Bridging Molecular Mechanism and Clinical Practice in Vitiligo Treatment: An Updated Review.

BACKGROUND: Treatment of vitiligo seeks to achieve three goals: cessation of disease progression, regeneration of pigmentation, and prevention of recurrence. SUMMARY: Number of nonsurgical interventions are available that suppress the autoimmune response and regenerate the melanocytes from the reservoir: phototherapy including psoralen and ultraviolet A, narrowband ultraviolet B, and 308-nm excimer and 311-nm Titanium:Sapphire lasers; topical agents including topical calcineurin inhibitors, topical corticosteroids, and topical 5-fluorouracil; and systemic agents including corticosteorids, mycophenolate mofetil, cyclosporine, methotrexate, minocycline, afamelanotide, and antioxidants. In recent years, a great advance has been made in the understanding of pathogenesis of vitiligo, and JAK inhibitors are being investigated as a new treatment. Minimally invasive procedures such as fractional lasers or microneedling can help achieve the optimal treatment outcome when used properly. KEY MESSAGES: Our review describes various treatment modalities for vitiligo based on their molecular mechanism of action. Bridging the gap between molecular mechanisms and therapeutic options would be a valuable reference for physicians in clinical practice.

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.

Has the core outcome (domain) set for vitiligo been implemented? An updated systematic review on outcomes and outcome measures in vitiligo randomized clinical trials.

BACKGROUND: In 2015, a major achievement in vitiligo research was the development of an internationally agreed upon core outcome domain set for randomized clinical trials (RCTs). Three outcomes were identified as being essential: repigmentation, side-effects/harms and maintenance of gained repigmentation. Four items were further recommended for inclusion. The following recommendations then followed: repigmentation should be assessed by measuring the percentage of repigmentation in quartiles (0-25%, 26-50%, 51-79%, 80-100%) and cosmetic acceptability of the results should be assessed using the Vitiligo Noticeability Scale. OBJECTIVES: The primary objective of this study was to assess uptake of the core outcome domain set for RCTs in vitiligo. Secondary objectives were to update the systematic review on outcomes reported in vitiligo RCTs, and to assess whether repigmentation and cosmetic acceptability of the results were measured using the above-mentioned recommended scales. METHODS: We searched PubMed, Cochrane Library (CENTRAL and Systematic Reviews) and ClinicalTrials.gov for vitiligo RCTs between November 2009 and March 2021. Screening and data extraction were independently performed on title and summary by two researchers. All outcomes and outcome measures reported in eligible RCTs were retrieved and collated. RESULTS: In total, 174 RCTs were identified: 62 were published between 2009 and 2015, and 112 were published between 2016 and 2021.Thirty-eight different outcomes were reported. Repigmentation was the primary outcome in 89% of trials (150 of 169). Forty-nine different tools were used to measure repigmentation. Side-effects and harms were reported in 78% of trials (136 of 174). Maintenance of gained repigmentation was reported in only 11% of trials (20 of 174) and duration of follow-up varied greatly from 1 to 14 months. Cosmetic acceptability of the results and cessation of disease activity were assessed in only 2% of trials (four of 174). Quality of life of patients with vitiligo was assessed in 13% of trials (22 of 174). Finally, only 11 of 112 RCTs (10%) published between 2016 and 2021 reported all three essential core outcome domains (repigmentation, side-effects and maintenance of gained repigmentation) and none of the trials reported both essential and recommended core outcome domains. CONCLUSIONS: Efforts are still needed to close the gap between set recommendations and RCT outcome reporting.

Risk of autoimmune skin and connective tissue disorders after mRNA-based COVID-19 vaccination.

BACKGROUND: Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited. OBJECTIVE: To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination. METHODS: This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared. RESULTS: A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status. LIMITATIONS: Possible selection bias and residual confounders. CONCLUSION: These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.

Development and validation of the fingertip unit for assessing Facial Vitiligo Area Scoring Index.

BACKGROUND: Facial involvement of vitiligo is an important factor in a patient's life and has often been evaluated separately from body surface area in clinical trials. However, no reliable tools to measure facial vitiligo specifically are available thus far. OBJECTIVE: To develop and validate a practical instrument for assessing facial vitiligo. METHODS: The ratios of a hand to a fingertip unit (FTU) of 98 healthy volunteers (age range, 2-69 years) were calculated to define the FTU. Facial Vitiligo Area Scoring Index was measured as the sum of all FTUs of each vitiligo lesion on the face (range, 0-112 FTU). In the validation study, 6 raters evaluated 11 patients with facial vitiligo twice at an interval of 2 weeks. RESULTS: One hand was measured at 32.1 ± 1.3 FTU, which was highly consistent among subjects across different age groups, sexes, and races. Facial Vitiligo Area Scoring Index showed remarkably high accuracy (concordance correlation coefficient, 0.946; smallest detectable change, 2.2 FTU) as well as high intrarater reliability (intraclass correlation coefficient, 0.903; inter-rater reliability, 0.903). LIMITATIONS: Lack of dynamic validation of responsiveness. CONCLUSION: Facial Vitiligo Area Scoring Index using the FTU is an intuitive, precise, and reliable instrument for assessing the extent of facial involvement in vitiligo patients.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Excimer laser/light treatment of alopecia areata: A systematic review and meta-analyses.

