{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T10:19:21Z","timestamp":1792318761420,"version":"4.4.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008880","name":"Kanae Foundation for the Promotion of Medical Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Immune checkpoint inhibitor (ICI)-related myositis with myocarditis is a rare but potentially fatal immune-related adverse event. However, its clinical features, response to immunosuppressive treatment, and prognosis remain poorly understood. Here, we describe the clinical course of patients with ICI-related myositis overlapping with myocarditis treated at our institution and a systematic review focusing on the response to immunosuppressive therapy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We identified patients who developed ICI-induced myositis with myocarditis and were treated at our hospital using a retrospective chart review of electronic medical records. For the systematic review, studies reporting ICI-induced myositis with myocarditis were identified using the Cochrane Library and PubMed databases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Of the 625 patients treated with ICIs, four developed myositis with concurrent myocarditis. All the patients received immunosuppressive therapy. We assessed the activity of myocarditis and myositis based on temporal changes in troponin and creatine kinase (CK) levels. In all patients, peak troponin values appeared later than the peak CK values (median, 17\u00a0days). The median time from the start of ICI therapy to the peak of troponin and CK levels was 42.5 and 28\u00a0days, respectively. In all patients, CK levels decreased rapidly and steadily after the initiation of immunosuppressants. However, troponin levels were unstable and increased. In all patients, CK levels normalized within one month (range, 12\u201327\u00a0days), but troponin levels took several months to normalize (range, 84\u2013161\u00a0days). Fourteen cases of ICI-related myositis with myocarditis were included in the systematic review. Of the 14 cases, 12 (86%) had their CK level decreased after the initial steroid treatment, but the troponin level increased and was higher than that before the start of treatment. In addition, the peak troponin values appeared later than the peak CK values (a median of 6.5\u00a0days). Eight (89%) of 9 long-term follow-up patients had troponin levels above the normal range even after CK normalization.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    In most cases of ICI-related myositis with myocarditis, troponin levels increased after the initial steroid treatment despite decreased CK levels, and exceeded pre-steroid levels. In addition, troponin remained elevated for several months after CK normalized.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.884776","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T01:24:34Z","timestamp":1652318674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Immune Checkpoint Inhibitor-Related Myositis Overlapping With Myocarditis: An Institutional Case Series and a Systematic Review of Literature"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuki","family":"Nakagomi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Tajiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Murakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoko","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Ieda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1002\/art.41604","article-title":"Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors","volume":"73","author":"Aldrich","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"102586","DOI":"10.1016\/J.AUTREV.2020.102586","article-title":"Immune Checkpoint Inhibitor-Induced Myositis, the Earliest and Most Lethal Complication Among Rheumatic and Musculoskeletal Toxicities","volume":"19","author":"Allenbach","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1161\/CIRCULATIONAHA.118.034497","article-title":"Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology","volume":"140","author":"Bonaca","year":"2019","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3870","DOI":"10.21037\/TCR-21-470","article-title":"Pembrolizumab-Induced Autoimmune Stevens-Johnson Syndrome\/Toxic Epidermal Necrolysis with Myositis and Myocarditis in a Patient with Esophagogastric Junction Carcinoma: a Case Report","volume":"10","author":"Cao","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.annonc.2019.10.023","article-title":"Management of Cardiac Disease in Cancer Patients throughout Oncological Treatment: ESMO Consensus Recommendations","volume":"31","author":"Curigliano","year":"2020","journal-title":"Ann. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"664809","DOI":"10.3389\/fonc.2021.664809","article-title":"Immune-Related Multiple-Organs Injuries Following ICI Treatment with Tislelizumab in an Advanced Non-Small Cell Lung Cancer Patient: A Case Report","volume":"11","author":"Deng","year":"2021","journal-title":"Front. Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nm730","article-title":"Tumor-Associated B7-H1 Promotes T-Cell Apoptosis: A Potential Mechanism of Immune Evasion","volume":"8","author":"Dong","year":"2002","journal-title":"Nat. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"223","DOI":"10.7453\/gahmj.2013.00810.1186\/1752-1947-7-223","article-title":"The CARE Guidelines: Consensus-Based Clinical Case Reporting Guideline Development","volume":"7","author":"Gagnier","year":"2013","journal-title":"J. Med. Case Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/J.HRCR.2020.07.015","article-title":"Complete Heart Block and Subsequent Sudden Cardiac Death from Immune Checkpoint Inhibitor-Associated Myocarditis","volume":"6","author":"Giancaterino","year":"2020","journal-title":"Hear. Case Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"iv119","DOI":"10.1093\/annonc\/mdx225","article-title":"Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"28","author":"Haanen","year":"2017","journal-title":"Ann. Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"803410","DOI":"10.3389\/FIMMU.2021.803410","article-title":"Incidence and Distinct Features of Immune Checkpoint Inhibitor-Related Myositis from Idiopathic Inflammatory Myositis: A Single-Center Experience with Systematic Literature Review and Meta-Analysis","volume":"12","author":"Hamada","year":"2021","journal-title":"Front. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"799077","DOI":"10.3389\/FIMMU.2021.799077","article-title":"Case Report: Glucocorticoid Effect Observation in a Ureteral Urothelial Cancer Patient with ICI-Associated Myocarditis and Multiple Organ Injuries","volume":"12","author":"Hu","year":"2021","journal-title":"Front. