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Erdheim–Chester disease

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Title: Erdheim–Chester disease  
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Subject: ECD, Letterer–Siwe disease, Skeletal disorders, Eosinophilic granuloma, Malignant histiocytosis
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Erdheim–Chester disease

Erdheim–Chester disease
Classification and external resources
ICD-10 C96.1
ICD-9 202.3
DiseasesDB 29792
MeSH D031249

Erdheim–Chester disease (also known as Erdheim–Chester syndrome or polyostotic sclerosing histiocytosis) is a rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell histiocytosis). Usually, onset is in middle age. The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.[1]


  • History 1
  • Clinical presentation 2
  • Histology 3
  • Diagnosis 4
  • Treatment 5
  • Prognosis 6
  • Support groups 7
  • References 8
  • Further reading 9
  • External links 10


The first case of ECD was reported by the American pathologist William Chester in 1930.[2]

Clinical presentation

ECD affects predominantly adults, with a mean age of 53 years.[3]

Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have some sort of extraskeletal involvement. This can include kidney, skin, brain and lung involvement, and less frequently retroorbital tissue, pituitary gland and heart involvement is observed.

Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and juxtaarticular in nature. Exophthalmos occurs in some patients and is usually bilateral, symmetric and painless, and in most cases it occurs several years before the final diagnosis. Recurrent pericardial effusion can be a manifestation,[4] as can morphological changes in adrenal size and infiltration.[5]

A review of 59 case studies by Veyssier-Belot, C et al. in 1996 reported the following symptoms in order of frequency of occurrence:[3]


Histologically, ECD differs from Langerhans cell histiocytosis (LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100 proteins or Group 1 CD1a glycoproteins, and electron microscopy of cell cytoplasm does not disclose Birbeck granules.[3] Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis. Bone biopsy is said to offer the greatest likelihood of reaching a diagnosis. In some, there is histiocyte proliferation, and on staining, the section is CD68+ and CD1a-.


Radiologic osteosclerosis and histology are the main diagnostic features. Diagnosis can often be difficult because of the rareness of ECD as well as the need to differentiate it from LCH. A diagnosis from neurological imaging may not be definitive. The presence of symmetrical cerebellar and pontine signal changes on T2-weighted images seem to be typical of ECD, however, multiple sclerosis and metabolic diseases must also be considered in the differential diagnosis.[6] ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive.[7] Video-assisted thoracoscopic surgery may be used for diagnostic confirmation and also for therapeutic relief of recurrent pericardial fluid drainage.[8]


Current treatment options include:

  • Surgical debulking
  • High-dose Corticosteroid therapy
  • Cyclosporin
  • Interferon[7]
  • Chemotherapy
  • vemurafenib It would appear that approximately half these patients harbor point mutations of the BRAF gene at codon 600 substituting the amino acid glutamine for valine. Vemurafenib an oral FDA approved targeted agent to the BRAF protein for melanoma shows dramatic activity in patients Erdheim-Chester disease whose tumor contains the same mutation. [9]

All current treatments have had varying degrees of success.

The vinca alkaloids and anthracyclines have been used most commonly in ECD treatment.[10]


Erdheim–Chester disease is associated with high mortality rates.[8][11] In 2005, the survival rate was below 50% at three years from diagnosis.[12]

Support groups

The Erdheim–Chester Disease Global Alliance is a support and advocacy group with the goal of raising awareness of and promoting research into ECD.[13]


