Vitiligo is an acquired, non-contagious disease in which progressive, patchy loss of pigmentation from the skin, overlying hair and oral mucosa results from the loss of melanocytes from the involved areas . Clinically, two large subsets of vitiligo are distinguished namely focal or segmental vitiligo and non-segmental or generalised vitiligo . Focal vitiligo presents with a limited number of small lesions while segmental vitiligo is typified by an asymmetric distribution involving segments of the skin surface, sometimes in a dermatomal fashion, by depigmented macules. Non-segmental vitiligo corresponds to all generalised, usually symmetrical, forms including acrofacial vitiligo. The course of the disease is unpredictable but is often episodically progressive with phases of stabilised depigmentation. Extending vitiligo with enlarging macules or the development of new lesions is classified as the active form of the disease .
Although vitiligo might be viewed as minor disorder, skin depigmentation can cause psychological stress in patients with respect to self-esteem and social interactions. This is particularly true for individuals with deeply pigmented skin , and for women who in some cultures face social and marital stigma . The prevalence of vitiligo has been reported to be 0.5 to 1% of the world population [6,7]. In India, the prevalence varies from 0.5 to 2.5 % , although the states of Gujarat and Rajasthan have a prevalence of 8.8% . Vitiligo affects all with no predilection for gender or race. The disease usually starts in childhood or young adulthood: the clinical manifestation begins before 20 years of age in 50% of cases, while in 25% of cases the onset is before the age of 14 years .
Many factors have been implicated in the aetiology and pathogenesis of the vitiligo including infections , stress , neural abnormalities , defective melanocyte adhesion , and genetic susceptibility (Figure 1) . The biochemical hypothesis argues that melanocyte destruction is due to the accumulation of toxic metabolites from melanogenesis, the break-down of free-radical defence and an excess of hydrogen peroxide [16-18]. In addition, many studies have indicated a role for both cellular  and humoral  immunity in the pathogenesis of vitiligo. This chapter will focus on the available evidence which supports the involvement of autoimmunity in the aetiology and pathogenesis of vitiligo.
2. Association with autoimmune diseases
Vitiligo is frequently associated with other autoimmune disorders, particularly autoimmune thyroid disease . Patients with vitiligo are also more likely to suffer from autoimmune conditions than those in the general population . For example, a survey of more than 2,600 unselected Caucasian vitiligo patients indicated elevated frequencies of autoimmune thyroid disease, Addison’s disease, systemic lupus erythematosus and pernicious anaemia, and, indeed, approximately 30% of patients were affected by at least one other autoimmune disease . Furthermore, the same autoimmune diseases were found at an increased prevalence in the first-degree relatives of vitiligo patients  and in multiplex vitiligo families . Such findings indicate that vitiligo can be part of a specific group of autoimmune diseases to which individuals can be genetically predisposed, and are also evidence for its autoimmune pathogenesis.
3. Immuno-regulatory genes
The involvement of immune-regulatory genes with vitiligo development has been extensively documented . For example, the association of certain major histocompatibility complex (MHC) alleles with vitiligo has suggested an important link between the aetiology of the disease and aberrant presentation of self-antigens to the immune system. Most recently, alleles of human leukocyte antigen (HLA) genes
Other immune-regulatory genes that contain single nucleotide polymorphisms associated with vitiligo susceptibility include
4. Immunological features of melanocytes
Several studies have shown abnormal expression of MHC class II antigen HLA-DR and increased expression of intercellular adhesion molecule-1 (ICAM-1) by perilesional melanocytes in vitiligo compared with melanocytes from normal skin [30-32]. These molecules have important roles in antigen presentation and in the activation of T helper cells, so their expression by melanocytes could contribute to the anti-melanocyte cellular immune responses that are observed in vitiligo [19,33].
Both vitiligo and normal melanocytes are also capable of expressing MHC class I molecules , which could allow interaction with destructive cytotoxic T cells. Indeed, melanocytes have an antigen processing and presenting capability which can make them target cells for T cell-mediated cytotoxicity . Finally, in perilesional vitiligo biopsies, melanocytes express macrophage markers CD68 and CD36  and reduced levels of membrane regulators of complement activation, including decay acceleration factor and membrane cofactor protein , which suggests a vulnerability of these cells to attack by macrophages and the complement system, respectively.
Melanocyte autoantibodies have been detected in the sera of vitiligo patients at a significantly higher frequency than in healthy individuals [20,36]. They are associated with the extent of vitiligo, being present in 93% of patients with 5-10% of skin area involvement, and in 50% of patients with less than 2% of skin depigmentation . In addition, patients with active vitiligo have increased levels of melanocyte autoantibodies compared to those with stable disease [38,39]. Characterisation of melanocyte autoantibodies has demonstrated that they belong to the subclasses IgG1, IgG2 and IgG3 , although studies have also found that IgA levels of melanocyte autoantibodies are associated with disease activity . Several melanocyte-specific autoantibody targets have been identified including tyrosinase [42-44], tyrosinase-related protein (TRP)-1 , dopachrome tautomerase (or TRP-2) [46,47], PMEL  and GTP-binding protein Rab38 .
Autoantibodies against targets not specifically expressed by melanocytes have also been detected in patients with vitiligo including the melanin-concentrating hormone receptor 1, gamma-enolase, alpha-enolase, heat-shock protein 90, osteopontin, ubiquitin-conjugating enzyme, translation-initiation factor 2, tyrosine hydroxylase and laminA [49-51]. In addition, organ-specific autoantibodies, particularly against the thyroid, adrenal glands, gastric parietal cells, and pancreatic islet cells are commonly found in vitiligo patients , along with anti-nuclear autoantibodies and IgM-rheumatoid factor . Keratinocyte autoantibodies which correlate with vitiligo extent and activity have been reported .
