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INTRODUCTION: Vitiligo is an acquired, sometimes familial skin depigmentation disorder. In about half of patients it occurs before the age of twenty. The aim of this study was to investigate the incidence and significance of autoantibodies (AT) and associated autoimmune and endocrine diseases in children with vitiligo, in relation to adults with vitiligo and children without vitiligo. MATERIAL AND METHODS: The research was conducted in fifty children with clinically diagnosed vitiligo from 2 to 16 years of age. Children were compared with control groups of children with other skin diseases (aged from 2 to 16) and with adults with vitiligo. Each group comprised 30 patients. A detailed history was obtained and physical examination was performed in each patient to determine presence of autoimmune and endocrine diseases in patients with family history of vitiligo. Routine blood examination, routine urinalysis and stool were performed in all patients. We evaluated the incidence of antinuclear (ANA) and antithyroid antibodies (ATA) in each patient, as well as the incidence of antibodies to gastric parietal cell (APCA), smooth muscle (SMA), cord (ACA) and mitochondrial antigens (AMA) in 38 children with vitiligo and in control groups. RESULTS: Children with vitiligo had positive family history of vitiligo more often compared to children without vitiligo (p<.05). Presence of ANA, ATA, APCA, SMA, ACA and AMA was not considerably increased in children with vitiligo compared with their age group. ANA was more common in adults with vitiligo, in comparison with children with vitiligo (p<0.05). None of the children with vitiligo had an associated autoimmune and endocrine disease in contrast to adults with vitiligo (p<0.05). DISCUSSION AND CONCLUSION: Several studies have shown a significant incidence of positive autoantibodies in children with vitiligo, compared to children without vitiligo. However, in our series, presence of ANA, ATA, APCA, SMA, ACA and AMA was not significantly increased in children with vitiligo, compared with children without vitiligo. Further studies are necessary in this area in order to draw more conclusions. In the previous studies, it has been established that children with vitiligo were generally healthy, whereas adults with vitiligo had an increased incidence of autoimmune and/or endocrine diseases. No studies have shown this association in children with vitiligo. Our results support findings of previous studies.
INTRODUCTION: Vitiligo is an acquired, sometimes familial skin depigmentation disorder due to selective destruction of melanocytes. Vitiligo is primarily a disease of the young; in about half of patients it occurs before the age of twenty. The aim of this study was to investigate some epidemiological and clinical characteristics of vitiligo in children, in relation to adults with vitiligo and children without vitiligo. MATERIAL AND METHODS: The research was conducted in fifty children with clinically diagnosed vitiligo (2 to 16 years of age). Children were compared with control groups of children with other skin diseases (age 2 to 16) and with adults with vitiligo. Each group comprised 30 patients. A detailed history was obtained and physical examination performed in each patient to determine the age of onset, clinical type (segmental or generalized), family history of vitiligo and other autoimmune and/or endocrine diseases, association with halo nevi, poliosis and Koebner phenomenon. RESULTS: Of the 50 children with vitiligo, 29 (58%) were girls and 21 (42%) boys. The mean age at first visit was 9 years and the mean age of onset was 7 years. Children with vitiligo had positive family history of vitiligo and autoimmune and endocrine diseases more often compared to children without vitiligo (p < 0.05). Children with vitiligo had poliosis, especially in cases of segmental vitiligo, more often compared to their age group (p < 0.001). Children had an increased incidence of segmental vitiligo compared to adults (p < 0.05). Halo nevi were more common in children with generalized vitiligo, in comparison with children without vitiligo (p < 0.01) and adults with vitiligo (p < 0.05). DISCUSSION AND CONCLUSION: Our results show that segmental vitiligo and halo nevi occurred significantly more often in children than adults with vitiligo.
