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

摘要

Rodrguez-Garca 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 (HHT~(~(1))). 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.~(~(4)~(6)) 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 65~(~(4)) and 27~(~(5)) 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,~(~(3)~(7)) 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)).