BACKGROUND: Metabolic syndrome (MetS) has been associated with various skin conditions including vitiligo. However, the association between these 2 conditions has yet to be determined by quantitative meta-analysis.
OBJECTIVE: The aim of this paper was to determine the association between vitiligo and metabolic syndrome via systematic review and meta-analysis.
METHODS: A systematic literature search of Pubmed, Embase, Cochrane, and Web of Science was performed for all published literature prior to August 16, 2020. Case control and prospective cross-sectional studies analyzing the association between vitiligo and MetS were included in this review. The primary outcome measures include the type of vitiligo, diagnostic criteria for MetS, components of MetS (waist circumference, blood pressure, triglycerides, fasting glycemic index, and high-density lipoprotein cholesterol), low-density lipoprotein cholesterol levels, and BMI. A meta-analysis was performed to evaluate the prevalence and association of MetS in patients with vitiligo.
RESULTS: A total of 6 studies (n=734 participants) meeting eligibility criteria were included for systematic review and meta-analysis. The pooled prevalence of MetS in patients with vitiligo was (0.296, 95% CI 0.206, 0.386; P<.001). Patients with vitiligo were no more likely to develop MetS compared to control patients (odds ratio 1.66, 95% CI 0.83, 3.33; P=.01). A leave-one-out sensitivity analysis showed a significant association between MetS and vitiligo (P<.001). Significant elevations in fasting glycemic index (mean difference 5.35, 95% CI 2.77, 7.93; P<.001) and diastolic blood pressure (mean difference 1.97, 95% CI 0.02, 3.92; P=.05) were observed in patients with vitiligo compared to control patients.
CONCLUSIONS: The association between vitiligo and metabolic syndrome carries important clinical implications. Dermatologists and other multidisciplinary team members should remain vigilant when treating this patient population in order to prevent serious cardiovascular complications that may arise as a result of metabolic disease.

Vitiligo patients may desire laser hair removal, skin rejuvenation, vascular treatments, and other laser or intense pulsed light (IPL) assisted treatments. However, there is a risk of inducing new depigmented patches (Koebner phenomenon). In absence of guidelines on the safe use of laser or IPL in vitiligo patients, dermatologists tend to be reluctant to administer these treatments. The aim of this survey study was to provide an estimation of the occurrence and related risk factors of laser/IPL-induced leukoderma or vitiligo. A cross-sectional survey study was performed among 15 vitiligo experts from 11 countries, with 14 questions about affected patients, involved laser/IPL treatments and the physicians\' approach. In a total of 11,300 vitiligo patients, laser/IPL-induced leukoderma or vitiligo was reported in 30 patients (0.27%). Of these, 12 (40%) patients had a medical history of vitiligo and seven (58%) of these patients had stable (> 12 months) vitiligo before the treatment. Most frequently reported were hair removal procedures and localization of the face and legs. Side effects like blistering, crusting, and erosions occurred in 56.7% of the cases. These vitiligo experts based their advice on the risk of the laser treatment on stability of the vitiligo (43%) and activity signs (50%), and 50% discuss the risks before starting a laser treatment. Relevant activity signs are the Koebner phenomenon (57.1%), confetti-like lesions (57.1%) and hypochromic borders (50%). Laser-induced leukoderma or vitiligo is an uncommon phenomenon. Remarkably, a minority had a medical history of vitiligo of which 58% were stable. Consequently, most cases could not have been prevented by not treating vitiligo patients. However, a majority had laser/IPL-induced skin damage. Therefore, caution is advised with aggressive settings and test-spots prior to the treatment are recommended. This study showed significant variation in the current recommendations and approach of vitiligo experts regarding laser/IPL-induced leukoderma or vitiligo.

Melanocyte cell death can lead to various melanocyte-related skin diseases including vitiligo and leukoderma. Melanocytotoxic chemicals are one of the most well-known causes of nongenetic melanocyte-related diseases, which induce melanocyte cell death through apoptosis. Various chemicals used in cosmetics, medicine, industry and food additives are known to induce melanocyte cell death, which poses a significant risk to the health of consumers and industrial workers. This review summarizes recently reported melanocytotoxic chemicals and their mechanisms of toxicity in an effort to provide insight into the development of safer chemicals.

Leukoderma, or hypomelanosis of the skin, can occur in response to various chemical and pharmacologic substances ranging from topical medications to optic preparations and systemic medications. In this case report, we present a 78-year-old man with a history of restless leg syndrome (RLS) who had been using rotigotine transdermal patches once daily for 1 year and developed leukoderma on the bilateral anterior shoulders in the area of patch application. Histopathologic examination showed an absence of melanocytes at the dermal-epidermal junction confirmed by Melan A stain. While the patient was not bothered by the depigmentation and elected to continue the rotigotine patch for his RLS, this case highlights leukoderma as a potential side effect of dopamine transdermal patches and offers insight into the potential mechanism of hypopigmentation in response to dopamine agonism.

