Increased Circulating CXCL10 in Non-Segmental Vitiligo Concomitant with Autoimmune Thyroid Disease and Alopecia Areata

BackgroundVitiligo is a common acquired pigmentary disease caused by destruction of epidermal melanocytes in underlying autoimmune response. Few studies have been focused on the role of chemokines in non-segmental vitiligo (NSV) concomitant with autoimmune thyroid disease (AITD) and alopecia areata (AA).ObjectiveThe aim of this study was to determine the best serum biomarker for predictive role in the progression of vitiligo and to evaluate the influence of AA and/or AITD on vitiligo by using the biomarker.MethodsThis prospective cohort study recruited 45 NSV patients: 14 without either AITD or AA, 12 with AITD, 11 with AA, and 8 with both AITD and AA. Serum levels of CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 were analyzed by ELISA. CXCR3 mRNA expression was detected on PBMCs by RT-PCR. Improvement was evaluated using repigmentation scales.ResultsSerum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with AITD or AA alone than in those without AITD or AA. Moreover, serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with both AITD and AA than in those with AITD or AA alone. Poorer repigmentation was observed in NSV patients with both AA and AITD than in those with AA or AITD alone.ConclusionCXCL10 could be a biomarker to predict the progression of NSV. Dermatologists should pay much attention to those NSV patients concomitant with AITD and/or AA, for comorbidity might lead to more active autoimmune reaction.     

Relevance of autoimmune thyroiditis in children and adolescents with vitiligo

Background Vitiligo is the most common pigmentation‐related disorder worldwide. An autoimmune etiology is widely considered, and genetic factors may play an important role in its pathogenesis. The purpose of this study was to assess the incidence of thyroid dysfunctions and autoimmune thyroiditis in children with vitiligo and to identify related factors. Methods Fifty children with vitiligo and 50 control children were enrolled. Data on age, onset, duration, disease activity, presence of thyroid disorder, other autoimmune diseases, halo nevi, poliosis, and mucosal vitiligo were determined. Serum free triiodothyronine, free thyroxine, total T3, total T4, thyroid‐stimulating hormone, and antibodies to thyroperoxidase and thyroglobulin were measured. Thyroid gland efficiency was evaluated. Results The mean age at onset of vitiligo was 7.26 ± 4.43 years. The duration of vitiligo was 2.26 ± 2.95 years. Vulgaris‐type vitiligo was the most common form in our patients (56%), and 42% reported at least one family member with thyroid disorder, autoimmune disease, or both. Overt hypothyroidism or hyperthyroidism were not detected. We found a significant association between autoimmune thyroiditis and both sex and disease duration (P = 0.046 and P = 0.07, respectively), but no association between autoimmune thyroiditis and age, age at onset of vitiligo, halo nevi, poliosis, mucosal involvement, disease activity, or family history of vitiligo, autoimmunity, or thyroid disorders. Conclusions Children with vitiligo show an increased incidence of autoimmune thyroiditis. Children with vitiligo, especially girls and subjects with generalized/vulgaris‐type vitiligo, should be screened annually for thyroid function and antithyroid antibodies to assist in the early diagnosis and therapy of autoimmune thyroiditis.     

Vitiligo in an urban academic setting*

Background Vitiligo is a depigmenting disease of unknown etiology. A more complete understanding of vitiligo and associated conditions will provide better insight into the etiology and potential treatment options for this condition. We sought to gather information regarding associated conditions and other epidemiologic data on vitiligo. Methods A retrospective chart review was performed of 135 patients with vitiligo seen between July 1, 2002 and June 30, 2005 at an academic medical center. Epidemiologic characteristics were recorded. Results The patient population consisted of 80 women and 55 men with mean age of presentation of 36.8 years and average disease duration of 5.7 years. Vitiligo vulgaris was the predominant type of vitiligo and hypothyroidism was the most common co‐morbidity. Anti‐thyroid peroxidase and anti‐thyroglobulin antibodies were found in 37% and 18% of patients, respectively. The highest proportion of thyroid abnormalities was found in age of onset category 21–30. Anti‐nuclear antibodies were found in 33% of patients. Conclusion The prevalence of anti‐nuclear and anti‐thyroid peroxidase antibodies was higher in our vitiligo study than that reported elsewhere. In addition, autoimmune thyroid disease may be more common in adult‐onset vitiligo.     

