A message on the lips

Abstract

Few systemic diseases present with such a diversity of cardiopulmonary manifestations as hereditary haemorrhagic telangiectasia (HHT), also known as Osler's disease or Rendu-Osler-Weber syndrome. HHT is one of the most common inherited diseases, with a prevalence of one in 5,000-10,000, and has been linked to mutations in at least five different genes, including endoglin and activated-receptor-like kinase (Alk)-1, both belonging to the transforming growth factor (TGF)-b superfamily of receptors [1]. Alk-1 and endoglin are abundantly expressed on endothelial cells and are involved in mediating the cellular effects of TGF-b and other members of the TGF-b superfamily. Loss-of-function mutations in the genes encoding for Alk-1 or endoglin cause the clinical syndrome of HHT, which is characterised by vascular dysplasia. The cardinal clinical features of HHT include mucocutaneous telangiectases, often prominently visible on the lips and tongue, and arteriovenous malformations (AVMs), which can involve several organs, such as liver, brain and lungs. Pulmonologists will encounter three main manifestations of HHT: pulmonary arterial hypertension; high cardiac output failure in the setting of large AVMs in the liver; and pulmonary AVMs. A forthcoming article by FAUGHNAN et al.[2], as part of the European Respiratory Journal's (ERJ) current series on pulmonary hypertension [2][3][4][5][6][7], will review the cardiopulmonary manifestations of HHT in detail.Pulmonary arterial hypertension and liver AVMs are predominantly seen in patients with Alk-1 mutations (also called HHT type 2) [8]. Isolated pulmonary arterial hypertension in patients with HHT is clinically and histologically indistinguishable from idiopathic pulmonary arterial hypertension, a disease that has been linked to mutations in another TGF-b superfamily receptor, termed bone morphogenetic protein receptor-II [9]. Many patients with HHT type 2, however, present with a distinct clinical picture, characterised by pulmonary hypertension and a state of high cardiac output caused by liver AVMs [10]. These patients are prone to developing refractory heart failure within weeks to months after presentation. Treating this condition is a major challenge and successful therapy often requires a combined approach, with embolisation of the liver AVMs to bring cardiac output back to a normal level [11] together with medical therapy of pulmonary hypertension.Pulmonary AVMs are another manifestation of HHT, occurring most often in patients with endoglin mutations (HHT type 1). With careful screening, including chest radiography, computed tomography and contrast echocardiography, pulmonary AVMs may be found in up to 50% of HHT patients ( fig. 1) [12]. These AVMs originate from the pulmonary rather than the bronchial arteries and are associated with the signs and complications of intrapulmonary right-to-left shunts. Smaller pulmonary AVMs are often clinically silent until the patients present with neurological catastrophes, such as ischaemic strokes or brain abscesses. Larger pul...

Management of pulmonary arteriovenous malformations in pulmonary hypertensive patients: a pressure to embolise?

“…However, most individuals with PAVMs have underlying hereditary haemorrhagic telangiectasia (HHT), now recognised to carry an independent risk of pulmonary hypertension (PH) [8]. HHT is inherited as an autosomal dominant trait, and is most commonly caused by mutations in the genes for endoglin (HHT type 1) or activin receptor-like kinase-1 (HHT type 2) [9].…”