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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., (© 2023. The Author(s).)

Purpose: 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)., Conclusion: 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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to assess the efficacy of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid, performed using a ready-to-use kit, compared with hyaluronic acid alone (neutral comparator) for repigmenting vitiligo and piebaldism lesions at 6 months. Two identified paired lesions per patient were randomized to be treated by either device. Devices with a ready-to-use kit were prepared by separate health professionals, to maintain blinding. A skin biopsy was digested using trypsin, and cells resuspended in hyaluronic acid solution. Among 38 patients screened, 36 (94.7%) patients, corresponding to 72 lesions, were analysed. For difficult-to-treat lesions, defined as those located on the wrist, elbow, and hands (n = 30), no repigmentation ≥ 50% was observed. For all other locations (n = 42), the success rate was significantly higher (p = 0.021) in the ready-to-use kit group (47.6% vs 9.5%) at 6 months and was maintained until 12 months. In conclusion, a single application of non-cultured epidermal cellular grafting using a ready-to-use kit was efficient at 6 months and at 1-year follow-up.

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., (© 2021 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Introduction: Endemic non-filarial elephantiasis also known as podoconiosis often affects bare footed farmers and is endemic in Ethiopia. The disease is prevented by wearing shoes. We recently observed several patients presenting to a dermatology clinic with skin depigmentation after wearing plastic shoes ("shoe-contact vitiligo") which may deter shoe-wearing. We report on their sociodemographic and clinical characteristics., Methodology: This is a retrospective study of 17 months at tertiary level Hospital in Ethiopia. Patient data was retrieved from medical record department. We compared sociodemographic and clinical characteristics of patients presenting with idiopathic and shoe-contact vitiligo. Data was presented descriptively., Results: Of 460 vitiligo cases, 190 (41%) were shoe-contact vitiligo and the rest, idiopathic. The former was more common in females (Odds Ratio, OR = 2.5, P < 0.001) and those in rural areas (OR = 4.8, P < 0.001). Fifty-five percent with shoe-contact vitiligo had itching and/or burning sensation, compared to just 2% with idiopathic vitiligo (P < 0.001) and some had ulcerations (8%). Idiopathic vitiligo had no such findings. Skin discoloration occurred within three weeks (on average) after wearing plastic shoes, 91% of lesions were symmetrical and involved areas of the feet covered with plastic shoes. Symmetric lesions were observed in only 11% of idiopathic vitiligo (OR = 81, P < 0.001)., Conclusions: Shoe-contact vitiligo was significantly associated with wearing cheap plastic shoes. The exact chemical culprit(s) needs to be identified. This will allow introducing quality control regulations and rigorous monitoring of shoe production sites., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Wendemagegn Enbiale, Kasanesh Abebe, Berhane Debru, Johan van Griensven, Kuda Takarinda, Marcel Manzi, Rony Zachariah.)

Postburn leukoderma is challenging to treat with different surgical and nonsurgical treatments resulting in variable outcomes. We report a case of a 56-year-old female with postburn leukoderma treated successfully with topical daylight psoralen UVA therapy for 6 months. The treatment was well tolerated and showed excellent improvement. In conclusion, we report the successful use of topical daylight PUVA for postburn leukoderma with almost complete repigmentation. This is a simple, convenient, and cheap nonsurgical treatment option., (© 2020 Wiley Periodicals, Inc.)

Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL). While many attempts have been made to clarify the mechanism underlying RIL, RIL has not been fully understood yet. Indeed, affected subjects showed uneven skin pigmentation, but the features are different from vitiligo, a skin hypopigmentary disorder, alluding to events more complex than simple melanocyte cytotoxicity. Here, we discovered that rhododenol treatment reduced the number of melanocytes in a pigmented 3D human skin model, Melanoderm™, confirming the melanocyte toxicity of RD. Of note, melanocytes that survived in the RD treated tissues exhibited altered morphology, such as extended dendrites and increased cell sizes. Consistently with this, sub-cytotoxic level of RD increased cell size and elongated dendrites in B16 melanoma cells. Morphological changes of B16 cells were further confirmed in the immunocytochemistry of treated cells for actin and tubulin. Even more provoking, RD up-regulated the expression of tyrosinase and TRP1 in the survived B16 cells. Evaluation of mRNA expression of cytoskeletal proteins suggests that RD altered the cytoskeletal dynamic favoring cell size expansion and melanosome maturation. Collectively, these results suggest that RD not only induces cytotoxicity in melanocytes but also can lead to a profound perturbation of melanocyte integrity even at sub-cytotoxic levels.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes.In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans.Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

