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Anti-thyroid peroxidase antibody and vitiligo: a controlled study.

BACKGROUND: Vitiligo is an acquired depigmenting disorder due to destruction of melanocytes. Although many theories have been suggested for its pathogenesis, the role of autoimmunity is the most popular one. The association of vitiligo with autoimmune thyroid diseases and the increased prevalence of autoantibodies including thyroid autoantibodies in vitiligo favor this role. Our objective was to compare the frequency of thyroid peroxidase antibody (anti-TPO) in vitiligo patients with healthy subjects in Iran. METHODS: Ninety-four cases of vitiligo (46 female and 48 male) and 96 control subjects (49 female and 47 male) were enrolled in this controlled study. Patients with known thyroid disease, history of thyroid surgery and those receiving thyroid medications were not included. The two groups were matched regarding gender and age. The demographic data, symptoms related to thyroid diseases and results of skin and thyroid examinations were recorded in a questionnaire for each subject. Thyroid function tests including free T3, free T4 and TSH-IRMA were performed. Anti-TPO levels were assessed as well. The collected data were analyzed by SPSS version-11 in vitiligo patients and subgroups according to gender, age, extent, and duration of the disease compared with the control group. RESULTS: Anti-TPO was detected in 17 (18.1%) of patients affected by vitiligo, while this figure was 7 (7.3%) in the control group; the difference was significant with p-value < 0.025 (Phi & Cramer's V = 0.162). When analyzing subgroups, the difference in the frequency of anti-TPO remained significant only in females (p-value < 0.044) (Phi & Cramer's V = 0.207) and in patients in the age ranges of 18-25 (p-value < 0.05) (Phi & Cramer's V = 0.28) and 26-35 year-old (p-value < 0.042) (Phi & Cramer's V = 0.304). The difference of the frequency of anti-TPO was not significant regarding the duration and extent of vitiligo. In addition, there was no significant difference in the levels of free T3, free T4, and TSH in vitiligo patients compared with the control group. CONCLUSION: According to our study, anti-TPO was shown to be significantly more common in vitiligo patients especially in young women, compared with control group. As this antibody is a relatively sensitive and specific marker of autoimmune thyroid disorders including Hashimoto thyroiditis and Graves' disease, and considering the fact that vitiligo usually precedes the onset of thyroid dysfunction, periodic follow-up of vitiligo patients for detecting thyroid diseases is further emphasized especially in young women with increased level of anti-TPO.

Adult↗

[Study on genetic epidemiology on 815 patients with vitiligo in Zhejiang area].

OBJECTIVE: Genetic factors are thought to be involved in the development of vitiligo. The aim of this study is to explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients from Zhejiang province. METHODS: Data for 815 patients with vitiligo together with their first- and second-degree relatives were obtained using a standardized questionnaire. All these information was requested to confirm the answers about family history in order to reduce the possibility of 'recall' bias. The 815 probands would include 411 (50.43%) males and 404 (49.57%) females with a varied age from 2 months to 71 years old. Since the information on general prevalence of vitiligo in this area was absent, a control group was set up to facilitate the calculations of heritability degree. 468 persons of the control group were from non-vitiligo population with a sex ratio of 241(male): 227(female) with varied age of 4 months to 80 years old. Both gender and age were comparable between the vitiligo and the control population. The inheritance pattern estimation, heritability calculation and complex segregation analysis were performed with Penrose method, Falconer regression method and SAGE-REGTL program. RESULTS: In 815 vitiligo probands, 128 had and 687 had not family histories, with a heritability rate of 15.7%. The vitiligo prevalence in proband's first degree relatives was 2.580%, higher than the prevalence of 0.618% in second degree relatives, and both of them were higher than general prevalence: 0.192%. By Penrose method, the rates on different catagories were as follows: sibling prevalence rates s = 0.080 18; population prevalence rate q = 0.001 92; s/q = 41.76. The ratio of s/q did not approach 1/2q (260.42) or 1/4q (130.21), but approached 1/square root of q(22.82), suggesting vitiligo was consistent with a mode of polygenic inheritance. Using Falconer's method, heritabilities of vitiligo in first-and second degree relatives of probands were 59.61% (95% confidence interval 65.37-53.84) and 55.20% (95% confidence interval 43.88-66.52), respectively. The weighted average of heritability in all relatives was 58.7% (95% confidence interval 53.56-63.83). The results of complex segregation analysis suggested that major gene model including the Mendelian dominant, recessive and additive hypotheses were not rejected (P > 0.05). Purely environmental model and no transmission model were rejected at a 0. 001 significance level. According to AIC, Mendelian dominant inheritance was the best-fitted hypothesis. CONCLUSION: Genetic factors played an important role in the occurrence of vitiligo, and the genetic model of vitiligo could serve as the polygenetic or multifactorial inheritance with major gene trait.

