Skin diseases
Barrier repair trumps immunology in the pathogenesis and therapy of atopic dermatitis

https://doi.org/10.1016/j.ddmec.2008.05.006Get rights and content

Until recently, the pathogenesis of atopic dermatitis (AD) has been attributed to primary abnormalities of the immune system [1-4]. Intensive study revealed the key roles played by TH1/TH2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD (op. cit). Hence, current therapy has been largely directed towards ameliorating TH2-mediated inflammation and pruritus (e.g.[5]). In this brief review, we will assess emerging evidence that inflammation in AD results from inherited and acquired insults to the barrier, and describe the features of certain barrier-repair alternatives as therapeutic products for the treatment of AD. A recently-developed approach, based upon lipid replacement with a ceramide-dominant, triple-lipid formulation that corrects the underlying lipid biochemical abnormality, potentially represents a new paradigm for therapy of AD.

Section editor:

Michael Roberts – School of Medicine, University of Queensland, Australia

Section snippets

Normal barrier function and barrier abnormalities in atopic dermatitis

The pathogenesis of atopic dermatitis (AD) has been attributed largely to abnormalities in the adaptive immune system, with key roles played by TH1/TH2 cell dysregulation, IgE production, dendritic cell signaling, as well as mast cell hyperactivity, resulting in the pruritic, inflammatory dermatosis that characterizes AD [1]. Accordingly, current therapy has been largely directed towards ameliorating TH2-mediated inflammation and pruritus (e.g. [2]). Instead, evidence is emerging that

Therapeutic implications

Together, the converging pathogenic features described above create a strong rationale for the deployment of specific strategies to restore normal barrier function in AD. When used under nursing supervision, moisturizers have been shown to reduce topical steroid usage [36]. Immunomodulators and anti-inflammatory approaches, which until recently were considered both specific and first-line therapy, should now become ancillary and second-line (back-up approaches). Moreover, because of the

Acknowledgements

We gratefully acknowledge the superb editorial assistance of Ms Joan Wakefield, including her preparation of the graphics. This work was supported by NIH grant AR19098, DOD grant W81XWH-05-2-0094 and the Medical Research Service, Department of Veterans Affairs. No company provided support for this article.

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