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Background: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking., Objectives: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo., Methods: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings., Results: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed., Conclusions: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed., Objectives: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo., Methods: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings., Results: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients., Conclusions: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Vitiligo is a common depigmentation disorder characterized by the selective loss of melanocytes. In our daily clinic experience, we noticed that the skin tightness of hypopigmented lesions would be more evident in comparison to that of uninvolved perilesional skin in vitiligo patients. Therefore, we hypothesized that collagen homeostasis might be maintained in vitiligo lesions, irrespective of the substantial excessive oxidative stress that occurs in association with the disease. We found that the expression levels of collagen-related genes and anti-oxidative enzymes were upregulated in vitiligo-derived fibroblasts. Abundant collagenous fibers were observed in the papillary dermis of vitiligo lesions in comparison to uninvolved perilesional skin by electron microscopy. The production of matrix metalloproteinases that degraded collagen fibers was suppressed. The deposition of acrolein adduct protein, which is a product of oxidative stress, was significantly reduced in vitiligo dermis and fibroblasts. As part of the mechanism, we found upregulation of the NRF2 signaling pathway activity, which is an important defense system against oxidative stress. Taken together, we demonstrated that the anti-oxidative action and collagen production were upregulated and that the collagen degeneration was attenuated in vitiligo dermis. These new findings may provide important clues for the maintenance of antioxidant ability in vitiligo lesions., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Vitiligo is a common depigmenting skin disease that is often difficult to treat. Even if repigmentation is achieved by treatment, recurrence in the same lesion is often found within a year after stopping treatment. As a background of these issues, a subset of CD8 + T cells that recognize melanocyte-specific antigens or CD49a + tissue-resident memory T cells that reside in the vitiligo lesion are thought to be involved. We investigated the MHC class I-restricted tyrosinase pentamer-positive CD8 + skin T cells in a progressive generalized vitiligo patient with HLA-A*02:01 who showed resistance to intravenous methylprednisolone pulse therapy. We found that HLA-A*02:01-restricted tyrosinase pentamer-positive CD8 + T cells remained in the lesions after the treatment and expressed IFN-γ and granzyme B. Interestingly, the expression of these cytokines in the pentamer-negative CD8 + T cells was decreased after intravenous methylprednisolone pulse therapy. These findings suggest that, in vitiligo patients, melanocyte-specific CD49a + CD8 + T cells are in a potent activation state that is uncontrolled despite systemic immunosuppressive treatment, which may contribute to treatment resistance and local recurrence., (© 2022 Japanese Dermatological Association.)

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.)

Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce leukoderma or vitiligo called RD-induced leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Vitiligo is an acquired disorder in which depigmented macules result from mostly autoimmune loss of melanocytes. The initiating process in vitiligo has still been uncertain. Here, we report the case of a 19-year-old man with undetermined/unclassified vitiligo with a new periphery-spreading vitiligo lesion on the right dorsal hand after rigorous sun exposure. Histopathological evaluation showed noticeable infiltration of CD68(+) macrophages, moderate infiltration of CD3(+) T cells, little infiltration of CD8(+) T cells and CD11c(+) myeloid dendritic cells, HMB45/CD11c double-positive cells, and Melan-A/MART1(+) deposits in the dermis. We surmised that melanocyte-derived deposits were mostly phagocytosed by CD68(+) macrophages and were faintly phagocytosed by CD11c(+) myeloid dendritic cells, referring distribution of CD68(+) mononuclear cells and melanocyte biomarkers. Complete repigmentation was achieved following topical application of hydrocortisone butyrate propionate 0.1% ointment. We summarize that prompt clearance of debris by macrophages would be essential to an excellent prognosis of complete repigmentation., (© 2013 Japanese Dermatological Association.)

Vitiligo is an acquired pigment disorder in which depigmented macules result from the loss of melanocytes from the involved regions of skin and hair. The color dissimilarity on the cosmetically sensitive regions frequently induces quality of life impairment and high willingness to pay for treatment in patients with vitiligo. The Vitiligo Japanese Task Force was organized to overcome this situation and to cooperate with the Vitiligo Global Issues Consensus Conference. This guideline for the diagnosis and treatment of vitiligo in Japan is proposed to improve the circumstances of Japanese individuals with vitiligo. Its contents include information regarding the diagnosis, pathogenesis, evaluation of disease severity and effectiveness of treatment, and evidence-based recommendations for the treatment of vitiligo. The therapeutic algorithm based on the proposed recommendation is designed to cure and improve the affected lesions and quality of life of individuals with vitiligo., (© 2013 Japanese Dermatological Association.)

