Oral dapsone in refractory rosacea: A prospective exploratory study defining a "high inflammatory burden" subtype and a testable precision treatment hypothesis.

Abstract

Refractory rosacea lacks evidence-based management. To preliminarily assess oral dapsone outcomes in strictly defined refractory rosacea, explore mechanisms via proteomics, and generate a testable subtyping hypothesis. This prospective, single-center, single-arm exploratory trial enrolled 124 refractory rosacea patients. Patients received dapsone 100 mg daily for 8 weeks. A nested substudy (N = 28) collected stratum corneum for proteomics. Using proteomic and clinical data, we defined a "high inflammatory burden" subtype and explored its association with treatment response. Patients failed a mean of 3.2 prior treatments. At week 8, 59.68% achieved Investigator Global Assessment 0/1. 82.26% achieved "deep remission" (both Investigator Global Assessment and Clinician Erythema Assessment improved)-a finding requiring interpretation within potential placebo effects (20% to 45%). Proteomics revealed 33 downregulated inflammation-related proteins. The "high inflammatory burden" subtype (54.03%) showed higher deep remission (88.06% vs 75.44%), absolute difference 12.62% (OR = 2.40, 95% CI: 0.925-6.23; P = .110), not reaching significance. Single-center, single-arm design. This exploratory study observed clinical improvements with oral dapsone in refractory rosacea and generated a testable hypothesis: the "high inflammatory burden" subtype may identify patients more likely to benefit. Providing a clear subtype definition, effect size estimates, and enrichment trial design, this study offers an actionable framework for future validation trials.