  1. ^ "Erdheim–Chester disease at the United States National Library of Medicine". Retrieved 2008-06-19. 
  2. ^ Chester, William (1930). "Über Lipoidgranulomatose". Virchows Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin 279 (2): 561–602.  
  3. ^ a b c Veyssier-Belot, Catherine; Cacoub, Patrice; Caparros-Lefebvre, Dominique; Wechsler, Janine; Brun, Bernard; Remy, Martine; Wallaert, Benoit; Petit, Henri et al. (1996). "Erdheim-Chester Disease". Medicine 75 (3): 157–69.  
  4. ^ Lutz, S; Schmalzing, M; Vogel-Claussen, J; Adam, P; May, A (2011). "Rezidivierender Perikarderguss als Erstmanifestation eines Morbus Erdheim-Chester" [Recurrent pericardial effusion as first manifestation of Erdheim-Chester disease]. Deutsche Medizinische Wochenschrift (in German) 136 (39): 1952–6.  
  5. ^ Haroche, Julien; Amoura, Zahir; Touraine, Philippe; Seilhean, Danielle; Graef, Claire; Birmelé, Béatrice; Wechsler, Bertrand; Cluzel, Philippe et al. (2007). "Bilateral Adrenal Infiltration in Erdheim-Chester Disease. Report of Seven Cases and Literature Review". Journal of Clinical Endocrinology & Metabolism 92 (6): 2007–12.  
  6. ^ Weidauer, Stefan; von Stuckrad-Barre, Sebastian; Dettmann, Edgar; Zanella, Friedhelm E.; Lanfermann, Heinrich (2003). "Cerebral Erdheim-Chester disease: Case report and review of the literature". Neuroradiology 45 (4): 241–5.  
  7. ^ a b "Erdheim Chester Disease". M. D. Anderson Cancer Center. Retrieved 2007-08-26. 
  8. ^ a b Egan, Aoife; Sorajja, Dan; Jaroszewski, Dawn; Mookadam, Farouk (2012). "Erdheim–Chester disease: The role of video-assisted thoracoscopic surgery in diagnosing and treating cardiac involvement". International Journal of Surgery Case Reports 3 (3): 107–10.  
  9. ^ 1: Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, Cluzel P, Drier A, Hervier B, Benameur N, Besnard S, Donadieu J, Amoura Z. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013 Feb 28;121(9):1495-500. doi: 10.1182/blood-2012-07-446286. Epub 2012 Dec 20. PubMed PMID: 23258922.
  10. ^ Gupta, Anu; Kelly, Benjamin; McGuigan, James E. (2002). "Erdheim-Chester Disease with Prominent Pericardial Involvement:". The American Journal of the Medical Sciences 324 (2): 96–100.  
  11. ^ Myra, C; Sloper, L; Tighe, PJ; McIntosh, RS; Stevens, SE; Gregson, RH; Sokal, M; Haynes, AP; Powell, RJ (2004). "Treatment of Erdheim-Chester disease with cladribine: A rational approach". British Journal of Ophthalmology 88 (6): 844–7.  
  12. ^ Braiteh, F.; Boxrud, C; Esmaeli, B; Kurzrock, R (2005). "Successful treatment of Erdheim-Chester disease, a non-Langerhans-cell histiocytosis, with interferon-". Blood 106 (9): 2992–4.  
  13. ^ "Erdheim–Chester Disease". ECD Global Alliance. Retrieved 2009-05-08. 

