Jump to content

Erdheim–Chester disease

From Wikipedia, the free encyclopedia
Erdheim–Chester disease
Other namesErdheim–Chester syndromeorPolyostotic sclerosing histiocytosis
Chester-Erdheim disease
SpecialtyOncologyEdit this on Wikidata

Erdheim–Chester disease (ECD)is an extremelyrare diseasecharacterized by theabnormal multiplicationof a specific type ofwhite blood cellscalledhistiocytes,or tissuemacrophages(technically, this disease is termed a non-Langerhans-cellhistiocytosis). It was declared a histiocytic neoplasm by theWorld Health Organizationin 2016.[1]Onset typically is in middle age, although younger patients have been documented. The disease involves an infiltration oflipid-laden macrophages, multinucleatedgiant cells,an inflammatory infiltrate oflymphocytesand histiocytes in thebone marrow,and a generalizedsclerosisof thelong bones.[2]

Signs and symptoms

[edit]

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 frequentlyretroorbitaltissue,pituitary glandand 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, andjuxtaarticularin nature.Exophthalmosoccurs in some patients and is usually bilateral, symmetric and painless, and in most cases it occurs several years before the final diagnosis. Recurrentpericardial effusioncan 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]

Diagnosis

[edit]

Radiologicosteosclerosisand 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 symmetricalcerebellarandpontinesignal changes on T2-weighted images seem to be typical of ECD, however,multiple sclerosisand metabolic diseases must also be considered in thedifferential 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 surgerymay be used for diagnostic confirmation and also for therapeutic relief of recurrent pericardial fluid drainage.[9]

Histology

[edit]

Histologically, ECD differs fromLangerhans cell histiocytosis(LCH) in a number of ways. Unlike LCH, ECD does not stain positive forS-100 proteinsorGroup 1 CD1aglycoproteins,andelectron microscopyof cellcytoplasmdoes not discloseBirbeck granules.[6]Tissue samples showxanthomatousorxanthogranulomatousinfiltration by lipid-laden or foamy histiocytes, and are usually surrounded byfibrosis.Bonebiopsyis said to offer the greatest likelihood of reaching a diagnosis. It would appear that approximately half these patients harbor pointmutations of theBRAFgeneatcodon 600 substituting the amino acid glutamine for valine.In some, there is histiocyte proliferation, and on staining, the section isCD68+ and CD1a-.[citation needed]

Treatment

[edit]

There are two FDA-approved targeted drugs to treat ECD.

  • Vemurafenib,an oral agent approved in 2019, targets the BRAF protein. It was approved after showing dramatic efficacy in ECD patients harboring theBRAFV600E mutation.[10][11]
  • Cobimetinib,an oral inhibitor of MEK1 and MEK2, was approved in November 2022.[12]

Other treatment options include:

Prognosis

[edit]

Erdheim–Chester disease was previously associated with high mortality rates.[14]However, long-term survival is now more promising. Recent studies have reported that some patients receiving targeted therapies showed no disease progression. Targeted therapies using BRAF, MEK and/or other inhibitors have been dramatically efficacious.[10][13][15][16]In 2019, theMayo Clinicpublished guidelines for the diagnosis and treatment of the disease, stressing the importance of genetic testing: "Recent insights into their genomic architecture demonstrating mitogen-activated protein kinase/extracellular signal-regulated kinase pathway mutations have now enabled potential treatment with targeted therapies in most patients."[17]

Epidemiology

[edit]

Approximately 500 cases had been reported in the literature as of 2014.[18]ECD affects predominantly adults, with a mean age of 53 years.[6]

History

[edit]

The first case of ECD was reported by the American pathologistWilliam Chesterin 1930, during his visit to theAustrianpathologistJakob ErdheiminVienna.[19]

Society and culture

[edit]

TheErdheim–Chester Disease Global Allianceis a support and advocacy group with the goal of raisingawarenessof and promoting research into ECD.[20][21]ECD families and patients are also supported by the Histiocytosis Association, Inc.[21][22]

Media

[edit]

In the TV showHouse,season 2 episode 17, "All In",the final diagnosis of a 6-year-old boy who presents with bloody diarrhea andataxiais Erdheim–Chester disease.[23]

