Serum level of S100B in vitiligo patients: Is it a marker of disease activity?

BACKGROUND: Vitiligo is a chronic depigmentary skin disorder, characterised clinically by the development of white macules and or patches caused by loss of epidermal melanocytes. S100B is a dual function protein released from epidermal melanocytes in response to injury. It considered a possible marker of disease activity in both malignant melanoma and vitiligo. AIM OF THE STUDY: To estimate the serum level of S100B level in vitiligo patients and correlate its level with disease activity and various disease parameters. PATIENTS AND METHODS: Sixty vitiligo patients and 60 healthy volunteers as controls were included in the study. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity (VIDA) scores were estimated for each patient. Quantitative assessment of S100B level using ELISA technique was done for all participants. RESULTS: S100B level was significantly correlated with the presence of vitiligo (P = 0.01), while it showed no correlation with the disease activity using VASI or VIDA scores. As regards the receiver operating characteristic (ROC) curve analysis of S100B for diagnosis and discrimination of vitiligo, serum S100B showed area under the curve (AUC) of 0.781 with 73.3% sensitivity and 80% specificity. CONCLUSION: The serum level of S100B was related to the presence of vitiligo, but its level did not show any relation to the disease activity using either VASI and VIDA scores or various disease parameters.

Increased level of cathelicidin (LL-37) in vitiligo: Possible pathway independent from vitamin D receptor gene polymorphism.

Vitiligo is a multifactorial skin disease with established role of genetics and autoimmunity in its pathogenesis. Vitamin D receptor (VDR) polymorphisms have been suggested to correlate with risk of vitiligo in some ethnic populations. On the other hand, cathelicidin, one of the innate immune system components, has a role in development of some chronic skin diseases and VDR regulates the expression of cathelicidin. We aimed to determine the plasma level of cathelicidin and its association with the VDR gene polymorphisms as well as plasma vitamin D level in patients with vitiligo. Ninety vitiligo patients and 90 non-vitiligo controls participated in this study. Blood levels of 25(OH) vitamin D and cathelicidin were determined with ELISA. Genotyping for VDR polymorphisms (ApaI, TaqI, FokI and BsmI) was done with RFLP-PCR method. Mean blood level of cathelicidin was significantly higher in vitiligo patients as compared to controls (P < .0001). Mean blood level of vitamin D was significantly lower in patients than controls (P = .01). Statistically significant differences were not observed for both genotype and allele frequencies of BsmI, ApaI and TaqI polymorphisms. There was a borderline increased risk of vitiligo in over-dominant model of FokI polymorphism with OR = 1.8 and P = .051. Our findings was suggestive of the potential role of cathelicidin in the pathogenesis of vitiligo; however, future evaluations are needed to determine its precise mechanism. Genetic study of VDR gene polymorphism was suggestive of increased risk of vitiligo in association with a FokI polymorphism in Iranian population.

Higher incidence of metabolic syndrome components in vitiligo patients: a prospective cross-sectional study

Abstract Background/Objectives: To investigate the association between vitiligo and metabolic syndrome. Methods: A prospective cross-sectional study was conducted between 2014 and 2016. Study (n = 155) and control groups (n = 155) were evaluated for metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III and the International Diabetes Federation criteria. Study group was divided into three groups according to their vitiligo area severity index and vitiligo disease activity score values (Group 1: 6.89 for VASI score, Group A: −1-0, Group B: 1-2 and Group C: 3-4 for vitiligo disease activity score respectively). MetS rates according to both criteria were compared between the vitiligo disease activity score and vitiligo area severity index groups. Results: Metabolic syndrome rates were 37.4% and 40% in the study group and 19.4% and 26.5% in the control group according to National CholesterolEducation Program Adult Treatment Panel III and International Diabetes Federation criteria, respectively (p < 001 and p = 0.011). Metabolic syndrome was more frequent in vitiligo area severity index Groups 2 and 3 compared to vitiligo area severity index Group 1, and in vitiligo disease activity score Group C compared to vitiligo disease activity score Groups A and B. Study limitations: Single center experience, absence of more specific oxidative-stress markers and lack of long-term follow-up of the patients. Conclusions: Frequency of metabolic syndrome was higher in patients with non-segmental vitiligo and the rate was higher in active/severe form of the disease.

