Autoimmune aspects of depigmentation in vitiligo

Autoimmune depigmentation of the skin, vitiligo, afflicts a considerable number of people, yet no effective therapeutic modalities have been developed to treat it. In part, this can be attributed to the obscure etiology of the disease, which has begun to reveal itself only recently. It is known that pigment is lost as a function of reduced melanocyte numbers in the epidermis, and that depigmentation is accompanied by T cell influx to the skin in the vast majority of patients. Characterizing such infiltrating T cells as type 1 proinflammatory cytokine-secreting cells reactive with melanocyte-specific antigen is a major step toward effective therapy. Melanoma research has shown that differentiation antigens, also expressed by normal melanocytes, can be immunogenic when expressed in the melanosomal compartment of the cell. Similar reactivity to melanosomal antigens is apparent for T cells infiltrating vitiligo skin. It may eventually be possible to treat patients with decoy antigens that anergize such Tcells, or to prevent recruitment of the T cells to the skin altogether. In this respect, it is important that T cells are recruited to the skin as a function of dendritic cell activation and that dendritic cells are likely activated at sites of epidermal trauma as a consequence of stress proteins that spill over into the microenvironment. Stress proteins chaperoning antigens representative of the cells from which they were derived are then processed by dendritic cells and contribute to their activation. Activated dendritic cells not only migrate to draining lymph nodes to recruit T cells but may execute cytotoxic effector functions as well. The contribution of the effector functions to actual depigmentation of the skin remains to be investigated.     

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.     

Inflammatory changes in vitiligo: stage I and II depigmentation

Frequent failure of early studies to demonstrate inflammatory changes in vitiligo led many investigators to consider the disease as noninflammatory. However, others found an inflammatory element in vitiliginous lesions. In this study we tried to verify that assumption. Twenty-five patients (10 males and 15 females) with common vitiligo and 11 normal healthy individuals were included. Histopathologic studies were carried out using epon-embedded sections stained with modified toluidine blue stain. Comparisons of the results of histopathologic examination of the stained specimens of vitiliginous lesions (both stage I and II), marginal areas, and uninvolved normal skin of vitiligo patients with normal healthy control were performed. Focal spongiosis was observed in 48% of the specimens of vitiligo patients and largely limited to the marginal areas and stage I vitiligo lesions. Epidermal mononuclear cell infiltration was seen in 80% of both the marginal areas and stage I vitiligo specimens. The number of these cells was significantly higher than that in stage II lesions and uninvolved skin. Many of the epidermotropic lymphocytes were grouped together, forming clusters resembling Pautrier microabscesses. The extent of epidermal mononuclear cell invasion did not always parallel the density of the subjacent dermal infiltrate. Vitiligo is an inflammatory disease, and the epidermal lymphocytic infiltration is most likely the primary immunologic event.     

虹膜脱色素为首发的白癜风一例

患儿女,6个月龄,因左眼周白斑伴睫毛变白3个月余来我院就诊。患儿家属3个月前发现患儿左眼睑白斑,未予重视,后白斑渐扩大至左眼鼻侧眼周,伴睫毛变白。患儿出生时双眼虹膜颜色一致,出生后10 d患结膜炎,愈后开始出现虹膜颜色渐变淡。患儿的父母及其三代亲属无相关疾病史。体检：全身各系统检查同一般正常同龄儿……     

HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo

Vitiligo is a T-cell-mediated autoimmune disease of the skin. Progressive depigmentation accelerates in response to stress. Personal trauma, contact with bleaching phenols, overexposure to UV, and mechanical injury can lead to progressive loss of melanocytes. This study was focused on the role of stress protein heat shock protein (HSP)70 for translating stress into an autoimmune disease to melanocytes. Intracellular HSP70 can act as a cytoprotectant, preventing apoptosis in cells under stress. Isoform HSP70i can be secreted by live cells, and in prior in vitro studies, HSP70 has been shown to activate dendritic cells and elicit an immune response to chaperoned proteins and peptides. Here, the role of HSP70 in precipitating and perpetuating vitiligo was assessed in vivo in a mouse model of autoimmune vitiligo. In this model, depigmentation was introduced by gene gun vaccination with eukaryotic expression plasmids encoding melanocyte differentiation antigens. Inclusion of human and mouse-derived inducible HSP70 in the vaccination protocol significantly increased and accelerated depigmentation in this model, accompanied by the induction of prolonged humoral responses to HSP70. Cytotoxicity toward targets loaded with a K(b)-restricted tyrosinase-related protein 2-derived peptide correlated with depigmentation. The data presented strongly support a role for HSP70i in progressive depigmentation in vivo.     

白癜风治疗进展

白癜风系色素脱失性皮肤病,易诊断,难治疗,一般可参考国内2009版白癜风治疗共识。近年来联合治疗成为临床最常用的治疗模式,如光疗联合外用药物治疗,手术治疗联合光疗等。新的治疗方法主要为手术方法的改进、非常规口服药及外用药、基因治疗及生物制剂如抗肿瘤坏死因子(TNF)-α制剂治疗,这些方法临床应用较少,其疗效尚需临床试验的验证。     

Oral dexamethasone pulse treatment for vitiligo

BACKGROUND: Oral corticosteroid pulse therapy has provided inconsistent results in the treatment of Indian patients with vitiligo. OBJECTIVE: We wanted to evaluate the efficacy, safety, and tolerability of oral dexamethasone pulse therapy in a cohort of Austrian patients with vitiligo. METHODS: Twenty-nine patients with vitiligo were included in the study. Of these, 25 had progressive and 4 had stable disease. The patients were given weekly pulses of 10 mg dexamethasone each on 2 consecutive days followed by 5 days off treatment for a maximum period of 24 weeks. Clinical response and side effects were evaluated in monthly intervals. Plasma cortisol and corticotropin levels were monitored before and up to 6 days after the dexamethasone pulse in the first and fourth week of treatment in 14 patients. RESULTS: After a mean treatment period of 18.2 +/- 5.2 weeks, the disease activity was arrested in 22 of 25 patients (88%) who had active vitiligo before the study. Marked repigmentation occurred in 2 patients (6.9%) and moderate or slight repigmentation in 3 patients (10.3%) each. No response was noted in 21 patients (72.4%). Side effects were recorded in 20 patients (69%) and included weight gain, insomnia, acne, agitation, menstrual disturbance, and hypertrichosis. Plasma cortisol and corticotropin values were markedly decreased 24 hours after the second dexamethasone dose, yet returned to baseline values within the off treatment period before the next dexamethasone pulse. CONCLUSION: Our data show that oral dexamethasone pulse treatment is effective in arresting progression of vitiligo yet fails to induce satisfactory repigmentation in the great majority of our patient cohort. Mild to moderate side effects are common with this treatment modality; however, sustained suppression of endogenous cortisol production does not occur with the pulse regimen.     

Mycosis fungoides with depigmentation secondary to treatment

A 51-year-old man presented with itchy, erythematous patches and plaques on his trunk, arms, and legs. A skin biopsy specimen showed mycosis fungoides. Initially the patient did not respond to PUVA photochemotherapy but later improved on NB-UVB phototherapy combined with bexarotene and interferon-alpha. The lesions progressed from erythematous patches and plaques to hyperpigmented patches with central depigmentation and localized areas of follicular repigmentation. The development of depigmentation after PUVA photochemotherapy for mycosis fungoides has been described in the literature and does not have associated prognostic implications. It is important to be cognizant of phototoxicity associated with PUVA photochemotherapy or NB-UVB phototherapy in patients with mycosis fungoides, who may be taking photosensitizing medications or have depigmented patches which renders them more sensitive to lower doses of ultraviolet light.