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Erdheim-Chester disease

Eric Jacobsen, MD
Section Editor
Arnold S Freedman, MD
Deputy Editor
Alan G Rosmarin, MD


Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytic disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocytes on biopsy, with or without histiocytic infiltration of extraskeletal tissues. ECD was first described by Erdheim and Chester in 1930 [1]. Only several hundred cases have been reported in the medical literature since that time.

Histocytic disorders are thought to be derived from mononuclear phagocytic cells (macrophages and dendritic cells) or histiocytes. This group has generally been divided into Langerhans cell histiocytosis and non-Langerhans histiocytosis. Langerhans cell histiocytosis is so named for its presumed derivation from the Langerhans cells, which are specialized dendritic cells found in the skin and mucosa. In contrast, non-Langerhans histiocytoses are thought to be derived from the monocyte-macrophage lineage.

The epidemiology, clinical manifestations, pathologic features, diagnosis, and management of ECD will be presented here. The diagnosis and management of Langerhans cell histiocytosis is presented separately. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis" and "Pulmonary Langerhans cell histiocytosis" and "Langerhans cell histiocytosis (eosinophilic granuloma) of bone in children and adolescents".)


ECD is a rare histiocytic disorder and the incidence is unknown. Fewer than 500 cases have been reported in the published literature [2]. ECD has been diagnosed in all age groups, but is most common in adults. The mean age at diagnosis is 53 years [2]. There is a slight male predominance. Although there is speculation that ECD and other histiocyte disorders may represent an aberrant response to infection, no infectious etiology has been identified. There is no evidence that ECD is an inheritable genetic disorder.


ECD, and the related histiocytic disorder Langerhans cell histiocytosis, are hematopoietic neoplasms that represent clonal proliferation of myeloid progenitor cells. This finding was demonstrated by tracking of the BRAF V600E mutation in subsets of dendritic cells, mature monocytes, committed myeloid progenitors, and CD34+ cells of affected ECD patients [3,4]. Furthermore, hematopoietic stem/progenitor cells that carry the BRAF V600E mutation can recapitulate the phenotype of ECD by differentiation in vitro and in a xenograft model.

