Treatment and recommendations

A rapid review of the literature led to the conclusion that there is no consensus about the most efficacious treatment.

Apart from standard orthopaedic treatment for fractures, non unions and deformities the medical treatment for Gorhams Disease falls into three groups :

1. Surgical intervention has been suggested as the method of choice when feasible and involves local resection of the affected bone, with or without replacement prostheses or bone grafts.

 

2. Anti-osteoclastic medication (biphosphonates) and interferon. Synergistic action of Zoledronic acid and Interferon is a powerful antiangiogenic therapy which is giving currently the best results.

 

3. Radiotherapy : Radiotherapy acts by accelerating sclerosis of the proliferating blood vessels and prevents regrowth of these vessels. Although the use of total doses from 30 to 45 Gy have been reported to be effective. Some authors showed excellent results using a total dose of 15 Gy in a case that involved the upper extremity. Others reported rapid relief of symptoms and prevention of further osseous destruction during a 6-year follow-up period with a total dose of 3000 rads. Regrowth of bone after radiation therapy is unusual but has been reported in some cases. There is a significant risk of long term sarcoma development in children.

Of course, the usefulness of all these treatments is also shaped by the severity of the disease (for example, surgery would be impractical in patients with widespread vertebral involvement) and the urgency of the patient's condition.

The prognosis varies from slight disability to death by involvement of vital skeletal structures. It has been reported that >15% of patients die as a result of their disease. Severe disability results from involvement of the pelvis, thorax, and cervical spine.

Neurological complications increase the mortality to 33.3%. However, the disease usually remains localized within a skeletal region and undergoes eventual spontaneous arrest.

Studies on genetic mechanisms are just beginning. A vascular endothelial growth factor receptor (VEGFr3) that is specific for lymphatics has been identified. Three genes associated with inherited lymphedema (generalized swelling due to lymphatic abnormality) have been identified. Animal models simulating lymphedema are currently being studied. It is possible that the pathogenesis of lymphangiomatosis and Gorham disease is different; lymphatic malformations that arise during early childhood might stem from aberrant sequestrations of lymphatic vessels, while the acquired proliferation of small lymphatics observed in Gorham's disease might be driven by lymphangiogenic growth factors. IL-6, in particular, appears to be a mediator of the massive osteolysis in patients with the Gorham-Stout syndrome.

We highlight the need to tailor therapy based on both the presence of therapeutic targets and the complications those therapies might induce in the individual patient.

Final recommendations :

1. Any child or adult with sudden progressive osteolysis should be considered as a potential Gorham disease patient.

2. We encourage patients and physicians to contact, as soon as the diagnosis is suspected, centers with multidisciplinary teams involved in the treatment of the disease with large experience and active protocols.

3. After analysis of the clinical presentation, imaging findings and histology specimens available they have to be classified in one of the following 5 groups considering characteristics of the bone and soft tissue involvement:

I. Focal osteolysis without soft tissue lymphatic anomaly -noticeable on MRI-.

II. Multifocal osteolysis without soft tissue lymphatic anomaly.

III. Focal osteolysis with soft tissue lymphatic anomaly.

IV. Multifocal osteolysis with soft tissue lymphatic anomaly.

V. Lymphatic Osteolysis in the context of vascular tumors or syndromes.

In summary, what action should be taken regarding Gorham´s disease treatment? Answer: there is no universal answer. Each child suffering from lymphatic osteolysis is unique and each treatment decision must be made individually.

JC Lopez-Gutierrez MD PhD

Vascular Anomalies Center

Hospital Infantil La Paz

Madrid. Spain