With respect to pathogenicity, vitiligo patient autoantibodies can mediate complement damage and antibody-dependent cellular cytotoxicity against melanocytes and melanoma cells
6. CD4+helper and CD8+cytotoxic T cells
The first evidence for a possible role for T cells in the pathogenesis of vitiligo came from studies on inflammatory vitiligo . Since then, circulating autoreactive CD8+cytotoxic T that recognise melanocyte antigens (MART1, PMEL and tyrosinase) have been detected in vitiligo patients [33,63-66]. Peripheral CD8+T cells are more prevalent in active cases of vitiligo as compared to stable cases, and their frequency correlates with the extent of depigmentation [53,67]. They also express high levels of the skin-homing receptor cutaneous lymphocyte-associated antigen and display cytotoxic reactivity towards melanocytes .
Histological studies of skin biopsies from vitiligo patients have demonstrated that infiltrating cytotoxic and helper T cells are most prominent at the periphery of vitiligo lesions [32,68]. Moreover, a significant increase in the number of CD4+and CD8+T cells are detected in the marginal skin in both stable and active vitiligo cases . These perilesional T cells exhibit a predominantly type-1-like cytokine secretion profile of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, the latter enhancing T cell trafficking to the skin by increasing ICAM-1 expression on target cells [70,71]. The majority of infiltrating T cells are activated, as indicated by the expression of the MHC class II antigen HLA-DR [32,68] and the presence of granzyme B+and perforin+cytotoxic T lymphocytes . There is also evidence for down-regulation of the T helper 2 cell-dependent CDw60 molecules in the vitiliginous epidermis. This observation correlates with infiltrating T cells exhibiting a T helper 1 cell-type cytokine production pattern consistent with cell-mediated organ-specific autoimmunity .
Using a skin explant model to investigate the effector functions of perilesional CD8+T cells, the latter, which are enriched for cytotoxic T lymphocytes that recognise melanocyte antigens (MART1, PMEL and tyrosinase), infiltrate normally pigmented skin and eradicate melanocytes . The capacity of cytotoxic T cells for damaging melanocytes has also been observed in an experimental murine model of vitiligo: melanocytes were destroyed by CD8+T cells recognising a single H2-Kb-binding peptide derived from dopachrome tautomerase .
7. T helper 17 cells
Increased numbers of T helper 17A+cells are found in the leading edge of vitiligo lesions as shown by immunohistochemistry and immunofluorescence [74,75]. Elevated levels of IL-17A mRNA are also present in the same locality , evidence that signifies active T helper 17 cells in vitiligo lesions.
8. Regulatory T cells
Natural Treg cells play a key role in maintaining peripheral tolerance through the active suppression of self-reactive T cell activation and expansion , thereby preventing the development of the autoimmune responses. To date, several studies have indicated perturbations in Treg cell numbers and/or function in vitiligo patients [67,77-79]. Such alterations might lead to the reported higher levels and activation of cytotoxic T cells in individuals with the disease [67,77].
Assessment of circulating Tregs by flow cytometric analysis has revealed a decrease in their numbers in vitiligo patients compared to controls [67,77,78]. Reduced peripheral Treg cell numbers have also been reported in early age-of-onset patients (1-20 years) compared to those with late onset vitiligo, and decreased circulating Treg cell counts have been demonstrated in patients with active vitiligo as compared to those with stable disease . Moreover, a striking reduction in the number of Tregs in the marginal and lesional skin of vitiligo patients has been observed [69,80]. Interestingly, some studies have demonstrated that peripheral or lesional skin CD4+CD25+FoxP3+Treg cell numbers remain unaltered in vitiligo [81-83], and even that either may be increased [67,84]. Interestingly, discrepancy between the relative abundance of Treg cells present in the circulation of vitiligo patients as compared to their skin was reported to be due to reduced expression of the chemo-attractant CCL22 within vitiligo patient skin so impairing migration of Tregs into the tissue .
As well as defects in Treg cell numbers, their function can also be impaired in vitiligo patients. Indeed, the suppressive effects of Tregs in vitiligo cases are significantly reduced as indicated by their impaired ability to inhibit proliferation and cytokine production from autologous CD8+T cells [77,78]. In line with this, the expression of FoxP3 (the dedicated mediator of the genetic program governing Treg cell development and function) in CD4+CD25hi Tregs is significantly decreased in vitiligo patients compared to controls . Moreover, the mean percentage area of positive immunostaining in skin biopsies and peripheral blood levels of FoxP3 are significantly lower in vitiligo patients compared to controls . Vitiligo area scoring index, vitiligo disease activity and stress score also correlate negatively with FoxP3 levels . The expression of CTLA-4 (a T cell surface molecule involved in regulation of T cell activation) is also decreased in vitiligo patients, an impairment that could perturb the normal suppressive capacity of Treg cells . Furthermore, decreased serum and tissue levels of transforming growth factor (TGF)-beta (important for imposing a Treg cell phenotype) are observed in individuals with vitiligo . Reduced levels of TGF-beta also correlate with increased disease activity  and the percentage of involved body area . Moreover, lowered IL-10 (contributes to Treg cell-mediated immunosuppression) levels are present in active cases of vitiligo [88,90]. Finally, and importantly, in a mouse model of vitiligo, the adoptive transfer of melanocyte-specific Tregs was found to induce a lasting remission of the disease , thus proposing Treg cells as a potential therapeutic target.
Macrophage infiltration has been demonstrated in vitiligo lesions, with increased numbers present in perilesional compared with normal skin [32,92]. There is evidence that macrophages are involved in the clearing of apoptosed melanocytes from the skin in vitiligo patients . In addition, macrophages expressing activating Fc-gamma receptors have been shown to mediate depigmentation in a mouse model of autoimmune vitiligo . Moreover, macrophage migration inhibitory factor, which is a potent activator of macrophages and is considered to play an important role in cell-mediated immunity, has been found at significantly higher levels in vitiligo patients compared to controls .