Monobenzone is a 4-substituted phenol that can induce vitiligo and antimelanoma immunity. We investigated the influence of the chemical structure on the biological activity of a series of structurally related 4-substituted phenols. All phenols inhibited cellular melanin synthesis, and eight of ten phenols inhibited tyrosinase activity, using the MBTH assay. These phenols also induced glutathione (GSH) depletion, indicative of quinone formation and protein thiol binding, which can increase the immunogenicity of melanosomal proteins. Specific T-cell activation was found upon stimulation with phenol-exposed pigmented cells, which also reacted with unexposed cells. In contrast, 4-tertbutylphenol induced immune activation was not restricted to pigment cells, analogous to contact sensitization. We conclude that 4-substituted phenols can induce specific T-cell responses against melanocytes and melanoma cells, also acting at distant, unexposed body sites, and may confer a risk of chemical vitiligo. Conversely, these phenols may be applicable to induce specific antimelanoma immunity., (© 2019 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd.)

Background: Persistence of pigmentation after a melanocyte-keratinocyte transplantation procedure (MKTP) is an important consideration for efficacy., Objective: We sought to determine long-term repigmentation of MKTP in vitiligo and other leukodermas., Methods: A retrospective review of electronic medical records was conducted for all MKTPs performed at Henry Ford Hospital between January 2009 and April 2014. Repigmentation was assessed by a 5-point grading scale (poor to excellent) and Vitiligo Area Scoring Index (VASI)., Results: One hundred patients had MKTP performed at 236 anatomically-based lesions (ABLs); 63 patients with 157 ABLs had long-term data available (12-72 months; median, 24 months). Segmental vitiligo, nonsegmental vitiligo, and physical leukoderma demonstrated improvement in VASI scores: -75.6 ± 24.6%, -59.2 ± 36.6%, and -32.4 ± 33.5%, respectively. In vitiligo, at 24, 48, and 72 months after MKTP, 53%, 64%, and 53% of ABLs, respectively, maintained >75% repigmentation. Skin phototype, age, and anatomic location of ABLs had no significant effect on the outcome of treatment., Limitations: Limitations of the study include the retrospective design with uncontrolled, postoperative adjuvant treatments and inconsistent compliance to scheduled follow-up evaluations., Conclusions: MKTP provides satisfactory long-term repigmentation in the majority of appropriately selected patients with leukoderma. MKTP can maintain repigmentation for at least 72 months., (Copyright © 2017. Published by Elsevier Inc.)

Vitiligo is a common autoimmune disease that progressively destroys melanocytes in the skin, resulting in the appearance of patchy depigmentation. This disfiguring condition frequently affects the face and other visible areas of the body, which can be psychologically devastating. The onset of vitiligo often occurs in younger individuals and progresses for life, resulting in a heavy burden of disease and decreased quality of life. Presentation patterns of vitiligo vary, and recognition of these patterns provides both diagnostic and prognostic clues. Recent insights into disease pathogenesis offer a better understanding of the natural history of the disease, its associations, and potential for future treatments. The first article in this continuing medical education series outlines typical and atypical presentations of vitiligo, how they reflect disease activity, prognosis, and response to treatment. Finally, we discuss disease associations, risk factors, and our current understanding of disease pathogenesis., (Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.)

