Active Non-segmental Vitiligo Research Articles

Immunohistochemical Expression of CXCL 10 in Vitiligo.

Vitiligo is a skin disorder characterized by the loss of melanocytes from the epidermis. Cysteine x cysteine motif chemokine ligand 10 (CXCL10) is linked to the Th1 pattern and has been suggested as one of the most relevant chemokine axes that promote T-cell migration in different autoimmune and inflammatory processes. The aim of this study was to assess the immunohistochemical (IHC) expression of CXCL 10 in skin lesions of patients with vitiligo to explore its possible role in the pathogenesis of the disease. In this prospective, case-control study, we examined biopsies from the lesional skin of 20 patients with vitiligo for IHC expression of CXCL 10: 10 patients presented with stable nonsegmental vitiligo (group A), 10 patients presented with active nonsegmental vitiligo (group B), and 10 apparently healthy volunteers were examined as controls (group C). Nine patients in group A had mild IHC expression of CXCL 10 (+1) and 1 patient had moderate expression (+2). In group B, 8 patients had strong expression of CXCL 10 (+3), and the remaining patients had moderate expression (+2). However, there was no expression of CXCL 10 in all skin specimens in the control group. CXCL10 IHC expression was increased in vitiligo lesions indicating a possible role in the pathogenesis of disease. The expression was significantly increased in active vitiligo compared with stable vitiligo.

Ritlecitinib, a JAK3/TEC family kinase inhibitor, stabilizes active lesions and repigments stable lesions in vitiligo

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Combination of total glucosides of paeony, narrow-band ultraviolet B, and oral corticosteroid mini-pulse therapy for nonsegmental vitiligo: A retrospective study.

The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV). The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up. The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements. The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.

The effect of narrowband ultraviolet B on tissue level of interleukin-15 and interleukin-15 receptor alpha subunit in active nonsegmental vitiligo cases: an interventional cohort study

Background Vitiligo is an acquired depigmenting skin disorder in which CD8 effector and memory T-cells contribute to its pathogenesis and recurrence. Interleukin (IL)-15 contributes to CD8 effector T-cell cytotoxicity and CD8 memory T-cell survival and maturation. Objective To evaluate the effect of total narrowband ultraviolet B (NB-UVB) on tissue levels of IL-15 and IL-15 receptor alpha (IL-15Ra) in active nonsegmental vitiligo. Patients and methods The patients were assessed clinically for vitiligo extent and activity before and after treatment. Perilesional skin biopsies were taken from 30 vitiligo patients before and after 48 sessions of NB-UVB and from 30 healthy controls. Tissue levels of IL-15 and IL-15 Ra were evaluated by enzyme-linked immunosorbent assay before and after treatment to evaluate the effect of NB-UVB on them. Results Before NB-UVB treatment, the tissue levels of both IL-15 and IL-15Ra were significantly higher in vitiligo patients than controls; moreover, they were significantly higher than those after NB-UVB treatment. In contrast, after NB-UVB treatment, no statistically significant difference was detected between the patients and controls. The levels of IL-15 and IL-15Ra were significantly correlated, whereas they were not correlated with either vitiligo activity or extent. Conclusion IL-15 and IL-15Ra were higher in vitiligo patients than controls before treatment. However, their tissue levels were normalized after treatment with NB-UVB, emphasizing its therapeutic potential.

Serum Inflammatory and Oxidative Stress Markers in Patients with Vitiligo.

