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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.

ABSTRACT Background Methods Results Conclusions Research on evaluating the efficacy of non‐cultured epidermal cell suspension (NCECS) combined with excimer lamps for the treatment of vitiligo is currently unavailable. This research aims to evaluate the efficacy of this combination in treating vitiligo.A prospective, controlled study was conducted from November 2021 to January 2024. Patients with stable vitiligo were randomly assigned into groups 1 (NCECS combined with excimer lamps) or 2 (NCECS alone). All patients were followed up 18 months after the procedure. Treatment effectiveness and adverse events were recorded.Sixty patients were randomly assigned to groups 1 (30 patients) and 2 (30 patients). A total of 33.3% of patients in group 1 achieved 100% repigmentation, significantly higher than the 6.7% in group 2 (p‐value = 0.021). Meanwhile, 63.3% of patients in group 1 achieved ≥ 90% repigmentation, higher than the 50% in group 2 but not statistically significant (p‐value = 0.435). The mean time to initial repigmentation in group 1 (2.35 ± 0.575 weeks) was significantly shorter than in group 2 (2.72 ± 0.665 weeks) (p‐value = 0.003). Both groups demonstrated a similar rate of good color match, but group 1 exhibited a lower incidence of the halo phenomenon. A total of 23.3% of patients in group 1 experienced mild erythema, which spontaneously resolved in a few days.The combination of NCECS and excimer lamps can substantially stimulate the onset of repigmentation and enhance 100% repigmentation compared to NCECS monotherapy. Excimer lamps may reduce the incidence of the halo phenomenon. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus, a topical calcineurin inhibitor (TCI) with immunomodulatory effects, is considered a viable treatment option for vitiligo. A consensus building exercise was undertaken to determine the role and clinical utility of topical tacrolimus in the management of vitiligo using input from experts in the field of dermatology. Methods: Seventeen experts collaborated to create consensus statements using a modified Delphi methodology. A questionnaire on effectiveness, safety and utility of topical tacrolimus in different types of vitiligo, duration, frequency, monotherapy and combination and other aspects was shared, and a concordance rate of 75% was preset to have consensus. A physical meeting was conducted to discuss statements, which did not achieve consensus. Results: Amongst 34 statements derived from round one, consensus was not achieved for 9 statements. In the second round, consensus was achieved for 2/9 statements, hence in the physical meeting, discussion was done to reframe the remaining seven statements. Apart from these 34 statements, questions pertaining to "Vitiligo: types and presentation in clinical practice", where consensus was not intended, are presented as descriptive statements. Conclusion: Topical tacrolimus ointment has a favorable risk benefit profile to be used as one of the first-line agents for vitiligo. Combination of topical tacrolimus and narrow band Ultraviolet-B (NBUVB) was recommended as an effective treatment for non-segmental vitiligo. Recommended frequency of application was once or twice daily for optimal results. Apart from a transient burning sensation, topical tacrolimus has a favorable safety profile. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is an acquired depigmentation condition. It affects around 0.1%-2% of the general population, regardless of ethnicity, gender, or socioeconomic status of the affected individuals. Vitiliginous patches contain either reduced melanin or no pigment at all. Objective: This study aimed to evaluate the efficacy of Erbium: YAG (Er: YAG) laser plus pimecrolimus and narrowband ultraviolet B (NB-UVB) (on the right side) in comparison with Er: YAG laser plus topical steroid and NB-UVB (on the left side of the same patient) in treatment of vitiligo in the resistant localizations. Patients and methods: The study comprised thirty patients with persistent non-segmental vitiligo and at least two symmetrical lesions on bony prominences and/or extremities. Patients were selected from the Outpatient Dermatological Clinic of Mataria Teaching Hospital. Results: Regarding the area of the lesion on the right side, there was statistically significant difference between the area of the lesion before and after treatment at the 1st, 2nd, 3rd and 6th month of treatment. On the left side, there was also statistically significant difference between the area of the lesion before and after treatment at the 1st, 2nd, 3rd and 6th month of treatment. The higher percentage of improvement was seen in the knees followed by the elbows, while the lateral malleolus has 0% of improvement on both the right and left sides. Conclusion: From this study we concluded that skin ablation by Er: YAG laser followed by NB-UVB in combination with either pimecrolimus or hydrocortisone is one of the alternative treatment modalities in treatment of stable, resistant vitiligo patches with almost no difference between the two treatment lines. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a chronic progressive depigmented skin disorder, characterized by extensive melanocytes destruction. The explanation for the skin problem remains unknown. Human paraoxonase-1 (PON1) is a hepatic calcium-dependent esterase. PON1 is related to high-density lipoprotein (HDL). Reduction in serum PON1 activity has been recorded to be accompanied by certain pathological conditions under oxidative stress situations. Objective: To evaluate the serum PON1 activity as an indicator of oxidative stress in patients with non-segmental vitiligo (NSV). Patients and Methods: This case-control study included 2 groups, group (A) included 20 patients with NSV and group (B) included 20 age and sex matched healthy controls. The Vitiligo Area Severity Index (VASI) score was used to assess the disease severity. Serum PON1 level was measured using enzyme-linked immunosorbent assay (ELISA). Results: The mean VASI score was 9.86±15.61. The mean PON1 level demonstrated a statistically significant difference between both groups (p=0.002), suggesting that vitiligo cases may be associated with low PON1 levels. PON1 levels showed a significant negative correlation with the severity score measured by the VASI. Only PON1 was found to be a significant predictor of vitiligo severity. Conclusion: Vitiligo cases were associated with a reduction in PON1 level, which emphasizes the underlying theory of disease progression and could emphasize the effect of free radicals and leading oxidative damage in vitiligo. Low PON1 was found to be a significant predictor of a higher VASI score. [ABSTRACT FROM AUTHOR]

Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In this study, we performed a comprehensive analysis of two vitiligo microarray datasets from the GEO database using bioinformatics tools to identify 297 up-regulated mRNAs and 186 down-regulated mRNAs, revealing important roles for pathways related to melanin synthesis, tyrosine metabolism, and inflammatory factors, such as "PPAR signaling pathway", "tyrosine metabolism", "nonalcoholic fatty liver disease (NAFLD) pathway", "melanogenesis", and "IL-17 signaling pathway". Combining the Search Tool for Interacting Chemicals (STITCH) database 5.0 and the drug-gene interaction database 3.0 (DGIdb), we identified that the PPAR-γ agonist rosiglitazone may promote melanin synthesis via EDNRB. Next, we investigated the mechanism of rosiglitazone and PPAR-γ pathway in promoting melanin production. Consistent with the results of bioinformatics analysis, the expression levels of PPAR-γ, EDNRB, and TYR were significantly reduced in human non-segmental vitiligo skin along with the reduction of MITF, a key gene for epidermal melanogenesis. Meanwhile, rosiglitazone increased melanin synthesis capacity in melanocytes and zebrafish by activating PPAR-γ and upregulating TYR, TYRP-1, and TYRP-2. Conversely, treatment of melanocytes with the PPAR-γ antagonist GW resulted in inhibition of melanin synthesis and expression of melanin-related factors. At the same time, simultaneous treatment of rosiglitazone with GW reversed the inhibitory effect of GW on melanin synthesis. In this study, we identified that rosiglitazone, an important insulin sensitizer, promotes melanin synthesis in melanocytes by increasing PPAR-γ activity and upregulating the expression levels of EDNRB and TYR. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of non-segmental vitiligo. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the efficacy of a combination therapy involving NB-UVB phototherapy, bFGF-related decapeptide, and fractional CO2 laser in stable non-segmental vitiligo cases. Method: A prospective interventional study was conducted on clinically stable, non-segmental vitiligo patients. The combination therapy was administered for 16 weeks, and patients were followed up for 12 weeks. Data analysis was performed using SPSS version 23.0, with statistical significance set at p < 0.05. Results: Twenty patients aged 12-60 years were enrolled. After 16 weeks, 65% of patients showed good to excellent repigmentation (> 50%) with perifollicular repigmentation being commonly observed. The time for initial repigmentation was as early as 4 weeks. Adverse effects were mild and transient, with no recurrence observed during the follow-up period. Conclusion: This novel combination therapy demonstrated significant repigmentation rates in stable non-segmental vitiligo and presents a potential safe and efficacious therapeutic option in clinical settings. [ABSTRACT FROM AUTHOR]

