• ·Myasthenia gravis (MG) is an autoimmune, postsynaptic neuromuscular disorder, characterized by fluctuating weakness of ocular, bulbar, respiratory, and limb muscles.

• ·Targeted immunotherapies, directed against immune checkpoint modulators such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1), and the PD-1 ligand (PD-L1), have become important treatments for malignancies, but are associated with autoimmune-related adverse events.

• ·Pembrolizumab (Keytruda) has been associated with 3 exacerbations and 7 de novo presentations of MG.

·A 73-year-old man presented with 3 days of fluctuating left eyelid droop and shortness of breath, after 3 weeks of receiving pembrolizumab for recurrent melanoma.

·Examination demonstrated increasing ptosis with sustained upgaze and reduced neck flexion, but motor power was otherwise normal. AChR-binding antibody was 6.4 nmoL.

·He required intubation and mechanical ventilation; NIF was ∼20 cm of H2O.

·Prednisone 60 mg daily was initiated with IVIg 2 g/kg, but later underwent plasmapheresis due to lack of improvement. After 5 weeks, he received another course of IVIg and was ultimately discharged home with home services.

·Pembrolizumab (PD-1 inhibitor) prevents T-cell activation and autoimmunity while promoting self-tolerance in metastatic melanoma and other cancers.

·Pembrolizumab has been associated with 3 exacerbations, and 7 de novo MG.

·Ipilimumab (CTLA-4 inhibitor) has been linked to 5 de novo MG cases.

·In a large retrospective series (3,763 patients) treated with nivolumab ± ipilimumab: 35 developed neurologic complications including encephalitis (5 cases), meningitis (5 cases), peripheral neuropathy (14 cases), and MG (1 case).

·MG exacerbation is a life-threatening complication that requires collaborative decision-making with the patient, neurologist, and oncologist to consider permanent discontinuation of the checkpoint inhibitor.

·Early detection and treatment of MG with checkpoint inhibitors will likely limit mortality and morbidity.