Vitiligo and pernicious anemia presenting as congestive heart failure

The skin often provides diagnostic clues to systemic disorders. Vitiligo is an acquired disease characterized by depigmentation of the skin due to destruction of melanocytes. Vitiligo may be an autoimmune disease and is associated with other disorders that may also arise due to autoimmune mechanisms. We present the unusual case of vitiligo associated with pernicious anemia in a patient who presented to the hospital because of hyperdynamic congestive heart failure.     

Do we have to pay more attention to vitiligo patients? Peculiar histopathological features of primary cutaneous melanoma preceded by vitiligo

Vitiligo is an acquired depigmenting skin disease characterized by the loss of functioning epidermal melanocytes. Vitiligo can be associated with an autoimmune disorder. An unusual and important aspect of vitiligo is its relationship to melanoma. We present herein a 34-year-old man who developed regional lymph node metastases of malignant melanoma 2 years after the diagnosis of vitiligo.     

Two therapeutic challenges: periocular and genital vitiligo in children successfully treated with pimecrolimus cream

Vitiligo is characterized by the selective destruction of melanocytes resulting in patches of skin depigmentation. Vitiligo is a therapeutic challenge. Eyebrows, eyelids and genital vitiligo are a therapeutic dilemma, especially in children. The possible side effects of topical corticosteroids and the difficulties for choosing any other adequate treatment option are a major concern. We present two children, one with vitiligo of the eyelids and the other with genital vitiligo, both treated with pimecrolimus 1% cream with almost full repigmentation of the lesions, showing pimecrolimus could be an adequate option for the treatment of vitiligo for these special vitiligo areas in children.     

What are those white patches on my patient's skin?

Vitiligo is a skin disease that affects 1% of the population. Vitiliginous skin does not contain pigment-producing cells called melanocytes. This leaves the appearance of white patches on the skin, which can either be generalized or localized. It is important for dermatology nurses to understand the basic pathophysiology of vitiligo, the various treatment methods, how to protect vitiliginous skin, and the psychological impact of the disease.     

Probable Mechanisms of Loss of Merkel Cells in Completely Depigmented Skin of Stable Vitiligo

Vitiligo is frequently associated with segmental involvement. It spares paralyzed limbs in transverse myelitis. There is spontaneous repigmentation of vitiligo lesional skin (VL) in diabetic neuropathy. Increased neuropeptide in VL and adjacent normal skin of vitiligo (ANS) along with thickened nerve fibers showing ultrastructural abnormalities all indicate a neural pathogenesis (1). Loss of Merkel cells has been observed in early vitiligo lesional skin (2). Recently, catecholamines have been found to play a major role in initiating the cascade of events leading to loss of melanocytes (1, 3, 4). To investigate the presence of Merkel cells in the completely depigmented skin of stable vitiligo (SV), a study was undertaken using TROMA 1, a monoclonal antibody specific for adult Merkel cells. No TROMA 1-positive cells were observed in SV, whereas normal numbers of these cells were seen in ANS. This new finding further supports the hypothesis of neural involvement in vitiligo.     

Vitiligo associated with other autoimmune diseases: polyglandular autoimmune syndrome types 3B+C and 4

Vitiligo is a common skin disease characterized by depigmented maculae resulting from a reduction of the number and function of melanocytes. Many studies suggest that vitiligo might be an autoimmune disease. Vitiligo has been frequently described in association with other autoimmune diseases. Among the diseases described in association with vitiligo are the so-called autoimmune polyglandular syndromes (APS). Vitiligo can be present in all types of APS but the most frequent association appears to be in APS-3. APS-3 was defined as the association between autoimmune thyroiditis and another autoimmune disease. Here we report one patient with thyroiditis, vitiligo and autoimmune gastritis (APS-3B+C), one patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS-3C), and one case of a young patient with type 1 diabetes mellitus and vitiligo (APS-4), according to the newest classification. We stress the importance of a thorough assessment for autoimmune diseases in selected patients with vitiligo.     

