Treatment Outcomes of Topical Calcineurin Inhibitor Therapy for Patients With Vitiligo: A Systematic Review and Meta-analysis.

IMPORTANCE: Topical calcineurin inhibitors (TCIs), including tacrolimus and pimecrolimus, have been widely used for the treatment of vitiligo; however, the efficacy of TCI monotherapy is often underestimated. OBJECTIVES: To estimate the treatment responses to both TCI monotherapy and TCI accompanied by phototherapy for vitiligo, based on relevant prospective studies, and to systematically review the mechanism of action of TCIs for vitiligo treatment. DATA SOURCES: A comprehensive search of the MEDLINE, Embase, Web of Science and Cochrane Library databases from the date of database inception to August 6, 2018, was conducted. The main key words used were vitiligo, topical calcineurin inhibitor, tacrolimus, pimecrolimus, and FK506. STUDY SELECTION: Of 250 studies initially identified, the full texts of 102 articles were assessed for eligibility. A total of 56 studies were identified: 11 studies on the TCI mechanism, 36 studies on TCI monotherapy, 12 studies on TCI plus phototherapy, and 1 study on TCI maintenance therapy. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data on study design, patients, intervention characteristics, and outcomes. Random-effects meta-analyses using the generic inverse variance weighting were performed for the TCI monotherapy and TCI plus phototherapy groups. MAIN OUTCOMES AND MEASURES: The primary outcomes were the rates of at least mild (≥25%), at least moderate (≥50%), and marked (≥75%) repigmentation responses to treatment. These rates were calculated by dividing the number of participants in an individual study who showed the corresponding repigmentation by the total number of participants who completed that study. RESULTS: In the 56 studies included in the analysis, 46 (1499 patients) were selected to evaluate treatment response. For TCI monotherapy, an at least mild response was achieved in 55.0% (95% CI, 42.2%-67.8%) of 560 patients in 21 studies, an at least moderate response in 38.5% (95% CI, 28.2%-48.8%) of 619 patients in 23 studies, and a marked response in 18.1% (95% CI, 13.2%-23.1%) of 520 patients in 19 studies after median treatment duration of 3 months (range, 2-7 months). In the subgroup analyses, face and neck lesions showed an at least mild response in 73.1% (95% CI, 32.6-83.5%) of patients, and a marked response in 35.4% (95% CI, 24.9-46.0%) of patients. For TCI plus phototherapy, an at least mild response to TCI plus phototherapy was achieved in 89.5% (95% CI, 81.1-97.9%) of patients, and a marked response was achieved in 47.5% (95% CI, 30.6-64.4%) of patients. CONCLUSIONS AND RELEVANCE: The use of TCIs, both as a monotherapy and in combination with phototherapy, should be encouraged in patients with vitiligo.

Classification of facial vitiligo: A cluster analysis of 473 patients.

Vitiligo has a substantial negative impact on quality of life in affected patients, especially those with the involvement of the face. However, the current system can barely distinguish between specific patterns of facial involvement except for the segmental type when focusing only on facial lesions. We classified facial vitiligo into three distinct subtypes using cluster analysis based on facial topography (n = 473): centrofacial vitiligo (72.9%), panfacial vitiligo (18.0%), and hairline vitiligo (9.1%). Centrofacial vitiligo was the most common type and is thought to comprise the typical facial involvement of generalized vitiligo. Panfacial vitiligo was a distinct subtype with onset in old age and less involvement of other body parts. Hairline vitiligo was another distinct subtype with onset in old age and a poor response to conventional phototherapy. A relevant classification system could help us to explore the causes, anticipate the prognosis, and manage the condition in patients with vitiligo.

Treatment of Laser Therapy-Induced Punctate Leukoderma Using a 308-nm Excimer Laser.

