Trial of Sirolimus in Gorham Disease

Background: Gorham Disease, also known as Gorham-Stout Disease, massive osteomyelitis, or vanishing bone disease, is a rare disorder of poorly understood etiology. Patients undergo bone resorption without proliferation and have significant soft-tissue swelling. No standard treatment is currently available. Novel use of the MTOR inhibitor sirolimus has shown some promise in slowing the progression of this devastating disorder. Immunosuppressant agents such as sirolimus have been used effectively in transplant patients for prophylaxis of organ rejection. We hypothesize that this agent can also successfully slow the progression of bone resporption in patients with Gorham Disease. This case series describes the diagnosis, progression, and therapy of three patients in the Cook Children’s Medical Center hematology-oncology department with varying levels of severity of Gorham Disease. Case Information: Three patients were diagnosed with Gorham Disease between 2011 and 2014 and are now being treated within the Cook Children’s Medical Center Hematology-Oncology practice. One patient has involvement of her skull base and ear canals, diagnosed after ear canal abnormalities were detected on CT following meningitis. The second patient has involvement of her posterior ribs and T7-T12 vertebral bodies, with thoracic instability and necessity of either remaining in the supine position or wearing a back brace. The third patient has involvement of his left lower extremity and left hemipelvis, necessitating a left above knee amputation and subsequent disease progression. The first two patients have had radiographic improvement after the addition of twice daily sirolimus, while the third patient has had steadying of his disease. Conclusions: Gorham Disease is a rare condition with possibly devastating effects. The introduction of sirolimus, in select cases, has appeared to either steady or slowly reverse the progression of the disease. While more studies need to be performed to understand the full effects of sirolimus on this disease, it has the potential to have a significant role in the treatment of Gorham.