Pre- vs. post-pubertal onset of vitiligo: multivariate analysis indicates atopic diathesis association in pre-pubertal onset vitiligo

Background Limited epidemiological data exist that compare clinical features of pre‐ and post‐pubertal nonsegmental vitiligo. Objectives To compare factors associated with pre‐ and post‐pubertal onset vitiligo. Patients and methods A prospective observational study was conducted of patients with vitiligo attending the clinic between 1 January 2006 and 1 July 2011. The Vitiligo European Task Force questionnaire was completed for each patient and thyroid function and antithyroid antibodies were screened. Other forms of vitiligo (segmental, focal, mucosal, not classifiable) were excluded. Results A total of 679 patients were included; 422 had post‐pubertal and 257 pre‐pubertal onset of vitiligo. Vitiligo universalis was seen only in post‐pubertal onset. In univariate analysis, there was no significant statistical difference for sex, Koebner phenomenon or disease activity between both groups; thyroid disease or presence of thyroid antibodies was more frequent in post‐pubertal onset [odds ratio (OR) 0·31, P < 0·003] whereas atopic dermatitis was more often associated with or preceding pre‐pubertal onset (OR 2·42, P = 0·006). In multivariate analysis, halo naevi, family history of vitiligo, premature hair greying, atopic dermatitis and previous episode of spontaneous repigmentation were independently associated with pre‐pubertal onset. In contrast, stress as onset factor, personal history of thyroid disease and acrofacial type were associated with post‐pubertal onset. Conclusions Pre‐pubertal onset vitiligo is strongly associated with personal and family history of atopy, suggesting that the predisposing immune background in vitiligo is not limited to autoimmunity, as also noted in alopecia areata. This study also suggests reconsidering the epidemiological data on sex ratio in vitiligo.     

白癜风并发自身免疫性甲状腺疾病的研究现状

白癜风常并发其他自身免疫性疾病,如自身免疫性甲状腺疾病(autoimmunne thyroid disease,AITD)、类风湿关节炎、1型糖尿病、恶性贫血、系统性红斑狼疮(systemic lupus erthematosus,SLE)、艾迪生病、斑秃等,其中以AITD最多见,包括Graves病、慢性淋巴细胞性甲状腺炎(桥本病)、亚急性甲状腺炎、甲状腺相关性眼病等,但有关白癜风并发AITD确切机制研究甚少。鉴于白癜风是一种多因素、多基因遗传性疾病,发病机制复杂,与遗传和各种非遗传因素相关,多数认为是由基因、环境和免疫系统的相互作用,导致共同的终末通路,即氧化应激-自身免疫介导的黑素细胞缺失,特别是非节段型白癜风(non-segmental vitiligo,NSV)。该文从白癜风的基因、自身免疫和氧化应激3个关联机制上综述、阐述其与AITD的关系。     

Multivariate analysis of factors associated with early-onset segmental and nonsegmental vitiligo: a prospective observational study of 213 patients

