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Vitiligo is an autoimmune skin disease of multiple etiology, for which there is no complete cure. This chronic depigmentation is characterized by epidermal melanocyte loss, and causes disfigurement and significant psychosocial distress. Mouse models have been extensively employed to further our understanding of complex disease mechanisms in vitiligo, as well as to provide a preclinical platform for clinical interventional research on potential treatment strategies in humans. The current mouse models can be categorized into three groups: spontaneous mouse models, induced mouse models, and transgenic mice. Despite their limitations, these models allow us to understand the pathology processes of vitiligo at molecule, cell, tissue, organ, and system levels, and have been used to test prospective drugs. In this review, we comprehensively evaluate existing murine systems of vitiligo and elucidate their respective characteristics, aiming to offer a panorama for researchers to select the appropriate mouse models for their study., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.

Vitiligo is a chronic skin condition marked by the gradual loss of pigmentation, leading to the emergence of white or depigmented patches on the skin. The exact cause of vitiligo remains not entirely understood, although it is thought to involve a blend of genetic, autoimmune, and environmental factors. While there is currently no definitive cure for vitiligo, diverse treatments exist that may assist in managing the condition and fostering repigmentation in specific instances. Animal models play a pivotal role in comprehending the intricate mechanisms that underlie vitiligo, providing valuable insights into the progression and onset of the disease, as well as potential therapeutic interventions. Although induced experimental models lack the nuanced characteristics observed in natural experimental models, relying solely on a single animal model might not fully capture the intricate pathogenesis of vitiligo. Different animal models simulate specific aspects of human vitiligo pathogenesis to varying degrees. This review extensively explores the array of animal models utilized in vitiligo research, shedding light on their respective advantages, disadvantages, and applications., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023. Published by Elsevier B.V.)

The reference to vitiligo-like lesions (VLLs) induced by immune checkpoint inhibitors (ICIs) as a valuable predictive marker of treatment success of immunotherapy with ICIs in melanoma has been mentioned in the literature. Its role in non-small cell lung cancer (NSCLC)-treated patients remains a poorly recognized phenomenon with uncertain significance regarding its predictive value. A retrospective, observational, single-center report was performed, with descriptive analysis of clinicopathological and treatment characteristics of patients with stage IV NSCLC who developed ICI-induced VLL between January 2018 and December 2022, contextualized in a comprehensive review of the literature and reported cases regarding this phenomenon. During the first 5 years' experience of ICI use in stage IV NSCLC treatment, three cases of ICI-induced VLLs were diagnosed. In line with the previous reports, two of the three presented cases exhibited treatment response and favorable prognosis. The recognition and understanding of the pathophysiological processes underlying ICI-induced VLLs may represent a promising opportunity to identify a predictive marker of tumor response to ICIs, with impact in treatment selection and patient management. It also may contribute to the recognition of new patterns of molecular expression that could lead to improvements in therapeutic development.

Importance: Vitiligo is a multifactorial, depigmenting skin disorder characterized by selective loss of melanocytes. Large-scale studies are lacking to determine the risk of vitiligo in transplant recipients with graft-vs-host disease (GVHD)., Objective: To investigate the incidence rates and risk of vitiligo in patients who had received solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) overall and by HSCT graft type and concomitant GVHD., Design, Setting, and Participants: This population-based cohort study included data from the National Health Insurance Service database of Korea for patients aged 20 years or older who had received a transplant (SOT or HSCT) between January 2010 and December 2017, with follow-up until December 2019. A cohort of age- and sex-matched (1:5) control individuals who did not receive a transplant was included for comparison. Data were analyzed from July 2021 to December 2021., Exposure: Transplant (SOT or HSCT) and GVHD., Main Outcomes and Measures: The main outcome was risk of vitiligo, assessed using multivariable Cox proportional hazards regression analyses adjusting for potential confounding factors., Results: The study included 23 829 patients who had undergone SOT or HSCT (62.78% male; mean [SD] age, 49.58 [11.59] years) and 119 145 age- and sex-matched controls. Patients who had undergone transplant had a significantly higher risk of vitiligo compared with controls (adjusted hazard ratio [AHR], 1.73; 95% CI, 1.35-2.22). Risk of vitiligo was also slightly higher in kidney transplant recipients and liver transplant recipients compared with the controls but was highest in HSCT recipients (AHR, 12.69; 95% CI, 5.11-31.50). Patients who had received allogeneic grafts (AHR, 14.43; 95% CI, 5.61-37.15), those who had received autologous grafts (AHR, 5.71; 95% CI, 1.20-3.18), those with comorbid GVHD (AHR, 24.09; 95% CI, 9.16-63.35), and those without GVHD (AHR, 8.21; 95% CI, 3.08-21.87) had a higher risk of vitiligo compared with controls., Conclusion and Relevance: In this study, risk of vitiligo was significantly higher in transplant recipients, especially in HSCT recipients and those with allogeneic grafts or comorbid GVHD. These findings provide new insights into the association between the risk of vitiligo and transplant and GVHD. Clinicians should be aware of these risks, implementing a multidisciplinary approach for monitoring.

