Whole-body and targeted narrowband ultraviolet B phototherapy effectively stabilize acral vitiligo with negligible repigmentation beyond wrists and ankles: Results from a split-body randomized controlled trial.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy promotes stability and repigmentation in vitiligo. No studies have compared targeted NB-UVB with whole-body NB-UVB in treatment of acral vitiligo. OBJECTIVES: This randomized split-body study compared whole-body NB-UVB with targeted NB-UVB in inducing stability and repigmentation in acral vitiligo. METHODS: Thirty-two patients with bilaterally symmetrical acral vitiligo lesions (distal to elbows and knees) were recruited. Patients received whole-body NB-UVB treatment, with one hand and one foot shielded until elbow and knee, followed by targeted NB-UVB treatment on the shielded side. Patients were assessed at 4-week intervals for 24 weeks using Vitiligo Disease Activity (VIDA) score, Vitiligo Skin Activity Score (VSAS), Vitiligo Area Scoring Index (determined through fingertip method, using the method to calculate facial-VASI) and degree of repigmentation. RESULTS: After 12 weeks, 87.5% of patients achieved a VIDA score of 3, with none having active disease at 24 weeks. Over 50% repigmentation was observed in 42.2% and 37.5% of limbs in whole-body and targeted groups, respectively (p = .95). No improvement in F-VASI scores of hands and feet (distal to wrist and ankles) was noted with either modality over the 24-week period. CONCLUSION: Our study showed comparable repigmentation rates between whole-body and targeted NB-UVB groups. Limited effectiveness of phototherapy in repigmentation of hands and feet underscores an important therapeutic gap.

Altered levels of lymphocyte enhancer-binding factor-1 modulates the pigmentation in acral and non-acral lesions of non-segmental vitiligo patients: a follow-up-based study in North India.

BACKGROUND: Lymphocyte enhancer-binding factor-1 (LEF1) is responsible for melanocyte proliferation, migration and differentiation and its downregulation may result in depigmentation in vitiligo. Narrowband UVB (NB-UVB) phototherapy is known to enhance melanocyte migration from hair follicles to lesional epidermis; hence, it may have a role in the upregulation of LEF1. OBJECTIVES: We intended to assess the expression of LEF1 both before and after NB-UVB therapy and correlate it with the extent of re-pigmentation. MATERIALS AND METHODS: In this prospective cohort study, 30 patients of unstable non-segmental vitiligo were administered NB-UVB phototherapy for 24 weeks. Skin biopsies were obtained from acral and non-acral sites in all patients, both prior to initiation and after completion of phototherapy and LEF1 expression was measured. RESULTS: Amongst the 16 patients who completed the study, at 24 weeks, all patients achieved > 50% re-pigmentation. However, > 75% re-pigmentation was achieved in only 11.1% of acral patches, whereas it was achieved in a significantly higher number of non-acral patches (66.6%) (p = 0.05). A significant increase was observed in the mean fluorescent intensity of the LEF1 gene in both acral as well as non-acral areas at 24 weeks as compared to baseline (p = 0.0078), However, no difference was observed between acral and non-acral lesions in the LEF1 expression at 24 weeks or the change in LEF1 expression from baseline. CONCLUSION: LEF1 expression modulates the re-pigmentation of vitiligo lesions after treatment with NBUVB phototherapy.

Oral cyclosporine is effective in stabilizing active vitiligo: Results of a randomized controlled trial.

Oral dexamethasone mini pulse (OMP) is an established treatment modality for active vitiligo. Cyclosporine may have therapeutic role in active vitiligo but current evidence supporting its role is scarce. The objective of study was to compare the efficacy and safety of oral cyclosporine with OMP in patients of active vitiligo. Fifty patients with active vitiligo were randomized into two groups of 25 patients. Group 1 was treated with OMP (2.5 mg dexamethasone) on two consecutive days/week for 4 months while group 2 was treated with cyclosporine (3 mg/kg/day) for 4 months. Laboratory monitoring was performed as per the prevalent protocol. The patients were followed up for another 2 months after stopping treatment. Arrest of disease progression (ADP) was defined as change of vitiligo disease activity score from 4+ to 3+ (time elapsed since last disease activity being more than 6 weeks upto 3 months) during the study period (6 months). ADP was attained in 21 patients in group 1 and 22 patients in group 2 (84% vs. 88%, p = 1.00) at the end of 6 months. However, mean time to achieve ADP was significantly lower in group 2 as compared to group 1 (10.92 [4.12] weeks vs. 13.90 [3.92] weeks, p = 0.01). Extent of repigmentation, improvement in patient assessment score, vitiligo quality of life and clinical markers of disease activity were marginal and comparable in both groups. Cyclosporine leads to earlier disease stabilization in active vitiligo as compared to OMP. Although considered a rescue drug in dermatology, low dose cyclosporine can be an effective therapeutic alternative in vitiligo patients.