Clinicians should be aware that vitiligo is not merely a cosmetic disease and that there are safe and effective treatments available for vitiligo. It is important to recognize common and uncommon presentations and those with active disease, as well as their implications for clinical management; these were discussed in the first article in this continuing medical education series. Existing treatments include topical and systemic immunosuppressants, phototherapy, and surgical techniques, which together may serve to halt disease progression, stabilize depigmented lesions, and encourage repigmentation. We discuss how to optimize the currently available treatments and highlight emerging treatments that may improve treatment efficacy in the future., (Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.)

Chemical-induced depigmentation of the skin has been recognized for more than 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. Because chemical-induced depigmentation is clinically and histologically indistinguishable from nonchemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as "chemical-induced vitiligo," rather than less accurate terms that have been previously used., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The relative genetic and immune protection against melanoma and nonmelanoma skin cancers in those with vitiligo is reassuring. The results of recent studies allow us to be cautiously optimistic when discussing the risk of skin cancer caused by therapeutic exposure to narrow-band ultraviolet B light. However, we should continue to recommend sun protection at all other times to avoid burning in vitiliginous skin and to decrease incidental ultraviolet exposure. It is also important to perform full skin checks regularly in light of the prolonged courses of phototherapy required to repigment vitiliginous skin and maintain repigmentation thereafter., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Confetti-like depigmentation was noted in patients reporting recent worsening of vitiligo., Objective: We sought to determine if confetti-like depigmentation is a marker of rapidly progressing vitiligo., Methods: Review of patient records and images of patients from a vitiligo registry resulted in 7 patients with 12 images that fit inclusion criteria and were evaluated for percent depigmentation by 3 independent reviewers. The Vitiligo Disease Activity Score and the Koebner Phenomenon in Vitiligo Score in an additional cohort of patients with confetti-like lesions were compared with patients who had vitiligo without confetti-like lesions., Results: The mean percentage of depigmentation at baseline was 19.2%, which increased to 43.9% in images obtained at a mean of 16 weeks of follow-up. Vitiligo Disease Activity Score and Koebner Phenomenon in Vitiligo Score were significantly higher in the patients with confetti-like lesions compared with those without confetti-like lesions. A skin biopsy specimen of a confetti-like lesion in 1 patient revealed an inflammatory infiltrate in the papillary dermis with CD8(+) T cells localized to the dermoepidermal junction., Limitations: Small, single-center retrospective review and lack of full-body photographs are limitations., Conclusions: A confetti-like pattern of depigmentation may be a negative prognostic indicator for patients with rapidly progressing vitiligo. Further, prospective studies to evaluate this physical finding should be performed., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Melanoma is an 'immunogenic tumor', often highly infiltrated with lymphocytes, which are capable of inducing regression of the primary tumor. The commonly observed phenomenon of regression suggests substantial cross-talk between immune cells and transformed melanocytes. An immune response to melanocyte differentiation antigens common to transformed and normal melanocytes manifests clinically at distant sites as melanoma-associated vitiligo or halo nevi. Despite similar antigenic targets, the pathogenesis and prognosis differ between the different melanoma-associated leukodermas. Understanding immunologic cross-talk between melanocytes and the immune system will aid the development of approaches to combat melanoma., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The treatment of postburn hypopigmentation was primarily surgical before the advent of new technologies. Medical devices and therapies are emerging to manage scar sequelae that can be disfiguring and associated with severe psychosocial impact. These innovations have been poorly investigated for hypopigmentation, but they represent a real hope. We reviewed all articles published on Pubmed up to June 2022. Included studies had to specifically focus on treating postburn hypopigmented scars. All articles evaluating transient solutions such as make-up, and articles describing inflammation-linked hypopigmentation with no etiological details or no burn injury history were excluded. Through this review, we have highlighted 6 different types of nonsurgical treatments reported in postburn leukoderma potentially allowing definitive results. Electrophoto-biomodulation or E light (combining intensive pulsed light, radiofrequency, and cooling), topical daylight psoralen UVA therapy, and lasers (fractional lasers using pulse energies or CO2FL devices, lasers-assisted drug delivery as local bimatoprost and tretinoin or pimecrolimus) have been explored with encouraging results in hypopigmented burns. Finally, other promising medical strategies include using FK506, a nonsteroidal anti-inflammatory drug, to induce melanogenesis or using melanocyte-stimulating hormones with fractional laser-assisted drug deliveries, which are expected to emerge soon. [ABSTRACT FROM AUTHOR]

