Clinical and Basic Investigations Into Erdheim Chester Disease

Erdheim-Chester Diseases (ECD) is a very rare non-Langerhans cell histiocytosis of unknown origin and pathogenesis. It has been reported mainly in adult males over the age of 40 years, although cases have been reported in females as well. Children are rarely affected by this condition. No causative gene has been identified; family studies have not been performed due to the rarity and sporadic nature of the disease. The clinical characteristics of ECD range from asymptomatic to multisystemic involvement; longitudinal progression and natural history have not been well documented. ECD commonly affects the bones, kidneys, retroperitoneal space, skin and brain. After diagnosis, the disease progresses rapidly, causing fatal outcomes due to severe lung disease, chronic renal failure, cardiomyopathy and other complications. The diagnosis of ECD relies upon imaging studies and specific pathologic findings in biopsies of affected organs, i.e., fibrosis and infiltration of the affected tissues with foamy histiocytes, lymphocytes, and plasma cells. Immunohistochemistry reveals cells positive for CD68 and negative for CD1a and S-100. There is no standard treatment for ECD, although chemotherapy, radiation, stem cell transplantion, alpha-interferon, steroids and sirolimus have been proposed. Symptomatic improvement has been reported with some of these therapies, but death within a few years after diagnosis remains the expected outcome. In this protocol, we will clinically evaluate ECD patients, obtain cells, plasma, and urine, search for genes that can be responsible for ECD, and perform other studies dictated by each patient's presentation.