Irritant dermatitis, irritancy and its role in allergic contact dermatitis

Irritant contact dermatitis is the clinical result of sufficient inflammation arising from release of pro-inflammatory cytokines from skin cells (principally keratinocytes) in response to (usually) chemical stimuli. Different clinical forms may arise. The three main pathophysiological changes seen are skin barrier disruption, epidermal cellular changes and cytokine release. An important role of irritancy in allergic contact dermatitis (ACD) comes from earlier animal and human studies. Evidence is outlined which is consistent with a "danger model" of ACD rather than one based on a traditional "self-nonself" immune model. In such a model an antigenic signal will produce sensitization only in the presence of a danger signal; in the absence of a danger signal tolerance will occur. We propose that the danger signal in ACD is cytokine release from nonimmune skin cells (principally keratinocytes) and that both the antigenic and "danger" signals arises from the hapten.