Diaphoresis, Dyspnea, and Discomfort: An Unusual Case of Epstein-Barr Virus-Associated Pericardial Effusion With Cardiac Tamponade

A 57-year-old man presented with a 1-day history of substernal chest pain, diaphoresis, palpitations, and lightheadedness while walking his dog.

History. He initially attributed his symptoms to a panic attack, however, his chest pain gradually worsened, prompting him to present to the emergency room. He reported a 1-month history of dyspnea on exertion but denied any prior history of chest pain, leg swelling, orthopnea, or paroxysmal nocturnal dyspnea.

His medical history was significant for polysubstance abuse with cocaine and alcohol, hypertension, hyperlipidemia, and panic disorder. He reported a 30-year history of cocaine insufflation and last used 2 days prior. He had a history of binge drinking alcohol every weekend, with the last drink 6 days prior. He had no history of cardiac disease or thrombotic events. He denied any other recent fever, respiratory, or gastrointestinal symptoms.

On presentation he had a blood pressure of 230/137 mm Hg, a heart rate of 122 beats/min, a respiratory rate of 20 breaths/min, a temperature of 98.1ºF, and an oxygen saturation of 96% on room air. A physical examination was significant for tachycardia with a regular rhythm, jugular venous distension, and decreased air-entry and crackles in the bilateral lung bases. There was no lower extremity edema. Laboratory investigations were significant for thrombocytopenia of 107x10³/L and elevated high-sensitivity troponin of 142 ng/dl (reference range 3.0 – 53.0 ng/dl). His urine drug screen was positive for cocaine. An electrocardiogram (EKG) showed sinus tachycardia with a rate of 111 beats/min with ST ischemic changes in leads aVL and V1 and ST depressions in I and V6 (Figure 1).

Figure 1. Electrocardiogram showing sinus tachycardia with a rate of 126 beats/min with ST elevations in leads aVR, V1 with ST depressions in I and V6.

A chest radiography was significant for an enlarged cardiac silhouette, low lung volumes, and pulmonary vascular congestion (Figure 2). A computed tomography (CT) scan of the chest, aorta, abdomen, and pelvis showed a large pericardial effusion and no evidence of acute intramural hematoma, aneurysm, or dissection of the thoracic or abdominal aorta (Figure 3). An urgent echocardiogram demonstrated a large circumferential pericardial effusion with more than 50% respiratory variation across the tricuspid valve, right ventricular diastolic collapse consistent with tamponade physiology, and left ventricle (LV) function within normal limits with ejection fraction (EF) of 65% (Figure 4).

Figure 2. The chest radiograph on admission showing an enlarged cardiac silhouette, low lung volumes, and pulmonary vascular congestion.

Figure 3. The computed tomography of the chest, aorta, abdomen, and pelvis showing a large pericardial effusion.

Figure 4. A parasternal long-axis view of the transthoracic echocardiogram showing the pericardial effusion with tamponade physiology.

The upper respiratory diagnostic panel was negative for common respiratory viruses, including respiratory syncticial virus, parainfluenza viruses, rhinovirus/enterovirus and non-COVID-19 coronaviruses, and was also negative for Mycoplasma pnuemoniae and Chlamydophia pneumoniae. COVID-19 and influenza A and B testing were negative. Human immunodeficiency virus (HIV), enteric cytopathic human orphan (echo) virus, and coxsackievirus testing were negative. Testing for tuberculosis and Lyme disease was negative. A thorough workup for autoimmune disease was negative.

Epstein-Barr virus (EBV) immunoglobulin (Ig) G was significantly elevated at greater than 750.00 U/ml (negative result < 18.00 U/ml). EBV DNA polymerase chain reaction (PCR) was positive with a very high titer of more than 600 U/ml (negative result < 18.00 U/ml), but EBV IgM was negative. These results supported a diagnosis of a chronic EBV infection leading to a chronic pericardial effusion.

Differential diagnosis. The differential diagnosis in this case included viral infections, tuberculosis, Lyme disease, and autoimmune causes, all of which were ruled out by diagnostic testing.

Tainted cocaine was also considered as a cause for the patient’s pericardial effusion, and while this diagnosis cannot be entirely ruled out, we felt as if it was significantly less likely to be the leading etiology of his final diagnosis based on the patient’s laboratory results.

Treatment and management. He was admitted to the coronary care unit (CCU) to manage his hypertensive emergency with non-ST elevated myocardial infarction and pericardial effusion with echocardiographic features of cardiac tamponade. Urgent pericardiocentesis drainage was planned.

While in the CCU, subsequent troponin levels remained elevated but did not trend upwards. Pericardiocentesis was attempted but was unsuccessful. Cardiothoracic surgeons were consulted, and he subsequently had a pericardial window and placement of a pericardial drain. 400 ml of cloudy, pink-tinged pericardial fluid was drained during the procedure. The pericardial fluid was exudative by Light criteria (Table).

