Current Paradigm Shift in the Treatment of Hereditary Hemorrhagic Telangiectasia: A Narrative Review

Background Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem vascular disorder characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations (AVMs). Pathogenic variants in ENG (endoglin), ACVRL1 (activin receptor-like kinase 1, ALK1), and SMAD4 (SMAD family member 4) disrupt signaling in the bone morphogenetic protein (BMP) 9/10 and transforming growth factor-beta (TGF-β) pathways, resulting in dysregulated angiogenesis and excess vascular endothelial growth factor (VEGF) activity. Clinically, HHT most commonly presents with recurrent epistaxis and chronic gastrointestinal (GI) bleeding, frequently leading to iron deficiency anemia and reduced quality of life (QoL). Complications from visceral AVMs involving the lungs, brain, and liver may also occur. Early diagnosis and systematic screening are essential to reduce preventable morbidity. Methods This narrative review synthesizes current primary literature on the diagnosis, screening, and treatment of HHT, with particular emphasis on evolving systemic therapies, supportive care strategies, and procedural interventions. Evidence from international guidelines, randomized trials, observational cohort studies, and narrowly focused systematic reviews was evaluated to summarize contemporary management approaches. Results HHT diagnosis is made with the Curaçao clinical criteria, genetic testing, and targeted imaging to identify visceral vascular malformations. Screening recommendations emphasize early detection of pulmonary and cerebral AVMs and ongoing surveillance for anemia and other complications. Therapeutic strategies increasingly prioritize systemic therapy over repeated local procedures. Antiangiogenic agents including intravenous bevacizumab, pomalidomide, thalidomide, and oral pazopanib have demonstrated efficacy in reducing bleeding severity, improving hemoglobin levels, and decreasing transfusion requirements in moderate-to-severe disease. Supportive care remains foundational and includes iron replacement, selective blood transfusion, routine monitoring, and assessment of patient-reported QoL. In patients with refractory epistaxis, surgical interventions such as septodermoplasty or nasal closure may provide durable bleeding control. Endovascular and neurosurgical management may also be required for selected vascular complications. Conclusions Management of HHT is undergoing a paradigm shift toward mechanism-based systemic therapy integrated with multidisciplinary care. Advances in antiangiogenic and precision-medicine approaches are improving bleeding control and long-term outcomes. Early recognition, comprehensive screening, individualized therapy, and coordinated management across specialties are critical for optimizing care in this complex multisystem disease.