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1002\/EHF2.13915","article-title":"Subtle\u2010but\u2010Smouldering Myocardial Injury after Immune Checkpoint Inhibitor Treatment Accompanied by Amyloid Deposits","volume":"9","author":"Ida","year":"2022","journal-title":"Esc. Heart Fail."},{"key":"B15","doi-asserted-by":"publisher","first-page":"ytab342","DOI":"10.1093\/ehjcr\/ytab342","article-title":"A Case Report of Immune Checkpoint Inhibitor-Related Steroid-Refractory Myocarditis and Myasthenia Gravis-Like Myositis Treated with Abatacept and Mycophenolate Mofetil","volume":"5","author":"Jespersen","year":"2021","journal-title":"Eur. Hear J. - Case Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1001\/jamacardio.2021.2241","article-title":"Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Myocarditis: A Narrative Review","volume":"6","author":"Lehmann","year":"2021","journal-title":"JAMA Cardiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"360","DOI":"10.21037\/tlcr.2020.02.05","article-title":"Nivolumab Resulting in Persistently Elevated Troponin Levels Despite Clinical Remission of Myocarditis and Myositis in a Patient with Malignant Pleural Mesothelioma: Case Report","volume":"9","author":"Lie","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1536\/ihj.20-162","article-title":"A Fatal Case of Myocarditis Following Myositis Induced by Pembrolizumab Treatment for Metastatic Upper Urinary Tract Urothelial Carcinoma","volume":"61","author":"Matsui","year":"2020","journal-title":"Int. Heart J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"E32","DOI":"10.1136\/ANNRHEUMDIS-2020-217018","article-title":"Rheumatic Disorders Associated with Immune Checkpoint Inhibitors: What about Myositis? an Analysis of the WHO's Adverse Drug Reactions Database","volume":"81","author":"Nguy\u1ec5n","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s40425-017-0296-4","article-title":"Smoldering Myocarditis Following Immune Checkpoint Blockade","volume":"5","author":"Norwood","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s12471-021-01655-7","article-title":"Immune Checkpoint Inhibitor-Associated Myocarditis","author":"Osinga","year":"2022","journal-title":"Neth Heart J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e013757","DOI":"10.1161\/JAHA.119.013757","article-title":"Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment","volume":"9","author":"Palaskas","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e418","DOI":"10.3747\/co.26.4381","article-title":"Fatal Myocarditis and Rhabdomyositis in a Patient with Stage IV Melanoma Treated with Combined Ipilimumab and Nivolumab","volume":"26","author":"Saibil","year":"2019","journal-title":"Curr. Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ehjcr\/ytaa126","article-title":"Fatal Cerebral Haemorrhagic Infarction Due to Left Ventricular Thrombus after Healing of Immune Checkpoint Inhibitor-Associated Myocarditis","volume":"4","author":"Sakai","year":"2020","journal-title":"Eur. Heart J. Case Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1056\/nejmc1901677","article-title":"Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis","volume":"380","author":"Salem","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1536\/ihj.21-653","article-title":"Asymptomatic Myocarditis with Mild Cardiac Marker Elevation Following Nivolumab-Induced Myositis","volume":"63","author":"Shindo","year":"2022","journal-title":"Int. Heart J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.ejca.2018.10.025","article-title":"Presence of Antibodies to Striated Muscle and Acetylcholine Receptor in Association with Occurrence of Myasthenia Gravis with Myositis and Myocarditis in a Patient with Melanoma Treated with an Anti-Programmed Death 1 Antibody","volume":"106","author":"Shirai","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"B29","doi-asserted-by":"publisher","first-page":"230","DOI":"10.6004\/JNCCN.2020.0012","article-title":"NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020: Featured Updates to the NCCN Guidelines","volume":"18","author":"Thompson","year":"2020","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"B30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/J.JACCAO.2020.12.001","article-title":"Management of Immune Checkpoint Inhibitor-Induced Myocarditis: The French Working Group's Plea for a Pragmatic Approach","volume":"3","author":"Thuny","year":"2021","journal-title":"JACC CardioOncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/iju5.12128","article-title":"Pembrolizumab-Induced Myasthenia Gravis with Myositis and Presumable Myocarditis in a Patient with Bladder Cancer","volume":"3","author":"Todo","year":"2020","journal-title":"IJU Case Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and Cellular Insights into T Cell Exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"250","DOI":"10.21037\/atm.2020.01.79","article-title":"Myositis-Myasthenia Gravis Overlap Syndrome Complicated with Myasthenia Crisis and Myocarditis Associated with Anti-Programmed Cell Death-1 (Sintilimab) Therapy for Lung Adenocarcinoma","volume":"8","author":"Xing","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3389\/fcvm.2021.797009","article-title":"Sintilimab-Induced Myocarditis Overlapping Myositis in a Patient with Metastatic Thymoma: A Case Report","volume":"8","author":"Yang","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1161\/CIRCULATIONAHA.119.042276","article-title":"Cardio-Immuno-Oncology","volume":"141","author":"Zaha","year":"2020","journal-title":"Circulation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1161\/CIRCULATIONAHA.119.044703","article-title":"Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis","volume":"141","author":"Zhang","year":"2020","journal-title":"Circulation"},{"key":"B37","doi-asserted-by":"publisher","first-page":"i157","DOI":"10.1136\/bmj.i157","article-title":"PRISMA Harms Checklist: Improving Harms Reporting in Systematic Reviews","volume":"352","author":"Zorzela","year":"2016","journal-title":"BMJ"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.884776\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T01:24:39Z","timestamp":1652318679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.884776\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":37,"alternative-id":["10.3389\/fphar.2022.884776"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.884776","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]},"article-number":"884776"}}