BACKGROUND: Vitiligo occurs with a frequency of 0.1% to 2% in various populations and is classified into several subtypes by its clinical presentation. Although genetic factors are thought to be involved in the cause of vitiligo, the genetic models for different phenotypes of vitiligo are unknown. OBJECTIVE: Our purpose was to explore potential genetic models for different phenotypes of vitiligo and analyze genetic epidemiologic characteristics of vitiligo in a Chinese population. METHODS: Information from 2247 patients and members in their families was collected using a uniform questionnaire. Patients' clinical characteristics and their family history were analyzed using software. A complex segregation analysis was conducted to propose potential genetic models for vitiligo. RESULTS: Different subtypes of vitiligo had different ages of disease onset. In relatives of patients with vitiligo, the risk of developing vitiligo increased with increasing relatedness to the patients with vitiligo. A polygenic additive model was the best model for focal vitiligo, vitiligo vulgaris, acrofacial vitiligo, and segmental vitiligo with approximately 50% heritability in each. For universal vitiligo, the best model was an environmental model. CONCLUSION: This study indicated that different phenotypes of vitiligo had different pathogeneses and genetic backgrounds. Onset of vitiligo is possibly affected by both genetic backgrounds and common environmental factors.
BACKGROUND: Spectroscopic methods have been used to analyze in vivo melanin in the past but the specific effect of melanin depth on autofluorescence and reflectance spectroscopy has not been determined. In patients with blue vitiligo, three distinctive clinicopathologic patterns are present: (1) normal skin with normal epidermal melanin pigmentation (2), skin of blue vitiligo with dermal melanin pigmentation, and (3) tissue of regular vitiligo with no melanin pigmentation. Blue vitiligo may thus serve as an in vivo model to assess dermal pigment using spectroscopic techniques. OBJECTIVES: To evaluate the reflectance and autofluorescence spectra of a patient with blue vitiligo in order to assess the effect of melanin pigmentation and its localization on the optical properties of the skin. METHODS: The blue-gray, normal and depigmented lesions of a patient with blue vitiligo were analyzed using reflectance and fluorescent spectroscopy. The condition was likely induced by a phototoxic reaction in a patient with pre-existing vitiligo. These data were then correlated to the histologic and electron microscopic findings present in the various types of lesions. RESULTS: Reflectance spectroscopy detected little difference in spectral shape between skin sites affected by blue vitiligo vs. vitiligo. Autofluorescence spectroscopy detected an apparent difference between the two types of lesions, with the blue-gray lesions (blue vitiligo) showing lower fluorescence intensity and spectral maximum position red-shifted compared with regular vitiligo, whereas regular vitiligo showed more intense hemoglobin absorption than the blue vitiligo. CONCLUSIONS: Dermal melanin present in blue vitiligo can be well characterized by autofluorescence spectroscopy, while little difference in reflectance spectral shape exists between vitiligo and blue vitiligo. Thus, autofluorescence spectroscopy may better identify deeper structures in skin tissue, such as melanin, than reflectance spectroscopy.
BACKGROUND: Patients with vitiligo have a markedly increased incidence of antibodies to melanocytes, referred to as vitiligo antibodies. Antibodies to tyrosinase have been reported in some patients with vitiligo, suggesting that vitiligo antibodies may be directed to this enzyme. However, there is considerable controversy as to the frequency with which these antibodies occur, and, hence, about their relevance to the pathogenesis of vitiligo. The frequency with which antityrosinase antibodies occur in vitiligo is critical to evaluate their potential role in the pathogenesis of this disease. OBJECTIVE: To examine the prevalence of antibodies to tyrosinase in a large group of patients with vitiligo. DESIGN: We examined the incidence of antibodies to enzymatically and immunologically active tyrosinase in patients with and without vitiligo. SETTING: Outpatient clinic in referral center. PATIENTS: The study was conducted on serum samples obtained from 54 patients with active (n = 40) and inactive (n = 14) uncomplicated vitiligo and from 52 age- and sex-matched individuals without vitiligo. MAIN OUTCOME MEASURE: Presence in the serum of antibodies to enzymatically and/or immunologically active tyrosinase. RESULTS: By immunoblotting, 20 patients (50%) with active vitiligo, 9 of those (64.3%) with inactive vitiligo, and 29 control individuals (55.8%) had antibodies to an antigen that comigrated with tyrosinase. However, by immunoprecipitation DOPA stain and by sandwich enzyme-linked immunosorbent assay, none of the vitiligo or control individuals had antibodies to tyrosinase, even though both assays easily detected control antityrosinase antibodies. CONCLUSION: These results indicate that while antibodies to an antigen(s) that comigrates with tyrosinase are common in patients with or without vitiligo, vitiligo antibodies are not directed to tyrosinase.
