Causes of Pericardial Effusion
Pericardial effusion results from infectious, neoplastic, autoimmune, metabolic, iatrogenic, and idiopathic causes, with tuberculosis dominating in developing countries (>60% of cases) and viral infections being most common in developed nations, though up to 50% remain idiopathic despite comprehensive evaluation. 1, 2
Geographic and Epidemiologic Framework
The etiology varies dramatically by geographic location and healthcare setting:
- In developing countries and TB-endemic regions: Tuberculosis accounts for over 60% of cases, frequently associated with HIV co-infection, particularly in sub-Saharan Africa 1, 2, 3
- In developed countries: Viral infections are the leading infectious cause, but idiopathic cases comprise up to 50% despite thorough diagnostic workup 1, 2
- Among hospitalized medical patients: Malignancy is the most common cause of cardiac tamponade (likelihood ratio 2.9) 2, 3
Major Etiologic Categories
Infectious Causes
Viral infections are the predominant infectious etiology in developed countries 1:
- Enteroviruses (Coxsackie A and B), echoviruses, adenoviruses 1, 2
- Cytomegalovirus (increased incidence in immunocompromised and HIV-infected patients) 1, 2
- Epstein-Barr virus, herpes simplex virus, influenza 1, 2
- Parvovirus B19, hepatitis C, HIV 1, 2
Bacterial infections require at least three cultures of pericardial fluid for aerobes and anaerobes 1:
- Staphylococcus aureus, Klebsiella pneumoniae 1
- Mycobacterium tuberculosis (dominant worldwide cause) 1, 2
- Mycobacterium avium (in immunocompromised hosts) 1
Fungal infections occur particularly in immunocompromised patients 1, 2
Neoplastic Causes
Malignancy accounts for 10-25% of cases in developed countries 2, 3:
Secondary metastatic tumors (40 times more common than primary tumors) 2, 3:
Primary pericardial tumors (rare): Pericardial mesothelioma is 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, chemotherapy effects, or opportunistic infections 2
Autoimmune and Inflammatory Disorders
These account for 5-15% of cases in developed countries 2, 3:
- Systemic lupus erythematosus 1, 2
- Sjögren syndrome 1, 2
- Rheumatoid arthritis 1, 2
- Scleroderma (with potential for pericardial fibrosis predisposing to tamponade) 1, 4
- Systemic vasculitides: eosinophilic granulomatosis with polyangiitis (Churg-Strauss), Horton disease, Takayasu disease, Behçet syndrome 1
- Sarcoidosis 1, 2
Post-cardiac injury syndromes (common delayed-onset causes) 1, 2:
- Post-myocardial infarction syndrome (Dressler syndrome) 1, 2
- Post-pericardiotomy syndrome 1, 2
- Post-traumatic pericarditis (including iatrogenic trauma from coronary intervention, pacemaker insertion, radiofrequency ablation) 1, 2
Metabolic and Endocrine Disorders
Hypothyroidism occurs in 5-30% of hypothyroid patients 2, 3:
- Effusions may be large but tamponade is rare 2, 3
- Characterized by relative bradycardia and low QRS voltage on ECG 2
- Diagnosed by elevated TSH levels 2
Uremia in chronic renal failure is a common cause 2, 3
Other metabolic causes: Anorexia nervosa 1
Cardiovascular Causes
- Heart failure: Causes transudative effusion due to increased systemic venous pressure and decreased reabsorption 2, 3
- Pulmonary arterial hypertension: Present in 25-30% of cases, typically small in size and rarely causing hemodynamic compromise 2, 3
- Aortic dissection: Hemopericardium occurs in 17-45% of patients with ascending aortic dissection 2
Iatrogenic and Traumatic Causes
- Penetrating thoracic injury (requires immediate thoracotomy if tamponade develops) 2, 3
- Esophageal perforation 1, 2
- Non-penetrating thoracic trauma 1, 2
- Radiation injury (causes effusion and/or constriction in 6-30% of patients) 2
Post-procedural causes 2:
- Cardiac surgery 2
- Percutaneous coronary intervention 1, 2
- Pacemaker lead insertion 1, 2
- Radiofrequency ablation 1, 2
Chemotherapy-associated 2:
- Anthracyclines (doxorubicin, daunorubicin) - often associated with cardiomyopathy 1, 2
- Cyclophosphamide, cytarabine, imatinib, dasatinib 2
- Interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib 2
Drug-Related Causes
Hypersensitivity pericarditis with eosinophilia 1:
- Amiodarone, methysergide, mesalazine, clozapine, minoxidil 1, 2
- Dantrolene, practolol, phenylbutazone, thiazides 1, 2
- Streptomycin, thiouracils, streptokinase, p-aminosalicylic acid 1, 2
- Sulfa drugs, cyclosporine, bromocriptine 1, 2
- Vaccines, GM-CSF, anti-TNF agents 1, 2
Rare Specific Types
Chylopericardium (pericardial effusion composed of chyle) 2:
- Causes: Trauma, surgery, congenital lymphangiomatosis, radiotherapy, subclavian vein thrombosis, infection, mediastinal neoplasms, acute pancreatitis 2
Cholesterol pericarditis: Occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma 2
Pericardial cysts: Rare mediastinal masses (incidence 1 in 100,000), representing 6% of mediastinal masses 2
Clinical Diagnostic Pearls
When inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP): Manage as pericarditis 2
Cardiac tamponade without inflammatory signs: Higher risk of neoplastic etiology (likelihood ratio 2.9) 2
Severe effusion without tamponade and without inflammatory signs: Usually chronic idiopathic etiology (likelihood ratio 20) 2
Post-myocardial infarction effusion >10 mm: Most frequently associated with hemopericardium, and two-thirds may develop tamponade or free wall rupture 2
Important Caveats
Fluid appearance is not diagnostic: Serosanguinous or hemorrhagic fluid occurs 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, 5
Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases 2