Adolescent↗

Pattern of familial aggregation of vitiligo.

BACKGROUND AND DESIGN: Vitiligo is a disorder whose cause is not well understood. This study was undertaken to clarify whether genetic factors are involved in the pathogenesis of vitiligo. Data on 160 white kindreds living in the United States have been collected. Each family was ascertained through a proband afflicted with vitiligo. The nature and extent of familial aggregation and other relevant epidemiologic features have been determined. RESULTS: The mean age at onset of vitiligo is about 19 years in male and about 24 years in female individuals. The percentage of probands reporting one or more first-degree relatives also afflicted with vitiligo is 20%. Children of probands are found to be afflicted about 1.7 times more commonly than other first-degree relatives. The relative risk (RR) for vitiligo is about 7 for parents, about 12 for siblings, and about 36 for children. For second-degree relatives, the RR varies between 1 and 16. Relative risks for all first- and second-degree relatives, except uncles and grandsons, are significant at the 5% level. In families in which one or more relatives of the proband are afflicted with vitiligo, the intrafamilial correlation of ages at onset of vitiligo is moderate (0.6). No statistically significant effect (at the 5% level) of parental age at first childbirth was seen on the proportion of offspring afflicted with vitiligo. No significant association of some commonly related diseases (eg, thyroid disorder or alopecia areata) was observed with vitiligo or with a family history of vitiligo. CONCLUSIONS: The extent of familial aggregation of vitiligo is statistically significant. The pattern of relationship between RR and degree of kinship indicates involvement of genetic factors, although it is not consistent with single-locus mendelian transmission.

Adolescent↗

Vitiligo: an under-estimated problem.

BACKGROUND AND OBJECTIVES: Vitiligo is a common skin complaint, affecting approximately 500000 people in the UK with cosmetically and psychologically devastating effects. An average GP will have 10 sufferers on his list. The aims of this survey were to determine the effects and extent of vitiligo, treatments used and whether these differed from those reported in the current medical literature. There has been no previous work in this area. METHOD: A self-administered questionnaire was distributed to 25% of the members of the Vitiligo Society (a patients' self-help group) who were likely to be concerned about their condition. The questionnaire covered demographic characteristics of the group, the vitiligo itself, treatment and sufferers attitudes towards vitiligo. RESULTS: The response rate was 77%: the median age of onset was 13 years. Half related the onset of their vitiligo to a stressful event (e.g. marital and financial problems). Only 14% had noticed any spontaneous improvement in their vitiligo [negatively related to the percentage of vitiligo on the body (P < 0.05)]; 80% had used no treatment. Use of camouflage was high (41% of males and 70% of females). Sunscreen use was suboptimal, and 20% were depressed about their vitiligo. DISCUSSION: In this self-help group it appears that improvement occurs less frequently with more extensive vitiligo, so treatment (for vitiligo and depression) should be offered early. Further work on this subject is needed. GPs should be ideally placed to help vitiligo sufferers. The suboptimal use of therapies suggests that GPs need education about the topic.

Adolescent↗

The development of guidelines for the treatment of vitiligo. Clinical Epidemiology Unit of the Istituto Dermopatico dell'Immacolata-Istituto di Recovero e Cura a Carattere Scientifico (IDI-IRCCS) and the Archives of Dermatology.

