What are the causes of pericardial effusion?

Causes of Pericardial Effusion

Pericardial effusion results from six major categories: infectious diseases (viral in developed countries, tuberculosis globally), neoplastic conditions (10-25% of cases), autoimmune disorders, metabolic/endocrine disorders, iatrogenic/traumatic injuries, and idiopathic causes (up to 50% in developed countries). 1

Infectious Causes

Viral Infections

• Viral infections are the most common infectious etiology in developed countries, including enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza virus, parvovirus B19, hepatitis C virus, and HIV 1, 2

Bacterial Infections

• Tuberculosis dominates as the leading cause globally and in endemic regions, accounting for over 60% of cases, particularly in developing countries and often associated with concurrent HIV infection 1, 2
• Bacterial pericarditis from other organisms can cause purulent effusions requiring aggressive treatment 3

Fungal Infections

• Fungal infections may lead to pericardial effusion, particularly in immunocompromised patients 1

Neoplastic Causes

Malignant Effusions

• Malignant effusions account for 10-25% of cases in developed countries, with lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias being the most common secondary tumors 1, 2
• Among medical patients, malignant disease is the most common cause of pericardial effusion with tamponade 3

Primary Tumors

• Primary tumors of the pericardium are rare (40 times less common than metastatic ones), with pericardial mesothelioma being the most common primary malignant tumor 1

Critical Pitfall

• In almost two-thirds of patients with documented malignancy, pericardial effusion is actually caused by non-malignant diseases such as radiation pericarditis, chemotherapy effects, or opportunistic infections—not the cancer itself 1, 2

Autoimmune and Inflammatory Causes

Systemic Autoimmune Diseases

• Systemic autoimmune diseases cause 5-15% of cases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides 1, 2
• Cardiac tamponade is rare in connective tissue disease despite common pericardial effusion 3

Post-Cardiac Injury Syndromes

• Post-myocardial infarction pericarditis, post-pericardiotomy syndrome, and post-traumatic pericarditis can lead to pericardial effusion 1
• Post-myocardial infarction effusion >10 mm is most frequently associated with hemopericardium, and two-thirds may develop tamponade or free wall rupture 1

Other Inflammatory Conditions

• Sarcoidosis can involve the pericardium causing effusion 1
• Autoreactive pericarditis (immune-mediated inflammation) is another cause 1

Metabolic and Endocrine Disorders

Hypothyroidism

• Hypothyroidism occurs in 5-30% of hypothyroid patients, producing effusions that may be large but rarely cause tamponade 1, 2

Renal Failure

• Uremia in patients with renal failure can cause pericardial effusion 1
• Renal failure is among the more common causes of pericardial effusion with tamponade 3

Cardiovascular and Pulmonary Causes

Cardiac Conditions

• Heart failure can cause transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 1
• Aortic dissection with hemopericardium occurs in 17-45% of patients with ascending aortic dissection 1, 2

Pulmonary Conditions

• Pericardial effusion is common (25-30%) in pulmonary arterial hypertension, typically small in size but rarely causing hemodynamic compromise 1

Iatrogenic and Traumatic Causes

Direct Injury

• Penetrating thoracic injury and esophageal perforation can cause pericardial effusion 1
• Immediate thoracotomy is indicated in cardiac tamponade due to penetrating trauma 1

Indirect Injury

• Non-penetrating thoracic injury and radiation injury can lead to pericardial effusion 1
• Radiation therapy causes pericardial effusion and/or constriction in 6-30% of patients 1, 2

Post-Procedural

• Cardiac surgery, percutaneous coronary intervention, pacemaker lead insertion, and radiofrequency ablation can cause pericardial effusion 1

Chemotherapy-Associated

• Anthracyclines (doxorubicin, daunorubicin), cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, and osimertinib can cause pericardial effusion 1

Drug-Related Causes

Lupus-Like Syndrome

• Procainamide, hydralazine, methyldopa, isoniazid, and phenytoin can cause pericardial effusion 1

Other Medications

• Amiodarone, methysergide, mesalazine, clozapine, minoxidil, dantrolene, practolol, phenylbutazone, thiazides, streptomycin, thiouracils, streptokinase, p-aminosalicylic acid, sulfa drugs, cyclosporine, bromocriptine, vaccines, GM-CSF, and anti-TNF agents can cause pericardial effusion 1

Rare Specific Types

Chylopericardium

• Pericardial effusion composed of chyle due to injury or blockage of the thoracic duct; causes include trauma, surgery, congenital lymphangiomatosis, radiotherapy, subclavian vein thrombosis, infection, mediastinal neoplasms, and acute pancreatitis 1

Cholesterol Pericarditis

• Occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma 1

Pericardial Cysts

• Rare mediastinal masses (incidence 1 in 100,000) representing 6% of mediastinal masses and 33% of mediastinal cysts 1

Idiopathic Causes

• In developed countries, many cases remain idiopathic (up to 50%) despite comprehensive diagnostic evaluation 1
• Severe effusion without cardiac tamponade and inflammatory signs is usually associated with chronic idiopathic etiology (likelihood ratio 20) 1

Clinical Pearls for Etiology Determination

• Cardiac tamponade without inflammatory signs is associated with a higher risk of neoplastic etiology (likelihood ratio 2.9) 1
• If inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), clinical management should follow that of pericarditis 1
• Serosanguinous or hemorrhagic fluid appearance cannot determine etiology alone, as it occurs in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions 1, 2