The tyrosinase inhibitor rhododendrol (RD), used as a skin whitening agent, reportedly has the potential to induce leukoderma. Although an immune response toward melanocytes was demonstrated to be involved in leukoderma, the molecular mechanism is not fully understood. We hypothesized that if RD is a pro-hapten and tyrosinase-oxidized RD metabolites are melanocyte-specific sensitizers, the sensitizing process could be reproduced by the human cell line activation test (h-CLAT) cocultured with melanocytes (h-CLATw/M) composed of human DC THP-1 cells and melanoma SK-MEL-37 cells. Cell surface expression, ROS generation and ATP release, mRNA expression, and the effects of several inhibitors were examined. When RD was added to the h-CLATw/M, the expression of cell-surface CD86 and IL-12 mRNA was greatly enhanced in THP-1 cells compared with those in the h-CLAT. The rapid death of melanoma cells was induced, with ROS generation and ATP release subsequently being greatly enhanced, resulting in the cooperative upregulation of CD86 and IL-12. Consistent with those observations, an ROS inhibitor, ATP receptor P2X7 antagonist, or PERK inhibitor antagonized the upregulation. CD86 upregulation was similarly observed with another leukoderma-inducible tyrosinase inhibitor, raspberry ketone, but not with the leukoderma noninducible skin-whitening agents ascorbic acid and tranexamic acid. RD is a pro-hapten sensitizer dependent on tyrosinase that induces ROS generation and ATP release from melanocytes for CD86 and IL-12 upregulation in DCs, possibly leading to the generation of tyrosinase-specific cytotoxic T lymphocytes. The coculture system h-CLATw/M may be useful for predicting the sensitizing potential to induce leukoderma. • A new h-CLATw/M composed of THP-1 cells and melanoma SK-MEL-37 cells was established. • RD upregulates CD86 and IL-12 in THP-1 via ROS and ATP production from SK-MEL-37. • h-CLATw/M can distinguish between leukoderma-inducible and non-inducible agents. • RD is a pro-hapten dependent on tyrosinase, possibly leading to CTL generation. • h-CLATw/M would be useful to predict the sensitizing potential to induce leukoderma. [ABSTRACT FROM AUTHOR]

Keywords: acrylates; allergic contact dermatitis; case report; construction worker; leukoderma; marble; methacrylates; methylisothiazolinone; occupational; resin EN acrylates allergic contact dermatitis case report construction worker leukoderma marble methacrylates methylisothiazolinone occupational resin 242 244 3 02/08/23 20230301 NES 230301 Plastics/resins have become an emerging cause of occupational allergic contact dermatitis (OACD) in construction workers, mainly related to exposure to epoxy resin systems. Allergic contact dermatitis, case report, construction worker, acrylates, marble, methacrylates, methylisothiazolinone, occupational, resin, leukoderma 5 d Toledo University Hospital Acrylate series: methyl methacrylate, butyl methacrylate, 2-HEMA, 2-HPMA, EGDMA, triethyleneglycol dimethacrylate, 1,4-butanediol dimethacrylate, urethane dimethacrylate, bisphenol-A-dimethacrylate, bisphenol A glycerolate dimethacrylate, 1,6 hexanediol diacrylate, tetrahydrofurfuryl methacrylate, tetraethyleneglycol dimethacrylate, dimethylaminoethyl methacrylate, ethyl cyanoacrylate, ethyl methacrylate, isobornyl acrylate, butyl acrylate, 2-hydroxyethyl acrylate, benzoyl peroxide, bisphenol A (Chemotechnique Diagnostics). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the efficacy of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid, performed using a ready-to-use kit, compared with hyaluronic acid alone (neutral comparator) for repigmenting vitiligo and piebaldism lesions at 6 months. Two identified paired lesions per patient were randomized to be treated by either device. Devices with a ready-to-use kit were prepared by separate health professionals, to maintain blinding. A skin biopsy was digested using trypsin, and cells resuspended in hyaluronic acid solution. Among 38 patients screened, 36 (94.7%) patients, corresponding to 72 lesions, were analysed. For difficult-to-treat lesions, defined as those located on the wrist, elbow, and hands (n = 30), no repigmentation ≥ 50% was observed. For all other locations (n = 42), the success rate was significantly higher (p = 0.021) in the ready-to-use kit group (47.6% vs 9.5%) at 6 months and was maintained until 12 months. In conclusion, a single application of non-cultured epidermal cellular grafting using a ready-to-use kit was efficient at 6 months and at 1-year follow-up.