OBJECTIVE: To develop and introduce evidence-based guidelines for the treatment of vitiligo in children and in adults. PATIENTS AND SETTING: Patients, residents, and dermatologists from the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Netherlands Institute for Pigmentary Disorders in Amsterdam. DESIGN: Scientific evidence obtained from 3 systematic reviews of the literature was combined with the results of 2 questionnaires and interviews of potential users of the guidelines, 3 internal expert meetings, and 1 local expert meeting, during which preliminary guidelines were presented and commented on. A final version of the guidelines was synthesized and disseminated among potential users. Six months after the introduction of these guidelines, their use was evaluated. RESULTS: Before the development of the guidelines, there was no uniformity in treatment selection, and there was a variability in estimates of treatment outcome. The metaanalysis showed class 3 corticosteroids and narrowband UV-B to be the most effective and safest therapies for localized and for generalized vitiligo, respectively. From another systematic review, it could be concluded that patients with segmental, stable, or lip-tip vitiligo could be successfully treated with most autologous transplantation methods. For vitiligo universalis, results of the systematic review showed that depigmentation using monobenzone or a Q-switched ruby laser was equally effective. The final version of the guidelines consisted of a treatment scheme together with detailed treatment protocols. Implementation of the guidelines was evaluated in 5 physicians. After the introduction of these guidelines, they were followed in most adult cases with vitiligo (71% of patients with localized vitiligo, 82% with generalized vitiligo, 100% with stable or segmental vitiligo, and 80% with universal vitiligo). In children with vitiligo, the physicians adhered to the guidelines for 52% of the cases. CONCLUSIONS: Guidelines for the treatment of vitiligo can be successfully developed and disseminated for daily clinical practice. The results of the implementation of these guidelines should be confirmed in other centers involving more clinicians.

Adrenal Cortex Hormones↗

Plasma alpha-melanocyte-stimulating hormone, beta-endorphin, met-enkephalin, and natural killer cell activity in vitiligo.

BACKGROUND: The immune system is important in the pathogenesis of vitiligo, and emotional stress has precipitated vitiligo in some patients. Opioid peptides, beta-endorphin, met-enkephalin, and alpha-melanocyte-stimulating hormone (MSH) act as immunomodulators, and their secretion increases during periods of stress. OBJECTIVE: To see whether these three neuropeptides might be related to vitiligo itself or to some alterations of the immune system in patients with vitiligo, we compared circadian variations in their plasma concentrations and natural killer cell activity of peripheral blood lymphocytes in 14 patients with vitiligo with those of 12 healthy subjects. METHODS: Plasma concentrations of neurohormones were evaluated by radioimmunoassay (immunoradiometric assay for beta-endorphin). Natural killer cell activity (NKCA) was assayed against K562 cells by 51Cr release technique. Data were compared by the Student t test and analyzed by cosinor analysis. RESULTS: The NKCA in vitiligo patients was higher than in controls but had similar circadian rhythm. alpha-MSH had no circadian rhythm in controls or in patients; plasma alpha-MSH levels were the same. Daily met-enkephalin and beta-endorphin oscillations in patients were no longer circadian. beta-Endorphin plasma levels in stable vitiligo were higher than in controls. There were no differences between patients with active vitiligo and normal subjects. Met-enkephalin plasma levels were generally higher in vitiligo patients, especially in the one with active vitiligo, than in controls. CONCLUSION: In vitiligo there are aberrations in neuropeptide, beta-endorphin, and met-enkephalin secretion. The plasma met-enkephalin level is positively correlated with the aggressiveness of the disease.

Adult↗

Clinical and histopathologic characteristics of trichrome vitiligo.