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Literature review current through: Oct 2017. | This topic last updated: Aug 07, 2017.
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  1. Chester W. Uber lipoidgranulomatose. Virchows Arch A Pathol Anat Histol 1930; 279:561.
  2. Cavalli G, Guglielmi B, Berti A, et al. The multifaceted clinical presentations and manifestations of Erdheim-Chester disease: comprehensive review of the literature and of 10 new cases. Ann Rheum Dis 2013; 72:1691.
  3. Milne P, Bigley V, Bacon CM, et al. Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults. Blood 2017; 130:167.
  4. Durham BH, Roos-Weil D, Baillou C, et al. Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells. Blood 2017; 130:176.
  5. Haroche J, Charlotte F, Arnaud L, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood 2012; 120:2700.
  6. Diamond EL, Durham BH, Haroche J, et al. Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms. Cancer Discov 2016; 6:154.
  7. Berres ML, Lim KP, Peters T, et al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med 2014; 211:669.
  8. Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood 2014; 124:3007.
  9. Emile JF, Diamond EL, Hélias-Rodzewicz Z, et al. Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood 2014; 124:3016.
  10. Brown NA, Furtado LV, Betz BL, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E-negative Langerhans cell histiocytosis. Blood 2014; 124:1655.
  11. Nelson DS, Quispel W, Badalian-Very G, et al. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood 2014; 123:3152.
  12. Nelson DS, van Halteren A, Quispel WT, et al. MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis. Genes Chromosomes Cancer 2015; 54:361.
  13. Arnaud L, Gorochov G, Charlotte F, et al. Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients. Blood 2011; 117:2783.
  14. Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, et al. Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases. Medicine (Baltimore) 1996; 75:157.
  15. Drier A, Haroche J, Savatovsky J, et al. Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings. Radiology 2010; 255:586.
  16. Dion E, Graef C, Miquel A, et al. Bone involvement in Erdheim-Chester disease: imaging findings including periostitis and partial epiphyseal involvement. Radiology 2006; 238:632.
  17. Haroche J, Cluzel P, Toledano D, et al. Images in cardiovascular medicine. Cardiac involvement in Erdheim-Chester disease: magnetic resonance and computed tomographic scan imaging in a monocentric series of 37 patients. Circulation 2009; 119:e597.
  18. Gianfreda D, Palumbo AA, Rossi E, et al. Cardiac involvement in Erdheim-Chester disease: an MRI study. Blood 2016; 128:2468.
  19. Haroche J, Amoura Z, Dion E, et al. Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review. Medicine (Baltimore) 2004; 83:371.
  20. Arnaud L, Pierre I, Beigelman-Aubry C, et al. Pulmonary involvement in Erdheim-Chester disease: a single-center study of thirty-four patients and a review of the literature. Arthritis Rheum 2010; 62:3504.
  21. Diamond EL, Dagna L, Hyman DM, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 2014; 124:483.
  22. Brun AL, Touitou-Gottenberg D, Haroche J, et al. Erdheim-Chester disease: CT findings of thoracic involvement. Eur Radiol 2010; 20:2579.
  23. Rush WL, Andriko JA, Galateau-Salle F, et al. Pulmonary pathology of Erdheim-Chester disease. Mod Pathol 2000; 13:747.
  24. Surabhi VR, Menias C, Prasad SR, et al. Neoplastic and non-neoplastic proliferative disorders of the perirenal space: cross-sectional imaging findings. Radiographics 2008; 28:1005.
  25. Brodkin CL, Wszolek ZK. Neurologic presentation of Erdheim-Chester disease. Neurol Neurochir Pol 2006; 40:397.
  26. Lachenal F, Cotton F, Desmurs-Clavel H, et al. Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: report of 6 cases and systematic review of the literature. J Neurol 2006; 253:1267.
  27. Diamond EL, Hatzoglou V, Patel S, et al. Diffuse reduction of cerebral grey matter volumes in Erdheim-Chester disease. Orphanet J Rare Dis 2016; 11:109.
  28. Volpicelli ER, Doyle L, Annes JP, et al. Erdheim-Chester disease presenting with cutaneous involvement: a case report and literature review. J Cutan Pathol 2011; 38:280.
  29. Barnes PJ, Foyle A, Haché KA, et al. Erdheim-Chester disease of the breast: a case report and review of the literature. Breast J 2005; 11:462.
  30. Gupta A, Aman K, Al-Babtain M, et al. Multisystem Erdheim-Chester disease; a unique presentation with liver and axial skeletal involvement. Br J Haematol 2007; 138:280.
  31. Kim MS, Kim CH, Choi SJ, et al. Erdheim-chester disease. Ann Dermatol 2010; 22:439.
  32. Jaffe R. Erdheim-Chester disease. In: WHO Classification of Tumours of Soft Tissue and Bone, 4, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (Eds), International Agency for Research on Cancer, Lyon 2013. p.358.
  33. Dagna L, Girlanda S, Langheim S, et al. Erdheim-Chester disease: report on a case and new insights on its immunopathogenesis. Rheumatology (Oxford) 2010; 49:1203.
  34. Gong L, He XL, Li YH, et al. Clonal status and clinicopathological feature of Erdheim-Chester disease. Pathol Res Pract 2009; 205:601.
