Gorham’s disease

Gorham’s (GOR-amz) disease is a very rare skeletal condition of uncertain etiology, 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.1, 2 Because of the loss of the affected bone, the condition has been referred to as disappearing bone disease, vanishing bone disease, and massive osteolysis. In medical terminology osteolysis means: bone (osteo) breaking down or destruction (lysis).

The case of Mr. Brown

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.3 Read more

 

In 1954 Gorham and three others published a two case series, with a brief review of 16 similar cases from the medical literature, that advanced the hypothesis that angiomatosis was responsible for this unusual form of massive osteolysis.8

That same year Gorham and Stout presented to the American Association of Physicians their paper (in abstract form), “MASSIVE OSTEOLYSIS (ACUTE SPONTANEOUS ABSORPTION OF BONE, PHANTOM BONE, DISAPPEARING BONE): Its Relation to Hemangiomatosis.”1 The paper was published in its entirety in October 1955 in The Journal of Bone and Joint Surgery, concluding that:

  1. There now exists the basis for a new syndrome which is supported by a remarkable similarity of clinical and [x-ray] findings in twenty-four cases, and by an equally convincing similarity of the histological picture in eight of these, which we have personally studied.
  2. However it is accomplished, the progressive osteolysis is always associated with an angiomatosis of blood and sometimes of lymphatic vessels, which seemingly are responsible for it.

The most typical presentation is that of osteolysis of a single bone or the bones connected by a shared joint, such as the shoulder. Although the disease can attack any bone, the shoulder is one of the most commonly involved areas, along with the skull and pelvic girdle. Spontaneous fractures are common and may be the first sign of the disease.9 A hallmark of the disease is the lack of bone healing following fracture.

More on Dr. Gorham and Dr. Stout

What causes Gorham’s disease?

To date, the specific etiology of Gorham’s disease remains undefined.

Bone mass and strength are obtained and maintained through a remarkable 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 clearly disrupted.1, 2, 8,  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.1, 8 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.8 Beginning in the 1990’s there are 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.9, 13

In 1999 Möller and colleagues9concluded, “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 vascularised 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.18

While there is consensus that Gorham’s is caused by deranged osteoclastic activity,1, 8, 9, 11 there is not yet conclusive evidence as to what causes this deranged behavior to begin.

Who has Gorham’s disease?

Gorham’s disease is extremely rare and may occur at any age, though it is most often recognized in children and young adults. It strikes males and females of all races and exhibits no inheritance pattern. The medical literature contains case reports from every continent. Because it is so rare, and commonly misdiagnosed, it is not known exactly how many people are affected by this disease. The literature frequently cites that fewer than 200 cases have been reported, though there is consensus building that there are many more cases around the world than have been reported.

References

 

Source: www.lgdalliance.org (April 5th, 2016)