BACKGROUND: The excimer laser/light (EL) has been reported to be effective for alopecia areata (AA), but its treatment response has not been systematically reviewed. OBJECTIVE: To determine the treatment response and safety of EL treatment of AA. METHODS: A comprehensive search of the Medline, EMBASE, Cochrane library, and Web of Science (from inception to December 31, 2018) was conducted to identify prospective clinical studies assessing the treatment response of EL for AA. The primary outcome was cosmetically acceptable hair regrowth (hair regrowth ≥75%); random-effects meta-analyses using generic inverse variance weighting were performed to estimate treatment responses. The study was registered with PROSPERO (CRD42019121092). RESULTS: Of 52 records initially identified, 13 full-text articles were finally assessed in terms of eligibility. A total of 9 prospective clinical studies (129 AA patients) including 5 controlled clinical trials were identified. Cosmetically acceptable hair regrowth was achieved in 50.2% (95% confidence interval 31.5%-68.9%; 8 studies). EL treatment significantly improved hair regrowth compared with untreated controls (relative risk 7.83; 95% confidence interval 2.11-29.11; 5 controlled clinical trials). No serious adverse effect was noted. CONCLUSIONS: EL treatment appeared to produce a favorable therapeutic response in AA patients. The use of EL should be encouraged for AA patients with the advantages of the non-invasiveness and no systemic effect.

A cross-sectional study on the association between vitamin D levels and caries in the permanent dentition of Korean children.

BACKGROUND: A recent study in Canada reported that vitamin D deficiency is associated with dental caries. Because Koreans have been reported to be deficient in vitamin D, we investigated the relationship between dental caries and reduced serum vitamin D levels in Korean children. The purpose of this study was to analyze the relationships between blood vitamin D [25(OH)D] concentrations and dental caries in the permanent dentition of Korean children. METHODS: Data were collected from the Korea National Health and Nutrition Examination Survey performed in 2008-2013. A total of 1688 children (10-12 years of age) were enrolled. Vitamin D intake was measured through analysis of 25-hydroxy vitamin D [25(OH)D] levels. Caries experience in permanent dentition was assessed using the decay-missing-filled teeth (DMFT) index and decayed-missing-filled (DMF) rate. Statistical analyses included complex samples Chi-square tests, complex samples logistic regression analyses, and Pearson's correlations. RESULTS: The group with 25(OH) D levels lower than 50 nmol/L had a higher proportion of children with caries in the permanent dentition and permanent first molar than the group with 25(OH)D levels of 50 nmol/L or more. When external factors, such as sex, were controlled, 25(OH)D levels were not significantly correlated with caries, but were significantly correlated with first molar caries. Children with 25(OH)D levels lower than 50 nmol/L were 1.295 times more likely to have first molar caries than those with 25(OH)D levels of 50 nmol/L or more. Additionally, 25(OH)D levels and DMFT were negatively correlated; however, the degree of correlation was not strong. CONCLUSIONS: The association between 25(OH)D and dental caries is still not clear. However, our findings suggested that vitamin D insufficiency may be a risk factor for dental caries.

All-Cause and Cause-Specific Mortality among Patients with Vitiligo: A Nationwide Population-Based Study in Korea.

Vitiligo is a common autoimmune skin disorder; however, there is limited information about risks of mortality among patients with vitiligo. Therefore, we aimed to investigate the mortality in patients with vitiligo. A population-based cohort study was conducted using the data linkage of the National Health Insurance Service database and the National Death Registry. Patients with incident vitiligo were matched with sociodemographic factors-matched controls without vitiligo in a 1:5 ratio. All-cause and cause-specific mortalities were compared between patients with vitiligo and controls. In total, 107,424 patients with incident vitiligo and 537,120 matched controls were included. The mortality rates were 34.8 and 45.3 per 10,000 person-years in patients and controls, respectively. Patients with vitiligo showed a significantly lower risk of mortality (adjusted hazard ratio = 0.75, 95% confidence interval = 0.72-0.78). The cause-specific mortality from infectious diseases, oncologic diseases, hematologic diseases, endocrine diseases, neurologic diseases, cardiovascular diseases, respiratory diseases, and renal/urogenital disease was significantly lower in patients with vitiligo. Patients with vitiligo were associated with a lower risk of mortality, suggesting that vitiligo-associated autoimmunity might contribute to reduced morbidity and mortality.