{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T09:03:40Z","timestamp":1786871020774,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: the role of the R202Q (c.605G&gt;A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods: a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results: the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions: the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant\u2019s role in pericardial inflammation and guide personalized treatment strategies.<\/jats:p>","DOI":"10.3390\/jcm13206051","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T03:53:47Z","timestamp":1728618827000},"page":"6051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anakinra-Dependent Recurrent Pericarditis: The Role of the R202Q Variant of the MEFV Gene"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1203-000X","authenticated-orcid":false,"given":"Alessandro","family":"Andreis","sequence":"first","affiliation":[{"name":"Advanced Cardiovascular Echocardiography Unit, Cardiovascular and Thoracic Department, Citt\u00e0 della Salute e della Scienza di Torino University Hospital, 10126 Turin, Italy"},{"name":"Division of Cardiology, Citt\u00e0 della Salute e della Scienza di Torino University Hospital, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica Curr\u00f2","family":"Dossi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Citt\u00e0 della Salute e della Scienza di Torino University Hospital, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4940-0876","authenticated-orcid":false,"given":"Gaetano Maria","family":"De Ferrari","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Citt\u00e0 della Salute e della Scienza di Torino University Hospital, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Torino, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Alunni","sequence":"additional","affiliation":[{"name":"Advanced Cardiovascular Echocardiography Unit, Cardiovascular and Thoracic Department, Citt\u00e0 della Salute e della Scienza di Torino University Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5722-0245","authenticated-orcid":false,"given":"Massimo","family":"Imazio","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), University of Udine, 33100 Udine, Italy"},{"name":"Cardiothoracic Department, University Hospital Santa Maria della Misericordia, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"A1298","DOI":"10.1016\/S0735-1097(15)61298-0","article-title":"Chest pain in patients under age 40: Are we getting it right?","volume":"65","author":"Morgenstern","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"A12863","DOI":"10.1161\/circ.130.suppl_2.12863","article-title":"Abstract 12863: Non-Cardiac Chest Pain: Is It Really?","volume":"130","author":"Boniface","year":"2014","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10067-021-05906-1","article-title":"Clinical significance of MEFV gene variation R202Q","volume":"41","author":"Kandur","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_4","unstructured":"(2024, June 17). r202q[VARNAME]-ClinVar-NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1093\/eurheartj\/ehv318","article-title":"2015 ESC Guidelines for the diagnosis and management of pericardial diseases","volume":"36","author":"Adler","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1001\/jama.289.9.1150","article-title":"Acute Pericarditis: Current Concepts and Practice","volume":"289","author":"Spodick","year":"2003","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.amjcard.2019.09.026","article-title":"Usefulness of Cardiac Magnetic Resonance for Recurrent Pericarditis","volume":"125","author":"Imazio","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Andreis, A., Solano, A., Balducci, M., Picollo, C., Ghigliotti, M., Giordano, M., Agosti, A., Collini, V., Anselmino, M., and De Ferrari, G.M. (2024). INFLA-score: A new diagnostic paradigm to identify pericarditis. Hell. J. Cardiol.","DOI":"10.1016\/j.hjc.2024.03.010"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1007\/s11739-021-02803-y","article-title":"The Torino Pericarditis Score: A new-risk stratification tool to predict complicated pericarditis","volume":"16","author":"Imazio","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0022-5223(19)35571-0","article-title":"The effective treatment of postpericardiotomy syndrome after cardiac operations. A randomized placebo-controlled trial","volume":"100","author":"Horneffer","year":"1990","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2459\/JCM.0000000000001079","article-title":"Colchicine for the treatment of cardiovascular diseases: Old drug, new targets","volume":"22","author":"Andreis","year":"2020","journal-title":"J. Cardiovasc. