Case Presentation: A 75-year-old man with bladder transitional cell carcinoma complicated by lung and renal metastases presented with one week of progressive shortness of breath at rest. His dyspnea worsened when reclining and improved with increased home oxygen. He denied chest pain, cough, or lower-extremity edema but noted diplopia, dysphagia, fatigue, and bowel and bladder incontinence. He had received a second cycle of nivolumab for his cancer one week prior to symptom onset. His past medical history included type 2 diabetes, heart failure, and COPD on home oxygen. Despite visits to clinic and a negative MRI brain, he did not receive a diagnosis and returned to the ER for worsening dyspnea.

On presentation, he had three-word dyspnea and could not lie back in bed. His respiratory rate was 24 and oxygen saturation 100% on 2L. His JVP was not elevated and his lungs were clear. He had bilateral ptosis with some fatigability with upward gaze. The rest of the neurologic examination was normal. Chest X-ray showed bibasilar atelectasis. There were no pulmonary emboli or increased lung metastases on chest CT. Labs showed BNP 197 (normal < 100) and normal TSH. Due to concern for a neuromuscular etiology, he underwent electromyography, which revealed decreased activity of the right median nerve with repetitive stimulation. Acetylcholine receptor antibody test returned positive (2.28 nmol/L) and the patient was diagnosed with nivolumab-induced myasthenia gravis. He received IVIG for five days with mild improvement in his symptoms. After transitioning to hospice, he went home on pyridostigmine and died two days later.

Discussion: Nivolumab-induced myasthenia gravis, a rarely reported condition, is a type of immune-related adverse event (irAE) that results from checkpoint inhibitor therapy. Approved to treat an array of cancers, including melanoma, transitional cell carcinoma, and non-small cell lung cancer, checkpoint inhibitors enhance the patient’s immune response to cancer cells but can also lead to immune-mediated end-organ damage.

As frequent caretakers of patients with cancer, hospitalists should understand the unique side effect profile of immunotherapy agents. The skin, gut, and endocrine systems are most frequently affected, so common symptoms may be manifestations of irAEs in patients on checkpoint inhibitors: rash, diarrhea, or fatigue may be dermatitis, colitis, or hypophysitis, respectively. In our patient, dyspnea was a late symptom of neuromuscular weakness from nivolumab-induced myasthenia gravis. Since irAEs occur unpredictably and non-specifically, increased awareness of them will lead to timely initiation of therapy with corticosteroids and drug cessation.

Conclusions: Checkpoint inhibitors are anti-neoplastic drugs that augment immune response to cancer cells while sometimes causing immune-related drug toxicities. Hospitalists should be familiar with checkpoint inhibitors’ unique side effect profiles in order to accurately diagnose irAEs.