Estimation of Homocysteine Level and Methylenetetrahydrofolate Reductase (MTHFR) Gene and Cystathionine B Synthase (CBS) Gene Polymorphisms in Vitiligo Patients.

BACKGROUND: Vitiligo is an acquired, multifactorial disorder of the skin and mucous membranes. An elevated homocysteine level has been described in vitiligo. Methylenetetrahydrofolate reductase (MTHFR) and cystathionine B synthase (CBS) are major determinants of the homocysteine metabolism. OBJECTIVES: Determine serum homocysteine levels in vitiligo patients as well as the association between MTHFR (C677T, A1298C) and CBSgene polymorphisms and susceptibility to vitiligo in a sample of those populations. METHODS: Homocysteine levels were estimated by radioimmunoassay while MTHFR (C677T, A1298C) and CBSgene polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism technique in 100 vitiligo patients and 80 healthy controls. RESULTS: The homocysteine level was significantly higher in vitiligo patients than controls (p = 0.000). Significant differences in the genotype and allele distributions of single nucleotide polymorphisms of the MTHFR (C677T, A1298C) with the mutant genotypes are more common in the controls than patients (p = 0.001, 0.029, respectively). CBS gene mutant genotypes and alleles are more common in vitiligo patients than controls (p = 0.002). CONCLUSION: CBSand MTHFRgene polymorphisms may play a major role in the genetic susceptibility to vitiligo.

Zinc-α2-Glycoprotein (ZAG): A New Deficiency in Vitiligo Patients.

Zinc-α2-glycoprotein (ZAG), a recently identified adipokine, is a multidisciplinary protein, which is secreted in various body fluids. The ZAG plays roles in lipolysis, regulation of metabolism, cell proliferation and differentiation, regulation of melanin synthesis, cell adhesion, and immunoregulation. The aim of this study is to estimate serum and tissue levels of ZAG in patients with vitiligo. The study included 30 vitiligo patients and 30 healthy controls. Lesional skin biopsy was performed, and blood sample was retrieved to determine the level of ZAG in blood using ELISA kit. In this study, the mean level of ZAG was found to be significantly lower in the vitiligo patients' tissue in comparison with the healthy control subjects' tissue ( p=0.001); the level of ZAG was also lower in vitiligo patients' serum in comparison with the healthy control subjects' serum ( p=0.001). A highly significant correlation was observed between the duration of the disease and the level of ZAG in the tissue of patients (r =0.9; p=0.001). Also a highly significant positive correlation was observed between the age of patients and the level of ZAG in the tissue (r =0.5; p=0.006). Diminishing of ZAG in serum and tissue of vitiligo patients is another important player sharing in the complex pathogenesis of vitiligo.

Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo.

T-cells play a crucial role in progression of autoimmunity, including vitiligo, yet the initial steps triggering their activation and tissue damage remain unknown. Here we demonstrate increased presence of type-1 innate lymphoid cells (NK and ILC1)-producing interferon gamma (IFNγ) in the blood and in non-lesional skin of vitiligo patients. Melanocytes of vitiligo patients have strong basal expression of chemokine-receptor-3 (CXCR3) isoform B which is directly regulated by IFNγ. CXCR3B activation by CXCL10 at the surface of cultured human melanocytes induces their apoptosis. The remaining melanocytes, activated by the IFNγ production, express co-stimulatory markers which trigger T-cell proliferation and subsequent anti-melanocytic immunity. Inhibiting the CXCR3B activation prevents this apoptosis and the further activation of T cells. Our results emphasize the key role of CXCR3B in apoptosis of melanocytes and identify CXCR3B as a potential target to prevent and to treat vitiligo by acting at the early stages of melanocyte destruction.

Oxidative Stress-Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo.

