Etiopathogenesis of atopic dermatitis--an overview.

Atopic eczema/dermatitis syndrome is a term that covers different subtypes of atopic dermatitis. The "intrinsic" type of atopic dermatitis is non-IgE-associated, and the "extrinsic" type is IgE-associated atopic eczema/dermatitis syndrome. In the etiopathogenesis of atopic dermatitis there are well known interactions among genetic, environmental, skin barrier, immune factors, and stress. Genetic factors determine the expression of atopic dermatitis as pure or mixed with concomitant respiratory or intestinal allergy, depending on genetic susceptibility. Immunologic abnormalities of type I and type IV reactions have been described in patients with atopic dermatitis. Immunologic triggers are aeroallergens, food allergens, microbial products, autoallergens and contact allergens. Immune reactions determine many features of atopic dermatitis. These immune reactions also include cell mediated or delayed hypersensitivity. The currently accepted model proposes a predominant Th2 cytokine milieu in the initiating stages of acute atopic dermatitis lesions, and a mixed Th1 and Th2 pattern in chronic lesions. A two-phase model includes Th2 initiation with attraction of macrophages and eosinophils, which in turn produce interleukin 12 that is the activator of Th1 type response. Atopic dermatitis skin contains an increased number of IgE-bearing Langerhans cells which bind allergens via the high-affinity IgE receptor (FcepsilonRI). Langerhans cells play an important role in cutaneous allergen presentation to Th2 cells via major histocompatibility molecules. Eosinophilia and IgE production are influenced by type 2 cytokines. Degranulation of eosinophils occurs in the dermis with the release of toxic proteins such as major basic protein and could account for much of the inflammation. Mast cells are increased in number and produce mediators other than histamine that induce pruritus and may have an effect on interferon gamma expression. Mast cells produce a number of proinflammatory cytokines. There is an elevated production of prostaglandin E2 by peripheral monocytes. Prostaglandin E2 has at least two potential roles in the initiation of atopic dermatitis. Firstly, it reduces interferon-gamma production by T helper cells, thereby favoring the initial, dominant Th2 immune response; and secondly, it directly enhances IgE production by B lymphocytes with an increased secretion of interleukin 4, interleukin 5 and interleukin 13. Many lesions of atopic dermatitis result from scratching, thus it is tempting to speculate that immune perturbations in genetically predisposed individuals provoke the release of local pruritogens and keratinocyte-derived cytokines, which then further exacerbate the previously described immune response.