To describe a case of immune checkpoint inhibitor associated myasthenia gravis with low density lipoprotein related protein-4 (LRP4) antibody positivity.

Immune checkpoint inhibitors have been associated with autoimmune complications including myasthenia gravis. These cases are typically positive for acetylcholine receptor antibodies. Cases positive for LRP4 in the setting of immune checkpoint therapy have not yet been presented in the literature.

We report a 64 year-old gentlemen with metastatic renal cell carcinoma treated with two cycles of ipilimumab and nivolumab who presented three weeks after his second cycle to an outside facility with progressive dyspnea, fatiguing diplopia, progressive head drop, dysphagia, and chest pain. He was originally treated for an NSTEMI and later transferred to our facility with worsening oculobulbar and respiratory weakness. He tested negative for acetylcholine receptor blinding/blocking/modulating and muscle-specific tyrosine kinase antibodies. He was treated with seven cycles of plasma exchange with improvement in his presenting symptoms. Later testing during the hospitalization revealed LRP4 antibody positivity and EMG findings consistent with a post-synaptic neuromuscular junction disorder. The patient was later started on steroids and intravenous immunoglobulin therapy that were continued on discharge.

Adverse effects of checkpoint inhibitors include myasthenia gravis which can lead to life-threatening complications at a higher rate of mortality than classical myasthenia gravis, requiring prompt diagnosis and treatment. Greater awareness of complications from this therapy can aid in faster identification, allowing for earlier intervention with discontinuation of immune checkpoint inhibitor therapy and aggressive treatments for myasthenia gravis.