Background: Vitiligo presents with varying clinical features based on the type and location. Treatment tends to be more effective on the face, neck, trunk, and mid-extremities, while the lips and distal extremities may be more resistant. Vitiligo in frequently exposed areas such as the face, arms, legs, and hands is typically associated with a lower Dermatology Life Quality Index., Objectives: We aimed to identify the characteristics and potential causes of vitiligo in challenging-to-treat regions, with particular focus on the hands., Methods: We analyzed the clinical data of 337 patients with generalized vitiligo who visited our hospital between 2016 and 2022. For this study, we focused on patients with non-segmental vitiligo (NSV) specifically on their hands. Of the 337 patients, 248 had NSV and 89 had segmental vitiligo; 119 (47%) of those with NSV had vitiligo on their hands. Logistic regression models were applied to identify factors the factors linked to hand vitiligo, such as age, sex, duration of the condition, and smoking and alcohol history., Results and Conclusions: We developed a model to predict the risk of hand vitiligo using several factors. Among the factors analyzed, only smoking history was significantly associated with an increased risk (odds ratio: 3.13). In addition, we used clinical photography to evaluate color-graded frequency heat maps comprising 528 pixels. Vitiligo in nonsmokers widely distributed over the hand, predominantly the fingertips and joints, whereas vitiligo in smokers tended to be distributed mostly at the fingertips., (© 2024 The Authors. Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

During the coronavirus disease 2019 (COVID-19) pandemic, vaccines help control the spread of infection. To date, 47 vaccines have been approved, with another 227 candidates in various stages of development. In the short period of time since the beginning of their use, evidence has begun to emerge of complications following vaccination in the form of the development or exacerbation of a number of pathological conditions (Block et al., 2022; Haseeb et al., 2022). For example, a population-based study in France identified 1612 cases of myocarditis and 1613 cases of pericarditis requiring hospital treatment within five months of vaccination (le Vu et al., 2022).

Vitamin D is one significant prohormone substance in human organ systems. It is a steroidal hormone produced in the skin upon exposure to UVB rays. This paper presents a systematic review of the utilization of topical vitamin D, specifically cholecalciferol, calcipotriol, and tacalcitol, in the treatment of vitiligo. It considers the role of vitamin D in stimulating the synthesis of melanin and melanogenesis, which can help with the process of repigmentation. The inclusion of calcipotriol or tacalcitol in Narrowband Ultraviolet Phototherapy (NB-UVB) has shown the potential to enhance therapeutic outcomes for vitiligo. However, their effectiveness in combination with Psoralens Long Wave Ultraviolet Radiation (PUVA) and Monochromatic Excimer Light (MEL) treatment for vitiligo is limited. In contrast, combining topical corticosteroids with vitamin D analogues has demonstrated superior efficacy in treating vitiligo compared to using vitamin D analogues alone, while also providing the added benefit of reducing corticosteroid-related adverse effects. In addition, treating stable vitiligo with topical cholecalciferol and microneedling has shown success. Future studies are needed to ascertain an efficient method of administering vitamin D topically as an anti-vitiligo agent.

