Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study.

Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.

Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the leading causes of death in developing countries. Non-tuberculous mycobacteria (NTM) infections are rising and prey upon patients with structural lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. All mycobacterial infections require lengthy treatment regimens with undesirable side effects. Therefore, new antimycobacterial compounds with novel mechanisms of action are urgently needed. Published indole-2-carboxamides (IC) with suggested inhibition of the essential transporter MmpL3 showed good potency against whole-cell M.tb, yet had poor aqueous solubility. This project focused on retaining the required MmpL3 inhibitory pharmacophore and increasing the molecular heteroatom percentage by reducing lipophilic atoms. We evaluated pyrrole, mandelic acid, imidazole, and acetamide functional groups coupled to lipophilic head groups, where lead acetamide-based compounds maintained high potency against mycobacterial pathogens, had improved in vitro ADME profiles over their indole-2-carboxamide analogs, were non-cytotoxic, and were determined to be MmpL3 inhibitors.

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

BACKGROUND: Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. OBJECTIVE: 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). METHODS: Patients were randomized to once-daily oral ritlecitinib ± 4-week loading dose (200/50 mg, 100/50 mg, 30 mg, or 10 mg) or placebo for 24 weeks (dose-ranging period). Patients subsequently received ritlecitinib 200/50 mg 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. RESULTS: 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 50 mg groups with (-21.2 vs 2.1; P < .001) or without (-18.5 vs 2.1; P < .001) a loading dose and ritlecitinib 30 mg group (-14.6 vs 2.1; P = .01). Accelerated improvement was observed after treatment with ritlecitinib 200/50 mg in the extension period (n = 187). No dose-dependent trends in treatment-emergent or serious adverse events were observed across the 48-week treatment. LIMITATIONS: Patients with stable vitiligo only were excluded. CONCLUSIONS: Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo.

Prevalence of Malignancy in Adrenal Nodules With Heterogeneous Microscopic Fat on Chemical-Shift MRI: A Multiinstitutional Study.

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.

Incidental Adrenal Nodules in Patients Without Known Malignancy: Prevalence of Malignancy and Utility of Washout CT for Characterization-A Multiinstitutional Study.

BACKGROUND. Washout CT is commonly used to evaluate indeterminate adrenal nodules, although its diagnostic performance is poorly established in true adrenal incidentalomas. OBJECTIVE. The purpose of this study was to compare, in patients without a known malignancy history, the prevalence of malignancy for incidental adrenal nodules with unenhanced attenuation more than 10 HU that do and do not show absolute washout of 60% or more, thereby determining the diagnostic performance of washout CT for differentiating benign from malignant incidental adrenal nodules. METHODS. This retrospective six-institution study included 299 patients (mean age, 57.3 years; 180 women, 119 men) without known malignancy or suspicion for functioning adrenal tumor who underwent washout CT, which showed a total of 336 adrenal nodules with a short-axis diameter of 1 cm or more, homogeneity, and unenhanced attenuation over 10 HU. The date of the first CT ranged across institutions from November 1, 2003, to January 1, 2017. Washout was determined for all nodules. Reference standard was pathology (n = 54), imaging follow-up (≥ 1 year) (n = 269), or clinical follow-up (≥ 5 years) (n = 13). RESULTS. Prevalence of malignancy among all nodules, nodules less than 4 cm, and nodules 4 cm or more was 1.5% (5/336; 95% CI, 0.5-3.4%), 0.3% (1/317; 95% CI, 0.0-1.7%), and 21.1% (4/19; 95% CI, 6.1-45.6%), respectively. Prevalence of malignancy was not significantly different for nodules smaller than 4 cm with (0% [0/241]; 95% CI, 0.0-1.2%) and without (1.3% [1/76]; 95% CI, 0.0-7.1%) washout of 60% or more (p = .08) or for nodules 4 cm or larger with (16.7% [1/6]; 95% CI, 0.4-64.1%) and without (23.1% [3/13]; 95% CI, 5.0-53.8%) washout of 60% or more (p = .75). Washout of 60% or more was observed in 75.5% (243/322; 95% CI, 70.4-80.1%) of benign nodules (excluding pheochromocytomas), 20.0% (1/5; 95% CI, 0.5-71.6%) of malignant nodules, and 33.3% (3/9; 95% CI, 7.5-70.1%) of pheochromocytomas. For differentiating benign nodules from malignant nodules and pheochromocytomas, washout of 60% or more had 77.5% sensitivity, 70.0% specificity, 98.8% PPV, and 9.2% NPV among nodules smaller than 4 cm. CONCLUSION. Prevalence of malignancy is low among incidental homogeneous adrenal nodules smaller than 4 cm with unenhanced attenuation more than 10 HU and does not significantly differ between those with and without washout of 60% or more; wash-out of 60% or more has suboptimal performance for characterizing nodules as benign. CLINICAL IMPACT. Washout CT has limited utility in evaluating incidental adrenal nodules in patients without known malignancy.

