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.     

Autoantibodies against tyrosine hydroxylase in patients with non-segmental (generalised) vitiligo

Vitiligo is an acquired idiopathic hypomelanotic skin disorder characterised by depigmented macules because of loss of cutaneous melanocytes. Although the exact cause of vitiligo remains obscure, evidence suggests that autoimmunity plays a role in the pathogenesis of the disease. Previously, tyrosine hydroxylase (TH) was identified as a putative autoantigen in vitiligo using phage-display technology. In this study, the prevalence of TH antibodies in patients with vitiligo was investigated. A radioimmunoassay (RIA) was used to detect TH antibodies in sera from patients with either non-segmental vitiligo (n=79), segmental vitiligo (n=8) or other autoimmune diseases without concomitant vitiligo (n=91). Sera from healthy individuals (n=28) were also tested. Patients with segmental vitiligo, healthy controls and patients with other autoimmune diseases without concomitant vitiligo were all negative for TH antibody reactivity. Of 79 patients with non-segmental vitiligo, 18 (23%) were positive for TH antibodies in the RIA, and a significant increase in the prevalence of TH antibodies in patients with non-segmental vitiligo was evident when compared with controls (P=0.003). TH antibody prevalence was also significantly elevated in patients with active vitiligo compared to those with stable disease (P=0.009). Overall, the results indicate that TH is an antibody target in non-segmental but not in segmental vitiligo and that TH antibodies appear to be more frequent in patients with active vitiligo.     

Vitiligo and thyroid dysfunction in children and adolescents

The link between vitiligo and thyroid disease has been proved in adult patients. The aim of our study was to assess the prevalence of thyroid dysfunction in children and adolescents with vitiligo and to identify any predisposing factors of this association. This retrospective study included 75 children and adolescents with vitiligo: 47 (62.66%) females and 28 (37.33%) males. Physical examination, thyroid ultrasonography and laboratory parameters of thyroid disease were performed in all study subjects. Various degrees of thyroid parameter alterations were found in 19 (25.33%) of 75 patients. Hashimoto's thyroiditis associated with non-segmental vitiligo was present in 11 (14.66%) patients. The most common site of vitiligo onset in patients with Hashimoto's thyroiditis were upper limbs, which was significantly more frequent compared with patients without Hashimoto's thyroiditis (χ(2); P<0.05). Since vitiligo usually appears before the development of thyroid disease, it may be useful to screen the children and adolescents with vitiligo for thyroid autoantibodies.     

培养的自体黑素细胞移植治疗伴自身免疫性甲状腺疾病的非节段型白癜风患者的疗效及安全性随访

【摘要】 目的 探讨培养的自体黑素细胞移植治疗伴自身免疫性甲状腺疾病的白癜风患者的临床疗效及安全性。方法 回顾2008年5月至2018年12月杭州市第三人民医院行培养的自体黑素细胞移植治疗的2 284例非节段型白癜风,其中伴自身免疫性甲状腺疾病75例,包括甲状腺功能亢进42例,甲状腺功能减退18例,桥本甲状腺炎15例。比较伴自身免疫性甲状腺疾病组与不伴自身免疫性甲状腺疾病组的疗效及安全性。计数资料的比较采用χ2检验。结果 2 284例患者中,男1 085例,女1 199例,年龄（25.0 ± 1.2）岁,病程（5.1 ± 2.3）年。术后6个月,2 209例不伴自身免疫性甲状腺疾病组中1 873例有效（84.8%）、1 162例痊愈（52.6%）;伴自身免疫性甲状腺疾病组46例有效（61.3%）、20例痊愈（26.7%）,伴自身免疫性甲状腺疾病组有效率及痊愈率均低于不伴自身免疫性甲状腺疾病组（χ2值分别为29.72、19.54,均P < 0.001）。甲状腺功能减退组有效率低于甲状腺功能亢进组（χ2 = 6.61,P = 0.010）。伴自身免疫性甲状腺疾病组供皮区同形反应发生率（9.3%）高于不伴自身免疫性甲状腺疾病组（4.3%,χ2 = 4.31,P = 0.038）,且移植部位1、3、5及10年白斑复发率（6.7%、14.7%、17.3%、8.7%）均高于不伴自身免疫性甲状腺疾病组（0.7%、1.4%、2.1%、3.6%,χ2值分别为29.96、70.69、67.23、41.61;均P < 0.001）。结论 伴发自身免疫性甲状腺疾病对于白癜风的自体黑素细胞移植治疗具有负相关效应,针对该类患者更应积极采取有效的预防同形反应和移植区复发的手段。     

