Rituximab in Refractory Myositis and Acute Neuropathy Secondary to Checkpoint Inhibitor Therapy

Checkpoint inhibitor immunotherapies have been one of the latest advances through the last decade in the treatment of various cancers. As their use is increasing so is the knowledge of their complications which can affect various organ systems including the central and peripheral nervous systems. Management of these complications requires stopping the offending agent and in some cases treating with immunosuppressive agents like intravenous steroids. Physicians can face challenging situations if patients are unresponsive to steroids, intravenous immunoglobulins (IVIG), and plasmapheresis (PLEX). There are no formal guidelines to help in the management of such patients.  We present an 85-year-old male with a past medical history of renal cell carcinoma status post nephrectomy who was admitted with diplopia, eyelid ptosis, dysphagia, dysphonia, dyspnea, and generalized weakness. He was started on nivolumab and ipilimumab 10 days prior to presentation. Laboratory studies showed an elevated erythrocyte sedimentation rate, C-reactive protein, and creatine phosphokinase, and an unrevealing lumbar puncture. Acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) antibodies were negative. Electromyography and nerve conduction studies showed axonal and demyelinating sensorimotor neuropathy with no significant decrement on 3 Hz repetitive stimulation. Thyroid function tests were concerning for thyroiditis and anti-thyroid peroxidase antibodies were positive. Together, these findings led to the diagnosis of refractory myositis and acute neuropathy along with autoimmune thyroiditis from nivolumab and ipilimumab immunotherapy. His symptoms were unresponsive to a 5-day course of steroids, intravenous immunoglobulins, and plasmapheresis. He was then started on rituximab with significant improvement in ptosis, dysphagia, dysphonia, and proximal weakness. Immune checkpoint inhibitors (ICI) are associated with an increased risk for the development of various autoimmune conditions. Treatment involves discontinuation of the offending drug and initiation of immunosuppressive therapy. This case is interesting as it demonstrates the importance of the awareness of the neurological complications of the checkpoint inhibitor therapies and the beneficial role of rituximab in patients who are unresponsive to initial immunosuppressive therapies including steroids, IVIG, and PLEX.