Erdheim–Chester disease

Erdheim-Chester disease (ECD) is a rare (approximately 500 known cases worldwide), non-inherited, nonLangerhans 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 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 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.

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“…Papulonodular lesions [31] and infiltrations of the vulva and of the clitoris may be observed, but are less frequent [1].…”

Section: Cutaneomucosal Involvementmentioning

confidence: 99%

Erdheim–Chester Disease

et al. 2014

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“…Papulonodular lesions [33] and infiltrations of the vulva and clitoris may also be observed, but are less frequent [1].…”

Section: Cutaneomucosal Involvementmentioning

confidence: 99%

The histiocytosis Erdheim–Chester disease is an inflammatory myeloid neoplasm

Haroche

Cohen‐Aubart

Charlotte

et al. 2015

Expert Review of Clinical Immunology

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Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis, characterized by the infiltration of tissues by foamy CD68(+)CD1a(-) histiocytes. (99)Technetium bone scintigraphy revealing almost constant tracer uptake by the long bones is highly suggestive of ECD, and a 'hairy kidney' appearance on abdominal computed tomography scan is observed in about half of all ECD cases. CNS involvement is a strong prognostic factor and independent predictor of death. IFN-α seems to be the best initial treatment for ECD. More than half of all ECD patients carry the BRAF(V600E) mutation. More than 30 patients worldwide harboring this mutation and displaying multisystemic, refractory ECD have been treated with vemurafenib, a BRAF inhibitor, which has proven highly beneficial. Other recurrent mutations of the MAPK and PIK3 pathways (NRAS, PIK3CA) have recently been described. These mutations should lead to a new classification of histiocytic disorders such that Langerhans cell histiocytosis and ECD are classified as inflammatory myeloid neoplasms.

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“…Involvement of the skin [4,5,68], gastrointestinal tract [69-71], testes [72], thyroid [72], skeletal muscle [73] and breast [74,75] were anecdotally reported. Involvement of the skin seems to be the most common among the rare presentations of ECD.…”

Section: Introductionmentioning

confidence: 99%

“…In the retrospective study performed by Veyssier-Belot, 11 out of 59 patients presented with ECD associated cutaneous involvement [5]. Among the most common dermatological presentations of ECD are xanthoma like papules [68] and periorbital xanthelasma like skin lesions [4,44,61]. …”

Section: Introductionmentioning

confidence: 99%

Erdheim-Chester Disease: a comprehensive review of the literature

Mazor

Manevich-Mazor

Shoenfeld

2013

Orphanet J Rare Dis

225

309

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Erdheim-Chester Disease (ECD) is a rare form of non Langerhans' cell histiocytosis. Individuals affected by this disease are typically adults between their 5th and 7th decades of life. Males and females are almost equally affected. The multi systemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. 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 99mTc 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(−) 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-α 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-α 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.

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Erdheim–Chester disease

Cited by 22 publications

References 19 publications

Erdheim–Chester Disease

Erdheim–Chester Disease

The histiocytosis Erdheim–Chester disease is an inflammatory myeloid neoplasm

Erdheim-Chester Disease: a comprehensive review of the literature

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