Acute myocarditis associated with coxsackievirus B4 mimicking influenza myocarditis: electron microscopy detection of causal virus of myocarditis.

A previously healthy 40-year-old man was admitted to our hospital complaining of dyspnea at rest and flu-like symptoms. Influenza virus type A was detected in the mucus from his nasal cavity. Chest radiographs showed an infiltrative shadow in the right upper lung field, so influenza pneumonia was diagnosed. An ECG showed newly developed complete right bundle-branch block, and ST-T–segment elevation was observed in all leads except for III, aVR, and aVF (Figure 1A). Because the cardiac enzymes, creatine phosphokinase (1023 U/L; normal value <200 U/L) and creatine phosphokinase myocardial band (38 ng/mL; normal value <7.5 ng/mL), were elevated and the troponin T quick assay was positive, we performed a trans-thoracic echocardiogram. Left ventricular (LV) wall motion was reduced diffusely, and the LV ejection fraction was 17% (Figure 2A). Coronary artery disease was excluded by coronary angiography (Figure 3). An endomyocardial biopsy (EMB) was performed from the LV posterior wall. Light microscopic examination revealed lymphocytic infiltration (Figure 4A). There were no multinucleated giant cells or plasma cells and very few eosinophils. Immunohistochemistry showed mac-rophages, lymphocytes, and T-cell predominance. Electron microscopy revealed spherical viruses of 20 to 30 nm in an area of myofilament lysis of cardiomyocytes (Figure 4B and 4C). Two weeks after admission, coxsackievirus B4 and influenza virus type A were elevated >4 times on examination. Both influenza virus and coxsackievirus are RNA viruses that proliferate in cytoplasm. Influenza virus is a bacillary type with a length of 80 to 120 nm. Coxsackievirus is icosahedral shaped with a diameter of 10 to 30 nm. For confirmation, we stained the EMB specimen using both viral antibodies. Cardiomyocytes reacted diffusely to the coxsackievirus B antibody (Figure 4D and 4E). Only acute-phase mechanical circulatory support by intra-aortic balloon pumping was needed. The patient was discharged 9 weeks after his admission. An ECG performed before the patient left our hospital showed that both right bundle-branch block and ST-T–segment elevation had disappeared (Figure 1B), and the patient's LV systolic function showed good recovery; his LV ejection fraction was 61% (Figure 2B). Diagnosis of viral myocarditis is based on the detection of viruses, viral genomes, or viral antibody in serum, excreta, or tissues. Timed examinations for viral infection and molecular biology–based assays of peripheral blood samples do not always show the exact cause of myocarditis. 1 In this case, electron microscopic observation and evaluation by molecular-based immunohistochemistry of an accurately timed EMB specimen enabled the detection …