A microscopy of the pericardial fluid showed many lymphocytes and mesothelial cells but was negative for malignant cells. A gram stain of pericardial fluid was negative for any organisms, and acid-fast testing of the pericardial fluid was negative. The culture of the pericardial fluid showed no growth of bacteria or fungi. A pericardial biopsy showed fibrotic tissue with chronic inflammatory infiltrate. The patient was then commenced on oral therapy with aspirin 350 mg three times daily and colchicine 0.6 mg twice daily.

 Within the following 2 days, there was a significant reduction in the volume of pericardial fluid drained and a repeat echocardiogram showed only a mild to moderate pericardial effusion without any evidence of cardiac tamponade. The drain was subsequently removed. He had resolution of his symptoms, remained hemodynamically stable, and was discharged home on a 3-month course of both aspirin and colchicine.

Outcome and follow-up. He was followed up in the outpatient setting within 2 weeks of discharge. A repeat transthoracic echocardiogram was conducted, which demonstrated only a small residual pericardial effusion with no features or parameters to suggest cardiac tamponade. He has not been readmitted in the 6 months following his discharge.

Discussion. A pericardial effusion refers to the accumulation of fluid within the pericardial sac – an area where only minimal fluid should exist to reduce any impedance or friction in surrounding heart structures. Pericardial effusions are most commonly the result of infectious processes, metabolic disturbances, malignancy, trauma, cardiac surgery, and autoimmune conditions.¹ When a pericardial effusion leads to compression of cardiac chambers with a compromise of ventricular function it is referred to as cardiac tamponade, a potentially lethal condition.²

Viruses are common causes of pericarditis and pericardial effusions, accounting for 30% to 50% of cases.³ Viral pericarditis is often the result of an immune-mediated response to viral infection. During the course of a viral infection, the body releases cells in an attempt to eliminate the virus. These cells may enter the cardiac tissue in numbers resulting in an inflammatory response that leads to an increased amount of fluid within the pericardial sac.⁴

Common viral causes of pericarditis include coxsackieviruses, adenoviruses, cytomegalovirus, and enteroviruses.^3,5 EBV, a human herpes virus, is transmitted mainly via oral secretions with sexual transmission implicated in some cases. EBV is most often associated with infectious mononucleosis and malignancies such as Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma.⁶ It has been reported as an uncommon cause of pericarditis, and less commonly is it associated with pericardial effusion, with only a few reported cases in the literature. As such, data regarding the epidemiology and risk factors of EBV-associated pericardial effusions are limited.⁷

Diagnosis of EBV infection is usually confirmed by serology. Elevated viral IgM antibody titers usually indicate an acute infection, whereas IgG-positive titers typically indicate a past, resolving, or resolved infection. However, a significant rise in virus-specific IgG titer, usually more than four times the upper limit of normal, may also be seen in recent infections.⁸

In our case, it is postulated that the patient’s pericardial effusion was a slow-developing product of an immune system still attempting to quell the effects of a likely asymptomatic EBV infection. Our patient revealed no prior symptoms possibly related to prior EBV infection, however, laboratory investigations showed significantly elevated levels of IgG viral titers in addition to high-titer positive PCR for EBV. More importantly, the aforementioned became more relevant in our case after a plethora of other known etiologies of pericardial effusion were ruled out.

Other than the large pericardial effusion, we believe his cocaine use also partly contributed to his presenting symptoms and overall presentation. There have been hypotheses and a few case reports of cocaine being tainted with levamisole, which in turn can trigger vasculitis that can lead to pleural and pericardial effusions.⁹ However, the significantly positive EBV DNA PCR and IgG titers better fit our leading differential for the patient. Additional evidence supporting the patient’s diagnosis is the result of the pericardial fluid analysis demonstrating an exudative sample by Light criteria, with microscopy showing many lymphocytes, few mesothelial cells, and no malignant cells, similar to the few other reported cases of EBV-associated pericardial effusions.^3,7,10

Currently, there are no evidence-backed guidelines regarding prevention of pericarditis. Avoidance of surgical instrumentation with the pericardium could be considered a preventative strategy. In our case, the patient was counseled in the cessation of his illicit substance abuse.

Conclusion. Although numerous cases of EBV infection occur each year, an overwhelming majority are self-limited, and cardiac complications of EBV infection, such as pericarditis or pericardial effusion, are uncommon. Similarly to the case we present here, a diagnosis of EBV-associated pericardial effusion is often made in the presence of an exudative pericardial effusion in the presence of positive EBV-serology, with negative work-up for other more common infectious and inflammatory causes. Epidemiological data and risk factors of cardiac involvement in EBV infection remain to be further elucidated.