A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Topical Tacrolimus Ointment Alone versus in Combination with Microneedling for Refractory Stable Vitiligo.

OBJECTIVE: To assess the efficacy of microneedling in combination with topical tacrolimus ointment 0.1% versus topical tacrolimus ointment 0.1% for treatment of refractory stable vitiligo. STUDY DESIGN: Comparative cross-sectional study. Place and Duration of the Study: Department of Dermatology, PNS Shifa, Karachi, Pakistan, from December 2022 to May 2023. METHODOLOGY: The study included 30 clinically diagnosed individuals of either gender who had refractory symptoms and aged between 20 and 60 years. For every patient, two comparable lesions on two comparable limb regions were selected. Group A (right side) received treatment with both topical tacrolimus ointment 0.1% twice daily in addition to microneedling every two weeks, whereas, Group B (left side) was treated with topical tacrolimus ointment 0.1% only. Every lesion was investigated as a separate entity. Both groups were subsequently observed for a further six months. RESULTS: When topical tacrolimus ointment 0.1% was combined with microneedling, the total re-pigmentation rate was substantially higher than the usage of tacrolimus ointment 0.1% alone. Fifty-three percent of lesions treated with topical tacrolimus ointment 0.1% alone and 76.7% of lesions treated with microneedling in conjunction with it showed a good-to-excellent response. No adverse negative effects were noted. During the follow-up period, no problems or recurrences were noted. CONCLUSION: Tacrolimus ointment combined with microneedling is a successful treatment for refractory stable vitiligo. KEY WORDS: Dermapen, Depigmentation, Microneedling, Tacrolimus ointment, Vitiligo.

Comparing the efficacy of 308-nm light-emitting diode and 308-nm excimer lamp for treating vitiligo: A randomized controlled trial.

BACKGROUND: In previous studies, the 308-nm light-emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308-nm LED and 308-nm excimer lamp (308-nm MEL) for the treatment of vitiligo are lacking. OBJECTIVE: To compare the efficacy of the 308-nm LED and 308-nm MEL for treating nonsegmental stable vitiligo. PATIENTS AND METHODS: This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308-nm LED or the 308-nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented. RESULTS: In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308-nm LED group, and 138 lesions were included in the 308-nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308-nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308-nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p = .968). The incidence of adverse effects with the two phototherapy devices was comparable (p = .522). CONCLUSIONS: Treatment of vitiligo with the 308-nm LED had a similar efficacy rate to the 308-nm MEL, and the incidence of adverse effects was comparable between the two devices.

Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases.

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.

The regenerative potential of autologous stem and somatic cells in vitiligo.

Vitiligo is a human pigmentary disorder characterized by autoimmune destruction of mature melanocytes in the skin. In addition to studies on the inflammatory component of the disease, current treatments tend to involve stimulation of local melanocyte stem cells or transplantation of functional melanocytes from uninjured areas, however, in some cases of extensive depigmentation, only a few healthy cells can be obtained. This review discusses examples in the literature of the use of different sources of autologous stem and somatic cells in order to obtain melanocyte progenitors or mature melanocytes, and compares the strategy of stem cell differentiation with that of somatic cell reprogramming. More specifically, this review illustrates the capability of stem cells to differentiate from dental pulp, bone marrow, and adipose tissue; the reprogramming of pluripotent cells and the transdifferentiation of fibroblasts and keratinocytes. Each of these approaches is capable of producing fully functional melanocytes, but all have advantages and disadvantages. Finally, the relevance for potential clinical application is discussed, along with the risks associated with each strategy and the major current barriers to their use.

Phototherapy for vitiligo: A narrative review on the clinical and molecular aspects, and recent literature.

BACKGROUND: Vitiligo is characterized by depigmented patches resulting from loss of melanocytes. Phototherapy has emerged as a prominent treatment option for vitiligo, utilizing various light modalities to induce disease stability and repigmentation. AIMS AND METHODS: This narrative review aims to explore the clinical applications and molecular mechanisms of phototherapy in vitiligo. RESULTS AND DISCUSSION: The review evaluates existing literature on phototherapy for vitiligo, analyzing studies on hospital-based and home-based phototherapy, as well as outcomes related to stabilization and repigmentation. Narrowband ultra-violet B, that is, NBUVB remains the most commonly employed, studied and effective phototherapy modality for vitiligo. Special attention is given to assessing different types of lamps, dosimetry, published guidelines, and the utilization of targeted phototherapy modalities. Additionally, the integration of phototherapy with other treatment modalities, including its use as a depigmenting therapy in generalized/universal vitiligo, is discussed. Screening for anti-nuclear antibodies and tailoring approaches for non-photo-adapters are also examined. CONCLUSION: In conclusion, this review provides a comprehensive overview of phototherapy for vitiligo treatment. It underscores the evolving landscape of phototherapy and offers insights into optimizing therapeutic outcomes and addressing the challenges ahead. By integrating clinical evidence with molecular understanding, phototherapy emerges as a valuable therapeutic option for managing vitiligo, with potential for further advancements in the field.