Vitiligo is a cutaneous depigmentation disorder caused by the destruction of epidermal melanocytes. The generation and the skin infiltration of autoreactive CD8+ cytotoxic T cells triggered by oxidative stress play a critical role in vitiligo. High-mobility group protein B1 (HMGB1) is a classic damage-associated molecular pattern molecule with strong proinflammatory effects in inflammatory reactions. A previous study reported an enhanced expression of HMGB1 in vitiligo lesions, but the role of HMGB1 in cutaneous inflammation of vitiligo is still unknown. In the present study, we initially found that HMGB1 was released from the nucleus of melanocytes in vitiligo perilesional skin. Furthermore, cultured normal human melanocytes could release HMGB1 under treatment with hydrogen peroxide. Moreover, HMGB1 facilitated the secretion of CXCL16 and IL-8 from keratinocytes by binding to the receptor for advanced glycation end products and activating NF-κB and extracellular signal-regulated kinase signaling pathways. Subsequently, HMGB1 led to the formation of chemotaxis for the migration of CD8+ T cells from patients with vitiligo by increasing the release of CXCL16 from keratinocytes. Additionally, HMGB1 promoted the maturation of dendritic cells from patients with vitiligo. Altogether, our study demonstrates that HMGB1 released from melanocytes contributes to the formation of oxidative stress-induced autoimmunity in vitiligo.

High incidence of MTHFR, CBS, and MTRR polymorphisms in vitiligo patients. Preliminary report in a retrospective study.

OBJECTIVE: Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis. It is related to both genetic and no genetic factors. The role of genetics is currently studied with several analytical approaches, such as genetic linkage, candidate gene association studies, genome-wide association studies (GWAS), deep DNA re-sequencing and gene expression studies. To date, there are no genetic traits directly related to vitiligo pathogenesis. PATIENTS AND METHODS: 43 cases of vitiligo patients and 30 healthy donors recruited as control, were screened by assaying the biochemical molecules involved in the self-cells cytotoxicity (haptoglobin and homocysteine) and candidate genes involved in the regulatory process of the re-methylation cycles and transsulfuration. Candidate genes and their polymorphisms screened are methylene-tetrahydrofolate-reductase (MTHFR) C677T and A1298C; cystathionine-beta-synthase enzyme (CBS) I278T and Ins68bp; and methionine-synthase-reductase (MTRR) A66G. RESULTS: A peculiar genetic profile in vitiligo patients are defined: 11.6% of vitiligo patients shown polymorphic variant MTHFR 677TT vs. 3.3% of healthy donor MTHFR 677CC profile (p=0.0017); 14.0% of vitiligo patients shown CBS polymorphic variant 278TT vs. 3.3% of healthy donor 278II profile (p=0.0012); and 11.6% of vitiligo patients shown MTRR 66GG vs. 3.3% of healthy donor MTRR 677AA profile (p>0.0001). CONCLUSIONS: This is the first study reporting the correlation between the polymorphic status of MTHFR C677T, CBS I278T, and MTRR A66G and vitiligo. The genetic screening of these polymorphisms could be useful for early detection of the inheritance risk factor in a subject carrying relatives with vitiligo. Although these data could suggest a kind of dysregulation, genetically based, of thiols production mechanisms. Based on these results, we have not been able to get hypothesis about the putative pathogenesis of vitiligo, and the precise cause remains unclear.

Cytokine profile (IL-2, IL-6, IL-17, IL-22, and TNF-α) in vitiligo-New insight into pathogenesis of disease.