Background Although mixed forms have been described recently, segmental (SV) and nonsegmental vitiligo (NSV) are considered as clinically distinct. However, limited epidemiological data are available to help distinguish associated factors, and recent genome‐wide association studies have been restricted to NSV. The higher prevalence of SV in children is helpful when comparing the two major presentations of the disease. Objective To compare factors associated with SV and NSV, especially for markers of autoimmunity or autoinflammation. Methods We conducted a single‐centre prospective observational study in patients aged 17 years or under with a confirmed diagnosis of SV or NSV at the vitiligo clinic between 1 January 2006 and 1 July 2010. The Vitiligo European Task Force questionnaire was completed for each patient, and thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Other forms of vitiligo (focal, mucosal, not classifiable) were excluded. Results A total of 213 children were included, 142 with NSV, 59 with SV and 12 with mixed vitiligo. There was no significant statistical difference for sex or age at onset between patients with SV and NSV. Halo naevi were significantly more frequent in NSV than in SV [odds ratio (OR) 7·58, P < 0·01). Patients with NSV more frequently had a positive family history of vitiligo (OR 2·25, P = 0·02) and a marked familial autoimmunity background (OR 2·22, P = 0·01). Conclusions Our study clearly shows that features of inflammation (pruritus)/autoimmunity (halo naevi, thyroid antibodies) are strongly linked to NSV, together with a familial background of vitiligo and autoimmunity.     

白癜风与自身免疫性甲状腺疾病的研究进展

临床流行病学研究发现,白癜风常伴发一些自身免疫性疾病,特别是自身免疫性甲状腺疾病.关于白癜风伴发自身免疫性甲状腺疾病已有许多的病例报道.相对于健康人群,白癜风患者中甲状腺相关抗体水平升高,伴发自身免疫性甲状腺疾病的白癜风患者往往患病年限长,皮损范围较大.白癜风患者体内Th17/Treg失衡,黑素细胞表达的相关蛋白被看作自身抗原,这些抗原有部分也表达于甲状腺组织,这是白癜风伴发自身免疫性甲状腺疾病的免疫基础.白癜风的易感基因位点有些与自身免疫疾病相关,这些位点是白癜风伴发自身免疫性甲状腺疾病的遗传因素.目前发现,-428T FoxD3变异与白癜风发生有密切关系,与抗TPO抗体及抗甲状腺球蛋白抗体升高相关.     

Effects of age of onset on disease characteristics in non‐segmental vitiligo

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non‐segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid‐stimulating hormone (TSH), thyroxine (T4) hormone, anti‐thyroid peroxidase (anti‐TPO), and anti‐thyroglobulin (anti‐TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult‐onset disease than in either pediatric patients or adults with childhood‐onset disease (P = 0.002). Both anti‐TG and anti‐TPO levels were significantly higher in adults with adult‐onset disease than in pediatric patients and adult patients with childhood‐onset disease. The prevalence of autoimmune disease was 22.2%. Anti‐TG levels were significantly higher in patients with treatment‐related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo.     

Experimental approaches to assess melanocytes mosaicism in segmental vitiligo

Vitiligo is an autoimmune disease of the skin that results in localized or disseminated white macules. One common feature of several existing classification protocols is the distribution of the disease into two main subtypes, non-segmental vitiligo (NSV) and segmental vitiligo (SV). SV is characterized by depigmentation spreading within one or more skin segments while NSV is widespread. Several clinical-epidemiological observations suggest that SV has distinct autoimmune pathophysiology compared to NSV. Furthermore, the clinical distribution pattern of SV lesions closely resembles other melanocyte mosaicism diseases. These observations led us to hypothesize that SV is caused by a localized autoimmune reaction targeting epidermal mosaicism melanocytes. Here, we proposed examples of experimental approaches to assess mosaicism in SV patients.     

The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients

Vitiligo is a common skin and hair depigmentary disorder that results from selective destruction of melanocytes. It occurs in a typical multifactorial, polygenic inheritance. Several studies have indicated that vitiligo is associated with some autoimmune diseases. In this paper we examined 6,516 vitiligo patients including clinical characteristics, familial involvement, and their association with other autoimmune diseases. Compared with sporadic vitiligo probands, familial vitiligo probands have earlier age onset and longer disease duration. The prevalences of four autoimmune diseases namely rheumatoid arthritis, chronic urticaria, alopecia areata and psoriasis, were significantly elevated in generalized vitiligo probands and their first-degree relatives. The prevalences of chronic urticaria, rheumatoid arthritis, psoriasis were much higher in familial generalized vitiligo probands. In addition, the prevalences of diabetes mellitus and asthma were also higher in familial vitiligo probands. These findings indicate that generalized vitiligo may share common genetic aetiologic links with other autoimmune diseases, and the genetic component of familial generalized vitiligo is stronger.     

