Therapeutic Efficacy of Sirolimus in Skeletal Manifestations of Gorham-Stout Disease in Adults: A Systematic Review

Gorham-Stout disease (GSD) is a rare condition characterized by progressive osteolysis and abnormal proliferation of lymphatic vessels. Its pathogenesis involves PI3K/AKT/mTOR pathway hyperactivation, providing a molecular basis for the application of targeted mTOR inhibitors such as sirolimus. This study aims to systematically review the efficacy and safety of sirolimus in treating adult patients with GSD presenting with skeletal manifestations. A systematic review was conducted in accordance with PRISMA 2020 guidelines using PubMed, Scopus, and EMBASE databases. Data from eligible case reports involving adult patients were extracted and analyzed through a qualitative narrative synthesis. Nine case reports involving 9 patients (mean age 39.3 years) met the inclusion criteria. Patients presented with extensive polyostotic involvement and severe complications such as massive pleural effusions or recurrent chylothorax. Sirolimus therapy yielded a therapeutic response in seven out of nine patients, including two complete and five partial responses. Data from these nine case reports suggest that the intervention may effectively halt active osteolysis and promote the resolution of effusions. While the therapy successfully arrested disease progression and induced significant localized bone formation, complete anatomical reossification of all osteolytic lesions was not achieved in the adult cohort. The treatment was generally well-tolerated, with manageable adverse events (acne, mild mouth sores, hyperlipidemia, nausea, and respiratory infection). Targeted sirolimus therapy serves as a potential therapeutic option for adult GSD. It necessitates a long-term, multimodal approach, including concurrent anti-resorptive and continuous imaging follow-up. Current evidence is limited by the reliance on heterogeneous case reports. Multicenter prospective registries or international collaborative cohorts are required to validate our results and establish standardized dosing guidelines.