title: Erdheim-Chester disease.
abstract: 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+. ⁹⁹Technetium 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 α (or pegylated interferon α), and prolonged treatment significantly improves survival; however, tolerance may be poor. Cases of ECD present with strong systemic immune activation, involving IFNα, 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 proto-oncogene 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.
authors: Department of Internal Medicine and French Reference Center for Rare Autoimmune and Systemic Diseases, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France, julien.haroche@psl.aphp.fr.
authors: Julien
authors: J
authors: Haroche
authors: Laurent
authors: L
authors: Arnaud
authors: Fleur
authors: F
authors: Cohen-Aubart
authors: Baptiste
authors: B
authors: Hervier
authors: Frédéric
authors: F
authors: Charlotte
authors: Jean-François
authors: JF
authors: Emile
authors: Zahir
authors: Z
authors: Amoura
mesh_terms: D031249:Erdheim-Chester Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D009154:Mutation; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D035583:Rare Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D016898:Interferon-alpha; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf