Prevention of serious infections in hereditary hemorrhagic telangiectasia: roles for prophylactic antibiotics, the pulmonary capillaries-but not vaccination

Rodríguez-García et al. recently suggested that vaccination against Haemophilus influenzae, streptococcus pneumonia, and influenza should be considered a potential route to prevent the major deep-seated infections observed in some patients with hereditary hemorrhagic telangiectasia (HHT1). However, as pointed out by Al-Samkari et al.,2 there is no current evidence that patients with HHT are more prone to pneumoccal, hemophilus or influenza infections, or would benefit from any different approach to vaccination than the general population. Furthermore, we are concerned that a focus on these pathogens risks missing the relevant necessary foci that require a different approach-transient bacteremias, prophylactic antibiotics, and pulmonary capillary clearance functions.

HHT is caused by pathogenic variants in ENG, ACVRL1, and SMAD4, and usually results in vascular abnormalities (telangiectasia, arteriovenous malformations (AVMs)), recurrent bleeds, and anemia.3 A subgroup of HHT patients develop occasional deep-seated infections including brain abscesses.64 HHT members of the European Reference Network for Rare Vascular Diseases (VASCERN) have contributed strongly to published primary data, including recent manuscripts detailing clinical and microbiological features of 654 and 275 consecutive brain abscess cases. Multidisciplinary discussions on optimal prevention strategies have been taking place with our microbiological colleagues for more than a decade.7 Additionally, in June 2017, a VASCERN HHT workshop specifically addressed infection in HHT, with proceedings published earlier this year.8 The workshop was prompted both by considerations on the infections,73 and the 2016 publication of a manuscript demonstrating modified responses by macrophages from a myeloid-restricted murine model of HHT (Eng^fl/fl LysMCre mice).9

Key microbiological considerations are:

Currently unsolved questions include:

We agree with Al-Samkari et al.,2 that patients with HHT should have the usual vaccination strategies, as for members of the general population. In most countries, this includes pneumococcal and haemophilus influenza type b which can cause invasive disease and meningitis in any individual – but there is no evidence that HHT patients are at any more or less risk of these infections than the general population. They are however at a significantly increased risk of polymicrobial, deep-seated infections and abscesses especially if they have pulmonary AVMs. Reducing risks of the abscesses and other infections associated with pulmonary AVMs in HHT patients will require a more fundamental understanding of transient dental and surgical bacteremias, with a focus on pulmonary capillary clearance functions. It is important that the question of vaccination, which should be a normal part of infection prevention for everyone, does not obscure the need for a better focus on how to prevent these bacteremias from causing life altering, deep-seated infections.