Evolving concepts of pathogenesis in atopic dermatitis and other eczemas

The Journal of Investigative Dermatology
Jon M Hanifin

Abstract

The eczemas represent a common and diverse group of inflammatory skin diseases whose definitions and pathogenic mechanisms have often been confused and controversial. Since the millennium, fresh approaches are providing better insight. Research has focused much more upon the epidermis and the very relevant signaling pathways that contribute to spongiosis, proliferation, generation of proinflammatory factors, and differentiation to form an effective stratum corneum barrier. A major step in understanding has come from the solidly confirmed association between filaggrin null mutations of ichthyosis vulgaris and atopic dermatitis. Similar associations relating to protease and lipid defects have highlighted the role of barrier disruption that allows greater access of environmental toxins, microbes, and allergens. Animal models are beginning to predict mechanisms in which such direct perturbation of keratinocytes may initiate inflammation and condition immune responses in irritant contact dermatitis and atopic dermatitis. These conceptual shifts are nurturing more balanced approaches to understanding eczema and hold the hope for better prevention efforts and more specific molecular targeting for therapy.

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