Abstract Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes. In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans. Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

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.

Leukoderma secondary to Q‐switched 1064‐nm neodymium‐doped yttrium aluminium garnet laser is usually refractory to treatment. The pathogenesis was cumulative phototoxic damage to melanocytes and eventually resulted in melanocytopenia. Wood's light or UV imaging can help observe early leukoderma before it becomes apparent clinically and determine the degree of melanocytopenia before conducting a biopsy. NB‐UVB phototherapy and 308‐nm excimer laser can potentially worsen the pre‐existing melasma lesions and may not be effective if the lesions have already become melanocytopenic. Epidermal grafting can replenish the hypopigmented area with melanocytes without worsening melasma. [ABSTRACT FROM AUTHOR]

Highlights • Elaborate hydroxyl radical detection after rhododendrol application to melanocytes. • Remarkable correlation of hydroxyl radical generation with melanocyte cytotoxicity. • Suppressing both hydroxyl radicals and cytotoxicity by enhancing glutathione levels. • Useful strategy to prevent leukoderma induced by phenol derivatives. Abstract Background Rhododendrol (4-(4-hydroxyphenyl)-2-butanol) has been used as a lightening/whitening cosmetic but was recently reported to induce leukoderma. Although rhododendrol has been shown to be transformed by tyrosinase to hydroxyl-rhododendrol, which is cytotoxic to melanocytes, its detailed mechanism of action including the involvement of reactive oxygen species is not clearly understood. Objective To confirm the relationship of hydroxyl radical generation to melanocyte cytotoxicity induced by rhododendrol, this study was performed. Methods An electron spin resonance method with a highly sensitive detection system was utilized to monitor hydroxyl radicals generated from two distinct normal human epidermal melanocyte lines with different levels of tyrosinase activity after the addition of various amounts of rhododendrol. Cytotoxicity of rhododendrol was analyzed by AlamarBlue assay under the same condition. Results Hydroxyl radicals were generated depending on the amounts of rhododendrol and/or tyrosinase. After the correlation between hydroxyl radical generation with melanocyte viability was confirmed, an inhibitor of oxidative stress, N -acetyl cysteine, was shown to dramatically diminish rhododendrol-induced generation of hydroxyl radicals and melanocyte cytotoxicity by increasing glutathione levels. In contrast, buthionine sulfoximine, which depletes glutathione, augmented both of those parameters. Conclusion Suppressing oxidative stress would prevent and/or mitigate some phenol derivative-induced leukoderma by avoiding hydroxyl radical-initiated melanocyte cytotoxicity. [ABSTRACT FROM AUTHOR]

Rhododendrol is a phenolic compound that shows a tyrosinase-dependent toxicity for melanocytes and occasionally induces a vitiligo-like skin depigmentation. The post-tyrosinase mechanisms determining melanocyte death or survival, however, are far from clear. Here, we find that rhododendrol treatment leads to a reduction in the levels of cellular glutathione but also induces a cellular antioxidant response that eventually increases glutathione levels. We further find that rhododendrol toxicity is enhanced when glutathione levels are experimentally reduced and alleviated when glutathione levels are increased. Hence, it appears that the size of the preexisting glutathione pool along with the capacity to supply glutathione via the antioxidant response determines whether melanocytes survive or die after rhododendrol exposure. It is conceivable, therefore, that rhododendrol-induced leukoderma depends on the capacity to maintain appropriate glutathione levels and that enhancement of glutathione levels may preserve a patient's melanocytes and potentially help in repigmentation. [ABSTRACT FROM AUTHOR]

