Infectious complications of vascular anomalies treated with sirolimus: A systematic review

Abstract

Background and objectivesInitially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition.MethodsThis was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1182 total patients and 316 infections (in 291 unique patients) were ultimately included.ResultsThe majority of infections were viral upper respiratory (n = 137, 54%), followed by pneumonia (n = 53, 20%), and cutaneous infections (n = 20, 8%). There were six total infection‐related fatalities, which all occurred in patients younger than 2 years. Two cases of Pneumocystis jirovecii pneumonia (PJP) were reported. These were infants with kaposiform hemangioendothelioma (KHE) who were also treated with steroids and did not receive PJP prophylaxis. Almost one‐third (n = 96, 32%) of infectious complications were graded 3–4 according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports.ConclusionsMost infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non‐severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.

Therapy with sirolimus in vascular anomalies: the experience of two Italian centers on 14 pediatric patients

“…Side effects reported in the literature are generally not severe and include mucositis in approximately 30% of patients, mild gastrointestinal symptoms, and dyslipidemia less frequently ( 10 , 13 ). An increased susceptibility to infections is also described, although these infections are generally not severe nor life-threatening ( 14 ).…”