Combination of 308-nm excimer laser and piperine promotes melanocyte proliferation, migration, and melanin content production via the miR-328/SFRP1 axis.

OBJECTIVE: Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. METHODS: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. RESULTS: The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/ß-catenin signaling pathway. CONCLUSION: The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/ß-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.

Application Effect of Comprehensive Noise Reduction Technology in Outpatients with Vitiligo: A Retrospective Study.

OBJECTIVE: Noise is a kind of perceived public nuisance that is closely related to people's subjective feelings and lives. This study explores the clinical application effect of comprehensive noise reduction technology in outpatients with vitiligo. METHODS: A total of 76 patients with vitiligo were selected in the Department of Dermatology at Baoding No. 2 Central Hospital from January 2020 to January 2021, as the control group (CG), receiving 5S management mode, and 80 patients with vitiligo from February 2021 to October 2022 were selected as the study group (SG), receiving comprehensive noise reduction technology combined with the 5S management mode for this retrospective study. The effects of different management modes on these patients were observed. RESULTS: SG had higher nursing quality scores in service attitude, service initiative, communication skills, environmental management and item management and overtly a lower noise level than CG (all P < 0.001). The Hamilton Anxiety Scale (HAMA) scores of the two groups at the end of treatment were significantly lower than those on admission (P < 0.05), with SG showing a lower score than CG (P < 0.001). Correlation analysis showed that noise levels and HAMA scores had a positive correlation (r = 0.423, P < 0.001). Patients with negative feelings about medical treatment caused by various noise sources in SG were obviously less than those in CG (P < 0.05). Both the groups had a statistical difference in overall satisfaction (P < 0.05). CONCLUSION: The investigation and data analysis demonstrated that comprehensive noise reduction in outpatients with vitiligo had a considerable effect. This technology can standardise the behaviour of medical staff, enhance nursing quality, reduce noise levels and alleviate patients' anxiety and improve their satisfaction. It has great benefits for the outpatient environment and patients.

Use of complementary and alternative medicine in vitiligo: a cross-sectional survey.

Vitiligo is characterized by skin depigmentation, which can lead to profound psychological effects and decreased quality of life, especially for those with skin of color. Individuals with vitiligo may utilize complementary and alternative medicine (CAM) due to limited treatment options with varying efficacy.An anonymous, multiple-choice, cross-sectional questionnaire was distributed to participants with vitiligo in the United States through online forums. Data on disease characteristics, use of prescription medications, use of topical therapies, supplements, and diets, and perceptions of CAM were collected.In total, 625 respondents completed the survey. Overall, 32.5% of participants (203/625) have tried CAM. Commonly reported CAM include supplements of vitamin D (57.7%, 116/203), vitamin B12 (46.3%, 93/203), vitamin C (27.4%, 55/203), topical Nigella sativa oil (26.4%, 53/203), oral omega-3 fatty acids (24.9%, 50/203), folic acid (22.9%, 46/203), and vitamin E (22.9%, 46/203). Frequently cited reasons for CAM use include desire to try "new" (40.4%, 82/203) or "more natural" (26.6%, 54/203) therapies, "frustration with conventional medicine" (24.6%, 50/203), and fear of "adverse side effects of conventional medicine" (23.6%, 48/203). Non-White participants were more likely than their White counterparts to report CAM use and have more positive perceptions of CAM therapies. Less than half (43.3%, 88/203) of CAM users reported that they disclosed their use of CAM with their physician.Dermatologists should be mindful of CAM and ask patients about their use. Further investigation of the role of CAM as adjuvant therapy for vitiligo is warranted to better advise patients.

Transcutaneous Auricular Vagus Nerve Stimulation Alleviates Monobenzone-Induced Vitiligo in Mice.

