Nivolumab and Ipilimumab-induced myositis and myocarditis mimicking a myasthenia gravis presentation

Valenti-Azcarate, Rafael; Vázquez, Inés; Toledano-Illán, Carlos; Gastearena, Miguel Ángel Idoate; Pérez-Larraya, Jaime Gállego

doi:10.1016/j.nmd.2019.10.006

Cited by 28 publications

(17 citation statements)

References 6 publications

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“…Occasionally, irMG co-existed with ir-myositis. Both present with limb weakness and even respiratory failure due to diaphragmatic involvement ( 63 , 64 ). Carefully distinguishing the two similar conditions was required because the co-existence of the two irAEs may increase the mortality rate (the mortality rate in irMG with ir-myositis is 35%; in irMG without myositis, it is 25%).…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis

et al. 2020

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The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis. Because of the high mortality of irMG, measures to increase the vigilance of medical teams are necessary to ensure the timely identification of the signs of irMG and early treatment, particularly in the early course of ICI therapy. The diagnostic plans should be comprehensive and include the evaluation of other organ systems, such as the dermatological, gastrointestinal, respiratory, neuromuscular, and cardiovascular systems, in addition to the traditional diagnostic tests for MG. Treatment plans should be individualized on the basis of the extent of organ involvement and clinical severity. Additional therapeutic studies on irMG in the future are required to minimize irAE-related mortality and increase the safety of patients with cancer in the ICI era.

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis

et al. 2020

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“…Electromyography (EMG) and/or nerve conduction studies were reported in 11 cases. (4,7,9,11,(19)(20)(21)(22)(23)(24)(25) Most cases reported proximal muscle myopathic patterns with moderate to severe muscle injury. EMG was reported as within normal limits in three cases.…”

Section: Electrodiagnostic Testsmentioning

confidence: 99%

Immune Checkpoint Inhibitor–Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

et al. 2021

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Background. The development of immune checkpoint inhibitors (ICI) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immunerelated adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature. Methods. Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.Results. A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICI (38%). The most-reported symptom was fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. 60% of the patients died in hospital due to acute complications. Conclusion. IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition. The Oncologist ;9999:• •

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“…The management of an irAE associated with ICI is based on corticosteroids and other immunomodulating therapies. Early recognition and prompt treatment are crucial for improving clinical outcomes (Valenti‐Azcarate et al., 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Early recognition and prompt treatment are crucial for improving clinical outcomes (Valenti-Azcarate et al, 2020).…”

Section: Myocarditismentioning

confidence: 99%

A systematic review of myasthenia gravis complicated with myocarditis

et al. 2021

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Among many of the autoimmune diseases observed in patients with myasthenia gravis (MG), myocarditis is one of the most critical. The goal of this review is to systematically describe and investigate the characteristics of MG complicated with myocarditis. We identified 183 records in PubMed (MEDLINE), Web of Science, and EMBASE from 1948 to September 10, 2020. Studies were included if they presented clinical data on MG complicated with myocarditis. Of the 35 patients from 28 studies in this review, 57.14% (20/35) were males, with a mean age of 59.11 ± 15.87. Dyspnea was the most common cardiac symptom accounting for over 60% in the study. Among the 35 patients, 13 cases of myocarditis occurred concomitantly with MG and the longest interval between MG and myocarditis was 7 years. Forty percent of patients developed myocarditis caused by immune checkpoint inhibitors (ICI). Among the patients with myocarditis, over half of the patients were diagnosed by myocardial biopsy. After active immune regulation and symptomatic treatment, only 15 of 35 patients with MG complicated with myocarditis improved, 18 patients died during hospitalization, one patient died due to tumor progression and 1patient died 5 years later. The prognosis of patients with MG complicated with myocarditis is poor, and myocardial enzymes and other indexes need to be monitored for patients taking ICI drugs. Patients with dyspnea who are still not ideally treated by mechanical ventilation should be vigilant against the occurrence of MG complicated with myocarditis. K E Y W O R D Simmune checkpoint inhibitors, myasthenia gravis, myocarditis, review INTRODUCTIONMyasthenia gravis (MG) is a chronic autoimmune disease that mainly involves acetylcholine receptors (AChR) on the postsynaptic membrane at the neuromuscular junction, and is mainly mediated by AChR antibodies, cellular immunity, and complement. The main clinicalThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Nivolumab and Ipilimumab-induced myositis and myocarditis mimicking a myasthenia gravis presentation

Cited by 28 publications

References 6 publications

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis

Immune Checkpoint Inhibitor-Induced Myasthenia Gravis

Immune Checkpoint Inhibitor–Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

A systematic review of myasthenia gravis complicated with myocarditis

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