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.semarthrit.2008.08.006","article-title":"Colchicine update: 2008","volume":"38","author":"Terkeltaub","year":"2009","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s11926-002-0073-2","article-title":"Update on colchicine and its mechanism of action","volume":"4","author":"Molad","year":"2002","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s10620-019-05729-w","article-title":"Acute Colchicine Poisoning Causes Endotoxemia via the Destruction of Intestinal Barrier Function: The Curative Effect of Endotoxin Prevention in a Murine Model","volume":"65","author":"Horioka","year":"2020","journal-title":"Dig. Dis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1007\/s11739-021-02654-7","article-title":"Colchicine efficacy and safety for the treatment of cardiovascular diseases","volume":"16","author":"Andreis","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2174\/1568010053622984","article-title":"Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: An update","volume":"4","author":"Cerquaglia","year":"2005","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJM198604173141601","article-title":"Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever","volume":"314","author":"Zemer","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.clinthera.2014.07.017","article-title":"Mechanism of action of colchicine in the treatment of gout","volume":"36","author":"Dalbeth","year":"2014","journal-title":"Clin. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/eurheartj\/ehi197","article-title":"Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: A multi-centre all-case analysis","volume":"26","author":"Artom","year":"2005","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.amjcard.2006.01.086","article-title":"Long-Term Outcomes in Difficult-to-Treat Patients With Recurrent Pericarditis","volume":"98","author":"Brucato","year":"2006","journal-title":"Am. J. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1001\/jama.298.23.2754","article-title":"\u2018False-positive\u2019 cardiac catheterization laboratory activation among patients with suspected ST-segment elevation myocardial infarction","volume":"298","author":"Larson","year":"2007","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e000944","DOI":"10.1136\/openhrt-2018-000944","article-title":"Quantitative assessment of pericardial delayed hyperenhancement helps identify patients with ongoing recurrences of pericarditis","volume":"5","author":"Kumar","year":"2018","journal-title":"Open Heart"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1136\/hrt.2003.026120","article-title":"Relapsing pericarditis","volume":"90","year":"2004","journal-title":"Heart Br. Card Soc."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lazaros, G., Antonatou, K., and Vassilopoulos, D. (2017). The Therapeutic Role of Interleukin-1 Inhibition in Idiopathic Recurrent Pericarditis: Current Evidence and Future Challenges. Front. Med., 4.","DOI":"10.3389\/fmed.2017.00078"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9262741","DOI":"10.1155\/2016\/9262741","article-title":"Anticardiac Antibodies in Patients with Chronic Pericardial Effusion","volume":"2016","author":"Karatolios","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/hrt.2009.187138","article-title":"Anti-heart and anti-intercalated disk autoantibodies: Evidence for autoimmunity in idiopathic recurrent acute pericarditis","volume":"96","author":"Caforio","year":"2010","journal-title":"Heart Br. Card Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.recesp.2016.06.021","article-title":"Recurrent Pericarditis as the Presenting Form of Adult Still\u2019s Disease","volume":"70","author":"Calabuig","year":"2017","journal-title":"Rev. Esp. De Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1177\/2047487319879534","article-title":"Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study","volume":"27","author":"Imazio","year":"2019","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1056\/NEJMoa2027892","article-title":"Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis","volume":"384","author":"Klein","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11886-020-01308-y","article-title":"Novel Pharmacotherapies for Recurrent Pericarditis: Current Options in 2020","volume":"22","author":"Tombetti","year":"2020","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1080\/14787210.2018.1483238","article-title":"Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs","volume":"16","author":"Goletti","year":"2018","journal-title":"Expert Rev. Anti. Infect Ther."},{"key":"ref_32","first-page":"1561","article-title":"Anakinra for constrictive pericarditis associated with incessant or recurrent pericarditis","volume":"106","author":"Andreis","year":"2020","journal-title":"Heart Br. Cardiol. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1017\/S1047951119000672","article-title":"Anaphylactic reaction to anakinra in a child with steroid-dependent idiopathic recurrent pericarditis and successful management with canakinumab","volume":"29","author":"Sahin","year":"2019","journal-title":"Cardiol. Young"},{"key":"ref_34","first-page":"1494","article-title":"Canakinumab for recurrent rheumatic disease associated-pericarditis: A case series with long-term follow-up","volume":"57","author":"Kougkas","year":"2018","journal-title":"Rheumatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ahj.2020.07.004","article-title":"RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1\u03b1 and interleukin-1\u03b2 trap, in patients with recurrent pericarditis","volume":"228","author":"Klein","year":"2020","journal-title":"Am. Heart J."},{"key":"ref_36","first-page":"802","article-title":"Recurrent pericarditis caused by a rare mutation in the TNFRSF1A gene and with excellent response to anakinra treatment","volume":"28","author":"Cantarini","year":"2010","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jacbts.2020.11.016","article-title":"The Role of NLRP3 Inflammasome in Pericarditis","volume":"6","author":"Mauro","year":"2021","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_38","unstructured":"(2024, June 30). Infevers-Tabular List. Available online: https:\/\/infevers.umai-montpellier.fr\/web\/search.php?n=1."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.3906\/sag-2008-11","article-title":"Familial Mediterranean fever, from pathogenesis to treatment: A contemporary review","volume":"50","author":"Tufan","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"ref_40","unstructured":"(2024, June 30). Familial Mediterranean Fever (FMF) in Turkey: Results of a Nationwide Multicenter Study-PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/15643295\/."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1093\/qjmed\/90.10.643","article-title":"Attacks of pericarditis as a manifestation of familial Mediterranean fever (FMF)","volume":"90","author":"Kees","year":"1997","journal-title":"QJM Mon. J. Assoc. Physicians"},{"key":"ref_42","first-page":"CS139","article-title":"Recurrent pericarditis as the initial manifestation of Familial Mediterranean fever","volume":"14","author":"Okutur","year":"2008","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_43","first-page":"5","article-title":"Familial Mediterranean fever; diagnosis, treatment, and complications","volume":"4","author":"Bashardoust","year":"2015","journal-title":"J. Nephropharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2459\/JCM.0000000000000520","article-title":"Refractory idiopathic recurrent pericarditis: Treatment with interleukin-1 receptor antagonist is an option!","volume":"18","author":"Ozturk","year":"2017","journal-title":"J. Cardiovasc. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12969-016-0097-1","article-title":"Distribution of MEFV gene mutations and R202Q polymorphism in the Serbian population and their influence on oxidative stress and clinical manifestations of inflammation","volume":"14","author":"Debeljak","year":"2016","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.14744\/zkmj.2021.85579","article-title":"Recurrent pericarditis caused by familial Mediterranean fever: A case report","volume":"52","author":"Karaman","year":"2021","journal-title":"Zeynep Kamil Med. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.immuni.2011.02.020","article-title":"Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1\u03b2 activation and severe autoinflammation in mice","volume":"34","author":"Chae","year":"2011","journal-title":"Immunity"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"A104","DOI":"10.1186\/1546-0096-11-S1-A104","article-title":"OR7-003\u2013MEFV genotype, IL1B and role of NLRP3 in FMF","volume":"11","author":"Omenetti","year":"2013","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"de Torre-Minguela, C., Mesa del Castillo, P., and Pelegr\u00edn, P. (2017). The NLRP3 and Pyrin Inflammasomes: Implications in the Pathophysiology of Autoinflammatory Diseases. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00043"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/eji.201746947","article-title":"Function and mechanism of the pyrin inflammasome","volume":"48","author":"Heilig","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_51","first-page":"1189","article-title":"Ab0021 Real Life Data on Tapering and Discontinuation of Anakinra Treatment in Recurrent Pericarditis: An International Registry","volume":"82","author":"Malandrino","year":"2023","journal-title":"Ann.. Rheum Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:01Z","timestamp":1760112661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/20\/6051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,11]]},"references-count":51,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["jcm13206051"],"URL":"https:\/\/doi.org\/10.3390\/jcm13206051","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,11]]}}}