Epidermal pathogenesis of inflammatory dermatoses.

It is generally assumed that dermatitis, whether of allergic or irritant origin, is primarily an immunological/inflammatory disorder. In this article, we review recent information that supports an epidermal contribution to these disorders, as well as several other dermatoses. We first review new concepts of the epidermal barrier, with recent evidence that the stratum corneum is a biosensor that regulates the epidermal lipid and DNA-metabolic responses to a variety of exogenous insults. Various signaling mechanisms, including changes in levels of epidermal cytokines and growth factors, are potential candidates to mediate these metabolic responses. Our results show that these signaling molecules may be generated not in response to permeability barrier requirements, but as an avoidable consequence of the epidermal injury that accompanies all types of acute barrier abrogation. Although the role of cytokines/growth factors as regulators of metabolic events leading to barrier recovery is still unknown, their role in initiating a cytokine cascade leading to cutaneous pathology seems more certain. We conclude that signaling molecules, released following injury to the stratum corneum, initiate a cytokine cascade that induces inflammation, which is responsible for the clinical features of specific dermatoses. Thus, 'outside-to-inside' signaling may contribute to the pathogenesis of a variety of dermatoses characterized by abnormal barrier function.