Retrospective Cohort Study of 1947 Thyroid Nodules: A Comparison of the 2017 American College of Radiology TI-RADS and the 2015 American Thyroid Association Classifications.

OBJECTIVE. The objective of our study was to compare diagnostic accuracy and reliability of the 2017 American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and 2015 American Thyroid Association (ATA) classifications for thyroid nodules. MATERIALS AND METHODS. This study was a retrospective cohort study of 1947 consecutive thyroid nodules sampled with fine-needle aspiration (FNA) from 2007 to 2016. Reviewers assigned TI-RADS scores to all nodules while blinded to clinical outcome and histologic diagnosis and compared TI-RADS scores with nodule-specific ATA scores from the same cohort. Five blinded radiologists independently assigned TI-RADS scores to a subset of 151 nodules (interrater agreement). The primary outcome was a comparison of the diagnostic accuracy of the TI-RADS and ATA classifications using ROC curve analysis. The reference standard was cytopathologic diagnosis according to the Bethesda system. Interrater agreement was determined using intraclass correlation (ICC) and kappa statistics. RESULTS. Of 1947 sampled thyroid nodules, 31.8% (n = 620) met TI-RADS criteria for FNA, 28.0% (n = 545) met TI-RADS criteria for follow-up, and 40.2% (n = 782) met TIRADS criteria to be ignored. Applying the 2015 ATA criteria resulted in recommendations of immediate FNA procedures for more nodules than applying the 2017 TI-RADS (ATA vs TIRADS: 62.3% [1213/1947] vs 31.8% [620/1947], p < 0.0001). Diagnostic accuracies (AUCs: TI-RADS score, 0.684 [95% CI, 0.644-0.724]; ATA, 0.686 [95% CI, 0.646-0.725]) and false-negative rates (TI-RADS, 2.2% [43/1947]; ATA, 2.4% [47/1947]) for the two classifications were similar (p = 0.75). Overall interrater agreement was fair for both (ICCs: TI-RADS, 0.437 [95% CI, 0.357-0.520]; ATA classification, 0.460 [95% CI, 0.391-0.533]). CONCLUSION. The 2017 ACR TI-RADS and 2015 ATA classifications have similar diagnostic accuracies and interrater agreement, but TI-RADS results in fewer nodules being recommended for immediate FNAs and more nodules being recommended for imaging surveillance.

Melasma Treatment: An Evidence-Based Review.

BACKGROUND: Melasma is an acquired, chronic pigmentary disorder predominantly affecting women. It may significantly affect quality of life and self-esteem due to its disfiguring appearance. Multiple treatments for melasma are available, with mixed results. OBJECTIVE: The aim of this article was to conduct an evidence-based review of all available interventions for melasma. METHODS: A systematic literature search of the PubMed electronic database was performed using the keywords 'melasma' and/or 'chloasma' in the title, through October 2018. The search was then limited to 'randomized controlled trial' and 'controlled clinical trial' in English-language journals. The Cochrane database was also searched for systematic reviews. RESULTS: The electronic search yielded a total of 212 citations. Overall, 113 studies met the inclusion criteria and were included in this review, with a total of 6897 participants. Interventions included topical agents, chemical peels, laser- and light-based devices, and oral agents. Triple combination cream (hydroquinone, tretinoin, and corticosteroid) remains the most effective treatment for melasma, as well as hydroquinone alone. Chemical peels and laser- and light-based devices have mixed results. Oral tranexamic acid is a promising new treatment for moderate and severe recurrent melasma. Adverse events from all treatments tend to be mild, and mainly consist of skin irritation, dryness, burning, erythema, and post-inflammatory hyperpigmentation. CONCLUSIONS: Hydroquinone monotherapy and triple combination cream are the most effective and well-studied treatments for melasma, whereas chemical peels and laser- and light-based therapies are equal or inferior to topicals, but offer a higher risk of adverse effects. Oral tranexamic acid may be a safe, systemic adjunctive treatment for melasma, but more studies are needed to determine its long-term safety and efficacy. Limitations of the current evidence are heterogeneity of study design, small sample size, and lack of long-term follow-up, highlighting the need for larger, more rigorous studies in the treatment of this recalcitrant disorder.

