Infectious Complications of Vascular Anomalies Treated with Sirolimus: A
Systematic Review
Abstract
Background and Objectives: Initially developed as immunosuppressive
agents, 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. Methods: This 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 1181 total patients
and 315 infections (in 290 unique patients) were ultimately included.
Results: The majority of infections were viral upper respiratory (n=137,
54%), followed by pneumonia (n=52, 20%), and cutaneous infections
(n=20, 8%). There were 6 total infection-related fatalities, which all
occurred in patients younger than 2 years. Only 1 case of
Pneumocystis jirovecii pneumonia (PJP) was reported. This was in
an infant with KHE who was also treated with steroids and did not
receive PJP prophylaxis. Almost 1/3 (n=95, 32%) of infectious
complications were graded 3 to 4 according to CTCAE criteria. Details of
patient age, subtype of VA, and timing of infection were lacking from
many reports. Conclusions: Most 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.