Nanja van Geel

Background: The 2015 core domain set (CDS) for vitiligo defines outcomes for clinical trials, comprising three essential and four recommended outcome domains/domain items. Periodic reassessment is required to ensure its continued relevance. Objectives: To evaluate the content validity (relevance, comprehensiveness and comprehensibility) of the 2015 vitiligo CDS to inform a consensus-based update as part of a core outcome set, including core outcomes and core measurement instruments. Methods: A roundtable discussion and three surveys reassessed the 2015 vitiligo CDS regarding relevance (≥ 70% agreement for ‘essential’), comprehensiveness (identification of missing domain items) and comprehensibility (clarity of terminology and descriptions). Results: Fifty-three patients with vitiligo (group 1) and 37 experts (36 dermatologists and 1 researcher; group 2) participated. Two previously essential domains (‘Repigmentation’ and ‘Side effects/harms’) were re-endorsed as essential by both groups. ‘Maintenance of gained repigmentation’ was rated essential by patients only. Among previously recommended domains, ‘Quality of life’ was considered essential by both groups, whereas ‘Cosmetic acceptability of repigmentation’ and ‘Cessation of spreading of vitiligo’ were rated essential by patients only. ‘Tolerability/burden of treatment’ was not considered essential by either group. Frequently suggested missing items (outcomes and contextual factors) included psychological impact, treatment session duration, overall treatment duration, treatment costs, patient education and evaluation of associated auto­immune diseases. Proposed updates included refining domain terminology (e.g. vitiligo-specific/health-related quality of life; replacing ‘harms’ with ‘adverse events’) and addressing feasibility-related timeframes. Conclusions: While the 2015 vitiligo CDS retains content validity for several domains, meaningful updates are warranted. These findings will inform the development of a revised and updated CDS.

Vitiligo and melasma frequently coexist, creating a treatment dilemma, since agents effective for one condition can destabilize the other, and no consensus currently exists on safe management. We conducted a scoping literature review (through June 2023) on treatment of patients with concomitant vitiligo and melasma, followed by a two‐round international e‐Delphi survey (22 experts from 14 countries; consensus defined as ≥ 70% agreement) and a final online consensus meeting. Only one study supported the safe use of oral tranexamic acid for melasma in vitiligo patients. Expert consensus favored prioritizing vitiligo treatment, particularly when active, while incorporating patient's preferences. Targeted phototherapy is suitable for localized facial lesions of vitiligo, and non‐facial vitiligo can be treated alongside melasma after covering the face. Topical calcineurin inhibitors, ruxolitinib, tretinoin, corticosteroids, and oral tranexamic acid can be used. Lasers and chemical peels were recommended only with caution by experienced pigment specialists. Until there is enough scientific evidence, hydroquinone would be replaced by other safer cosmetic lightening agents (e.g., niacinamide, ascorbic acid, thiamidol, melasyl), which show comparable efficacy with less theoretical risk. This first international consensus offers practical, patient‐centered guidance for managing coexisting vitiligo and melasma, emphasizing individualized, disease‐activity‐based treatment sequencing. Trial Registration: PROSPERO reference number: RD42023395586 Significance . Depigmenting agents used for melasma inhibit melanogenesis, a mechanism that can further compromise the already‐stressed melanocyte populations characteristic of vitiligo. This consensus gives clinicians an expert‐informed pathway through a common but understudied comorbidity. It also identifies a clear research gap: controlled, mechanistic comparisons of hydroquinone against newer tyrosinase inhibitors specifically in vitiligo‐prone skin are still lacking.