Oral mycophenolate mofetil as a stabilizing treatment for progressive non-segmental vitiligo: results from a prospective, randomized, investigator-blinded pilot study.

Dexamethasone oral mini-pulse (OMP) is commonly used to halt progression of non-segmental vitiligo (NSV). There is an unmet need for non-phototherapy, non-corticosteroid therapeutic options for stabilizing actively spreading NSV. To assess the efficacy of oral mycophenolate mofetil in stabilizing active NSV in comparison to OMP. In this prospective, randomized, investigator-blinded study, 50 patients of active vitiligo [baseline vitiligo disease activity (VIDA) score 4] were randomized into two groups in 1:1 ratio. Group A received oral dexamethasone (2.5 mg on two successive days a week) and group B received mycophenolate mofetil (up to 2 g) for 180 days with a treatment-free follow-up period of 90 days. Assessment was done using VIDA, number of new lesions in past 30 days, and Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in past 30 days. Twenty-five patients received OMP (group A, 11 males, 14 females), and 25 received mycophenolate (group B, 12 males, 13 females). In both groups, Kruskal-Wallis revealed a significant trend for reduction in VIDA and the number of new lesions in last 30 days, over the treatment and follow-up duration when compared to baseline (p < 0.001). The first significant reduction in VIDA was noticed on 90th day in groups A and B (p < 0.001). In both groups, VIDA reduced significantly at the 180th day compared to baseline (p < 0.001, WMP), only to increase significantly at the 270th day (p < 0.001, WMP). VIDA in group B was marginally higher at 270 days than group A (p 0.03; Mann-Whitney). Eighteen and 17 patients achieved VIDA 2 + on the 180th day in groups A and B, respectively. The mean number of new lesions in last 30 days reduced significantly in both groups at the 180th day (p < 0.001) and 270th day [p < 0.001; Wilcoxon matched pairs (WMP)] when compared to baseline; but increased significantly at the 270th day compared to the 180th day (p 0.006 WMP). Twenty patients in group A and 18 patients in group B had arrest of the disease activity with treatment. Mean duration to arrest disease progression was 47.2 ± 12.1 days in group A, and 52.5 ± 9.3 days in group B; p 0.21. The difference between VASI at baseline and VASI at the 180 and 270th days was non-significant in both groups (p 0.18 WMP). Five patients in each group failed the respective treatments. Acne (n = 3), weight gain (n = 3), headache, insomnia and menstrual irregularity (n = 1 each) were the important adverse effects noted with dexamethasone pulse; whereas nausea (n = 6) and diarrhea (n = 4) were the commonest adverse effects noted with mycophenolate. Two patients in group B discontinued treatment because of leucopenia (n = 1) and transaminitis (n = 1) that resolved after the discontinuation of mycophenolate. Both OMP and mycophenolate mofetil halt actively spreading vitiligo, and have distinct adverse effect profiles. These should be offered in progressive vitiligo, especially in circumstances precluding the use of phototherapy. Relapse occurred significantly earlier with mycophenolate, and relapse rate was higher (though non-significant) than dexamethasone OMP. The repigmentation potential is minimal for both therapies. This study was approved by Institute Ethics Committee, and retrospectively registered with clinical trial registry of India (CTRI/2018/02/011,664).

Role of IL-17A receptor blocking in melanocyte survival: A strategic intervention against vitiligo.

Cytokines regulate immune response and inflammation and play an important role in depigmentation process of an autoimmune disease, vitiligo. We sought to determine how inflammatory cytokines influence the progression of vitiligo, and based on that, we develop a logical therapeutic intervention using primary melanocyte culture. Melanocytes were cultured and exposed to IL-17A, IL-1ß, IFN-γ and TGF-ß for 4 days. Melanocytes proliferation, tyrosinase assay and melanin content were measured. Real-Time PCR was used to analyse mRNA expression of genes specific for melanocytes growth and pigmentation. Anti-IL-17A receptor antibody was used to block IL-17A receptors expressed on melanocytes. Protein expression of MITF and TYR was assessed by immunofluorescence and Western blotting. A gradual decline in the melanocyte population, melanin content and tyrosinase activity was observed after different cytokine treatment. The expression of MITF and its downstream genes after blocking with anti-IL-17RA, an increased melanin content, increased expression of TYR, MITF along with its downstream genes, and cell proliferation was observed.