Rare Lung Disease II

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General Information About LGD

rare

Rare diseases are those affecting less than 200,000 individuals. Gorham's disease, sometimes called vanishing bone syndrome, is certainly one of these rare diseases as there are only about 200 reports of this in the medical literature. An early description in the nineteenth century notes a man with an arm fracture after trauma who had disappearance of the bone and recurrent fractures. The majority of reports of Gorham's disease are from the orthopedic literature as the process frequently starts in bone; however, the spread to the pleural surfaces of the lung heralds concern for rapid progression. Lymphangiomatosis is a rare process with onset in childhood that also is characterized by abnormal lymphatic channels, and not infrequently chylous pleural effusions. There is debate as to whether lymphangiomatosis and Gorham's syndrome are the same condition or simply share the same tissue of origin in the vascular system.

Gorham's disease, also called massive osteolysis, can present with acute fracture or insidious onset of bone pain and swelling. An early clue to its presence may be the lack of bone healing after fracture or a recurrent fracture in the same bone site. Bones most involved include the scapula, ribs, clavicle or vertebral bones. Some with Gorham's disease have stabilization and live for many years. About 17% of those affected have a chylous pleural effusion or chylothorax adjacent to the involved bones. Those with a chylothorax may have a rapid progression of symptoms over months to years. Complications include malnutrition with subsequent weight loss and infection as well as shortness of breath and ultimately respiratory failure and early death.

The cause of Gorham's disease is unclear and in need of further investigation. Tissue pathology involves bone disintegration and replacement by vascular fibrous tissue. Vascular and lymphatic channels in the absence of malignancy are a pathologic hallmark of this condition.  Osteoclasts which function to dissolve bone seem to show hyperactivity relative to osteoblasts, or bone formation cells in the ongoing process of bone remodeling. Why this happens has led to investigation of monocytes cells as an early mediator in the overall bone remodeling process.  Others have wondered whether a transcription factor Runx2 is a key participant in general bone remodeling. This seems a fertile area for investigation in Gorham's disease and lymphangiomatosis.  In addition to stimulating bone cell differentiation, Runx2 and related transcription factors stimulate endothelial cell migration and vascular invasion of developing bones. New insights are needed to provide effective treatments for these two potentially related conditions.

Of course the ultimate goal for patient, scientist and physician alike is to find successful treatments. No controlled trials have been performed in Gorham's disease as this is truly a rare disease. Up to the present time, skeletal involvement has been treated with resection of involved areas, radiation therapy, surgery to stabilize bony structures such as vertebral bodies, interferon alpha and/or bisphosphonates.  Similarly, treatment of the serious complication of chylothorax has included resection or radiation as well as thoracic duct ligation and pleurodesis or sclerosis. Interferon alpha, thalidomide and even lung transplantation have been tried. There are reports of successful therapy although some fail all treatments.

Source:
Carolyn Welsh, MD  
Univ. of Colorado Denver
Denver Veterans Affairs Med Ctr
Past Chair, ATS Council of Chapter Representatives


Four Facts About LGD
  1. Lymphangiomatosis and Gorham’s disease are thought to be a spectrum of disease:
      • Lymphangiomatosis is marked by the presence of cysts that result from an increase both in the size and number of thin-walled lymphatic channels that are abnormally interconnected and dilated
        • Gorham’s disease results from a derangement of osteoclast activity that is always accompanied by vascular anomaly (often lymphatic in origin and having the same features characteristic of lymphangiomatosis) that may extend into the soft tissues, particularly in the chest.
        1. When it involves the lungs, LGD causes chylothorax, chylopericardium, and interstitial disease that result in chronic respiratory failure. Pulmonary lymphangiomatosis is most aggressive in the youngest children.
        2. Affects males and females of all ethnicities equally and most commonly presents by age 20 years
        3. Pulmonary LGD is separate and distinct from lymphangiectasis, lymphangioleiomyomatosis (LAM), pulmonary capillary hemangiomatosis, Kaposi’s sarcoma, and kaposiform hemangioendothelioma.

        (Source: www.lgdalliance.org)