A phase 2 trial (NCT04818346) of the oral Janus kinase 1 inhibitor povorcitinib demonstrated substantial total body and facial repigmentation over 52 weeks in adults with extensive nonsegmental vitiligo (NSV). Here, post hoc analyses evaluated povorcitinib efficacy in patients based on demographic and clinical characteristic subgroups, as well as affected body regions. Data were pooled for 103 patients in the extension-evaluable population who received povorcitinib (15, 45, or 75 mg once daily) throughout the 52-week study. Efficacy among subgroups was evaluated using achievement of ≥ 50% reduction from baseline in total Vitiligo Area Scoring Index (T-VASI50) and ≥ 50%/≥ 75% reduction from baseline in facial VASI (F-VASI50/F-VASI75). Efficacy in the affected body regions was evaluated using VASI50 responses. Data were analyzed using descriptive statistics, and missing values were imputed as nonresponders. At Week 52, 34.0% (35/103) of patients achieved T-VASI50, 61.2% (63/103) achieved F-VASI50, and 45.6% (47/103) achieved F-VASI75. Repigmentation occurred across subgroups regardless of patient age, sex, race, Fitzpatrick skin type, affected body surface area, other autoimmune comorbidities, disease duration, or prior NSV treatment. In addition, VASI50 response rates increased consistently and, in most cases, without plateauing for each body region, ranging from 25.8% for the feet to 57.3% for the head and neck (excluding the face). Decreased rates of disease activity were also evident across body regions. In this exploratory post hoc analysis of adults with extensive NSV, oral povorcitinib produced clinically meaningful repigmentation (as measured by achievement of T-VASI50 and F-VASI75) across patient characteristic subgroups and body regions through 1 year of treatment. Response rates varied by body region, reinforcing the lengthy repigmentation process, especially in nonfacial areas, and highlighting the need to manage patient expectations and encourage adherence to long-term therapy. ClinicalTrials.gov identifier, NCT04818346.

Repigmentation is an essential outcome in vitiligo assessment, yet it remains broadly defined. While perspectives from vitiligo experts have been explored, gaining insights from patients is crucial for a more comprehensive understanding. Ultimately, this could contribute to the development and refinement of core outcome sets for vitiligo. This study aimed to determine aspects of repigmentation patients consider most important. Two surveys and one focus group were conducted, involving 34 patients/patient caregivers and 20 patient representatives. In the surveys, aspects were deemed important if ≥ 70% of participants rated them as such. The focus group used the nominal group technique to rank the five most important self‐suggested aspects. The survey results indicate reduction of target lesion surface area, maintenance of repigmentation, and cessation of spread as important. The focus group identified additional aspects, including “time to repigment,” “location of lesions,” and “color match”. This study identified key aspects of repigmentation important to vitiligo patients. While survey results in general aligned with the core domain set for vitiligo clinical trials, the focus group highlighted additional factors. Incorporating these patient‐centered priorities into future core outcome sets could enhance the clinical relevance of vitiligo research and ensure outcomes reflect patient perspectives.

Vitiligo is a chronic autoimmune depigmenting disorder with a complex clinical course and highly heterogeneous therapeutic response. Many disease‐specific and patient‐related factors determine the best personalized management in vitiligo. Despite recent advances, a one‐size‐fits‐all approach remains insufficient, often leading to suboptimal outcomes and patient dissatisfaction. In this review, we outline a pragmatic framework for personalized vitiligo management based on clinical subtype, disease activity, extent, anatomical location, patient age, sex, skin phototype, comorbidities and psychosocial context. We discuss the clinical application of emerging data on clinical and dermoscopic activity signs, specific skin symptoms (e.g., halo naevi or poliosis), laboratory biomarkers and imaging modalities. Special populations such as children, the elderly, pregnant patients and autoimmune or psychiatric comorbidities are also considered. This guide can be used to achieve a comprehensive assessment for a personalized vitiligo practice.

The assessment of patient-centered outcomes in clinical practice is essential for optimal care. While a core domain set (CDS) for vitiligo clinical trials was established in 2015 (CDS for trials) to standardize outcomes, no CDS currently exists for clinical practice, resulting in inconsistent assessment complicating effective disease management. This study aimed to investigate outcomes and characteristics currently assessed by vitiligo experts in clinical practice and represents one of the steps toward developing a core outcome set (COS) including outcomes and outcome measurement instruments for clinical practice. A cross-sectional survey was conducted among 31 vitiligo experts from six continents. The survey consisted of 28 predefined outcomes and characteristics. Participants were given the opportunity to propose additional options, which were considered 'generally assessed' when assessed by ≥ 70%. Six outcomes and 21 characteristics were 'generally assessed'. The most frequently chosen outcomes included vitiligo evolution, tolerability of treatment/adverse events, followed by disease activity and vitiligo extent. This study shows similarities but also remarkable differences in assessed outcomes compared to the CDS for clinical trials. These results serve as a preparatory step toward developing a COS for clinical practice with the involvement of expert and non-expert dermatologists and patients.

