Vitiligo is an acquired depigmenting disorder that affects 0.5% to 2% of the world population. Three different forms are classified according to the distribution of lesions; namely non-segmental, segmental and mixed vitiligo. Vitiligo is associated with polymorphisms in genes involved in the immune response and in melanogenesis. However, environmental factors are required for the development of manifest disease. In general, the diagnosis is clinical and no laboratory tests or biopsies are required. Metabolic alterations are central to current concepts in pathophysiology. They induce an increased generation of reactive oxygen species and susceptibility to mild exogenous stimuli in the epidermis. This produces a senescent phenotype of skin cells, leads to the release of innate immune molecules, which trigger autoimmunity, and ultimately causes dysfunction and death of melanocytes. Clinical management aims to halt depigmentation, and to either repigment or depigment the skin, depending on the extent of disease. New therapeutic approaches include stimulation of melanocyte differentiation and proliferation through α-melanocyte-stimulating hormone analogues and through epidermal stem cell engineering. Several questions remain unsolved, including the connection between melanocyte depletion and stem cell exhaustion, the underlying degenerative mechanisms and the biological mediators of cell death. Overall, vitiligo is an excellent model for studying degenerative and autoimmune processes and for testing novel approaches in regenerative medicine. For an illustrated summary of this Primer, visit: http://go.nature.com/vIhFSC
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Gauthier, Y. et al. in Vitiligo. Ch.1.1 (eds Picardo, M. & Taïeb, A. ) 3–10 (Springer, 2010).
Nair, B. K. Vitiligo—a retrospect. Int. J. Dermatol. 17, 755–757 (1978).
Ezzedine, K. et al. Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference. Pigment Cell Melanoma Res. 25, E1–E13 (2012). This is the last consensus document on vitiligo classification and management from the International Vitiligo Conference.
Ezzedine, K. et al. Segmental vitiligo associated with generalized vitiligo (mixed vitiligo): a retrospective case series of 19 patients. J. Am. Acad. Dermatol. 65, 965–971 (2011).
Prignano, F., Betts, C. M. & Lotti, T. Vogt-Koyanagi-Harada disease and vitiligo: where does the illness begin? J. Electron. Microsc. 57, 25–31 (2008).
Park, S., Albert, D. M. & Bolognia, J. L. Ocular manifestations of pigmentary disorders. Dermatol. Clin. 10, 609–622 (1992).
Anbar, T. S., El-Badry, M. M., McGrath, J. A. & Abdel-Azim, E. S. Most individuals with either segmental or nonsegmental vitiligo display evidence of bilateral cochlear dysfunction. Br. J. Dermatol. 172, 406–411 (2014).
Ozuer, M. Z., Sahiner, T., Aktan, S., Sanli, B. & Bayramoglu, I. Auditory evoked potentials in vitiligo patients. Scand. Audiol. 27, 255–258 (1998).
Angrisani, R. M., Azevedo, M. F., Preira, L. D., Lopes, C. & Garcia, M. V. A study of otoacoustic emissions and suppression effects in patients with vitiligo. Braz. J. Otorhinolaryngol. 75, 111–115 (2009).
Silverberg, N. B. Update on childhood vitiligo. Curr. Opin. Pediatr. 22, 445–452 (2010).
Hann, S. K. & Lee, H. J. Segmental vitiligo: clinical findings in 208 patients. J. Am. Acad. Dermatol. 35, 671–674 (1996).
Taïeb, A., Picardo, M. & VETF Members. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res. 20, 27–35 (2007).
van Geel, N. et al. New insights in segmental vitiligo: case report and review of theories. Br. J. Dermatol. 166, 240–246 (2012).
Howitz, J., Brodthagen, H., Schwartz, M. & Thomsen, K. Prevalence of vitiligo. Epidemiological survey on the Isle of Bornholm, Denmark. Arch. Dermatol. 113, 47–52 (1977).
Boisseau-Garsaud, A. M. et al. Epidemiology of vitiligo in the French West Indies (Isle of Martinique). Int. J. Dermatol. 39, 18–20 (2000).
Behl, P. N. & Bhatia, R. K. 400 cases of vitiligo. A clinico-therapeutic analysis. Indian. J. Dermatol. 17, 51–56 (1972).
Sehgal, V. N. & Srivastava, G. Vitiligo: compendium of clinico-epidemiological features. Indian J. Dermatol. Venereol. Leprol. 73, 149–156 (2007).
Wang, X. et al. Prevalence and clinical profile of vitiligo in China: a community-based study in six cities. Acta Derm. Venereol. 93, 62–65 (2013).