10. Dendritic cells
Enhanced populations of CD11c+myeloid dermal dendritic cells and CD207+Langerhans cells have been observed in the leading edges of vitiligo lesions [75,96,97]. Dendritic cell-LAMP+and CD1c+sub-populations were also found to be significantly expanded in the lesional edges of vitiligo skin . More recently, dendritic cell-mediated destruction of melanocytes has been demonstrated
11. Natural killer cells
Alterations in natural killer (NK) cells have been demonstrated in vitiligo patients indicating a role for them in the pathogenesis of the disease . The percentages of NK cells with activatory receptors, as denoted by the expression of CD16+CD56+and CD3+CD16+CD56+, are significantly increased in vitiligo patients compared with the controls, while the percentage of NK cells expressing the inhibitory receptor CD158a+is significantly reduced.
Various studies have implicated cytokine involvement in the pathogenesis of vitiligo . For example, increased serum levels of soluble IL-2 receptor are associated with vitiligo activity, indicating T cell activation , and elevated production of IL-6, which can induce ICAM-1 expression on melanocytes thereby facilitating leukocyte interactions, and IL-8, which can attract neutrophils to amplify destructive inflammatory responses, are found in vitiligo patients . In addition, other pro-inflammatory cytokines including IL-1, IL-4, IFN-gamma and TNF-alpha, which are paracrine inhibitors of melanocytes or initiators of apoptosis, are detected at significantly higher levels in vitiligo patients compared with healthy controls [71,100,103-105], and IL-17 levels are positively correlated with the extent of body area involvement . In contrast, the level of TGF-beta, required for the maturation of Treg cells, is significantly decreased in vitiligo patients compared with controls . Finally, imbalances of keratinocyte-derived cytokines that affect melanocyte activity and survival are found in vitiligo lesional skin: significantly lower expression of granulocyte-macrophage colony-stimulating factor, stem cell factor and endothelin-1 is detected in depigmented vitiligo lesions compared with normal skin .
13. Immuno-regulatory micro RNAs
MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression. Abnormal expression of miRNAs which play crucial roles in regulating immunity has been reported in vitiligo. In a mouse model of the disease , dysregulated miRNAs included miRNA-146a, which contributes to the regulation of Treg cell function  and is implicated in autoimmune disease development in mice , as well as miR-191, which mediates in the proliferation and survival of melanocytes . In addition, there is an increase in the expression of immune-regulatory miRNAs miRNA-133b, miRNA-135a, miRNA-9 and miRNA-1 in the lesional skin of vitiligo patients, suggesting an important role for these in vitiligo pathogenesis .
14. Treatment modalities
Repigmentation in vitiligo patients receiving treatment with immunosuppressive agents indirectly supports the theory that immune-mediated processes are involved in vitiligo pathogenesis. Topically applied tacrolimus (FK506), a therapeutic agent which exerts a potent immunosuppressive effect on T cells by blocking the action of the cytokine gene-activating cofactor calcineurin , has resulted in successful repigmentation responses in vitiligo patients [113,114] Topical corticosteroids, which have anti-inflammatory and immunosuppressive actions, are considered to be an effective first-line treatment in children and adults with segmental or non-segmental vitiligo of recent onset [3,115], and, indeed, following treatment of vitiligo patients with systemic steroids, a reduction in anti-melanocyte antibody levels and in antibody-mediated anti-melanocyte cytotoxicity has been demonstrated [116,117].
Psoralen with ultraviolet radiation (PUVA) is used as a second-line therapy for vitiligo [3,118]. Following PUVA treatment, a reduction in the number of Langerhans cells and a decrease in the expression of vitiligo-associated melanocyte antigens, which could lead to a blocking of antibody-dependent cell-mediated cytotoxicity against melanocytes, have been noted in vitiligo patients [119,120]. In addition, ultraviolet radiation can induce the expression of anti-inflammatory cytokines, modulate the expression of intercellular adhesion molecule-1, and induce apoptosis of skin-infiltrating T lymphocytes [121,122].
Despite the many available therapeutic modalities [115,123], repigmentation in the majority of vitiligo patients is rarely complete or long-lasting, so a better understanding of the precise aetiology and pathogenesis of the disease is crucial to improving the efficacy of treatment regimens.
As detailed in this chapter, there is strong evidence for the involvement of autoimmunity in the aetiology and pathogenesis of vitiligo. However, it is most likely that several interacting factors (Figure 1) are responsible for the clinical manifestations of the disease . Indeed, although the evidence for the role of immune-related genes in the aetiology of vitiligo is clear , the limited concordance in identical twins  indicates that other factors, probably environmental, are also involved in its development, making the disease complex, polygenic, and multi-factorial.
Of note is the finding that oxidative-stress in melanocytes [16-18] results in the secretion of heat-shock protein 70 and chaperoned melanocyte antigens which mediates dendritic cell-activation with the consequential dendritic cell effector functions then playing a role in the destruction of melanocytes [96,125]. This has led to the convergence theory of vitiligo aetiology, which suggests that several factors act synergistically or independently to induce the disappearance of cutaneous melanocytes (Figure 1) . During the elicitation phase of the disease, physical trauma to the skin , emotional stresses , or imbalances of endogenous neural factors , metabolites, cytokines or hormones  can lead to oxidative stress within melanocytes, which then respond by actively secreting heat-shock protein 70 and chaperoned melanocyte antigens . In the immune activation stage, these ‘danger’ signals promote the activation of antigen-presenting dendritic cells with the subsequent activation and recruitment of anti-melanocyte autoreactive cytotoxic T lymphocytes to the skin . Intrinsic damage to melanocytes could, therefore, be the initiating event in vitiligo development followed by a destructive secondary anti-melanocyte immune response from cytotoxic T cells [19,126,127]. Notably, 50% of vitiligo patients experience a Koebner phenomenon, whereby vitiligo develops at a site previously affected by a physical trauma . In addition, different pathogenic mechanisms could account for the various clinical types of vitiligo: pathogenic neural factors are usually related to segmental vitiligo, whereas autoimmunity is most often associated with the non-segmental (generalised) form .