Vitiligo is an autoimmune disorder marked by the progressive loss of skin melanocytes, increasingly linked to immune dysregulation as a key driver of disease onset and progression. Regulatory T (Treg) cells are essential for maintaining immune homeostasis by suppressing autoreactive immune responses. Mounting evidence implicates functional and numerical alterations in Treg cells in the pathogenesis of vitiligo. This study reviews findings on lesional and circulating Treg cells in vitiligo patients compared to healthy controls (HCs), examining Treg cell frequency, their ability to suppress CD4 ⁺ and CD8 ⁺ T cell activity, levels of the immunoregulatory cytokines interleukin‐10 (IL‐10) and transforming growth factor‐β (TGF‐β), expression of the key suppressive marker FOXP3, as well as levels of the pro‐inflammatory cytokines interleukin‐17 (IL‐17) and interleukin‐22 (IL‐22). A comprehensive systematic search was performed across Embase, MEDLINE/PubMed, and Scopus databases to identify eligible studies. A total of 21 studies comprising 1016 vitiligo patients and 846 HCs were included in the review. The analysis revealed a significant reduction in peripheral Treg cell counts ( p = 0.01), impaired overall suppressive capacity of CD4+ and CD8+ T cells ( p = 0.01), reduced levels of IL‐10 ( p = 0.02), increased levels of IL‐17 ( p ≤ 0.01) and IL‐22 ( p ≤ 0.01) in the blood of vitiligo patients compared to HCs. No statistically significant difference was observed in circulating TGF‐β levels ( p = 0.1). Most studies reported reduced FOXP3 expression in both skin and blood of vitiligo patients. Current evidence suggests vitiligo involves both reduced numbers and impaired function of Treg cells, supporting further study of Treg pathways as targets for immunomodulatory therapy.

Introduction Vitiligo is a chronic autoimmune disease characterized by destruction of pigment-producing melanocytes in the skin. This study explores the patient and treatment history of vitiligo and associated mental health burden in EU5 countries. Methods The cross-sectional global Vitiligo and Life Impact Among International Communities (VALIANT) study recruited people with vitiligo via an online panel and surveyed them regarding clinical characteristics, vitiligo treatment, quality of life (QoL), and mental health. Results A total of 1151 patients were surveyed in EU5 countries (France, n = 250; Germany, n = 250; Italy, n = 200; Spain, n = 200; UK, n = 251). Half of patients (50.3%) reported a family history of vitiligo, with highest rates in France (66.4%) and Germany (58.8%). Many patients experienced flares during periods of stress (65.1%) or itching before/during a flare (61.5%), with highest rates in Germany (78.4%/78.8%, respectively; P < 0.01 vs all). German patients used the greatest mean number of vitiligo treatments (6.5; P < 0.0001 vs all), and French patients reported the highest rates of current non-treatment (20.8%; P < 0.05 vs Germany). Half of patients (53.9%) reported frequently hiding their vitiligo lesions, with highest rates in Germany (60.4%) and France (58.4%; both P < 0.05 vs Italy/Spain). German and French patients also reported highest disease burden (P < 0.05 vs Italy/Spain/UK). Over half (58.3%) of patients reported diagnosed mental health conditions (anxiety [26.5%]; depression [23.4%]). Rates of moderate to severe depressive symptoms were highest in Germany (64.8%; P < 0.05 vs all). Conclusion Among EU5 countries, patients from Germany and France generally reported higher burden than those from Italy, Spain, or the UK, although the impact of vitiligo on these patients cannot be discounted. Patients reported flares during periods of stress and great impact of vitiligo on their QoL and mental health. There is continued need for improved management strategies for patients with vitiligo, including the reduction of QoL and mental health burden. Graphical Abstract A graphical abstract is available for this article.