What are the common causes of pericardial effusion?

Common Causes of Pericardial Effusion

The most common causes of pericardial effusion vary dramatically by geographic location: in developed countries, idiopathic cases (up to 50%), malignancy (10-25%), infections (15-30%), iatrogenic causes (15-20%), and autoimmune diseases (5-15%) predominate, whereas tuberculosis dominates in developing countries, accounting for over 60% of cases in endemic regions. 1, 2

Geographic and Epidemiologic Considerations

The etiology of pericardial effusion is fundamentally shaped by local epidemiology:

• Developed countries: Idiopathic effusions represent the largest proportion (up to 50% of cases), followed by malignancy, viral infections, and iatrogenic causes 1, 2
• Developing/endemic regions: Tuberculosis is the dominant cause worldwide, responsible for >60% of cases, often associated with concurrent HIV infection 2, 3

Major Etiologic Categories

Infectious Causes

Viral infections are the most common infectious etiology in developed countries 2:

• Common viral pathogens include enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza virus, parvovirus B19, hepatitis C virus, and HIV 2

Tuberculosis remains the leading infectious cause globally and must be considered in any patient from endemic areas or with HIV infection 2, 3

Bacterial and fungal infections can cause pericardial effusion, particularly in immunocompromised patients 2, 4

Neoplastic Causes

Malignancy accounts for 10-25% of pericardial effusions in developed countries 1, 2:

• Secondary metastatic tumors (most common): lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias 1, 2
• Primary pericardial tumors are 40 times less common than metastatic disease, with mesothelioma being the most frequent primary malignancy 1, 2

Critical caveat: In almost two-thirds of patients with documented malignancy, pericardial effusion is actually caused by non-malignant processes such as radiation pericarditis or opportunistic infections, not the cancer itself 1, 2

Autoimmune and Inflammatory Causes

Connective tissue diseases account for 5-15% of cases 1, 2:

• Systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides 2
• Sarcoidosis with pericardial involvement 2

Post-cardiac injury syndromes represent important inflammatory causes 2:

• Post-myocardial infarction pericarditis (pericardial effusion >10 mm is associated with hemopericardium, with two-thirds at risk for tamponade or free wall rupture) 1, 2
• Post-pericardiotomy syndrome following cardiac surgery 2
• Post-traumatic pericarditis 2

Metabolic and Endocrine Disorders

Hypothyroidism is the primary metabolic cause, occurring in 5-30% of hypothyroid patients; effusions may be large but tamponade is rare 2

Uremia in renal failure patients commonly causes pericardial effusion 2, 4

Cardiovascular Causes

• Heart failure causes transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 1, 2
• Pulmonary arterial hypertension is associated with pericardial effusion in 25-30% of cases, typically small and rarely causing hemodynamic compromise 2
• Aortic dissection (ascending): pericardial effusion with hemopericardium occurs in 17-45% of patients 1, 2

Iatrogenic and Traumatic Causes

Direct injury 2:

• Penetrating thoracic trauma
• Esophageal perforation

Post-procedural complications 2:

• Cardiac surgery
• Percutaneous coronary intervention
• Pacemaker lead insertion
• Radiofrequency ablation

Radiation therapy causes pericardial effusion and/or constriction in 6-30% of patients 2

Chemotherapy-associated 2:

• Anthracyclines (doxorubicin, daunorubicin)
• Cyclophosphamide, cytarabine
• Tyrosine kinase inhibitors (imatinib, dasatinib, osimertinib)
• Other agents: interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil

Drug-Induced Causes

Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin 2

Other medications: amiodarone, methysergide, mesalazine, clozapine, minoxidil, thiazides, cyclosporine, anti-TNF agents 2

Rare Specific Types

• Chylopericardium: caused by thoracic duct injury from trauma, surgery, radiotherapy, or mediastinal neoplasms 2
• Cholesterol pericarditis: occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma 2

Clinical Approach to Etiology

When inflammatory signs are present (chest pain, fever, pericardial friction rub, ECG changes): acute idiopathic pericarditis is most likely, regardless of effusion size or tamponade presence 5

When severe effusion exists without inflammatory signs and without tamponade: chronic idiopathic pericardial effusion is most probable 5

When tamponade occurs without inflammatory signs: neoplastic pericardial effusion should be strongly suspected 5