BACKGROUND: The term trichrome vitiligo describes lesions that have a tan zone of varying width between normal and totally depigmented skin, which exhibits an intermediate hue. However, the pathogenesis and the histopathologic characteristics of trichrome vitiligo are unknown. OBJECTIVE: Our purpose was to investigate the clinical and histopathologic characteristics and the pathogenesis of trichrome vitiligo. METHODS: Four punch biopsy specimens were taken from 21 patients with trichrome vitiligo; they were from vitiliginous skin, light brown skin, perilesional normal skin, and normal skin as far as 5 cm from the nearest vitiligo spot. The sections were stained with hematoxylin-eosin; in selected cases, we performed immunohistochemical staining with S-100 protein and CD1a. RESULTS: Trichrome vitiligo occurred most frequently on the trunk in active vitiligo vulgaris. Focal vacuolar degeneration of the basal cell layer and mild inflammatory cell infiltration of the epidermis and dermis were more prominent in light brown skin and perilesional normal skin than in vitiliginous skin and normal skin. The number of melanocytes was decreased in light brown skin compared with perilesional normal skin (P <.05) and in vitiliginous skin compared with light brown skin (P <.05); a few melanocytes were observed even in skin affected by trichrome vitiligo. The number of Langerhans cells was increased in the epidermis of light brown skin and perilesional normal skin compared with vitiliginous and normal skin (P <.05). PUVA therapy yielded excellent repigmentation. CONCLUSION: Trichrome vitiligo is a variant of active vitiligo. The changes of melanocytes, keratinocytes, and Langerhans cells may be involved in the pathogenesis of depigmentation in trichrome vitiligo.

Adult↗

Herpesvirus connection in the expression of autoimmune vitiligo in Smyth line chickens.

The Smyth line (SL) chicken is an animal model for human vitiligo, a common acquired depigmentary disorder affecting about 1-2% of people worldwide. The vitiligo-like depigmentation in SL chickens typically develops when the birds are between 6 and 14 weeks of age and may affect 70-95% of hatch mates. The development of SL vitiligo is considered to depend on two interacting components, namely an inherent melanocyte defect and an autoimmune reaction to melanocytes. Recently, a role for an environmental factor in the expression of vitiligo was suggested by the observation that only 10% of SL chicks imported from the University of Massachusetts (UM) and reared in isolation at biosecurity level 2 (BSL 2) at the University of Arkansas (UA) exhibited vitiligo. Following further assessment of environmental differences between UA and UM SL chickens, three environmental factors that may have influenced the expression of SL vitiligo were identified. Included were housing condition, status of Mycoplasma synoviae infection, and turkey herpesvirus (HVT) vaccination status. Studies were subsequently conducted at UA and UM to assess the role of these environmental factors in the expression of SL vitiligo. M. synoviae infection was not found necessary for vitiligo expression in SL chickens. However, HVT emerged as a strong candidate for an important environmental factor in SL vitiligo. The connection between HVT and SL vitiligo was confirmed for both BSL 2 and conventional housing. Therefore, the observations reported here suggest a strong causative link between HVT infection and SL vitiligo.

Age Factors↗

Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families.

Generalized vitiligo is an autoimmune disorder characterized by acquired white patches of skin and overlying hair, the result of loss of melanocytes from involved areas. The most common disorder of pigmentation, vitiligo occurs with a frequency of 0.1-2.0% in various populations. Family clustering of cases is not uncommon, in a non-Mendelian pattern suggestive of multifactorial, polygenic inheritance. We surveyed 2624 vitiligo probands from North America and the UK regarding clinical characteristics, familial involvement, and association with other autoimmune disorders, the largest such survey ever performed. More than 83% of probands were Caucasians, and the frequency of vitiligo appeared approximately equal in males and females. The frequency of vitiligo in probands' siblings was 6.1%, about 18 times the population frequency, suggesting a major genetic component in disease pathogenesis. Nevertheless, the concordance of vitiligo in monozygotic twins was only 23%, indicating that a non-genetic component also plays an important role. Probands with earlier disease onset tended to have more relatives affected with vitiligo, suggesting a greater genetic component in early onset families. The frequencies of six autoimmune disorders were significantly elevated in vitiligo probands and their first-degree relatives: vitiligo itself, autoimmune thyroid disease (particularly hypothyroidism), pernicious anaemia, Addison's disease, systemic lupus erythematosus, and probably inflammatory bowel disease. These associations indicate that vitiligo shares common genetic aetiologic links with these other autoimmune disorders. These results suggest that genomic analysis of families with generalized vitiligo and this specific constellation of associated autoimmune disorders will be important to identify the mechanisms of genetic susceptibility to autoimmunity.