Punctate leukoderma presents as numerous, distinct, round or oval depigmented spots. Recently, laser therapy-induced punctate leukoderma associated with various Q-switched laser and carbon dioxide laser have been reported. A 25-year-old man presented with numerous, discrete, round, confetti-like, depigmented macules on his left neck. He had undergone 3 sessions of 532-nm Q-switched Neodymium: Yttrium-Aluminum-Garnet laser treatment for café-au-lait macules three years ago. After the last laser treatment session, the punctate leukoderma had been developed. We started treatment with the 308-nm excimer laser twice a week. After 7 months of treatment duration, complete repigmentation was achieved without serious adverse effects. We recommend the 308-nm excimer laser as an effective treatment modality for laser therapy-induced punctate leukoderma.

Phototherapy for Vitiligo: A Systematic Review and Meta-analysis.

Importance: References to the expected treatment response to phototherapy would be helpful in the management of vitiligo because phototherapy requires long treatment durations over several months. Objective: To estimate the treatment response of vitiligo to phototherapy. Data Sources: A comprehensive database search of MEDLINE, EMBASE, and the Cochrane library from inception to January 26, 2016, was performed for all prospective studies. The main keywords used were vitiligo, phototherapy, psoralen, PUVA, ultraviolet, NBUVB, and narrowband. Study Selection: All prospective studies reporting phototherapy outcome for at least 10 participants with generalized vitiligo were included. Of 319 studies initially identified, the full texts of 141 studies were assessed for eligibility, and 35 were finally included in the analysis. Of these, 29 studies included 1201 patients undergoing narrowband UV-B (NBUVB) phototherapy, and 9 included 227 patients undergoing psoralen-UV-A (PUVA) phototherapy. Data Extraction and Synthesis: Two reviewers independently extracted the following data: study design, number and characteristics of the participants, phototherapy protocol, and rate of repigmentation based on the quartile scale. Single-arm meta-analyses were performed for the NBUVB and PUVA groups. Sample size-weighted means were calculated using a random-effects model for the repigmentation rates of the included studies. Main Outcomes and Measures: The primary outcomes were at least mild (≥25%), at least moderate (≥50%), and marked (≥75%) responses on a quartile scale. Response rates were calculated as the number of participants who showed the corresponding repigmentation divided by the number of all participants enrolled in the individual studies. Results: The meta-analysis included 35 unique studies (1428 unique patients). For NBUVB phototherapy, an at least mild response occurred in 62.1% (95% CI, 46.9%-77.3%) of 130 patients in 3 studies at 3 months, 74.2% (95% CI, 68.5%-79.8%) of 232 patients in 11 studies at 6 months, and 75.0% (95% CI, 60.9%-89.2%) of 512 patients in 8 studies at 12 months. A marked response was achieved in 13.0% (95% CI, 2.1%-23.9%) of 106 patients in 2 studies at 3 months, 19.2% (95% CI, 11.4%-27.0%) of 266 patients in 13 studies at 6 months, and 35.7% (95% CI, 21.5%-49.9%) of 540 patients in 9 studies at 12 months. For PUVA phototherapy, an at least mild response occurred in 51.4% (95% CI, 28.1%-74.7%) of 103 patients in 4 studies at 6 months and 61.6% (95% CI, 20.2%-100%) of 72 patients in 3 studies at 12 months. In the subgroup analyses, marked responses were achieved on the face and neck in 44.2% (95% CI, 24.2%-64.2%), on the trunk in 26.1% (95% CI, 8.7%-43.5%), on the extremities in 17.3% (95% CI, 8.2%-26.5%), and on the hands and feet in none after at least 6 months of NBUVB phototherapy. Conclusions and Relevance: Long-duration phototherapy should be encouraged to enhance the treatment response in vitiligo. The greatest response is anticipated on the face and neck.

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

BACKGROUND: Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. OBJECTIVE: To investigate the incidence and risk factors of subsequent vitiligo after HSCT. METHODS: A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. RESULTS: A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. LIMITATIONS: Medical record review was not available. CONCLUSION: Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors.

Association Between Metabolic Syndrome and Atopic Dermatitis in Korean Adults.

