Pulmonary vascular manifestations of hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age. HHT commonly presents with epistaxis and telangiectasia, while visceral arteriovenous malformations are not uncommon. Mutations in the ENG, ACVRL1 and MADH4 genes account for 97% of all HHT cases, and it is recommended that genetic tests are used in combination with the clinical Curaçao criteria to confirm the diagnosis. HHT can be complicated by significant pulmonary vascular disease including pulmonary arteriovenous malformations, pulmonary arterial hypertension and high output cardiac failure. These are associated with substantial morbidity and mortality and therefore timely diagnosis is important to mitigate complications and optimise preventative strategies. This article outlines important advances in our understanding of the pathobiology of HHT and current recommendations regarding the diagnosis and screening of HHT with a specific focus on adult patients with pulmonary vascular disease. Important therapeutic advances, novel therapies on the horizon and unmet needs are also explored.