Exploring the natural and treatment history of vitiligo: perceptions of patients and healthcare professionals from the global VALIANT study.

BACKGROUND: Vitiligo is a chronic autoimmune disease affecting melanocytes, resulting in skin depigmentation. Patients with vitiligo often have reduced quality of life and comorbid autoimmune conditions and have reported a lack of available treatments for their vitiligo. OBJECTIVES: The Vitiligo and Life Impact Among International Communities (VALIANT) study is the first global survey to explore the natural history and management of vitiligo from the perspectives of patients and healthcare professionals (HCPs). METHODS: The survey recruited adults (≥ 18 years) diagnosed with vitiligo and HCPs treating patients with vitiligo via an online panel in 17 countries. Patients were queried regarding clinical characteristics and vitiligo treatment. HCPs were queried regarding diagnosis and management of patients with vitiligo. RESULTS: Included in the analysis were 3541 patients and 1203 HCPs. Nearly half (45.2%) of the patients had > 5% affected body surface area; 57.1% reported family history. Patients obtained formal diagnosis after a mean (SD) of 2.4 (4.1) years; 44.9% reported previous misdiagnosis. Many patients (56.7%) reported being told that vitiligo could not be treated; 53.9% of HCPs believed patients who never treated their vitiligo had been told that vitiligo could not be treated. One-quarter of HCPs (26.3%) did not believe that an effective therapy for vitiligo exists; 44.6% of patients reported giving up on finding an effective therapy. Top treatment goals for patients and HCPs, respectively, were reduction or cessation of spread (24.7% and 18.5%) and repigmentation (22.5% and 37.2%). Patient perception of effective care was similar for treatment by dermatologists (66.9%) and primary care HCPs (67.0%). CONCLUSIONS: Patients with vitiligo and HCPs reported similar treatment goals and expressed frustration with the lack of effective therapies. Patients reported high rates of initial misdiagnosis; many ceased seeking healthcare because they perceived that vitiligo could not be treated. The findings highlight the need for earlier diagnosis and improved disease management for vitiligo.

Emerging drugs for the treatment of vitiligo.

Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments.Areas covered: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localized vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy.Expert opinion: The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB.

Therapeutic options in vitiligo with special emphasis on immunomodulators: A comprehensive update with review of literature.

Vitiligo is a relatively common disorder characterized by areas of depigmented skin. It may be associated with social stigma and adversely affects the quality of life. Although many treatment options are available, none is curable. The search continues for an effective therapeutic option. New targeted options include biologics and other immunomodulatory agents, with varying degrees of evidence. We have discussed briefly the therapeutic options with special emphasis on the newer immunomodulatory agents. We undertook a comprehensive English literature search across multiple databases such as PubMed, SCOPUS, EMBASE, MEDLINE, and Cochrane using keywords (alone and in combination) and MeSH items such as "vitiligo," "treatment," "recent," and "immunomodulators" to obtain several relevant articles, priority being given to prospective randomized controlled trials. We scanned all the relevant articles and summarized them to obtain the latest information about the treatment of this condition to prepare the current article.

Controversial issues in vitiligo patients: a review of old and recent treatments.

Vitiligo is quite a common hypopigmentary disorder, which may affect both children and adults with important psychological effects due to the well-known leopard skin-like appearance. The authors summarize in the present study the published evidence on vitiligo with particular interest on the controversial aspects of the disease, such as its definition and the available treatments.

Functional nutrition as integrated approach in vitiligo management.

Vitiligo is a common disease of unknown cause that produces disfiguring white patches of depigmentation that can be treated using various new and experimental therapies, such as narrow-band ultraviolet B (NB-UVB) microphototherapy, NB-UVB excimer laser, and monochromatic excimer light. Medical treatments include topical corticosteroids and other topical treatments, such as antioxidants, tacrolimus and pimecrolimus, prostaglandin E, and vitamin D derivatives (Lotti, Berti, & Moretti, 2009). The goal of treating vitiligo is to make it less noticeable either by restoring lost pigment or by eliminating remaining pigment. Functional foods and healthy diet, with nutrients, form a variety of sources, could be considered an integral part, as well as helpful, of vitiligo's medical therapy.

Patient-reported outcomes: A 5-year long study reveals previously unreported therapeutic, demographic, socio-economic, and other correlations in vitiligo.

