Vitiligo puzzle: the pieces fall in place

A review. Over the years, the role of biochem., immunol., genetic, and other biol. aspects in the pathogenesis of vitiligo has been studied. So far, no convincing model describing the interplay of these contributing factors has been formulated. Based on existing research, we propose that vitiligo has a multi-factorial etiol., characterized by multiple steps, but always involving an increase of external or internal phenol/catechol concn., serving as a preferred surrogate substrate of tyrosinase, competing with its physiol. substrate tyrosine. The conversion of these substrates into reactive quinones is reinforced by a disturbed redox balance (increasing hydrogen peroxide). Such reactive quinones can be covalently bound to the catalytic center of tyrosinase (haptenation). This could give rise to a new antigen, carried by Langerhans cells to the regional lymph node, stimulating the proliferation of cytotoxic T cells. However, the activation of such cytotoxic cells is only a first step in skin melanocyte killing, which also depends on a shift in the balance between immune defense and tolerance, e.g. resulting from a decrease in properly functioning T-regulatory cells. With this new model, based on a synthesis of several of the existing theories, in mind, the external and internal factors involved in the etiopathogenesis of vitiligo are reviewed, against the background of reported clin. data, exptl. studies and existing and potential new therapies. A similar complex mechanism may also lead to some other autoimmune diseases.