Vitiligo in an Italian Outpatient Center

Background: Vitiligo is a depigmentation disorder resulting from destruction of cutaneous melanocytes that affects 0.1–2% of the world’s population, irrespective of sex and race. Objective: To investigate the clinical and immunopathologic characteristics of a series of Italian vitiligo patients. Methods: We examined clinical and immunopathologic data of 204 patients affected by vitiligo at a university-based dermatology outpatient hospital (second clinic) between January 1998 and March 2008. In particular, the clinical-epidemiologic characteristics of our patients, serologic parameters suggestive of immune/autoimmune activity (autoantibodies, immune complexes, complement, immunoglobulins), and the association between vitiligo and HLAs were investigated. Results: Upon comparison of our results with control and literature values, the following aspects appeared to be in complete agreement: the frequency of clinical subtypes of vitiligo, an earlier onset of segmental compared with non-segmental vitiligo, the association of familial vitiligo with other autoimmune diseases, the greater association of non-segmental vitiligo than segmental vitiligo with autoimmune diseases, and some features of pediatric vitiligo. Other data were partially consistent with the literature, such as the association between vitiligo and autoimmune diseases/autoantibody activities, and the association between vitiligo and HLAs. Finally, a portion of our data did not concur with the literature, including the sex distribution and mean age of onset, the lack of association between halo nevi and autoimmune diseases, and some aspects of pediatric vitiligo. Conclusions: This study provides novel information regarding clinical features and serologic parameters in different subgroups of vitiligo, namely a significant association between active vitiligo and autoantibody activities, and significant clinical differences (i.e. activity of disease, age of onset, and coexistence of other autoimmune diseases) between vitiligo associated with autoantibodies and vitiligo negative for autoantibodies.     

Evaluation of the effects of NB-UVB in both segmental and non-segmental vitiligo affecting different body sites

BACKGROUND: Narrow band (NB)-UVB has been used in the treatment of vitiligo for years but statistical evaluation of the clinical response in both segmental and non-segmental vitiligo patients has yet to be assessed. OBJECTIVES: Statistical evaluation of the clinical response of vitiligo patients to NB-UVB in both segmental and non-segmental types affecting different body sites. METHODS: This study included 150 patients with vitiligo either segmental (10%) or non-segmental (90%). NB-UVB therapy was given twice weekly till reaching our end point of 100% re-pigmentation or a cut point in unresponsive cases. Evaluation of the percentage of re-pigmentation was performed by total body photography and planimetry every 8 weeks. RESULTS: The overall response to therapy in the non-segmental vitiligo group demonstrated that 48% of the patients showed marked response, 27% showed moderate response and 25% showed mild response after UVB therapy. The patients showed marked response in 76.3% in face lesions, 41.9% in trunk lesions and 37.6% in limbs lesions. None of the patients in the acral areas achieved marked response. The mean duration of therapy was 7.8 months. Moreover, the results demonstrated that the earlier the patient was treated, the better the response was especially for lesions on the face, trunk and limbs. On the other hand, in the segmental vitiligo group, patients showed no more than mild response to NB-UVB whatever the site of the lesion was. No side effects were encountered with NB-UVB therapy except for aggravation of the disease in two cases and erythema in one patient who was an outdoor worker and was skin type II. CONCLUSION: The type of vitiligo, the affected anatomical area and the disease duration are important factors that influence potential re-pigmentation.     