Vitiligo is a common chronic hypomelanotic skin disorder. An intricate pool of markers associated with a complex combination of biological and environmental factors is thought to be implicated in etiology. This study aims to investigate the most important markers associated with vitiligo pathogenesis, including redox status, inflammation, and immune profile, in patients with vitiligo. The study included a total of 96 subjects: 30 patients with active non-segmental vitiligo, 30 patients with stable non-segmental vitiligo, and 36 controls. The vitiligo area severity index (VASI) and vitiligo disease activity score (VIDA) were determined. The following serum parameters were assessed: antioxidant status (TAS), superoxide dismutase activity (SOD), catalase activity (CAT), glutathione peroxidase activity (GPx), glutathione-S-transferase activity (GST), malondialdehyde (MDA), advanced oxidation protein products (AOPP), C reactive protein (CRP), interleukin-15 (IL-15), and chemokines (CXCL9, CXCL10). The VASI score was not significantly different between active and stable vitiligo patients, as it was approximately 0.1. TAS, CAT, GPx, and GST were significantly lower in vitiligo patients compared to controls (p < 0.05). They were also significantly lower in active vitiligo when compared to stable vitiligo (p < 0.05). However, SOD levels were significantly higher in vitiligo patients than in controls and in the active vitiligo group than in the stable vitiligo group (p < 0.05). MDA and AOPP levels were significantly higher in patients with active and stable vitiligo compared to controls (p < 0.05). However, they did not significantly differ between active and stable vitiligo patients (p < 0.05). In both active and stable vitiligo, CRP and IL-15 were significantly higher than controls (p < 0.05). Whereas CRP was significantly higher in active (range = 2.0-7.2, mean = 4.46 ± 1.09) than in stable vitiligo (range = 1.6-6.7, mean = 3.75 ± 1.08) (p < 0.05). There was no significant difference in IL-15 levels between active and stable vitiligo. In both active and stable vitiligo, CXCL9 and CXCL10 were significantly higher than controls (p < 0.05), and they were significantly higher in active than stable vitiligo (p < 0.05). In vitiligo, oxidative damage induces an increase in pro-inflammatory IL-15, which in turn promotes IFN-γ-inducible chemokines such as CXCL9 and CXCL10. Further, there seems to be a link between the VASI score and IL-15 levels. These data imply that inhibiting IL-15 could be a promising method for developing a potentially targeted treatment that suppresses the early interplay between oxidant stress and IL-15 keratinocyte production, as well as between resident and recirculating memory T cells.

A Comparative Study on the Efficacy and Safety of Using Azathioprine Alone, Combining It with Narrow Band (UVB) and to Oral Minipulse Steroids Plus NB-UVB in Stabilizing Active Non-Segmental Vitiligo

Abstract Background Vitiligo is an acquired, non-contagious, pigmentary disease resulting from the loss of melanocytes from skin, hair and mucous membranes. The pathogenesis of vitiligo is still not fully understood and mounting evidences have suggested that it might be related to autoimmunity and oxidative stress. Aim of the Work To evaluate the efficacy and safety of AZA in stabilizing disease progression of active vitiligo, compare it with its combined therapy with NB-UVB and with OMP steroids combined with NB-UVB. Patients and Methods This study included Forty five patients complaining of active non-segmental vitiligo divided into three groups: Group (A): 15 patients received narrow band therapy with oral mini-pulse steroid therapy (dexamethasone) as a single dose on two consecutive days repeated every week for 3 months, Group (B): 15 patients received narrow band therapy (same regimen as in group A) combined with oral azathioprine 50 mg twice daily for 3 months, and group (C): 15 patients received oral azathioprine alone for 3 months. Results Evaluation of treatment response was done at 4, 8 and 12 weeks of treatment by assessing the onset of stoppage of disease activity as well as the onset of repigmentation and its extent using VES, VES plus and VIDA scores. Encountered side effects were also documented. Conclusion Both oral minipulse steroid therapy and azathioprine are effective in stopping the activity of vitiligo, either as monotherapy or better combininig with NBUVB, though azathioprine being inferior to OMP steroid therapy in arresting disease progression and inducing re-pigmentation. Thus, it can be used as a good alternative when there is contraindication to use systemic steroids.

Comparative Analysis of the Most Used Versus the Recently Developed Vitiligo Activity and Extent Scores and Their Change with Treatment.

