Case Presentation: A 79-year-old Caucasian male presented to the hospital with complaints of worsening generalized weakness, difficulty swallowing, and shortness of breath for about 3 weeks. His past medical history was significant for metastatic melanoma (metastasis to brain, lung). He received his first session of immunotherapy with Ipilimumab and Nivolumab one month before his presentation to our hospital. The patient stated that his symptoms began 3-4 days after his immunotherapy and progressed over the next 3 weeks to the point where he could not carry out activities of daily living. On presentation, his vitals were stable except for hypotension (75/60 mmHg) that responded to crystalloids. Physical exam was notable for oral thrush, abdominal breathing, and proximal muscle weakness (4/5 upper extremities (UE), 3+/5 lower extremity (LE)) with preserved strength in distal muscles. Labs were significant for CPK of 1066 IU/L, LDH 620 IU/L, aldolase 63.5 U/L. CT scan revealed metastatic lesions in the brain, lung, right axilla and left iliac bone. MRI brain showed stable metastatic disease and no other acute findings. The patient was started on 1mg/kg Methylprednisolone for possible irAE leading to myositis. EMG showed evidence of muscle inflammation of the proximal, distal, and facial muscles with no features of myasthenia gravis. Over the course of the next two days, he developed worsening dysphagia, new dysarthria and new diplopia. Barium swallow study showed severe oropharyngeal dysphagia. Due to his worsening clinical status and concern for overlap with myasthenia gravis, the patient was started on IVIG. He subsequently showed improvement in proximal muscle strength, but no change in his other symptoms. Two days later, the patient was transferred to the ICU for non-invasive ventilation after developing respiratory distress and negative inspiratory force (NIF) of -15 cm H2O. He was started on a 3-day course of pulse dose of steroids for worsening myositis. For presumed myasthenia crisis, he was also started on plasmapheresis. He completed 5 sessions of plasmapheresis and was continued on a 1 mg/kg dose of IV methylprednisolone. CPK, aldolase continued to trend down. Acetylcholine Receptor Binding Antibody came back positive (0.61 nmol/L). His symptoms improved over a course of 5 days but unfortunately, over the next few days his respiratory status worsened. With the poor prognosis and readdressing goals of care, the family decided to make the patient comfortable, and he passed away the following day.

Discussion: Improved survival rates in patients with melanoma have been shown in immune checkpoint inhibitors that target programmed cell death protein-1 and cytotoxic T-lymph associated protein-4; however, potentially life-threatening adverse effects (irAE: immune-related adverse event) have also been identified. Overall neurological complications were observed in 6% of irAE but myositis occurred in less than 1% of cases. In patients developing neurological irAEs, overlap syndromes with combined syndromes of myositis and myasthenia gravis can occur.

Conclusions: This case aims to increase clinical awareness that some irAEs may present with complex overlapping clinical features. Early recognition of aberrant immune activation in patients receiving immune checkpoint inhibitors is necessary for the effective treatment of irAEs. Prompt recognition and treatment with the help of a multidisciplinary team might help improve the outcomes of this life-threatening condition.