References

[edit]
  1. ^"Erdheim-Chester Disease Declared a Histiocytic Neoplasm"(PDF).18 May 2016.Retrieved2018-07-18– via erdheim-chester.org.
  2. ^"Erdheim–Chester disease".Medical Subject Headings.United States National Library of Medicine. 8 July 2008.Retrieved19 June2008.
  3. ^"Erdheim-Chester Disease".Histiocytosis Association.Retrieved2017-12-21.
  4. ^Lutz SZ, Schmalzing M, Vogel-Claussen J, Adam P, May AE (September 2011). "[Recurrent pericardial effusion as first manifestation of Erdheim-Chester disease]" [Recurrent pericardial effusion as first manifestation of Erdheim-Chester disease].Deutsche Medizinische Wochenschrift(in German).136(39): 1952–1956.doi:10.1055/s-0031-1286368.PMID21935854.
  5. ^Haroche J, Amoura Z, Touraine P, Seilhean D, Graef C, Birmelé B, et al. (June 2007)."Bilateral adrenal infiltration in Erdheim-Chester disease. Report of seven cases and literature review".The Journal of Clinical Endocrinology and Metabolism.92(6): 2007–2012.doi:10.1210/jc.2006-2018.PMID17405844.
  6. ^abcVeyssier-Belot C, Cacoub P, Caparros-Lefebvre D, Wechsler J, Brun B, Remy M, et al. (May 1996)."Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases".Medicine.75(3): 157–169.doi:10.1097/00005792-199605000-00005.PMID8965684.S2CID32150913.
  7. ^Weidauer S, von Stuckrad-Barre S, Dettmann E, Zanella FE, Lanfermann H (April 2003). "Cerebral Erdheim-Chester disease: case report and review of the literature".Neuroradiology.45(4): 241–245.doi:10.1007/s00234-003-0950-z.PMID12687308.S2CID9513277.
  8. ^ab"Erdheim Chester Disease".M. D. Anderson Cancer Center.Retrieved2007-08-26.
  9. ^Egan A, Sorajja D, Jaroszewski D, Mookadam F (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): 107–110.doi:10.1016/j.ijscr.2011.12.001.PMC3267285.PMID22288060.
  10. ^abHaroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, et al. (February 2013)."Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation".Blood.121(9): 1495–1500.doi:10.1182/blood-2012-07-446286.PMID23258922.
  11. ^"FDA Approves First Treatment for Erdheim-Chester Disease".Pharmacy Practice News.6 November 2017.
  12. ^Rosa K (2 November 2022)."FDA Approves Cobimetinib for Histiocytic Neoplasms".OncLive.Retrieved2022-11-19.
  13. ^abAbeykoon JP, Lasho TL, Dasari S, Rech KL, Ranatunga WK, Manske MK, et al. (March 2022)."Sustained, complete response to pexidartinib in a patient with CSF1R-mutated Erdheim-Chester disease".American Journal of Hematology.97(3): 293–302.doi:10.1002/ajh.26441.PMC9536810.PMID34978715.
  14. ^Myra C, Sloper L, Tighe PJ, McIntosh RS, Stevens SE, Gregson RH, et al. (June 2004)."Treatment of Erdheim-Chester disease with cladribine: a rational approach".The British Journal of Ophthalmology.88(6): 844–847.doi:10.1136/bjo.2003.035584.PMC1772168.PMID15148234.
  15. ^Aziz SN, Proano L, Cruz C, Tenemaza MG, Monteros G, Hassen G, et al. (June 2022)."Vemurafenib in the Treatment of Erdheim Chester Disease: A Systematic Review".Cureus.14(6): e25935.doi:10.7759/cureus.25935.PMC9282605.PMID35844342.
  16. ^The ASCO Post Staff (2 November 2022)."FDA Approves Oral MEK Inhibitor Cobimetinib for Histiocytic Neoplasms".The ASCO Post.Retrieved2022-11-19.
  17. ^Goyal G, Young JR, Koster MJ, Tobin WO, Vassallo R, Ryu JH, et al. (October 2019)."The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease".Mayo Clinic Proceedings.94(10): 2054–2071.doi:10.1016/j.mayocp.2019.02.023.PMID31472931.S2CID201713697.
  18. ^Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, Amoura Z (April 2014)."Erdheim-Chester disease".Current Rheumatology Reports.16(4): 412.doi:10.1007/s11926-014-0412-0.PMID24532298.
  19. ^Chester W (1930). "Über Lipoidgranulomatose".Virchows Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin.279(2): 561–602.doi:10.1007/BF01942684.S2CID27359311.
  20. ^"Erdheim–Chester Disease".ECD Global Alliance.Retrieved2009-05-08.
  21. ^ab"Erdheim Chester disease".NORD (National Organization for Rare Disorders).Retrieved2016-03-01.
  22. ^"What Do I Do Now? - Erdheim-Chester Disease".Histiocytosis Association.Retrieved2016-03-01.
  23. ^"Internet Movie Database".IMDB.Retrieved27 October2021.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Erdheim–Chester_disease&oldid=1241901323"