  35. Al-Quran S, Reith J, Bradley J, Rimsza L. Erdheim-Chester disease: case report, PCR-based analysis of clonality, and review of literature. Mod Pathol 2002; 15:666.
  36. Vencio EF, Jenkins RB, Schiller JL, et al. Clonal cytogenetic abnormalities in Erdheim-Chester disease. Am J Surg Pathol 2007; 31:319.
  37. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
  38. Hervier B, Haroche J, Arnaud L, et al. Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood 2014; 124:1119.
  39. Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol 1990; 7:19.
  40. Pulsoni A, Anghel G, Falcucci P, et al. Treatment of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): report of a case and literature review. Am J Hematol 2002; 69:67.
  41. Utikal J, Ugurel S, Kurzen H, et al. Imatinib as a treatment option for systemic non-Langerhans cell histiocytoses. Arch Dermatol 2007; 143:736.
  42. Frater JL, Maddox JS, Obadiah JM, Hurley MY. Cutaneous Rosai-Dorfman disease: comprehensive review of cases reported in the medical literature since 1990 and presentation of an illustrative case. J Cutan Med Surg 2006; 10:281.
  43. Wang KH, Chen WY, Liu HN, et al. Cutaneous Rosai-Dorfman disease: clinicopathological profiles, spectrum and evolution of 21 lesions in six patients. Br J Dermatol 2006; 154:277.
  44. Jaffe R. The diagnostic histopathology of Langerhans cell histiocytosis. In: Histiocytic Disorders of Children and Adults. Basic Science, Clinical Features, and Therapy, Weitzman S, Egeler RM (Eds), Cambridge University Press, Cambridge 2005. p.14.
  45. Steňová E, Steňo B, Povinec P, et al. FDG-PET in the Erdheim-Chester disease: its diagnostic and follow-up role. Rheumatol Int 2012; 32:675.
  46. Arnaud L, Malek Z, Archambaud F, et al. 18F-fluorodeoxyglucose-positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim-Chester disease. Arthritis Rheum 2009; 60:3128.
  47. Arnaud L, Hervier B, Néel A, et al. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood 2011; 117:2778.
  48. Haroche J, Amoura Z, Trad SG, et al. Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients. Arthritis Rheum 2006; 54:3330.
  49. Haroche J, Cohen-Aubart F, Emile JF, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood 2013; 121:1495.
  50. Haroche J, Cohen-Aubart F, Emile JF, et al. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol 2015; 33:411.
  51. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 2015; 373:726.
  52. Nordmann TM, Juengling FD, Recher M, et al. Trametinib after disease reactivation under dabrafenib in Erdheim-Chester disease with both BRAF and KRAS mutations. Blood 2017; 129:879.
  53. Cohen Aubart F, Emile JF, Maksud P, et al. Efficacy of the MEK inhibitor cobimetinib for wild-type BRAF Erdheim-Chester disease. Br J Haematol 2016.
  54. Myra C, Sloper L, Tighe PJ, et al. Treatment of Erdheim-Chester disease with cladribine: a rational approach. Br J Ophthalmol 2004; 88:844.
  55. Bourke SC, Nicholson AG, Gibson GJ. Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone. Thorax 2003; 58:1004.
  56. Goyal G, Shah MV, Call TG, et al. Clinical and Radiologic Responses to Cladribine for the Treatment of Erdheim-Chester Disease. JAMA Oncol 2017.
  57. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood 2013; 121:5006.
  58. Aouba A, Georgin-Lavialle S, Pagnoux C, et al. Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease. Blood 2010; 116:4070.
  59. Tran TA, Pariente D, Guitton C, et al. Treatment of Erdheim-Chester disease with canakinumab. Rheumatology (Oxford) 2014; 53:2312.
  60. Courcoul A, Vignot E, Chapurlat R. Successful treatment of Erdheim-Chester disease by interleukin-1 receptor antagonist protein. Joint Bone Spine 2014; 81:175.
  61. Killu AM, Liang JJ, Jaffe AS. Erdheim-Chester disease with cardiac involvement successfully treated with anakinra. Int J Cardiol 2013; 167:e115.
  62. Aubert O, Aouba A, Deshayes S, et al. Favorable radiological outcome of skeletal Erdheim-Chester disease involvement with anakinra. Joint Bone Spine 2013; 80:206.
  63. Tran TA, Pariente D, Lecron JC, et al. Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs. Arthritis Rheum 2011; 63:4031.
  64. Cohen-Aubart F, Maksud P, Saadoun D, et al. Variability in the efficacy of the IL1 receptor antagonist anakinra for treating Erdheim-Chester disease. Blood 2016; 127:1509.
  65. Haroche J, Amoura Z, Charlotte F, et al. Imatinib mesylate for platelet-derived growth factor receptor-beta-positive Erdheim-Chester histiocytosis. Blood 2008; 111:5413.
  66. Janku F, Amin HM, Yang D, et al. Response of histiocytoses to imatinib mesylate: fire to ashes. J Clin Oncol 2010; 28:e633.
  67. Jeon IS, Lee SS, Lee MK. Chemotherapy and interferon-alpha treatment of Erdheim-Chester disease. Pediatr Blood Cancer 2010; 55:745.
  68. Gianfreda D, Nicastro M, Galetti M, et al. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood 2015; 126:1163.
  69. Dagna L, Corti A, Langheim S, et al. Tumor necrosis factor α as a master regulator of inflammation in Erdheim-Chester disease: rationale for the treatment of patients with infliximab. J Clin Oncol 2012; 30:e286.
  70. Miller RC, Villà S, Kamer S, et al. Palliative treatment of Erdheim-Chester disease with radiotherapy: a Rare Cancer Network study. Radiother Oncol 2006; 80:323.