The Role of Sweat in the Pathogenesis of Atopic Dermatitis

Abstract

Although atopic dry skin is believed to be caused by defects in skin genes that are important for maintaining skin barrier function, the role of sweat has been apparently underestimated despite its great capacity to increase skin hydration. It has become clear that sweating responses can be divided into two types depending on their functions. Under baseline conditions, sweat glands/ducts located at the dermal folds secrete basal levels of sweat in an unrecognized fashion, which is referred to as “insensible” sweating and could serve to maintain skin hydration. In contrast, another type of sweating is called “sensible” sweating that is induced by physical exercise and hot/humid environment and could function as a major thermoregulator: this type of sweating is largely delivered from sweat glands/ducts at the dermal ridges. Atopic dermatitis (AD) would initially arise from a localized defect in “insensible” sweating responses from sweat glands/ducts at the folds: this defect could start with leakage of sweat from the glands/ducts, thereby not only providing an inflammatory milieu but also resulting in dry skin. As a next step, compensatory hyperhidrosis would occur preferentially in the sweat glands/ducts at the ridges, which may exacerbate the inflammatory responses. In the final stage, patients eventually manifest the phenotype with systemic hypohidrosis. This three-stage model for the pathogenesis of AD has significant implications both in terms of future research and therapies. Therapies directed at correcting the defects at early times, while ameliorating inflammatory responses, may prove efficacious for preventing further progression of the disease.