Singh, M., Singh, G., Kanwar, A. J. & Belhaj, M. S. Clinical pattern of vitiligo in Libya. Int. J. Dermatol. 24, 233–235 (1985).
Alikhan, A., Felsten, L. M., Daly, M. & Petronic-Rosic, V. Vitiligo: a comprehensive overview Part, I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J. Am. Acad. Dermatol. 65, 473–491 (2011).
Al-Refu, K. Vitiligo in children: a clinical-epidemiologic study in Jordan. Pediatr. Dermatol. 29, 114–115 (2012).
Krüger, C. & Schallreuter, K. U. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int. J. Dermatol. 51, 1206–1212 (2012).
Das, S. K., Majumder, P. P., Chakraborty, R., Majumdar, T. K. & Haldar, B. Studies on vitiligo. I. Epidemiological profile in Calcutta, India. Genet. Epidemiol. 2, 71–78 (1985).
Taieb, A. & Picardo, M. in Vitiligo. Ch.1.2.1 (eds Picardo, M. & Taïeb, A. ) 13–24tf (Springer, 2010).
Ezzedine, K. et al. Pre- versus post-pubertal onset of vitiligo: multivariate analysis indicates atopic diathesis association in pre-pubertal onset vitiligo. Br. J. Dermatol. 167, 490–495 (2012).
Nicolaidou, E. et al. Childhood- and later-onset vitiligo have diverse epidemiologic and clinical characteristics. J. Am. Acad. Dermatol. 66, 954–958 (2012).
Halder, R. M. Childhood vitiligo. Clin. Dermatol. 15, 899–906 (1997).
Halder, R. M. et al. Childhood vitiligo. J. Am. Acad. Dermatol. 16, 948–954 (1987).
Hu, Z., Liu, J. B., Ma, S. S., Yang, S. & Zhang, X. J. Profile of childhood vitiligo in China: an analysis of 541 patients. Pediatr. Dermatol. 23, 114–116 (2006).
Le Poole, I. C., Das, P. K., van den Wijngaard, R. M., Bos, J. D. & Westerhof, W. Review of the etiopathomechanism of vitiligo: a convergence theory. Exp. Dermatol. 4, 145–153 (1993). This is the first convergent approach to understanding vitiligo pathogenesis.
Schallreuter, K. U. et al. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp. Dermatol. 2, 139–140; discussion 139–160 (2008).
Dell'anna, M. L. & Picardo, M. A review and a new hypothesis for non-immunological pathogenetic mechanisms in vitiligo. Pigment Cell Res. 5, 406–411 (2006).
Shin, S., Shin, Y., Lee, H. & Oh, S. H. Spreading of pre-existing segmental vitiligo after immunotherapy with house dust mite in a patient with atopic dermatitits. Clin. Exp. Dermatol.http://dx.doi.org/10.1111/ced.12443 (2014).
Liu, L. et al. Promoter variant in the catalase gene is associated with vitiligo in Chinese people. J. Invest. Dermatol. 11, 2647–2653 (2010).
Sravani, P. V. et al. Determination of oxidative stress in vitiligo by measuring superoxide dismutase and catalase levels in vitiliginous and non-vitiliginous skin. Indian J. Dermatol. Venereol. Leprol. 3, 268–2671 (2009).
Schallreuter, K. U., Wood, J. M. & Berger, J. Low catalase levels in the epidermis of patients with vitiligo. J. Invest. Dermatol. 97, 1081–1085 (1991).
Maresca, V. et al. Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo. J. Invest. Dermatol. 3, 310–313 (1997).
Bulut, H. et al. Lack of association between catalase gene polymorphism (T/C exon 9) and susceptibility to vitiligo in a Turkish population. Genet. Mol. Res. 4, 4126–4132 (2011).
Kostyuk, V. A. et al. Dysfunction of glutathione S-transferase leads to excess 4-hydroxy-2-nonenal and H(2)O(2) and impaired cytokine pattern in cultured keratinocytes and blood of vitiligo patients. Antioxid. Redox Signal. 5, 607–620 (2010).
Vafaee, T., Rokos, H., Salem, M. M. & Schallreuter, K. U. In vivo and in vitro evidence for epidermal H2O2-mediated oxidative stress in piebaldism. Exp. Dermatol. 10, 883–887 (2010).
Ozturk, I. C. et al. Comparison of plasma malondialdehyde, glutathione, glutathione peroxidase, hydroxyproline and selenium levels in patients with vitiligo and healthy controls. Indian J. Dermatol. 53, 106–110 (2008).
Dell'Anna, M. L. et al. Membrane lipid alterations as a possible basis for melanocyte degeneration in vitiligo. J. Invest. Dermatol. 5, 1226–1233 (2007).
