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.

Modifying skin pigmentation – approaches through intrinsic biochemistry and exogenous agents

“…Contact with certain chemicals can lead to cutaneous depigmentation [64][65][66] and a recent description of all agents that can induce depigmentation of the skin is available [67]. The majority of these agents are derivatives of phenol and catechols [68]. Generally, these agents induce chemical leucoderma (depigmentation at the contact sites), but in subjects with a genetic predisposition and chronic exposure, the initial depigmentation can extend and lead to progressive generalized vitiligo.…”

Therapeutic implications of autoimmune vitiligo T cells

“…In this respect there are many reports of melanocytes with aberrant morphology in pigmented skin from vitiligo patients, suggesting that these melanocytes are increasingly sensitive to stress [15,16]. Indeed, 'occupational vitiligo' in response to phenolic agents will occur only in a subset of individuals [17]. It appears that melanocytes from vitiligo patients will respond differently to stress: we have demonstrated that vitiligo melanocytes will release more HSP70 in response to model stressor compound 4-TBP [18].…”

Fenóis totais, atividade antioxidante e inibição da enzima tirosinase de extratos de Myracrodruon urundeuva Fr. All. (Anacardiaceae)

“…O potencial dos diferentes extratos metanólicos de M. urundeuva em sequestrar radicais livres foi expresso como con centração final do extrato necessária para inibir a oxidação do radical DPPH em 50%, e os resultados são descritos na Tabela 2. fenólicos produzidos por plantas podem interagir com a tirosinase inibindo-a ou ativando-a (Okombi et al, 2006). Existem relatos de que compostos fenólicos podem ser usados como agentes despigmentantes, pelo fato de possuírem em sua estrutura química, compostos semelhantes ao da tirosina, o substrato da tirosinase (Boissy & Manga, 2004). Portanto, a ação das substâncias utilizadas como agentes despigmentantes da pele, deve-se em parte, à ação de componentes fenólicos (Rao, 2003).…”