Sirolimus for Venous Malformations: A Systematic Review of Efficacy and Safety

Background: Venous malformations can cause substantial morbidity and long-term complications. There are no Food and Drug Administration (FDA)-approved therapies for the treatment of venous malformations. However, off-label use of sirolimus has demonstrated clinical benefit in these patients. This systematic review evaluates the efficacy and safety of sirolimus in the management of venous malformations. Methods and Results: A systematic literature search identified 26 studies comprising 98 patients treated with sirolimus for venous malformations. Most studies were case reports or case series (77%), with 15% prospective trials and 8% retrospective analyses. Sirolimus, primarily administered orally, yielded some level of clinical improvement in 72% of reported patients, with consistent symptomatic relief observed in coagulopathy, bleeding, anemia, pain, and improved function. However, reduction in the size of the malformation varied and treatment-limiting side effects were observed. Conclusions: Oral sirolimus is a promising treatment option for venous malformations, especially for those with deep venous malformations. A direct, targeted topical treatment could provide clinical benefit for the cutaneous manifestation without the risk of off-target effects as occur with oral sirolimus. Further prospective, controlled studies are warranted to elucidate sirolimus's role in managing venous malformations.