Plasma exosomal microRNAs (miRNAs) have been used as potential biomarkers for various diseases and have been investigated for their possible involvement in the pathogenesis of vitiligo. However, the miRNA expression profile of plasma exosomes in patients with non-segmental vitiligo (NSV) has not been determined yet. To screen differentially expressed microRNAs in plasma exosomes derived from patients with NSV and explore their roles in the pathogenesis of NSV. High-throughput sequencing was performed to determine the expression profiles of exosomal miRNAs in NSV. The effect of upregulated miR-1469 in NSV circulating exosomes on natural killer (NK) cells was further investigated using various molecular biological techniques. MiR-1469 was identified as a candidate biomarker whose expression was significantly increased in circulating exosomes of NSV patients. Circulating exosomes were internalized by NK cells and increased NK cell proliferation viability and IFN-γ secretion capacity delivering miR-1469. Further studies revealed that the upregulation of CD122, the predicted target of miR-1469, could partially reverse the effect of miR-1469 on natural killer cells. Alterations in plasma exosomal cargo occur in NSV and appear to contribute to NK cell dysfunction. Exosomal miR-1469 may be a biomarker of disease activity and could be used as a therapeutic drug target against innate immunity in NSV patients. The present study provides new insights into the role of exosomal miRNAs in NSV and suggests a novel miR-1469-CD122-IFN-γ pathway of NK cell underlying pathogenesis of NSV. • MiR-1469 derived from plasma exosomes of patients with non-segmental vitiligo is significantly elevated. • MiR-1469 is negatively correlated with the frequency of IFN-γ+ natural killer cells in non-segmental vitiligo. • MiR-1469 downregulates proliferation viability and IFN-γ secretion of natural killer cells by inhibiting CD122. [ABSTRACT FROM AUTHOR]

Non-segmental vitiligo (NSV) is an autoimmune disorder due to the destruction of melanocytes, where cytokines like interleukin 17 (IL-17) and biomolecules like vitamin D play a theoretical role in pathogenesis. Previous studies in this regard yielded inconsistent results. This study aimed to compare the serum levels of IL-17 and vitamin D between NSV patients and healthy controls and to know the association of these biomarkers with disease activity and extent. This was a case-control study including adult patients with NSV and age and gender-matched healthy controls. Cases and controls with conditions likely to alter the serum levels of IL-17 and vitamin D were excluded. Serum levels of IL-17 were estimated by ELISA and vitamin D levels by chemiluminescence assay. 42 adult patients of NSV and 42 age and sex-matched healthy controls were recruited over a period of eighteen months. The mean value of serum vitamin D levels in the control group was 19.053 ± 5.340 ng/ml, whereas in the case group, it was 17.336 ± 6.931 ng/ml (P > 0.05). The mean value of serum IL-17 levels in the control group was 199.824 ± 51.244 pg/ml and 213.566 ± 69.018 pg/ml in the case group (P > 0.05). These molecules did not show any association with the disease activity and extent. In contrast to the previous studies, we could not establish the role of IL-17 in the pathogenesis of vitiligo. Furthermore, we could not find any association between vitamin D and vitiligo in our study, even though there is an inconsistent association between the two in the available literature. [ABSTRACT FROM AUTHOR]

Damage-associated molecular patterns (DAMPs) play a role in the pathogenesis of vitiligo. It has been established that the cold-inducible RNA-binding protein (CIRP), a member of the family of cold-shock proteins that respond to stress, is a DAMP molecule that promotes inflammation. The objective was to evaluate the serum and tissue CIRP expression in non-segmental vitiligo (NSV) patients. A sample of 40 participants, 20 NSV patients and 20 control groups of age- and sex-matched healthy individuals were included in this case–control study where the enzyme-linked immunosorbent assay was used in detecting the serum and tissue CIRP levels in participants. The serum and tissue CIRP levels significantly increased in NSV patients compared with the healthy controls, (165.35 ± 24.42, 226.29 ± 24.00 versus 59.81 ± 12.10, 105.86 ± 11.27 pg/ml, respectively) (P < 0.01). Serum and tissue CIRP are significantly correlated with each other (r = 0.641, P = 0.002). Except for a statistically significant positive correlation between CIRP tissue level and VASI (r = 0.539, P = 0.014), the CIRP Serum and tissue did not show any statistically significant correlations with different clinical parameters in patients. ROC curve shows that the cut-off point for serum and tissue CIRP level to differentiate between patients and controls was 86.5, 124.3 pg/ml, respectively, with 100.0% sensitivity, 100.0% specificity and 1.000 AUC for each of them. It is concluded that CIRP may have a crucial role in the pathogenesis of NSV and could be used as a marker for vitiligo and its extent with the need for further large-scale study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ziwei Du,1 Hepeng Wang,1 Yang Gao,1 Shumao Zheng,1 Xiaoli Kou,1 Guoqiang Sun,1 Jinxian Song,2 Jingfei Dong,3 Genhui Wang4 1Department of Dermatology, Hebei Academy of Traditional Chinese Medicine, Shijiazhuang, Hebei, 050031, People’s Republic of China; 2Department of Dermatology, Quyang County People’s Hospital, Baoding, People’s Republic of China; 3Department of Clinical Laboratory, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of China; 4Department of Dermatology, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yang Gao, Department of Dermatology, Hebei Academy of Traditional Chinese Medicine, No. 209 Jianhua South Street, Shijiazhuang, Hebei, 050031, People’s Republic of China, Tel +86-15833969687, Email gaoyang2218@163.comBackground: Non-segmental vitiligo is a common decolorized skin disease. The purpose of this study was to reveal the active components of Sijunzi decoction (SJZD) and the target genes for the treatment of non-segmental vitiligo.Methods: Based on TCMSP and GEO databases, effective components and targets of SJZD in the treatment of non-segmental vitiligo were revealed by network pharmacology. GO and KEGG were used to analyze the biological functions of SJZD targets. The Cytoscape-cytoHubba plugin was used to identify hub target genes. SsGSEA method was used to analyze the infiltration level of immune cells in non-segmental vitiligo. Molecular docking was performed to predict the interaction between active compounds and hub target genes. Finally, real-time PCR detection was also performed.Results: It was found that 104 active compounds may be effective ingredients in the treatment of non-segmental vitiligo. These 104 compounds acted on 42 differentially expressed target genes. KEGG analysis showed that target genes were significantly enriched in immune-related pathways such as MAPK and TNF signaling pathways. A total of 6 hub target genes (AKT1, CASP3, PPARG, SIRT1, TNF and TP53) were identified using the Cytoscape-cytoHubba plugin. Molecular docking showed that active compounds quercetin, kaempferol, formononetin and naringenin had good binding to hub target genes. We also found that Type 2 T helper cells, CD56bright natural killer cell and CD56dim natural killer cell infiltration levels were abnormal in non-segmental vitiligo and correlated with AKT1.Conclusion: The results of this study indicate that quercetin, kaempferol, formononetin and naringenin in SJZD may play an important role in the treatment of non-segmental vitiligo by acting on AKT1, CASP3, PPARG, SIRT1, TNF and TP53 to regulate immune cell infiltration and multiple signaling pathways.Keywords: Sijunzi decoction, non-segmental vitiligo, network pharmacology, molecular docking, immune, gene