There are diverse assessment tools for vitiligo, with no standardized approach that helps unify treatment outcome measures. Thus, comparing different treatment modalities and developing evidence-based recommendations for vitiligo management has been quite challenging. We compared the most commonly used tools assessing both vitiligo activity and extent, namely, Vitiligo Disease Activity Score (VIDA) and Vitiligo Area and Severity Index (VASI) score to their newly developed counterparts, namely, Vitiligo Extent Score Plus (VES plus) and Vitiligo Signs of Activity score (VSAS), to provide insights that would help set recommendations for a unified outcome assessment protocol for vitiligo patients. Thirty-six active non-segmental vitiligo cases were recruited, 30 of whom completed 48 sessions of narrow band ultraviolet B (NB-UVB). Patients were assessed for both extent and activity both before and after treatment with NB-UVB. Scores were correlated. Additionally, VES plus was assessed for its reliability in comparison to VASI score. Both extent (VASI and VES plus) and activity scores (VIDA and VSAS) showed significant improvement following treatment. Additionally, VES plus and VASI were positively correlating both before and after treatment as well as their percent change. Furthermore, VES plus proved as reliable as VASI. Regarding activity scores, total, hypochromic and Koebner VSAS only correlated with VIDA following treatment. Confetti VSAS neither correlated with VIDA before nor after treatment. VES plus and VASI scores have proven of comparable reliability. While examination-based VSAS score comes as an additive tool to the history-based VIDA score.

1215 Ritlecitinib, an oral dual JAK3/TEC family kinase inhibitor, induces differential changes in immunological protein levels across Fitzpatrick skin types (FST) in patients with active nonsegmental vitiligo (NSV)

1215 Ritlecitinib, an oral dual JAK3/TEC family kinase inhibitor, induces differential changes in immunological protein levels across Fitzpatrick skin types (FST) in patients with active nonsegmental vitiligo (NSV)

Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, stabilizes active lesions and promotes re-pigmentation of stable lesions in patients with active nonsegmental vitiligo: results from a phase 2b, randomized, placebo-controlled, dose-ranging study

Abstract Patients with active nonsegmental vitiligo (NSV) may experience active lesions (confetti-like and trichrome lesions) or stable lesions (where lesions may remain unchanged for ∼1 year or more). In a phase 2b trial, the oral JAK3/TEC inhibitor ritlecitinib demonstrated a significant improvement in the Facial-Vitiligo Area Scoring Index at Week 24 for patients with active NSV at 50 mg daily with or without a loading dose (100 or 200 mg daily for 4 weeks). To evaluate the efficacy of ritlecitinib on active vs. stable lesions in patients with active NSV who participated in the phase 2b trial (NCT0371529). Patients were randomized to daily ritlecitinib or placebo for 24 weeks, with or without a 4-week loading dose: 200/50, 100/50, 50, 30, 10 mg, or placebo. Mean percent change from baseline (%CFB) in depigmentation extent (100%, 90%, 75%, 50%, 25%, or 10%) within the lesion at baseline and Week 24 was evaluated centrally using photographs obtained from both active (clinical signs including confetti-like and trichrome lesions) and stable target lesions, other than on the face. The analysis included 317 patients who had active and stable lesions simultaneously among 364 treated patients. Within active lesions, ritlecitinib induced a statistically significant reduction in depigmentation extent [%CFB: 200/50 mg, +0·8 (P = 0·0388); 100/50 mg, −1·7 (P = 0·0035); 30 mg, −1·6 (P = 0·0086)] compared with a progressive increase in depigmentation in the placebo group (%CFB: +5·6). No significant reduction was seen with ritlecitinib 50 mg (+2·8) or 10 mg (+1·4%). Within stable lesions, ritlecitinib showed a statistically significant reduction in depigmentation extent, reflecting re-pigmentation [%CFB: 200/50 mg, −7·2 (P = 0·0045); 100/50 mg, −6·1 (P = 0·0082); 50 mg, −5·9 (P = 0·0134); 30 mg, −8·0 (P = 0·0092)] compared with the placebo group, where %CFB in de-pigmentation increased (%CFB: +0·5). No significant reduction was seen with ritlecitinib 10 mg (−3·3%). The magnitude of the re-pigmentation was numerically greater in stable lesions compared with that in active lesions. In patients with active NSV, ritlecitinib treatment for 24 weeks stabilized active lesions and promoted re-pigmentation of stable lesions.

Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, shows efficacy in patients with active nonsegmental vitiligo and either a lighter or darker Fitzpatrick skin type: results from a phase 2b, randomized, dose-ranging study with an extension period

Abstract Ritlecitinib, an oral JAK3/TEC inhibitor, inhibits cytokines IL-15 and IFN-γ that play a critical role in vitiligo pathogenesis. In a phase 2b trial, ritlecitinib demonstrated a significant improvement on the centrally read Facial Vitiligo Area Scoring Index (crF-VASI) at Week 24 in patients with active nonsegmental vitiligo (NSV) at 50 mg daily with or without a loading dose (100 or 200 mg daily for 4 weeks). Improvement on the crF-VASI was observed up to Week 48 in patients receiving ritlecitinib 50 mg daily with a 200 mg daily loading dose for 4 weeks in the 24-week extension period. We evaluated the efficacy and safety of ritlecitinib, an oral JAK3/TEC inhibitor, in patients with active NSV and lighter Fitzpatrick skin types (FST; I–III) or darker FST (IV–VI) from the Phase 2b study (NCT03715829). Patients with active NSV were randomized to placebo or ritlecitinib 50 mg daily with or without a loading dose (200 or 100 mg, 4-week) or low doses (30 or 10 mg) in a 24-week, dose-ranging period, followed by a 24-week extension wherein patients were allocated to 200/50 mg (200 mg, 4-week; 50 mg, 20-week). Percent change from baseline (%CFB) in F-VASI was evaluated. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs). A total of 253 patients (lighter FST, n = 170; darker FST, n = 83) completed the dose-ranging period. Placebo-adjusted mean %CFB in F-VASI at Week 24 among the 50 mg and low-dose groups, respectively, were −15·2 (P = 0·0043) and −5·5 (P = 0·1991) in lighter FST and −37·4 (P &amp;lt; 0·0001) and −15·7 (P = 0·0401) in darker FST. In the extension, 187 patients received 200/50 mg and 136 (lighter FST, n = 96; darker FST, n = 40) completed Week 48. Continuous re-pigmentation without plateau of effect was observed across FST through Week 48; mean %CFB in F-VASI at Week 48 in patients initially treated with 50 mg, low doses or placebo in the dose-ranging period, respectively, were −63·1, −51·0 and −51·3 for lighter FST and −66·8, −51·0 and −52·5 for darker FST. TEAE incidence in the dose-ranging period was similar between lighter and darker FST (range, 69·2–81·0%). Ritlecitinib was generally safe with similar efficacy in vitiligo patients with lighter or darker FST.

Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: A randomized phase 2b clinical trial

Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. To evaluate the efficacy and safety of ritlecitinib, an oral JAK3 (Janus kinase)/TEC (tyrosine kinase expressed in hepatocelluar carcinoma) inhibitor, in patients with active nonsegmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to once-daily oral ritlecitinib ± 4-week loading dose (200/50mg, 100/50mg, 30mg, or 10mg) or placebo for 24weeks (dose-ranging period). Patients subsequently received ritlecitinib 200/50mg daily in a 24-week extension period. The primary efficacy endpoint was percent change from baseline in Facial-Vitiligo Area Scoring Index at week 24. A total of 364 patients were treated in the dose-ranging period. Significant differences from placebo in percent change from baseline in Facial-Vitiligo Area Scoring Index were observed for the ritlecitinib 50mg groups with (-21.2 vs 2.1; P<.001) or without (-18.5 vs 2.1; P<.001) a loading dose and ritlecitinib 30mg group (-14.6 vs 2.1; P=.01). Accelerated improvement was observed after treatment with ritlecitinib 200/50mg in the extension period (n=187). No dose-dependent trends in treatment-emergent or serious adverse events were observed across the 48-week treatment. Patients with stable vitiligo only were excluded. Oral ritlecitinib was effective and well tolerated over 48weeks in patients with active nonsegmental vitiligo.

