Can excessive washing really be regarded as the major cause of atopic dermatitis?

Abstract

I read with interest the Opinion article by Callard and Harper published in the July 2007 issue of Trends in Immunology [1xThe skin barrier, atopic dermatitis and allergy: a role for Langerhans cells?. Callard, R.E. and Harper, J.I. Trends Immunol. 2007; 28: 294–298Abstract | Full Text | Full Text PDF | PubMed | Scopus (49)See all References][1]. Based on the observation that removal of the skin barrier by tape stripping results in dominant Th2 responses to protein antigens, the authors propose that lifestyle choices that result in loss of integrity of the skin barrier, such as excessive washing and exfoliation of the skin, could result in atopic dermatitis. In this way, the authors explain the higher prevalence of atopic dermatitis in the developed world. However, this view is not compatible with the clinical features of the disease. The lesions of atopic dermatitis frequently start on the face. When a child begins to crawl, the extensor aspects of the knees are the most affected. From 18 to 24 months onward, the most characteristically affected sites are the elbow and knee flexures, the sides of the neck, the wrists, and the ankles. Though other body regions may be afftected, the area around the diapers, which is most frequently washed, is relatively spared [2xAtopic dermatitis. Friedmann, P.S. and Holden, C.A. : 18.1–18.31See all References][2], which would therefore argue against the pathomechanism put forward by Callard and Harper. This would indicate that excessive washing is not the cornerstone of the pathobiology of atopic dermatitis, although it may contribute to it. Another criticism regarding this paper is that the authors try to explain the potent induction of Th2 responses by application of antigen to the epidermis devoid of the stratum corneum by speculating that, in the absence of additional inflammatory or “danger” signals, Langerhans cells, which have taken up antigen, preferentially initiate a Th2 response after migration to the draining lymph node. It is known that antigen presentation in the absence of danger signals leads to tolerance, not to an immune response [3xCell death and autoimmunity. Casiano, C.A. and Pacheco, F.J. : 107–137Crossref | Scopus (6)See all References][3]. However, it is demonstrated that barrier damage induced, for example, by skin stripping causes the release and production of cytokines, such as IL-1α, IL-1β, and TNF-α, indicating that barrier disruption alone leads to cytokine production and inflammation [4xNew perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions. Cork, M.J. et al. J. Allergy Clin. Immunol. 2006; 118: 3–21Abstract | Full Text | Full Text PDF | PubMed | Scopus (321)See all References][4]. Moreover, in the absence of stratum corneum, the increased penetration of allergens through the epidermis could promote the initiation of an inflammatory response within the stratum granulosum by inducing the release of proinflammatory cytokines from keratinocytes [5xEpidermal pathogenesis of inflammatory dermatoses. Elias, P.M. et al. Am. J. Contact Dermatitis. 1999; 10: 119–126Crossref | PubMed | Scopus (176)See all References][5].The paper by Callard and Harper is interesting because it can provide an explanation for the transformation of the eczematous response from the Th2 type in the acute phase into the Th1 type in the chronic phase [2xAtopic dermatitis. Friedmann, P.S. and Holden, C.A. : 18.1–18.31See all References][2]. Because breaching the integrity of the epidermis allows antigen presentation by dermal dendritic cells that produce Th1 responses, it could be speculated that these cells are responsible for the Th1 response of the chronic phase of eczema because they present antigens that have gained access to the dermis as the result of breakage of the epidermis. By contrast, presentation of antigens in the acute phase of eczema by Langerhans cells leads to the development of the Th2 response observed in this phase of the illness.