In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects

The in vitro growth characteristics of melanocytes obtained from uninvolved and perilesional skin of vitiligo vulgaris subjects have been investigated in comparison to those from healthy adult donors. Normal human melanocytes have been found to grow exponentially in the presence of 10(-11) M cholera toxin and 10 ng/ml of 12-O-tetradecanoylphorbol-13-acetate in routine tissue culture media. They could be trypsinized up to 3-4 passages. Melanocytes of the uninvolved skin of vitiligo subjects manifested a lag of 8-11 days for the onset of growth and they could not be passaged. Melanocytes obtained from both hypo- and hyper-pigmented perilesional skin failed to grow under these conditions. Only in a few cases where the perilesional skin was normally pigmented did the melanocytes manifest some growth after a lag of 15 days. The initial seeding capacity of the melanocytes from uninvolved and perilesional skin of vitiligo patients were, respectively, 50% and 25% of the normal individuals. Vitiligo lesions themselves gave rise to unidentified dendritic cells that survived for 10-15 days without manifesting any growth. Our results suggest that melanocytes of individuals with vitiligo are defective. This fact has to be taken into account in any theory on the etiology of vitiligo.     

BIOLOGIC CHARACTERISTICS OF CULTURED HUMAN VITILIGO MELANOCYTES

Background. Vitiligo is a pigmentary disorder of unknown cause characterized by depigmented patches due to destruction of melanocytes. Recently, the inherent cellular defect theory has been discussed. To investigate the biologic characteristics of cultured melanocytes from normal and vitiligo subjects, this study had the purpose to examine the functional and ultrastructural characteristics of these melanocytes and to observe the morphologic and functional changes of melanocytes in response to ultraviolet B irradiation. Methods. Melanocytes were isolated and cultured from foreskin and arm skin of normal and vitiligo subjects. The DNA synthesis, tyrosinase activity assay, transmission and scanning electron microscopic examination, and the effects of ultraviolet B(uvB)-irradiation on cultured melanocytes were studied. Results. Vitiligo melanocytes showed no significant differences in DNA synthesis and tyrosinase activity compared with normal melanocytes, but the vitiligo melanocytes contained dilated and/or circular rough endoplasmic reticulum (RER) on transmission electron microscopic examination. Exposure of the cultured melanocytes to UVB resulted in increased protein synthesis and tyrosinase activity. Morphologic alterations and changes in DNA synthesis were also noted. Compared with normal melanocytes, the responses of vitiligo melanocyte to UVB showed no significant difference. Conclusions. Normal and vitiligo melanocytes showed similar biologic characteristics except in the changes of RERS in the vitiligo melanocytes. The ultrastructural aberrations in vitiligo subjects do not seem to be directly related to the biologic characteristics and the responses to UVB irradiation in vitiligo melanocytes.     

Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy

BACKGROUND: Vitiligo is the most common pigmentary disorder with a global incidence from 0.1% to 2% in different geographical areas. Histopathology and histochemistry have shown the reduction of melanocytes in achromic patches, but microscopic changes of lesional and non-lesional skin are still not completely understood. Reflectance confocal microscopy (RCM), based on the different light reflectance index of cutaneous structures, allowed in vivo, en face microscopic evaluation of superficial skin layers with a resolution similar to skin histology. AIM: The purpose of this study was to evaluate RCM features of lesional and non-lesional skin of vitiligo patients. Moreover, re-pigmented areas were taken into consideration in order to evaluate melanocyte response to ultraviolet B (UVB) radiation. SUBJECTS AND METHODS: Sixteen patients of different phototypes affected by active non-segmental vitiligo and 10 controls were enrolled in the study. In vivo skin imaging was done using a commercially available RCM (Lucid, Vivascope 1500. Re-pigmented areas from 6 to 16 patients (after UVB narrow-band therapy) were also examined. RESULTS: Vitiligo lesions showed the disappearance of the bright rings normally seen at the dermo-epidermal junction. Moreover, non-lesional skin of vitiligo patients showed unexpected changes as the presence of half-rings or scalloped border-like features of the bright papillary rings. In re-pigmented areas after UVB narrow band therapy, the presence of activated, dendritic melanocytes was seen. CONCLUSIONS: Considering our results, and following further studies, RCM clinical applications could be used in the therapeutic monitoring and evaluation of the evolution of vitiligo.     

白癜风与黑素瘤关系的研究进展

白癜风是以皮肤黑素细胞破坏导致的获得性色素脱失性疾病;黑素瘤是皮肤、黏膜黑素细胞异常增生导致的一种恶性肿瘤。近年来研究发现黑素瘤患者的白癜风发生率远远高出正常人群,这一现象的发生可能是机体抗黑素瘤的细胞及体液免疫应答作用于正常黑素细胞的结果。     

Two Cases of Vitiligo Developed on the Persisting Dermal Melanocytosis: Is There a Difference between Epidermal Melanocytes and Dermal Melanocytes?