1 125例非节段型白癜风皮损分布的相关因素分析

目的 分析非节段型白癜风皮损分布与性别、发病年龄、病程、自身免疫病病史或家族史、白癜风家族史等因素的相关性。方法 回顾性分析2009年1月至2019年1月在北京医院皮肤科确诊的1 125例非节段型白癜风患者的临床资料,应用SPSS 20.0软件通过独立样本t检验及χ2检验对数据进行统计学分析。结果 1 125例非节段型白癜风患者中,男599例,女526例,男女比例1.14∶1,发病年龄（27.9 ± 17.1）岁,病程（5.2 ± 8.0）年。皮损累及率最高的部位是躯干（544例,48.4%）和面部（535例,47.6%）,其次是肢端（430例,38.2%）、四肢（297例,26.4%）和颈部（231例,20.5%）。599例男性口周（17.2%）、手部（47.9%）及外生殖器部位（14.5%）的受累率高于526例女性（9.7%、22.6%、6.3%,χ2值分别为13.33、77.66、20.01,均P＜0.001）,而女性颈部（27.0%）的受累率则高于男性（14.9%,χ2 = 25.29,P＜0.001）。下肢、膝部、足部、躯干、外生殖器及眼周受累的白癜风患者发病年龄显著低于相应部位未受累者（均P＜0.05）,而上肢和手部受累者发病年龄显著高于上述部位未受累者（均P＜0.05）。自身免疫性甲状腺病病史或家族史阳性的患者手部受累率（50.0%）高于阴性者（27.9%,χ2 = 6.62,P = 0.010）。有白癜风家族史者躯干受累率（59.6%）高于无白癜风家族史者（45.7%,χ2 = 13.36,P＜0.001）。结论 非节段型白癜风皮损的分布模式与性别、发病年龄、自身免疫病病史或家族史以及白癜风家族史等因素均有一定相关性。     

Childhood Vitiligo in China

Background: Childhood vitiligo is a common pediatric skin disorder. The pathogenesis of vitiligo is unclear, and immunological dysfunction may play an important role. Objectives: This prospective study aimed to profile childhood vitiligo and to discuss its correlation with immunological dysfunction. Methods: All of the 620 enrolled patients were aged younger than 14 years, and were assessed with a standard questionnaire. The levels of immunoglobulins, complement, and T-lymphocyte subsets were measured in 270 of these 620 patients. Results: Of the 620 children, 302 (48.71%) were boys and 318 (51.29%) were girls, with an average disease onset age of 7.57 years. The average duration was 13.45 months. 453 (73.06%) children had head and neck involvement and 160 (25.81%) children had segmental vitiligo. 84 (13.55%) children had a family history. There was a correlation between the disease and seasons. The onset or progression usually occurred in summer and spring. Halo nevus was seen in both segmental and non-segmental vitiligo. Precipitating factors such as stress appeared more commonly in segmental vitiligo. As to the immunological findings, in segmental vitiligo, the levels of C3 and C4 were lower in the active relative to the quiescent stage (p < 0.05); and in non-segmental vitiligo, the percentages of CD3+ and CD4+ lymphocytes and the CD4+/CD8+ ratio were lower in the active relative to the quiescent stage (p < 0.01). Conclusions: Childhood vitiligo has its own clinical features. The different types of vitiligo have different characteristics. There is immunological dysfunction in children with vitiligo. Dysfunction of humoral immunity may play a role in the progression of segmental vitiligo, while non-segmental vitiligo is more related to cellular immunity.     

The co-occurrence of segmental vitiligo and linear morphea in a pediatric patient and a review of the literature

Linear morphea and segmental vitiligo are both autoimmune diseases that are observed in the pediatric population, with rare reports of their co-existence. We describe a case of linear morphea and segmental vitiligo with an overlapping distribution in a pediatric patient and review the literature. Including our own case, we summarize 10 cases of co-occurring segmental vitiligo and morphea in pediatric patients; most of these lesions follow a blaschkolinear distribution, and none of the patients had autoimmune thyroid disease. Although uncommon, the coexistence of segmental vitiligo and linear morphea within lines of Blaschko can occur, and this case suggests that linear morphea and segmental vitiligo may be disorders related to genetic mosaicism.     

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.     

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。     

Increased interleukin-6 and granulocyte-macrophage colony stimulating factor levels in the sera of patients with non-segmental vitiligo

BACKGROUND: Although the cause of vitiligo is unknown, an autoimmune theory has been proposed, and there is now convincing evidence that cytokines have an important role in pathogenesis of autoimmunity. OBJECTIVE: To study the possible role of interleukin-1, beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of vitiligo. METHODS: The authors measured the serum levels of the above-mentioned cytokines from 50 patients with the vitiligo compared with 20 healthy volunteers, employing the method of radioimmunoassay. RESULTS: The results showed that the serum levels of both IL-6 and GM-CSF of the patients with both focal type and generalized type of vitiligo, and the serum level of IL-1 beta of the generalized type,were significantly, higher than those of normal controls in the patients with segmental vitiligo, the serum levels of all the cytokines tested were not significantly different from those of the normal controls. The GM-CSF levels of both focal type and generalized type, and the IL-6 level of the generalized type in progressive stage were significantly higher than those in stable state. CONCLUSION: It is speculated that IL-6 and GM-CSF may be involved in the autoimmune mechanism of non-segmental vitiligo. However, more evidence is required before a definite conclusion can be drawn.     