Jimbow, K., Chen, H., Park, J. S. & Thomas, P. D. Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo. Br. J. Dermatol. 1, 55–65 (2001).
Boissy, R. E. & Manga, P. On the etiology of contact/occupational vitiligo. Pigment Cell Res. 3, 208–214 (2004).
Hasse, S., Gibbons, N. C., Rokos, H., Marles, L. K. & Schallreuter, K. U. Perturbed 6-tetrahydrobiopterin recycling via decreased dihydropteridine reductase in vitiligo: more evidence for H2O2 stress. J. Invest. Dermatol. 2, 307–313 (2004).
Schallreuter, K. U., Elwary, S. M., Gibbons, N. C., Rokos, H. & Wood, J. M. Activation/deactivation of acetylcholinesterase by H2O2: more evidence for oxidative stress in vitiligo. Biochem. Biophys. Res. Commun. 2, 502–508 (2004).
Dell'Anna, M. L. et al. Membrane lipid defects are responsible for the generation of reactive oxygen species in peripheral blood mononuclear cells from vitiligo patients. J. Cell. Physiol. 1, 187–193 (2010).
Le Poole, I. C., van den Wijngaard, R. M., Westerhof, W. & Das, P. K. Tenascin is overexpressed in vitiligo lesional skin and inhibits melanocyte adhesion. Br. J. Dermatol. 2, 171–178 (1997).
Wagner, R. et al. Altered e-cadherin levels and distribution in melanocytes precedes clinical manifestations of vitiligo. J. Invest. Dermatol.http://dx.doi.org/10.1038/jid.2015.25 (2015).
Gauthier, Y., Cario-Andrè, M., Lepreux, S., Pain, C. & Taieb, A. Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo. Br. J. Dermatol. 148, 95–101 (2003).
Rokos, H., Beazley, W. D. & Schallreuter, K. U. Oxidative stress in vitiligo: photo-oxidation of pterins produces H(2)O(2) and pterin-6-carboxylic acid. Biochem. Biophys. Res. Commun. 4, 805–811 (2002).
Moore, J., Wood, J. M. & Schallreuter, K. U. Evidence for specific complex formation between alpha-melanocyte stimulating hormone and 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin using near infrared Fourier transform Raman spectroscopy. Biochemistry 46, 15317–15324 (1999).
Schallreuter, K. U. et al. Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes? J. Invest. Dermatol. 1, 167–174 (2001).
Bellei, B. et al. Vitiligo: a possible model of degenerative diseases. PLoS ONE 3, e59782 (2013).
Salem, M. M. A. E. L. et al. Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage. FASEB J. 23, 3790–3807 (2009).
Xavier, J. M., Morgado, A. L., Solá, S. & Rodrigues, C. M. Mitochondrial translocation of p53 modulates neuronal fate by preventing differentiation-induced mitochondrial stress. Antioxid. Redox Signal. 21, 1009–1024 (2014).
Paradisi, A. et al. Markedly reduced incidence of melanoma and nonmelanoma skin cancer in a nonconcurrent cohort of 10,040 patients with vitiligo. J. Am. Acad. Dermatol. 71, 1110–1116 (2014).
Teulings, H. E. et al. Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners. Br. J. Dermatol. 168, 162–171 (2013).
Dell'Anna, M. L. et al. Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients. Pigment Cell Res. 16, 553–559 (2003).
Dell'Anna, M. L. et al. Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo. J. Invest. Dermatol. 117, 908–913 (2001).
Nakagawa, T. & Guarente, L. SnapShot: sirtuins, NAD, and aging. Cell. Metab. 20, 192 (2014).
Imai, S. & Guarente, L. NAD+ and sirtuins in aging and disease. Trends Cell. Biol. 24, 464–471 (2014).
Shulyakova, N. et al. Over-expression of the Sirt3 sirtuin protects neuronally differentiated PC12 Cells from degeneration induced by oxidative stress and trophic withdrawal. Brain Res. 1587, 40–53 (2014).
Vega-Naredo, I., Cunha-Oliveira, T., Serafim, T. L., Sardao, V. A. & Oliveira, P. J. Analysis of pro-apoptotic protein trafficking to and from mitochondria. Methods Mol. Biol. 1241, 163–180 (2015).
Green, D. R., Galluzzi, L. & Kroemer, G. Cell biology. Metabolic control of cell death. Science 345, 1250256 (2014). This study supports the point of view that metabolic changes lead to cell impairment in vitiligo.
Martel, C., Wang, Z. & Brenner, C. VDAC phosphorylation, a lipid sensor influencing the cell fate. Mitochondrion 19, 69–77 (2014).