Vitiligo is one of the most common pigmentary skin disorders; it is characterized by circumscribed depigmented macules due to the destruction of melanocytes. Although the etiology of vitiligo has not been fully elucidated, multiple factors including autoimmune and oxidative stress have been implicated in the pathogenesis of vitiligo. In contrast, dermal melanocytosis is histologically characterized by the presence of dermal melanocytes. It has been described that there are ectopic dermal melanocytes, which have failed to reach their proper location. A literature search revealed very few reports of patients with vitiligo developing vitiligo within dermal melanocytosis. Here, we report two cases of patients with vitiligo that occurred at pre-existing sites of dermal pigmented lesions. The histopathology showed the loss of epidermal melanocytes in spite of the existence of melanocytes in the dermis. There was no significant infiltration of inflammatory cells in the dermis. These cases illustrate unknown environmental factors as well as heterogeneity.     

Vitiligo: a review of some facts lesser known about depigmentation

Vitiligo is a disorder that causes the destruction of melanocytes. It has three important factors underlying this destruction. The depigmented skin has many aberrant functions such as a muted response to contact allergens, a phenomenon also seen in mice that depigment. The white skin of those with vitiligo does not form non-melanoma skin cancers although the white skin of albinos, which has a similar color as vitiligo, is highly susceptible to skin cancer.     

Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: The role of lesional expression of tumor necrosis factor-α and interferon-γ in Fas-mediated melanocyte apoptosis

Vitiligo is an acquired skin depigmentation disorder resulting from the selective loss of epidermal melanocytes, and previous studies have suggested that a T lymphocyte-mediated mechanism has a role in melanocyte loss. Although Fas-Fas ligand (FasL) interactions are important for T lymphocytes to mediate cytotoxicity, there are only few reports examining the involvement of the Fas-FasL pathway in vitiligo using in vivo mouse models. In addition, there have been no reports concerning Fas-mediated apoptosis in human melanocytes in vitro. In this study, we found that the Fas-mediated pathway is involved in cytotoxic T lymphocyte (CTL)-dependent vitiligo in a mouse model and FasL-induced apoptosis of human melanocytes. Tumor necrosis factor (TNF)-α and interferon (IFN)-γ, the expression levels of which have been reported to be elevated in lesional skin of patients with vitiligo, synergistically upregulated Fas expression on human melanocytes but inhibited the Fas-mediated apoptosis. Treatment with TNF-α and IFN-γ synergistically upregulated the expression of the anti-apoptotic genes, c-IAP2, c-FLIP and MCL1. A siRNA knock-down study showed that c-FLIP and MCL1, but not c-IAP2, were involved in inducing synergistic inhibitory effects on Fas-mediated apoptosis. Furthermore, we found that FasL and TNF-related apoptosis - inducing ligand (TRAIL) synergistically induced apoptosis on human melanocytes. In conclusion, our results suggest that the Fas-FasL pathway is involved in CTL-dependent vitiligo and the elevated expression levels of TNF-α and IFN-γ in lesional skin may act synergistically on melanocytes to suppress Fas-mediated apoptosis.     

Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo

Vitiligo is an acquired skin disease, characterized by white areas on the skin due to loss of functional melanocytes. The pathogenesis of the disease is still unclear. Published data show the involvement of oxidative stress in the pathophysiology of vitiligo. A total of 30 vitiligo patients and 30 healthy controls were included in this study. We estimated serum levels of malondialdehyde (MDA), vitamins E and C, total antioxidant activity and whole blood levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in vitiligo patients and controls. We found significantly higher levels of MDA and significantly lower levels of SOD, GPx, vitamins C and E and total antioxidant activity in vitiligo patients compared with controls. This study is a maiden attempt to report on antioxidant parameters of both generalized/localized-type Indian vitiligo patients. Our results confirmed that oxidative stress may play an important role in the pathogenesis of vitiligo and cause melanocyte damage in vitiligo.     

Investigation of hearing and outer hair cell function of the cochlea in patients with vitiligo

Vitiligo is a systemic disease that affects not only the skin but also other areas that contain melanocytes, such as the inner ear. Studies of the effect of vitiligo on hearing loss have shown inconsistent results, and it is not clear which parameters related to the disease affect hearing. The aim of this study was to determine which disease‐related parameters trigger damage to cochlear melanocytes in vitiligo patients and the effect of vitiligo on the outer hair cells and hearing. Thirty‐one vitiligo patients and 40 sex‐ and age‐matched healthy volunteers were evaluated. The conventional pure tone audiometry (C‐PTA) test and the distortion product otoacoustic emission (DPOAE) test were performed. There was no significant difference between vitiligo patients and controls in C‐PTA test results, but the DPOAE test results were abnormal in vitiligo patients. The duration of the disease was significantly related to hypoacusis. As the duration of the disease increases, cochlear dysfunction may increase. Especially in patients with longer disease duration, otoacoustic emission tests should be performed in addition to conventional audiometry tests for early detection of damage to the outer hair cells.     

