New Insights and New Therapies in Vitiligo

Abstract

VITILIGO IS A RELATIVELY COMmon, acquired pigmentary disorder characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. The prevalence of this disease varies from 0.1% to 2% in various global populations. Onset may occur at any age, but the incidence usually peaks in the second and third decades of life. Patterns of distribution of the disease include the generalized, acral or acrofacial, localized, and segmental types. The generalized distribution is the most common pattern and is characterized by symmetrically distributed areas of depigmentation. Segmental vitiligo is the least common pattern and occurs in a dermatomal or quasi-dermatomal distribution, often following the distribution of the trigeminal nerve. The course of the disease is unpredictable. Vitiliginous skin lesions may remain stable or slowly progress for years. In some instances, however, patients undergo rapid, complete depigmentation in 1 or 2 years. The disease shows no racial, ethnic, or socioeconomic predilection. However, given the contrast between the depigmented areas and healthy skin, the disease ismostdisfiguring indarkerracial or ethnic groups. Vitiligo is one of the most psychologically devastating skin diseases. The psychological effects of vitiligo are influenced and exacerbated by societal perceptions of skin disfigurement and irregularities in skin color. Patientswithvitiligoexperience lowselfesteem, job discrimination, depression, and embarrassment in social and sexual relationships. Genetic studies support a nonmendelian inheritance pattern for vitiligo and suggest that vitiligo is a multifactorial, polygenic disorder. Twenty percent to 30% of patients report vitiligo in firstand second-degree relatives. The disease has been associated with specific HLA haplotypes including HLA-DR4, Dw7, DR7, DR1, B13, Cw6, DR53, and A19; however, haplotypes may vary considerably with the population studied. Recently, a genome-wide linkage scan was performed in 71 white multiplex families with vitiligo. Linkage was assessed by a multipoint nonparametric linkage analysis. AIS1 located at 1p31 showed highly significant linkage, suggesting that it is a major susceptibility locus in whites. Additional signals on chromosomes 1, 7, 8, 11, 19, and 22 have met genome criteria for suggestive linkage. Other candidate genes reported to mediate vitiligo susceptibility include the catalase gene, VIT1 at chromosome 2p16, and the guanosine triphosphate cyclohydrolase I gene.