Absence of cellular atypia.
Little or no osteoblastic response or dystrophic calcification.
Local progressive osseous resorption.
A nonexpansile, nonulcerative lesion.
An osteolytic radiographic pattern.And no hereditary, metabolic, neoplastic, immunological, or infectious cause.
This bone disorder is largely attributed to focal lymphatic endothelial proliferation, whereby the bone is progressively destroyed and resorbed. The expected course of events after a fracture in a bone affected by Gorhams Disease is failure of healing followed by progressive reabsorption of bone around the fracture site. Progression of the disease has been observed to cease without treatment in many cases, but regeneration of the destroyed bone is not expected. The self-limited course correlates well with two phases of evolution of the histopathological lesions with neoplastic-like proliferation of lymphatic endothelial cells corresponding to the rapid and massive bone destruction, and a later
The criteria for what is and is not Gorham's Disease are not well worked out. The most easily separable group is that of multicentric osteolysis of which the great majority primarily affect the hands and feet, so-called acro-osteolysis. A subset has been described which is clearly inherited and two syndromes are recognised. Yet another group of multicentric osteolysis patients has an associated nephropathy.
Apart from standard orthopaedic treatment for fractures, non unions and deformities the medical treatment for Gorhams Disease falls into three groups :
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.
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.
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:
> Multifocal osteolysis without soft tissue lymphatic anomaly.
> Focal osteolysis with soft tissue lymphatic anomaly.
> Multifocal osteolysis with soft tissue lymphatic anomaly.
> Lymphatic Osteolysis in the context of vascular tumors or syndromes.
Dr Juan Carlos López-Gutiérrez
Vascular Anomalies Center
Hospital Infantil La Paz