Background: Vitiligo is a common autoimmune disease of skin depigmentation. The disease presents with many challenges, such as progression, resistance to treatment and recurrence. Recent studies reported a possible role of IL-15 in the pathogenesis, activity and recurrence of the disease. Objective: Evaluation of tissue and serum levels of IL-15 in nonsegmental vitiligo patients. Methods: This Case-control study included 31 participants; 20 vitiligo patients and 11 controls. In patient group, we took serum samples and three punch biopsies (3mm) from active and recurrent vitiliginous patches as well as non-vitiliginous skin. In control group, we took serum sample and one tissue biopsy. IL-15 was assessed by ELISA technique in all samples. Results: There was no statistically significant difference between IL-15 levels in tissue and serum of control group. All levels of IL-15 in patients were significantly higher than in control. In patients, level of IL-15 in serum was significantly higher than in active and stable patches but lower than in recurrent patches. IL-15 level, in recurrent patches, was significantly the highest of all parameters. Conclusion: IL-15 may have an important role in the pathogenesis, activity and mainly recurrence of vitiligo. It seems to be a potential therapeutic target to control the disease and prevent recurrence. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C>A), NRROS (c.197C>T) and HERC2 (c.10969G>A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families. [ABSTRACT FROM AUTHOR]

Greco-Arab medicine is an ancient system of medicine with greater treasure on therapeutics of vitiligo. The trial Unani formulations have not been scientifically explored for their safety and efficacy, but have been repeatedly prescribed by the great Unani physicians in the management of Baraṣ (vitiligo). Hence, these interventions were selected for the trial. In this randomized, controlled, open-label clinical trial, 82 participants with non-segmental vitiligo aged 18–40 years were block randomized to either receive Unani interventions or control for 16 weeks. Out of 82 participants, 42 were randomized to the Unani group and 40 were randomized to the control group. The primary outcome measure was change in vitiligo area scoring index (VASI), which was assessed on weeks 4, 8, 12 and 16. The secondary outcome measures included the patient's global assessment on VAS and investigator's global assessment based on photographic evaluation at baseline and after the treatment. Safety parameters included hemogram, LFTs, RFTs, CXR, ECG, urine, and stool examinations, which were evaluated at baseline and after the treatment. The per-protocol analysis was done on 30 participants in each group and the response in Unani group was not inferior to those receiving control group. The mean ± SD of vitiligo area scoring index (VASI) decreased from 4.09 ± 2.87 and 5.50 ± 5.73 at baseline to 3.13 ± 2.20 and 4.29 ± 4.95 at the end of the trial in both the Unani and control groups respectively. The study inferred that both the interventions are equally effective and well-tolerated in patients with non-segmental vitiligo. [ABSTRACT FROM AUTHOR]

Background: Unfolded protein response (UPR) is a misfolded protein that occurs because oxidative stress disrupts cellular redox potential that extends to the endoplasmic reticulum (ER). Binding immunoglobulin protein (BiP) and inducible heat shock protein (HSP70i) as ER chaperons play critical roles in melanocyte apoptosis. Our study aims to compare BiP and HSP70i as markers of UPR in patients with segmental vitiligo (SV) and non-segmental vitiligo (NSV). Methods: The subjects were composed of 64 patients diagnosed with vitiligo, of whom 33 had NSV and 31 had SV. Skin biopsy and immunofluorescence were performed. We used BiP and HSP70i as markers of UPR. Descriptive statistics were used to analyze the data. Results: UPR-BiP expression and UPR-HSP70i in the SV group was 2.66 ± 3.07 and 3.85 ± 4.92, respectively, with a p-value of 0.001 ( Conclusions: HSP70i is superior to BiP as a marker for expressing UPR.

Background Vitiligo is a progressive depigmentation of the skin with unclear etiology. Cell-mediated immunity has been suggested to play an important role in the pathogenesis of vitiligo’s progression. Melan-A has a high affinity for specific CD8+ T cells and is one of the critical markers for detecting damage to melanocytes. Our study aims to demonstrate the differences in Melan-A expression associated with apoptosis of melanocytes in patients with segmental vitiligo (SV) and those with non-segmental vitiligo (NSV). Methods A cross-sectional study with 64 patients diagnosed with vitiligo, of whom 33 had NSV and 31 had SV. Skin biopsy and direct immunofluorescence were used to examine Melan-A, and the TUNEL staining method was performed to examine melanocyte apoptosis in both groups. Group comparisons were conducted using appropriate statistical methods. Results Melan-A expression was significantly higher in the NSV group than in the SV group, and there was a significant difference between the two groups (p=0.001). The median of melanocyte apoptosis in the NSV group was relatively higher than in the SV group, and a significant difference was found between the two groups (p=0.001). The Spearman’s rank correlation test between Melan-A expression and melanocyte apoptosis in the NSV group was 0.767 (76.7%) and showed a significant relationship (p Conclusion Melan-A expression and melanocyte apoptosis are positively correlated. Higher Melan-A expression and melanocyte apoptosis in NSV indicates more severe vitiligo disease compared to SV.

