Efficacy and safety of tretinoin 0.05% cream to prevent hyperpigmentation during narrowband UV-B phototherapy in patients with facial vitiligo: a randomized clinical trial.

BACKGROUND: Narrowband UV-B (NBUVB) phototherapy is the mainstay of vitiligo treatment, but hyperpigmentation is one of the limitations. Meanwhile, topical tretinoin is effective against pigmentary disorders. OBJECTIVE: To determine whether tretinoin 0.05% cream would prevent hyperpigmentation when patients with facial vitiligo underwent phototherapy. METHODS: A randomized, controlled, split-face trial was conducted. Adult patients with stable, non-segmental facial vitiligo were enrolled. The left/right sides of the face were randomly allocated to receive either topical tretinoin 0.05% cream or moisturizer twice daily. The entire face was subjected to NBUVB phototherapy twice weekly for 12 weeks. The degree of hyperpigmentation was assessed as the delta L* (brightness) value of the darkest spot in each side of the face at baseline and every 4 weeks. The degree of repigmentation was assessed. RESULTS: Twenty-five patients were enrolled; 21 completed the study. The delta L* value was significantly different between the two groups: -0.5% in the tretinoin group and -8.7% in the control group at 12 weeks (p = .002). Marked repigmentation was achieved in 15 patients of both groups. CONCLUSIONS: Tretinoin 0.05% cream prevented hyperpigmentation during NBUVB phototherapy in patients with facial vitiligo, and did not compromise the overall treatment response. TRIAL REGISTRATION: ClinicalTrials.gov NCT03933774.

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.

Systemic Comorbidities in Korean Patients with Rosacea: Results from a Multi-Institutional Case-Control Study.

Recent evidence links rosacea to systemic disease, but there are not enough methodologic studies addressing this association in Asians. Our aim was to identify rosacea comorbidities in Koreans and establish a reference database. A multi-center, case-control study was performed where a total of 12,936 rosacea patients and 12,936 age- and sex-matched control subjects were identified from 2007 to 2018. Logistic regression was performed to find significant association between rosacea and Sjögren syndrome (odds ratio [OR] 2.05; 95% confidence interval, 1.40-3.00), systemic sclerosis (OR 6.56; 95% CI, 1.50-28.7), rheumatoid arthritis (OR 1.72; 95% CI, 1.50-1.98), ankylosing spondylitis (OR 2.32; 95% CI, 1.42-3.84), autoimmune thyroiditis (OR 1.96; 95% CI, 1.40-2.73), alopecia areata (OR 1.77; 95% CI, 1.27-2.45), vitiligo (OR 1.90; 95% CI, 1.30-2.77), lung cancer (OR 1.54; 95% CI, 1.06-2.21), hepatobiliary cancer (OR 1.38; 95% CI, 1.06-1.77), alcohol abuse (OR 1.59; 95% CI, 1.05-2.39), diabetes mellitus (OR 1.11; 95% 1.02-1.19), obesity (OR 1.72; 95% CI, 1.22-2.41), allergic rhinitis (OR 1.65; 95% CI, 1.54-1.76), allergic conjunctivitis (OR 1.57; 95% CI, 1.27-1.94), chronic rhinosinusitis (OR 1.28; 95% CI, 1.14-1.42), herpes infection (OR 1.69; 95% CI, 1.53-1.86), and human papillomavirus infection (OR 2.50; 95% CI, 2.06-3.02). Higher odds for Sjogren syndrome, systemic sclerosis, ankylosing spondylitis, thyroiditis, vitiligo, hepatobiliary cancer, and obesity was exclusive in female subjects with rosacea, whereas increased prevalence of alopecia areata and alcohol abuse was confined to men. Only those who were 50 years and older exhibited higher odds for vitiligo, lung cancer, and gastroesophageal reflux disease while individuals younger than 50 were exclusively associated with hepatobiliary cancer, allergic conjunctivitis, and irritable bowel syndrome. Our study suggests that Koreans with rosacea are more likely to experience systemic comorbidity. Clinicians should acknowledge these interrelations and employ comprehensive care with an individual-based approach.

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.

Evaluation for Skin Cancer and Precancer in Patients With Vitiligo Treated With Long-term Narrowband UV-B Phototherapy.

Importance: Narrowband UV-B (NBUVB) phototherapy has been the mainstay in the treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established. Objectives: To investigate the risks of skin cancer and precancerous lesions among patients with vitiligo undergoing NBUVB phototherapy, based on the number of NBUVB phototherapy sessions. Design, Setting, and Participants: This nationwide population-based retrospective cohort study enrolled 60 321 patients with vitiligo 20 years or older between January 1, 2007, and December 31, 2017. Patients and outcomes were identified through nationwide cohort data from the Korean national health insurance claims database, and frequency matching by age and sex was performed. Exposures: The number of phototherapy sessions each patient received between 2008 and 2017. Patients were classified into 5 groups according to the number of phototherapy sessions (0 sessions, 20 105 patients; 1-49 sessions, 20 106 patients; 50-99 sessions, 9702 patients; 100-199 sessions, 6226 patients; and ≥200 sessions, 4182 patients). We also identifed patients who underwent at least 500 phototherapy sessions (717 patients). Main Outcomes and Measures: Primary outcomes were the development of actinic keratosis, Bowen disease, nonmelanoma skin cancer, or melanoma after enrollment. Results: Among the 60 321 patients with vitiligo in this study (33 617 women; mean [SD] age, 50.2 [14.9] years), the risks of Bowen disease (<50 sessions of phototherapy: hazard ratio [HR], 0.289 [95% CI, 0.060-1.392]; 50-99 sessions: HR, 0.603 [95% CI, 0.125-2.904]; 100-199 sessions: HR, 1.273 [95% CI, 0.329-4.924]; ≥200 sessions: HR, 1.021 [95% CI, 0.212-4.919]), nonmelanoma skin cancer (<50 sessions: HR, 0.914 [95% CI, 0.533-1.567]; 50-99 sessions: HR, 0.765 [95% CI, 0.372-1.576]; 100-199 sessions: HR, 0.960 [95% CI, 0.453-2.034]; ≥200 sessions: HR, 0.905 [95% CI, 0.395-2.073]), and melanoma (<50 sessions: HR, 0.660 [95% CI, 0.286-1.526]; 50-99 sessions: HR, 0.907 [95% CI, 0.348-2.362]; 100-199 sessions: HR, 0.648 [95% CI, 0.186-2.255]; ≥200 sessions: HR, 0.539 [95% CI, 0.122-2.374]) did not increase after phototherapy. The risk of actinic keratosis increased significantly for those who had undergone 200 or more NBUVB phototherapy sessions (HR, 2.269 [95% CI, 1.530-3.365]). A total of 717 patients with vitiligo underwent at least 500 sessions of NBUVB phototherapy; their risks of nonmelanoma skin cancer and melanoma were no greater than those of the patients who did not undergo NBUVB phototherapy (nonmelanoma skin cancer: HR, 0.563 [95% CI, 0.076-4.142]; melanoma: HR, not applicable). Conclusions and Relevance: Our results suggest that long-term NBUVB phototherapy is not associated with an increased risk of skin cancer in patients with vitiligo and that NBUVB phototherapy may be considered a safe treatment.