1 [VCAM-1] expression on vascular endothelial cells; IL-5 attracts and activates eosinophils), and other factors that attract and activate inflammatory cells (e.g., lymphocytes and monocytes). IgE-bearing Langerhans cells have been shown to be highly efficient in activating Th2-type lymphocytes. Repeated allergen exposure provokes chronic inflammation, secondary to IgE-mediated mast cell and lymphocytic responses and contributes to the pathogenesis of atopic dermatitis. CD4⁺ T_h2 lymphocytes specific for various allergens (e.g., milk, peanuts, dust mites, grass pollen) have been cloned from the eczematous lesions of patients with atopic dermatitis, implicating these allergens in the pathogenesis of lesional skin.

Skin biopsies from the chronic eczematous lesions of patients with atopic dermatitis also reveal large quantities of major basic protein, secreted by eosinophils, in the superficial dermis; this indicates that eosinophils were in the area, whereas actual eosinophils may be seen in more acute lesions. Major basic protein is not seen in uninvolved skin sites in these same patients or in the lesions of patients with contact dermatitis. In one study, food-allergic subjects developed a pruritic, erythematous, morbilliform rash and elevation of plasma histamine levels after double-blind, placebo-controlled food challenges. Skin biopsy specimens obtained 4 to 14 hours later revealed an infiltration of eosinophils and major basic protein deposition, which indicated that food allergen–induced mast-cell activation triggered both an immediate and a late-phase response in the skin. Another eosinophil product, eosinophil-derived neurotoxin, may be responsible for the demyelination of nerves in the dermal layer seen in eczematous skin.

Inhalant allergens (pollens, molds, and dust mites) also may play a role in IgE-induced pathology. Normal individuals passively sensitized to ragweed absorb sufficient pollen allergen
via nasal challenge to produce a wheal-and-flare response at a distal skin site. In addition, eczematous skin changes have been provoked by bronchial challenges in some dust mite–sensitive patients. Using a modified patch technique with dust mite antigen, the infiltration of antigen-specific CD4⁺ Th2 lymphocytes, eczematous changes and, later, increased mast-cell numbers have been induced in patients with IgE antibodies to dust mites.

In addition to allergen IgE–initiated immediate and late-phase hypersensitivity responses, histamine-releasing factors (e.g., lymphokines, monokines) have been discovered that bind to surface-bound IgE molecules and activate mast cells and basophils, leading to the release of various cytokines and inflammatory mediators. IgE autoantibodies also have been found in approximately 80% of patients with atopic disorders. Because low-affinity IgE receptors (FcεII) have been found on B cells, T cells, monocytes, macrophages, eosinophils, and platelets, histamine-releasing factors and IgE autoantibody immune complexes may affect a number of immunologic responses and provoke inflammation.

Atopic dermatitis is a chronic cutaneous inflammatory disorder that typically begins in early infancy. The skin symptoms generally present as an erythematous, papulovesicular eruption that progresses to a scaly, lichenified dermatitis over time. The distribution of the rash typically varies with age:

Unlike most dermatoses, atopic dermatitis has no primary skin lesion but is identified by a constellation of symptoms. The classification system proposed by Hanifin and Rajka (Box 423.1) remains an internationally accepted criterion for diagnosing atopic dermatitis. A modification of this criterion for the young infant is outlined in Box 423.2. Emphasis is placed on the extremely pruritic nature of the rash, its typical morphology and distribution, and its tendency toward a chronic or relapsing course. Some features, such as anterior subcapsular cataracts, nipple eczema, and upper lip cheilitis are uncommon but more specific for the diagnosis of atopic dermatitis. Other symptoms such as allergic shiners, Dennie-Morgan infraorbital folds, and hyperlinearity of the palms are common but less specific.