Case presentation - A 62-year-old male with stage IV BRAF+ metastatic melanoma to the brain and lungs presented to the hospital with a 2- day history of right-sided facial weakness, dysarthria, bilateral purulent eye discharge, bilateral leg rash, and fevers. He denied eye pain, headaches, and confusion. The patient had been receiving immune checkpoint inhibitors (ICI) with Nivolumab and Ipilimumab within 3 months of presentation. Neurological exam was notable for right-sided facial droop and decreased taste on the left, rear tongue, and dysarthria. Brain MRI was significant for hyperenhancement of bilateral facial nerves and geniculate ganglia, which was consistent with bilateral facial nerve palsy. There was no evidence of new brain metastasis on imaging or CSF cytology. There was pitting edema through both his calves, more significant on his left leg, associated with significant erythema, warmth, and tenderness. Ultrasound imaging was negative of deep venous thrombosis. Ophthalmic exam was notable for poor visual acuity, irregular and sluggish pupils, corneal dusting, and keratic precipitates which were consistent with bilateral anterior uveitis. Infectious work-up for uveitis was negative. His constellation of symptoms was consistent with checkpoint inhibitor toxicity, thus, he was started on high dose glucocorticoids for his facial nerve palsy and steroid eye drops for his uveitis with significant improvement in his symptoms.

Discussion - Ipilimumab, an anti-CTLA-4 agent, and Nivolumab, an anti-PD-1 agent, are both associated with immune-related adverse events (irAE). These irAE typically occur within 3 months of starting therapy, and more common with combination therapy versus monotherapy with either class. Most commonly, these irAE include diarrhea, colitis, pruritus, rash, and endocrinopathies. Peripheral neuropathy involving cranial nerves is treated with prednisone. Anterior uveitis is treated with topical steroids, systemic steroids, and cycloplegic agents. ICI may be resumed once systemic steroids are tapered down and symptoms improve. While neurologic and ocular toxicities are associated with checkpoint inhibitors, both are exceedingly uncommon and occur in <1% of cases. Our patient had a unique combination of symptoms from these agents which have only rarely been described in the literature. Individually, cases with uveitis or Bell's palsy are associated within weeks after administration of Ipilimumab, not Nivolumab. In the cases where the patient was on both Ipilimumab and Nivolumab, the irAE resolve and do not return with a steroid course and discontinuation of Ipilimumab.

Conclusion • ICI may present with neurologic and ocular irAE months after treatment. • ICI may be continued after irAE depending on the severity of symptoms and response to treatment.