As indicated, it is most likely that immune responses in vitiligo are of a secondary nature following melanocyte damage. Indeed, as several vitiligo-associated autoantigens such as tyrosinase and gp100 are located intracellularly, it has been suggested that the formation of neo-antigens due to haptenation, the exposure of cryptic epitopes or the modification of proteins during apoptosis could account for immune responses against these proteins [128,129]. In this scenario, after processing by mature Langerhans cells, antigenic peptides are presented to T cells which have escaped clonal deletion or to naïve T lymphocytes which are not tolerised to cryptic epitopes [128,129]. Activated cytotoxic T cells can then attack directly melanocytes expressing antigenic peptides in the context MHC class I molecules [31,34], and anti-melanocyte autoantibodies can be produced following the stimulation of B lymphocytes by activated helper T cells .
In summary, autoimmunity has an important role to play in vitiligo development with key contributions from anti-melanocyte autoreactive cytotoxic T cells , T helper 17 cells [74,75], and Treg cells [77-79].
Taïeb A, Picardo M. Epidemiology, definitions and classification. In: Taïeb A, Picardo M. (eds) Vitiligo. Berlin: Springer-Verlag; 2010. p13-24.
Taïeb A. Intrinsic and extrinsic pathomechanisms in vitiligo. Pigment Cell Res 2000;13: 41-47.
Gawkrodger DJ, Ormerod AD, Shaw L, Mauri-Sole I, Whitton ME, Watts MJ, Anstey AV, Ingham J, Young K. Vitiligo: concise evidence based guidelines on diagnosis and management. Postgrad Med J 2010;86: 466-471.
Kent G, Al'Abadie M. Psychologic effects of vitiligo: A critical incident analysis. J Am Acad Dermatol 1996;35: 895-898.
Parsad D, Dogra S, Kanwar AJ. Quality of life in patients with vitiligo. Health Qual Life Outcomes 2003;1: 58.
Boisseau-Garsaud AM, Garsaud P, Cales-Quist D, Helenon R, Queneherve C, Claire RC. Epidemiology of vitiligo in the French West Indies (Isle of Martinique). Int J Dermatol 2000;39: 18-20.
Howitz J, Brodthagen H, Schwartz M, Thomsen K. Prevalence of vitiligo: Epidemiological survey on the Isle of Bornholm, Denmark. Arch Dermatol 1977;113: 47-52.
Handa S, Kaur I. Vitiligo: clinical findings in 1436 patients. J Dermatol 1999;10: 653-657.
Sehgal VN, Srivastava G. Vitiligo: compendium of clinico-epidemiological features. Indian J Dermatol Venereol Leprol 2007;73: 149-156.
Kakourou T. Vitiligo in children. World J Pediatr 2009;5: 265-268.
Grimes PE, Sevall JS, Vojdani A. Cytomegalovirus DNA identified in skin biopsy specimens of patients with vitiligo. J Am Acad Dermatol 1996;35: 21-26.
Al'Abadie MS, Kent GG, Gawkrodger DJ. The relationship between stress and the onset and exacerbation of psoriasis and other skin conditions. Br J Dermatol 1994;130: 199-203.
Al'Abadie MS, Senior HJ, Bleehen SS, Gawkrodger DJ. Neuropeptide and neuronal marker studies in vitiligo. Br J Dermatol 1994;131; 160-165.
Gauthier Y, Cario-Andre M, Taieb A. A critical appraisal of vitiligo etiologic theories. Is melanocyte loss a melanocytorrhagy? Pigment Cell Res 2003;16: 322-332.
Spritz RA. Six decades of vitiligo genetics: genome-wide studies provide insights into autoimmune pathogenesis. J Invest Dermatol 2012;132: 268–273.
Dell'Anna ML, Picardo, M. A review and a new hypothesis for non-immunological pathogenetic mechanisms in vitiligo. Pigment Cell Res 2006;19: 406-411.
Schallreuter KU, Moore J, Wood JM, Beazley WD, Peters EMJ, Marles LK, Behrens-Williams SC, Dummer R, Blau N, Thony B. Epidermal H2O2 accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes? J Invest Dermatol 2001;116: 167–174.
Schallreuter KU, Wood JM, Berger, J. Low catalase levels in the epidermis of patients with vitiligo. J Invest Dermatol 2001;97: 1081–1085.
Van den Boorn JG, Konijnenberg D, Dellemijn TA, van der Veen JP, Bos JD, Melief CJ, Vyth-Dreese FA, Luiten RM. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol 2009;129: 2220-2232.
Kemp EH, Weetman AP, Gawkrodger DJ. Humoral immunity. In: Taïeb A, Picardo M. (eds) Vitiligo. Berlin: Springer-Verlag; 2010. p.248-256.
Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, Manji N, Allahabadia A, Armitage M, Chatterjee KV, Lazarus JH, Pearce, S.H., Vaidya B, Gough SC, Franklyn JA. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med 2010;123: 183.e1-183.e9.
Birlea SA, Fain PR, Spritz RA. A Romanian population isolate with high frequency of vitiligo and associated autoimmune diseases. Arch Dermatol 2008;144: 310-316.
Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their relatives. Pigment Cell Res 2003;16: 208-214.
Laberge G, Mailloux CM, Gowan K, Holland P, Bennett DC, Fain PR, Spritz RA. Early onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Pigment Cell Res 2005;18: 300-305.
Singh A, Sharma P, Kar HK, Sharma VK, Tembhre MK, Gupta S, Laddha NC, Dwivedi M, Begum R, Indian Genome Variation Consortium, Gokhale RS, Rani R. HLA alleles and amino-acid signatures of the peptide-binding pockets of HLA molecules in vitiligo. J Invest Dermatol 2012;132: 124–134.
Jin Y, Birlea SA, Fain PR, Gowan, K., Riccardi SL, Holland PJ, Mailloux CM, Sufit AJ, Hutton, SM, Amadi-Myers A, Bennett DC, Wallace MR, McCormack WT, Kemp EH, Gawkrodger, D.J., Weetman, A.P., Picardo M, Leone G, Taieb A, Jouary T, Ezzedine K, van Geel N, Lambert J, Overbeck A, Spritz RA. Variant of TYRand autoimmunity susceptibility loci in generalized vitiligo. N Engl J Med 2010;362:1686–1697.
