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J Allergy Clin Immunol. 1995 Sep;96(3):302-18; quiz 319.

Atopic dermatitis: the skin as a window into the pathogenesis of chronic allergic diseases.

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1
Division of Pediatric Allergy-Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.

Abstract

This review has attempted to highlight several important advances in our understanding of the immunopathogenesis of AD. These include the observation that IgE has a multifunctional role in the pathogenesis of allergic inflammation. Aside from its involvement in IgE-mediated degranulation of mast cells and basophils, it is also involved in the activation of macrophage/monocytes and the stimulation of TH2 cells. Recent data also suggest that the pattern of cytokine expression in AD depends on the acuity or duration of the skin lesion. The acute onset of skin inflammation in AD is associated with a predominance of T lymphocytes and IL-4 gene expression. In chronic AD, macrophage and eosinophil activation dominate. These effector cells overexpress IL-5, IL-10, GM-CSF, and PGE2, all of which may contribute to the persistence of this disease. Although AD is not simply "asthma of the skin," similar principles may be operative in these associated atopic diseases. Both involve local infiltration of IL-4--and IL-5--secreting TH2-like cells, and both show pathologic evidence of epithelial damage, which likely serves to amplify tissue inflammation. In the case of AD, keratinocyte damage caused by scratching or microbial agents (e.g., S. aureus) is accompanied by the release of proinflammatory cytokines. In the case of asthma, bronchial epithelial damage (e.g., damage caused by viruses or eosinophil cationic proteins) and cytokine release from airway epithelium are believed to play an important role in the pathogenesis of airway inflammation. The observation that chronic AD is associated with lichenification and dermal fibrosis, which are only slowly responsive to topical corticosteroids, is somewhat analogous to the recent concerns over airway remodeling (e.g., subepithelial airway fibrosis) is asthma and the finding that early intervention with inhaled corticosteroids is needed for optimal responses. Differences in the clinical manifestations of disease in these important target organs are likely to lie in their distinct resident cells, environment exposures that occur in the skin but not the lung, and the immune response to allergen sensitization of specialized lymphoid systems. Although the major focus of research in allergy to date has been on understanding of generic mechanisms underlying IgE regulation and action, it is well known that although IgE responses are necessary, they are not sufficient to account for the chronicity or tissue specificity of different allergic diseases.(ABSTRACT TRUNCATED AT 400 WORDS).

PMID:
7560632
DOI:
10.1016/s0091-6749(95)70049-8
[Indexed for MEDLINE]

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