Basak, N. P., Roy, A. & Banerjee, S. Alteration of mitochondrial proteome due to activation of Notch1 signaling pathway. J. Biol. Chem. 11, 7320–7334 (2014).
de Moura, M. B., Uppala, R., Zhang, Y., Van Houten, B. & Goetzman, E. S. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells. PLoS ONE 9, e106028 (2014).
Dai, S. H. et al. Sirt3 attenuates hydrogen peroxide-induced oxidative stress through the preservation of mitochondrial function in HT22 cells. Int. J. Mol. Med. 34, 1159–1168 (2014).
Wu, Y. T., Wu, S. B. & Wie, Y. H. Roles of sirtuins in the regulation of antioxidant defense and bioenergetic function of mitochondria under oxidative stress. Free Radic. Res. 48, 1070–1084 (2014). This study elegantly explores the mitochondria-nucleus network and intra- and extracellular links.
Giblin, W., Skinner, M. E. & Lombard, D. B. Sirtuins: guardians of mammalian healthspan. Trends Genet. 30, 271–286 (2014).
Prignano, F. et al. Ultrastructural and functional alterations of mitochondria in perilesional vitiligo skin. J. Dermatol. Sci. 54, 157–167 (2009).
Bondanza, S. et al. Keratinocyte cultures from involved skin in vitiligo patients show an impaired in vitro behaviour. Pigment Cell Res. 20, 288–300 (2007).
Bastonini, E., Kovacs, D., Ottaviani, M., Dell'Anna, M. L. & Picardo, M. in XXII International Pigment Cell Conference (IPCC) http://www.ifpcs.org/ipcc2014/docs/IPCC%202014%20-%20Pigment%20Cell%20Melanoma%20Research%20Journal.pdf (2014).
Zhang, C. F. et al. Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes. J. Invest. Dermatol.http://dx.doi.org/10.1038/jid.2014.439 (2014).
Ainger, S. A. et al. DCT protects human melanocytic cells from UVR and ROS damage and increases cell viability. Exp. Dermatol. 23, 916–921 (2014).
Lee, A.-Y., Kim, N.-H., Choi, W.-I. & Youm, Y.-H. Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J. Invest. Dermatol. 124, 976–983 (2005).
Choi, C. P., Kim, Y. I., Lee, J. W. & Lee, M. H. The effect of narrowband ultraviolet B on the expression of matrix metalloproteinase-1, transforming growth factor-beta1 and type I collagen in human skin fibroblasts. Clin. Exp. Dermatol. 32, 180–185 (2007).
Cario-André, M., Pain, C., Gauthier, Y., Casoli, V. & Taoeb, A. In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal pigmentation. Pigment Cell Res. 19, 434–442 (2006).
Imokawa, G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res. 17, 96–100 (2004).
Shi, Y. et al. Premature graying as a consequence of compromised antioxidant activity in hair bulb melanocytes and their precursors. PLoS ONE 9, e93589 (2014).
Kim, J. et al. p53 induces skin aging by depleting Blimp1+ sebaceous gland cells. Cell Death Dis. 5, e1141 (2014).
Laddha, N. C. et al. Role of oxidative stress and autoimmunity in onset and progression of vitiligo. Exp. Dermatol. 5, 352–353 (2014).
Mosenson, J. A. et al. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci. Transl. Med. 5, 174ra128 (2013).
Richmond, J. M., Frisoli, M. L. & Harris, J. E. Innate immune mechanisms in vitiligo: danger from within. Curr. Opin. Immunol. 25, 676–682 (2013).
Alkhateeb, A., Fain, P. R., Thody, A., Bennett, D. C. Spritz, R. A. Epidemiology of vitiligo and associated aut oimmune diseases in Caucasian probands and their families. Pigment Cell Res. 16, 208–214 (2003). This study is a genomic analysis of families with generalized vitiligo, and it revealed mechanisms of genetic susceptibility to autoimmunity.
Yu, R. et al. Transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin. PLoS ONE 7, e51040 (2012).
van den Boorn, J. G. et al. Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy. J. Invest. Dermatol. 131, 1240–1251 (2011).
Kroll, T. M. et al. 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo. J. Invest. Dermatol. 124, 798–806 (2005).
Al-Shobaili, H. A. & Rasheed, Z. Mitochondrial DNA acquires immunogenicity on exposure to nitrosative stress in patients with vitiligo. Hum. Immunol. 10, 1053–1061 (2014).
Passeron, T. & Ortonne, J. P. Activation of the unfolded protein response in vitiligo: the missing link? J. Invest. Dermatol. 11, 2502–2504 (2012).
Toosi, S., Orlow, S. J. & Manga, P. Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8. J. Invest. Dermatol. 11, 2601–2609 (2012). This study provides experimental evidence for the link between oxidative and autoimmune pathways, taking into account the different intracellular compartments and processes.