Whether metabolic syndrome (MetS) and its components are risk factors for atopic dermatitis (AD) remains unclear. This study investigated the association between MetS and AD in Korean adults. Nationally representative data for 5,007 Korean adults, aged 19-40 years, from the cross-sectional Korea National Health and Nutrition Examination Survey 2010-2011 were analysed. AD in female patients was associated with MetS (p = 0.02) and increased triglyceride level (p = 0.05). After adjusting for confounding factors, the odds ratio for female participants with MetS was 2.92; for central obesity (waist circumference ≥ 85 cm), 1.73; and for hypertriglyceridaemia, 2.20. In this large-scale nationwide study in Korean adults, MetS and its components (central obesity and hypertriglyceridaemia) correlated positively with the presence of AD in women.

Association Between Obesity, Abdominal Obesity, and Adiposity and the Prevalence of Atopic Dermatitis in Young Korean Adults: the Korea National Health and Nutrition Examination Survey 2008-2010.

PURPOSE: Whether obesity is a risk factor for atopic dermatitis (AD) remains unclear. The aim of the present study was to investigate the association between obesity and AD in Korean young adults. METHODS: We included nationally representative data of 5,202 Korean adults aged 19-40 years, obtained from the cross-sectional Korea National Health and Nutrition Examination Survey 2008-2010. RESULTS: Single (unmarried) status was more frequently observed in AD patients (male, [P=0.0002] and female, [P<0.0001]). AD prevalence exhibited a U-shape trend in relation to body mass index (BMI), waist circumference (WC), and total body fat (BF) percentage, especially in young adult women. Women with BMI ≥25 kg/m², WC ≥80 cm, and highest quartile (Q4) of total BF percentage had the highest prevalence of AD. The odds ratio (OR) for participants with both BMI ≥25 kg/m² and WC ≥80 cm was 3.29 (95% confidence interval [CI] 1.71-3.55); therefore, having both general and abdominal obesity was considered a prominent risk factor for AD in young women. After adjustment for confounding factors, including age, smoking, alcohol drinking, exercise, vitamin D, income level, and single status, high BMI (≥30 kg/m²) (OR=4.08, 95% CI: 1.53-10.93), high WC (≥80 cm) (OR=2.05, 95% CI: 1.07-3.94), and high BF percentage (Q4) (OR=2.10, 95% CI: 1.24-3.57) were shown to be significantly associated with AD in young adult women. CONCLUSIONS: In this large-scale nation-wide study of Korean adults, obesity was positively related to the presence of AD in women. Our findings suggest that weight management may help prevent AD.

Hair regrowth through wound healing process after ablative fractional laser treatment in a murine model.

BACKGROUND AND OBJECTIVE: Alopecia is one of the most common dermatological problems in the elderly; however, current therapies for it are limited by low efficacy and undesirable side effects. Although clinical reports on fractional laser treatment for various alopecia types are increasing, the exact mechanism remains to be clarified. The purposes of this study were to demonstrate the effect of ablative fractional laser treatment on hair follicle regrowth in vivo and investigate the molecular mechanism after laser treatment. MATERIALS AND METHODS: Ablative CO2 fractional laser was applied to the shaved dorsal skin of 7-week-old C57BL/6 mice whose hair was in the telogen stage. After 12 mice were treated at various energy (10-40 mJ/spot) and density (100-400 spots/cm(2) ) settings to determine the proper dosage for maximal effect. Six mice were then treated at the decided dosage and skin specimens were sequentially obtained by excision biopsy from the dorsal aspect of each mouse. Tissue samples were used for the immunohistochemistry and reverse transcription polymerase chain reaction assays to examine hair follicle status and their related molecules. RESULTS: The most effective dosage was the 10 mJ/spot and 300 spots/cm(2) setting. The anagen conversion of hair was observed in the histopathological examination, while Wnt/ß-catenin expression was associated with hair regrowth in the immunohistochemistry and molecular studies. CONCLUSIONS: Ablative fractional lasers appear to be effective for inducing hair regrowth via activation of the Wnt/ß-catenin pathway in vivo. Our findings indicate that fractional laser treatment can potentially be developed as new treatment options for stimulating hair regrowth.