Adolescent↗

High prevalence of vitiligo in lepromatous leprosy.

BACKGROUND: Leprosy and vitiligo are common affections in the West Indies. Vitiligo frequently occurs in lepromatous patients, an observation rarely reported in the literature. METHODS: We studied the prevalence of vitiligo in patients affected by leprosy by performing a retrospective study between 1978 and 1999 in the French West Indies (Martinique). RESULTS: Eleven patients presented with vitiligo among 101 with lepromatous (multibacillary) leprosy. None presented with vitiligo among the 364 with the tuberculoid (paucibacillary) form. The mean age of the vitiligo patients was 55. 4 years at vitiligo onset. The sex ratio was 0.8. Vitiligo occurred 19 years after the diagnosis of leprosy, with a range from 3 to 42 years. The prevalence of vitiligo in lepromatous patients was 10.9%, compared to 0% in tuberculoid patients. Such an increase in prevalence compared with that in the general population (0.34%) was shown to be highly significant (P< 0.0001). CONCLUSIONS: Our data confirmed that the association of vitiligo and leprosy was not fortuitous. The physiopathology leading to this high rate of vitiligo in lepromatous leprosy is unclear, despite the fact that autoimmunity plays a major role in both diseases.

Adult↗

Effect of vitiligo on self-reported health-related quality of life.

BACKGROUND: Vitiligo is a pigmentary disorder affecting at least 1% of the total population. Although the disease does not produce direct physical impairment, it may considerably influence the psychological well-being of the patients. It has been suggested that patients suffer from low self-esteem, poor body image and a poor quality of life. The majority of the studies on the psychosocial impact of vitiligo were conducted in the U.S.A. and England. OBJECTIVES: This study aims to quantify the burden of vitiligo by estimating health-related quality of life in the Dutch-speaking Belgian population (Flanders). This is compared with the level of disability caused by psoriasis in a similarly recruited population. It is also our purpose to detect those at risk of experiencing a poor quality of life and to identify variables that might predict this impairment. PATIENTS AND METHODS: Patients with vitiligo (n = 119) and 162 patients with psoriasis were included in a postal survey. In order to obtain a patient-based measurement of quality of life we used the Dermatology Life Quality Index (DLQI), a widely validated questionnaire that is easy to use and allows comparison between several skin disorders. Other survey questions were related to demographic data and disease-related characteristics. RESULTS: We obtained excellent response rates in both patient groups. The overall mean DLQI score for vitiligo (4.95) was lower than that for psoriasis (6.26) (P = 0.01). Patients with vitiligo experienced significantly less impairment of life quality from the symptoms and treatment of the disease (P < 0.001). The highest individual mean scores in vitiligo were found for Q2 (feelings), Q4 (clothing), Q5 (social and leisure activities) and Q3 (daily routine). The interaction of disease and sex on the DLQI score was highly significant (P = 0.001). While men with vitiligo scored significantly lower than men with psoriasis (P < 0.001), we found a comparable overall DLQI score for women in these disease groups. The number of consultations (P = 0.005) and severity of the disease (P < 0.001) were independently related to the DLQI. CONCLUSIONS: Our study quantifies the burden on the quality of life caused by vitiligo and indicates specific areas of patients' lives which are most affected by the disease. Sex, number of consultations and subjective disease severity independently predict the quality of life. The quality of life impairment in women affected with vitiligo equals the impairment caused by psoriasis in our study population. These results should awake the interest of physicians in this 'cosmetic' disease, since appropriate treatment is likely to improve the quality of life of vitiligo patients.

Adult↗

Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo.

Generalized vitiligo is an autoimmune disorder in which acquired white patches of skin and overlying hair result from autoimmune loss of melanocytes from involved areas. Although usually sporadic, family clustering of vitiligo may occur, in a non-Mendelian pattern typical of multifactorial, polygenic inheritance. Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus; these same disorders occur at increased frequency in patients' first-degree relatives. Here, we studied 133 'multiplex' generalized vitiligo families, with multiple affected family members. The age of onset of vitiligo is earlier in these 'multiplex' families than in patients with sporadic vitiligo. Affected members of the multiplex vitiligo families have elevated frequencies of autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anemia, and Addison's disease. Probands' unaffected siblings have elevated frequencies of most of these same autoimmune diseases, particularly if the proband had non-vitiligo autoimmune disease. Familial generalized vitiligo is thus characterized by earlier disease onset and a broader repertoire of associated autoimmune diseases than sporadic vitiligo. This mostly likely reflects a greater inherited genetic component of autoimmune susceptibility in these families. These findings have important implications for autoimmune disease surveillance in families in which multiple members are affected with vitiligo.

