Erdheim Chester Disease
First reported by the American pathologist William Chester in 1930, Erdheim-Chester disease (aka Erdheim-Chester syndrome or polyostotic sclerosing histiocytosis) is a rare condition characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell histiocytosis). Usually, onset is in middle age, but people of all ages can have it. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.
ECD affects predominantly adults, with a mean age of 53 years. Long bone (i.e. arms, forearms, thighs, legs) involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 1/2 of cases have some sort of extraskeletal involvement which can include kidney, skin, brain and lung, and less frequently retroorbital tissue, pituitary gland and heart. Papules develop in these tissues which demonstrate the diagnostic cellular infiltrate seen by microscopy. Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and juxtaarticular in nature. Exophthalmos (protrusion of the eyes) occurs in some patients and is usually bilateral, symmetric and painless. In most cases it occurs several years before the final diagnosis.
A review of 59 case studies by Veyssier-Belot, C et al. in 1996 reported the following symptoms in order of frequency of occurrence:
- Bone pain
- Retroperitoneal fibrosis
- Diabetes insipidus
- Neurological signs (including Ataxia)
- Dyspnea caused by interlobular septal and pleural thickening.
Histologically, ECD differs from Langerhans cell histiocytosis (LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100 or CD 1a, and electron microscopy of cell cytoplasm does not disclose Birbeck granules. Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis. Bone biopsy offers the best chance of diagnosis. Radiologic osteosclerosis and histology are the main diagnostic features. Diagnosis is often difficult because ECD is so rare and it must be differentiated from LCH. A diagnosis from neurological imaging may not be definitive. The presence of symmetrical cerebellar and pontine signal changes on T2-weighted images seem to be typical of ECD, however, multiple sclerosis and metabolic diseases must also be considered in the differential diagnosis.
All current treatments have had varying degrees of success. Current treatments includes:
- Vinca alkaloids and anthracyclines
- Surgical debulking
- High-dose corticosteroids
- Radiation therapy