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Updated: Jul 11, 2025
A Patient-Derived Xenograft Model for Venous Malformation
Published on: June 15, 2020
Infectious complications of vascular anomalies treated with sirolimus: A systematic review
Rachel Kalbfell1, Sally Cohen-Cutler2, Eric Grisham3
1Washington University School of Medicine, St. Louis, Missouri, USA.
Background And Objectives:
Initially 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.
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 1182 total patients and 316 infections (in 291 unique patients) were ultimately included.
Results:
The 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.
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.
Insights
Infections in vascular anomalies (VA) patients on mammalian target of rapamycin (mTOR) inhibitors are mostly mild viral respiratory types. Severe infections, fatalities, and Pneumocystis pneumonia are rare, but warrant monitoring in young children.
Area of Science:
- Oncology
- Immunology
- Pediatrics
Background:
- Mammalian target of rapamycin (mTOR) inhibitors are used for vascular malformations (VM) and tumors.
- Infectious complication rates in vascular anomalies (VA) patients on mTOR inhibitors are not well-defined.
Approach:
- Systematic review following PRISMA guidelines.
- Included 30 articles with 1182 patients and 316 infections.
Key Points:
- Most infections were viral upper respiratory (54%) and pneumonia (20%).
- Severe infections (CTCAE grade 3-4) occurred in 32% of cases.
- Infection-related fatalities (6) and Pneumocystis jirovecii pneumonia (2) were rare, primarily in infants.
Conclusions:
- Viral respiratory infections are the most common complications in VA patients on mTOR inhibitors.
- Bacteremia, fatalities, and PJP are rare but serious concerns.
- Further research is needed to guide infection prevention strategies.