Addison Disease↗

Increased prevalence of chronic autoimmune (Hashimoto's) thyroiditis in children and adolescents with vitiligo.

BACKGROUND: An increased prevalence of autoimmune (Hashimoto's) thyroiditis in adult patients with vitiligo has been described. This association has scarcely been studied in children. OBJECTIVE: We sought to assess children and adolescents with vitiligo for autoimmune thyroid disorder and to identify any predisposing factors of this association. METHODS: In all, 54 children and adolescents (23 boys, 31 girls; mean age 11.4 years) with known vitiligo were studied by physical examination and laboratory studies. RESULTS: Four patients with vitiligo were already known to have Hashimoto's thyroiditis. In 9 of the remaining 50 patients, autoimmune thyroiditis was revealed at the time of the investigation. Of the 54 patients with vitiligo, 13 (24.1%) had autoimmune thyroiditis as compared with 9.6% of school-aged children from an iodine-replete area of Greece ( P = .002). There was no association between thyroiditis and clinical type of vitiligo, age at onset, mean duration of vitiligo, or sex. CONCLUSIONS: Hashimoto's thyroiditis is 2.5 times more frequent among children and adolescents with vitiligo than in a healthy age- and sex-matched population. It usually follows the onset of vitiligo. We propose that children and adolescents with vitiligo should be screened annually for thyroid dysfunction, particularly autoimmune thyroiditis.

Adolescent↗

Cutaneous blood flow and adrenoceptor response increase in segmental-type vitiligo lesions.

It has been proposed that two types of vitiligo exist from the physiological and clinical points of view. Nonsegmental-type vitiligo is associated with autoimmune diseases while segmental-type vitiligo results from the dysfunction of sympathetic nerves in the affected area. Using laser Doppler flowmetry and iontophoresis for cutaneous microcirculatory assessments, we evaluated these two types of vitiligo in regard to their physiological changes. Ten patients with facial stable stage segmental-type vitiligo and ten stable nonsegmental-type vitiligo patients were selected for this study. Our results revealed that a nearly threefold increase in cutaneous blood flow was noticed in segmental-type vitiligo as compared to contralateral normal skin. In contrast, a 1.4-1.5 times difference was found among nonsegmental-type vitiligo, lesion side clinically normal skin and contralateral normal skin. There was a significant increase in cutaneous alpha- and beta-adrenoceptor response in segmental-type vitiligo lesions. However, no change in plasma catecholamines or adrenoceptor densities on blood cells was noticed. Our findings suggest that a dysfunction of the sympathetic nerves exists in the affected skin and plays a role in the pathogenesis of segmental-type vitiligo.

Adolescent↗

Direct evidence to support the role of antigen-specific CD8(+) T cells in melanoma-associated vitiligo.

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of melanocytes. An autoimmune mechanism is strongly suspected to be involved in this affection given that it is frequently associated with autoimmune hormonal disorders, and because antibodies directed against melanocytic antigens are found in the serum of patients with vitiligo. We examined the role of cellular immunity in melanoma-associated vitiligo by expanding infiltrating lymphocytes from fresh biopsy specimens of vitiligo patches in melanoma patients. The vitiligo-infiltrating lymphocytes were almost exclusively T lymphocytes, and most were CD8(+). Following in vitro expansion, vitiligo-infiltrating lymphocytes remained predominantly CD8(+) and expressed the cutaneous homing receptor CLA. Furthermore, vitiligo-infiltrating lymphocytes had a clonal or oligoclonal T cell receptor profile, possibly reflecting specific antigenic stimulation. Finally, vitiligo- infiltrating lymphocytes specifically recognized differentiation antigens shared by normal melanocytes and melanoma cells. This direct demonstration of CD8(+) T cell involvement in vitiligo suggests that, in melanoma patients, vitiligo may be a visible effect of a spontaneous antitumoral immune response.

