Pulmonary Vascular Manifestations of Hereditary Hemorrhagic Telangiectasia (Rendu-Osler Disease)

Abstract

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic disorder with autosomal dominance and variable penetrance, characterized by epistaxis, telangiectasia and visceral manifestations of the disease. The estimated minimal prevalence is 1/10,000 inhabitants. The diagnosis is established on clinical criteria, and may be further confirmed by the identification of causative mutations in either the ENG or the ACVRL1 gene coding for endoglin and ALK1, respectively. Pulmonary vascular manifestations of HHT include pulmonary arteriovenous malforma- tions (PAVMs; especially in patients with ENG mutations) and less frequently pulmonary hypertension (especially in patients with ACVRL1 mutations). In 15–33% of patients with HHT, PAVMs consist of abnormal communications between pulmonary arteries and pulmonary veins, causing right-to-left shunting, and thus, frequently hypoxemia and dyspnea on exertion, although PAVMs may remain asymptomatic and frequently undiagnosed unless complications occur. PAVMs result in severe and frequent complications often at a young age, which may reveal the diagnosis, e.g. transient ischemic attack and cerebral stroke (10–19% of patients), systemic severe infections and abscesses (including cerebral abscess in 5–19% of patients), and rarely massive hemoptysis or hemothorax. Infections in HHT are related to the right-to-left shunting that bypasses the pulmonary capillaries and facilitates the passage of septic or aseptic emboli into the systemic and especially cerebral circulation, and potentially to minor defects in innate immunity. Treatment of PAVMs based on transcatheter coil vaso-occlusion of the feeding artery significantly decreases right-to-left shunting, hypoxemia and dyspnea on exertion, and reduces the risk of systemic complications. Long-term follow-up is warranted after transcatheter vaso-occlusion of PAVMs due to frequent recanalization of treated PAVMs and development or growth of untreated PAVMs. Patients with HHT should be informed of the risk of PAVM and potentially severe complications occurring in heretofore asymptomatic subjects. All adult patients with HHT should be proposed systematic screening for PAVM, by contrast echocardiography (preceded by anteroposterior chest radiograph) or computed tomography of the chest. Pulmonary hypertension is rare in HHT, and may be due either to systemic arteriovenous shunting in the liver increasing cardiac output or be clinically and histologically indistinguishable from idiopathic pulmonary arterial hypertension. Pulmonary hypertension is detected by systematic examination of right cardiac cavities and tricuspid regurgitation flow at echocardiography, and the diagnosis is established by right heart catheterization.

Implications of Mutations of Activin Receptor-Like Kinase 1 Gene (<i>ALK1</i>) in Addition to Bone Morphogenetic Protein Receptor II Gene (<i>BMPR2</i>) in Children With Pulmonary Arterial Hypertension

“…Additionally, radionuclide perfusion lung scanning, computed tomography scan, and angiography were performed in the probands to exclude the possibility of arteriovenous shunt of lung and liver as a complication of HHT. 33,34 ALK1 Mutation In this study, 5 different ALK1 mutations were identified in 5 of the 21 unrelated probands with PAH, including 2 IPAH probands (11.8%) and 3 FPAH probands (75%) ( Table 2, Fig 1). The 3 FPAH probands with the ALK1 mutations included 1 child whose sister had the same mutation but was without symptoms (Proband 18).…”

A case of intrapulmonary transmission of air while transitioning a patient from a sitting to a supine position after venous air embolism during a craniotomy

“…These can present either in the form of a classic arteriovenous malformation, as with hereditary hemorrhagic teleangiectasia, [17][18][19] or during hyperdynamic circulation and/or when the alveolar-arterial partial pressure gradient of oxygen is high, as in the case of this patient whose lungs were ventilated with F I O 2 = 0.5.…”

The Intersection of Genes and Environment

“…2 Genetic mutations may impact PAH progression and prognosis. In HHT associated with PAH, carriers of ACVRL1 mutations present at a younger age and have worse outcome than patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations.…”