EYES WIDE SHUT: AN UNUSUAL CAUSE OF PTOSIS

Abstract

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor (ICI) known to cause a variety of side effects. Here is a case of a lung cancer patient on pembrolizumab presented with dyspnea and chest pain and was found to have a rare side effect. CASE PRESENTATION: A 74-year-old female, with stage IV adenocarcinoma of the lung, presented to the hospital with chest pain & shortness of breath. She admitted to fatigue, new-onset left-sided ptosis for 2 weeks and RUE weakness. Patient was admitted the day before her 3rd treatment. She required supplemental O2 due to hypoxia. Physical exam was significant for ptosis (L > R), UE weakness (L > R), otherwise unremarkable. Labs were significant for AKI, elevated CK and CRP, with a borderline high leukocytosis. Imaging ruled out stroke and PE. Her mass was stable radiographically. Cardiac causes were ruled out. Despite initial treatment for post-obstructive pneumonia, she remained symptomatic and desaturated with exertion, requiring non-invasive ventilation at times. Diaphragmatic paralysis, neuromuscular weakness or paraneoplastic syndromes were considered as possible etiologies. Serologies for myasthenia gravis (MG), Lambert-Eaton and myositis were ordered. Hemi-diaphragmatic paralysis was ruled out. ABG showed evidence of hypercapnia and sitting and supine spirometry demonstrated a drop in FVC >20%, suggesting neuromuscular weakness. Anti-AChR Ab was positive, while anti-MUSK Ab, anti-voltage-gated Ab and auto-antibodies for myositis were all negative. She was diagnosed with MG induced by pemrolizumab and was started on prednisone, pyridostigmine and IVIG. On follow-up, she noted slow improvement and her chemotherapy remained on hold due to her high steroid dose. DISCUSSION: Most ICI-induced MG (iciMG) cases were from melanoma patients, it is rare to see them in lung cancer patients, especially with adenocarcinoma. iciMG can present as exacerbation or new-onset disease. The cause for our patient's respiratory distress was confounded by possible post-obstruction pneumonia. There was also uncertainty on the functioning of her diaphragm, which could result from ICI-induced myositis. To differentiate the two, Sekiguchi et al. recommended using ultrasound over needle EMG to assess for diaphragm dysfunction to avoid pneumothorax. The current recommendation is to treat with plasmapheresis and pulse-dose steroids. ICI can trigger underlying autoimmune diseases. However, pre-existing autoimmune conditions should not be considered as contraindications to ICI therapy, as there was a report on a patient tolerating a re-challenge despite having iciMG. Thus, limiting therapeutic options based on adverse events should be decided on a case-by-case basis. CONCLUSIONS: Pembrolizumab can cause de novo myasthenia gravis. These symptoms tend to develop within the first few cycles of treatment. Physicians should consider this as a differential when encountering similar patients. REFERENCE #1: Hibino M, Maeda K, Horiuchi S, Fukuda M, Kondo T. Pembrolizumab-induced myasthenia gravis with myositis in a patient with lung cancer. Respirol Case Rep. 2018;6(7):e00355. Published 2018 Aug 7. doi:10.1002/rcr2.355 REFERENCE #2: Sekiguchi K, Hashimoto R, Noda Y, et al. Diaphragm involvement in immune checkpoint inhibitor-related myositis. Muscle Nerve. 2019;60(4):E23-E25. doi:10.1002/mus.26640 REFERENCE #3: Tedbirt B, De Pontville M, Branger P, et al. Rechallenge of immune checkpoint inhibitor after pembrolizumab-induced myasthenia gravis. Eur J Cancer. 2019;113:72-74. doi:10.1016/j.ejca.2019.03.006 DISCLOSURES: No relevant relationships by Rumon Chakravarty, source=Web Response No relevant relationships by Vernon Chan, source=Web Response