There have been several case reports regarding newly developed vitiligo following the coronavirus disease 19 (COVID-19) vaccination. However, the relationship between COVID-19 vaccine and vitiligo progression remains unclear. To explore the relationship between COVID-19 vaccine and vitiligo progression and its potential influencing factors, A cross-sectional study was conducted on 90 patients with vitiligo who received inactivated COVID-19 vaccination. Detailed information covering demographic characteristics (age and sex), vitiligo clinical features (disease subtypes, duration, stage and comorbidities) and disease activity was collected through an electronic questionnaire. Ninety patients with vitiligo included 44.4% males, with an average age of 38.1 years (standard deviation, SD = 15.0). Patients were divided into progress group (29, 32.2%) and normal group (61, 67.8%) based on whether they experienced vitiligo progression after inactivated COVID-19 vaccination. 41.3% of patients in the progress group experienced vitiligo progression within 1 week after vaccination, and disease progression mainly occurred after the first dose inoculation (20, 69.0%). Logistic regression revealed that patients aged <45 years (odds ratio (OR) was 0.87, 95% confidence interval (CI): 0.34-2.22) and male patients (OR = 0.84, 95% CI: 0.34-2.05) had lower risk for vitiligo progression, while patients with segmental vitiligo (SV) subtype (OR = 1.68, 95% CI: 0.53-5.33), with <5 years disease duration (OR = 1.32, 95% CI: 0.51-3.47) had higher risk for vitiligo progression after COVID-19 vaccination, but without statistical significance. Over 30% patients experienced vitiligo progression after inactivated COVID-19 vaccination, and female patients, elder age, shorter disease duration and SV subtype are potential risk factors for vitiligo progression., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest None disclosed.

Vitiligo is an acquired chronic depigmenting disorder of skin. It is mostly asymptomatic and characterized by amelanotic macules and patches that affects 0.5% to 2% of the world's population. The etiology of vitiligo has not been clearly elucidated and multiple theories have been proposed regarding the causes of the disorder. Among the most prevalent theories, the genetic predisposition, oxidative stress theory, promotion of cellular stress and pathologic influence of lymphocytes T have been highlighted. As a result of increases in in-depth knowledge concerning the pathogenetic processes in vitiligo, we review the most recent information concerning its etiopathogenesis and treatment methods including topical and oral Janus kinase inhibitors, prostaglandins and their analogues, namely afamelanotide, Wnt/β-catenin-signaling agonists and cell-based therapies. Topical ruxolitinib has been registered for vitiligo treatment, whereas other agents as oral ritlecitinib, afamelanotide and latanoprost have been studied in ongoing clinical trials. New highly effective therapeutic strategies may be developed thanks to molecular and genetic studies.

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

Competing Interests: Conflicts of interest None disclosed.

Background: Autoimmune and metabolic disturbances have been reported in association with vitiligo, highlighting possible systemic associations that should be considered., Aims: To assess the possible association of metabolic syndrome (MetS) as well as insulin resistance (IR) with vitiligo in different age groups., Methods: This case-control study included 142 patients with vitiligo aging ≥ 6 years and 142 age- and sex-matched controls. Participants were assessed for MetS using the International Diabetes Federation (IDF) criteria in addition to IR via homeostasis model assessment of IR (HOMA-IR). The study was registered at Clinical Trials.gov, Identifier: NCT03622320, on August 9, 2018., Results: As per the IDF criteria, patients with vitiligo showed significantly more frequent association with high fasting plasma glucose levels, high blood pressure readings, central obesity, dyslipidemia, and MetS than controls (p = 0.020, p = 0.034, p = 0.014, p < 0.001, and p = 0.002, respectively). Moreover, patients with vitiligo have significantly higher levels of fasting insulin and HOMA-IR (p ≤ 0.001). Results obtained from patients with vitiligo and controls with coexistent MetS/IR demonstrated vitiligo as a risk factor for both MetS and IR. Univariate and multivariate logistic regression highlighted that older age was the significant independent predictor for MetS and IR., Conclusion: Patients with vitiligo showed a significantly higher incidence of MetS than controls. Vitiligo per se can be considered a risk factor for MetS and IR. Therefore, regular follow-up and early metabolic derangement diagnoses are mandatory., (© 2022 Wiley Periodicals LLC.)

