Medicine:Erdheim–Chester disease

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Erdheim–Chester disease
Other namesErdheim–Chester syndrome or Polyostotic sclerosing histiocytosis
Maladie de Chester-Erdheim.png
Chester-Erdheim disease

Erdheim–Chester disease (ECD) is an extremely 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). It was declared a histiocytic neoplasm by the World Health Organization in 2016.[1] Onset typically 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.[2]

Signs and symptoms

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.[3]

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 et al. in 1996 reported the following symptoms in order of frequency of occurrence:[6]


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.[7] ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive.[8] Video-assisted thoracoscopic surgery may be used for diagnostic confirmation and also for therapeutic relief of recurrent pericardial fluid drainage.[9]


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.[6] 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-.


Current treatment options include:

All current treatments have had varying degrees of success.

The vinca alkaloids and anthracyclines have been used most commonly in ECD treatment.[12]


Erdheim–Chester disease was previously associated with high mortality rates.[9][13] In 2005, the survival rate was below 50% at three years from diagnosis.[14] More recent reports of patients treated with Interferon therapy describe an overall 5-year survival of 68%.[15] Long-term survival is currently even more promising, although this impression is not reflected in the recent literature.[16] More recent studies have reported that patients receiving targeted therapies showed no disease progression. It was concluded that targeted therapies (BRAF and/or MEK inhibitors) were dramatically efficacious.


Approximately 500 cases have been reported in the literature to date.[17] ECD affects predominantly adults, with a mean age of 53 years.[6]


The first case of ECD was reported by the American pathologist William Chester in 1930, during his visit to the Austrian pathologist Jakob Erdheim in Vienna.[18]

Society and culture

The Erdheim–Chester Disease Global Alliance is a support and advocacy group with the goal of raising awareness of and promoting research into ECD.[19][20] ECD families and patients are also supported by the Histiocytosis Association, Inc.[20][21]


In the TV show House, season 2 episode 17, "All In", the final diagnosis of a 6-year-old boy who presents with bloody diarrhea and ataxia is Erdheim–Chester disease.[22]


  1. "Erdheim-Chester Disease Declared a Histiocytic Neoplasm". 
  2. "Erdheim–Chester disease at the United States National Library of Medicine". 
  3. "Erdheim-Chester Disease - Histiocytosis Association" (in en-us). 
  4. Lutz, S; Schmalzing, M; Vogel-Claussen, J; Adam, P; May, A (2011). "Rezidivierender Perikarderguss als Erstmanifestation eines Morbus Erdheim-Chester" (in de). Deutsche Medizinische Wochenschrift 136 (39): 1952–6. doi:10.1055/s-0031-1286368. PMID 21935854. 
  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. doi:10.1210/jc.2006-2018. PMID 17405844. 
  6. 6.0 6.1 6.2 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. doi:10.1097/00005792-199605000-00005. PMID 8965684. 
  7. 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. doi:10.1007/s00234-003-0950-z. PMID 12687308. 
  8. 8.0 8.1 "Erdheim Chester Disease". M. D. Anderson Cancer Center. 
  9. 9.0 9.1 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. doi:10.1016/j.ijscr.2011.12.001. PMID 22288060. 
  10. "Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation". Blood 121 (9): 1495–500. Feb 2013. doi:10.1182/blood-2012-07-446286. PMID 23258922. 
  11. FDA Approves First Treatment for Erdheim-Chester Disease. Nov 2017
  12. 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. doi:10.1097/00000441-200208000-00008. PMID 12186113. 
  13. Myra, C; Sloper, L; Tighe, PJ; McIntosh, RS; Stevens, SE; Gregson, RH; Sokal, M; Haynes, AP et al. (2004). "Treatment of Erdheim-Chester disease with cladribine: A rational approach". British Journal of Ophthalmology 88 (6): 844–7. doi:10.1136/bjo.2003.035584. PMID 15148234. 
  14. 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. doi:10.1182/blood-2005-06-2238. PMID 16020507. 
  15. Arnaud, L. et al. (2011). "CNS involvement and treatment with interferon are independent prognostic factors in Erdheim-Chester Disease; a multicenter survival analysis of 53 patients". Blood 117 (10): 2778–2782. doi:10.1182/blood-2010-06-294108. PMID 21239701. 
  16. Diamond, E et al. (2014). "Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease". Blood 124 (4): 483–492. doi:10.1182/blood-2014-03-561381. PMID 24850756. 
  17. Haroche J1 Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, Amoura Z (2014). "Erdheim-Chester disease". Curr Rheumatol Rep 16 (4): 412. doi:10.1007/s11926-014-0412-0. PMID 24532298. 
  18. Chester, William (1930). "Über Lipoidgranulomatose". Virchows Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin 279 (2): 561–602. doi:10.1007/BF01942684. 
  19. "Erdheim–Chester Disease". ECD Global Alliance. 
  20. 20.0 20.1 "Erdheim Chester disease - NORD (National Organization for Rare Disorders)" (in en-US). 
  21. "What Do I Do Now? - Erdheim-Chester Disease - Histiocytosis Association". 
  22. "Internet Movie Database". 

Further reading

External links