33304 Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, shows efficacy in patients with active nonsegmental vitiligo and either a lighter or darker Fitzpatrick skin type: Results from a phase 2b, randomized, dose-ranging study with an extension period

Introduction: We evaluated the efficacy of ritlecitinib, an oral JAK3/TEC inhibitor, in patients with active nonsegmental vitiligo who participated in a phase 2b study (NCT03715829) and who were grouped according to lighter skin type (Fitzpatrick skin types [FST] I–III) or darker skin type (FST IV–VI). Methods: Patients were randomized to placebo or ritlecitinib with or without a 4-week loading dose (200/50 mg, 100/50 mg, 50 mg, 30 mg, or 10 mg) in a 24-week, dose-ranging period (DR), followed by a 24-week extension wherein patients were allocated to ritlecitinib 200/50 mg. Percent change from baseline (%CFB) in Facial-Vitiligo Area Scoring Index (F-VASI) was evaluated at Weeks 24 and 48. Results: 364 patients initiated treatment and 253 (170 and 83 with lighter or darker FST, respectively) completed the DR. For patients with lighter FST, placebo-adjusted mean %CFB in F-VASI at Week 24 among the 200/50 mg, 100/50 mg, 50 mg, and 30 mg groups were −14.3, −16.8, −14.6, and −10.4, respectively (P < .05 for each group except 30 mg). For patients with darker FST, placebo-adjusted mean %CFB in F-VASI at Week 24 were −37.5, −37.3, −37.9, and −26.7, respectively (P < .05 for each group). In the extension, 187 patients were allocated to ritlecitinib 200/50 mg and 136 (96 and 40 with lighter or darker FST, respectively) completed Week 48. Continuous repigmentation without plateau of effect was observed in all FST through Week 48. Conclusion: Ritlecitinib 50 mg for up to 48 weeks, with or without a loading dose during the DR, showed efficacy in patients with active nonsegmental vitiligo and either lighter or darker FST.

33300 Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, stabilizes active lesions and promotes repigmentation of stable lesions in patients with active nonsegmental vitiligo: Results from a phase 2b, randomized, placebo-controlled, dose-ranging study

33300 Ritlecitinib (PF-06651600), an oral JAK3/TEC inhibitor, stabilizes active lesions and promotes repigmentation of stable lesions in patients with active nonsegmental vitiligo: Results from a phase 2b, randomized, placebo-controlled, dose-ranging study

Association Among MIF, IFIH1, and IL6 Gene Polymorphisms and Non-Segmental Vitiligo in a Chinese Han Population.

ObjectiveThe aim of the present study was to investigate the association of single-nucleotide polymorphisms (SNPs) in the macrophage migration inhibiting factor (MIF), interferon-induced Helicase C domain 1 (IFIH1), interleukin-6 (IL6) genes, circulating levels with non-segmental vitiligo (NSV) susceptibility in the Chinese population, and to analyze the relationships between gene polymorphisms and clinical characteristics of vitiligo.MethodsIn this study, genotyping was conducted in 155 patients with NSV and 117 unaffected controls using polymerase chain reaction and snapshot technique. Serum concentrations were determined by ELISA kit.ResultsThere were strong associations between IFIH1 H843R and IL6-572G/C polymorphisms and NSV susceptibility (p = 0.013; p = 0.009). In contrast to previous studies, we found no significant difference in the MIF-173G/C polymorphism between the two groups. In addition, the frequency of allelic distribution for MIF-173G/C in patients with active NSV was significantly higher than stable NSV (p = 0.011), and IFIH1 H843R with early-onset (≤ 20), active or family history of NSV was significantly higher than late-onset (> 20), stable or no family history of NSV (p = 0.033; p = 0.045; p = 0.039). Serum concentrations of MIF were higher in patients with active NSV, serum IFIH1 and IL6 concentrations were related to the presence of polymorphisms in patients with NSV (p = 0.009; p = 0.011).ConclusionOur results suggested that IFIH1 H843R and IL6-572G/C gene polymorphisms and expression levels are obviously correlated with the onset of NSV. MIF-173G/C allele and serum concentrations may be associated with active NSV, and IFIH1 H843R allele may be associated with youth, active or family history of NSV.