Introduction: Vitiligo is an acquired chronic pigmentation disorder of the skin. Even if the role of the immune system seems to be well established, new pathogenetic hypothesis are rising in these years. It has been recently suggested by the development of an animal model that a protein called Melanoma Inhibitory Activity (MIA) is involved in the pathogenesis of vitiligo. This protein interacts with the adhesion molecules expressed on the melanocytes causing its detachment from extracellular matrix proteins and creating the depigmented macules. A topical preparation based on oligopeptides able to inhibit the actions of the MIA protein has been introduced to the market, claiming activity on vitiligo., Patient Concerns and Diagnosis: A patient affected by non-segmental vitiligo for 10 years, recalcitrant to any treatment (such as steroids, immunomodulators, kellin, UVB-NB and UVA) came to our observation., Interventions: We used this topical preparation containing the MIA inhibitors peptides in selected areas (face and sides of the trunk) leaving untreated other areas as control (legs and arms). The patient was required to be sun exposed or to have some UVA sessions during the treatment to stimulate the melanocytes replications., Outcomes: After 9 months of treatments, he recovered from 50% to 80% of repigmentation only in the treated areas, without any side effects locally or systemically., Conclusion: Even if other studies are required to better determine the efficacy of this approach, this first observation about the use of the MIA-inhibitors peptides for the treatment of non-segmental vitiligo indicates that this topical preparation containing the MIA inhibitors peptides could be a very promising option for the cure of this disease., Competing Interests: The authors have no funding and conflicts of interest to disclose. Authors Sergi Hernandez Navarro, Jordi Segura Tejedor, Marta Bajona Roig are employers at Bella Aurora Labs; Author Matteo Bordignon is consultant for Bella Aurora Labs; Authors Roberto Luisetto, Marny Fedrigo, Chiara Castellani, Annalisa Angelini, Mauro Alaibac declare that they have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo., Objective: This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients., Method: 48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd)., Results: Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p < 0.05). No difference was seen between Group A and Group B or Group A and Group C (p > 0.05). More patients complained higher pain score in Group A as compared with Group C (p < 0.05)., Conclusion: The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Vitiligo is a pigment-related disease with a global prevalence of 0.2% to 1.8% associated with considerable burden on quality of life. The treatment is still a challenge because of relapses and/or incomplete re-pigmentation. Although the exact cause is still unclear, its pathogenesis seems to be justifiable with the autoimmune theory, supported by the results of clinical research. In this narrative review, we aimed to summarize the evidence related to cytokines and vitiligo development. This review is consisted of English articles published in PubMed and Google Scholar concerning levels of inflammatory mediators, especially interleukins, in vitiligo patients over the last 20 years. References of relevant articles were also considered for review. Crucial role of dysregulated levels of interleukins and their synergistic function to each other, in the onset or progression of the disease is evident. The theory of autoimmune vitiligo is reinforced by the results of the studies in the literature, due to the association of pathogenesis with increased secretion of pro-inflammatory mediators and reduction of anti-inflammatory mediators. Decreased vitamin D levels may have a considerable role in vitiligo development by affecting Th1- and Th17-related immune responses. Cytokines play an important role in the pathogenesis or progression of the disease. Moreover, we believe that decreased vitamin D level has a considerable role in vitiligo development by affecting Th1- and Th17-related immune responses., (© 2022 Wiley Periodicals LLC.)

Background: Treatment of vitiligo with intralesional steroid (ILS) injections has shown to be successful in quite a few studies. It is a simple and safe treatment when used with caution with a better response in localized lesions., Objectives: The aim of the present study is to explore the efficacy and safety of using different concentrations of intralesional corticosteroid combined with NB-UVB phototherapy in the treatment of non-segmental vitiligo (NSV) patients., Methodology: Twenty patients with non-segmental vitiligo were subjected to different concentrations of ILS injections (triamcinolone acetonide); that was carried out monthly for six sessions. All patients were also subjected to twice-weekly sessions of NB-UVB for 6 months. Punch biopsy was taken from each patch before and at the end of treatment sessions. Each biopsy was stained with hematoxylin and eosin (H&E), Orcein, and Masson's trichrome stains., Results: There was a significant difference between all groups in their repigmentation response (P = 0.017). After treatment, the epidermal thickness (histometry) was decreased (epidermal atrophy), especially with concentrations of 2.5 and 5 mg/ml of intralesional triamcinolone acetonide injection with decreased and disorganized collagen fibers., Conclusion: Intralesional corticosteroid injections combined with NB-UVB showed a good and well-tolerated therapeutic option for vitiligo. The concentrations of 0.625 and 1.25 mg/ml of triamcinolone acetonide were the safest with fewer side effects and complications. However, higher concentrations of 2.5 and 5 mg/ml were more effective but with more side effects., (© 2021 the International Society of Dermatology.)