Jin Y, Ferrara T, Gowan K, Holcomb C, Rastrou M, Erlich HA, Fain PR, Spritz RA. Next-generation re-sequencing identifies common variants of TYRand HLA-Athat modulate the risk of generalized vitiligo via antigen presentation. J Invest Dermatol 2012;132: 1730–1733.
Liu J1, Tang H, Zuo X, Liang B, Wang P, Sun L, Yang S, Zhang X. A single nucleotide polymorphism rs9468925 of MHC region is associated with clinical features of generalized vitiligo in Chinese Han population. J Eur Acad Dermatol Venereol 2012;26: 1137–1141.
Quan C, Ren YQ, Xiang LH, Sun LD, Xu AE, Gao XH, Chen HD, Pu XM, Wu RN, Liang CZ, Li JB, Gao TW, Zhang JZ, Wang XL, Wang J, Yang RY, Liang L, Yu JB, Zuo XB, Zhang SQ, Zhang, SM, Chen G, Zheng XD, Li P, Zhu J, Li YW, Wei XD, Hong WS, Ye Y, Zhang Y, Wu WS, Cheng H, Dong PL, Hu DY, Li Y, Li M, Zhang X, Tang HY, Tang XF, Xu SX, He SM, Lv YM, Shen M, Jiang HQ, Wang Y, Li K, Kang XJ, Liu YQ, Sun L, Liu ZF, Xie SQ, Zhu CY, Xu Q, Gao JP, Hu, WL, Ni C, Pan TM, Yao S, He CF, Liu YS, Yu ZY, Yin XY, Zhang FY, Yang S, Zhou Y, Zhang XJ. Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nat Genet 2010;42: 614–618.
Al Badri AM, Fouli AK, Todd PM, Gariouch JJ, Gudgeon JE, Stewart DG, Gracie JA, Goudie RB. Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo. J Pathol 1993;169: 203-206.
Hedley SJ, Metcalfe R, Gawkrodger DJ, Weetman AP, MacNeil S. Vitiligo melanocytes in long-term culture show normal constitutive and cytokine-induced expression of intercellular adhesion molecule-1 and major histocompatibility complex class I and class II molecules. Br J Dermatol 1998;139: 965-973.
Van den Wijngaard R, Wankowicz-Kalinska A, Le Poole C, Tigges AJ, Westerhof W, Das P. Local immune response in skin of generalised vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+T cells at the perilesional site. Lab Invest 2000;80: 1299-1309.
Ogg GS, Dunbar PR, Romero P, Chen JL, Cerundolo V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J Exp Med 1998; 188:1203–1208.
Le Poole IC, Mutis T, van den Wijngaard RM, Westerhof W, Ottenhoff T, de Vries RR, Das PK. A novel, antigen-presenting function of melanocytes and its possible relationship to hypopigmentary disorders. J Immunol 1993;151: 7284-7292.
Van den Wijngaard RM, Asghar SS, Pijnenborg AC, Tigges AJ, Westerhof W, Das P. Aberrant expression of complement regulatory proteins, membrane cofactor protein and decay accelerating factor, in the involved epidermis of patients with vitiligo. Br J Dermatol 2002;146: 80-87.
Cui J, Arita Y, Bystryn J-C. Characterisation of vitiligo antigens. Pigment Cell Res 1995;8: 53-59.
Naughton GK, Reggiardo MD, Bystryn J-C. Correlation between vitiligo antibodies and extent of depigmentation in vitiligo. J Am Acad Dermatol 1986;15: 978-981.
Harning R, Cui J, Bystryn, J-C. Relation between the incidence and level of pigment cell antibodies and disease activity in vitiligo. J Invest Dermatol 1991;97: 1078-1080.
Laddha NC, Dwivedi M, Mansuri MS, Singh M, Gani AR, Panchal V, Khan F, Dave D, Patel A, Shajil EM, Gupta R, Marfatia Z, Marfatia YS, Begum R. Role of oxidative stress and autoimmunity in onset and progression of vitiligo. Exp Dermatol 2014;23: 345-368.
Xie P, Geohegan WD, Jordan RE. Vitiligo autoantibodies. Studies of subclass distribution and complement activation. J Invest Dermatol 1991;96: 627.
Aronson PJ, Hashimoto K. Association of IgA anti-melanoma antibodies in the sera of vitiligo patients with active disease. J Invest Dermatol 1987;88: 475.
Kemp EH, Gawkrodger DJ, MacNeil S, Watson PF, Weetman AP. Detection of tyrosinase autoantibodies in patients with vitiligo using 35S-labeled recombinant human tyrosinase in a radioimmunoassay. J Invest Dermatol 1997;109: 69-73.
Baharav E, Merimski O, Shoenfeld Y, Zigelman R, Gilbrud B, Yecheskel G, Youinou P, Fishman P. Tyrosinase as an autoantigen in patients with vitiligo. Clin Exp Immunol 1996;105: 84–88.
Song YH, Connor E, Li Y, Zorovich B, Balducci P, Maclaren N. The role of tyrosinase in autoimmune vitiligo. Lancet 1994;344: 1049-1052.
Kemp EH, Waterman EA, Gawkrodger DJ, Watson PF, Weetman AP. Autoantibodies to tyrosinase-related protein-1 detected in the sera of vitiligo patients using a quantitative radiobinding assay. Br J Dermatol 1998;139: 798-805.
Kemp EH, Gawkrodger DJ, Watson PF, Weetman AP. Immunoprecipitation of melanogenic enzyme autoantigens with vitiligo sera: evidence for cross-reactive autoantibodies to tyrosinase and tyrosinase-related protein-2 (TRP-2). Clin Exp Immunol 1997;109: 495–500.
Okamoto T, Irie RF, Fujii S, Huang S, Nizze AJ, Morton DL, Hoon DS. Anti-tyrosinase-related protein-2 immune response in vitiligo and melanoma patients receiving active-specific immunotherapy. J Invest Dermatol 1998;111: 1034-1039.
Kemp EH, Gawkrodger DJ, Watson PF, Weeman AP. Autoantibodies to human melanocyte-specific protein Pmel17 in the sera of vitiligo patients: a sensitive and quantitative radioimmunoassay (RIA). Clin Exp Immunol 1998;114:333-338.