Vitiligo is a complex skin disorder that involves oxidative stress and inflammatory responses and currently lacks a definitive cure. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method for targeting the auricular branch of the vagus nerve and has gained widespread attention for potential intervention in the autonomic nervous system. Although previous research has suggested that vagus nerve stimulation can potentially inhibit inflammatory responses, its specific role and mechanisms in vitiligo treatment remain unknown. This study aimed to explore the therapeutic effects of taVNS in a mouse model of vitiligo induced by monobenzone. Initially, a quantitative assessment of the treatment effects on vitiligo mice was conducted using a scoring system, revealing that taVNS significantly alleviated symptoms, particularly by reducing the depigmented areas. Subsequent immunohistochemical analysis revealed the impact of taVNS treatment on melanocyte granules, mitigating pigment loss in the skin of monobenzone-induced vitiligo mice. Further analysis indicated that taVNS exerted its therapeutic effects through multiple mechanisms, including the regulation of oxidative stress, enhancement of antioxidant capacity, promotion of tyrosine synthesis, and suppression of inflammatory responses. The conclusions of this study not only emphasize the potential value of taVNS in vitiligo therapy, but also lay a foundation for future research into the mechanisms and clinical applications of taVNS.

Phototherapy for vitiligo: Quality and readability of online health information.

BACKGROUND/PURPOSE: Vitiligo is a depigmenting disorder that affects up to 2% of the population. Due to the relatively high prevalence of this disease and its psychological impact on patients, decisions concerning treatment can be difficult. As patients increasingly seek health information online, the caliber of online health information (OHI) becomes crucial in patients' decisions regarding their care. We aimed to assess the quality and readability of OHI regarding phototherapy in the management of vitiligo. METHODS: Similar to previously published studies assessing OHI, we used 5 medical search terms as a proxy for online searches made by patients. Results for each search term were assessed using an enhanced DISCERN analysis, Health On the Net code of conduct (HONcode) accreditation guidelines, and several readability indices. The DISCERN analysis is a validated questionnaire used to assess the quality of OHI, while HONcode accreditation is a marker of site reliability. RESULTS: Of the 500 websites evaluated, 174 were HONcode-accredited (35%). Mean DISCERN scores for all websites were 58.9% and 51.7% for website reliability and treatment sections, respectively. Additionally, 0/130 websites analyzed for readability scored at the NIH-recommended sixth-grade reading level. CONCLUSION: These analyses shed light on the shortcomings of OHI regarding phototherapy treatment for vitiligo, which could exacerbate disparities for patients who are already at higher risk of worse health outcomes.

Evaluation of efficacy and safety of vitiligo treatment with micro-needling combined with N-Acetylcysteine and micro-needling alone: A double-blinded randomized controlled clinical trial.

INTRODUCTION: Vitiligo is a skin pigmentation disorder caused by the selective degradation of melanocytes. This study investigates the therapeutic effects of microneedling with and without N-acetylcysteine (NAC) in patients with persistent and limited vitiligo. METHOD: This research employed a clinical trial design with double-blind randomization. Individuals affected by vitiligo and seeking treatment at Rasool Akram Medical Complex were divided into two separate treatment groups. In the intervention group, 24 affected areas underwent meso-microneedling using 5% NAC ampoules over six sessions, in addition to the application of 4.7% NAC cream once daily on the specified area. Conversely, the control group, consisting of 22 lesions, underwent microneedling using distilled water during six sessions. The severity of lesions and the extent of repigmentation were gauged using the Modified VETI Score. Assessment of treatment efficacy was determined through both physician evaluations and patient feedback. RESULTS: Twenty patients with a mean age of 36.4 years were recruited. The mean percentage of lesions and their intensity were significantly improved 2 weeks after the third session and 1 month after the end of the treatment (p < 0.01). There was no statistically significant difference between the intervention and control groups. Gender, age, family history, duration of disease, duration of disease stability, and history of hypothyroidism had no statistically significant relationship with patients' treatment outcomes (p > 0.05). CONCLUSION: Microneedling with or without the application of NAC appears to be an effective treatment option for persistent vitiligo lesions. However, despite the higher improvement rate with the application of NAC, the difference was not significant.

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

BACKGROUND: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. RESULTS: ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. CONCLUSIONS: ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. TRIAL REGISTRATION: registered with Chictr.org.cn (ChiCTR2100051405).

The Pediatric Dermatologist's View of Pediatric Vitiligo.

BACKGROUND: No guidelines exist for pediatric vitiligo. OBJECTIVE: To identify practice patterns of pediatric dermatologists treating vitiligo. METHODS: A PeDRA survey was completed online by 56 pediatric dermatologists. RESULTS: Practitioners reported feeling most comfortable treating 13- to 17-year-olds and least comfortable treating infants. Quality of life was assessed by interview in 89.3%. Topical calcineurin inhibitors (TCIs), topical corticosteroids (TCSs), narrowband UVB, coverup makeup, topical JAK inhibitors (tJAKis), and 308-nm laser were the leading vitiligo therapeutics chosen. 94.5% of practitioners reported experiencing frustration due to difficulties procuring therapies. CONCLUSION: Pediatric vitiligo has notable effects on quality of life. Some therapeutic options exist which are preferred by pediatric dermatologists. There is a need for more data on therapeutics in infants and young children, J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7572e.

