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

Abstract

Background: Gorham-Stout disease (GSD) is a rare disease characterized by bone lesions and osteolysis. Therapy usually involves surgical resection. Sirolimus (Rapamycin) is used in some patients with GSD but the efficacy and safety of Sirolimus remains unclear. We propose that Sirolimus may be a novel therapeutic for GSD and present a case and review of literature that supports this. Case presentation: We presented a 1-year-old boy with GSD involving osteolysis of the right humerus with fracture of the left femur complicated by an effusion in the right pleural cavity. X-rays showed osteolysis in the right clavicle. A large pleural effusion was observed on the right-side, and the left lung was significantly compressed. Xrays also showed a fracture of the left femur. A femoral biopsy was performed that showed necrotic tissue in the cortical bone and a large number of irregularly shaped capillaries that proliferated within the necrotic tissue. Dilated lymphatic vessels were seen adjacent to the cortex, with fibrous tissue hyperplasia. We prescribed sirolimus, which is an oral mTOR inhibitor, for two consecutive years. The boy recovered well without other progressive bone lesions and participates in normal daily activities. His growth and development are the same as that of his peers. Discussion and conclusion: Gorham-Stout disease is a rare and enigmatic disease characterized by the presentation of an intraosseous lymphatic anomaly (LM), which results in progressive bone resorption. Based on this case report and a literature review, we conclude that sirolimus may be an effective alternative medication for GSD.

Stimulation of Treg Cells to Inhibit Osteoclastogenesis in Gorham-Stout Disease

“…An increase of the number of Treg is achievable by Treg transfer or treatment with mTOR (mammalian target of rapamycin) inhibitors (von Boehmer and Daniel, 2013). Recent studies (Ozeki and Fukao, 2019;Ricci et al, 2019;Liang et al, 2020) reported that effectiveness of mTOR inhibitor Sirolimus in the treatment of GSD patients; indeed Sirolimus is known to inhibit lymphangiogenesis and is thought to act on lymphatic tissue within lesions regulating production and leakage of lymph (Ozeki and Fukao, 2019). Sirolimus also stimulates Treg (Battaglia et al, 2006;Strauss et al, 2009), that according with our results, could inhibit bone erosion.…”

Gorham-Stout case report: a multi-omic analysis reveals recurrent fusions as new potential drivers of the disease

“…Main therapies consist of surgical excision and reconstruction of bone tissue, radiotherapy, and sirolimus (rapamycin) treatment. Rapamycin treatment represents a novel approach whose safety and efficacy remain unclear [ 5 ].…”

“A case of vanishing bone disease complicated by chylothorax- diagnosis and treatment”

“…This option could be particularly useful in younger patients, who might not tolerate well other therapeutic regimens, as radiotherapy, bisphosphonates or interferon. 7 Hou et al 8 have shown, through lymphoscintigraphy, that chylous effusion, observed in up to a quarter of patients with this condition, occurs because of occlusion of the thoracic duct and lymphatic hyperplasia in the pleura and thoracic bones. Chylothorax carries a 69% mortality rate, due to massive protein loss, in those treated with medical management alone, and a 36% rate if surgical intervention is attempted.…”