Purpose of Review
Erdheim-Chester disease (ECD) is a very rare neoplasm of the non-Langerhans cell histiocytes. Pericardial involvement is uncommon, and we aim to review the current knowledge on the epidemiology, clinical manifestations, and management of recurrent pericarditis due to ECD. We also aim to raise awareness of the importance of considering ECD as a differential diagnosis for recurrent pericarditis in the appropriate clinical settings.
The prevalence of pericardial involvement in ECD is estimated to be 40% and is getting more recognized recently. Up to 68% of patients carry the BRAFV600E mutation, and targeted treatment with vemurafenib, an inhibitor of BRAF kinase, showed an excellent response in those who carry this mutation.
Pericardial disease appears to be the most common cardiac presentation (in 80% of cases). Although pericardial involvement is frequently asymptomatic, patients with ECD can present with typical pericarditis chest pain and signs of right heart failure if constriction is present. The diagnosis of ECD requires a biopsy of the pericardium or another affected organ. If BRAFV600E mutation is absent, limited data exist, and many medications have been tried, like interferon alfa, anakinra, and infliximab.
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Swerdlow SH, Campo E, Pileri SA, Lee Harris N, Stein H, Siebert R, et al. The 2016 Revision of the World Health Organization classification of lymphoid neoplasms. Vol. 127, Blood. American Society of Hematology. 2016:2375–90.
Chester W. Über lipoidgranulomatose. Virchows Arch Pathol Anat Physiol Klin Med. 1930 Dec 1;279(2):561–602.
Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. American Society of Hematology. 2014:124, 483–92.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun 27;417(6892):949–54.
Cavalli G, Guglielmi B, Berti A, Campochiaro C, Sabbadini MG, Dagna L. The multifaceted clinical presentations and manifestations of Erdheim-Chester disease: comprehensive review of the literature and of 10 new cases. Ann Rheum Dis. 2013 Oct;72(10):1691–5.
Arnaud L, Gorochov G, Charlotte F, Lvovschi V, Parizot C, Larsen M, et al. Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients. Blood. 2011 Mar 10;117(10):2783–90.
Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, et al. Erdheim-chester disease. Curr Rheumatol Rep. 2014 Apr;16(4):412.
Gianfreda D, Palumbo AA, Rossi E, Buttarelli L, Manari G, Martini C, et al. Cardiac involvement in erdheim-chester disease: an MRI study Vol. 128, Blood American Society of Hematology; 2016. p. 2468–71.
•• Haroche J, Cluzel P, Toledano D, Montalescot G, Touitou D, Grenier PA, 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 Jun 30;119(25):e597–8. This large case series of 37 patients suggests that cardiac involvement in Erdheim-Chester disease can be initially asymptomatic, and stresses on the importance of systematic cardiac screening since 70% of patients had abnormal imaging of the heart.
Haroche J, Amoura Z, Dion E, Wechsler B, Costedoat-Chalumeau N, Cacoub P, et al. Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease report of 6 new cases and a literature review. 83, Medicine. 2004. p371–92.
Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, Wechsler J, Brun B, Remy M, et al. Erdheim-Chester disease clinical and radiologic characteristics of 59 cases Medicine (Baltimore). 1996;75(3).
Loeffler AG, Memoli VA. Myocardial involvement in Erdheim-Chester disease. Arch Pathol Lab Med. 2004 Jun;128(6):682–5.
• Ghotra AS, Thompson K, Lopez-Mattei J, Bawa D, Hernandez R, Banchs J, et al. Cardiovascular manifestations of Erdheim–Chester disease. Echocardiography. 2019;36(2):229–36. This study reports the different cardiovascular manifestations of Erdheim-Chester disease that include theinvolvement of the pericardium, myocardium, endocardium, valves, vessels and conduction system.
Brun AL, Touitou-Gottenberg D, Haroche J, Toledano D, Cluzel P, Beigelman-Aubry C, et al. Erdheim-Chester disease: CT findings of thoracic involvement. Eur Radiol. 2010 Nov;20(11):2579–87.
Erdheim-Chester disease - Genetics Home Reference - NIH [Internet]. [cited 2020 Mar 16]. Available from: https://ghr.nlm.nih.gov/condition/erdheim-chester-disease#statistics
Arnaud L, Hervier B, Néel A, Hamidou MA, Kahn JE, Wechsler B, 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 Mar 10;117(10):2778–82.
Vaglio A, Corradi D, Maestri R, Callegari S, Buzio C, Salvarani C. Pericarditis heralding Erdheim-Chester disease. Circulation. 2008 Sep 30;118(14):e511–2.
• Ding F, Chahine J, Deshwal H, Ghosh S, Tan C, Simpfendorfer C, et al. Mysterious quad of constrictive pericarditis, recurrent pleural effusions, bone involvement and interstitial lung disease. Oxford Med Case Reports. 2019 Mar;1:2019(3). This study reports a unique case of recurrent pericarditis complicated by pericardial constriction caused by Erdheim-Chester disease diagnosed three years after the first episode of pericarditis.
Palazzuoli A, Mazzei MA, Ruocco G, Volterrani L. Constrictive pericarditis in Erdheim-Chester disease: an integrated echocardiographic and magnetic resonance approach. Int J Cardiol. 2014 Jun 15;174(2):e38–41.
Mishra AK, Mani S, George AA, Sudarsanam TD. Recurrent pericardial effusion and tamponade in a patient with Erdheim-Chester disease (ECD). BMJ Case Rep. 2015;2015(C):1–5.
Gupta A, Kelly B, McGuigan JE. Erdheim-Chester disease with prominent pericardial involvement: clinical, radiologic, and histologic findings. Am J Med Sci. 2002;324(2):96–100.