Differential expression analysis of miRNA in peripheral blood mononuclear cells of patients with non‐segmental vitiligo

Vitiligo is a common depigmentary skin disease that may follow a pattern of multifactorial inheritance. The essential factors of its immunopathogenesis is thought to be the selective destruction of melanocytes. As a new class of microregulators of gene expression, miRNA have been reported to play vital roles in autoimmune diseases, metabolic diseases and cancer. This study sought to characterize the different miRNA expression pattern in the peripheral blood mononuclear cells (PBMC) of patients with non‐segmental vitiligo (NSV) and healthy individuals and to examine their direct responses to thymosin α1 (Tα1) treatment. The miRNA expression profile in the PBMC of patients with NSV was analyzed using Exiqon's miRCURY LNA microRNA Array. The differentially expressed miRNA were validated by real‐time quantitative polymerase chain reaction. We found that the expression levels of miR‐224‐3p and miR‐4712‐3p were upregulated, and miR‐3940‐5p was downregulated in the PBMC. The common clinical immune modulator Tα1 changed the miRNA expression profile. Our analysis showed that differentially expressed miRNA were associated with the mechanism of immune imbalance of vitiligo and that Tα1 could play an important role in changing the expression of these miRNA in the PBMC of patients with NSV. This study provided further evidence that miRNA may serve as novel drug targets for vitiligo therapeutic evaluation.     

Vitiligo and polyglandular autoimmune endocrinopathy

Vitiligo is probably an autoimmune disorder of the skin and is commonly associated with a number of known autoimmune endocrinopathies. We present a patient with vitiligo associated with diabetes mellitus and autoimmune thyroid disease. Further, we present evidence that vitiligo and autoimmune disorders coexist and discuss the interrelationship between vitiligo and autoimmune endocrine disorders.     

Human beta-defensin 1 circulating level and gene polymorphism in non-segmental vitiligo Egyptian patients

BackgroundVitiligo is an acquired depigmented skin disorder. It has a genetic and autoimmune background. Human beta defensin-1(HBD-1) plus its gene polymorphism were linked to some autoimmune disorders.ObjectiveTo elucidate the possible role of HBD-1 in the pathogenesis of non-segmental vitiligo (NSV) through evaluation of HBD-1 serum levels and its single nucleotide polymorphism (SNP) in patients having NSV, in addition, to correlating the results with the extent of vitiligo in those patients.MethodsA current case-control study included 50 patients having NSV and 50 controls. The authors used Vitiligo Area Scoring Index (VASI) score to assess vitiligo severity and laboratory investigations to assess serum HBD-1 level using ELISA and defensin-beta1 (DEFB1) SNP using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThere were significantly lower HBD-1 serum levels in NSV cases than in controls (p < 0.001). There was a significant predominance of GG DEFB1 genotype and G allele in NSV patients in comparison to controls (p < 0.001). The levels of serum HBD-1 and DEFB1 genotypes were not associated or correlated significantly with any of the personal and clinical parameters of vitiligo patients.Study limitationThe small sample size.ConclusionsDEFB1 gene polymorphism (GG genotype and G allele) may modulate vitiligo risk and contribute to vitiligo development in Egyptian populations. Decreased circulating HBD-1 levels might have an active role in vitiligo etiopathogenesis that could be mediated through its possible anti-inflammatory effects.     