Waterman EA, Gawkrodger DJ, Watson PF, Weetman AP, Kemp EH. Autoantigens in vitiligo identified by the serological selection of a phage-displayed melanocyte cDNA expression library. J Invest Dermatol 2010;130: 230-240.
Kemp EH, Waterman EA, Hawes BE, O'Neill K, Gottumukkala RV, Gawkrodger DJ, Weetman AP, Watson PF. The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo. J Clin Invest 2002;109: 923-930.
Li Q, Lv Y, Li C, Yi X, Long HA, Qiao H, Lu T, Luan Q, Li K, Wang X, Wang G, Gao, T. Vitiligo autoantigen VIT75 is identified as lamin A in vitiligo by serological proteome analysis based on mass spectrometry. J Invest Dermatol 2010;131: 727-734.
Mandry RC, Ortiz LJ, Lugo-Somolinos A, Sanchez JL. Organ-specific autoantibodies in vitiligo patients and their relatives. Int J Dermatol 1996;35: 18-21.
Farrokhi S, Farsangi-Hojjat M, Noohpisheh MK, Tahmasbi R, Rezaei N. Assessment of the immune system in 55 Iranian patients with vitiligo. J Eur Acad Dermatol Venereol 2005;19: 706-711.
Yu HS, Kao CH, Yu CL.Coexistence and relationship of antikeratinocyte and antimelanocyte antibodies in patients with non-segmental-type vitiligo. J Invest Dermatol 1993:100; 823-828.
Fishman P, Azizi E, Shoenfeld Y, Sredni, B, Yecheskel G, Ferrone S, Zigelman R, Chaitchik S, Floro S, Djaldetti M. Vitiligo autoantibodies are effective against melanoma. Cancer 1993;72: 2365-2369.
Gottumukkala RVSRK, Gavalas NG, Akhtar S, Metcalfe RA, Gawkrodger DJ, Haycock JW, Watson, PF, Weetman AP, Kemp EH. Function blocking autoantibodies to the melanin-concentrating hormone receptor in vitiligo patients. Lab Invest 2006;86: 781-789.
Norris DA, Kissinger RM, Naughton GM, Bystryn J-C. Evidence for immunologic mechanisms in human vitiligo: patients' sera induce damage to human melanocytes in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity. J Invest Dermatol 1998;90: 783-789.
Gilhar A, Zelickson B, Ulman Y, Etzioni A. In vivo destruction of melanocytes by the IgG fraction of serum from patients with vitiligo. J Invest Dermatol 1995;105: 683-686.
Yi YL, Yu CH, Yu HS. IgG anti-melanocyte antibodies purified from patients with active vitiligo induce HLA-DR and intercellular adhesion molecule-1 expression and an increase in interleukin-8 release by melanocytes. J Invest Dermatol 2000;115: 969-973.
Cario-Andre M, Pain C, Gauthier Y, Taieb A. The melanocytorrhagic hypothesis of vitiligo tested on pigmented, stressed, reconstructed epidermis. Pigment Cell Res 2007;20: 385-393.
Ruiz-Argüelles A, Brito GJ, Reyes-Izquierdo P, Pérez-Romano B, Sánchez-Sosa S. Apoptosis of melanocytes in vitiligo results from antibody penetration. J Autoimmun 2007;29 :281–286.
Michaëlsson G. Vitiligo with raised borders. Report of two cases. Acta Derm Venereol 1968;48: 158-161.
Lang KS, Caroli CC, Muhm D, Wernet D, Moris A, Schittek B, Knauss-Scherwitz E., Stevanovic S, Rammensee H-G, Garbe C. HLA-A2 restricted, melanocyte-specific CD8+T lymphocytes detected in vitiligo patients are related to disease activity and are predominantly directed against MelanA/MART1. J Invest Dermatol 2001;116: 891-897,
Le Gal, FA, Avril M, Bosq J, Lefebvre P, Deschemin JC, Andrieu M, Dore MX, Guillet JG. Direct evidence to support the role of antigen-specific CD8 (+) T-cells in melanoma-associated vitiligo. J Invest Dermatol 2001;117: 1464-1470.
Mandelcorn-Monson RL, Shear NH, Yau E, Sambhara S, Barber BH, Spaner D, DeBenedette MA. Cytotoxic T lymphocyte reactivity to gp100, MelanA/MART-1, and tyrosinase, in HLA-A2-positive vitiligo patients. J Invest Dermatol 2003;121: 550-556.
Palermo B, Campanelli R, Garbelli S, Mantovani S, Lantelme E, Brazzelli V, Ardigó M, Borroni G, Martinetti M, Badulli C, Necker A, Giachino C. Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo. J Invest Dermatol 2001;117: 326–32.
Dwivedi M, Laddha NC, Arora P, Marfatia YS, 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 2013;26: 586-591.
Al Badri AMT, Todd PM, Garioch JJ, Gudgeon JE, Stewart DG, Goudie RB. An immunohistological study of cutaneous lymphocytes in vitiligo. J Pathol 1993;170: 149-155.
Abdallah M, Lotfi R, Othman W, Galal R. Assessment of tissue FoxP3+, CD4+and CD8+T-cells in active and stable nonsegmental vitiligo. Int J Dermatol 2014;53: 940-946.
Wankowicz-Kalinska A, van den Wijngaard RM, Tigges BJ, Westerhof W, Ogg GS, Cerundolo V, Storkus WJ, Das PK. Immunopolarization of CD4+and CD8+T cells to type-1-like is associated with melanocyte loss in human vitiligo. Lab Invest 2003;83: 683-695.
Dwivedi M, Laddha NC, Shah K, Shah BJ, Begum R. Involvement of interferon-gamma genetic variants and intercellular adhesion molecule-1 in onset and progression of generalized vitiligo. J Interferon Cytokine Res 2013;33: 646-659.
Le Poole IC, Stennett LS, Bonish BK, Dee L, Robinson JK, Hernandez C, Hann SK, Nickoloff BJ. Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin. Br J Dermatol 2003;149: 739-748.