An increased prevalence of autoimmune thyroiditis (AT) in vitiligo patients is well known. The aim of this study was firstly, to evaluate the clinical course of patients with both vitiligo and AT and secondly, to identify additional autoimmune disorders affecting the thyroid gland in a large cohort of vitiligo patients. We analysed a study group of 106 vitiligo patients and 38 controls. A detailed thyroid examination including sonography was performed in all study participants. In addition, the study participants were HLA typed and screened for various autoimmune disorders. AT was significantly more frequent in vitiligo patients than in controls (21%versus 3%; P < 0.01). In 12 of the 22 patients with AT, vitiligo was the initial disease preceding AT by 4-35 years. In the other 10 patients with AT, both vitiligo and AT were diagnosed within one year. There were two individuals with diabetes mellitus type 1 and a single patient with Addison's disease. Anti-nuclear antibody (ANA), anti-smooth muscle cell antibody, and parietal cell antibody levels occurred with a similar frequency in patients and controls. In all vitiligo patients with both elevated ANA levels and AT (n = 6), the atrophic but not the goitrous variant was diagnosed. These vitiligo patients with both AT and elevated ANA levels had a significantly smaller thyroid volume compared to the vitiligo patients with AT whose ANA levels were normal (6.7 +/- 4.5 ml versus 13.4 +/- 9.1 ml, respectively; P < 0.05). The same was found in the entire study group: Thyroid volume of all vitiligo patients (with or without concomitant AT) was significantly smaller in the presence of ANA (6.9 +/- 5.3 versus 10.5 +/- 5.9 ml, respectively; P < 0.05). However, this phenomenon was not observed in the control group. There was a trend for a decreased frequency of HLA-DR3 (6.7%versus 23%) in our study group, but after correction for the number of comparisons, no HLA-allele was statistically significant associated neither with vitiligo nor with multiple autoimmune diseases in our patient sample. Our findings suggest that AT is the most frequent autoimmune disease associated with vitiligo. In our patients, AT presented simultaneously or after the onset of vitiligo but not before. Elevated ANA levels were associated with the atrophic variant of AT and may affect the volume of the thyroid gland, and there was no statistically significant association with the HLA system.
Vitiligo is often classified into three types, generalized, segmental, and localized, on the basis of their distribution pattern. It is also classified into type A (non-dermatomal or non-segmental) and type B (dermatomal or segmental) vitiligo on the basis of both the distribution pattern and physiological function. The natural courses of type A and type B vitiligo are characteristic and quite different from each other. Whereas type A vitiligo appears at any age and progresses throughout the patient's life span, type B vitiligo affects the young and stabilizes within a few years. Segmental type vitiligo corresponds to type B, and generalized type vitiligo is the late stage of type A. However, no one has observed the course and character of localized type vitiligo, and its nosological position in A/B classification is unclear. We followed 44 cases of localized type vitiligo for periods of 6 months to 8 years. In 3 of the 44 patients, new white patches developed within the same dermatome as their affected areas in the first 12 months and stabilized in a short period. Therefore, these patients were diagnosed as type B vitiligo. In 15 patients, vitiligo developed in other dermatomal areas; the earliest case at 9 months, and others later on. The new white patches continue to develop for a long period, so these patients were diagnosed with type A vitiligo. In 26 of the 44 patients, the vitiligo remained localized within the period of observation. It is concluded that most localized type vitiligo is the early stage of type A, but a small number of cases belong to the early stage of type B.