Further reading

  • Aouba, Achille; Georgin-Lavialle, Sophie; Pagnoux, Christian; Silva, Nicolas Martin; Renand, Amédée; Galateau-Salle, Françoise; Le Toquin, Sophie; Bensadoun, Henri et al. (2010). "Rationale and efficacy of interleukin-1 targeting in Erdheim–Chester disease". Blood 116 (20): 4070–6.  
  • Arnaud, Laurent; Malek, Zoulikha; Archambaud, Frédérique; Kas, Aurélie; Toledano, Dan; Drier, Aurélie; Zeitoun, Delphine; Cluzel, Philippe et al. (2009). "18F-fluorodeoxyglucose-positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim-Chester disease". Arthritis & Rheumatism 60 (10): 3128–38.  
  • Arnaud, Laurent; Pierre, Isabelle; Beigelman-Aubry, Catherine; Capron, Frédérique; Brun, Anne-Laure; Rigolet, Aude; Girerd, Xavier; Weber, Nina et al. (2010). "Pulmonary involvement in Erdheim-Chester disease: A single-center study of thirty-four patients and a review of the literature". Arthritis & Rheumatism 62 (11): 3504–12.  
  • Boissel, Nicolas; Wechsler, Bertrand; Leblond, Véronique (2001). "Treatment of Refractory Erdheim–Chester Disease with Double Autologous Hematopoietic Stem-Cell Transplantation". Annals of Internal Medicine 135 (9): 844–5.  
  • Braiteh, Fadi; Boxrud, Cynthia; Esmaeli, Bita; Kurzrock, Razelle (2005). "Successful treatment of Erdheim-Chester disease, a non–Langerhans-cell histiocytosis, with interferon-α". Blood 106 (9): 2992–4.  
  • Brun, Anne-Laure; Touitou-Gottenberg, Diane; Haroche, Julien; Toledano, Dan; Cluzel, Philippe; Beigelman-Aubry, Catherine; Piette, Jean-Charles; Amoura, Zahir; Grenier, Philippe A. (2010). "Erdheim-Chester disease: CT findings of thoracic involvement". European Radiology 20 (11): 2579–87.  
  • De Abreu, Marcelo Rodrigues; Castro, Miguel Oliveira; Chung, Christine; Trudell, Debra; Biswal, Sandip; Wesselly, Michelle; Resnick, Donald (2009). "Erdheim–Chester disease: Case report with unique postmortem magnetic resonance imaging, high-resolution radiography, and pathologic correlation". Clinical Imaging 33 (2): 150–3.  
  • Drier, A.; Haroche, J.; Savatovsky, J.; Godeneche, G.; Dormont, D.; Chiras, J.; Amoura, Z.; Bonneville, F. (2010). "Cerebral, Facial, and Orbital Involvement in Erdheim-Chester Disease: CT and MR Imaging Findings". Radiology 255 (2): 586–94.  
  • Haroche, J; Amoura, Z; Dion, E; Wechsler, B; Costedoat-Chalumeau, N; Cacoub, P; Isnard, R; Généreau, T et al. (2004). "Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: Report of 6 new cases and a literature review". Medicine 83 (6): 371–92.  
  • Haroche, J.; Cluzel, P.; Toledano, D.; Montalescot, G.; Touitou, D.; Grenier, P. A.; Piette, J.-C.; Amoura, Z. (2009). "Cardiac Involvement in Erdheim-Chester Disease: Magnetic Resonance and Computed Tomographic Scan Imaging in a Monocentric Series of 37 Patients". Circulation 119 (25): e597–8.  
  • Haroche, Julien; Amoura, Zahir; Trad, Salim G.; Wechsler, Bertrand; Cluzel, Philippe; Grenier, Philippe A.; Piette, Jean-Charles (2006). "Variability in the efficacy of interferon-α in Erdheim-Chester disease by patient and site of involvement: Results in eight patients". Arthritis & Rheumatism 54 (10): 3330–6.  
  • Haroche, Julien; Amoura, Zahir; Charlotte, Frédéric; Salvatierra, Juan; Wechsler, Bertrand; Graux, Carlos; Brousse, Nicole; Piette, Jean-Charles (2008). "Imatinib mesylate for platelet-derived growth factor receptor-beta–positive Erdheim-Chester histiocytosis". Blood 111 (11): 5413–5.  
  • Janku, F.; Amin, H. M.; Yang, D.; Garrido-Laguna, I.; Trent, J. C.; Kurzrock, R. (2010). "Response of Histiocytoses to Imatinib Mesylate: Fire to Ashes". Journal of Clinical Oncology 28 (31): e633–6.  
  • Lachenal, Florence; Cotton, François; Desmurs-Clavel, Hélène; Haroche, Julien; Taillia, Hervé; Magy, Nadine; Hamidou, Mohamed; Salvatierra, Juan et al. (2006). "Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: Report of 6 cases and systematic review of the literature". Journal of Neurology 253 (10): 1267–77.  
  • Mossetti, G; Rendina, D; Numis, FG; Somma, P; Postiglione, L; Nunziata, V (2003). "Biochemical markers of bone turnover, serum levels of interleukin-6/interleukin-6 soluble receptor and bisphosphonate treatment in Erdheim-Chester disease". Clinical and experimental rheumatology 21 (2): 232–6.  
  • Perlat, Antoinette; Decaux, Olivier; Sébillot, Martine; Grosbois, Bernard; Desfourneaux, Véronique; Meadeb, Jean (2009). "Erdheim-Chester disease with predominant mesenteric localization: Lack of efficacy of interferon alpha". Joint Bone Spine 76 (3): 315–7.  

External links

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