Steitz J, Wenzel J, Gaffal E, Tüting T. Initiation and regulation of CD8+T cells recognizing melanocytic antigens in the epidermis: implications for the pathophysiology of vitiligo. Eur J Cell Biol 2004; 83: 797–803.
Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, Fujimoto M, Serada S, Naka T, Katayama I. Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res 2012;25: 219-230.
Wang CQ, Cruz-Inigo AE, Fuentes-Duculan J, Moussai D, Gulati N, Sullivan-Whalen M, Gilleaudeau P, Cohen JA, Krueger JG. Th17 cells and activated dendritic cells are increased in vitiligo lesions. PLoS One 2011;6: e18907.
Levings MK, Sangregorio R, Roncarolo MG. Human CD25(+)CD4(+) T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001;193: 1295-1302.
Lili Y, Yi W, Ji Y, Yue S, Weimin S, Ming L. Global activation of CD8+cytotoxic T lymphocytes correlates with an impairment in regulatory T cells in patients with generalized vitiligo. PLoS One 2012;7: e37513.
Ben Ahmed M, Zaraa I, Rekik R, Elbeldi-Ferchiou A, Kourda N, Belhadj Hmida N, Abdeladhim M, Karoui O, Ben Osman A, Mokni M, Louzir H. Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo. Pigment Cell Melanoma Res 2012;25: 99-109.
Dwivedi M, Kemp EH, Laddha NC, Mansuri MS, Weetman AP, Begum R. Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics. Autoimmunity Rev 2014;doi: 10.1016/j.autrev.2014.10.002.
Ono S, Tanizaki H, Otsuka A, Endo Y, Koyanagi I, Kataoka TR, Miyachi Y, Kabashima K. Coexistent skin lesions of vitiligo and psoriasis vulgaris. Immunohistochemical analyses for IL-17A-producing cells and regulatory T cells. Acta Derm Venereol 2014;94: 329-330.
Terras S, Gambichler T, Moritz RK, Altmeyer P, Lambert J. Immunohistochemical analysis of FOXP3+regulatory T cells in healthy human skin and autoimmune dermatoses. Int J Dermatol 2014;53: 294-299.
Zhou L, Li K, Shi YL, Hamzavi I, Gao TW, Henderson M, Huggins RH, Agbai O, Mahmoud B, Mi X, Lim HW, Mi QS. Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells. Pigment Cell Melanoma Res 2012;25: 602-611.
Klarquist J, Denman CJ, Hernandez C, Wainwright DA, Strickland FM, Overbeck A, Mehrotra S, Nishimura MI, Le Poole IC. Reduced skin homing by functional Treg in vitiligo. Pigment Cell Melanoma Res 2010;23: 276-286.
Abdallah M, Saad A. Evaluation of circulating CD4+CD25highFoxP3+T lymphocytes in active non-segmental vitiligo. J Pan-Arab League Dermatol 2009;20: 1.
Elela MA, Hegazy RA, Fawzy MM, Rashed LA, 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 2013;23: 350-355.
Dwivedi M, Laddha NC, Imran M, Shah BJ, Begum R. Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) in isolated vitiligo: a genotype-phenotype correlation. Pigment Cell Melanoma Res 2011;24: 737-740.
Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M, Fabbri P. New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 2002;15: 87-92.
Tembhre MK, Sharma VK, Sharma A, Chattopadhyay P, Gupta S. T helper and regulatory T cell cytokine profile in active, stable and narrow band ultraviolet B treated generalized vitiligo. Clin Chim Acta 2013;424:27-32.
Tu CX, Jin WW, Lin M, Wang ZH, Man MQ. Levels of TGF-β(1) in serum and culture supernatants of CD4(+)CD25(+) T cells from patients with non-segmental vitiligo. Arch Dermatol Res 2011;303:685-9.
Taher ZA, Lauzon G, Maguiness S, Dytoc MT. Analysis of interleukin-10 levels in lesions of vitiligo following treatment with topical tacrolimus. Br J Dermatol 2009;161: 654-659.
Chatterjee S, Eby JM, Al-Khami AA, Soloshchenko M, Kang HK, Kaur N, Naga OS, Murali A, Nishimura MI, Le Poole IC, Mehrotra S. A quantitative increase in regulatory T cells controls development of vitiligo. J Invest Dermatol 2014;134:1285-1294.
Le Poole IC, van den Wijngaard RMJGJ, Westerhof W, Das, PK. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol1996;148: 1219-1228.
Oiso N, Tanemura A, Kotobuki Y, Kimura M, Katayama I, Kawada A. Role of macrophage infiltration in successful repigmentation in a new periphery-spreading vitiligo lesion in a male Japanese patient. J Dermatol 2013; 40: 915-918.
Trcka J, Moroi Y, Clynes RA, Goldberg SM, Bergtold A, Perales MA, Ma M, Ferrone CR, Carroll MC, Ravetch JV, Houghton AN. Redundant and alternative roles for activating Fc receptors and complement in an antibody-dependent model of autoimmune vitiligo. Immunity 2002;16: 861-868.
Serarslan G, Yönden Z, Söğüt S, Savaş N, Celik E, Arpaci A. Macrophage migration inhibitory factor in patients with vitiligo and relationship between duration and clinical type of disease. Clin Exp Dermatol 2010;35: 487-490.
Kroll TM, Bommiasamy H, Boissy RE, Hernandez C, Nickoloff BJ, Mestril R, Le Poole IC. 4-tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo. J Invest Dermatol 2005;124: 798–806.
Itoi S, Tanemura A, Kotobuki Y, Wataya-Kaneda M, Tsuruta D, Ishii M, Katayama I. Coexistence of Langerhans cells activation and immune cells infiltration in progressive nonsegmental vitiligo. J Dermatol Sci 2014;73: 83-85.
Denman CJ, McCracken J, Hariharan V, Klarquist J, Oyarbide-Valencia K, Guevara-Patiño JA, Le Poole IC. HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo. J Invest Dermatol 2008;128: 2041-2048.