Introduction/Background Ritlecitinib, a JAK3/TEC family kinase inhibitor, demonstrated efficacy in a Phase 2b trial of patients with NSV. Objectives To evaluate the efficacy and tolerability of ritlecitinib with or without nbUVB add-on therapy in patients with NSV. Methods In a Phase 2b trial, following a 24-week placebo-controlled dose-ranging period, patients with NSV received ritlecitinib 200 mg for 4 weeks then 50 mg for 20 weeks, with or without nbUVB phototherapy 2x/week. Missing data were handled using observed case (OC) and last observation carried forward (LOCF). Results 43 and 187 patients received ritlecitinib+nbUVB and ritlecitinib-monotherapy, respectively. Nine patients receiving ritlecitinib+nbUVB discontinued due to nbUVB group-specific efficacy criteria requiring >10% improvement in %change from baseline (CFB) in Total-Vitiligo Area Scoring Index (T-VASI) at Week 12. At Week 24, mean (90% CI) %CFB in Facial-VASI (F-VASI) was -69.6 (-79.1, -60.1) vs -55.1 (-59.4, -50.7) (OC; P =0.009) and -57.0 (-65.3, -48.7) vs -51.5 (-55.9, -47.1) (LOCF; P =0.158), for ritlecitinib+nbUVB vs ritlecitinib-monotherapy, respectively. 60.9% (43.1%, 77.2%) vs 29.2% (22.8%, 35.9%) (OC; P =0.007) and 44.4% (30.2%, 59.1%) vs 27.4% (21.7%, 33.4%) (LOCF; P =0.081) of patients, respectively, achieved ≥75% improvement in F-VASI. Mean (90% CI) %CFB in T-VASI at Week 24 was -46.8 (-54.5, -39.2) vs -24.5 (-28.1, -21.0) (OC; P <0.001) and -29.4 (-36.5, -22.2) vs -21.2 (-25.0, -17.4) (LOCF; P =0.043) for ritlecitinib+nbUVB vs ritlecitinib-monotherapy, respectively. 50.0% (33.3%, 66.7%) vs 15.2% (11.1%, 20.3%) (OC; P <0.001) and 32.6% (22.1%, 44.7%) vs 14.4% (10.6%, 19.0%) (LOCF, P =0.014) of patients, respectively, achieved ≥50% improvement in T-VASI. nbUVB addition to ritlecitinib was well-tolerated with no new safety signals. Conclusions Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well-tolerated. nbUVB may improve ritlecitinib efficacy. [ABSTRACT FROM AUTHOR]

Background: Topical tacrolimus is increasingly used nowadays in the treatment of vitiligo. Objective: We evaluated therapeutic outcomes of tacrolimus 0.03% in non‐segmental vitiligo (NSV). Patients and methods: Sixty‐three patients with NSV were divided into groups A and B. Group A received 0.03% tacrolimus ointment (n = 31) and group B received 1% hydrocortisone acetate ointment (n = 32) for 24 weeks. Vitiligo area and severity index (VASI) and repigmentation rates were determined at baseline and 4‐week intervals. Results: In group A, 24‐week VASI [0.5 (0.3, 1.95)] was significantly lower than baseline VASI [0.75 (0.5, 2.1); p = 0.030]. In group B, 24‐week VASI [0.75 (0.4, 2.3)] was not significantly different from baseline VASI [0.73 (0.4, 2.1); p = 0.111]. Repigmentation was observed in 14/31 (45.2%) of patients in group A versus 0/32 (0.0%) in group B (p < 0.001). Repigmentation was graded as poor in 6/31 (19.4%), fair in 4/31 (12.9%), good in 1/31 (3.2%), and excellent in 3/31 (9.7%). Conclusion: Repigmentation was achieved in 45% of patients with NSV following treatment with tacrolimus 0.03% monotherapy for 24 weeks. Tacrolimus‐induced repigmentation is more likely in patients with vitiligo vulgaris, head and neck lesions, skin phototype III, and young age. [ABSTRACT FROM AUTHOR]

Non-segmental vitiligo (NSV) is a chronic autoimmune disease characterized by progressive depigmentation of the skin. Oxidative stress (OS) has been proposed as one among the main principal causes in the development and establishment of a sustained autoimmune state in patients with NSV. However, the disease-associated OS biomarkers in clinical practice are not well studied. In this study, we found significantly reduced antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD)], total antioxidant capacity (TAC), and increased levels of lipid oxidation product malondialdehyde (MDA) and oxidative DNA damage byproduct [8-hydroxy-2-deoxyguanosine (8-OHdG)] in serum of NSV patients compared with healthy controls (HC). Serum TAC, MDA, and 8-OHdG levels were correlated with disease activity in all patients with NSV and much lower in patients receiving conventional treatment in the past 1 year compared to that without treatment. In addition, both serum MDA and 8-OHdG levels were significantly correlated with CXCL10 expression in patients with NSV. And the serum TAC, MDA, and 8-OHdG levels were also correlated with affected body surface area and Vitiligo Area Scoring Index score in patients with NSV. This study demonstrates dysregulated OS status in patients with NSV and provides the evidence that the serum TAC, MDA, and 8-OHdG have a capacity to indicate the activity and severity in patients with NSV.

Background: Vitiligo is an acquired chronic depigmenting disorder of the skin, characterized by the development of milky white macules and patches resulting from a selective loss of epidermal melanocytes. There are various theories about its pathogenesis and the etiology is multifactorial associating genetic and environmental factors together with metabolic and immune alterations. Objective: To demonstrate the role of circulating T regulatory cells (Treg) (specifically CD4+, CD4+25+, CD4+25+FoxP3) and serum level of IL-17 in pathogenesis of non-segmental vitiligo (NSV) in Egyptian patients. Patients and methods: This case-control study was carried out on eighty subjects in the period from January 2018 to March 2020, attending Dermatology, Andrology & STDs Outpatient Clinic of Mansoura University Hospital. Subjects were classified into two groups: Group (1): patients group included forty patients suffering from NSV (vitiligo patients group). Group (2): control group included forty persons who were selected from hospital workers with no personal or family history of vitiligo or systemic autoimmune diseases in their first-degree relatives. Results: After NBU-VB treatment, there was a highly statistically significant increase in CD4+%, CD4+25+% and CD4+25+FoxP3% expression with a mean of 12.1 ± 4 versus 10 ± 3.2, 3.5 ± 1.1 versus 3.2 ± 1 and 1.8 ± 0.6 versus 1.1 ± 0.3 when compared to before treatment levels respectively. Also, a highly statistically significant decrease in IL-17 level with the mean of 14.3 ± 4.1 versus 19.9 ± 6 pg/mL when compared to before treatment levels. There was a highly statistically significant positive correlation between CD4+25+% expression and CD4+% expression in vitiligo group before and after treatment. Conclusion: Lower CD4+%, CD4+25+% and CD4+25+FoxP3% expression and elevated serum levels of IL-17 positively were correlated with disease severity. [ABSTRACT FROM AUTHOR]

Introduction: Narrow-band (NB) ultraviolet B (UVB) phototherapy has been shown to halt disease progression in vitiligo, but whether there is any difference in the response to NB-UVB seen in patients with progressive vitiligo versus non-progressive vitiligo has not been evaluated. Objectives: To evaluate the effect of NB-UVB on progressive versus non-progressive non-segmental vitiligo. Study Design: Prospective observational comparative study. Duration: April 2016-November 2017. Methods: Adult patients having non-segmental vitiligo involving 2-50% body surface area were divided into two subsets; patients developing >5 lesions in the last 1 month or >15 lesions in the last 3 months (progressive vitiligo, Group I) and patients with static disease for the last 6 months (non-progressive vitiligo, Group II). Both groups were treated with NB-UVB for 6 months (26 weeks) cumulatively and its efficacy in halting disease progression, re-pigmentation, side effects and psychosocial impact were evaluated. Results: Nineteen out of 24 patients with progressive vitiligo had arrest of disease progression. Rest five patients developed lesions at a slower pace. Group II had earlier onset of re-pigmentation, while Group I had more NB-UVB fluence (34.73 J/cm2 vs 25.2 J/cm2, P value = 0.034), more time for the fluence to be fixed (P value = 0.001) and more pruritus (P value = 0.001). Conclusions: NB-UVB has the potential to halt disease progression in some patients with progressive vitiligo; but is associated with more total NB-UVB fluence and time taken for fixing it. Progressive vitiligo patients have more pruritus as compared to patients with non-progressive vitiligo. [ABSTRACT FROM AUTHOR]

