Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment.

Vitiligo is a cosmetically disfiguring condition, and, although there is no therapeutic full solution yet, some treatment may induce good results in most patients. The disease can be successfully treated with various medical options. Both nonfocused or focused narrowband ultraviolet B phototherapy represents the current treatment of choice, to minimize side effects and reach optimal clinical results. Topical novel approaches are also considered. Surgical methods, consisting of autologous transplantation methods, is generally recommended for focal/stable vitiligo, after medical therapy has failed. Finally, for patients with extensive vitiligo, depigmentation of the residual melanin should be taken into account.

Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo.

Behçet's disease is a multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. The cause of Behçet's disease remains unknown, but epidemiologic findings suggest that an autoimmune process is triggered by an environmental agent in a genetically predisposed individual. An infectious agent could operate through molecular mimicry, and subsequently the disease could be perpetuated by an abnormal immune response to an autoantigen in the absence of ongoing infection. Potentia bacterial are Saccharomyces cerevisiae, mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphylococcus aureus, and Mycoplasma fermentans, but the most commonly investigated microorganism is Streptococcus sanguinis. The relationship between streptococcal infections and Behçet's disease is suggested by clinical observations that an unhygienic oral condition is frequently noted in the oral cavity of Behçet's disease patients. Several viral agents, including herpes simplex virus-1, hepatitis C virus, parvovirus B19, cytomegalovirus, Epstein-Barr virus and varicella zoster virus, may also have some role.

Phyllanthus emblica, vitamin E, and caroteinods are compounds showing antioxidative, anti-inflammatory, and repigmenting effects, whose role in vitiligo treatment has not been evaluated so far. Sixty-five subjects (group A) were treated with one tablet of an oral supplement containing P. emblica (100 mg), vitamin E (10 mg), and carotenoids (4.7 mg) three times/day for 6 months and compared with a control group (group B, 65 patients), which instead was not treated with antioxidants. Both groups were simultaneously treated with a comparable topical therapy and/or phototherapy. After a 6 months follow-up, a significantly higher number of patients in group A had a mild repigmentation on the head/neck regions (p = 0.019) and on the trunk (trend, p = 0.051). The number of patients who presented no repigmentation in head/neck, trunk, upper, and lower limbs was significantly higher in group B (respectively, p = 0.009, p = 0.001, p = 0.001, p = 0.025). Moreover, group B patients showed higher signs of inflammation (p = 0.002), a more rapid growth of the lesions (p = 0.039), a higher percentage of worsening disease (p = 0.003), and more erythema (p = 0.059), whereas group A patients showed a higher percentage of steady disease (p = 0.065). Our results suggest that the supplement with antioxidants in patients with vitiligo might represent a valuable instrument to increase the effectiveness of other vitiligo treatments. [Correction added after online publication 06-Oct-2014: the dosages of vitamin E and carotenoids have been updated.].