The aim of this study was to determine whether CD4(+) IL-17A(+) Th17 cells infiltrate vitiligo skin and to investigate whether the proinflammatory cytokines related to Th17 cell influence melanocyte enzymatic activity and cell fate. An immunohistochemical analysis showed Th17 cell infiltration in 21 of 23 vitiligo skin samples in addition to CD8(+) cells on the reticular dermis. An in vitro analysis showed that the expression of MITF and downstream genes was downregulated in melanocytes by treatment with interleukin (IL)-17A, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. Treatment with these cytokines also induced morphological shrinking in melanocytes, resulting in decreased melanin production. In terms of local cytokine network in the skin, IL-17A dramatically induced IL-1β, IL-6, and TNF-α production in skin-resident cells such as keratinocytes and fibroblasts. Our results provide evidence of the influence of a complex Th17 cell-related cytokine environment in local depigmentation in addition to CD8(+) cell-mediated melanocyte destruction in autoimmune vitiligo., (© 2011 John Wiley & Sons A/S.)

Vitiligo is a common depigmenting skin disease that is often difficult to treat. Even if repigmentation is achieved by treatment, recurrence in the same lesion is often found within a year after stopping treatment. As a background of these issues, a subset of CD8+ T cells that recognize melanocyte‐specific antigens or CD49a+ tissue‐resident memory T cells that reside in the vitiligo lesion are thought to be involved. We investigated the MHC class I‐restricted tyrosinase pentamer‐positive CD8+ skin T cells in a progressive generalized vitiligo patient with HLA‐A*02:01 who showed resistance to intravenous methylprednisolone pulse therapy. We found that HLA‐A*02:01‐restricted tyrosinase pentamer‐positive CD8+ T cells remained in the lesions after the treatment and expressed IFN‐γ and granzyme B. Interestingly, the expression of these cytokines in the pentamer‐negative CD8+ T cells was decreased after intravenous methylprednisolone pulse therapy. These findings suggest that, in vitiligo patients, melanocyte‐specific CD49a+CD8+ T cells are in a potent activation state that is uncontrolled despite systemic immunosuppressive treatment, which may contribute to treatment resistance and local recurrence. [ABSTRACT FROM AUTHOR]

We report the case of a 73-year-old woman with leukoderma induced by cosmetics containing ascorbic acid. She had noticed the sudden appearance of a hypopigmented macule on the cheek within 1 month after use of the cosmetics with the brand name Obaji C Serum. No history of use of rhododenol-containing cosmetics was declared. Histopathological analysis revealed that the number of matured melanocytes was apparently decreased, and T lymphocytes abundantly infiltrated mainly the perifollicular region. In addition to the discontinuation of using Obaji C Serum, phototherapy by excimer light was noticeably effective for repigmentation. To our knowledge, there has been no other report so far showing hypopigmented lesions induced by this cosmetic. [ABSTRACT FROM AUTHOR]

As reported in the mass media on July 2013, numerous consumers who had used the cosmetic ingredient containing rhododendrol (4-(4-hydroxyphenyl)-2-butanol, Trade name; rhododenol), which is a melanin inhibitor isolated from Acer nikoense Maxim, released from Kanebo Cosmetics Inc. (Tokyo, Japan) noticed leukoderma patches on their face, neck and hands. We have experienced 32 cases that developed leukoderma after using such cosmetics so far and skin biopsy samples in some cases were obtained from both leukoderma and pigmented lesions. A histopathological analysis for skin lesions obtained from such patients notably showed basal hypo-pigmentation, melanin incontinence, and remaining melanocytes in most patients which is not relevant in vitiligo vulgaris. Subsequently, we comprehensively carried out immunohistochemical analyses of immune-competent cells infiltration to assess the effect of the cellular immune response to inducible hypopigmentation. Furthermore, detailed morphological observations performed by electron-microscopy notably showed the presence of melanocytes with only a small number of melanosomes, dermal fibroblasts containing melanosome globules and melanophages whereas no damage associated with melanosome transfer and the basal layer apparatus. These findings provide a cue to diagnose as rhododenol-induced leukoderma differentiate from vitiligo vulgaris and for rhododendrol to induce local immunity in addition to melanocyte damage. [ABSTRACT FROM AUTHOR]