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Published on: May 28, 2019
Checkpoint inhibitor-induced fulminant myocarditis, complete atrioventricular block and myasthenia gravis-a case
Antonio Portolés Hernández1, Mariola Blanco Clemente2, Daniel Escribano García1
1Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy over the last decade. Pembrolizumab, a humanized monoclonal IgG4 antibody, binds to the programmed death 1 (PD-1) receptor, blocking its interaction with programmed death-ligand 1 (PD-L1) and thereby increasing the anti-tumor activity of the host immune system. These drugs are associated with immune-mediated side effects that can be life threatening, and myocarditis is among the most serious events. We present a 48-year-old woman with a history of progressive thymoma who developed complete atrioventricular block associated with fulminant myocarditis and myasthenia gravis 2 weeks after starting treatment with pembrolizumab. She had also presented a couple of days before to the emergency department due to dyspnea that was related to pleural effusion. Electrocardiogram (ECG) and echocardiogram were unremarkable, but she had very mildly increased troponin levels that were attributed to acute respiratory compromise, so she was discharged after successful thoracentesis. Despite aggressive treatment combination of high-dose corticosteroids, immunosuppressive agents and anti-thymocyte globulin, the disease rapidly progressed to the fatal outcome. This report remarks on the importance of rapid consideration of ICI-induced myocarditis even if cardiac biomarkers are slightly elevated, as a mild presentation can go unnoticed and progress to a severe case. Therefore, a high index of suspicion is warranted in these patients and cardiac imaging techniques such as magnetic resonance could have a role diagnosing incipient cardiac inflammation.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy over the last decade. Pembrolizumab, a humanized monoclonal IgG4 antibody, binds to the programmed death 1 (PD-1) receptor, blocking its interaction with programmed death-ligand 1 (PD-L1) and thereby increasing the anti-tumor activity of the host immune system. These drugs are associated with immune-mediated side effects that can be life threatening, and myocarditis is among the most serious events. We present a 48-year-old woman with a history of progressive thymoma who developed complete atrioventricular block associated with fulminant myocarditis and myasthenia gravis 2 weeks after starting treatment with pembrolizumab. She had also presented a couple of days before to the emergency department due to dyspnea that was related to pleural effusion. Electrocardiogram (ECG) and echocardiogram were unremarkable, but she had very mildly increased troponin levels that were attributed to acute respiratory compromise, so she was discharged after successful thoracentesis. Despite aggressive treatment combination of high-dose corticosteroids, immunosuppressive agents and anti-thymocyte globulin, the disease rapidly progressed to the fatal outcome. This report remarks on the importance of rapid consideration of ICI-induced myocarditis even if cardiac biomarkers are slightly elevated, as a mild presentation can go unnoticed and progress to a severe case. Therefore, a high index of suspicion is warranted in these patients and cardiac imaging techniques such as magnetic resonance could have a role diagnosing incipient cardiac inflammation.
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