Adult↗

Evidence for immunologic mechanisms in human vitiligo: patients' sera induce damage to human melanocytes in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity.

Human vitiligo is a common depigmenting disorder that is often associated with polyendocrinopathies. The etiology of vitiligo is unknown although there is indirect evidence of a strong association between antimelanocyte antibodies in animal and human vitiligo. We report direct evidence that vitiligo patients' sera containing antimelanocyte antibodies can lyse cultured human melanocytes by both complement activation and antibody-dependent cellular cytotoxicity (ADCC). Melanocyte cytotoxicity was measured using an ethidium bromide/acridine orange viability assay, after 4 and 16 h incubation with sera from vitiligo patients and from normal controls. Significant melanocyte cytotoxicity was seen with vitiligo patients' sera as an antibody source with both complement-mediated cytotoxicity (p less than 0.01) and ADCC (p less than 0.05) as effector mechanisms. Nine of 11 vitiligo patients' sera produced cytotoxicity by complement-mediated lysis or ADCC. No cytotoxicity was seen using fibroblast targets and vitiligo patients' sera. The lysis of human melanocytes by vitiligo patients' sera by two different effector mechanisms provides direct support for the autoimmune hypothesis of human vitiligo.

Antibody-Dependent Cell Cytotoxicity↗

Relationship between levels of soluble interleukin-2 receptors and the types and activity of vitiligo.

Levels of serum-soluble interleukin-2 receptors (serum sIL-2R) are thought to indicate the activation of immunocompetent cells, mainly lymphocytes. Elevated levels of serum sIL-2R have been observed in various infectious and autoimmune diseases and also after organ transplantation. It has been hypothesized that autoimmune mechanisms are involved in the pathogenesis of vitiligo. Therefore, we studied serum sIL-2R levels in relation to disease types and activity of vitiligo. We used sera separated from venous blood samples from 12 patients with dermatomally distributed type B vitiligo, 17 patients with non-dermatomally distributed type A vitiligo during the active stage, 9 patients with type A vitiligo during the inactive stage, and 12 normal control subjects. Serum sIL-2R levels were similar in type B vitiligo patients and the controls but were significantly elevated in patients with active type A vitiligo compared with controls and inactive type A vitiligo patients. It is suggested that the immune system is activated in patients with type A vitiligo during the active stage and that autoimmune mechanisms may play a role only in type A vitiligo.

Autoimmunity↗

Neuropeptide and neuronal marker studies in vitiligo.

Neuropeptide and neuronal marker immunoreactivity was studied in skin biopsies from lesional and marginal areas in 12 patients with vitiligo, and in seven normal controls. The vitiligo was active in seven, static in two, and of unknown activity in three. Antibodies against general neuronal marker PGP 9.5 (PGP 9.5), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY), were used. The epidermis, dermo-epidermal junction, papillary and reticular dermis, and appendages, were assessed semiquantitatively for reactivity with each antibody. Staining with PGP 9.5 in the upper dermis was assessed quantitatively by image analysis. An increase in reactivity against NPY antibody was seen in five of 10 cases (three with active vitiligo) in the marginal areas, and in three of 12 subjects (all with active vitiligo) in the lesional vitiligo areas. VIP antibody reactivity showed a minimal increase in the marginal and lesional vitiligo areas (in two cases each, both of whom had active vitiligo). SP and CGRP reactivities did not differ from normal. PGP 9.5 staining was minimally increased at the dermo-epidermal junction and lower Malpighian layer in biopsies from marginal areas in three of 10 subjects (all with active vitiligo). Quantitative analysis of PGP 9.5 reactivity in the upper dermis showed no difference between vitiligo and normal biopsies. These findings support the concept of neuronal or neuropeptide involvement in vitiligo, and in particular suggest that NPY may have a role in the pathogenesis of the disease.

Biomarkers↗