What are the etiologies of pericarditis?

Causes of Pericarditis

Primary Etiologic Classification

Pericarditis has diverse infectious and non-infectious causes, with viral infections being the most common etiology in developed countries (accounting for 80-90% of idiopathic cases), while tuberculosis dominates globally, particularly in developing nations where it causes >60% of cases. 1, 2, 3

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Infectious Causes

Viral Etiologies

• Viruses are the leading infectious cause in developed countries, including enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza virus, parvovirus B19, hepatitis C virus, and HIV 1, 4
• Most idiopathic cases (42-49% in tertiary centers) are presumed viral when conventional diagnostic evaluation fails to identify a specific pathogen 2, 3

Bacterial Etiologies

• Tuberculosis is the most common cause worldwide, responsible for >90% of cases in HIV-infected individuals and 50-70% in non-HIV-infected individuals in TB-endemic developing countries 2, 5
• Untreated tuberculous pericarditis carries an ≈85% mortality rate and progresses to constrictive pericarditis in 30-50% of cases 4
• Purulent bacterial pericarditis (S. aureus, K. pneumoniae, M. avium) is uncommon in developed countries but carries 17-40% mortality at 6 months and 20-30% risk of progression to constriction 2, 6

Other Infectious Agents

• Fungal infections may cause pericarditis, particularly in immunocompromised patients 4, 7

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Non-Infectious Causes

Autoimmune and Inflammatory Disorders

• Systemic autoimmune diseases account for 5-15% of cases in developed countries, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, systemic vasculitides (eosinophilic granulomatosis with polyangiitis, Horton disease, Takayasu disease, Behçet syndrome), and sarcoidosis 1, 2, 4
• Familial Mediterranean fever and other autoinflammatory conditions are associated with pericarditis 2

Post-Cardiac Injury Syndromes

• Post-myocardial infarction syndrome (Dressler syndrome) results from autoimmune pericardial reaction following infarction 4, 5
• Post-pericardiotomy syndrome accounts for 11-37% of cases in developed countries, occurring more often after valve surgery than coronary artery bypass grafting 2, 4
• Post-traumatic pericarditis can follow iatrogenic cardiac injury from coronary percutaneous intervention, pacemaker lead insertion, or radiofrequency ablation 1, 4

Neoplastic Causes

• Primary tumors (rare) include pericardial mesothelioma 1, 2
• Secondary metastatic tumors (common) account for 10-25% of cases in developed countries, particularly from lung cancer, breast cancer, and lymphomas—these are 40 times more common than primary tumors 1, 2, 4
• Critically, in almost two-thirds of patients with documented malignancy, pericardial disease is caused by non-malignant conditions such as radiation pericarditis or opportunistic infections 4

Metabolic and Endocrine Disorders

• Uremia develops in 6-10% of patients with advanced renal failure and affects up to 13% of patients on maintenance hemodialysis 1, 4, 8
• Hypothyroidism causes pericardial effusion in 5-30% of hypothyroid patients, though tamponade is rare 2, 4
• Anorexia nervosa and other rare metabolic disorders can cause pericarditis 1

Traumatic and Iatrogenic Causes

• Direct injury: penetrating thoracic injury, esophageal perforation 1, 4
• Indirect injury: non-penetrating thoracic trauma 1, 4
• Radiation-induced pericarditis accounts for 9-31% of cases, occurring in 6-30% of patients receiving thoracic radiotherapy, mostly after treatment for Hodgkin's disease or breast cancer 2, 4

Drug-Related Causes

• Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin 1, 4, 8
• Antineoplastic drugs (often associated with cardiomyopathy): doxorubicin, daunorubicin, anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib 1, 4
• 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, 4

Cardiovascular Causes

• Hypertension and chronic heart failure are associated with pericarditis 1, 2
• Heart failure can cause transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 4, 7

Congenital Abnormalities

• Congenital partial and complete absence of the pericardium (uncommon) 1

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Key Epidemiologic and Prognostic Considerations

• Men aged 16-65 years have higher risk for pericarditis compared to women, with the highest risk difference among young adults 2
• Risk of progression to constrictive pericarditis varies dramatically by etiology: <1% for viral/idiopathic, 2-5% for immune-mediated and neoplastic, and 20-30% for bacterial (especially purulent) pericarditis 2
• In developed countries, up to 50% of cases remain idiopathic despite comprehensive diagnostic evaluation 4, 7, 3

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Clinical Pitfalls

• Do not assume serosanguinous or hemorrhagic fluid indicates a specific etiology—it can occur in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral forms 4
• In uremic patients, autonomic dysfunction may keep heart rate 60-80 bpm during tamponade despite fever and hypotension, and the ECG typically lacks diffuse ST/T elevation 4
• Cardiac tamponade without inflammatory signs (no chest pain, fever, pericardial rub, elevated CRP) has a higher risk of neoplastic etiology (likelihood ratio 2.9) 4, 7
• Severe effusion without tamponade and without inflammatory signs is usually chronic idiopathic etiology (likelihood ratio 20) 4, 7