title: On the etiology of contact/occupational vitiligo.
abstract: Vitiligo is an acquired depigmentary disorder of the skin that results from the selective destruction of melanocytes, generally during the second decade of life and affecting approximately 1% of the population worldwide. Loss of cutaneous pigment appears to render the skin susceptible to premature aging and cancer. In addition this disease can be socially devastating for afflicted individuals. The etiology of vitiligo is poorly understood. The present dogma suggests that genetic factors render the melanocyte fragile thus predisposing individuals to developing vitiligo. When subjected to instigating factors, these susceptible, fragile melanocytes undergo apoptosis. Autoimmune factors then perpetuate the removal of the melanocyte component from the skin. In the majority of cases the instigating factors are not known (idiopathic vitiligo), however a small sub-set of individuals develop contact/occupational vitiligo following exposure to particular chemicals. Many of these chemicals have been implicated in both contact/occupational vitiligo and chemical leukoderma. Both conditions present with well-defined, depigmented skin lesions that develop following exposure. Only in the case of vitiligo does the depigmentation spread beyond the areas of contact, probably via an immune-mediated mechanism. The largest class of chemicals known to trigger contact/occupational vitiligo is the phenolic/catecholic derivatives. Many have been demonstrated to be preferentially cytotoxic to melanocytes, with high-dose exposure resulting in the initiation of apoptosis. Phenolic/catecholic derivatives are structurally similar to the melanin precursor tyrosine, and therefore tyrosinase was originally implicated as a mediator of cytotoxicity. However, our data suggests that tyrosinase-related protein-1, rather than tyrosinase, facilitates toxicity, possibly by catalytic conversion of the compounds, which results in the generation of radical oxygen species. The ensuing oxidative stress then triggers activation of cellular free radical scavenging pathways to prevent cell death. Genetic inability of melanocytes to tolerate and/or respond to the oxidative stress may underlie the etiology of contact/occupational vitiligo.
authors.affiliation: Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0592, USA. boissyre@ucmail.uc.edu
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Boissy
authors.forename: Prashiela
authors.initials: P
authors.lastname: Manga
mesh_terms: D002396:Catechols / Q000009:adverse effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D008544:Melanocytes / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D015394:Molecular Structure; D016273:Occupational Exposure; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010088:Oxidoreductases / Q000378:metabolism; D010636:Phenols / Q000009:adverse effects* / Q000378:metabolism; D014820:Vitiligo / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism
chemical_list: D002396:Catechols; D008562:Membrane Glycoproteins; D010636:Phenols; D010088:Oxidoreductases; C489799:TYRP1 protein, human