Introduction/Background Pediatric Vitiligo affects 1.52% of 4-11-year-olds within the United States and 2.16% of 12-17-year-olds with non-segmental disease affecting 65% and 69% respectively (1). The FDA has not approved any medications for vitiligo for children younger than 12 years of age. Additionally, about one-third of pediatric vitiligo is segmental (1), and there is no FDA-approved topical agent for segmental vitiligo in any pediatric age group (2). Objectives: To identify the efficacy of 1.5% ruxolitinib cream for pediatric vitiligo in clinical practice. Methods: An IRB-exempted pediatric chart review was conducted addressing the usage of 1.5% ruxolitinib cream, currently FDA-approved for non-segmental vitiligo affecting 10% of body surface area or less for 12 years of age or older. All children and adolescents using topical 1.5% ruxolitinib cream including segmental, non-segmental, and mixed vitiligo including individuals up to age 17 years. Results: Twelve children were identified with topical usage of 1.5% ruxolitinib cream for vitiligo ages 3-16 years (average age: 10.75 years). Demographics included 9 males, 3 females and race/ethnicity included Black (n=1), Hispanic/Latin X (n=4), Indian (n=1), and White (n=6). Vitiligo subtype included: Non-segmental vitiligo (n=7), Mixed type vitiligo (n=1), and segmental vitiligo (n=4). Regarding treatment subgroup of Non-segmental vitiligo and the non-segmental component of the Mixed type included 8 children, average age of 10.4 years (range 3-15 years), including 5 children under the age of 12 years (one 3-year-old, two 9 year-olds, and two 10 yearolds). Treatment was once daily in 1 child and twice daily in 7 children. One was lost to follow-up. Of the 6 children with documented response, average maximum repigmentation occurred at 6.14 months (range 3-12 months), with five achieving complete repigmentation, one partial repigmentation with only a three-month trial. The average length of disease before treatment began was 1.25 years (1 month to 6 years). The onset of response was 1.57 months on average (range 1-3 months). The initial location of response was the face (n=3), arms (n=2), and abdomen (n=1). No adverse events were reported. Four children had a complete blood count while on medication, with no laboratory abnormalities, including the 3-year-old. Two had a parent with vitiligo. Four patients previously failed tacrolimus topically, two patients failed topical class 2 corticosteroids, and one previously failed narrowband UVB, with no notable difference in response in these patients. Regarding treatment subgroup of Segmental vitiligo including five SV patients average age 11.2 years (range 5-16 years). One had facial segmental, one face and neck lesion (solitary stripe), one chest/back, and one on the lower abdomen. The five year-old did not repigment after 6 months of neck application, but never developed poliosis. The ten-yearold with segmental disease for 6 years had no response. The eleven-year-old SV of the chest/back failed topical tacrolimus and responded with 40% repigmentation over 3 months, increasing to 90% after 5 months and 12 concurrent sessions of 308-nm laser. The 14-year-old developed slight poliosis, but started repigmenting within 3 weeks, with continuous usage and subtotal repigmentation at 14 months. The 16-year-old began to repigment after 1 month, with a concurrent weekly 308-nm laser, and subtotal repigmentation after 5 months. Repigmentation was One facial SV (12 treatments), one chest/back SV (12 treatments), and one NSV had concurrent 308-nm laser (24 treatments) with pulsed dexamethasone, without any notable adverse events. Two teenage males (ages 15 and 16 years) developed acne on sites of application on the face. Laboratory screening including complete blood count was normal during treatment for 2 patients evaluated. Conclusions: NSV responds to 1.5% topical ruxolitinib consistently, with a solitary patient responding to once daily, and efficacy in children as young as three years of age with no notable lab abnormalities in screened patients. Topical 1.5% ruxolitinib cream appears very effective in repigmenting SV in children if used twice-daily and in combination with 308-nm laser sessions in the first 6 months. Topical ruxolitinib can cause acne in teenagers with facial segmental vitiligo. Early institution of topical 1.5% ruxolitinib cream appears to have a rapid onset of repigmentation (average 1.57 months) and rapid complete response (6.14 months). Clinical trials of 1.5% topical ruxolitinib in children are needed to identify outliers and long term outcomes. Early institution of therapy appears to speed up the response. Adjunctive 308-nm laser is promising but requires placebo-controlled trials. [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Janus kinase (JAK) inhibition is a promising approach for the treatment of vitiligo. Here, we report the clinical efficacy and safety of upadacitinib (UPA), an oral JAK inhibitor, in a phase 2b multicenter, randomized, double-blind, placebo-controlled study of adults with extensive non-segmental vitiligo (NSV). Materials & Methods: Eligible patients were aged 18-65 years with NSV, a Facial Vitiligo Area Scoring Index (F-VASI) of ≥0.5, and a Total Vitiligo Area Scoring Index (T-VASI) of ≥5 at baseline. This 52-week study (NCT04927975) comprised 2 periods. In period 1, patients were randomly assigned to once daily UPA 22 mg (UPA22), UPA 11 mg (UPA11), UPA 6 mg (UPA6), or placebo (PBO) for 24 weeks of treatment. In a 28-week blinded extension (period 2), patients receiving UPA during period 1 continued their respective regimens; patients who received PBO in period 1 were pre-assigned to either UPA11 or UPA22. Clinical efficacy endpoints evaluated through week 36 included percent change from baseline (%CFB) in F-VASI (week 24, primary endpoint), reductions from baseline in F-VASI of ≥50% (F-VASI 50) and ≥75% (F-VASI 75), %CFB in T-VASI, and reduction from baseline in T-VASI of ≥50% (T-VASI 50). Safety data as of January 13, 2023 (data cutoff date) are presented. Results: Of the 185 patients enrolled in period 1, 165 (89.2%) continued to period 2. At baseline, 68% of patients had extensive vitiligo (T-VASI > 10), and 71% had active vitiligo. At week 24, the %CFB in F-VASI was greater with UPA11 (-35.6%) and UPA22 (-34.0%) vs PBO (-14.4%; nominal P = .005 and P = .013, respectively). A greater proportion of patients achieved F-VASI 50 and F-VASI 75 with UPA11 (38.3%, 19.1%) and UPA22 (39.5%, 14.0%) vs PBO (10.9%, 2.2%; nominal P < .05 for both doses and for both endpoints). Likewise, the %CFB in T-VASI was greater with UPA11 (-17.3%) and UPA22 (-20.7%) vs PBO (-6.4%; nominal P = .026 and P = .005, respectively). A higher percentage of patients achieved T-VASI 50 with UPA22 (11.6%) than with PBO (2.2%; nominal P = .027). UPA efficacy continued to improve through week 36, with %CFB in F-VASI for UPA6, UPA11, and UPA22 of -20.8%, -44.9% and -47.7%, respectively. At week 36, F-VASI 50 was achieved with UPA6, UPA11, and UPA22 by 34.2%, 54.3% and 61.5% of patients and F-VASI 75 by 15.8%, 40.0%, and 30.8%, respectively. At week 36, %CFB in T-VASI for UPA6, UPA11 and UPA22 were -24.3%, -32.0% and -37.6%, with 10.5%, 20.0% and 19.2% of patients, respectively, achieving T-VASI 50. Treatment-emergent adverse event (TEAE) rates were generally similar with UPA and PBO in period 1 (most common TEAEs: COVID-19, acne, fatigue, and headache) and were similar across treatment arms in period 2. One death adjudicated as undetermined/unknown cause and deemed by the investigator to have no reasonable possibility of being related to study drug occurred in the UPA22 group (period 1). One adjudicated event of nonfatal ischemic stroke occurred with UPA11 (period 2). There were no adjudicated events of venous thromboembolism, gastrointestinal perforation, or events of opportunistic infection, active tuberculosis, or malignancy. Conclusion: Treatment with UPA for 24 weeks resulted in greater improvements vs PBO in the clinical outcomes of adults with extensive NSV. Observed clinical efficacy continued to improve through week 36 with UPA treatment. UPA was generally well tolerated, with no new safety signals identified. [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Vitiligo has a considerable negative impact on patients' health-related quality of life (HRQoL). Patients often experience social stigma, low self-esteem, anxiety, and depression. Assessment of HRQoL is therefore recommended as part of the evaluation of disease severity and treatment benefits. Accordingly, the impacts of treatment with upadacitinib (UPA), an oral Janus kinase inhibitor, on a range of patient-reported HRQoL outcomes were evaluated as part of a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study in adults with non-segmental vitiligo. Materials & Methods: Adults aged 18-65 years with non-segmental vitiligo with a Facial Vitiligo Area Scoring Index score =0.5 and a Total Vitiligo Area Scoring Index score =5 at baseline were included in this 52-week study (NCT04927975). During a 24-week, double-blind, placebo-controlled treatment period (period 1), patients were randomly assigned to receive UPA 6 mg (UPA6), UPA 11 mg (UPA11), UPA 22 mg (UPA22), or placebo once daily (QD). Patient-reported HRQoL outcomes assessed at the week 24 primary analysis timepoint (ie, end of period 1) included change from baseline in vitiligo QoL (VitiQoL) total score (lower scores reflect better HRQoL), achievement of a Vitiligo Noticeability Scale (VNS) response of 4 ("a lot less noticeable") or 5 ("no longer noticeable"), change from baseline in Dermatology Life Quality Index (DLQI; lower scores reflect better HRQoL), change from baseline in Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores (where lower scores reflect less anxiety and/or depression), and achievement of a Patient's Global Impression of Change-Vitiligo (PaGIC-V) response of 1 ("much better") or 2 ("a little better"). Results: A total of 185 patients were enrolled in the study (UPA6 n=49; UPA11, n=47; UPA22, n=43; placebo n=46). Mean reductions in VitiQoL scores from baseline to week 24 with UPA22 (-6.6) and UPA6 (-7.5) were numerically larger than with placebo (-5.5), although not statistically significant. At week 24, more patients treated with UPA22 reported a VNS response of "a lot less noticeable" or "no longer noticeable" than with placebo (11.6% vs 0%, respectively; P < .05). Mean reductions in DLQI scores from baseline to week 24 were significantly larger with UPA22 than with placebo (-2.2 vs -0.6; P < .05). HADS anxiety scores decreased from baseline to week 24 in the UPA6 and UPA22 groups, with similar reductions in HADS depression scores observed for the UPA11 and UPA22 groups; changes in HADS scores were not significantly different vs placebo. A significantly greater proportion of patients achieved a PaGIC-V response of "much better" or "a little better" with any UPA dose vs placebo: UPA6 (34.7%), UPA11 (55.3%), and UPA22 (60.5%) vs placebo (19.6%; P < .05 vs placebo for all UPA doses). Conclusion Among adults with non-segmental vitiligo, 24 weeks of treatment with UPA at all doses resulted in improvements compared to placebo in patient impressions of disease improvement based on PaGIC results. These initial findings suggest that UPA22 may improve patient HRQoL and perceptions of vitiligo noticeability; longer term data from the extension phase of this study will further clarify the impact of UPA treatment on QoL. [ABSTRACT FROM AUTHOR]

