Topical Intranasal Treatments for Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Systematic Review.

OBJECTIVE: To characterize the landscape of topical intranasal therapies in hereditary hemorrhagic telangiectasia (HHT) associated epistaxis, evaluate comparative effectiveness versus placebo, and define their potential adjunctive role within evolving treatment paradigms. DATA SOURCES: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the WHO-ICTRP were searched through May 2025. REVIEW METHODS: English-language studies of adults with HHT treated with topical agents for epistaxis were included. Study selection and data extraction were performed using Covidence in accordance with PRISMA guidelines. Risk of bias was assessed using Joanna Briggs Institute (JBI) checklists. Due to study heterogeneity, results were synthesized narratively. RESULTS: Of 310 records, 20 studies met inclusion (n = 590). Within-group reductions in Epistaxis Severity Score (ESS) were frequently observed; however, no topical class demonstrated consistent superiority over placebo in randomized controlled trials. Bevacizumab showed the largest reduction in ESS among case series (mean -3.3, n = 26). Across all agents, adverse events were uncommon and primarily limited to mild localized irritation. CONCLUSIONS: Current evidence does not support durable or clinically meaningful efficacy of topical intranasal monotherapy beyond placebo for HHT-related epistaxis. However, this absence of definitive efficacy reflects a structural evidence gap rather than a lack of biologic plausibility or patient-centered benefit. Given the phenotypic heterogeneity of HHT and the biologic variability in treatment response, topical agents remain clinically relevant as frontline adjunctive options for otolaryngologists managing this condition before systemic therapies become necessary. This review provides a framework for evidence-informed agent selection in the context of multimodal HHT care.