Gorham's (GOR-amz) disease is a rare musculoskeletal condition in which spontaneous, progressive resorption of the bone occurs. It is known variously as massive osteolysis, disappearing bone, or vanishing bone disease, and a variety of other names (see synonyms list). In medical terminology osteolysis means: bone (oste/o) breaking down or destruction (lysis). Gorham's disease was first reported in 1838, again in 1872, and was finally defined in 1955 by Gorham and Stout as a specific disease entity. Although described long ago, this rare and potentially catastrophic disease remains understudied, thus, poorly understood. It is thought to be closely related to or even a severe form of lymphangiomatosis that is characterized by a proliferation of thin-walled vascular capillaries or lymphatic vessels that starts within the bone. As these vessels proliferate, they aggressively invade the adjacent bone leading to resorption and replacement of angiomatous tissue.

What causes Gorham's disease?

The cause or exact nature of this mysterious disorder remains unknown and it is not usually recognized by clinicians until a fracture occurs, with subsequent improper bone healing. Several theories have been proposed postulating the role of osteoclastic activity. Some studies report that osteoclastosis is not associated with Gorham's disease and that angiomatosis might be the cause. Recently, it has been reported that elevated levels of IL-6 were detected early on in the course of the disease leading to suggest osteoclastic activity. The exact cause of Gorham's disease is controversial to this day. Focused research is needed to determine the exact cause of Gorham's disease.

Who has Gorham's disease?

Gorham's disease is extremely rare and may occur at any age. It has been cited many times that "there are fewer than 200 cases reported in medical literature". It is most often recognized in children and young adults, without gender, race predilection, or inheritance pattern. Because it is so rare, and commonly misdiagnosed, it is not known exactly how many people are affected by this disease.

What are the symptoms of Gorham's disease?

Gorham's disease presents as progressive osteolysis of one bone or contiguous bones around one focus, without respect of anatomical boundaries. It may affect any part of the skeleton, but most commonly involved sites are the skull, mandible, shoulder, rib cage, and pelvis. The degree of complications ranges from mild to severe, even death depending on the site of bony involvement.

During the acute onset, patients may experience localized pain, swelling, or pathological fracture as the disease process occurs. Others however may be asymptomatic. The rate of progression is unpredictable and the prognosis can be difficult. The disease can stabilize after a number of years, go into spontaneous remission, or prove fatal. Recurrence of the disease 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's disease is severe deformity and functional disability.

If the disease is present in the ribs, scapula, or thoracic vertebrae, it may lead to the development of chylous pleural and pericardial effusions from the direct extension of the lesion into the pleural cavity or invasion of the thoracic duct. This can have serious consequences, including loss of protein, malnutrition, and respiratory distress and failure.

How is Gorham's disease diagnosed?

The diagnosis is, essentially one of exclusion and must be based on combined clinical, radiological and histopathological findings. Heffez, et al suggested eight criteria for a definitive diagnosis of Gorham's disease.

• Positive biopsy with the presence of angiomatous tissue
  
• Absence of cellular atypia
• Minimal or no osteoclastic response and of dystrophic calcifications
• Evidence of local bone progressive resorption
• Non-expansile, non-ulcerative lesions
• Osteolytic radiographic pattern
• Negative hereditary, metabolic, neoplastic, immunologic, or infectious etiology.

Radiographically, Gorham's disease progresses through four stages. It initially presents resembling patchy osteoporosis. Next, bone deformity increases with further loss of bone mass. The cortex is then disrupted with endothelial invasion into adjacent soft tissues and/or across joints. Finally, there is shrinkage of the ends of the affected bones producing a "sucked candy" appearance.

CT, MRI, ultrasound, and nuclear medicine have all been used but none have the ability alone to produce a definitive diagnosis. These modalities however, can show the extent and be used to monitor the progression of the disease.

Gorham's disease must always be included in differential diagnosis when associated with osteolytic lesions and chylothorax. There are a number of additional disorders which have been cited in the differential considerations. These include: Langerhans cell, histiocytosis X, fibrous dysplasia, fibromatosis, hemangiomatosis, eosinophilic granulomatosis, acro-osteolysis of Hadju and Cheney, idiopathic multi-centric osteolysis, and multi-centric osteolysis with nephropathy. There are many more listed in the medical literature. It has been observed that the histologic, radiologic, and clinical characteristics of lymphangiomatosis overlap those of Gorham's disease, massive osteolysis and those of hemangiomatosis, so that these entities are grouped together as angiomatous bone lesions.

What are the treatments for Gorham's disease?

The treatments for Gorham's disease have been reported to vary a great deal from patient. It is for the most part palliative and is usually started due to a new symptom in an affected area. There is no standard approach and different treatments have been reported as working for some and not others. Sometimes several methods are exhausted before finding one that is effective and in some cases, no treatment has been reported as needed at all. For many cases reported though, intense intervention has been indicated, especially if the disease was reported as being diffuse, or if the cardiothoracic region spine, or skull were reported as involved. All interventions (pharmacological and surgical) are all still considered to be experimental since there have been no studies done to examine the effectiveness of anything used to date. To summarize, no single treatment modality has been reported to be proven effective for arresting this disease and there are no known treatments that prevent or control the disease itself.

 

Treatment modalities reported
Cardiothoracic		Pleurodesis, ligation of thoracic duct, pleurperitoneal shunt, radiation therapy, pleurectomy, surgical resection, thalidomide, Interferon Alpha2b, TPN nutrition, thoracentesis, medium chain triglyceride and high protein diet, chemotherapy, sclerotherapy, transplantation
Skeleton		Interferon Alpha2b, bisphosphonates (i.e. pamidronate), surgical resection, radiation therapy, sclerotherapy, percutaneous bone cement, bone grafts, prosthesis, surgical stabilization, amputation

Synonym, homonyms, and miscellaneous names used in the literature to describe Gorham's disease*:

Gorham's disease, Gorham-Stout syndrome, Gorham's syndrome, Gorham's lymphangiomatosis, Morbus-Gorham-Stout disease, disappearing bone disease, vanishing bone disease, phantom bone disease, massive osteolysis, disseminated osseous bone disease, disseminated lymphangiomatosis, thoracic lymphangiomatosis, idiopathic massive osteolysis, essential osteolysis, acro-osteolysis syndrome, lymphangiomatosis, hemangiomatosis.

*There is a great deal of debate and confusion surrounding the terminology used when a patient is given the diagnosis of Gorham's disease (or variation of the name). It is apparent that there's a need for a universal name and definition for this disease that can be agreed upon and then communicated to the medical community so we're all on the same page. This will help physicians and we as a community to get a better grasp on how many people actually have this disease. We are making it a goal for the LGD Alliance to work with the medical community to try to find a consensus.

It is our hope that through the work of the LGD Alliance, progress will be made to help better understand the symptoms, diagnosing techniques and treatments for Gorham's disease. With increased research, discovering the cause, improving treatment and finding a cure may be well within our reach.

References:

The foregoing has been extracted from information provided from among the several hundred case reports in the medical literature. Abstracts are available from PubMed, the NIH medical database; full text is available generally from the publishing journal at a reprint fee. In addition the following references have been consulted:

Winegard, Bruce. Unlocking Medical Terminology. Prentice Hall 2006.

Taber, Clarence W. Taber's Cyclopedic Medical Dictionary. 20th edition. Philadelphia: F.A. Davis, 2005.