Abstract Background The macrophage migration inhibiting factor (MIF) is a protein that promotes the activation of immune cells and the production of other proinflammatory cytokines such as TNF‐α, IL‐1β, and IFN‐γ, which have proposed to play an essential role in the pathogenesis of vitiligo. The study aimed to assess the association between MIF polymorphisms (−794 CATT5‐8 and −173 G>C), MIF in situ expression, and MIF serum concentrations with susceptibility and disease activity in patients with non‐segmental vitiligo (NSV) from western Mexico. Methods The study included 111 patients with NSV and 201 control subjects. Genotyping was performed by conventional PCR (−794 CATT5‐8) and PCR‐RFLP (−173 G>C) methods. MIF mRNA expression was quantified by real‐time PCR and MIF serum concentrations were determined by ELISA kit. Histopathological samples were analyzed by automated immunohistochemistry. Results The MIF polymorphisms were associated with NSV susceptibility. Serum concentrations of MIF were higher in patients with active NSV and correlated negatively with the years of evolution. The depigmented skin from patients with active vitiligo showed a high expression of MIF. Conclusion MIF polymorphisms increase the risk of NSV in the western Mexican population. The serum concentrations of MIF and in situ expression are associated with active NSV.

Background: Vitiligo is a common autoimmune skin disorder, which is characterized by incomplete penetrance and genetic heterogeneity. It is classified into two types: segmental and non-segmental, and most cases suffer from non-segmental vitiligo. The disease affects about 2-10 in 1000 people in different population with no sex predilection. Furthermore, the genetics of vitiligo cannot be described by Mendelian pattern of inheritance. We herein report three female relatives (niece, aunt, grandmother) with non-segmental vitiligo in a family. Case description: The symptoms and severity of the disease varied between the cases. Incomplete penetrance was completely evident in this family. The grandmother had not received any treatment, but the aunt and niece were receiving medication and phototherapy. However, these treatments were not beneficial for them. Conclusion: Currently there is no effective treatment or screening method for vitiligo. Thus, genetic counseling, risk determination and identification of other genetic contributors could be beneficial.

