What are the causes of pericardial effusion?

Causes of Pericardial Effusion

Pericardial effusion results from diverse etiologies including infectious diseases (viral in developed countries, tuberculosis in endemic regions), malignancies (especially lung and breast cancer), autoimmune disorders, metabolic conditions (hypothyroidism, uremia), iatrogenic/traumatic injuries, and idiopathic causes, with up to 50% remaining idiopathic in developed countries despite comprehensive evaluation. 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

Tuberculosis

• Tuberculosis is the leading cause of pericardial effusion in developing countries and worldwide, especially in areas where TB is endemic and often associated with HIV infection 1
• TB dominates as the cause in over 60% of cases in endemic regions 2

Other Infections

• Fungal infections may lead to pericardial effusion, particularly in immunocompromised patients, including endemic fungi (Histoplasma, Coccidioides) and opportunistic fungi (Candida, Aspergillus) 2, 1
• Bacterial infections can cause purulent pericarditis requiring urgent surgical drainage 3

Neoplastic Causes

Secondary Malignancies (Most Common)

• The most common secondary malignant tumors causing pericardial effusion are lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias 2
• Malignant effusions account for 10-25% of cases in developed countries 2
• Critically, in almost two-thirds of patients with documented malignancy, pericardial effusion is caused by non-malignant diseases such as radiation pericarditis, other therapies, or opportunistic infections 2

Primary Tumors (Rare)

• Primary tumors of the pericardium are 40 times less common than metastatic ones 2
• Mesothelioma is the most common primary malignant tumor and is almost always incurable 2
• Benign primary tumors include lipomas and fibromas 2

Autoimmune and Inflammatory Causes

• Systemic autoimmune diseases including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides can cause pericardial effusion, accounting for 5-15% of cases 2, 1
• Sarcoidosis can involve the pericardium causing effusion 1
• Post-cardiac injury syndromes including post-myocardial infarction pericarditis (Dressler syndrome), post-pericardiotomy syndrome, and post-traumatic pericarditis lead to pericardial effusion 1
• Autoreactive (immune-mediated) pericarditis is another inflammatory cause 1

Metabolic and Endocrine Disorders

Hypothyroidism

• Hypothyroidism is the main metabolic cause, occurring in 5-30% of patients with hypothyroidism, though effusions may be large, tamponade is rare 1, 4

Uremia

• Pericardial effusion occurs in up to 20% of patients with end-stage renal disease (ESRD), with two distinct forms: uremic pericarditis and dialysis-associated pericarditis 1, 4

Cardiovascular and Pulmonary Causes

• Pericardial effusion is common (25-30%) in pulmonary arterial hypertension, typically small in size but rarely causing hemodynamic compromise 1
• Heart failure can cause transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 2, 1
• Aortic dissection with hemopericardium occurs in 17-45% of patients with ascending aortic dissection 2

Iatrogenic and Traumatic Causes

Direct Injury

• Penetrating thoracic injury and esophageal perforation can cause pericardial effusion 1
• Immediate thoracotomy is indicated in cardiac tamponade due to penetrating trauma 2

Post-Procedural

• Cardiac surgery, percutaneous coronary intervention, pacemaker lead insertion, and radiofrequency ablation can cause pericardial effusion 1
• Post-myocardial infarction: pericardial effusion >10 mm is most frequently associated with hemopericardium, and two-thirds may develop tamponade or free wall rupture 2

Radiation

• Radiation therapy can cause pericardial effusion and/or constriction in 6-30% of patients 1

Drug-Related Causes

Chemotherapy

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

Lupus-Like Syndrome

• Procainamide, hydralazine, methyldopa, isoniazid, and phenytoin can cause pericardial effusion 1

Other Medications

• Amiodarone, methysergide, mesalazine, clozapine, minoxidil, thiazides, anti-TNF agents, and various other medications have been implicated 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 with incidence of 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 2, 1
• The relative frequency of different causes depends on local epidemiology, hospital setting, and diagnostic protocol adopted 5

Clinical Pitfalls

A critical caveat: The presence of elevated inflammatory markers and other criteria (chest pain, pericardial rubs, ECG changes) suggests pericarditis rather than isolated effusion, which changes management significantly 5. Additionally, serosanguinous or hemorrhagic fluid can be found in malignant, post-pericardiotomy, rheumatologic, traumatic, and iatrogenic effusions, but also in idiopathic and viral forms, so fluid appearance alone cannot determine etiology 2.