Ogg, G. S., Rod Dunbar, P., Romero, P., Chen, J. L. & Cerundolo, V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J. Exp. Med. 188, 1203–1208 (1998).
Wankowicz-Kalinska, A. et al. Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo. Lab. Invest. 83, 683–695 (2003).
Le Poole, I. C., van den Wijngaard, R. M., Westerhof, W. & Das, P. K. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am. J. Pathol. 148, 1219–1228 (1996).
van den Wijngaard, R. et al. Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+ T cells at the perilesional site. Lab. Invest. 80, 1299–1309 (2000).
van den Boorn, J. G. et al. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J. Invest. Dermatol. 129, 2220–2232 (2009).
Harris, J. E. et al. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin. J. Invest. Dermatol. 132, 1869–1876 (2012).
Rashighi, M. et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci. Transl. Med. 6, 223ra223 (2014).
Bertolotti, A. et al. Type I interferon signature in the initiation of the immune response in vitiligo. Pigment Cell. Mel. Res. 27, 398–407 (2014).
Bassiouny, D. A. & Shaker, O. Role of interleukin-17 in the pathogenesis of vitiligo. Clin. Exp. Dermatol. 36, 292–297 (2011).
Wang, C. Q. et al. TH17 cells and activated dendritic cells are increased in vitiligo lesions. PLoS ONE 6, e18907 (2011).
Elela, M. A., Hegazy, R. A., Fawzy, M. M., Rashed, L. A. & Rasheed, H. Interleukin 17, Interleukin 22 and FoxP3 expression in tissue and serum of non-segmental vitiligo: a case- controlled study on eighty-four patients. Eur. J. Dermatol. 23, 350–355 (2013).
Chatterjee, S. et al. A quantitative increase in regulatory T cells controls development of vitiligo. J. Invest. Dermatol. 134, 1285–1294 (2014).
Gregg, R. K., Nichols, L., Chen, Y., Lu, B. & Engelhard, V. H. Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase-specific TCR transgenic mice. J. Immunol. 184, 1909–1917 (2010).
Dwivedi, M., Laddha, N. C., Arora, P., Marfatia, Y. S. & Begum, R. Decreased regulatory T-cells and CD4+/CD8+ ratio correlate with disease onset and progression in patients with generalized vitiligo. Pigment Cell Melanoma Res. 26, 586–591 (2013).
Klarquist, J. et al. Reduced skin homing by functional TReg in vitiligo. Pigment Cell Melanoma Res. 23, 276–286 (2010).
Lili, Y. et al. Global activation of CD8+ cytotoxic T lymphocytes correlates with an impairment in regulatory T cells in patients with generalized vitiligo. PLoS ONE 7, e37513 (2012).
Tembhre, M. K., Parihar, A. S., Sharma, V. K., Chattopadhyay, P. & Gupta, S. Alteration in regulatory T cells in active generalized vitiligo and their clinical correlation. Br. J. Dermatol. 172, 940–950 (2014).
Tu, C. X., Jin, W. W., Lin, M., Wang, Z. H. & Man, M. Q. Levels of TGF-beta(1) in serum and culture supernatants of CD4(+)CD25(+) T cells from patients with non-segmental vitiligo. Arch. Dermatol. Res. 303, 685–689 (2011).
Zhou, L. et al. Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells. Pigment Cell Melanoma Res. 25, 602–611 (2012).
Maeda, Y. et al. Detection of self-reactive CD8+T cells with an anergic phenotype in healthy individuals. Science 346, 1536–1540 (2014).
Yang, F., Sarangarajan, R., Le Poole, I. C., Medrano, F. & Boissy, R. E. The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase activity. J. Invest. Dermatol. 114, 157–164 (2000).
Wang, Q. et al. Stress-induced RNASET2 overexpression mediates melanocyte apoptosis via the TRAF2 pathway in vitro. Cell Death Dis. 5, e1022 (2014).
Becatti, M. et al. SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival. J. Cell. Mol. Med. 18, 514–529 (2014).
Mosenson, J. A. et al. Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress. Pigment Cell Melanoma Res. 27, 209–220 (2014).
Wu, J., Zhou, M., Wan, Y. & Xu, A. CD8+ T cells from vitiligo perilesional margins induce autologous melanocyte apoptosis. Mol. Med. Rep. 7, 237–241 (2013).
Kumar, R. & Parsad, D. Melanocythorragy and apoptosis in vitiligo: connecting jigsaw pieces. Indian J. Dermatol. Venereol. Leprol. 78, 19–23 (2012).
