Atopic dermatitis: recent trends in pathogenesis and therapy

Abstract

Emerging concepts in the areas related to the pathogenesis and treatment of atopic dermatitis are reviewed. In particular, recent findings have revealed several key steps in the maintenance of a vicious circle of spongiotic dermatitis associated with elevated T-lymphocyte activation, hyperstimulatory Langerhans cells, defective cell-mediated immunity, and B-cell IgE overproduction. The discovery of specific IgE-binding structures on Langerhans cells provides a mechanism for Langerhans cells to capture and present IgE-targeted allergens to allergen-specific T cells. Furthermore, certain microbial allergens that tend to preferentially elicit IgE-type responses also elicit a T-cell response dominated by the IgE-inducing lymphokine interleukin 4. Repeated stimulation by activated Langerhans cells appears to induce just such a response. Abnormal biochemical responsiveness and mediator release by AD monocytes, mast cells, and eosinophils also participate in the sustainment or initiation of such a vicious circle, and contribute directly to the dermatitis as well. Developments in the areas of neuropeptides, genetics, microbial superantigens, and cytokine networks in the skin also appear to have promise in providing a rational link between immune defects and the inflammatory events in AD. Conventional therapy remains the mainstay of atopic dermatitis management; however, new therapies based upon the above concepts are being tested in clinical trials. Although the difficulty of objectively grading AD lesional activity and the high placebo response of AD patients hampers the interpretation of many reports, several types of approaches are coming into focus. The effectiveness of cyclosporin A, which targets T-cell activation and antigen presentation, indicates that additional agents with such activity should be effective, and verifies the criticality of these cells in AD pathogenesis. Therapy with biologic response modifiers, such as interferon gamma or thymopentin, is oriented toward normalization of imbalanced immune responsiveness, rather than direct suppression of the immune system. The mechanism of action of and toxicities of Chinese herbal mixtures require further investigation, but may reveal hitherto unconsidered avenues. Other recent therapeutic trials have focused on reduction of trigger factors, such as house dust mite exposure, foods, and the abnormal epidermal lipid barrier to irritation.