Background: The treatment of vitiligo is often challenging and requires a multi-modality approach. Fractional carbon dioxide (FCO2) laser has been studied as an adjuvant therapy in cases of vitiligo. Autologous platelet-rich plasma (PRP) is rich in growth factors, which may contribute to the growth of melanocytes, and thus help in the repigmentation of vitiligo patches. We aimed to study the combination of these two modalities for the treatment of vitiligo. Aims and Objective: The aim of this study was to compare the efficacy and safety of FCO2 laser with PRP and FCO2 laser alone as an adjuvant therapy in stable non-segmental vitiligo (NSV) patients. Settings and Design: A prospective, randomized, comparative, open-label interventional study was carried out for a period of 18 months from December 2017 to June 2019, at a tertiary care hospital. Materials and Methods: Seventy patients with stable, NSV were assessed for eligibility; 66 patients were randomized equally into two groups. Group A received treatment with FCO2 laser with intralesional PRP, whereas Group B was treated with FCO2 laser alone. Patients in both the groups were treated with one therapy session and were followed up monthly for a period of 3 months. All the patients received topical psoralen with ultraviolet A (UVA) PUVA-sol treatment. Baseline and monthly assessments were done by VITILIGO AREA SEVERITY INDEX and standardized photographs. Results: VASI score reduction was significantly more in the Group A with (mean ± standard deviation [SD]) 9.5 ± 0.22, 5.8 ± 1.12, and 3.6 ± 1.81 as compared to Group B 11.9 ± 2.83, 9.9 ± 3.11, and 8.9 ± 3.46 at each subsequent follow-up visits, respectively. Side effects such as burning sensation, erythema, and crusting were seen less frequently and lasted for a short period in Group A in comparison to those in Group B. Conclusion: Combination of FCO2 laser and autologous intralesional PRP has a synergetic effect in treating patients with vitiligo as an adjuvant therapy with minimal adverse effects. [ABSTRACT FROM AUTHOR]

Background: The macrophage migration inhibiting factor (MIF) is a protein that promotes the activation of immune cells and the production of other proinflammatory cytokines such as TNF‐α, IL‐1β, and IFN‐γ, which have proposed to play an essential role in the pathogenesis of vitiligo. The study aimed to assess the association between MIF polymorphisms (−794 CATT5‐8 and −173 G>C), MIF in situ expression, and MIF serum concentrations with susceptibility and disease activity in patients with non‐segmental vitiligo (NSV) from western Mexico. Methods: The study included 111 patients with NSV and 201 control subjects. Genotyping was performed by conventional PCR (−794 CATT5‐8) and PCR‐RFLP (−173 G>C) methods. MIF mRNA expression was quantified by real‐time PCR and MIF serum concentrations were determined by ELISA kit. Histopathological samples were analyzed by automated immunohistochemistry. Results: The MIF polymorphisms were associated with NSV susceptibility. Serum concentrations of MIF were higher in patients with active NSV and correlated negatively with the years of evolution. The depigmented skin from patients with active vitiligo showed a high expression of MIF. Conclusion: MIF polymorphisms increase the risk of NSV in the western Mexican population. The serum concentrations of MIF and in situ expression are associated with active NSV. [ABSTRACT FROM AUTHOR]

Introduction: Non-segmental vitiligo (NSV) is an immune-mediated skin depigmentation disease. Cytokine-mediated interaction between T lymphocytes and melanocytes leads to death of melanocytes, causing a defect in melanin synthesis and thereby depigmentation. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in NSV. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is rarely studied. Aim: To study the immunophenotype of the different T-helper/Treg cell subsets in patients with NSV, in comparison to healthy controls. Material and methods: A total of 80 patients with NSV and eighty age- and gender-matched healthy controls were recruited in this cross-sectional study. Disease activity was determined by vitiligo index of disease activity (VIDA) scoring. Peripheral blood mononuclear cells were separated by Ficoll-Paque density centrifugation, and T-cell immunophenotyping was done by flow cytometric analysis. Results: In patients with NSV, we observed an imbalance in T-cell immunophenotype, characterized by an increase in Th1 (p < 0.0001) and Th17 cells (p = 0.01). There is no difference in relative percentage of Th2/Treg cells, as compared to the healthy controls (p > 0.05). Conclusions: There is a significant immune-dysregulation with a preponderance of circulatory Th1/Th17 phenotype in NSV patients. [ABSTRACT FROM AUTHOR]

Polyglandular autoimmune syndrome (PAS) type 3 consists of autoimmune thyroid disease (AITD) coexisting with ≥1 non-thyroidal autoimmune disease (NTAID) other than Addison’s disease and hypoparathyroidism. We evaluated the prevalence and repertoire of thyroid hormones antibodies (THAb) in PAS-3 patients. Using a radioimmunoprecipation technique, we measured THAb (T3IgM, T3IgG, T4IgM, and T4IgG) in 107 PAS-3 patients and 88 controls (patients with AITD without any NTAID). Based on the selective coexistence of AITD with one NTAID (chronic autoimmune gastritis, non-segmental vitiligo or celiac disease), patients were divided into group 1 (chronic autoimmune gastritis positive, n = 64), group 2 (non-segmental vitiligo positive, n = 24), and group 3 (celiac disease positive, n = 15). At least one of the four THAb was detected in 45 PAS-3 patients (42.1%) and 28 controls (31.8%, P = 0.14), with similar rates in the three PAS-3 groups. The rates of T3Ab, T4Ab, and T3 + T4Ab were similar in groups 1 and 2, while in group 3, T3Ab was undetected (P = 0.02). In PAS-3 patients, the rate of levothyroxine treatment was greater in THAb-positive patients compared to THAb-negative patients (76.7 vs. 56.1%, P = 0.03, RR = 1.4, 95% CI 1.03–1.81). Not unexpectedly, levothyroxine daily dose was significantly higher in group 1 and group 3, namely in patients with gastrointestinal disorders, compared to group 2 (1.9 ± 0.4 and 1.8 ± 0.3 vs. 1.5 ± 0.2 μg/kg body weight, P = 0.0005 and P = 0.004). Almost half of PAS-3 patients have THAb, whose repertoire is similar if chronic autoimmune gastritis or celiac disease is present. A prospective study would confirm whether THAb positivity predicts greater likelihood of requiring levothyroxine treatment.

Polyglandular autoimmune syndrome (PAS) type 3 consists of autoimmune thyroid disease (AITD) coexisting with ≥1 non-thyroidal autoimmune disease (NTAID) other than Addison's disease and hypoparathyroidism. We evaluated the prevalence and repertoire of thyroid hormones antibodies (THAb) in PAS-3 patients. Using a radioimmunoprecipation technique, we measured THAb (T3IgM, T3IgG, T4IgM, and T4IgG) in 107 PAS-3 patients and 88 controls (patients with AITD without any NTAID). Based on the selective coexistence of AITD with one NTAID (chronic autoimmune gastritis, non-segmental vitiligo or celiac disease), patients were divided into group 1 (chronic autoimmune gastritis positive, n = 64), group 2 (non-segmental vitiligo positive, n = 24), and group 3 (celiac disease positive, n = 15). At least one of the four THAb was detected in 45 PAS-3 patients (42.1%) and 28 controls (31.8%, P = 0.14), with similar rates in the three PAS-3 groups. The rates of T3Ab, T4Ab, and T3 + T4Ab were similar in groups 1 and 2, while in group 3, T3Ab was undetected (P = 0.02). In PAS-3 patients, the rate of levothyroxine treatment was greater in THAb-positive patients compared to THAb-negative patients (76.7 vs. 56.1%, P = 0.03, RR = 1.4, 95% CI 1.03-1.81). Not unexpectedly, levothyroxine daily dose was significantly higher in group 1 and group 3, namely in patients with gastrointestinal disorders, compared to group 2 (1.9 ± 0.4 and 1.8 ± 0.3 vs. 1.5 ± 0.2 µg/kg body weight, P = 0.0005 and P = 0.004). Almost half of PAS-3 patients have THAb, whose repertoire is similar if chronic autoimmune gastritis or celiac disease is present. A prospective study would confirm whether THAb positivity predicts greater likelihood of requiring levothyroxine treatment. [ABSTRACT FROM AUTHOR]

