Case Presentation: We report a case of myasthenia gravis presenting with myasthenia crisis associated with inflammatory myositis caused by pembrolizumab.Our patient is a 77-year-old male with the past medical history of recently diagnosed metastatic clear cell renal carcinoma undergoing the third cycle of chemotherapy with pembrolizumab who presented with generalized weakness, dyspnea, dysarthria, and dysphagia. Due to worsening difficulty in breathing after admission, the patient was sedated, intubated and was monitored in the Intensive Care Unit (ICU). The patient was extensively evaluated for motor weakness without sensory involvement with blood tests including autoimmune antibodies, paraneoplastic panel, and lumbar puncture. Blood tests were remarkable for elevated CPK of 1415 IU/L, anti-striated muscle (anti-SM) with a level of 1:160(reference < 1:40) and acetylcholine receptor (AChR) antibodies with the titer of 2.27 nmol/L(reference <0.50 nmol/L ). The patient was diagnosed with myasthenic crisis with myositis most likely secondary to immune therapy with pembrolizumab and was treated with high dose methylprednisone, pyridostigmine and intravenous immunoglobulin(IVIG). The patient had a prolonged hospital course with multiple ICU transfers requiring intubation three times. Considering the possibility of myasthenia gravis unresponsive to initial treatment, patient was treated with 6 cycles of IVIG and 5 cycles of plasmapheresis and was started on rituximab. Eventually patient underwent tracheostomy due to the failure of multiple weaning trials off the ventilator. The patient is currently being treated with monthly plasmapheresis and rituximab.
Discussion: Checkpoint inhibitor immunotherapy has shown remarkable benefits in the treatment of a wide range of cancer types by blocking programmed cell death-1(PD-1) or its ligand. However, these immune checkpoint inhibitors (ICIs) have also been found to be associated with a myriad of immune-related adverse effects (irAEs). Life-threatening neuromuscular emergencies like myasthenia gravis with late-onset can occur in such patients without any previous evidence of disease.
Conclusions: This case illustrates the denovo onset of myasthenia gravis with multiple myasthenic crisis associated with myositis which was unresponsive to initial therapy. Until now, only a few cases of myasthenia gravis complicated by multiple myasthenic crisis not responsive to initial therapy secondary to pembrolizumab therapy have been reported in the literature. There is a hypothesis, that blocking the PDL1 pathway can lead to the production of autoantibodies against neuromuscular junction but still, there is a limited understanding of the complete pathophysiology. Currently, there are no biomarkers available to identify the patients more prone to develop autoimmune side effects associated with usage of ICIs. Further research is required to understand the pathophysiology of myasthenia gravis associated with ICIs not responding to initial therapy