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Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated myopathy predominantly affecting diaphragmatic muscles was diagnosed. Treatment included intravenous methylprednisolone, infliximab, abatacept, rituximab, and plasmapheresis. He underwent tracheostomy placement on hospital day 11 due to minimal improvement. He was discharged to a long-term acute care hospital, but unfortunately, he died less than 1 month later due to recurrent infections. irAEs can affect any organ system, but diaphragmatic dysfunction is uncommon. Use of diaphragmatic EMG, NCS, ultrasound study, or biopsy can support the diagnosis. Treatment includes systemic steroids, plasmapheresis, immunosuppressive medications, respiratory support, and cessation of causative medications. ICI-related diaphragmatic dysfunction should be suspected in those patients at risk with hypoxia, hypercapnia, or prolonged invasive or noninvasive ventilation without a distinct etiology. This case report exemplifies the importance of multidisciplinary workup and management of respiratory symptoms and insufficiency to identify and ameliorate irAEs. Diaphragmatic involvement can be associated with significant morbidity and mortality despite early aggressive multimodal therapy.
Walder et al. (Tue,) studied this question.