Gorham syndrome is a very rare skeletal condition of unknown cause, characterized by the uncontrolled proliferation of distended, thin-walled vascular or lymphatic channels within bone, which leads to resorption and replacement of bone with angiomas and/or fibrosis.
The symptoms of Gorham Syndrome vary depending on the bones involved. It may affect any part of the skeleton, but the most common sites of disease are the shoulder, skull, pelvic girdle, jaw, ribs, and spine.
In some cases there are no symptoms until a fracture occurs either spontaneously or following minor trauma, such as a fall. There may be an acute onset of localized pain and swelling. More commonly there is pain of no apparent cause that increases in frequency and intensity over time and may eventually be accompanied by weakness and noticeable deformity of the area. The rate of progression is unpredictable and the prognosis can be difficult. The disease may stabilize after a number of years, go into spontaneous remission, or, in cases involving the chest and upper spine, prove fatal. Recurrence of the disease following remission can also occur. Involvement of the spine and skull base may cause a poor outcome from neurological complications. In many cases, the end result of Gorham syndrome is severe deformity and functional disability.
Symptoms such as difficulty breathing and chest pain may be present if the disease is present in the ribs, scapula, or thoracic vertebrae. These may indicate that the disease has spread from the bone into the chest cavity. The breathing problems may be misdiagnosed as asthma, because the damage done to the lungs can cause the same types of changes to lung function testing that are seen in asthma. Extension of the lesions into the chest may lead to the development of chylous pleural and pericardial effusions. Chyle is rich in protein and white blood cells that are important in fighting infection. The loss of chyle into the chest can have serious consequences, including infection, malnutrition, and respiratory distress and failure. These complications or their symptoms, such as difficulty breathing, chest pain, poor growth or weight loss, and infection have sometimes been the first indications of the condition.
To date, the specific cause of Gorham syndrome remains unknown.
Bone mass and strength are obtained and maintained through a process of bone destruction and replacement that occurs at the cellular level throughout a person's life. Cells called osteoclasts secrete enzymes that dissolve old bone, allowing another type of cells called osteoblasts to form new bone. Except in growing bone, the rate of breakdown equals the rate of building, thereby maintaining bone mass. In Gorham syndrome that process is disrupted.
Gorham and Stout found that vascular anomalies always occupied space that normally would be filled with new bone and speculated that the presence of angiomatosis may lead to chemical changes in the bone. Gorham and others speculated that such a change in the bone chemistry might cause an imbalance in the rate of osteoclast activity to osteoblast activity such that more bone is dissolved than is replaced. Beginning in the 1990s there were reports of elevated levels of a protein called interleukin-6 (IL-6) being detected in patients with the disease, leading some to suggest that increased levels of IL-6 and vascular endothelial growth factor (VEGF) may contribute to the chemical changes Gorham and others believed were the cause of this type of osteolysis.
In 1999 Möller and colleaguesconcluded, "The Gorham-Stout syndrome may be, essentially, a monocentric bone disease with a focally increased bone resorption due to an increased number of paracrine – or autocrine – stimulated hyperactive osteoclasts. The resorbed bone is replaced by a markedly vascularized fibrous tissue. The apparent contradiction concerning the presence or absence or the number of osteoclasts, may be explained by the different phases of the syndrome." They further stated that their histopathological study provided good evidence that osteolytic changes seen in Gorham syndrome are the result of hyperactive osteoclastic bone. However, others have concluded that lymphangiomatosis and Gorham syndrome should be considered as a spectrum of disease rather than separate diseases.
While there is consensus that Gorham's is caused by deranged osteoclastic activity, there is not yet conclusive evidence as to what causes this deranged behavior to begin.
In 1983 Heffez and colleagues published a case report in which they suggested eight criteria for a definitive diagnosis of Gorham syndrome:
- Positive biopsy with the presence of angiomatous tissue
- Absence of cellular atypia
- Minimal or no osteoblastic response or dystrophic calcifications
- Evidence of local bone progressive osseous resorption
- Non-expansile, non-ulcerative lesions
- No involvement of viscera
- Osteolytic radiographic pattern
- Negative hereditary, metabolic, neoplastic, immunologic, or infectious etiology.
In the early stages of the disease x-rays reveal changes resembling patchy osteoporosis. As the disease progresses bone deformity occurs with further loss of bone mass and, in the tubular bones (the long bones of the arms and legs), a concentric shrinkage is often seen which has been described as having a "sucked candy" appearance. Once the cortex (the outer shell) of the bone has been disrupted, vascular channels may invade adjacent soft tissues and joints. Eventually, complete or near-complete resorption of the bone occurs and may extend to adjacent bones, though spontaneous arrest of bone loss has been reported on occasion. Throughout this process, as the bone is destroyed it is replaced by angiomatous and/or fibrous tissue.
Often Gorham syndrome is not recognized until a fracture occurs, with subsequent improper bone healing. The diagnosis essentially is one of exclusion and must be based on combined clinical, radiological, and histopathological findings. X-rays, CT scans, MRIs, ultrasounds, and nuclear medicine (bone scans) are all important tools in the diagnostic workup and surgical planning, but none have the ability alone to produce a definitive diagnosis. Surgical biopsy with histological identification of the vascular or lymphatic proliferation within a generous section of the affected bone is an essential component in the diagnostic process.
Recognition of the disease requires a high index of suspicion and an extensive workup. Because of its serious morbidity, Gorham's must always be considered in the differential diagnosis of osteolytic lesions.
Sometimes Gorham syndrome regress without any obvious cause, sometimes it can be much serious if the vitale strucutres are affected (Exp:Lung support). Disability depends of the part of Skeleton affected, but it stay rare.
Treatment of Gorham's disease is for the most part palliative and limited to symptom management.
Sometimes the bone destruction spontaneously ceases and no treatment is required. But when the disease is progressive, aggressive intervention may be necessary. Duffy and colleagues reported that around 17% of patients with Gorham's disease in the ribs, shoulder, or upper spine experience extension of the disease into the chest, leading to chylothorax with its serious consequences, and that the mortality rate in this group can reach as high as 64% without surgical intervention.
A search of the medical literature reveals multiple case reports of interventions with varying rates of success as follows:
Cardiothoracic (Heart & Lung)
- Ligation of thoracic duct
- Pleurperitoneal shunt
- Radiation therapy
- PleurectomySurgical resection
- Interferon alpha-2b
- TPN (total parenteral nutrition)
- Diet rich in medium-chain triglycerides and protein
- Interferon alpha-2b
- Bisphosphonate (e.g. pamidronate)
- Surgical resection
- Radiation therapy
- Percutaneous bone cement
- Bone graft
- Surgical stabilization
To date, there are no known interventions that are consistently effective for Gorham's and all reported interventions are considered experimental treatments, though many are routine for other conditions. Some patients may require a combination of these approaches. Unfortunately, some patients will not respond to any intervention.