• Julien Haroche, Matthias Papo, Fleur Cohen-Aubart, Frédéric Charlotte, Philippe Maksud, Philippe A Grenier, Philippe Cluzel, Alexis Mathian, Jean-François Emile, and Zahir Amoura.
• Assistance publique-Hôpitaux de Paris, hôpital Pitié-Salpêtrière, université Pierre-et-Marie-Curie Paris 6, institut E3M, centre de référence des maladies rares auto-immunes et systémiques, service de médecine interne 2, Paris, France. Electronic address: julien.haroche@aphp.fr.
• Presse Med. 2017 Jan 1; 46 (1): 96-106.

AbstractIn a compatible clinico-radiological setting, the diagnosis of Erdheim-Chester disease (ECD) involves the analysis of histiocytes in tissue biopsies: they are typically foamy and CD68+ CD1a, whereas in Langerhans cell histiocytosis (LCH) they are CD68+ CD1a+. Overlap forms of histiocytoses are frequent. Technetium bone scintigraphy showing 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 more than half ECD cases. CNS involvement is a strong prognostic factor and an independent predictor of death in cases of ECD. Optimal initial therapy for ECD appears to be administration of IFN-α (and/or pegylated IFN-α) and prolonged treatment significantly improves survival; however, tolerance may be poor. Best alternative therapies are anakinra, mainly effective for mild forms of the disease, infliximab, and sirolimus. Cases of ECD present with strong systemic immune activation, involving IFN-α, IL-1/IL1-RA, IL-6, IL-12, and MCP-1, consistent with the systemic immune Th-1-oriented disturbance associated with the disease. Between 57 and 75 % of ECD patients carry the BRAFV600E mutation, an activating mutation of the proto-oncogene BRAF. More than 50 cases harboring BRAF mutation and with severe multisystemic and refractory ECD (sometimes associated with LCH) have been treated worldwide with vemurafenib, a BRAF inhibitor that proved to be very beneficial. Other recurrent mutations of the MAPK (NRAS, MAP2K1) and PIK3 pathways (PIK3CA) have been found among ECD patients. As recurrent mutations in the MAPK pathway are found in ECD and LCH on a background of chronic inflammation, we believe that both conditions should be redefined as an inflammatory myeloid neoplasia.Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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