08-30-2021-1955 - Rapid degeneration of bone w/ or w/o replacement by fibrous tissue - Spindular/Directional/Tissular/Channular/etc. Infiltration of Bone (Tissue, self, genetic; fibrosis/angioma) - Gorham's disease vanishing bone disease phantom bone disease - angioma fibrosis vascular lymphatic channel channels cause skeletal condition angiomatosis fibromatosis interleukin 6 osteolysis lysis lytic autocrine paracrine histopathology dystrophic calcification osseous resorption nonulcerative lesion disequilibrium homeostatic-disruption homeostasis decoherence Thalidomide interferon alpha 2b thoracentesis pleurodesis shunt radiation percutaneous bone cement bone graft bisphosphonate (sometimes and little only) 1838 boneless arm - autoimmune

 Gorham's disease (pronounced GOR-amz), also known as Gorham vanishing bone disease and phantom bone disease,^[1] 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.^[2][3]

The specific cause of Gorham's disease 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's disease, that process is disrupted.^{[2][3][4][9][10][11]}

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.^[2][9] Gorham and others speculated that such a change in the bone chemistry might cause an imbalance in the rate of osteoclast to osteoblast activity such that more bone is dissolved than is replaced.^[9] Beginning in the 1990s, elevated levels of a protein called interleukin-6 (IL-6) being detected in people with the disease were reported, 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.^[4][12]

In 1999, Möller and colleagues^[4] concluded, "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's disease are the result of hyperactive osteoclastic bone. However, others have concluded that lymphangiomatosis and Gorham's disease should be considered as a spectrum of disease rather than separate diseases.^[13]

While a consensus exists that Gorham's is caused by deranged osteoclastic activity,^{[2][4][9][11]} no conclusive evidence has been found as to what causes this behavior to begin.

In 1983, Heffez and colleagues^[10] published a case report in which they suggested eight criteria for a definitive diagnosis of Gorham's disease:^{[citation needed]}

• 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
• Nonexpansile, nonulcerative 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, and 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.^{[2][3][4][11][14]}

Often, Gorham's disease 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.^[4] X-rays, CT scans, MRIs, ultrasounds, and nuclear medicine (bone scans) are all important tools in the diagnostic workup and surgical planning, but none has 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.^[4][5][8]

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.^[3]

Management[edit]

Treatment of Gorham's disease is for the most part palliative and limited to symptom management.^{[citation needed]}

A search of the medical literature reveals multiple case reports of interventions with varying rates of success as follows:^{[citation needed]}

Cardiothoracic (heart and lung):

• Pleurodesis
• Ligation of thoracic duct
• Pleurperitoneal shunt
• Radiation therapy
• Pleurectomy
• Surgical resection
• Thalidomide
• Interferon alpha-2b
• TPN (total parenteral nutrition)
• Thoracentesis
• Diet rich in medium-chain triglycerides and protein
• Chemotherapy
• Sclerotherapy
• Transplantation

Skeletal:

• Interferon alpha-2b
• Bisphosphonate (e.g. pamidronate)
• Surgical resection
• Radiation therapy
• Sclerotherapy
• Percutaneous bone cement
• Bone graft
• Prosthesis
• Surgical stabilization
• Amputation

To date, no known interventions are consistently effective for Gorham's, and all reported interventions are considered experimental treatments, though many are routine for other conditions. Some people may require a combination of these approaches. Unfortunately, some people will not respond to any intervention.^{[citation needed]}

^{The first known report of the condition came in 1838 in an article titled "A Boneless Arm" in what was then The Boston Medical and Surgical Journal (now The New England Journal of Medicine).[15] I}

https://en.wikipedia.org/wiki/Gorham%27s_disease