Clinical and radiological improvement in Gorham-Stout disease after sirolimus treatment.

Gorham-Stout disease (GSD) is a rare syndrome characterized by lymphatic malformations, mainly in bone structures, causing progressive osteolysis. Lymphatic endothelial cell proliferation depends on several growth factors that use the phosphoinositide-3 kinase (PI3K)/Akt pathway and converge on the mammalian target molecule of the rapamycin (mTOR) pathway. These findings have allowed treating GSD with mTOR pathway inhibitors such as sirolimus or everolimus. We present the case of a one-year-old female patient referred to our institution after a right femur fracture and progressive limb volume increase, disproportionately to the trauma. After several episodes of soft tissue infections, imaging studies showed pseudarthrosis, lytic lesions, and progressive loss of the right femur that ended in total absence. A femur biopsy showed lymphatic structures positive with D2-40 staining, diagnosing GSD. After six months of non-response to traditional treatments, the limb was disarticulated at the hip level, and oral sirolimus treatment was initiated, showing clinical and radiological improvement with minor lytic lesions and evidence of ossification after 20 months of treatment. Oral sirolimus treatment for GSD inhibits angiogenesis and osteoclastic activity, stimulating bone anabolism and leading to arrested osteolysis progression and improved ossification, quality of life, and patient prognosis. Therefore, sirolimus should be considered a therapeutic option for this rare disease.

Barnes-Saldaña F ，Venegas-Andrade A ，Colin-Martínez Ó ，Lizardo-Rodríguez A ，García-Romero MT ，Durán-McKinster C ... -  《-》

Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature.

Liang Y ，Tian R ，Wang J ，Shan Y ，Gao H ，Xie C ，Li J ，Xu M ，Gu S ... -  《BMC MUSCULOSKELETAL DISORDERS》

Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease.

Generalized lymphatic anomaly (GLA) and Gorham-Stout disease (GSD) are rare complicated lymphatic malformations that occur in multiple body sites and are associated with significant morbidity and mortality. Treatment options have been limited, and conventional medical therapies have been generally ineffective. Emerging data suggest a role for sirolimus as a treatment option for complex lymphatic anomalies. Disease response was evaluated by radiologic imaging, quality of life (QOL), and clinical status assessments in children and young adults with GLA and GSD from a multicenter systematic retrospective review of patients treated with oral sirolimus and the prospective phase 2 clinical trial assessing the efficacy and safety of sirolimus in complicated vascular anomalies (NCT00975819). Sirolimus dosing regimens and toxicities were also assessed. Eighteen children and young adults with GLA (n = 13) or GSD (n = 5) received oral sirolimus. Fifteen patients (83%) had improvement in one or more aspects of their disease (QOL 78%, clinical status 72%, imaging 28%). No patients with bone involvement had progression of bone disease, and the majority had symptom or functional improvement on sirolimus. Improvement of pleural and pericardial effusion(s) occurred in 72% and 50% of affected patients; no effusions worsened on treatment. Sirolimus appears effective at stabilizing or reducing signs/symptoms of disease in patients with GLA and GSD. Functional impairment and/or QOL improved in the majority of individuals with GLA and GSD with sirolimus treatment.

Ricci KW ，Hammill AM ，Mobberley-Schuman P ，Nelson SC ，Blatt J ，Bender JLG ，McCuaig CC ，Synakiewicz A ，Frieden IJ ，Adams DM ... -  《-》

Sirolimus on Gorham-Stout disease. Case report.

García V ，Alonso-Claudio G ，Gómez-Hernández MT ，Chamorro AJ ... -  《Colombia Medica》

The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies.

Ozeki M ，Nozawa A ，Yasue S ，Endo S ，Asada R ，Hashimoto H ，Fukao T ... -  《Orphanet Journal of Rare Diseases》