Validation of a physician global assessment tool for vitiligo extent: Results of an international vitiligo expert meeting.

Currently, vitiligo lacks a validated Physician Global Assessment (PGA) for disease extent. This PGA can be used to stratify and interpret the numeric scores obtained by the Vitiligo Extent Score (VES). We investigated the interrater reliability of a 5-point PGA scale during an international vitiligo workshop. Vitiligo experts from five different continents rated photographs of non-segmental vitiligo patients with varying degrees of extent with the PGA score. Good interrater agreements (intraclass correlation coefficient >0.6) were observed between the raters overall and within each continent. All hypotheses to evaluate construct validity were confirmed. Median VES values per category were for limited 1.10 [IQR: 0.21-1.67], moderate 3.17 [IQR: 1.75-6.21], extensive 9.58 [IQR: 6.21-13.03] and very extensive 42.67 [IQR: 21.20-42.67]. Defined categories for vitiligo extent can be valuable for inclusion criteria and may impact future reimbursement criteria.

Disorders of Hypopigmentation

Hypopigmentation and depigmentation of the skin can be due to multiple causes and has a broad differential diagnosis. The most common cause of depigmentation worldwide is vitiligo. This disorder affects 1-2% of the world's population and is seen in all races. Vitiligo is an autoimmune disorder in which the predominant cause is an attack by CD8+ cytotoxic T cells on melanocytes in the epidermis. This condition can have a significant negative impact on the quality of life of affected individuals. Treatment options currently include psychological counseling, topical therapy, systemic therapy, phototherapy, surgical therapy, and depigmentation. In patients with stable, refractory disease, successful repigmentation has been achieved using mini-punch grafting, blister grafting, and non-cultured epidermal suspension (NCES) grafting. Emerging therapies include the Janus kinase (JAK) inhibitors ruxolitinib and tofacitinib. Further studies exploring the pathogenesis of vitiligo are warranted in order to optimize treatment for affected patients. J Drugs Dermatol. 2019;18(3 Suppl):s115-116.

Discovery of 2-aminoimidazole and 2-amino imidazolyl-thiazoles as non-xanthine human adenosine A3 receptor antagonists: SAR and molecular modeling studies.

A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl resin. The generated compound library was tested against all the human adenosine receptors subtypes. The 2-aminoimidazole derivatives (6a-6l) showed weak to moderate affinity towards the human adenosine receptors. Further modification to 2-aminoimidazolyl-thiazole derivatives (12a-12l) resulted in an improvement of affinity at adenosine A1, A2A and A3 receptor subtypes. Compound 12b was the most potent and selective non-xanthine human adenosine A3 receptor antagonist of this series. A receptor-based modeling study was performed to explore the possible binding mode of these novel 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives into human adenosine A1, A2A and A3 receptor subtypes.

Limitations of the 2015 ATA Guidelines for Prediction of Thyroid Cancer: A Review of 1947 Consecutive Aspirations.

Background: The 2015 American Thyroid Association (ATA) guidelines have been proposed to aid in the management of thyroid nodules by determining whether fine needle aspiration is indicated. Objective: To determine whether the ATA guidelines contribute to the overdiagnosis of thyroid cancer. Patients and Methods: This was a retrospective cohort study of ultrasound-imaged thyroid nodules (n = 1947) consecutively aspirated at a tertiary care center from 1 October 2009 to 22 February 2016. Nodules were retrospectively reviewed, assigned a 2015 ATA morphology, and placed into one of five 2015 ATA categories of risk (ATA-1, <1% risk of malignancy; ATA-2, <3% risk; ATA-3, 5% to 10% risk, ATA-4: 10% to 20% risk; ATA-5, >70% to 90% risk) by a reader who was blinded to cytology. ATA category was compared with cytopathology. The positive predictive value (PPV) of each ATA category was calculated with respect to cancer. Numbers needed to aspirate and Pearson correlations were calculated. Interrater agreement for ATA category across five readers was assessed. Results: The PPV for cancer increased by ATA category [category 1 to 5, respectively: 0% (0/14), 2% (4/249), 5% (36/733), 12% (104/850), 28% (28/101)]. The number needed to sample to detect one papillary cancer was 125 (ATA-2), 49 (ATA-3), 13 (ATA-4), and 5 (ATA-5). The overall interrater agreement for ATA score across all five readers was fair (intraclass correlation coefficient 0.460). Conclusions: The 2015 ATA guidelines stratify risk for thyroid cancer; however, the stratification system is overly optimistic regarding cancer detection rates for the higher-risk nodules, and there is only fair interrater agreement.

