What are the causes of pericardial effusion?

Causes of Pericardial Effusion

Pericardial effusion results from a wide spectrum of infectious, neoplastic, autoimmune, metabolic, iatrogenic, and idiopathic etiologies, with the dominant cause varying dramatically by geographic region—viral infections and idiopathic causes predominate in developed countries, while tuberculosis accounts for over 60% of cases in endemic regions. 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

Bacterial Infections

• Tuberculosis is the leading cause of pericardial effusion globally and in developing countries, dominating in over 60% of cases in endemic regions, often associated with concurrent HIV infection 1, 2
• Purulent bacterial pericarditis from other organisms can cause effusion and requires urgent surgical drainage 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
• Primary pericardial tumors (primarily mesothelioma) are 40 times less common than metastatic disease 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
• Cardiac tamponade without inflammatory signs is associated with higher risk of neoplastic etiology (likelihood ratio 2.9) 4

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
• Sarcoidosis can involve the pericardium causing effusion 1

Post-Cardiac Injury Syndromes

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

Uremia

• Uremia in patients with renal failure can cause pericardial effusion 1

Cardiovascular Causes

Heart Failure

• Heart failure can cause transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 1

Aortic Dissection

• Aortic dissection with hemopericardium occurs in 17-45% of patients with ascending aortic dissection 1, 2

Pulmonary Arterial Hypertension

• 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 and Indirect Injury

• Penetrating thoracic injury and esophageal perforation can cause pericardial effusion 1
• Non-penetrating thoracic injury and radiation injury can lead to 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

Drug-Related Causes

Chemotherapy Agents

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

Lupus-Like Syndrome Drugs

• 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, with causes including 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) 4

Key Clinical Pearls

• Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases 4
• 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
• If inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), clinical management should follow that of pericarditis 4