BACKGROUND: Vitiligo is an autoimmune disease associated with alteration in levels of various cytokines. However, there are very few studies in this regard. OBJECTIVES: To assess the serum levels of cytokines secreted by Th1 (IL-2, TNF-α), Th2 (IL-6), and Th17 cells (IL-17, IL-22) in patients with localized vitiligo and generalized vitiligo and to correlate their levels with the extent, duration, and activity of disease. MATERIAL AND METHODS: Sixty patients of vitiligo (30 each of localized and generalized) and 30 controls were recruited in the study. Serum IL-2, -6, -17, -22, and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA) in all patients and healthy controls, and their levels were correlated with the extent, duration, and activity of vitiligo. RESULTS: We observed significantly raised levels of IL-2, -6, -17, -22, and TNF-α in both localized vitiligo and generalized vitiligo (P < .05). IL-2 was significantly raised (P = .028) in localized vitiligo, whereas IL-17 and IL-22 were significantly raised in generalized vitiligo (P = .00 and P = .019, respectively). Activity of disease showed positive correlation with serum TNF-α levels (P = .015) in localized vitiligo. Positive correlation of IL-17 (R = .238) with body surface area (BSA) was observed in patients with generalized vitiligo. CONCLUSIONS: Our study shows that cytokines secreted by Th17 cells play an important role in maintenance and spread of vitiligo as they increase in line with extent of disease. Also TNF-α increases in proportion with activity of disease, hence may act as biomarker for identifying patient with aggressive disease.

The impact of positive antinuclear antibody on narrowband ultraviolet B phototherapy in patients with vitiligo: A retrospective chart review.

BACKGROUND/PURPOSE: Screening antinuclear antibody (ANA) is not recommended prior to initiating narrowband ultraviolet B (NBUVB) phototherapy in vitiligo patients, unless concern for photosensitivity exists. Guidelines on prescribing NBUVB phototherapy in vitiligo patients with positive ANA are unavailable, prompting this study to uncover trends. METHODS: This retrospective chart review investigated patients 12 years of age or older with a diagnosis of vitiligo between January 2015 and September 2017, positive serum ANA, and NBUVB phototherapy. Demographic information, vitiligo type, ANA titer/pattern, starting dose, peak dose without phototoxicity, phototherapy frequency, total number of phototoxic events and treatments, coexisting photosensitizing disorders, and concomitant photosensitizing medications were collected. RESULTS: Seven (two males, five females) of 1485 charts met inclusion criteria. One Caucasian, two African-Americans, one Asian, and three Hispanic/Latinos patients were represented. Six of seven patients had generalized vitiligo and one had focal vitiligo. ANA titer/patterns and phototherapy frequencies were evaluated. Peak doses of NBUVB without phototoxic event were available in six of seven patients: 274, 290, 532, 618, 700, and 734 mJ/cm2 . Total number of phototoxic events varied: 1 (n = 1), 2 (n = 1), 4 (n = 1), 6 (n = 2), or 8 (n = 1). Total NBUVB treatments ranged between 6 and 132. Coexisting photosensitizing disorders were not identified. One patient had phototoxic events in association with photosensitizing medications. CONCLUSION: With regard to phototoxicity, meaningful trends were not identified that may guide prescription of phototherapy in vitiligo patients with positive ANA, suggesting ANA may not be exclusionary criteria when prescribing NBUVB.

Macrophage migration inhibitory factor as an incriminating agent in vitiligo

Abstract: Background: Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. Objective: To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Methods: Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. Results: There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Study limitations: Small number of investigated subjects. Conclusions: Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

Comparative study on some oxidative stress parameters in blood of vitiligo patients before and after combined therapy.

Currently accepted that oxidative stress is a triggering event in the melanocytic destruction and is probably involved in the etiopathogenesis of vitiligo disease. Despite numerous investigations, contradictory results were reported about the levels of oxidative stress biomarkers measured in the skin and blood of vitiligo patients. By Electron Paramagnetic Resonance spectroscopy (EPR) and spectrophotometry, we have investigated and compared some oxidative stress biomarkers in the blood of vitiligo patients' before and after UVB Narrow Band 311 nm phototherapy combined with the antioxidant nutritional supplement containing - Vitamin C, Vitamin B1, L -Cysteine, Lipoic Acid, and polyunsaturated fatty acids. Before therapy was found significantly higher levels of CAT activity and MDA compared to the patients after therapy and control group (p < 0.05). Moreover, levels of Asc* radicals in patients before therapy were significantly lower than those measured in controls and patients undergoing therapy (p < 0.05). Our finding, the combined therapy applied to vitiligo patients provoked an increase in the Asc* levels and a decrease in MDA products and also initial repigmentation in the vitiligo spots, made us believe that a combined antioxidant therapy, enriched with vitamin C could lead to improvement of the oxidant-antioxidant balance in vitiligo patients treated with UVB 311 phototherapy.

Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3.

Vitiligo is a chronic autoimmune depigmenting skin disorder that results from a loss of melanocytes. Multiple combinatorial factors have been involved in disease development, with a prominent role of the immune system, in particular T cells. After repigmentation, vitiligo frequently recurs in the same area, suggesting that vitiligo could involve the presence of resident memory T cells (TRM). We sought to perform a thorough characterization of the phenotype and function of skin memory T cells in vitiligo. We show that stable and active vitiligo perilesional skin is enriched with a population of CD8 TRM expressing both CD69 and CD103 compared with psoriasis and control unaffected skin. CD8 TRM expressing CD103 are mainly localized in the epidermis. Expression of CXCR3 is observed on most CD8 TRM in vitiligo, including the population of melanocyte-specific CD8 T cells. CD8 TRM displayed increased production of IFN-γ and tumor necrosis factor-α with moderate cytotoxic activity. Our study highlights the presence of functional CD8 TRM in both stable and active vitiligo, reinforcing the concept of vitiligo as an immune memory skin disease. The CD8 TRM that remain in stable disease could play a role during disease flares, emphasizing the interest in targeting this cell subset in vitiligo.

Narrow-band UVB effects on cutaneous vitamin D receptor expression and serum 25-hydroxyvitamin D in generalized vitiligo.

BACKGROUND/PURPOSE: Vitamin D has a role in variety of autoimmune diseases including vitiligo. Narrow-band UVB (NB-UVB) treatment of vitiligo might act through its effects on vitamin D and its receptor.This study is the first to elucidate NB-UVB effects on immunohistochemical vitamin D receptor (VDR) expression in generalized vitiligo and correlate it with serum vitamin D and repigmentation response. METHODS: Using immunohistochemistry, VDR expression was estimated in skin biopsies of 30 controls and 30 vitiligo patients; from vitiligo lesion, perilesional skin at baseline and from repigmented and nonresponding skin after 24 NB-UVB sessions. Baseline serum 25-hydroxyvitamin D [25(OH)D] was investigated and repeated after 24 NB-UVB sessions. RESULTS: Vitamin D receptor expression and serum 25(OH)D in controls were significantly higher compared to vitiligo patients. After NB-UVB therapy, there was a significant rise in VDR expression and serum 25(OH)D. VDR expression was significantly higher in repigmented skin compared to nonresponding lesion. Improvement in the clinical outcome score was associated with higher baseline VDR expression and higher serum 25(OH)D. CONCLUSIONS: NB-UVB phototherapy is associated with improved cutaneous VDR expression and vitamin D synthesis. Better repigmentation response to NB-UVB may be related to higher baseline VDR expression and its upregulation after phototherapy.

CXCL-10 and Interleukin-6 are reliable serum markers for vitiligo activity: A multicenter cross-sectional study.

This cross-sectional multicenter study aimed to evaluate serum CXCL-10, as an activity marker for vitiligo, and compare it with other putative serum and tissue markers. Serum CXCL-10 was compared to interferon gamma (IFN-γ), interleukin 6 (IL-6), and IL-17 using ELISA in 55 non-segmental vitiligo patients (30 active and 25 stable) and 30 healthy controls. Marginal skin biopsy was taken for immunohistochemical evaluation of CD8+T cells and CXCL-10+ve cells. Serum levels of CXCL-10, IL-17, and IL-6 were elevated in all vitiligo patients compared to controls (p < .05). All investigated serum markers were higher in active versus stable vitiligo. Tissue expression of CXCL-10+ve cells and CD8+ve T cells was stronger in vitiligo patients compared to controls, and tissue CXCL-10+ve cell expression was stronger in active versus stable cases. Positive correlations were noted between the different serum and tissue markers. CXCL-10 was the most specific, whereas IL-6 was the most sensitive serum marker to distinguish active from stable disease.