Low yield of routine screening for thyroid dysfunction in asymptomatic patients with vitiligo

Background Nonsegmental vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. Screening patients with nonsegmental vitiligo for thyroid function and for the presence of thyroid autoantibodies has been recommended. Objective To investigate the prevalence of thyroid dysfunction and thyroid peroxidase‐specific (TPO) antibodies in a large cohort of patients with nonsegmental vitiligo in order to help decide whether routine screening is justified. Methods A total of 434 adults with nonsegmental vitiligo who were referred to our institute were enrolled. Thyroid function and anti‐TPO antibody titres were assessed in those patients who had no history of thyroid disease or recent thyroid screening. Results Forty‐three patients had already been diagnosed with thyroid dysfunction, and in 27 patients the general practitioner had performed a thyroid function test with negative results < 3 months previously. In these patients, thyroid function assessment was not repeated. The remaining 364 patients were screened for thyroid dysfunction. Overt hypothyroidism was newly diagnosed in three (0·8%) patients; subclinical disease was found in 10 (2·7%) patients and increased levels of TPO antibodies, without thyroid disease, were found in 49 (13·5%) patients. An elevated risk for thyroid disease was found among older women and in women with a positive family history of thyroid disease. Conclusion The overall prevalence of thyroid dysfunction in adult patients with nonsegmental vitiligo was higher than reported in the general population. However, the number of newly diagnosed cases with overt and subclinical thyroid dysfunction in our population was low. Most patients had already been diagnosed by their general practitioner and had symptoms indicative for thyroid disease. Thyroid disease was found predominantly among older women and in subjects with a positive family history of thyroid disease. Thyroid screening including anti‐TPO antibodies is advisable in these high‐risk subpopulations.     

Incidence and significance of organ-specific autoimmune disorders (clinical, latent or only autoantibodies) in patients with vitiligo

The frequency of autoimmune disorders was determined in 373 vitiligo patients and in controls matched for sex, age and race. Vitiligo patients had an increased frequency of clinical autoimmune diseases of thyroid (7.5%), stomach (0.8%), parathyroid (1%), adrenal gland (1.3%). Vitiligo patients, without clinical signs of overt autoimmune diseases, also had a statistically significant increase in the frequency of gastric parietal cell (p less than 0.001), thyroid microsomal (p less than 0.05) and adrenal autoantibodies (p less than 0.05). This increased incidence of autoimmune manifestations was correlated with the duration of vitiligo. Furthermore in 94% of the patients with parietal cell autoantibodies a gastric biopsy showed atrophic gastritis. In addition, in 48% of the patients with thyroid microsomal autoantibodies and in 2 out of 6 patients with adrenal autoantibodies without overt diseases at the beginning of the study, the functional investigation of the target organs during the follow-up allowed the detection of the presence or that of the subsequent development of clinical or subclinical dysfunction.     

An approach to the correlation between vitiligo and autoimmune thyroiditis in Chinese children

Background. Vitiligo is a common skin depigmenting disease, which is thought to have, at least partly, an autoimmune aetiology. Aim. To explore the correlation between paediatric vitiligo and other associated diseases, with an emphasis on autoimmune thyroiditis (AT). Methods. In total, 363 paediatric patients (198 boys, 165 girls) with vitiligo and 93 healthy children (55 boys, 38 girls) were screened for autoimmune thyroiditis. The two groups were matched for age and gender. Children with vitiligo were split into two groups according to type (segmental and nonsegmental vitiligo). Demographic data, clinical features and examinations were recorded using questionnaires. Thyroid function tests including free triiodothyronine, free thyroxine and thyroid‐stimulating hormone were performed. Anti‐thyroid peroxidase antibody) and anti‐thyroglobulin antibody levels were assessed as well. Other associated diseases were also monitored in this study. Results. Of the 363 patients, 43 (11.8%) had abnormal levels of studied thyroid parameters, compared with 4 of the 93 controls (4.3%); the difference was significant (P = 0.04). The alterations of thyroid parameters and the incidence of AT in patients with nonsegmental vitiligo were both significantly different (P < 0.05, P = 0.04) relative to the segmental vitiligo group. Of the 363 patients, 67 (18.5%) had other associated diseases. There were no differences in the rates of other associated diseases between patients with segmental vitiligo and those with nonsegmental vitiligo (P > 0.05). Conclusions. A significant incidence of thyroid dysfunction was found in paediatric patients with nonsegmental vitiligo. As vitiligo usually appears before the development of the thyroid disease, it may be advantageous to screen thyroid functions and antibody levels in all paediatric patients with vitiligo, especially those with nonsegmental vitiligo.     