Objective: We explored the patterns of long non-coding RNA (lncRNA) expression in peripheral blood mononuclear cells (PBMCs) from patients with non-segmental vitiligo., Methods: We used high-throughput RNA sequencing technology to generate sequence data from five patients with non-segmental vitiligo alongside five normal healthy individuals, and then performed bioinformatics analyses to detect the differential expression of lncRNA in PBMCs. Gene Ontology (GO) and pathway analyses were performed for functional annotation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify gene expression. Target miRNAs and mRNAs of differentially expressed lncRNAs were predicted using bioinformatics analysis., Results: A total of 292 lncRNAs were differentially expressed in non-segmental vitiligo (fold change ≥ 2.0, P < .05), of which 171 were upregulated and 121 were downregulated. Six differentially expressed lncRNAs were selected, namely ENST00000460164.1, ENST00000393264.2, NR-046211.1, NR-135491.1, NR-135320.1, and ENST00000381108.3, for validation by qRT-PCR. The results showed that ENST00000460164.1 and NR-046211.1 were highly expressed in PBMCs of non-segmental vitiligo. An lncRNA-miRNA-mRNA network containing two lncRNAs, 17 miRNAs, and 223 mRNAs was constructed., Conclusion: Our results revealed patterns of differentially expressed lncRNAs in the PBMCs of non-segmental vitiligo individuals. ENST00000460164.1, and NR-046211.1 may be potential biomarkers and drug targets for the treatment of non-segmental vitiligo., Competing Interests: The authors declare that they have no conflicts of interest with regard to any commercial or associative interests., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Vitiligo is a common depigmentation disease characterized by melanocyte death, which is attributed to various mechanisms such as apoptosis and autoimmune destruction. However, whether necroptosis, a newly discovered way of cell death, plays a key role in the pathogenesis of vitiligo is still elusive and has not been well-studied. In this study, we found that necroptosis markers, including phosphorylated RIP3 and phosphorylated-MLKL, were positive in melanocytes from vitiligo perilesional skin, which supported the existence of necroptosis in vitiligo. Furthermore, the expression of RIP1 was remarkably upregulated in melanocytes treated with hydrogen peroxide. Then, RIP1 intervention suppression and MLKL deficiency could significantly enhance the resistance of melanocytes to hydrogen peroxide‒induced necroptosis. Mechanistically, we confirmed that RIP1 and RIP3 could form necrosomes under oxidative stress and further trigger phosphorylated MLKL translocation to the cell membrane, which led to the destruction of melanocytes. Finally, we showed that RIP1-mediated generation of mitochondrial ROS contributed to necrosome formation in melanocytes. Collectively, our study confirms that necroptosis significantly facilitates oxidative stress‒induced melanocyte death through the RIP1 signaling pathway, offering insight into vitiligo., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The combination of BRAF and MEK inhibitors, such as dabrafenib and trametinib, respectively, is an established treatment option for patients with advanced BRAFV600-mutated melanoma. With the wide adoption of these therapies, a range of cutaneous adverse effects has been reported. We describe the case of a 47-year-old woman with BRAFV600E-mutated stage IV melanoma treated with dabrafenib and trametinib for 30 months who presented to our attention for painful skin lesions that had been present on her limbs since the start of targeted therapy. We also observed vitiligo-like lesions on the extensor surface of both legs. Despite achieving a complete oncological response, the patient had to discontinue the treatment because of persisting fever, nausea and painful skin nodules that significantly impaired her quality of life. The recognition of cutaneous signs of efficacy of such drugs for advanced melanoma is of primary importance in order to identify patients with potential long-term clinical benefits., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Vitiligo is a multifactorial reversible skin disorder characterized by distinct white patches that result from melanocyte destruction. Activated CXCR3 + CD8 + T cells promote melanocyte detachment and apoptosis through interferon-gamma (IFN-γ secretion and chemokines secreted by keratinocytes through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-1 signaling pathway results in further recruitment of CXCR3 + CD8 + T cells and the formation of a positive-feedback loop. JAK inhibitors target the JAK/STAT pathway and are now approved to treat many immune-related diseases. In the treatment of vitiligo, JAK inhibitors, including ruxolitinib, baricitinib, and tofacitinib, are effective, supporting the implication of the IFN-γ-chemokine signaling axis in the pathogenesis of vitiligo. However, more studies are required to determine the ideal dosage of JAK inhibitors for the treatment of vitiligo, and to identify other inflammatory pathways that may be implicated in the pathogenesis of this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qi, Liu and Gao.)