Selenium, zinc, copper, Cu/Zn ratio and total antioxidant status in the serum of vitiligo patients treated by narrow-band ultraviolet-B phototherapy.

BACKGROUND: Vitiligo is a chronic, depigmenting skin disorder, whose pathogenesis is still unknown. Narrow band ultraviolet-B (NB-UVB) is now one of the most widely used treatment of vitiligo. It was suggested that trace elements may play a role in pathogenesis of vitiligo. AIM: The aim of this study was to estimate the concentration of selenium (Se), zinc (Zn), copper (Cu) and Cu/Zn ratio as well as total antioxidant status (TAS) in the serum of patients with vitiligo. METHODS: We assessed 50 patients with vitiligo and 58 healthy controls. Serum levels of Se, Zn and Cu were determined by the atomic absorption spectrometry method, and the Cu/Zn ratio was also calculated. TAS in serum was measured spectrophotometrically. RESULT: Serum concentration of Se in patients with vitiligo before and after phototherapy was significantly lower as compared to the control group. Zn level in the serum of patients decreased significantly after phototherapy. We observed higher Cu/Zn ratio (p < .05) in examined patients than in the control group and after NB-UVB. We have found decrease in TAS in the serum of vitiligo patients after NB-UVB. CONCLUSIONS: The current study showed some disturbances in the serum levels of trace elements and total antioxidant status in vitiligo patients.

Role of chemokines and the corresponding receptors in vitiligo: A pilot study.

To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)-γ or tumor necrosis factor (TNF)-α were tested by quantitative real-time polymerase chain reaction and Luminex. The serum levels of CCL5, CXCL8 and CXCL10 in active vitiligo were significantly elevated compared with those in stable vitiligo patients. Furthermore, the levels of CCL3 and CCL4 had weak and positive correlations with the Vitiligo Area Scoring Index. In the peripheral blood of active vitiligo patients, the percentages of CD3+ CD8+ CCR5+ and CD3+ CD8+ CXCR3+ T cells were significantly increased compared with those in stable vitiligo and healthy controls. In the epidermis of lesions, the expression levels of CCL5 and CXCL10 in active vitiligo were significantly increased. In addition, the mRNA and protein levels of CCL5, CXCL8 and CXCL10 were significantly elevated in HaCaT cells after stimulation with TNF-α or IFN-γ. The CCR5/CCL5 and CXCR3/CXCL10 axes may play an important role in the progression and maintenance of vitiligo. Moreover, keratinocytes stimulated with TNF-α and IFN-γ may be a primary source of CCL5 and CXCL10.

Vitiligo and thyroid disease: a systematic review and meta-analysis.

Vitiligo is associated with (autoimmune) thyroid disease. However, confounding factors, including type and onset of vitiligo, require elucidation. We conducted a meta-analysis to identify vitiligo patients with increased risk of (autoimmune) thyroid disease. Studies were identified based on searches in PubMed, MEDLINE, Embase, and the Cochrane Library from inception of these databases to August 31st, 2017. Odds ratios (ORs) for the prevalence of (autoimmune) thyroid disease and thyroid antibodies in vitiligo patients were pooled, and subgroup analysis was performed. Thirty-seven studies with 78,714 vitiligo patients met the inclusion criteria. The prevalence of thyroid disease (TD) (OR: 3.932; 95% CI: 2.230-6.933), autoimmune TD (OR: 5.879; 95% CI: 2.682-12.885), anti-thyroperoxidase (TPO) antibody (OR: 3.838; 95% CI: 2.968-4.963), and anti-thyroglobulin antibody (OR: 3.513; 95% CI: 2.346-5.260) was significantly higher in vitiligo patients than in controls. Notably, the prevalence of TD and anti-TPO antibody was significantly higher in patients with non-segmental vitiligo, compared to those with segmental vitiligo. In contrast, the prevalence of TD was significantly lower in early-, compared to the late-onset vitiligo group (OR: 0.333; 95% CI: 0.244-0.453). Physicians should be aware of the increased risk of (autoimmune) thyroid disease in vitiligo patients. We recommend routine screening for anti-thyroid antibodies in vitiligo patients.