The role of Langerhans cells in the pathogenesis of nonsegmental type vitiligo is still unknown. In this study, biopsies were taken from 26 patients at various stages of nonsegmental type vitiligo and morphometrically observed to investigate the kinetics of Langerhans cells in patients at various stages of the disease. A marked depletion of OKT6-positive and ATPase-positive epidermal dendritic cells was noted in patients with active nonsegmental type vitiligo. A repopulation of both OKT6-positive and ATPase-positive epidermal dendritic cells was noted in patients with stable nonsegmental type vitiligo. Profound depletion of epidermal OKT6-positive and ATPase-positive dendritic cells was noted in patients with repigmenting nonsegmental type vitiligo receiving treatments involving topical use of 0.05% Fluocinonide cream or PUVA photochemotherapy. Transmission electron microscopy confirmed the absence of epidermal dendritic cells (Langerhans cells and intermediate cells) in patients with active and repigmenting nonsegmental type vitiligo. In active nonsegmental type vitiligo, two possible explanations are proposed for the depletion of OKT6-positive and ATPase-positive epidermal dendritic cells (presumptive Langerhans cells): 1) the cells are destroyed by cytotoxic factors released during the course of destruction of melanocytes in active vitiligo, and/or 2) they leave the epidermis and migrate to regional lymph nodes to present certain antigens which are released from certain destroyed epidermal cells (keratinocytes or melanocytes) during the course of active vitiligo. The repopulated epidermal Langerhans cells may result from phenotypically transformed dermal dendritic cells in the depigmented lesions of patients with stable vitiligo. Since various therapies which result in repigmentation deplete the density of epidermal Langerhans cells markedly, it is suggested that depletion of epidermal Langerhans cells in stable vitiligo may aid in repigmentation. It is also proposed that the repopulated epidermal Langerhans cells may play a role in inhibiting the proliferation of epidermal melanocytes in depigmented lesions of stable vitiligo, thus various methods of treatment which deplete the Langerhans cells may eventually aid in the repigmentation of nonsegmental type vitiligo.
BACKGROUND: Serological typing of the human leucocyte antigen (HLA) has shown discrepancies in HLA associations with vitiligo in different ethnic populations. OBJECTIVE: To evaluate the distributions of HLA at class I and II loci that may contribute to the genetic susceptibility of vitiligo patients in Chinese Hans population. METHODS: We analysed the allelic frequencies of HLA class I and II by using the polymerase chain reaction sequence-specific primer (PCR-SSP) method in 187 patients with vitiligo and 273 controls in Chinese Hans. The linkage disequilibrium was calculated from a 2 x 2 table. RESULTS: Two-locus haplotypes including HLA-A25-B13, HLA-A25-B27, HLA-A25-Cw*0602, HLA-A25-DQA1*0302, HLA-A25-DQA1*0601, HLA-A25-DQB1*0303, HLA-B13-Cw*0602, HLA-B13-DQA1*0302, HLA-B13-DQA1*0601, HLA-B27-Cw*0602, HLA-B27-DQA1*0302, HLA-B27-DQA1*0601, HLA-B27-DQB1*0303, HLA-B27-DQB1*0503, HLA-Cw*0602-DQA1*0302, HLA-Cw*0602-DQA1*0601, HLA-Cw*0602-DQB1*0303, HLA-Cw*0602-DQB1*0503 and HLA-DQA1*0302-DQB1*0503 were associated with all types of vitiligo in Chinese Hans. The extended haplotypes HLA-A25-B13-Cw*0602, HLA-A25-B27-Cw*0602, HLA-DQA1*0302-DQB1*0303-Cw*0602 and HLA-B13-DQB1*0303-Cw*0602 were found to be associated with all types of vitiligo in Chinese Hans, whereas the frequency of HLA-A25-Cw*0602-DQA1*0302 was significantly increased in generalized vitiligo but not in localized vitiligo. The frequencies of HLA-A25-DQA1*0302-DQB1*0503 and HLA-A30-DQA1*0302-DQB1*0303 were higher in childhood vitiligo than in adult vitiligo, and the frequency of HLA-A25-B13-DQB1*0303-Cw*0602 was shown to be associated with adult vitiligo but not childhood vitiligo. CONCLUSION: This study demonstrates not only the differential association between HLA markers and types of vitiligo according to distribution or age at onset but also newly found high-risk haplotypes in Chinese vitiligo patients.
BACKGROUND: Despite the availability of various medical treatments for vitiligo, a large percentage of patients fail to achieve satisfactory results. Surgical techniques offer a potential solution for patients with vitiligo who fail to respond to medical treatments. OBJECTIVE: We evaluated the practicality in treating vitiligo by using cultured autologous pure melanocytes and investigated the different results among stable localized vitiligo, stable generalized vitiligo, and active generalized vitiligo. METHODS: In all, 120 patients with vitiligo were treated with transplantation of autologous cultured pure melanocyte suspension after carbon-dioxide laser abrasion. RESULTS: Patients with stable localized vitiligo experienced the highest percentage of excellent repigmentation with 84% achieving 90% to 100% coverage, followed by 54% of patients with stable generalized vitiligo, whereas only 14% of patients with active generalized vitiligo experienced good repigmentation. Age and sex of the patients, and size and location of the lesions, did not show significant influence on the results of transplantation. CONCLUSION: Autologous cultured pure melanocyte suspension combined with carbon-dioxide laser abrasion is an effective treatment for patients with stable vitiligo who fail to respond to medical treatments, especially for those with stable localized vitiligo.