OBJECTIVE: Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis.
METHODS: A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated.
RESULTS: Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR : 0.23; 95% CI 0.11-0.44, p < 0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N = 153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR: 0.17; 95% CI 0.06-0.44).
CONCLUSIONS: Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.

Sanqi, a traditional Chinese herb, is widely used for cardiovascular diseases, and its neuroprotective effects against oxidative stress were recently discovered. The purpose of this study was to investigate whether Sanqi-derived compound K (Sanqi-CK), an active metabolite of Sanqi, could protect melanocytes from oxidative stress. Cultured human primary skin epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of Sanqi-CK. Sanqi-CK exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, treatment with Sanqi-CK reversed the decreased glutathione reductase activity and decreased ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) seen in H2O2-treated melanocytes. Furthermore, topical application of Sanqi-CK alleviated leukoderma in guinea pigs, a disorder characterized by melanocyte cell death resulting from rhododendrol-induced oxidative stress. Taken together, these data suggest that Sanqi-CK protects melanocytes against oxidative stress, and its protective effects are associated with modulating the redox balance between GSH and GSSG and activating glutathione reductase. Thus, Sanqi-CK may be a good candidate for preventing melanocyte loss in oxidative-stress-associated pigmentary disorders.

Idiopathic leukoderma is a skin disorder characterized by patchy loss of skin pigmentation due to melanocyte dysfunction or deficiency. Rhododendrol (RD) was approved as a cosmetic ingredient in Japan in 2008. However, it was shown to induce leukoderma in approximately 20,000 customers. The prediction of cytotoxicity, especially to melanocytes in vivo, is required to avoid such adverse effects. Since the use of higher vertebrates is prohibited for medicinal and toxicological assays, we used zebrafish, whose melanocytes were regulated by mechanisms similar to mammals. Zebrafish larvae were treated with RD in breeding water for 3 days, which caused body lightening accompanied by a decrease in the number of melanophores. Interestingly, black particles were found at the bottom of culture dishes, suggesting that the melanophores peeled off from the body. In addition, RT-PCR analysis suggested that the mRNA levels of melanophore-specific genes were significantly low. An increase in the production of reactive oxygen species was found in larvae treated with RD. The treatments of the fish with other phenol compounds, which have been reported to cause leukoderma, also induced depigmentation and melanophore loss. These results suggest that zebrafish larvae could be used for the evaluation of leukoderma caused by chemicals, including RD.

The role of Langerhans cells (LCs) in vitiligo pathogenesis remains unclear, with published studies reporting contradictory results regarding the quantity of LCs and no data on the features of LCs in vitiligo. Here, we aimed to analyze the presence, density, and morphological features of LCs in the epidermis of patients with vitiligo. Skin biopsies were stained for LCs using anti-CD1a/anti-langerin antibodies and analyzed by immunocytochemistry with light and electron microscopy. Compared with healthy controls, we detected significantly increased numbers of epidermal LCs in lesional skin from vitiligo in the progressive state. These LCs exhibited striking morphological alterations, including an elevated number of dendrites, with increased length and more branches than dendrites from controls. Ultrastructure examination via immuno-electron microscopy revealed markedly reduced Birbeck granules (BGs) and shorter BG rods in LCs from progressive vitiligo, with higher expression of langerin. Additionally, expression of S100B, the activity biomarker of vitiligo, was increased in these LCs. This work provides new insight on the cellular composition of LCs in vitiliginous skin, revealing altered morphology and increased LC numbers, with elevated S100B expression. Our data suggest LCs might play a critical role in vitiligo pathogenesis and thus may represent a novel therapeutic target for this disease.

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.

Cutaneous malignant melanoma is a rapidly progressing skin tumor accounting for most deaths from skin malignancies. Four morphological variants (nodular, superficial spreading, lentigo maligna, and acral lentiginous) are described in the literature. Here we are reporting malignant melanoma in a 35-year-old male who presented with depigmented plaques with few hyperpigmented areas and extensive overlying scaling. The patient progressed to the nodular stage within 2 weeks and succumbed to death during chemotherapy. We are reporting such rare presentation of malignant melanoma to create awareness among dermatologists to avoid misdiagnosis and delayed treatment which can lead to rapid progression and fatal outcome.