Background: Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown., Purpose: To explore whether MC's autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation., Methods: PIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H 2 O 2 , and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined., Results: When treated with 0.8 mM H 2 O 2 , ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H 2 O 2 , while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens., Conclusion: Vitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity., Competing Interests: The authors declared no conflict of interest., (Copyright © 2021 Jun Tian et al.)

Vitiligo is an acquired depigmenting disorder. Vitiligo universalis is a rare form responsible for significant aesthetic damage. To date, the exact pathogenesis remains unknown. Its treatment, a real challenge, consists rather in removing the still pigmented areas. We report a case of a patient followed for stable vitiligo universalis from an early age who presented with repigmentation shortly after initiation of hemodialysis., (Copyright © 2021 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Background: Checkpoint inhibitors have revolutionized advanced melanoma care; however, their cutaneous side effects have not been definitively elucidated., Objective: To identify the prevalence of cutaneous toxicity in patients with melanoma treated with immune checkpoint inhibitors as monotherapy and/or in combination with chemotherapy and/or radiotherapy., Materials and Methods: We performed a systematic review and meta-analysis, which encompassed both clinical trials and observational studies describing the dermatological toxicities in patients treated with immune checkpoint inhibitors. The protocol was registered in the International Prospective Register of Systematic Review under the number CRD42018091915. The searches were performed using the CINAHL, Cochrane CENTRAL, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases. The methodological quality of the studies was evaluated with the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data., Results: A total of 9,802 articles were identified in the databases. The final sample comprised 39 studies. The evaluated drugs were ipilimumab, tremelimumab, pembrolizumab, and nivolumab. The results suggest that the most prevalent side effect was grade 1 and 2 pruritus (24%), followed by grade 1 and 2 rash (21%) and grade 1 and 2 vitiligo (10%)., Conclusion: The most prevalent side effects in patients treated with checkpoint inhibitors are pruritus, rash, and vitiligo, and they are rated mostly as grades 1 and 2 adverse events. Remarkably, vitiligo is most commonly found in patients treated with PD-1 inhibitors., Competing Interests: The authors have declared that no competing interests exist.

This is an exciting phase of vitiligo research with the current understanding of vitiligo pathogenesis and its translation to successful treatment. The pathogenetic origin of vitiligo revolves around autoimmunity with supporting role from many other factors like oxidative stress, inherent melanocyte defects, or defective keratinocytes and fibroblasts. Vitiligo can be classified into segmental or non-segmental depending upon the clinical presentation, or it can be classified as progressing or stable based on the activity of the disease. Vitiligo treatments need to be stratified depending upon which type of vitiligo we are treating and at which phase the vitiligo patient presents to us. There are two different aims of treatment of vitiligo. The first involves rescuing the melanocytes from the damage to arrest the depigmentation. The second strategy focuses on replenishing the melanocytes so that successful repigmentation is achieved. It is also important to maintain the disease in a stable phase or prevent relapse. As stability in non-segmental vitiligo is a dynamic process, maintenance of the stability of repigmentation is also an important consideration in the management of vitiligo. In this review, we shall briefly discuss the current options and future insight into the management of vitiligo., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: JH is a Scientific Founder of Villaris Therapeutics, Inc. JS and KB received financial support from Sanofi Genzyme and Calypso Biotech that is separate from this proposed editorial. IP is the CSO for Temprian Therapeutics, a company hoping to bring an HSP70iQ435A-based treatment to clinical trials for vitiligo. The approach for this treatment is different and separate from the proposed Research Topic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the essential brakes expressed on T cells that prevent T-cell hyperactivation-associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population., Methods: The CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real-time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated., Results: A higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61-5.35, p < 0.001), dominant (OR = 1.87, 95% CI = 1.14-3.06, p = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73-6.42, p = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34-1.75) than A/A (median = 1.43, IQR = 0.39-4.25, p = 0.018) and A/G carriers (median = 1.68, IQR = 0.49-3.92, p = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed., Conclusion: The CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large-scale studies in different populations are warranted., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response. Finally, the relevance of therapeutic strategies targeting this pathway to improve this inflammatory and autoimmune condition is also discussed., Competing Interests: JS has been an advisor, speaker or investigator for Abbvie, Calypso Biotech, Lilly, Novartis, Pierre Fabre, Sanofi-Genzyme. KB has been an advisor, investigator for Calypso Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boniface, Passeron, Seneschal and Tulic.)

Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients' responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient's response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving > 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Zhang, Su, Leung, Lui, Zhou, Wu, Zhou, Xu, Zhang and Zhou.)

Epidermal melanocytes are constantly exposed to environmental stressors such as ultraviolet light (UV) and chemotoxins. Several evolutionarily conversed survival mechanisms are deployed to ensure melanocyte recovery after damage including the unfolded protein response (UPR) and integrated stress response (ISR). The UPR/ISR promote restoration of homeostasis, by modulating transcription and translation as well as activating nuclear factor erythroid 2-related factor 2 (NRF2)-mediated antioxidant activity. If repair fails, the UPR/ISR either stimulate cell death, or adaptation that can lead to survival of damaged cells and promote disease. For example, the UPR/ISR may support melanomagenesis by allowing UV-damaged, mutated cells to survive and adapt to a hostile tumor microenvironment that subjects cells to hypoxia, nutrient deprivation, and sub-optimal pH. The UPR and ISR can also promote transcriptional changes that support tumor growth and/or metastasis. Furthermore, these pathways may also underlie acquisition of chemoresistance and modulation of protein expression that alters the efficacy of immunotherapies. UPR activation has also been implicated in the pathogenesis of vitiligo and may promote increased expression of chemokines such as interleukin 6 and interleukin 8 that trigger an autoimmune response against melanocytes. We herein review the potential roles of the UPR/ISR in the etiology of melanoma and vitiligo., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Vitiligo is the most common depigmenting disorder affecting 0.1%-2% of the population worldwide. The characteristic white patches result from the selective loss of melanocytes. Sustained recent efforts have resulted in a detailed understanding of the genetic architecture of vitiligo. About 80% of vitiligo risk is attributable to genetic factors; and the rest (20%) is attributable to the environment. Over the past decade, substantial progress has been made in our understanding of the pathogenesis of vitiligo which is now clearly classified as an autoimmune disease. Melanocytes from patients with vitiligo are more susceptible to oxidative stress which begets the release of exosomes and inflammatory cytokines that will lead to activation of the innate immune response and subsequently to adaptive immune response through activation of autoreactive cytotoxic CD8+ T cells. These produce interferon-γ (IFN-γ) which promotes disease progression through IFN-γ-induced chemokine secretion from surrounding keratinocytes to further recruit T cells to the skin through a positive feedback loop. CD8 tissue-resident memory T cells are in turn responsible for long-term maintenance and potential relapse of vitiligo in human patients through cytokine-mediated recruitment of T cells from the circulation. This review summarizes the current knowledge on vitiligo and attempt to give an overview of the future in vitiligo treatment., (© 2021 Japanese Dermatological Association.)