Taieb, A. & Ezzedine, K. Vitligo: the white armour? Pigment Cell Melanoma Res. 26, 286–299 (2013).
Spritz, R. A. Modern vitiligo genetics sheds new light on an ancient disease. J. Dermatol. 40, 310–318 (2013).
Chen, J. X. et al. Genetic polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and risk of vitiligo in Han Chinese populations: a genotype-phenotype correlation study. Br. J. Dermatol. 170, 1092–1099 (2014).
Ren, Y. et al. Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo. PLoS Genet. 5, e1000523 (2009).
Wood, J. M., Gibbons, N. C., Chavan, B. & Schallreuter, K. U. Computer simulation of heterogeneous single nucleotide polymorphisms in the catalase gene indicates structural changes in the enzyme active site, NADPH-binding and tetramerization domains: a genetic predisposition for an altered catalase in patients with vitiligo? Exp. Dermatol. 4, 366–371 (2008).
Naveh, H. P., Rao, U. N. & Butterfield, L. H. Melanoma-associated leukoderma — immunology in black and white? Pigment Cell Melanoma Res. 26, 796–804 (2013).
Circosta, P. et al. T cell receptor (TCR) gene transfer with lentiviral vectors allows efficient redirection of tumor specificity in naive and memory T cells without prior stimulation of endogenous TCR. Hum. Gene Ther. 20, 1576–1588 (2009).
Spritz, R. A. The genetics of generalized vitiligo: autoimmune pathways and an inverse relationship with malignant melanoma. Genome Med. 2, 78 (2010).
Marie, J. et al. Inflammasome activation and vitiligo/nonsegmental vitiligo progression. Br. J. Dermatol. 170, 816–823 (2014).
Dammak, I. et al. Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo. Int. J. Dermatol. 5, 476–480 (2009).
Scioli, M. G. et al. Antioxidant treatment prevents serum deprivation- and TNF-α-induced endothelial dysfunction through the inhibition of NADPH oxidase 4 and the restoration of β-oxidation. J. Vasc. Res. 51, 327–337 (2014).
Hedstrand, H. et al. The transcription factors SOX9 and SOX10 are vitiligo autoantigens in autoimmune polyendocrine syndrome type I. J. Biol. Chem. 276, 35390–35395 (2001).
Das, S. K. et al. Studies on vitiligo. II. Familial aggregation and genetics. Genet. Epidemiol. 2, 255–262 (1985).
Spritz, R. A. in Vitiligo. Ch.2.2.1 (eds Picardo, M. & Taïeb, A. ) 155–163 (Springer, 2010).
Gauthier, Y. & Benzekri, L. in Vitiligo. Ch.184.108.40.206 (eds Picardo, M. & Taïeb, A. ) 167–173 (Springer, 2010).
van Geel, N. et al. Clinical significance of Koebner phenomenon in vitiligo. Br. J. Dermatol. 167, 1017–1024 (2012).
Stinco, G., Buligan, C., Grimaldi, F., Valent, F. & Patrone, P. Serological screening for autoimmune polyendocrine sindrome in patients with vitiligo. J. Eur. Acad. Dermatol. Venereol. 26, 1041–1042 (2012).
Laberge, G. et al. Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Pigment Cell Res. 18, 300–305 (2005).
Tuelings, H.-E. et al. The antibody response against MART-1 differs in patients with melanoma-associated leucoderma and vitiligo. Pigment Cell Melanoma Res. 27, 1086–1096 (2014).
Oiso, N., Fukai, K., Kawada, A. & Suzuki, T. Piebaldism. J. Dermatol. 40, 330–335 (2013).
Hann, S. K., Gauthier, Y. & Benzekri, L. in Vitiligo. Ch.1.3.2 (eds Picardo, M. & Taïeb, A. ) 41–49 (Springer, 2010).
Gey, A. et al. Autoimmune thyroid disease in vitiligo: multivariate analysis indicates intricate pathomechanisms. Br. J. Dermatol. 168, 756–761 (2013).
Cunningham, E. T. Jr, Rathinam, S. R., Tugal-Tutkun, I., Muccioli, C. & Zierhut, M. Vogt-Koyanagi-Harada disease. Ocul. Immunol. Inflamm. 22, 249–252 (2014).
Taieb, A. et al. Vitiligo European Task Force (VETF); EuropeanAcademy of Dermatology and Venereology (EADV); Union Europe´enne des MédecinsSpécialistes (UEMS). Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br. J. Dermatol. 168, 5–19 (2013).
Boissy, R. in Vitiligo. Ch.220.127.116.11 (eds Picardo, M. & Taïeb, A. ) 175–180 (Springer, 2010).
