Case Presentation: A 59 year old man with stage IV lung adenocarcinoma of the right lower lobe with metastases to the ribs and thoracic vertebra presented with shortness of breath, diplopia, and dysphagia. Six weeks prior to presentation he was treated with one cycle of carboplatin, pemetrexed, and pembrolizumab along with palliative radiation therapy to the rib and spine. He subsequently developed progressive generalized weakness, dyspnea, and dysphagia over the past month. Two days prior to admission, he had an episode of diplopia with drooping of his left eyelid. After admission, he had worsening respiratory distress requiring intubation. Negative inspiratory force (NIF) was -13 cm H2O. His labs were remarkable for an arterial blood gas showing a pH of 7.32, pCO2 of 12.7 kPa, and pO2 of 12 kPa. His acetylcholine receptor (AChR) antibody returned positive at 9 nmol/L. He failed multiple subsequent spontaneous breathing trials due to poor respiratory effort. Chest radiograph and computed tomography showed no acute abnormalities. Myasthenia gravis (MG) was suspected based on his overall clinical presentation. After consultation with the neuro-oncology team, he was given methylprednisolone and pyridostigmine. He also received one course of intravenous immunoglobulin (IVIG) and underwent five cycles of plasmapharesis. After these interventions his work of breathing improved and he was successfully extubated. He was discharged on pyridostigmine and a prednisone taper.
Discussion: This case demonstrates a rare and life-threatening autoimmune neurological disorder induced by pembrolizumab, an immune checkpoint inhibitor targeting programmed cell death protein-1 (PD-1). As immune checkpoint inhibitors become increasingly common in the treatment of various malignancies, it is important to recognize MG as a serious autoimmune adverse event associated with this class of medications. MG is an autoimmune disorder caused by antibodies to the AChR in the neuromuscular junction. Key symptoms of MG include ocular symptoms (blurred vision, ptosis, diplopia) and bulbar symptoms (ptosis, dysphagia, and dysarthria). Acetylcholinesterase inhibitors, such as pyridostigmine, are considered first-line treatment for MG. Many patients require additional treatments such as IVIG, steroids, and plasmapharesis. 10-20% of patients with MG experience myasthenic crisis, which is MG requiring intubation and mechanical ventilation. Elective intubation should be considered in patients with a forced vital capacity less than 15 L or a NIF between 0 and -30 cm H2O. Early recognition of impending respiratory arrest and subsequent intubation has decreased the mortality of patients with MG to less than 5% today.
Conclusions: MG is a serious, life-threatening condition that requires prompt detection and treatment. Recognition of myasthenic crisis as one of the serious autoimmune adverse effects of immune checkpoint inhibitors, such as pembrolizumab, is vital to preventing significant morbidity and mortality.