Assessment of CXCL10 Before and After Narrow Band UVB Phototherapy in Non-Segmental Vitiligo Patients.

Vitiligo is a common depigmenting skin disorder characterized by white macules and patches accompanied by local melanocyte loss, caused by autoimmune destruction. Vitiligo is classified into two major forms: segmental vitiligo (SV) and non-segmental vitiligo (NSV). It was also found that the IFN-ȣ/CXCL10 axis is functionally required for both progression and maintenance of the disease. Chemokine 10 (CXCL10) is a pro-inflammatory chemokine which was found to be elevated in the serum of vitiligo patients. UVB has been found to be a useful therapy that results in rapid repigmentation in NSV patients. To evaluate CXCL10 in vitiligo patients before and after narrow band UVB (NB-UVB) phototherapy, which if targeted could provide new insights for therapeutic intervention for vitiligo. The study included 25 active NSV patients who were able to comply with the study protocol in the Center of Excellence, Dermatology Outpatient Clinic, National Research Center, Egypt (February 2020-2021). All recruited patients were subjected to documentation of complete history. Dermatological assessment of vitiligo lesions, including vitiligo area score index (VASI) score, CXCL10 and extent of the disease were performed. A 3 mm punch biopsy from active vitiligo lesion (site of biopsy) was taken before and after treatment by NB-UVB, and then immunohistochemical staining was performed to evaluate expression of CXCL10. After treatment by NB-UVB there was a significant decrease in VASI score, extent of the disease and CXCL10 expression. The decrease in CXCL10 levels could be attributed to the effect of NB-UVB which leads to decrease in IFN-γ level, necessary to release CXCL10 through its pathway resulting in repigmentation and decrease in the extent of the disease and VASI scores.

Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, randomized, placebo-controlled, prospective, multicenter study.

NB-UVB has long been the vitiligo management pillar with capability of achieving the main treatment outcomes; repigmentation and stabilization. Its stabilizing effect in dark skin has been debatable. However, randomized controlled trials regarding NB-UVB ability to control disease activity are lacking. To assess stabilizing effect of NB-UVB in comparison to systemic corticosteroids, the mainstay in vitiligo stabilization, in skin photo-types (III-V). This is a multicenter, placebo-controlled, randomized, prospective study. Eighty patients with active nonsegmental vitiligo (NSV) (Vitiligo disease activity (VIDA) ≥2) were randomized to either NB-UVB and placebo (NB-placebo) or NB-UVB and dexamethasone oral mini-pulse (OMP) therapy (NB-OMP) for 6months. Sixty four patients completed the study, 34 in the NB-OMP group and 30 in the NB-placebo group. Patients were evaluated fortnightly according to presence or absence of symptoms/signs of activity. In spite of earlier control of disease activity observed in the NB-OMP group, it was comparable in both groups by the end of the study period. Disease activity prior to therapy, but not extent, was found to influence control of activity in both groups. Thus, NB-UVB is a safe sole therapeutic tool in vitiligo management. Not only does it efficiently achieve repigmentation, but also it is a comparable stabilizing tool for systemic corticosteroids in spite of slightly delayed control. NB-UVB is the only well-established vitiligo therapy that can be used solely whenever corticosteroids are contraindicated or immune-suppression is unjustified. Nonetheless, its combination with corticosteroids expedites response and improves compliance.