Oral Tranexamic Acid for the Treatment of Melasma: A Review.

BACKGROUND: Melasma is a common acquired disorder of hyperpigmentation that commonly affects those with skin of color. Tranexamic acid (TXA) is a novel treatment for melasma that has a multimodal mechanism of action. OBJECTIVE: To provide a comprehensive review of the literature regarding the evidence on the mode of action, safety profile, and efficacy of TXA in the treatment of melasma. MATERIALS AND METHODS: The literature was searched for publications on TXA in the treatment of melasma using MEDLINE, Scopus, and Google Scholar. RESULTS: Oral TXA has clearly demonstrated the efficacy for melasma in Asian skin, even in low doses (e.g., 500 mg daily) over short periods (8-12 weeks). It is also a safe therapeutic option, which is easy to administer with few and mild side effects. Studies have shown that TXA does not increase the thromboembolic risk, although patients should be screened carefully for contraindications and risk factors prior to commencement of the therapy. CONCLUSION: Oral TXA is a safe and efficacious treatment for refractory melasma. It should be considered in cases that are unresponsive to topical hydroquinone and combination topical therapy over a period of approximately 12 weeks and without contraindications to oral TXA.

Lichen planus pigmentosus and its variants: review and update.

Lichen planus pigmentosus (LPP) is considered a rare variant of lichen planus (LP). It is characterized by acquired dark brown to gray macular pigmentation located on sun-exposed areas of the face, neck, and flexures, commonly found in dark-skinned patients. In patients with LPP, an inflammatory lichenoid response results in marked pigmentary incontinence. It has been associated with hepatitis C virus, sun exposure, and contactants such as mustard oil and nickel. LPP-inversus affects fair and dark skin, predominantly involving flexural and intertriginous areas, while sun-exposed areas are spared; friction is an associated trigger. LPP along Blaschko's lines has been associated with susceptibility to genetic mosaicisms. LPP can present concomitantly with other variants of LP such as frontal fibrosing alopecia, as well as endocrinopathies, and autoimmune diseases. Treatment is difficult and consists of avoidance of triggers and topical and systemic medications in order to stop the inflammatory reaction and reduce pigmentation, improving aesthetic appearance and quality of life.

Imidazo[1,2-a]pyridines linked with thiazoles/thiophene motif through keto spacer as potential cytotoxic agents and NF-κB inhibitors.

A series of new imidazo[1,2-a]pyridine linked with thiazole/thiophene motif through a keto spacer were synthesized and tested for their cytotoxic potential against three human cancer cell lines including A549, HeLa and U87-MG using MTT assay. Compounds A2, A3, A4, C1 and C2 showed cytotoxicity against all the three cell lines. The selectivity index for compound A4 for A549 and HeLa cells was comparable to that of doxorubicin. Among the synthesized compounds, B5 showed the maximum inhibition of NF-κB activity as ascertained by NF-κB reporter assay (IC50 = 6.5 ±â€¯0.6 µM). Treatment of NCI-H23 cells (EGFR overexpressed, KRAS G12V mutant) with erlotinib and gefitinib along with compounds A4 and B5 indicated synergistic and additive potential of combination therapy.

The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo.

BACKGROUND: Treatment of vitiligo with narrowband ultraviolet B light (NBUVB) is an important component of the current standard of care. However, there are no consistent guidelines regarding the dosing and administration of NBUVB in vitiligo, reflected by varied treatment practices around the world. OBJECTIVE: To create phototherapy recommendations to facilitate clinical management and identify areas requiring future research. METHODS: The Vitiligo Working Group (VWG) Phototherapy Committee addressed 19 questions regarding the administration of phototherapy over 3 conference calls. Members of the Photomedicine Society and a group of phototherapy experts were surveyed regarding their phototherapy practices. RESULTS: Based on comparison and analysis of survey results, expert opinion, and discussion held during conference calls, expert recommendations for the administration of NBUVB phototherapy in vitiligo were created. LIMITATIONS: There were several areas that required further research before final recommendations could be made. In addition, no standardized methodology was used during literature review and to assess the strength of evidence during the development of these recommendations. CONCLUSION: This set of expert recommendations by the VWG is based on the prescribing practices of phototherapy experts from around the world to create a unified, broadly applicable set of recommendations on the use of NBUVB in vitiligo.

Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference.

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained repigmentation' are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.