Diallo, A. et al. Development and validation of the K-VSCOR for scoring Koebner's phenomenon in vitiligo/non-segmental vitiligo. Pigment Cell Melanoma Res. 26, 402–407 (2013).
Gawkrodger, D. J. et al. Guideline for the diagnosis and management of vitiligo. Br. J. Dermatol. 159, 1051–1076 (2008).
Vrijman, C. et al. The prevalence of thyroid disease in patients with vitiligo: a systematic review. Br. J. Dermatol. 167, 1224–1235 (2012).
Whitton, M. E., Ashcroft, D. M., Barrett, C. W. & Gonzalez, U. Interventions for vitiligo. Cochrane Database Syst. Rev.http://dx.doi.org/10.1002/CD003263.pub3 (2006).
Whitton, M. E. et al. Interventions for vitiligo. Cochrane Database Syst. Rev.http://dx.doi.org/10.1002/14651858.CD003263.pub4 (2010).
Whitton, M. E. et al. Interventions for vitiligo. Cochrane Database Syst. Rev.http://dx.doi.org/10.1002/14651858 (2015). A complete analysis of the current therapeutic approaches.
Taieb, A. et al. Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br. J. Dermatol. 168, 5–19 (2013).
Sapam, R., Agrawal, S., Phil, M. & Dhali, T. K. Systemic PUVA versus narrowband UVB in the treatment of vitiligo: a randomized controlled study. Int. J. Dermatol. 51, 1107–1115 (2012).
Lim, H. W. et al. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: A randomized multicenter trial. JAMA Dermatol. 151, 42–50 (2015).
Dong, D. et al. The effects of NB-UVB on the hair follicle-derived neural crest stem cells differentiating into melanocyte lineage in vitro. J. Dermatol. Sci. 66, 20–28 (2012).
Eleftheriadou, V., Thomas, K. S., Whitton, M. E., Batchelor, J. M. & Ravenscroft, J. C. Which outcomes should we measure in vitiligo? Results of a systematic review and a survey among patients and clinicians on outcomes in vitiligo trials. Br. J. Dermatol. 167, 804–814 (2012).
Kim, S. R., Han, K. D. & Kim, C. Y. Repigmentation of vitiligo using the follicular unit extraction technique. Dermatol. Surg. 40, 1425–1427 (2014).
Mapar, M. A., Safarpour, M., Mapar, M. & Haghighizadeh, M. H. A comparative study of the mini-punch grafting and hair follicle transplantation in the treatment of refractory and stable vitiligo. J. Am. Acad. Dermatol. 70, 743–747 (2014).
Singh, C., Parsad, D., Kanwar, A. J., Dogra, S. & Kumar, R. Comparison between autologous noncultured extracted hair follicle outer root sheath cell suspension and autologous noncultured epidermal cell suspension in the treatment of stable vitiligo: a randomized study. Br. J. Dermatol. 169, 287–293 (2013).
Mulekar, S. V. & Isedeh, P. Surgical interventions for vitiligo: an evidence-based review. Br. J. Dermatol. 169, 57–66 (2013).
Kumar, A., Mohanty, S., Sahni, K., Kumar, R., Gupta, S. Extracted hair follicle outer root sheath cell suspension for pigment cell restoration in vitiligo. J. Cutan. Aesthet. Surg. 6, 121–125 (2013).
Sharquie, K. E., Noaimi, A. A. & Al-Mudaris, H. A. Melanocytes transplantation in patients with vitiligo using needling micrografting technique. J. Drugs Dermatol. 12, e74–e78 (2013).
Kovacs, D. et al. Vitiligo: characterization of melanocytes in repigmented skin after punch grafting. J. Eur. Acad. Dermatol. Venereol. 29, 581–590 (2015).
Wakao, S., Akashi, H., Kushida, Y. & Dezawa, M. Muse cells, newly found non-tumorigenic pluripotent stem cells, reside in human mesenchymal tissues. Pathol. Int. 64, 1–9 (2014).
Zhou, M. N. et al. Dermal mesenchymal stem cells (DMSCs) inhibit skin-homing CD8+ T cell activity, a determining factor of vitiligo patients’ autologous melanocytes transplantation efficiency. PLoS ONE 8, e60254 (2013).
Simerman, A. A., Perone, J. J., Gimeno, M. L., Dumesic, D. A. & Chazenbalk, G. D. A mystery unraveled: nontumorigenic pluripotent stem cells in human adult tissues. Expert Opin. Biol. Ther. 14, 917–929 (2014).
Shenefelt, P. D. & Shenefelt, D. A. Spiritual and religious aspects of skin and skin disorders. Psychol. Res. Behav. Manag. 7, 201–212 (2014).