Vitiligo is a common chronic skin depigmentation disorder that seriously decreases the patients' overall quality of life. Human blood metabolites could contribute to unraveling the underlying biological mechanisms of vitiligo. We used GWAS summary statistics to assess the causal association between genetically predicted 1400 serum metabolites and vitiligo risk by Mendelian randomization (MR). Then, after constructing the mouse model of vitiligo, we did non-targeted metabolomics analysis on the mouse serum and validated MR's pathway enrichment results ulteriorly. In the initial phase, MR analysis revealed causative associations between 36 metabolites and vitiligo risk, including 8 metabolite ratios and 28 individual metabolites (19 known and 9 unknown metabolites). In the validation stage, 7 metabolites were successfully validated. Of the 28 individual metabolites, most are related to lipid metabolism. Genetically predicted higher 4-oxo-retinoic acid showed the strongest protective effect on vitiligo, while the most potent risk effect was the increase in quinate. The metabolites associated with vitiligo risk are mainly enriched in alpha-linolenic acid metabolism, linoleic acid metabolism, arginine biosynthesis and metabolism pathways, validated through the serum metabolomics of vitiligo mouse. By integrating genomics and metabolomics, this study provides new insights into the association between metabolites and vitiligo, highlighting the potential roles of specific metabolites in the pathogenesis of vitiligo. These metabolites associated with vitiligo could serve as new biomarkers, further research could help to reveal how these metabolites influence specific pathways in the development of vitiligo.
Very few articles have aimed to illuminate the clinical profiles of vitiligo in China. We conducted this retrospective survey involving 4118 outpatients with vitiligo in order to identify the differences among various clinical types of vitiligo and their associated disorders. Completed questionnaires (3742) were validated and analysed. Of this large cohort, 1565 (41.8%) individuals presented vitiligo vulgaris, followed by focal, segmental, acrofacial, and universal, in that order. The mean age of vitiligo onset was 18.88 years. More than 60% of the patients were affected before 20 years of age. Patients with segmental vitiligo were affected earlier than those with other types of vitiligo (15.55 years; (P < 0.001). More than 74% of the patients presented with focal vitiligo at onset. After 3-5 years, 99% of active vitiligo was worse and shifted from one clinical type to another. However, there was no transformation between acrofacial vitiligo and segmental vitiligo. Compared with the general population, the patients with vitiligo were more likely to be affected by rheumatoid arthritis (P < 0.01), ichthyosis (P < 0.01), chronic urticaria (P < 0.01), or alopecia areata (P < 0.01).
From July to December 2002, we collected data from 2247 vitiligo patients in order to establish the clinical and epidemiologic profile of vitiligo in China. Of these patients, 541 (24.1%) were children aged equal to or less than 12 years. Of the 541 children, 274 (50.6%) were boys and 267 (49.4%) were girls, with a mean age of 8.87 years and a mean onset age of 7.28 years. Similar to adult patients, boys and girls were affected by vitiligo with equal frequency. The most frequent age of onset was between 4 and 8 years (42.5%). The mean duration of vitiligo was 19.71 months (range: 0-132 months). The most common type of vitiligo was vitiligo vulgaris, the frequency of which was 38.1%, followed by focal vitiligo (34.6%), segmental vitiligo (19.4%), acrofacial vitiligo (7.6%), and universal vitiligo (0.4%). Segmental vitiligo had an earlier the other types. Of the 541 children with vitiligo, 60 (11.1%) had a family history, and 3 (0.6%) had more than one family member who was affected. Forty-one (7.6%) children had an associated autoimmune disease: halo nevi and alopecia areata, which were observed in 39 (7.2%) and 2 (0.4%) children, respectively.