Vitiligo is a non-lethal, non-communicable, immune-mediated, and generally progressive skin disease, with poorly understood etiopathogenesis and weak evidence base. The aim of the study is to contribute to the scant research on the patient-reported outcomes in vitiligo, and to examine the presence of associations between various inputs for possible use in clinical practice. The study was designed as a web-based questionnaire with 40 inputs across seven dimensions. The questions include demographics, skin type, eye and natural hair color, age of respondent and age of onset, possible triggers, disease extent, localization, progression and activity, the efficacy of most common treatment modalities, medication side-effects, heredity and diseases among parents, and out-of-pocket expenses for treatments to date. The analysis presented with this work contributes to the discussion about the relation between therapies, socio-economic factors, and treatment outcomes in vitiligo. All physicians should adequately manage patient expectations in terms of overall treatment duration and expected out-of-pocket expenses, and actively evaluate patients at shorter intervals. A more aggressive therapeutic approach using telehealth devices should be considered to supplement therapy, monitor treatment progress, and protocol compliance.

Mental Health and Psychosocial Quality-of-Life Burden Among Patients With Vitiligo: Findings From the Global VALIANT Study.

Importance: Patients with vitiligo often have impaired quality of life (QOL) and experience substantial psychosocial burden. Objective: To explore the global association of vitiligo with QOL and mental health from the patient perspective. Design, Setting, and Participants: This qualitative study of the cross-sectional population-based Vitiligo and Life Impact Among International Communities (VALIANT) study was conducted from May 6, 2021, to June 21, 2021. Potential participants for this qualitative study were recruited from an online panel in 17 countries. Of 5859 surveyed adults (aged ≥18 years) who reported a vitiligo diagnosis, 3919 (66.9%) completed the survey, and 3541 (60.4%) were included in the analysis. Exposures: Patients were asked questions regarding their emotional well-being, including QOL and mental health. Main Outcomes and Measures: Reported analyses are descriptive and hypothesis generating. Vitiligo Impact Patient scale (VIPs) scores ranged from 0 to 60, with higher scores indicating more psychosocial burden. Results: The median age of the 3541 patients was 38 years (range, 18-95 years), and 1933 (54.6%) were male; 1602 patients (45.2%) had more than 5% affected body surface area (BSA; Self-Assessment Vitiligo Extent Score assessed), and 1445 patients (40.8%) had Fitzpatrick skin types IV to VI (ie, darker skin). The mean (SD) global short-form VIPs score was 27.3 (15.6) overall; patients from India (mean [SD], 40.2 [14.1]) reported the highest scores (ie, most burden). The QOL burden according to the scale was profound for patients with more than 5% affected BSA (mean [SD] score, 32.6 [14.2]), darker skin (mean [SD] score, 31.2 [15.6]), and lesions on the face (mean [SD] score, 30.0 [14.9]) or hands (mean [SD], 29.2 [15.2]). At least 40% of patients globally reported that vitiligo frequently affected aspects of their daily lives, including choosing clothes to wear (1956 of 3541 [55.2%]). Most patients (2103 of 3541 [59.4%]) reported concealing their vitiligo frequently. More than half of patients (2078 of 3541 [58.7%]) reported diagnosed mental health conditions, including anxiety (1019 of 3541 [28.8%]) and depression (866 of 3541 [24.5%]). The Patient Health Questionnaire-9 depression screener showed that 55.0% of patients (1948 of 3541) had moderate to severe depressive symptoms; the highest rates were in India (271 of 303 [89.4%]) and among patients with more than 5% affected BSA (1154 of 1602 [72.0%]) and darker skin (987 of 1445 [68.3%]). Conclusions and Relevance: This qualitative study found that, globally, patients with vitiligo reported being substantially affected in their emotional well-being, daily lives, and psychosocial health; the burden was typically greatest among patients with more than 5% affected BSA, darker skin types, and lesions on the face or hands. Survey findings suggest that patients reported having altered their behavior, expressed clear discontent, and have symptoms consistent with depression, which may be underdiagnosed.

Multidisciplinary approach to R&D in vitiligo, a neglected skin disease.

A global interest in therapies for neglected diseases is rising, but traditional biopharma research and development (R&D) process is prohibitively expensive to justify cost of their development. Vitiligo is a multifactorial orphan disease that affects at minimum 35 million people worldwide, yet no therapeutic solutions exist. The present authors describe a budget-minded pursuit of the new therapy development for vitiligo, which includes a multidiscipline collaboration and effective bridging between academic research, biobanking, and bioinformatics. The present authors anticipate that the present authors' "theoretically induced and empirically guided" discovery process will enable development of more leads, with a much greater probability of success and under tighter budgets compared with those of the biopharma company. Ultimately, the multidisciplinary approach described below facilitates the collaborative development of personalized treatments for different patient subpopulations in vitiligo and other neglected diseases.

