What are the causes of pericardial effusion?

Causes of Pericardial Effusion

The most common causes of pericardial effusion include infectious diseases (particularly viral and tuberculosis), neoplastic conditions, autoimmune disorders, metabolic/endocrine disorders, iatrogenic/traumatic injuries, and idiopathic causes. 1

Infectious Causes

• 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 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
• Bacterial infections (purulent pericarditis) can cause pericardial effusion, requiring surgical drainage typically through subxiphoid pericardiotomy 2
• Fungal infections may also lead to pericardial effusion, particularly in immunocompromised patients 1

Autoimmune and Inflammatory Causes

• Systemic autoimmune diseases including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides 1
• Sarcoidosis can involve the pericardium causing effusion 1
• Post-cardiac injury syndromes including post-myocardial infarction pericarditis, post-pericardiotomy syndrome, and post-traumatic pericarditis 1
• Autoreactive pericarditis (immune-mediated inflammation) 1

Neoplastic Causes

• Primary tumors of the pericardium (rare, primarily pericardial mesothelioma) 1
• Secondary metastatic tumors (common, especially lung and breast cancer, lymphoma) 1
• Malignant disease is the most common cause of pericardial effusion with tamponade among medical patients 3

Metabolic and Endocrine Disorders

• Hypothyroidism is the main cause in this category, occurring in 5-30% of patients with hypothyroidism; effusions may be large but tamponade is rare 1
• Uremia in patients with renal failure 1, 3
• Other metabolic causes include myxedema, anorexia nervosa 1

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 1, 3
• Aortic dissection can lead to hemorrhagic pericardial effusion and tamponade 3

Iatrogenic and Traumatic Causes

• Direct injury: penetrating thoracic injury, esophageal perforation 1
• Indirect injury: non-penetrating thoracic injury, radiation injury 1
• Post-procedural: cardiac surgery, percutaneous coronary intervention, pacemaker lead insertion, radiofrequency ablation 1
• Chemotherapy-associated: anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib 1, 4
• Radiation therapy can cause pericardial effusion and/or constriction in 6-30% of patients 1

Rare Specific Types of Pericardial Effusion

• Chylopericardium: pericardial effusion composed of chyle due to injury or blockage of the thoracic duct; causes include trauma, surgery (especially for congenital heart disease), 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 (incidence 1 in 100,000) representing 6% of mediastinal masses and 33% of mediastinal cysts 1

Drug-Related Causes

• Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin 1
• Antineoplastic drugs (often associated with cardiomyopathy): doxorubicin, daunorubicin 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

Idiopathic Causes

• In developed countries, many cases remain idiopathic (up to 50%) despite comprehensive diagnostic evaluation 1
• Idiopathic pericardial effusion should be a diagnosis of exclusion after ruling out other potential causes 2

Clinical Pearls and Pitfalls

• The relative frequency of different causes depends on local epidemiology, hospital setting, and diagnostic protocols 5
• When evaluating pericardial effusion, it's important to assess size, hemodynamic significance, and possible associated diseases 5
• The presence of inflammatory signs (chest pain, fever, pericardial friction rub) suggests acute pericarditis regardless of effusion size 2
• Severe effusion without inflammatory signs or tamponade suggests chronic idiopathic pericardial effusion, while tamponade without inflammatory signs suggests neoplastic etiology 2
• The rate of fluid accumulation, rather than absolute volume, often determines the hemodynamic impact and urgency of intervention 6