Silverberg, J. I. & Silverberg, N. B. Association between vitiligo extent and distribution and quality-of-life impairment. JAMA Dermatol. 149, 159–164 (2013). In this paper the often-underestimated aspect of quality of life is studied and considered in relation to epidemiologic data.
Porter, J. R., Beuf, A. H., Nordlund, J. J. & Lerner, A. B. Personal responses to vitiligo. Arch. Dermatol. 114, 1348–1385 (1978).
Mattoo, S. K., Handa, S., Kaur, I., Gupta, N. & Malhotra, R. Psychiatric morbidity in vitiligo: prevalence and correlates in India. J. Eur. Acad. Dermatol. Venereol. 16, 573–578 (2002).
Wong, S. M. & Baba, R. Quality of life among Malaysian patients with vitiligo. Int. J. Dermatol. 51, 158–161 (2012).
Krüger, C. & Schallreuter, K. U. Cumulative life course impairment in vitiligo. Curr. Probl. Dermatol. 44, 102–117 (2013).
Teovska Mitrevska, N., Eleftheriadou, V. & Guarneri, F. Quality of Life in vitiligo patients. Dermatol. Ther. 25 (Suppl. 1), S28–S31 (2012).
Parsad, D., Dogra, S. & Kanwar, A. J. Quality of life in patients with vitiligo. Health Qual. Life Outcomes 1, 58 (2013).
Ingordo, V. et al. Dermatology Life Quality Index score in vitiligo patients: a pilot study among young Italian males. G. Ital. Dermatol. Venereol. 147, 83–90 (2012).
Noh, S., Kim, M., Park, C. O., Hann, S.-K. & Oh, S. H. Comparison of the psychological impacts of asymptomatic and symptomatic cutaneous diseases: vitiligo and atopic dermatitis. Ann. Dermatol. 25, 454–461 (2013).
Lilly, E. et al. Development and validation of a vitiligo-specific quality-of-life instrument (VitiQoL). J. Am. Acad. Dermatol. 69, e11–e18 (2013).
Senol, A., Yucelten, A. D. & Ay, P. Development of a quality of life scalefor vitiligo. Dermatology 226, 185–190 (2013).
Gupta, V. Sreenivas, V., Mehta, M., Khaitan, B. K. & Ramam, M. Measurement properties of the Vitiligo Impact Scale-22 (VIS-22), a vitiligo-specific quality-of-life instrument. Br. J. Dermatol. 171, 1084–1090 (2014). This is a comparative advantage–disadvantage analysis of the different instruments currently available to measure the impact of vitiligo on quality of life.
Shah, R., Hunt, J., Webb, T. L. & Thompson, A. R. Starting to develop self-help for social anxiety associated with vitiligo: using clinical significance to measure the potential effectiveness of enhanced psychological self-help. Br. J. Derm. 171, 332–337 (2014).
Alghamdi, K. M., Khurrum, H., Taieb, A. & Ezzedine, K. Treatment of generalized vitiligo with anti-TNF-a agents. J. Drugs Dermatol. 11, 534–539 (2012).
Tsuda, K. et al. Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naïve T cells into cytokine-producing mature T cells. PLoS ONE 7, e31465 (2012).
Yaar, M. & Park, H. Y. Melanocytes: a window into the nervous system. J. Invest. Dermatol. 132, 835–845 (2012). This review considers the similarity between melanocytes and neurons to provide a valuable model for studies of diseases that involve the nervous system and of innovative therapies.
Jian, Z. et al. Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response: a possible mechanism for melanocyte degeneration in vitiligo. J. Invest. Dermatol. 8, 2221–2230 (2014).
Introduction (M.P.); Epidemiology (K.E., I.H., D.P.); Mechanisms/pathophysiology (M.L.D., M.P., J.E.H.); Diagnosis, screening and prevention (K.E., I.H., D.P., A.T.); Management (K.E., A.T.); Quality of life (I.H., D.P., M.P.); Outlook (M.P.); overview of Primer (M.P.).
M.P. received research grants from Giuliani, Cantabria, Stealth Peptides, Fidia, and he was speaker for Pierre Fabre. J.E.H. received research grants from AbbVie, Sanofi/Genzyme, Combe, Gliknik; he was consultant for Pfizer and Biomedical System; he was a speaker for Alkem Pharmauceticals. I.H. was an investigator for Clinuvel, Estee Lauder, and Ferndale Laboratories and he received equipment from Canfield. A.T. received research grants from Galderma and Astellas. M.L.D. and D.P. declare no competing interests.
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Picardo, M., Dell'Anna, M., Ezzedine, K. et al. Vitiligo. Nat Rev Dis Primers 1, 15011 (2015). https://doi.org/10.1038/nrdp.2015.11
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