Quality and Patient Safety Articles-Immune Checkpoint Inhibitors Related Neuromuscular Adverse Effects

Immune Checkpoint Inhibitors Related Neuromuscular Adverse Effects

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This case describes a 68-year-old man who developed weakness, ptosis, diplopia, elevated creatine kinase, elevated troponin, and reduced ejection fraction shortly after starting combination immune checkpoint inhibitor therapy with ipilimumab and nivolumab. The most likely diagnosis is <strong>ICI-induced triple-M syndrome</strong>, also called <strong>myositis, myocarditis, and myasthenia overlap syndrome</strong>.

Immune checkpoint inhibitors can trigger immune-related adverse events by unleashing T-cell activity against tumors but also against normal tissues. Neuromuscular complications are uncommon but can be severe. They may include inflammatory myopathies, myasthenia gravis-like syndromes, neuropathies, and cranial neuropathies. The triple-M overlap syndrome is especially dangerous because muscle, neuromuscular junction, and cardiac involvement can occur together, creating major respiratory and cardiac risk.

This syndrome often appears early after treatment begins, especially with combination therapy such as anti-CTLA-4 plus anti-PD-1 agents. Diagnosis depends on clinical suspicion plus testing such as CK, troponin, EMG/NCS, autoantibodies, and cardiac imaging.

Management requires immediate stopping of the immune checkpoint inhibitor and starting high-dose corticosteroids. Severe or refractory cases may need IVIG, plasma exchange, mycophenolate, rituximab, or possibly eculizumab.

Correct answer: <strong>B. ICI-induced triple-M syndrome (myositis, myocarditis and myasthenia overlap syndrome)</strong>.

Keywords

immune checkpoint inhibitor

triple-M syndrome

myositis

myocarditis

myasthenia gravis

ipilimumab

nivolumab

elevated creatine kinase

troponin elevation

high-dose corticosteroids