Background Rhododendrol (RD), a skin-whitening agent, is believed to be associated with cases of cosmetics-related leukoderma that have been reported in Japan. Recently, we have shown that RD is catalyzed by tyrosinase to produce putative toxic metabolites RD-catechol and RD-cyclic catechol. Objective To examine the cytotoxicity and production of reactive oxygen species (ROS) in melanocytic cells by RD and its metabolic products. Methods The growth inhibitory effect of RD or its metabolite on the normal human epidermal melanocyte (NHEM) and B16F1 cells was assessed by cell counting or WST assay. ROS production was detected by flow cytometry and confocal microscopy after cells were treated with 2′,7′-dichlorofluorescein and RD or its metabolite. Results Growth of NHEM derived from African American (NHEMb) and B16F1 cells was suppressed by 300 μM or more RD. Growth inhibitory activity of RD (IC50 of B16F1: 671 μM) was weaker than hydroquinone (IC50 of B16F1: 28.3 μM) or resveratrol (IC50 of B16F1: 27.1 μM). Flow cytometric analysis detected ROS production in the NHEMb and B16F1 cells exposed to RD. However, neither RD nor H 2 O 2 increased the subG1 fraction of these melanocytic cells. RD-catechol and RD-cyclic catechol inhibited growth of NHEMb and B16F1 cells much more strongly than did RD. RD-catechol, as well as RD, produced ROS detected by both flow cytometry and immunostaining, while RD-cyclic catechol produced a hardly detectable amount of ROS in B16F1 cells. Conclusions These results suggest that RD exerts the cytotoxicity in melanocytic cells through its oxidative metabolites and that ROS plays a role in RD-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

A 15-year-old Iraqi male patient with acute lymphoblastic leukemia received an allogeneic bone marrow transplant from his brother. On the 18th day after the transplant, the patient developed grade II acute graft-versus-host disease, and treatment included methylprednisolone. On day 140, the patient was diagnosed with leukoderma. On day 150, the patient was admitted to hospital because of numbness and muscle weakness in the extremities and a disturbance of the gait. Neurologic examination showed muscle weakness in the upper and lower extremities and there were no deep tendon reflexes. Nerve conduction studies showed reduced conduction speeds of the motor nerves with demyelinating features. The patient was diagnosed as having a chronic inflammatory demyelinating polyradiculoneuropathy (CIDB) based on clinical and electrophysiological findings. Treatment included methylprednisolone and intravenous immunoglobulin. The neurologic function improved but the skin lesions persisted. This case shows that graft-versus-host disease can act as a triggering factor for the appearance of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Summary Recently, an unexpected outbreak of patients with leukoderma occurred in Japan with the use of brightening/lightening cosmetics containing rhododendrol (RD). Patients developed leukoderma mostly on the skin sites repeatedly applied with RD, but some patients also had vitiligo-like lesions on the non-applied sites. RD is a tyrosinase-competitive inhibiting substance, thereby serving as an inhibitor of melanin synthesis. Upon inhibition of tyrosinase, RD is converted to new products such as tyrosinase-catalyzed hydroxyl-metabolite, which damage melanocytes. The melanocyte cell lysates seem to induce T-cell response. The frequencies of CD8 + T cells in both lesional skin and peripheral blood are significantly higher in the RD leukoderma as well as non-segmental vitiligo patients than in normal controls. In HLA-A*02:01 positive cases, circulating Melan-A-specific cytotoxic T cells can be detected at a high frequency. It is thus suggested that RD-induced leukoderma is induced by not only cytolysis of melanocytes but also subsequent immune reactions toward melanocytes. [ABSTRACT FROM AUTHOR]