Gorhams Disease

Gorham’s disease is a rare bone disorder characterized by bone loss, often associated abnormal blood vessel growth. The disease is a rare congenital disorder involving the abnormal overgrowth of lymphatic vessels. The vessels that transport fluid around the body to remove waste and toxins. In Gorham’s disease, these lymphatic vessels dilate and spread into bone, resulting in bone loss, commonly in the skull, collarbone, pelvis, ribs, spine or jaw. The lost bone may be replaced with scar tissue or new blood vessels.

The cause of Gorham’s disease is currently unknown. Most cases occur sporadically.

The disease was first described in 1838. The first case of Gorham’s disease affecting the face described in 1924. Fewer than 200 cases of Gorham’s disease have been documented in medical literature, although it’s likely that many cases go unreported. Normally Gorham’s disease is not fatal, but can have serious consequence for health, especially because the disease is often associated with abnormalities in the growth of blood vessels.

Symptoms and Diagnosis of Gorham’s Disease

Gorham’s disease is typically diagnosed in children and young adults, with most cases diagnosed before the age of 40. Symptoms vary among affected people and depend on the area(s) of the body involved. As it is very rare, it may be misdiagnosed initially or go undiagnosed for some time. Gorham’s disease is also sometimes referred to as cystic angiomatosis of bone diffuse, Gorham-Stout syndrome, and Gorham-Stout disease, as well as disappearing bone disease, vanishing bone disease, and massive osteolysis. Osteo is the medical word for bone, and lysis means destruction or breakdown.

In Gorham’s disease, vascular or lymphatic channels develop in bone, leading to a loss of bone. The lost bone is replaced by fibrosis (scar tissue) and/or angiomas (blood vessels).

There are eight inclusion criteria for a diagnosis of Gorham’s disease:

• Positive biopsy for angiomatous tissue (blood vessels where there should be bone)
• Absence of cellular atypia (i.e. irregularities in the structure of cells)
• Minimal or no osteoblastic response and the absence of dystrophic calcification (two healing reactions to bone breakdown that increase bone density and calcification)
• Evidence of local progressive osseous resorption (the breakdown of bone, releasing minerals into the blood)
• Non-expansile, non-ulcerated lesion status (i.e. no ulcer or growth of the lesion but localized bone loss and replacement with blood vessels)
• Absence of visceral involvement (i.e. not affecting internal organs)
• Osteolytic radiographic pattern (evidence of bone loss on x-rays)
• No evidence of a hereditary, metabolic, neoplastic, immunological, or infectious cause.

What Causes Gorham’s Disease?

The specific cause of the disease remains unknown. Gorham’s disease is congenital, but no genetic predisposition has been identified. 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. Several theories have been suggested, however, including the idea that trauma may alter the pH in bone and trigger bone breakdown (osteolysis). Others have speculated that acidosis and oxygen deprivation in bone may lead to increased activity in the enzymes that break down bone. An error in the lymphatic system may also play a role in Gorham’s disease, as might errors in blood vessel growth leading to increased blood flow to areas of connective tissue and bone that are healing from trauma.

Symptoms of Gorham’s Disease

Symptoms of Gorham’s disease may develop quickly, requiring aggressive treatment, but may progress more slowly over time, with periods of remission or reversal with treatment. In some individuals, the disease may not cause any symptoms. Typically, Gorham’s disease first presents as swelling and pain with no obvious cause. Some people are diagnosed after a fracture occurs, with radiography showing bone loss. Symptoms of Gorham’s disease can include:

• An acute onset of localized pain and swelling
• Reduced range of motion and generalized weakness
• Increased risk of fracture
• Difficulty breathing and chest pain may be present if the disease is present in the ribs.

When Gorham’s disease affects the maxillofacial (jaw) bones, symptoms can include jaw pain, loose teeth, fractures, and facial deformity

Some people with Gorham’s disease may develop pleural effusion, a condition where there is ‘water on the lungs’ due to the build-up of excess fluid between the pleura or thin membranes that line the lungs and the inside of the chest cavity. Because the pleura help to lubricate and are important for healthy respiratory function, Gorham’s disease can lead to respiratory distress (i.e. breathing problems) and even respiratory failure.

Treating Gorham’s Disease

Treatment for the disease is tailored to the individual and depends on their symptoms and the progression of the disease. Currently available treatments are still considered experimental, however, due to a lack of studies investigating their benefits. Treatment of Gorham’s disease is for the most part palliative and limited to symptom management.

In some people, spontaneous recovery may occur. In most people, however, the disorder is treated aggressively with surgery and radiation therapy, as well as vitamin D and calcitonin, especially if the disease is affecting the spine and skull or if it has spread to several areas of the body. Bone grafts may be necessary in some patients, but these tend to also be broken down over time; artificial prostheses or bone cements may prove helpful in this regard. Drugs such as bisphosphonates (including pamidronate and zoledronic acid) and alpha-2b interferon may be helpful to reduce bone loss.

There are also several treatment options for people with pleural involvement in Gorham’s disease, including:

• Pleurectomy (the removal of part of the pleural membranes)
• Pleurodesis (where two or more membranes are fused to eliminate the pleural cavity)
• Thoracic duct ligation (surgery to close off the main vessel of the lymphatic system)
• Radiation therapy (to destroy abnormal blood cells)
• Interferon therapy (interferons affect the growth of cells, in this case abnormal blood cells)
• Bleomycin (a chemotherapy drug sometimes used to treat abnormal blood vessels)
• Sirolimus (rapamycin; an immunosuppressant that targets lymphatic vessel formation).

Prognosis for Gorham’s Disease

It is hard to predict the long-term outcome for Gorham’s disease, with the disease’s progression different in every individual. For some people, the disease stabilizes after several years, while others may go into remission. The disease has been known to spontaneously reoccur, and in some patients the disease may continue to progress, leading to more severe symptoms that can eventually prove fatal.

More severe symptoms and serious complications are seen more in patients with lesions in the vertebrae, ribs, or sternum. This is because the abnormalities in these bones may spread to affect the pleura (the membranes around the lungs), as well as the spinal cord. When this happens, a patient may develop neurological problems and breathing difficulties that could prove fatal.

Because Gorham’s disease is very rare, few physicians have ever encountered a case. Most patients are referred to a specialist physician or clinic such as Boston’s Children’s Hospital after diagnosis or where a diagnosis is proving difficult. These clinics are currently working to identify the underlying causes of Gorham’s disease and are also working on developing more effective treatments for the condition.