Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a vascular disorder with a global prevalence ranging from 1:5000 to 1:8000. It most commonly manifests through nosebleeds, which can be frequent and severe, exposing patients to major iron losses, anemia, and considerable physical and emotional distress. To date, no drug has received the FDA or EMA approval for preventing or treating HHT associated epistaxis, limiting access to therapies and intensifying the burden on patients and clinicians. Based on peer-reviewed evidence, the Second International HHT Guidelines provided a stepwise approach to help physicians manage HHT-related epistaxis highlighting the role of anti-fibrinolytic and systemic antiangiogenic drugs. However, experience from clinical practice and trials indicates marked variability in patient responses, and none of the recommended approaches has demonstrated sufficient placebo-controlled efficacy to gain regulatory approval. Striking insights in HHT physiopathology shed light on complex dysregulated signaling pathways with a triggering role not only by angiogenesis as widely recognized, but also by inflammation, injury and other stimuli, pointing to novel therapeutic targets. This review outlines current recommendations for preventing and managing nosebleeds in HHT patients, highlights the latest insights into the development of telangiectasic lesions, and discusses potential therapeutic treatments currently under clinical investigation.
Keywords: HHT; clinical trials; epistaxis; new therapeutic approaches.