Hereditary hemorrhagic telangiectasia (HHT) leads to hemorrhage, particularly nosebleeds (epistaxis), because of vascular telangiectasia and arteriovenous malformations.¹ Thrombotic conditions, including venous thromboemboli and ischemic stroke, are relatively common in patients with HHT.^2,3 These emergencies are managed by clinicians who may not be very familiar with HHT. Current guidance on the use of antiplatelet and anticoagulant agents in HHT is based on anecdotal evidence and expert opinion.⁴

Objectives/Hypothesis: To identify factors influencing the severity of epistaxis in hereditary hemorrhagic telangiectasia (HHT).Study Design: Participants with and without HHT were recruited from a specialist service and online following advertisement by the HHT Foundation International. Both groups were asked to complete a nonbiased questionnaire.Methods: The reported effects of specific treatments or lifestyle factors on epistaxis were assigned positive values if beneficial, negative values if detrimental, or zero if “no difference” and were summed to enable statistical analysis.Results: Epistaxis affected 649 of 666 (97%) participants with HHT and was significantly more frequent than in control participants. Specialist invasive treatments were reported as beneficial, laser therapy more frequently than cauterization. Medical treatments commonly used for HHT epistaxis (female hormones, antiestrogens, tranexamic acid, aminocaproic acid, nasal creams, and bevacizumab) also had significantly positive (beneficial) scores. Lifestyle and dietary factors were generally detrimental, but room humidification, nasal lubrication, and saline treatments were all reported as beneficial (95% confidence intervals greater than zero). Multiple food items were volunteered as being detrimental to epistaxis. The most frequently reported items were alcohol (n = 45; 6.8% of participants) and spices (n = 26, 3.9% of participants). Remaining foods reported to exacerbate epistaxis were also found to be high in salicylates (including red wine, spices, chocolate, coffee, and certain fruits), natural antiplatelet activity (garlic, ginger, ginseng, ginkgo biloba, and vitamin E15), or omega‐3 acids (oily fish, salmon).Conclusions: This study supports existing treatments and suggests lifestyle and dietary maneuvers that may also improve nosebleeds in HHT.Level of Evidence: 2c.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterised by multisystemic vascular dysplasia. Heritable pulmonary arterial hypertension (HPAH) is a rare but severe complication of HHT. Both diseases can be the result of genetic mutations in ACVLR1 and ENG encoding for proteins involved in the transforming growth factor-beta (TGF-β) superfamily, a signalling pathway that is essential for angiogenesis. Changes within this pathway can lead to both the proliferative vasculopathy of HPAH and arteriovenous malformations seen in HHT. Clinical signs of the disease combination may not be specific but early diagnosis is important for appropriate treatment. This review describes the molecular mechanism and management of HPAH and HHT.

In this review, we discuss the role of transforming growth factor-beta (TGF-β) in the development of pulmonary vascular disease (PVD), both pulmonary arteriovenous malformations (AVM) and pulmonary hypertension (PH), in hereditary hemorrhagic telangiectasia (HHT). HHT or Rendu-Osler-Weber disease is an autosomal dominant genetic disorder with an estimated prevalence of 1 in 5000 persons and characterized by epistaxis, telangiectasia and AVMs in more than 80% of cases, HHT is caused by a mutation in the ENG gene on chromosome 9 encoding for the protein endoglin or activin receptor-like kinase 1 (ACVRL1) gene on chromosome 12 encoding for the protein ALK-1, resulting in HHT type 1 or HHT type 2, respectively. A third disease-causing mutation has been found in the SMAD-4 gene, causing a combination of HHT and juvenile polyposis coli. All three genes play a role in the TGF-β signaling pathway that is essential in angiogenesis where it plays a pivotal role in neoangiogenesis, vessel maturation and stabilization. PH is characterized by elevated mean pulmonary arterial pressure caused by a variety of different underlying pathologies. HHT carries an additional increased risk of PH because of high cardiac output as a result of anemia and shunting through hepatic AVMs, or development of pulmonary arterial hypertension due to interference of the TGF-β pathway. HHT in combination with PH is associated with a worse prognosis due to right-sided cardiac failure. The treatment of PVD in HHT includes medical or interventional therapy.

Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disease associated with epistaxis, arteriovenous malformations and telangiectasias. Disease complications may result in premature death. We investigated life-expectancies of parents of HHT patients compared with their non-HHT partners using self- or telephone-administered questionnaires sent to their children. Patients were extracted from the databases of 2 participating HHT Centres: the Toronto HHT Database (Toronto, Canada) and the St. Antonius Hospital HHT Database (Nieuwegein, The Netherlands). Two hundred twenty five/407 (55 %) of respondents were included creating HHT- (n = 225) and control groups (n = 225) of equal size. Two hundred thirteen/225 (95 %) of the HHT group had not been screened for organ involvement of the disease prior to death. The life expectancy in parents with HHT was slightly lower compared to parents without (median age at death 73.3 years in patients versus 76.6 years in controls, p0.018). Parents with ACVRL 1 mutations had normal life expectancies, whereas parents with Endoglin mutations died 7.1 years earlier than controls (p = 0.024). Women with Endoglin mutations lived a median of 9.3 years shorter than those without (p = 0.04). Seven/123 (5 %) of deaths were HHT related with a median age at death of 61.5 years (IQ range 54.4–67.7 years). Our study showed that the life expectancy of largely unscreened HHT patients was lower than people without HHT. Female patients with Endoglin mutations were most strikingly at risk of premature death from complications. These results emphasize the importance of referring patients with HHT for screening of organ involvement and timely intervention to prevent complications.

Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease, is characterized by telangiectases and arteriovenous malformations (AVMs). Untreated AVMs, especially in the lungs—pulmonary AVMs (PAVMs)—can result in morbidity with a decreased life expectancy. We have investigated whether HHT patients, systematically screened for HHT-related organ involvement and treated if needed, have a similar survival as persons without HHT. We included all individuals screened for HHT between 2004 and 2016 with a genetically or clinically confirmed diagnosis (HHT group) or excluded diagnosis (non-HHT control group). The social security number was used to confirm status as dead or alive in December 2019. We included 717 HHT patients and 471 controls. There was no difference in survival between the HHT and the non-HHT control group. The HHT group had a life expectancy of 75.9 years (95% confidence interval (CI) 73.3–78.6), comparable to the control group (79.3 years, 95% CI 74.8–84.0, Mantel–Cox test: p = 0.29). In conclusion, the life expectancy of HHT patients systematically screened for HHT-related organ involvement and treated if needed in an HHT center of excellence was similar compared to their controls, justifying systematic screening and treatment in HHT patients.