Abstract 4358302: A Case of Immune Checkpoint Inhibitor-Induced Myocarditis with Myositis and/or Myasthenia Gravis Overlap Syndrome with New Right Bundle Branch Block and Negative Cardiac MRI

Abstract

Case Description: The patient is an 85-year-old male with hypertension, paroxysmal atrial fibrillation, and stage IV prostate cancer on pembrolizumab (last dose 10 days ago) presenting with three days of shortness of breath, fatigue, and eye weakness. He denies chest pain, palpitations, fevers, recent illness, GI symptoms, or proximal muscle weakness. Vital signs are stable. Physical exam reveals bilateral ptosis, right deltoid fatigable weakness, and maculopapular rash of the chest. Pertinent labs include: hs-cTnI 1241.3 pg/mL, total CK 12666 U/L, CPK 11735 U/L, aldolase >56.0 U/L, LDH 831 U/L, ESR 36 mm/hr, CRP 7.4 mg/L, AST 308 U/L, ALT 199 U/L, and negative acetylcholine receptor-binding antibody. Methylprednisolone 1g IV is administered in the ED. ECG shows normal sinus rhythm with new RBBB (QRS 142 ms). TTE demonstrates LVEF 60-65%, stage 1 diastolic dysfunction, dilated IVC, and normal RVSP. Cardiac MRI reveals LVEF 61%, RVEF 33%, moderate LV and RV dilation, and no specific MRI features of acute inflammation. Fat suppression MRI shows mild intramuscular edema in the bilateral thigh, proximal leg, and pelvic muscles. Rosuvastatin and metoprolol are held with concern for myositis and myasthenia gravis, respectively. He is started on pyridostigmine. Clinical status and negative inspiratory force do not necessitate intubation. His symptoms fully resolve with five days of methylprednisolone 1g IV daily and IVIG. Troponin, CK, AST, and ALT normalize prior to discharge. He is sent with a 10-week steroid taper. ECG obtained one week after hospitalization is without RBBB. Discussion: This is an example of immune checkpoint inhibitor-induced myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS), a rare condition that can occur even after one dose of immunotherapy. The symptom profile (shortness of breath, fatigue, ocular weakness), labs (elevated troponin, CK, inflammatory markers, transaminitis), and overall clinical picture in the context of recent pembrolizumab infusion support the diagnosis. Fatigue and muscle weakness are the two most common symptoms. Arrhythmias may occur in more than half of cases, though the association with bundle branch block is unknown. Reduced EF may occur in nearly twenty percent of cases. Only 11/60 cases demonstrated cardiac MRI findings of myocarditis in a recent systematic review. Early recognition is critical to ensure timely treatment with IV steroids as in-hospital mortality may exceed fifty percent.