Erdheim-Chester Disease

Erdheim-Chester disease (ECD) is a rare (approximately 500 known cases worldwide), non-inherited, non-Langerhans form of histiocytosis of unknown origin, first described in 1930. It is characterized by xanthomatous or xanthogranulomatous infiltration of tissues by foamy histiocytes, "lipid-laden" macrophages, or histiocytes, surrounded by fibrosis. Diagnosis of ECD involves the analysis of histiocytes in tissue biopsies: these are typically foamy and CD68+ CD1a- in ECD, whereas in Langerhans cell histiocytosis (LCH) they are CD68+ CD1a+. (99)Technetium bone scintigraphy revealing nearly constant tracer uptake by the long bones is highly suggestive of ECD, and a "hairy kidney" appearance on abdominal CT scan is observed in approximately half of ECD cases. Central nervous system involvement is a strong prognostic factor and an independent predictor of death in cases of ECD. Optimum initial therapy for ECD seems to be administration of interferon alpha (or pegylated interferon alpha), and prolonged treatment significantly improves survival; however, tolerance may be poor. Cases of ECD present with strong systemic immune activation, involving IFN alpha, IL-1/IL1-RA, IL-6, IL-12, and MCP-1, consistent with the systemic immune Th-1-oriented disturbance associated with the disease. More than half of ECD patients carry the BRAF(V600E) mutation, an activating mutation of the protooncogene BRAF. A small number of patients harboring this mutation and with severe multisystemic and refractory ECD have been treated with vemurafenib, a BRAF inhibitor, which was proved very beneficial.