Abstract
Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, telangiectasia, and visceral vascular manifestations. Infectious and ischemic central nervous system (CNS) manifestations due to embolism through pulmonary arteriovenous malformations (PAVMs) represent the main causes of morbidity. To improve the phenotypic characterization of HHT with PAVM, we conducted a retrospective multicenter study of patients with HHT and at least 1 PAVM detected by chest computed tomography (CT) and/or pulmonary angiography, with particular attention to CNS and infectious manifestations. The study included 126 patients (47 men, 79 women), with a mean age of 43.1 +/- 17.4 years; 45 patients had a mutation of the ENG gene and 16 had a mutation of ACVRL1. PAVMs were diagnosed as a result of systematic screening procedures (29%), incidental imaging findings (15%), dyspnea (22%), or CNS symptoms (13%). The PAVMs were diagnosed at a mean age of 43 +/- 17 years, with a linear distribution of diagnosis between 20 and 75 years. Dyspnea on exertion was present in 56% of patients. Four patients had a hemothorax, including 1 during pregnancy. Fifty-three CNS events directly related to HHT (excluding migraine) were observed in 35% of patients: cerebral abscess (19.0%), ischemic cerebral stroke (9.5%), transient cerebral ischemic attack (6.3%), and cerebral hemorrhage (2.4%). The median age of onset was 33 years for cerebral abscesses (range, 11-66 yr), and 53.5 years for ischemic cerebral events (range, 2-72 yr). Migraine was reported in 16% of patients. The diagnoses of PAVM and HHT were made at the time of the cerebral abscess in 13 cases (54%). Forty-three percent of patients were hypoxemic at rest. Contrast echocardiography showed intrapulmonary right-to-left shunting in 87% of tested patients. PAVMs were seen on chest radiograph in 54% of patients, and on the CT scan in all patients. One hundred five patients (83%) underwent treatment of the PAVM, by percutaneous embolization (71%) and/or by surgical resection (23%). A high frequency of CNS and infectious complications was observed in this large series of patients with HHT-related PAVM. Physicians may not be sufficiently aware of the clinical manifestations of this orphan disorder. Patients diagnosed with HHT should be informed by physicians and patient associations of the risk of PAVM-related complications, and systematic screening for PAVM should be proposed, regardless of a patient's symptoms, familial history, or genetic considerations.
Highlights
Hereditary hemorrhagic telangiectasia (HHT), or RenduOsler-Weber disease, is an orphan disorder of genetic origin, characterized by recurrent epistaxis, mucocutaneous telangiectasia, and vascular visceral involvement[95,109] including arteriovenous communications that may develop in virtually any organ, especially in the lung
While everyday symptoms of the patients are dominated by epistaxis that may markedly alter their quality of life[91], more severe manifestations of the disease are due to the consequences of pulmonary arteriovenous malformations (PAVMs), and less often to liver or brain involvement
Diagnostic criteria for a definite or possible HHT were eventually not met in 7 patients, since isolated PAVM was the only criterion for the diagnosis of HHT, so 126 patients were included in the study
Summary
Hereditary hemorrhagic telangiectasia (HHT), or RenduOsler-Weber disease, is an orphan disorder of genetic origin, characterized by recurrent epistaxis, mucocutaneous telangiectasia, and vascular visceral involvement[95,109] including arteriovenous communications that may develop in virtually any organ, especially in the lung. According to the Curacao criteria, the diagnosis of HHT is considered definite when at least 3 out of 4 of the above criteria are present, and suspected when 2 criteria are present[109]. While everyday symptoms of the patients are dominated by epistaxis that may markedly alter their quality of life[91], more severe manifestations of the disease are due to the consequences of pulmonary arteriovenous malformations (PAVMs), and less often to liver or brain involvement. The first clinical manifestations of HHT were described successively by Benjamin Guy Babington in 18659 and John Wickham Legg[75] in 187641. Rendu distinguished the disease[106] from hemophilia, and Medicine Volume 86, Number 1, January 2007
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