Pembrolizumab Induced Myasthenia Gravis

Abstract

Anti-programmed cell death 1 protein monoclonal antibodies are a novel and exciting treatment for several malignancies. Their mechanism of action involve blocking the protective programmed cell death protein-1 receptor, thereby allowing for lymphocytes to identify and destroy cancer cells. Although effective, side effects and complications can ensue. We present a case of Horner's syndrome, myositis, and myasthenia gravis (MG) in a patient treated with pembrolizumab. Case Presentation: A 59 year-old-female with stage IV cervical cancer complicated by carcinomatosis and a large bowel obstruction requiring diverting loop colostomy presented with two weeks of ptosis, blurry/double vision, and worsening orthopnea. Two weeks prior to this, she received her second round of pembrolizumab. Horner's Syndrome was suspected and outpatient imaging was arranged however during imaging, she developed severe orthopnea and was sent to the emergency room. On presentation, her vitals were within normal parameters except for hypertension of 174/116 mmHg. Laboratory findings were notable for a TSH of 0.03mIU/L, free T4 of 2.54ng/dL and creatinine kinase of 2829 U/L. Chest radiograph was unremarkable. MRI and MRV of the brain were obtained to rule out thromboembolic or central nervous system processes, both unremarkable. Given the recent initiation of pembrolizumab, symptomatology, hyperadrenergic vital signs, and initial testing, the diagnosis of pembrolizumab induced Horner's syndrome, ocular myasthenia gravis, and myositis were likely. Empiric treatment with pyridostigmine, corticosteroids, and intravenous immunoglobulin G (IVIG) was initiated. Her myasthenia gravis panel revealed an acetylcholine receptor (AChR) binding-Ab of 2.22nmol/L, AChR blocking-Ab of <15% inhibition, and AChr Modulating antibody 52% inhibition (NL < 35%): all of which indicated an anti-AChR binding antibody positive myasthenia gravis. She received five sessions of IVIG and was discharged on a prednisone taper and pyridostigmine, with complete resolution of her symptoms. Discussion: Myasthenia gravis is a rare neuromuscular disorder that is characterized by diplopia, skeletal muscle weakness, and respiratory depression. Patients of all ages can be affected. Although rare, PD-1 inhibitors have been associated with autoimmune-related myositis and myasthenia gravis. The etiology of these complications have not been fully elucidated. Nascent literature suggests early identification of MG is crucial in preventing poor outcomes, and that longitudinal prospective studies are required for establishing an ideal approach to management. Conclusion: This case highlights to need for close monitoring of patients on immune checkpoint inhibitor with unexplained respiratory failure.