Association of TXNDC5 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population

Background Vitiligo is a pigmentary skin disorder characterized by a chronic and progressive loss of melanocytes. Although the aetiology of vitiligo is currently unknown, several theories have been proposed to explain the pathogenesis of this disease, including autoimmune, neural, self‐destruction, oxidative stress, and genetic theories. Thioredoxin domain containing 5 (TXNDC5) is a newly identified member of the thioredoxin family. TXNDC5 has a protein disulphide isomerase‐like domain which plays an important role in protein folding and chaperone activity, against endoplasmic reticulum (ER) stress induced by oxidative stress within the ER. Objectives To determine whether variation in the TXNDC5 gene contributes to the risk of developing nonsegmental vitiligo (NSV) in the Korean population. Methods We conducted a case–control association study of 230 patients with NSV and 417 matched, unaffected controls. Seven single nucleotide polymorphisms (SNPs) in the TXNDC5 gene were selected for study. Results Of the selected SNPs, three exonic SNPs (rs1043784, rs7764128 and rs8643) were statistically associated with NSV. Among them, rs1043784 remained a statistically significant association following Bonferroni correction. These three SNPs were located within a block of linkage disequilibrium; the haplotypes AGG and GAA, consisting of rs1043784, rs7764128 and rs8643, demonstrated a significant association with NSV. Conclusions These results suggest that TXNDC5 gene polymorphisms are associated with the development of NSV in the Korean population.     

Vitiligo patients from India (Mumbai) show differences in clinical,demographic and autoantibody profiles compared to patients in western countries

Background Vitiligo is a common, idiopathic skin disorder characterized by depigmented skin due to the loss of cutaneous melanocytes. Several studies have reported the clinical and demographic characteristics of Indian vitiligo patients, however, none has characterized their antibody profiles. Objective To establish the clinical, demographic and serological details of a population of vitiligo patients from Mumbai, India, and to evaluate the data for any associations between clinical presentations and the occurrence of antibody responses. Methods Vitiligo patients (n = 79) were recruited to the study and their clinical and demographic details recorded. Serum antibodies, including those against melanocyte‐specific antigens, thyroid antigens and keratinocytes, were evaluated. Results The prevalence of vitiligo was independent of sex, and non‐segmental vitiligo was the most common form of the disease occurring in 65% of the patients. Patients with segmental vitiligo (mean age = 14.4 ± 4.6 years) presented at a younger age than those with non‐segmental disease (mean age = 32.5 ± 17.8 years). Personal and family histories of other autoimmune diseases occurred in 3% and 8% of patients, respectively. Antibodies were detected against tyrosinase, tyrosine hydroxylase, thyroid peroxidase, thyroglobulin and keratinocytes at frequencies of 11%, 22%, 18%, 24% and 27%, respectively. Overall, antibodies were more common in patients with non‐segmental vitiligo (50–67%) than in those with segmental disease (0–17%), and were detected more frequently in patients with shorter disease durations (<10 years). Conclusion Our study provides novel information relative to the clinical details, demographic features and serological parameters of a population of vitiligo patients from Mumbai, India. Important distinctions from similar surveys conducted in European patients were evident such as an infrequency of family history, a low prevalence of clinical autoimmune disease, and an absence of particular antibody specificities. These differences may have a bearing on the pathogenesis and course of the disease in Indian patients.