Alexiev BA, Staats PN. Erdheim-Chester disease with prominent pericardial effusion: cytologic findings and review of the literature Vol 42, Diagnostic Cytopathology Wiley-Liss Inc.; 2014. p. 530–4.
•• Goyal G, Young JR, Koster MJ, Tobin WO, Vassallo R, Ryu JH, et al. 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 Clin Proc. 2019;94(10):2054–71. This consensus statement includes recommendations regarding the diagnosis and management of patients with Erdheim-Chester disease, based on evidence and expert opinion. It also describes the various clinical manifestations of this disease.
Alharthi MS, Calleja A, Panse P, Appleton C, Jaroszewski DE, Tazelaar HD, et al. Multimodality imaging showing complete cardiovascular involvement by Erdheim–Chester disease. Eur J Echocardiogr. 2010;11(7):E25–E25.
Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, et al. 2015 ESC guidelines for the diagnosis and management of pericardial diseases: the task force for the diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) endorsed by: the European Association for Cardio-Thoracic Surg. Eur Heart J. 2015 Nov 7;36(42):2921–64.
Mazor RD, Manevich-Mazor M, Shoenfeld Y. Erdheim-Chester disease: a comprehensive review of the literature. Orphanet J Rare Dis. 2013;8(1):1.
Chetrit M, Xu B, Kwon DH. Ramchand J. Tan CD, et al. Imaging-Guided Therapies for Pericardial Diseases. JACC Cardiovasc Imaging: Rodriguez RE; 2019 Nov 9.
Klein AL, Abbara S, Agler DA, Appleton CP, Asher CR, Hoit B, et al. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial diseaseJ Am Soc Echocardiogr [Internet]. 2013 Sep [cited 2018 Mar 5];26(9):965-1012.e15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23998693 .
Troughton RW, Asher CR, Klein AL. Pericarditis. Lancet (London, England). 2004 Feb 28;363(9410):717–27.
Das JP, Xie L, Riedl CC, Hayes SA, Ginsberg MS, Halpenny DF. Cardiothoracic manifestations of Erdheim-Chester disease Br J Radiol. 2019;92(1104).
Ponsiglione A, Puglia M, Barbuto L, Solla R, Altiero M, Lubrano V, et al. Cardiac involvement in Erdheim-Chester disease: MRI findings and literature revision. Acta Radiol Open. 2015 Sep;4(9):205846011559227.
Young JR, Johnson GB, Murphy RC, Go RS, Broski SM. 18 F-FDG PET/CT in Erdheim-Chester disease: imaging findings and potential BRAF mutation biomarker. J Nucl Med. 2018;59(5):774–9.
Alharthi MS, Calleja A, Panse P, Appleton C, Jaroszewski DE, Tazelaar HD, et al. Multimodality imaging showing complete cardiovascular involvement by Erdheim-Chester disease. Eur J Echocardiogr. 2010;11(7):11–4.
Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, 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 Feb 28;121(9):1495–500.
Berti A, Ferrarini M, Ferrero E, Dagna L, Ferrarini M. Review Cardiovascular manifestations of Erdheim-Chester disease 2009;8–10.
Hervier B, Arnaud L, Charlotte F, Wechsler B, Piette JC, Amoura Z, et al. Treatment of Erdheim-Chester disease with long-term high-dose interferon-α. Semin Arthritis Rheum. 2012;41(6):907–13.
Dagna L, Corti A, Langheim S, Guglielmi B, De Cobelli F, Doglioni C, 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(28):e286–90.
Berti A, Cavalli G, Guglielmi B, Biavasco R, Campochiaro C, Tomelleri A, et al. Tocilizumab in patients with multisystem Erdheim–Chester disease. Oncoimmunology. 2017;6(6):1–6.
Tomelleri A, Cavalli G, De Luca G, Campochiaro C, D’Aliberti T, Tresoldi M, et al. Treating heart inflammation with interleukin-1 blockade in a case of Erdheim-Chester disease. Front Immunol 2018;9(JUN):1–6.
Mazor RD, Manevich-Mazor M, Kesler A, Aizenstein O, Eshed I, Jaffe R, et al. Clinical considerations and key issues in the management of patients with Erdheim-Chester disease: a seven case series. BMC Med. 2014;12(1):1–18.
Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, et al. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015;126(10):1163–71.
Haroche J, Amoura Z, Charlotte F, Salvatierra J, Wechsler B, Graux C, et al. Imatinib mesylate for platelet-derived growth factor receptor-beta positive Erdheim-Chester histiocytosis. Vol. 111, Blood American Society of Hematology; 2008. p. 5413–5.
Janku F, Amin HM, Yang D, Garrido-Laguna I, Trent JC, Kurzrock R. Response of histiocytoses to imatinib mesylate: fire to ashes. J Clin Oncol. 2010 Nov;1:28(31).
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92(3):205–16.
Conflict of Interest
Johnny Chahine, Jafar Alzubi, Hanan Alnajjar, Jay Ramchand, and Michael Chetrit declare that they have no conflict of interest.
Allan L. Klein reports a research grant from Kiniksa and being on the advisory board for Kiniksa, and being on the advisory board for Pfizer.
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This article is part of the Topical Collection on Pericardial Disease
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Chahine, J., Alzubi, J., Alnajjar, H. et al. Erdheim-Chester Disease: a Rare but Important Cause of Recurrent Pericarditis. Curr Cardiol Rep 22, 75 (2020). https://doi.org/10.1007/s11886-020-01307-z
- Erdheim-Chester disease
- Recurrent pericarditis