Atopic dermatitis: immunobiology and treatment with immune modulators.

Atopic dermatitis (AD), a chronic inflammatory skin disease, is frequently seen in patients with a personal or family history of asthma and allergic rhinitis. Population studies suggest an increasing prevalence of AD in children since World War II, with 10-15% of the population being affected by AD at some time during childhood. In patients with moderate to severe AD, involvement can be life-long, causing significant interference with school, work and social interactions. The term atopic dermatitis was introduced to reflect the close association between AD and respiratory allergy. During the past decade, extraordinary progress has been made in our understanding of the immunopathogenesis of allergic diseases. In particular, this constellation of inherited illnesses has now been demonstrated to be associated with activation of a specific group of cytokine genes encompassing IL-3, IL-4, IL-5, IL-13 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The molecular basis for selective activation of this cytokine gene cluster and the immunological consequences are now being pursued actively by many laboratories. However, it is clear that allergic diseases result from a polygenic inheritance pattern which involves not only cytokine gene activation but also activation of other less well defined gene products. Furthermore, the clinical expression of allergic diseases is highly dependent on a complex interaction between the host and its environment, e.g. allergen exposure. The genetic predisposition to develop allergic responses may be similar in patients with AD and other allergic diseases, such as asthma. However, targeting of the allergic immune response may relate to the organ in which allergen sensitization first occurs; the capacity of immune effector cells, e.g. T lymphocytes, to home preferentially to the skin versus the respiratory mucosa; and the programmed response of resident cells, e.g. epithelial cells, to injury and inflammation. This review examines the cellular and immunological mechanisms that are thought to play an important role in the pathogenesis of chronic AD. An understanding of the immunological basis of AD is likely to have important clinical implications in our approach to the management of this common illness, and the development of immunomodulators for its treatment.