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Importance: Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. Objective: To examine the effectiveness, tolerability, and safety of erenumab, an anti-CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. Design, Setting, and Participants: This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024. Intervention: 140 mg of erenumab every 4 weeks for 12 weeks. Main Outcomes and Measures: The primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test. Results: A total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by -6.9 days (95% CI, -10.4 to -3.4 days; P < .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by -8.1 days (95% CI, -12.5 to -3.7 days; P < .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time. Conclusions and Relevance: These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT04419259.
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BACKGROUND: Understanding the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of rosacea might provide new therapeutic avenues for individuals with this disease. OBJECTIVE: To compare plasma levels of CGRP between individuals with rosacea and healthy controls. METHODS: In this cross-sectional case-control study conducted in Copenhagen, Denmark, we collected blood samples from the antecubital vein from adults with rosacea and from healthy controls. RESULTS: We enrolled 123 individuals with rosacea and 68 healthy controls. After adjusting for age and sex, plasma levels of CGRP were significantly higher in individuals with rosacea (mean, 95% confidence interval: 140.21 pmol/L, 128.50-151.92 pmol/L), compared with controls (110.77 pmol/L, 99.91-120.14 pmol/L, p = 0.002). Plasma levels of CGRP were not affected by age, sex, BMI, concomitant migraine, rosacea sub- or phenotype, concomitant disease or current treatment. LIMITATIONS: Participants were not age-, sex- and BMI-matched. CONCLUSIONS AND RELEVANCE: Elevated plasma levels of CGRP in individuals with rosacea suggest a role of CGRP in the pathogenesis of rosacea. Targeting CGRP signalling might hold therapeutic promise in people affected by this disease. GOV LISTING: NCT03872050.
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Background: An overlap between the skin disease rosacea and the headache disease migraine has been established; however, the magnitude of this overlap and the distribution between subtypes/phenotypes remains unclear. Objective: The aim was to determine the magnitude of the overlap between rosacea and migraine, and to determine which subtypes/phenotypes were present in patients with concomitant rosacea and migraine. Methods: In this cross-sectional study, 604 patients with a diagnosis of either rosacea or migraine were phenotyped through a face-to-face interview with clinical examination, to determine prevalence and phenotype of rosacea, and prevalence and subtype of migraine. Results: We found a prevalence of migraine of 54% in patients with rosacea, and a prevalence of rosacea of 65% in patients with migraine. Concomitant migraine was significantly associated with the rosacea features flushing (odds ratio = 2.6, 95% confidence interval = 1.4-4.7, p = 0.002), ocular symptoms (odds ratio = 2.4, 95% confidence interval = 1.5-3.9, p < 0.001), and burning (odds ratio = 2.1, 95% confidence interval = 1.3-3.4, p = 0.002), whereas papules/pustules were inversely related with concomitant migraine (odds ratio = 0.5, 95% confidence interval = 0.3-0.8, p = 0.006). No association was found between concomitant migraine and centrofacial erythema, rhinophyma, telangiectasia, edema, or dryness. Concomitant rosacea was not associated with any specific migraine subtype in patients with migraine. Conclusion: This study highlights a substantial overlap between rosacea and migraine, particularly in patients with certain rosacea features. Individuals with rosacea should be asked about concomitant migraine, and comorbidities should be considered when choosing between treatments.
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Importance: Four distinct rosacea subtypes have traditionally been recognized, but the frequency of these subtypes among patients with rosacea remains unknown. Objective: To assess the frequency of 4 rosacea subtypes. Data Sources: This systemic review and meta-analysis included a search of 2 databases, PubMed and Embase, from inception of the databases to November 2, 2021. The search was filtered to include only studies of human participants published in English, French, and German. Study Selection: Studies were screened independently by 2 of the authors and were included if they were original with a sample size of 25 or more patients and reported absolute numbers or frequency of patients affected by rosacea subtypes. Studies that did not report sufficient data to calculate the proportions of subtypes were excluded. Data Extraction and Synthesis: Data extraction was performed independently and in duplicate by 2 of the authors, using the search term rosacea, according to the Preferred Reporting items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search term, objectives, and study protocol methods were defined before the study was initiated. A total of 292 studies were included for full-text assessment. Owing to the heterogeneity of the included studies, a random-effects model was used. Main Outcome and Measures: The main outcome was the proportion of patients with rosacea in each of the 4 major subtype groups defined by the 2002 National Rosacea Society classification system. Measures were absolute numbers or frequency of patients affected by each of the 4 rosacea subtypes. Results: A total of 39 studies examining 9190 patients with rosacea were included. The pooled proportion of erythematotelangiectatic rosacea was 56.7% (95% CI, 51.4%-62.0%), of papulopustular rosacea was 43.2% (95% CI, 38.8%-47.6%), of phymatous rosacea was 7.4% (95% CI, 6.1%-8.9%), and of ocular rosacea was 11.1% (95% CI, 6.7%-16.3%). Subtype distribution occurred equally among men and women except for phymatous rosacea, which was more prevalent in men. Studies from Africa showed the lowest proportion of erythematotelangiectatic rosacea. Differences in frequency of subtypes were observed when stratification by publication year was performed. Conclusion and Relevance: In this systematic review and meta-analysis, differences were found in rosacea subtypes by patient sex and by continent of origin and publication year of included studies. Erythematotelangiectatic and papulopustular rosacea were the most prevalent subtypes, but data should be interpreted with caution. Future studies should use the phenotype-based rosacea approach.