Severe Viral Myopericarditis With Autoantibodies Directed Against RNA Polymerase III

Severe Viral Myopericarditis With Autoantibodies Directed Against RNA Polymerase III Background: Viruses cause most cases of acute myopericarditis (1). Antibodies against RNA polymerase III (RNApol3) are rare (2) and usually associated with severe systemic sclerosis, especially when the disease includes diffuse and progressive skin involvement, renal crisis, gastric vascular ectasia, or cancer (3, 4). Objective: To report an association between severe viral myopericarditis and antibodies against RNApol3 in the absence of severe systemic sclerosis. Methods and Findings: Our intensive care unit provides extracorporeal membrane oxygenation annually to approximately 250 patients who are referred from throughout greater Paris. Using a database that is registered at the Commission Nationale de l’Informatique et des Libertés (2211698 v 0), we identified patients admitted to the unit from January 2013 to January 2019 who had suspected viral myocarditis. In accordance with French law, we did not obtain written informed consent but did inform patients of their inclusion in the study. The Table describes patient characteristics and immunologic findings. During the study, 56 patients were admitted with suspected viral myocarditis; 11 of these patients had antibodies against RNApol3, and all 9 patients who were retested for antibodies against RNApol3 after a median of 4 months (range, 1 to 68 months) had positive test results. The 11 patients with antibodies against RNApol3 had 16 admissions. Four patients had at least 1 relapse, with a median time to relapse of 30.5 months (range, 4 to 192 months). One patient died during a second hospitalization for myocarditis 4 years after the first hospitalization. Only 2 of the 11 patients had definite systemic sclerosis according to the American College of Rheumatology and European League Against Rheumatism 2013 classification system, and those 2 patients had mild phenotypes. No patient had diffuse cutaneous involvement, renal crisis, interstitial lung disease, pulmonary hypertension, or cancer. Except for Raynaud phenomenon (63.6%), which we believed was physiologic and unrelated to systemic sclerosis, clinical findings suggestive of systemic sclerosis were uncommon (for example, sclerodactyly of the fingers [18.2%], polyarthritis [18.2%], and puffy fingers [9.1%]). We detected the influenza virus during at least 1 admission in 7 of the 8 patients who were tested for it. Compared with the 45 patients with myocarditis who did not have antibodies against RNApol3, the 11 patients with these antibodies were statistically significantly more likely to have influenza, to be women, and to have pericardial effusion. We tested 20 additional patients who had acute respiratory distress syndrome with influenza for antibodies against RNApol3, and all had negative test results (Figure). Discussion: We report 11 consecutive patients with severe myopericarditis and antibodies against RNApol3, which, to our knowledge, has not been previously reported. The association is highly unlikely to have occurred by chance because acute myocarditis is rare (22 of 100 000 persons [5]), and antibodies against RNApol3 are also rare in the absence of severe systemic sclerosis. We believe that none of our 11 patients with antibodies against RNApol3 had myocarditis because of systemic sclerosis. For example, some patients with systemic sclerosis have chronic fibrotic cardiomyopathy, but acute myocarditis occurs uncommonly and is limited to patients with systemic sclerosis who have borderline forms with inflammatory myositis or systemic lupus erythematosus. In addition, after a median follow-up of 48 months, only 2 patients had definite systemic sclerosis, and they had mild phenotypes. Instead, we believe that our 11 patients developed acute viral myopericarditis and were then found to have antibodies against RNApol3. These antibodies were present before the viral infection and facilitated development of severe infection or participated in virus-induced myocardial injury. For example, the influenza virus was found in all but 1 of the patients who we tested for it. In addition, besides the 2 patients who had cardiac transplantation, all patients recovered without receiving anti-inflammatory agents, which argues against the presence of an underlying autoimmune cause of cardiac inflammation. Furthermore, antibodies against RNApol3 remained detectable for several months after resolution of the viral infection, which is consistent with them being present before the illness. Finally, none of the 20 patients with severe influenza-related acute respiratory distress syndrome had antibodies against RNApol3, which suggests that influenza itself does not provoke antibodies against RNApol3. Nevertheless, further studies should investigate the pathophysiologic mechanisms involved in this entity.