What are the causes of pericardial effusion?

Causes of Pericardial Effusion

Geographic and Epidemiologic Framework

Tuberculosis dominates as the cause of pericardial effusion in developing countries (>60% of cases), while in developed nations, idiopathic causes account for up to 50% of cases, followed by neoplastic disease (10-25%). 1, 2

The approach to etiology must be framed by geographic location and patient population:

• In TB-endemic regions and HIV-prevalent areas: Tuberculosis is the leading cause worldwide and should be the primary consideration 1, 2
• In developed countries: The distribution shifts dramatically toward idiopathic, viral, and neoplastic etiologies 1, 2

---

Major Etiologic Categories

Infectious Causes

Viral infections are the most common infectious etiology in developed countries 1:

• Enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza virus, parvovirus B19, hepatitis C virus, and HIV 1

Tuberculosis remains the dominant cause globally, particularly in endemic regions and with HIV co-infection 1, 2

Fungal infections occur primarily in immunocompromised patients 1

Neoplastic Causes

Malignancy is the most common cause of cardiac tamponade among medical patients (likelihood ratio 2.9) 1, 2:

• Secondary metastatic tumors (40 times more common than primary): lung cancer, breast cancer, lymphoma, malignant melanoma, leukemias 1, 2
• Primary pericardial tumors (rare): pericardial mesothelioma is the most common primary malignant tumor 1

Critical caveat: In almost two-thirds of patients with documented malignancy, pericardial effusion is caused by non-malignant diseases such as radiation pericarditis, chemotherapy effects, or opportunistic infections 1

Autoimmune and Inflammatory Disorders

These account for 5-15% of cases in developed countries 1, 2:

• Systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, systemic vasculitides 1, 2
• Sarcoidosis 1
• Post-cardiac injury syndromes: post-myocardial infarction pericarditis, post-pericardiotomy syndrome, post-traumatic pericarditis 1
• Autoreactive (immune-mediated) pericarditis 1

Metabolic and Endocrine Disorders

Hypothyroidism is the main metabolic cause, occurring in 5-30% of hypothyroid patients 3, 1:

• Effusions may be quite large but tamponade occurs rarely 3, 1
• Diagnosed by elevated TSH level, characterized by relative bradycardia and low QRS voltage on ECG 3

Uremia in end-stage renal disease causes pericardial effusion in up to 20% of patients, with two distinct forms: uremic pericarditis and dialysis-associated pericarditis 2, 4

Cardiovascular and Pulmonary Causes

Pulmonary arterial hypertension causes effusion in 25-30% of cases, typically small in size but rarely causing hemodynamic compromise 3, 1:

• Results from right ventricular failure, increased right-sided filling pressures, right atrial hypertension, and increased pressure in thebesian veins and coronary sinus 3
• Diagnosis of tamponade is challenging because high right-sided pressures mask typical findings; left atrial early diastolic collapse is more commonly seen than right-sided chamber collapse 3

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

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

Iatrogenic and Traumatic Causes

Direct injury 1, 2:

• Penetrating thoracic injury (requires immediate thoracotomy if tamponade develops) 1
• Esophageal perforation 1

Indirect injury 1, 2:

• Non-penetrating thoracic trauma 1
• Radiation injury (causes effusion and/or constriction in 6-30% of patients) 1

Post-procedural 1:

• Cardiac surgery, percutaneous coronary intervention, pacemaker lead insertion, radiofrequency ablation 1
• Post-myocardial infarction: effusion >10 mm is most frequently associated with hemopericardium, and two-thirds may develop tamponade or free wall rupture 1

Important note: In the setting of iatrogenic pericardial effusion, full anticoagulation may be a risk factor for tamponade and complications, though in acute pericarditis without iatrogenic injury, anticoagulation has not been shown to increase tamponade risk 3

Drug-Related Causes

Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin 1

Chemotherapy-associated: anthracyclines (doxorubicin, daunorubicin), cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib 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, anti-TNF agents 1

Foreign substance reactions: polymer fume inhalation, serum sickness from blood products or foreign antisera, venoms (scorpion fish sting), direct pericardial application of talc, magnesium silicate, silicones, tetracyclines, sclerosants, asbestos, iron in β-thalassemia 3

Rare Specific Types

Chylopericardium (pericardial effusion composed of chyle) 3, 1:

• Causes: trauma, surgery (especially for congenital heart disease), congenital lymphangiomatosis, radiotherapy, subclavian vein thrombosis, infection (TB), mediastinal neoplasms, acute pancreatitis 3, 1
• Often associated with chylothorax 3
• CT with/without contrast or combined with lymphangiography/lymphoscintigraphy can identify thoracic duct injury or blockage 3

Cholesterol pericarditis (distinct from chylopericardium): occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma; fluid is clear with cholesterol concentration equal to or exceeding blood levels 3, 1

---

Clinical Diagnostic Clues

Cardiac tamponade without inflammatory signs is associated with higher risk of neoplastic etiology (likelihood ratio 2.9) 1

Severe effusion without cardiac tamponade and without inflammatory signs is usually associated with chronic idiopathic etiology (likelihood ratio 20) 1, 2

If inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), clinical management should follow that of pericarditis 1, 4

Important caveat: Serosanguinous or hemorrhagic fluid appearance alone cannot determine etiology, as it occurs in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions 1, 2

---

Risk Stratification

Large chronic effusions (>3 months) carry up to one-third risk of progression to cardiac tamponade 2, 5

Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases, emphasizing the importance of comprehensive evaluation 1