What are the common causes of pericardial effusion?

Common Causes of Pericardial Effusion

The most common causes of pericardial effusion vary dramatically by geography: in developed countries, idiopathic cases (up to 50%), malignancy (10-25%), viral infections (15-30%), and iatrogenic causes (15-20%) predominate, while tuberculosis dominates in developing countries, accounting for over 60% of cases, particularly in HIV-endemic regions. 1, 2, 3

Geographic and Epidemiologic Framework

The etiology of pericardial effusion must be understood through a geographic lens:

• Developing countries: Tuberculosis is the overwhelming cause (>60% of cases), especially where TB is endemic and HIV co-infection is prevalent 1, 2
• Developed countries: The distribution is more heterogeneous, with many cases remaining idiopathic despite comprehensive evaluation 1, 2

Major Etiologic Categories

Infectious Causes

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

• Enteroviruses, echoviruses, adenoviruses 2
• Cytomegalovirus, Epstein-Barr virus, herpes simplex virus 2
• Influenza virus, parvovirus B19 2
• Hepatitis C virus and HIV 2

Bacterial infections 1, 2:

• Tuberculosis remains the leading cause worldwide and the most common cause in developing countries 1, 2
• Purulent pericarditis is less common in developed countries 1

Fungal infections may occur, particularly in immunocompromised patients 2

Neoplastic Causes

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

• Secondary metastatic tumors are 40 times more common than primary pericardial tumors 2, 3
• Most common: lung cancer, breast cancer, lymphoma, malignant melanoma, leukemias 2, 3
• Primary pericardial tumors are rare, with mesothelioma being the most common primary malignant tumor 2

Critical caveat: In almost two-thirds of patients with documented malignancy, pericardial effusion is actually caused by non-malignant diseases such as radiation pericarditis, other therapies, or opportunistic infections 2

Autoimmune and Inflammatory Disorders

Systemic autoimmune diseases account for 5-15% of cases 1, 2:

• Systemic lupus erythematosus 1, 2
• Sjögren syndrome 1, 2
• Rheumatoid arthritis 1, 2
• Scleroderma 1, 2
• Systemic vasculitides, Behçet syndrome 1
• Sarcoidosis 1, 2
• Inflammatory bowel diseases 1

Post-cardiac injury syndromes have an autoimmune pathogenesis 1:

• Post-myocardial infarction pericarditis (Dressler syndrome) 1
• Post-pericardiotomy syndrome 1
• Post-traumatic pericarditis (iatrogenic or accidental) 1

Metabolic and Endocrine Disorders

Renal failure is a major metabolic cause 1:

• Uremic pericarditis (before or within 8 weeks of dialysis initiation) 1
• Dialysis pericarditis (≥8 weeks after dialysis stabilization) 1
• Patients with ESRD are more likely to develop chronic pericardial effusion due to continuous volume overload 1
• Pericardial effusion is often bloody in uremic patients 1

Hypothyroidism occurs in 5-30% of hypothyroid patients 2, 3:

• Effusions may be large but tamponade is rare 2, 3

Iatrogenic and Traumatic Causes

Direct injury 2, 3:

• Penetrating thoracic injury 2, 3
• Esophageal perforation 2, 3

Indirect injury 2, 3:

• Non-penetrating thoracic trauma 2, 3
• Radiation injury (causes effusion and/or constriction in 6-30% of patients) 2

Post-procedural causes 2:

• Cardiac surgery 2
• Percutaneous coronary intervention 2
• Pacemaker lead insertion 2
• Radiofrequency ablation 2

Chemotherapy-associated 2:

• Anthracyclines (doxorubicin, daunorubicin) 2
• Cyclophosphamide, cytarabine 2
• Imatinib, dasatinib 2
• Multiple other agents including 5-fluorouracil, osimertinib 2

Drug-induced lupus-like syndrome 2:

• Procainamide, hydralazine, methyldopa 2
• Isoniazid, phenytoin 2

Cardiovascular Causes

Heart failure causes transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 1, 2:

Pulmonary arterial hypertension causes effusion in 25-30% of cases 2:

• Typically small in size 2
• Rarely causes hemodynamic compromise 2

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

Idiopathic Causes

Up to 50% of cases in developed countries remain idiopathic despite comprehensive diagnostic evaluation 1, 2, 3

Clinical Diagnostic Pearls

Cardiac tamponade without inflammatory signs is associated with higher risk of neoplastic etiology (likelihood ratio 2.9) 2

Severe effusion without cardiac tamponade and without inflammatory signs is usually associated with chronic idiopathic etiology (likelihood ratio 20) 2

If inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), clinical management should follow that of pericarditis 2

Important Caveats

Fluid appearance alone cannot determine etiology: Serosanguinous or hemorrhagic fluid can be found in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions 2

Large chronic effusions (>3 months) carry up to one-third risk of progression to cardiac tamponade 3, 4

Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases, making a thorough systemic evaluation essential 2