Basak PY, Adiloglu AK, Koc IG, Tas T, Akkaya VB. Evaluation of activatory and inhibitory natural killer cell receptors in non-segmental vitiligo: a flow cytometric study. J Eur Acad Dermatol Venereol 2008;22: 970-976.
Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M, Fabbri P. New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 2002;15: 87-92.
Yeo UC, Yang YS, Park KB, Sung HT, Jung SY, Lee ES, Shin MH. Serum concentration of the soluble interleukin-2 receptor in vitiligo patients. J Dermatol Sci 1999;19: 182-188.
Yu HS, Chang KL, Yu CL, Li HF, Wu MT, Wu CS, Wu CS. Alterations in IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma release by peripheral mononuclear cells in patients with active vitiligo J Invest Dermatol 1997;108: 527-529.
Laddha NC, Dwivedi M, Begum R. Increased tumor necrosis factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo. PLoS One 2012;7:e52298.
Imran M, Laddha NC, Dwivedi M, Mansuri MS, Singh J, Rani R, Gokhale RS, Sharma VK, Marfatia YS, Begum R. Interleukin-4 genetic variants correlate with its transcript and protein levels in patients with vitiligo. Br J Dermatol 2012;167: 314-323.
Birol A, Kisa U, Kurtipek GS, Kara F, Kocak M, Erkek E, Caglayan O. Increased tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL1-alpha) levels in the lesional skin of patients with nonsegmental vitiligo. Int J Dermatol 2006;45: 992-993.
Basak PY, Adiloglu AK, Ceyhan AM, Tas T, Akkaya VB. The role of helper and regulatory T cells in the pathogenesis of vitiligo. J Am Acad Dermatol 2009;60: 256-60.
Shi YL, Weiland M, Lim HW, Mi QS, Zhou L. Serum miRNA expression profiles change in autoimmune vitiligo in mice. Exp Dermatol 2014;23:140-142.
Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T, Yoshimura A, Baltimore D, Rudensky AY. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 2010;142: 914-929.
Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J, Sun G, Tay J, Linsley PS, Baltimore D. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med 201;208: 1189-1201.
Mueller DW, Rehli M, Bosserhoff AK. miRNA expression profiling in melanocytes and melanoma cell lines reveals miRNAs associated with formation and progression of malignant melanoma. J Invest Dermatol 2009;129: 1740-1751.
Mansuri MS, Singh M, Dwivedi M, Laddha NC, Marfatia YS, Begum R. miRNA profiling revealed differentially expressed miRNA signatures from skin of non-segmental vitiligo patients. Br J Dermatol 2014;doi: 10.1111/bjd.13109.
Homey B, Assmann T, Vohr HW, Ulrich P, Lauerma AI, Ruzicka T, Lehmann P, Schuppe HC. Topical FK506 suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during primary skin immune responses. J Immunol 1998;160: 5331-5340.
Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert JM. Topical pimecrolimus in the treatment of vitiligo. Eur J Dermatol 2007;17: 55-61.
Hartmann A, Brocker EB, Hamm H. Occlusive treatment enhances efficacy of tacrolimus 0.1% ointment in adult patients with vitiligo: results of a placebo-controlled 12-month prospective study. Acta Derm Venereol 2008;88: 474-479.
Abu Tahir M, Pramod K, Ansari SH, Ali J. Current remedies for vitiligo. Autoimmun Rev 2010;9: 516-520.
Hann SK, Kim HI, Im S, Park YK, Cui J, Bystryn JC. The change of melanocyte cytotoxicity after systemic steroid treatment in vitiligo patients. J Dermatol Sci 1993;6: 201-205.
Takei M, Mishima Y, Uda H. Immunopathology of vitiligo vulgaris, Sutton's leukoderma and melanoma-associated vitiligo in relation to steroid effects. I. Circulating antibodies for cultured melanoma cells. J Cutan Pathol 1984;11: 107-113.
Alomar, A. PUVA and related treatment. In: Taïeb A, Picardo M. (eds) Vitiligo. Berlin: Springer-Verlag; 2010. p345-350.
Kao CH, Yu HS. Comparison of the effect of 8-Methoxypsoralen (8-MOP) plus UVA (PUVA) on human melanocytes in vitiligo vulgaris and in vitro. J Invest Dermatol 1992; 98: 734-740.
Viac J, Groujon C, Misery L, Staniek V, Faure M, Schmitt D, Claudy A. Effect of UVB 311 mm irradiation on normal human skin. Photodermatol Photoimmunol Photomed 1997;13: 103-108.
Krutmann J, Morita A. Mechanisms of ultraviolet (UV) B and phototherapy. J Invest Dermatol Symp Proc 1999;4: 70-72.
Duthie MS, Kimber I, Norval M. The effects of ultraviolet radiation on the immune system. Br J Dermatol 1999;140: 995-1009.
Olsson MJ. Surgical therapies. In: Taïeb A, Picardo M. (eds) Vitiligo. Berlin: Springer-Verlag; 2010. p394-406.
Le Poole IC, Das PK, van den Wijngaard RM, Bos JD, Westerhof W. Review of the etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol 1993;2: 145-153.
Hariharan V, Klarquist J, Reust MJ, Koshoffer A, McKee MD, Boissy RE, Le Poole IC. Monobenzyl ether of hydroquinone and 4-tertiary butyl phenol activate markedly different physiological responses in melanocytes: relevance to skin depigmentation. J Invest Dermatol 2010;130: 211-220.
Mosenson JA, Zloza A, Klarquist J, Barfuss AJ, Guevara-Patino JA, Poole IC. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell Melanoma Res 2012;25: 88-98.
Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo. Curr Dir Autoimmun 2008;10: 227-243.
Namazi MR Neurogenic dysregulation, oxidative stress, and melanocytorrhagy in vitiligo: can they be interconnected? Pigment Cell Res 2007;20: 360-363.
Westerhof W, d’Ischia M. Vitiligo puzzle: the pieces fall in place. Pigment Cell Res 2007;20: 345-359.