Background Non-segmental vitiligo (NSV) results from autoimmune destruction of melanocytes. The altered levels of various cytokines have been proposed in the pathogenesis of vitiligo. However, the exact immune mechanisms have not yet been fully elucidated. Objectives To investigate the role of epidermal and systemic cytokines in active and stable NSV patients. Methods Serum levels of inflammatory cytokines were checked in 42 active and 30 stable NSV patients with 30 controls. The lesional, perilesional and normal skin sections were subjected to H&E staining. The mRNA expression of inflammatory cytokines and their respective receptors were assessed by quantitative PCR in lesional skin of both active and stable NSV skin. The MITF and IL-17A were immunolocalized in lesional, perilesional and normal skin tissue. Results Significant increase in the expression of inflammatory cytokines, IL-17A, IL-1β and TGF-β was observed in active patients, whereas no change was observed in stable patients. A marked reduction in epidermal thickness was observed in lesional skin sections. Significant increase in IL-17A and significant decrease in microphthalmia associated transcription factor (MITF) expression was observed in lesional and perilesional skin sections. Moreover, qPCR analysis showed significant alterations in the mRNA levels of IL-17A, IL-1β, IFN-γ, TGF-β and their respective receptors in active and stable vitiligo patient samples. Conclusion Increased levels of IL-17A and IL-1β cytokines and decreased expression of MITF suggested a possible role of these cytokines in dysregulation of melanocytic activity in the lesional skin and hence might be responsible for the progression of active vitiligo. [ABSTRACT FROM AUTHOR]

It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (HO) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm that represents the absolute concentration of HO was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of HO in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of HO was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of HO, whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of HO; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal HO is not increased in NSV as previously thought and may not be responsible for the oxidative stress that leads to the melanocytes destruction, the hallmark of vitiligo pathogenesis. [ABSTRACT FROM AUTHOR]

Vitiligo is a common established depigmentation skin disease characterized by the presence of activated T lymphocytes anti melanocytes within the skin. T-cell immunity mainly mediates the destruction of melanocytes and is one of the main mechanisms involved in the pathogenesis of non-segmental vitiligo. Our previous study had identified several differentially expressed miRNAs and found that the expression of miR-3940-5p was downregulated in vitiligo patients. According to the research findings, we hypothesized that the novel miRNA plays a potential role on human cutaneous T lymphocytes in the action mechanism of immune imbalance in vitiligo. [ABSTRACT FROM AUTHOR]

Accumulating studies have indicated that vitiligo, especially non-segmental vitiligo (NSV), is one kind of autoimmune diseases and CD4 T cells play important roles in the pathogenesis. However, there have been very limited data on the detailed changes of each of the CD4 T cell subsets in periphery in active NSV. To clarify this issue, we collected the peripheral blood mononuclear cells (PBMCs) from 30 patients with active NSV and 30 age- and sex-matched healthy controls. The percentages of circulating Th1, Th2, Th17 and Tregs were evaluated using flow cytometry and the expressions of their specific transcription factors T-bet, GATA3, RORγt and FOXP3 at mRNA level and protein levels were qualified by qPCR and flow cytometry, respectively. Meanwhile, the expression levels of IFN-γ, IL-4, TGF-β, and IL-17A in serum were measured. We found that in patients with NSV, the percentages and absolute numbers of circulating Th1 and Th17 were both significantly higher than those of healthy controls, while the percentages of Th2 and Tregs and absolute numbers showed no significant difference compared to healthy controls. Moreover, the ratios of Th1/Tregs and Th17/Tregs in circulation were both statistically elevated in active NSV. Similar results were got in qualification of their corresponding transcription factors at mRNA level and protein levels. Compared with healthy controls, the expression level of IL-17A was significantly increased in serum of patients with NSV, while the productions of IFN-γ, IL-4, TGF-β had no significant change. These data suggested that in circulating CD4 T cell subsets, Th1 and Th17 played the major role in cellular immunity in the progression of vitiligo. The immune lever in circulation was inclined to effector CD4 T cells not suppressor CD4 T cells that may result in the loss of self-tolerance to melanocytes. [ABSTRACT FROM AUTHOR]

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sharma et al.)

Although non-segmental vitiligo ( NSV) results from the autoimmune destruction of melanocytes, the detailed immune mechanisms have not yet been fully elucidated. Th17 cells have been identified to be implicated in human autoimmune diseases. In this study, the frequencies of peripheral blood Th17 cells and serum levels of IL-17A and Th17 cell-related cytokines were examined in 45 patients with active NSV compared to 45 race-, gender-, and age-matched healthy controls. Our results showed increased circulating Th17 cell frequencies and elevated serum IL-17A, TGF- β1, and IL-21 levels in patients with NSV. Meanwhile, the increased Th17 cell frequencies are positively correlated with serum TGF- β1 level, and the body surface area of lesions is positively correlated with elevated TGF- β1 and IL-21 levels and Th17 cell frequencies. Furthermore, positive correlation was identified between Th17 and Th1 cell frequencies in patients with NSV. These results further indicate the potential involvement of Th17 cells and the collaborative contribution of Th17 and Th1 in NSV development, and suggest that the elevated serum TGF- β1 and IL-21 levels could contribute to enhanced Th17 cell differentiation in NSV. [ABSTRACT FROM AUTHOR]

Vitiligo is a common depigmentary skin disease that may follow a pattern of multifactorial inheritance. The essential factors of its immunopathogenesis is thought to be the selective destruction of melanocytes. As a new class of microregulators of gene expression, mi RNA have been reported to play vital roles in autoimmune diseases, metabolic diseases and cancer. This study sought to characterize the different mi RNA expression pattern in the peripheral blood mononuclear cells ( PBMC) of patients with non-segmental vitiligo ( NSV) and healthy individuals and to examine their direct responses to thymosin α1 (Tα1) treatment. The mi RNA expression profile in the PBMC of patients with NSV was analyzed using Exiqon's miRCURY LNA microRNA Array. The differentially expressed mi RNA were validated by real-time quantitative polymerase chain reaction. We found that the expression levels of miR-224-3p and miR-4712-3p were upregulated, and miR-3940-5p was downregulated in the PBMC. The common clinical immune modulator Tα1 changed the mi RNA expression profile. Our analysis showed that differentially expressed mi RNA were associated with the mechanism of immune imbalance of vitiligo and that Tα1 could play an important role in changing the expression of these mi RNA in the PBMC of patients with NSV. This study provided further evidence that mi RNA may serve as novel drug targets for vitiligo therapeutic evaluation. [ABSTRACT FROM AUTHOR]

Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4+CD25+FoxP3+ Treg cells and invariant natural killer T ( iNKT) cells, as well as naïve and memory CD4+ and CD8+ T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4+ and CD8+ T cells and the percentage of CD4+CD25+FoxP3+ Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4+CD25+FoxP3+ Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV. [ABSTRACT FROM AUTHOR]