Comparison of various excimer laser (EL) combination therapies for vitiligo: a systematic review and network meta-analysis.

AIM: This study aimed to compare the efficacy and safety of excimer laser (EL)-based combination regimens in improving repigmentation. METHODS: A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, and Embase on July 1, 2023, to include randomized controlled trials of EL combination treatments for vitiligo that met the criteria. The primary outcome measure was a repigmentation rate ≥ 75%, and the secondary outcome measures were a repigmentation rate of ≤ 25% and adverse events. RESULTS: Eleven studies involving 348 patients were included. Network Meta-Analysis showed that EL combined with antioxidants (SUCRA = 98.8%), EL combined with calcipotriol (SUCRA = 59.8%) and EL combined with tacalcitol (SUCRA = 59.6%) were the three optimal interventions achieving repigmentation rates ≥ 75%. EL alone (SUCRA = 77.6%), EL combined with tacalcitol (SUCRA = 61.7%) and EL combined with antioxidants (SUCRA = 57.2%) were the three interventions with the highest rates of treatment failure. Adverse events in all groups mainly included erythema, burning sensation and hyperpigmentation. Based on the results of the current study, EL combination therapies were safe with mild adverse events. CONCLUSION: EL combined with antioxidants was the preferred regimen for vitiligo, whereas EL alone was the regimen with the highest rate of treatment failure in vitiligo.

The correlation analysis between alterations of serum vitamin D, IL-33 levels, and clinical improvement after narrow-band UVB treatment in vitiligo patients: A case-control study.

BACKGROUND: The etiology of vitiligo has not been completely elucidated. Recently, 25-hydroxyvitamin D (25(OH)D) and IL-33 levels were found to be associated with the development of the vitiligo. The aim was to assess relationship between 25(OH)D, IL-33 levels, and clinical improvement after narrow-band UVB treatment in vitiligo. METHOD: Patients with vitiligo who underwent at least 48 sessions of narrow-band UVB treatment were included in this study. Age, gender, smoking status, family history of vitiligo, type of vitiligo, body surface area affected by vitiligo, and vitiligo activity were recorded. 25(OH)D and IL-33 were measured and compared at baseline, second month, and fourth month. RESULTS: Twenty patients with vitiligo and 20 healthy controls were included in this study. The mean baseline 25(OH)D level of vitiligo group was statistically significantly lower than the control group's (p < .05). The mean baseline IL-33 level was higher in vitiligo group with no statistically significantly difference (p > .05). The increase in 25(OH)D level and the decrease in vitiligo-affected body surface area were found to be statistically significant during treatment (p < .05). The mean IL-33 levels were found to be lower at the second and fourth month compared to baseline. However, there were no statistical significance (p > .05). CONCLUSION: Low levels of 25(OH)D are thought to play a role in the etiopathogenesis of vitiligo. 25(OH)D increase due to phototherapy may have a role in repigmentation independently from the direct effect of narrow-band UVB.

Single-cell sequencing reveals increased LAMB3-positive basal keratinocytes and ZNF90-positive fibroblasts in autologous cultured epithelium.

Autologous cultured epithelium grafting (ACEG) presents a promising treatment for refractory vitiligo, yet concerns regarding infections and immunological reactions hinder its surgical use due to serum and feeder dependencies. Addressing this, we culture autologous epithelium under serum- and feeder-free (SFF) conditions, comparing its safety and efficacy with serum- and feeder-dependent (SFD) conditions in stable vitiligo patients, and we discover no significant differences in repigmentation between the SFF and SFD grafts. Single-cell RNA transcriptomics on SFF- and SFD-cultured epithelium alongside healthy skin reveal increased populations of LAMB3+ basal keratinocytes and ZNF90+ fibroblasts in the SFF sheets. Functional analyses showcase active cellular metabolism in LAMB3+ basal keratinocytes, vital in extracellular matrix homeostasis, while ZNF90+ fibroblasts demonstrate increased differentiation, essential in collagen formation for cell adhesion. Importantly, these cell populations in SFF sheets exhibit enhanced interactions with melanocytes compared to SFD sheets. Further, knockdown experiments of LAMB3 in keratinocytes and ZNF90 in fibroblasts lead to a downregulation in melanocyte ligand-receptor-related genes. Overall, SFF sheets demonstrate comparable efficacy to SFD sheets, offering superior safety. LAMB3+ basal keratinocytes and ZNF90+ fibroblasts act as potential drivers behind repigmentation in ACEG under SFF conditions. This study provides translational insights into ACEG repigmentation and potential therapeutic targets for vitiligo.