Vitiligo road map.

Vitiligo is a depigmenting disorder stemming from melanocyte loss or dysfunction. It has a complex, multifaceted etiology. We constructed a "vitiligo road map," consisting of basic science, clinical, and treatment components, in order to better portray our current understanding of vitiligo pathogenesis and reflect upon novel biomarkers and therapeutic targets for future research. The melanocyte map elaborates on the molecular processes and intracellular signaling pathways initiated by various external autocrine/paracrine factors in representing normal melanocyte homeostatic functions modulating its viability, proliferation, differentiation, dendricity, migration, and melanogenic processes. This vitiligo map identifies known inducers/triggers of vitiligo onset and progression that cultivate a microenvironment for melanocyte disappearance, real or functional. This map describes the molecular mechanisms of currently utilized clinical and experimental treatments of vitiligo that facilitate repigmentation.

Treatments of vitiligo: what's new at the horizon.

Vitiligo is a manageable disease. However, current vitiligo treatments can be considered suboptimal as they do not guarantee high efficacy and cannot be standardized for most patients. Recently, combination therapies have been introduced in order to obtain better results and reduce risks in the management of the disease. Novel efficacious products are hereunder discussed to improve the therapeutic options for vitiligo patients.

An Innovative Therapeutic Protocol for Vitiligo: Experience with the Use of Fraxel Herbium Laser, Topical Latanoprost and Successive Irradiation with UVA - 1 Laser.

Despite the continuous introduction of innovative therapies for vitiligo, today none of them provide constant and excellent results in term of repigmentation. The authors report their experience in treating a localised form of vitiligo with a new protocol consisting in the use of a Fraxel Herbium laser, and in the following application of topical Latanoprost solution and, one day after, in lesional irradiation with UVA1 laser.

Artificial Hair: By the Dawn to Automatic Biofibre® Hair Implant.

Since the beginning of the twentieth century, there have been attempts at creating artificial hair to treat baldness. Major evolution took place at the end of 1970's when, unfortunately, artificial hair treatments were applied without appropriate medical controls, resulting in sub-standard results from the use of unsuitable materials and technique. The large improper use of this technique in North America from no medical personnel and with dangerous fibres led the Food and Drug Administration (FDA) to suspend the procedure in 1983. In Europe, a new trial on artificial hair procedure started at the beginning of 1990's. In 1995 the European Union (UE) recognised the artificial hair implant as a legitimate medical treatment and outlined the rules related to that procedure. In 1996, biocompatible fibres (Biofibre®) produced by Medicap® Italy were approved by the UE Authorities and by the Australian Therapeutic Goods Administration (TGA) as medical devices for hair implant. An effective medical protocol was developed during the following years to provide correct guidelines for appropriate treatment, and to reduce possible related complications. Automatic Biofibre® hair implant represents the last achievement in this hair restoration technique with significant advantages for the patients.

Micro - Focused Phototherapy Associated To Janus Kinase Inhibitor: A Promising Valid Therapeutic Option for Patients with Localized Vitiligo.

BACKGROUND: Vitiligo is an acquired pigmentary cutaneous disease, characterised by the progressive loss of melanocytes, resulting in hypopigmented skin areas which progressively become amelanotic. Classically, vitiligo treatments are unsatisfactory and challenging. Despite the continuous introduction of new therapies, phototherapy is still the mainstay for vitiligo repigmentation. AIM: The aim of this multicenter observational retrospective study was to evaluate the efficacy and safety of the nb - UVB micro - phototherapy (BIOSKIN EVOLUTION®), used alone or in associations with an oral Janus kinase inhibitor (Tofacitinib citrate), in the treatment of stable or active forms of localised vitiligo. MATERIAL AND METHODS: Fifty eight patients had been treated with n-UVB micro-photootherapy (Group A); 9 patients had been treated with phototherapy plus Tofacitinb citrate (Group B). RESULTS: Among Group A, 42 patients (72%) obtained a re-pigmentation rate higher than 75%, with a medium value of 77%. 11 patients (19%) achieved a marked improvement of the clinical findings with a repigmentation rate between 50-75%; 4 patients (8%) showed a moderate response with a lesional repigmentation of 25-50%. Only one patient (1%) had a poor response to the phototherapeutic treatment. CONCLUSION: Nb - UVB micro-focused phototherapy is one of the most effective therapeutic options for vitiligo treatment. The association of micro-focused phototherapy to Tofacitinib citrate seems to provide better clinical results in term of repigmentation rate.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.