Background: Vitiligo is a frequent acquired depigmentation skin disease due to a loss of melanocytes. This study sought to characterize the expression pattern of microRNA (miRNA) in the peripheral blood mononuclear cells (PBMCs) of non-segmental vitiligo (NSV) patients. We also screened for molecular markers that can be used to evaluate the clinical stages of NSV., Methods: The miRNA expression profile in the PBMCs of four patients with progressive NSV and four healthy controls was determined using high-throughput RNA sequencing. The divergently expressed miRNA was verified via qRT-PCR in 26 progression, 26 stable NSV, and 26 healthy controls., Results: Our findings posited that 323 miRNAs were differentially expressed in the PBMCs of NSV patients. The top 10 up-regulated miRNAs in patients were hsa-miR-335-5p, hsa-miR-20a-5p, hsa-miR-514a-3p, hsa-miR-144-5p, hsa-miR-450b-5p, hsa-miR-369-3p, hsa-miR-101-3p, hsa-miR-142-5p, hsa-miR-19b-3p, and hsa-miR-340-5p. The top 10 down-regulated miRNAs in patients were hsa-miR-4443, hsa-miR-1248, hsa-miR-6859-3p, hsa-miR-668-3p, hsa-miR-7704, hsa-miR-323a-5p, hsa-miR-1237-3p, hsa-miR-3127-3p, hsa-miR-6735-3p, and hsa-miR-127-3p. The expressions of hsa-miR-20a-5p in PBMCs of progressive and stable NSV were remarkably elevated relative to the healthy controls. In the characteristics curve analysis of hsa-miR-20a-5p for differentiating progressive and stable NSV from normal subjects in PBMCs, the area under curve (AUC) was 0.92 and 0.81. Compared with patients in stable NSV, the hsa-miR-20a-5p was markedly increased in PBMCs of progressive NSV patients, and the AUC was 0.81., Conclusion: Our results showed that divergently expressed miRNAs contribute to the pathogenesis of NSV and that hsa-miR-20a-5p can be applied as a biosignature for stage assessment in PBMCs of patients with NSV., (© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.)

Vitiligo is a complex disease in which autoimmune destruction of epidermal melanocytes results in patches of depigmented white skin. Vitiligo has an estimated prevalence of about 0.2-2% in different populations and approximately 0.4% in the European-derived white (EUR) population. The fraction of disease risk attributable to genetic variation, termed heritability, is high, with estimates from family studies in EUR of 0.75-0.83 and from SNP based studies estimated at 0.78. About 70% of genetic risk comes from common genetic variants and about 30% from rare genetic variants. Through candidate gene, genomewide linkage, and genomewide association studies, over 50 vitiligo susceptibility loci have been discovered. These have been combined into a vitiligo polygenic risk score, which has allowed various aspects of vitiligo genetic architecture in the EUR population to be better understood. Vitiligo has thus proved to be a particularly tractable model for investigation of complex disease genetic architecture. Here, we summarize progress to date including dissection of heritability, discovery of vitiligo susceptibility loci through candidate gene, genomewide linkage, and genomewide association studies, relationships to other autoimmune diseases, polygenic architecture of vitiligo risk, vitiligo triggering, and disease onset, and provide suggestions for future directions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

As the outermost barrier of the body, skin is a major target of oxidative stress. In the brain, estrogen has been reported synthesized locally and protects neurons from oxidative stress. Here, we explored whether estrogen is also locally synthesized in the skin to protect from oxidative stress and whether aberrant local estrogen synthesis is involved in skin disorders. Enzymes and estrogen receptor expression in skin cells were examined first by quantitative real-time PCR and Western blot analyses. Interestingly, the estrogen synthesis enzyme was mainly localized in epidermal keratinocytes and estrogen receptors were mainly expressed in melanocytes among 13 kinds of cultured human skin cells. The most abundant estrogen synthesis enzyme expressed in the epidermis was 17β-hydroxysteroid dehydrogenase 1 (HSD17β1) localized in keratinocytes, and the most dominant estrogen receptor expressed in the epidermis was G protein-coupled estrogen receptor 1 (GPER1) in melanocytes. To investigate whether keratinocyte-derived estradiol could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with H 2 O 2 in the presence or absence of 17β estradiol or co-cultured with HSD17β1 siRNA-transfected keratinocytes. Keratinocyte-derived estradiol exhibited protective effects against H 2 O 2 -induced cell death. Further, reduced expression of HSD17β1 in the epidermis of skin from vitiligo patients was observed compared to the skin from healthy donors or in the normal portions of the skin in vitiligo patients. Our results suggest a possible new target for interventions that may be used in combination with current therapies for patients with vitiligo.