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Among the more common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum) and skin. The most common presenting symptom of ECD is bone pain. The etiology of ECD is unknown yet thought to be associated with an intense TH1 immune response. It may also be associated with the V600E BRAF mutation, as described in as many as half of the patients in recent studies. Bilateral symmetric increased tracer uptake on <jats:sup>99m<\/jats:sup>Tc bone scintigraphy affecting the periarticular regions of the long bones is highly suggestive of ECD. However, definite diagnosis of ECD is established only once CD68(+), CD1a(\u2212) histiocytes are identified within a biopsy specimen. At present, this obscure ailment embodies numerous challenges to medical science. Given its rarity, it is diagnostically elusive and requires a high level of clinical suspicion. Therapeutically, it is of limited alternatives. Currently, interferon-\u03b1 is the most extensively studied agent in the treatment of ECD and serves as the first line of treatment. Treatment with other agents is based on anecdotal case reports and on the basis of biological rationale. Nevertheless, cladribine (2CDA), anakinra and vemurafenib are currently advocated as promising second line treatments for patients whose response to interferon-\u03b1 is unsatisfactory. Overall, the 5 year survival of ECD is 68%. Herein, the authors mustered and brought about a panoramic consolidation of all the relevant facts regarding ECD. This work highlights the different clinical, radiological and pathological manifestations associated with ECD, the differential diagnoses, the various treatment options and the acknowledged science explaining the disease.<\/jats:p>","DOI":"10.1186\/1750-1172-8-137","type":"journal-article","created":{"date-parts":[[2013,9,8]],"date-time":"2013-09-08T06:17:13Z","timestamp":1378621033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":231,"title":["Erdheim-Chester Disease: a comprehensive review of the literature"],"prefix":"10.1186","volume":"8","author":[{"given":"Roei D","family":"Mazor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirra","family":"Manevich-Mazor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehuda","family":"Shoenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,9,8]]},"reference":[{"key":"631_CR1","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1182\/blood-2010-06-294108","volume":"117","author":"L Arnaud","year":"2011","unstructured":"Arnaud L, Hervier B, Neel A, Hamidou MA, Kahn JE, Wechsler B, Perez-Pastor G, Blomberg B, Fuzibet JG, Dubourguet F, et al: CNS involvement and treatment with interferon-alpha are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. 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