DEFB1 gene polymorphisms modify vitiligo extent and response to NB‐UVB phototherapy

Human beta defensin-1(hBD-1); an antimicrobial peptide, has immune regulatory effects which may be involved in autoimmunity. The aims were to evaluate the association between defensin beta 1 (DEFB1) (-44 C/G) and (-20 G/A) gene polymorphisms with the risk of vitiligo development, the extent of the disease and the response to NB-UVB treatment in a sample of Egyptian population. 178 active nonsegmental vitiligo patients and 182 control subjects were included in this prospective case control study. Vitiligo extent was evaluated using vitiligo area scoring index (VASI). Gene polymorphisms in all participants were studied by RFLP PCR technique. Patients were treated by three narrowband UVB (NB-UVB) treatment sessions per week. After 12 weeks, the patients were reevaluated clinically to assess the extent of the disease using VASI scoring again and to evaluate the type of repigmentation, if any. AA genotype of DEFB1 (-20G/A) has a protective role against vitiligo development, while (DEFB1 -44 C/G) GG genotype and G allele increase the risk of vitiligo development about two folds. Patients carrying polymorphism in DEFB1 (-20G/A) only showed the lowest VASI scores (14.23 ± 2.77) and the highest percentage of improvement (66.12 ± 18.01%), while patients carrying polymorphism in DEFB1(-44 C/G) only showed the highest baseline VASI scores (38.87 ± 6.7) and the lowest therapeutic response (23.79 ± 19.42%) among all patients groups. Different DEFB1 gene polymorphisms may modify the risk of vitiligo development, the disease extent and the response to NB-UVB phototherapy.

16210 Altered expression of microRNA-16 promotes narrowband UVB–induced repigmentation in vitiligo

Background: The role of microRNA is implicated in myriad immunologic processes and their role has been suggested in variety of autoimmune disorders. miRNA may play a role in the development of vitiligo and pigmentation. Objective: To study the effect of narrowband (NB) UVB treatment on the expression of miRNA in peripheral blood, lesional and non-lesional skin in active nonsegmental vitiligo (aNSV) and correlation with clinical parameters.

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT.

Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). In total, 517 participants were randomised (adults, n = 398; and children, n = 119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. Current Controlled Trials ISRCTN17160087. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.

Immunohistochemical study of perforin and apoptosis stimulation fragment ligand (FasL)in active vitiligo.

Several studies demonstrated a major pathological role of melanocyte-specific cytotoxic CD8+ T cells in the pathogenesis of vitiligo. It has been suggested that apoptosis, rather than necrosis, is the mechanism of melanocyte depletion in vitiligo. The aim of this study was to evaluate the expression and distribution of perforin and apoptosis stimulation fragment ligand (FasL) in the epidermis and dermis of the perilesional and non-lesional skin of vitiligo patients in comparison to controls, to assess their possible role in mediating apoptosis in vitiligo. Twenty patients with active non-segmental vitiligo and 20 healthy controls were enrolled in the study. Skin biopsies were taken from perilesional and non-lesional skin of patients with vitiligo, as well as covered skin of controls. Immunostaining for perforin and FasL was performed and the quantitative analysis for the expression of perforin and FasL was carried out in the epidermis and dermis of biopsied specimens. Epidermal perforin, dermal perforin, epidermal FasL, dermal FasL were significantly higher in perilesional as well as non-lesional skin than controls. There was a statistically significant positive correlation between epidermal and dermal perforin in perilesional skin. There was a statistically significant positive correlation between epidermal and dermal perforin, as well as epidermal and dermal FasL in non-lesional skin. In conclusion, the significant expression of perforin and FasL in the epidermis and dermis of both perilesional and non-lesional skin of active vitiligo patients suggests the role of cytotoxic granules and apoptotic cell death pathways in the pathogenesis of active vitiligo.