白癜风并发自身免疫性甲状腺疾病的危险因素分析及列线图预测模型的建立

目的：分析白癜风并发自身免疫性甲状腺疾病的危险因素并建立列线图预测模型。方法：收集2017年2月至2019年1月我院276例白癜风患者的临床资料，使用Logistic回归分析白癜风并发自身免疫性甲状腺疾病的独立危险因素。采用R（R 3.5.3）软件包，rms程序包，建立列线图预测模型。同时应用caret程序包进行Bootstrap法重复抽样1000次做内部验证，采用rms程序包计算一致性指数（C-index）。采用ROCR及rms程序包制作ROC曲线。结果：本研究白癜风并发自身免疫性甲状腺疾病的发生率为17.75%，高血糖、白癜风病程、白癜风类型、负性情绪、吸烟、自身免疫性甲状腺病家族史及其他自身免疫性疾病家族史为白癜风并发自身免疫性甲状腺疾病的独立危险因素（均P<0.05）。基于筛选的独立危险因素，建立预测列线图模型结果显示，实际发生率与预测发生率基本一致（χ2=3.854，P=0.724），C-index指数高达0.857（95% CI：0.829~0.885）。结论：白癜风患者应尽可能筛查自身免疫性甲状腺疾病，特别是在有危险因素的白癜风患者中。     

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.     

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.     

儿童白癜风与甲状腺功能指标异常及其他免疫性疾病的关系

目的 探讨儿童白癜风与甲状腺功能指标异常及其他免疫性疾病的关系。方法 对363例白癜风儿童（男198例 ,女165例 ）和 93 例对照儿童（男55例,女38例）进行甲状腺功能指标的检查。结果 363例白癜风儿童中有43例（11.8%）儿童有不同程度的甲状腺功能指标的异常,93例对照组正常儿童中有4例儿童甲状腺功能指标异常,两者比较差异有统计学意义。白癜风儿童甲状腺功能指标异常发生率明显增高（P < 0.05）。而43例甲状腺功能异常的白癜风儿童中,寻常型白癜风儿童为39 例（13.6%）,节段型白癜风儿童为4 例（5.3 %）,寻常型比节段型白癜风儿童甲状腺功能指标异常发生率有明显增高（P < 0.05）。结论 儿童寻常型白癜风患者的甲状腺功能指标异常的发生率明显增高。     

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.     

白癜风243例临床分析及与HLA-DQB1相关性研究

目的 总结和分析白癜风的临床特征及与两种HLA-DQB1等位基因的相关性,探讨白癜风的病因.方法 登记243例白癜风门诊患者的临床资料,利用聚合酶链反应-序列特异引物(PCR-SSP)法,对243例白癜风患者和250例健康人进行等位基因检测,对各项指标进行统计分析.结果 白癜风平均初发年龄男性为23.1岁,女性为23.7岁;首发类型以局限型为主,77%的节段型为儿童,家族史阳性患者发病年龄早于家族史阴性患者.白癜风与HLA-DQB1等位基因相关.结论 ①寻常型与节段型白癜风发病机制不同;②有阳性家族史者符合多基因遗传规律,有家族史和无家族史白癜风患者在其遗传背景上可能存在差异;③HLA-DQB1*0201可能是寻常型白癜风的易感基因或与易感基因相连锁.     

On the pathophysiology of vitiligo: Possible treatment options

Vitiligo is an acquired depigmenting disorder usually classified as non-segmental and segmental types with a higher incidence of the non-segmental ones. The cause of non-segmental vitiligo is still unknown. Currently, it is a dogma that there are several genes affecting the immune system and the pigment system that predisposes someone to develop vitiligo. A precipitating factor must then ellicit an interaction between the immune system and the melanocyte, resulting in destruction of the melanocyte population in discrete areas of the skin. Starting from the overlapping but distinct pathomechanisms, treatment should be finalized to the cellular targets and possibly related to the disease phase.