Recognize, Escalate, Survive: A Rare Case of Immune Checkpoint Inhibitor-induced Myasthenia Gravis, Myocarditis and Myositis Overlap Syndrome Triggered by Pembrolizumab
Ritesh Baddam1, Bhavya Chadalavada2, Anthony Donato2
1Neurology, 2Internal Medicine, Tower Health Reading Hospital
Objective:
We present a rare case of a triad of myasthenia gravis (MG), myositis, and myocarditis following a single cycle of pembrolizumab, highlighting the importance of early recognition and aggressive management of refractory neuromuscular immune-related adverse events (irAEs).
Background:
Immune checkpoint inhibitors (ICIs) have transformed oncologic care, but their neurological complications remain underappreciated. ICI-induced myasthenia gravis (MG) is uncommon yet far more dangerous, presenting with oculo-bulbar predominance and requiring ventilatory support up to seven times more frequently. The concurrent development of myositis and myocarditis, the IM3OS triad, escalates mortality from approximately 30% to 38–60%. No prospective treatment trials exist, and clinicians must rely on retrospective data and expert consensus to guide management.
Results:
A 77-year-old woman with stage IV serous endometrial carcinoma, treated with one cycle of pembrolizumab, was admitted after developing ptosis, generalized weakness, and myalgias. Examination revealed ophthalmoplegia with bilateral exotropia, fatigable extremity weakness, dysphagia, and dysarthria. MG was suspected and serial NIF and vital capacity monitoring were initiated. Despite negative acetylcholine receptor, MuSK, and LRP4 antibodies, clinical findings were consistent with ICI-induced MG. Creatine kinase peaked at 13,883 IU/L and troponin I at 15,060 ng/L, with atrioventricular conduction abnormalities and echocardiographic evidence of global left ventricular dysfunction (EF 45%), supporting the IM3OS triad. Additionally, the patient also developed ICI-induced hepatitis and destructive thyroiditis. Treatment included high-dose methylprednisolone, plasmapheresis, and rituximab. Cardiac function recovered, but refractory neuromuscular symptoms necessitated escalation to abatacept and ruxolitinib, after which the patient was discharged with gradual improvement.
Conclusions:
This case illustrates a rare but life-threatening occurrence of ICI-induced multi-system immune injury, where Myasthenia gravis emerged as the most refractory component. Early recognition of the IM3OS triad, stepwise escalation of immunosuppression for refractory neuromuscular symptoms, and coordinated multidisciplinary care are essential to improving survival outcomes in this challenging syndrome.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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