Vitiligo: a review of the published work

Vitiligo is a common depigmenting skin disorder, characterized by acquired, idiopathic, progressive, circumscribed hypomelanosis of the skin and hair, with total absence of melanocytes microscopically. It occurs worldwide, with an incidence rate of between 0.1% and 2%. Vitiligo is an important skin disease having a major impact on the quality of life of the patient suffering from it. The causes of this condition are uncertain but seem to be dependent on the interaction of genetic, immunological and neurological factors. Vitiligo coexists with other autoimmune disorders, Sutton or halo nevus, and malignant melanoma. The substantial disfigurement associated with vitiligo can cause serious emotional stress for the patient, which necessitates treatment. Because its pathogenesis is still not understood, there is a plethora of different treatments. Among them, topical steroids and narrowband ultraviolet B monotherapy were the most common as current treatments for localized and generalized vitiligo, respectively. Cosmetic improvement can be achieved by camouflage products and self-tanning dyes. The course of vitiligo is unpredictable, but often progressive. Spontaneous repigmentation may occur in a few people (10–20%), mainly in children, but this tends to be only partial and on sun-exposed areas. In this article, we review vitiligo as a whole, including epidemiology, pathogenesis and etiology, histopathology, clinical manifestations, classification, clinical variants, diagnosis and differential diagnoses, specific investigation, treatment, prognosis, psychosocial view and its association with other disorders.     

T淋巴细胞在白癜风免疫学发病机制中的研究进展

白癜风是一种皮肤色素脱失性疾病,以表皮功能性黑素细胞破坏为主要特征.目前研究支持其发病与遗传、免疫、氧化应激、神经-体液等机制有关.其中,T淋巴细胞介导的免疫反应在白癜风发病中起重要作用.CD4+T细胞亚群Th1、Th2、Th17、调节性T细胞通过分泌多种细胞因子调节其他免疫细胞的功能、诱导黑素细胞凋亡.CD8+T细胞可经由细胞毒作用直接杀伤黑素细胞.另一方面,自身耐受功能障碍、自身反应性T细胞数量和活性的增加可以增强T细胞对黑素细胞的免疫反应.除此以外,恒定型自然杀伤T细胞、记忆性T细胞等对白癜风免疫相关发病有一定的作用.     

Molecular and cellular basis of depigmentation in vitiligo patients

Vitiligo is a chronic skin disease characterized by the appearance of zones of depigmentation. It is mostly described as an autoimmune disease in which the immune system destroys the melanocytes. Consistent with this origin, genetic studies have implicated genes encoding proteins mediating the immune response targeting melanocytes in the aetiology of this disease, together with proteins specific to these cells. However, the destruction of melanocytes by the immune system is neither global nor complete, because the patients do not display total depigmentation. The etiopathology of vitiligo is clearly complex and cannot be simply reduced to an autoimmune reaction directed against pigmented cells. Intrinsic changes have been observed in the melanocytes, keratinocytes and dermal cells of vitiligo patients. Identification of the molecular and cellular changes occurring in normally pigmented skin in vitiligo patients, and an understanding of these changes, is essential to improve the definition of trigger events for this disease, with a view to developing treatments with long‐term efficacy. This review focuses on the early events identified to date in the non‐lesional regions of the skin in vitiligo patients and discusses the process of repigmentation from melanocyte stem cells.     

光疗在白癜风治疗中的临床应用

白癜风是一种常见的慢性获得性色素减少性疾病,其发病机制尚不清楚,可能的机制有自身免疫、黑素细胞自毁、神经精神因素、表皮因子失衡及遗传因素等.临床上治疗白癜风的方法很多,光疗及其联合疗法是目前有效的治疗方法之一,尤其适用于泛发性及难治性白癜风.而临床应用中,光疗疗效受多因素影响,如疾病分型、患病年龄、皮损部位等.因此了解各种光疗的作用机制,适应证,临床疗效及不良反应,有助于临床医生选择最佳的治疗方案.     

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.