Causes of Pericardial and Pleural Effusions
Pericardial Effusion Causes
Infectious Etiologies
Viral infections are the most common infectious cause in developed countries, including enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza, parvovirus B19, hepatitis C, and HIV 1. However, tuberculosis dominates globally and in endemic regions, accounting for over 60% of cases, particularly in areas with high HIV prevalence 1. Fungal infections occur primarily in immunocompromised patients 1.
Malignant Causes
Malignant effusions account for 10-25% of cases in developed countries, with lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias being the most common secondary tumors 1. Primary pericardial tumors (mainly mesothelioma) are 40 times less common than metastatic disease 1.
Critical pitfall: 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, 1. This underscores the importance of confirming malignant infiltration through pericardial fluid cytology and biopsy rather than assuming malignant etiology 2.
Autoimmune and Inflammatory Causes
Systemic autoimmune diseases cause 5-15% of cases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides 1. Post-cardiac injury syndromes (post-myocardial infarction pericarditis, post-pericardiotomy syndrome, post-traumatic pericarditis) and autoreactive pericarditis represent additional inflammatory causes 1.
Metabolic and Endocrine Disorders
Hypothyroidism occurs in 5-30% of hypothyroid patients, producing effusions that may be large but rarely cause tamponade 1. Uremia in renal failure patients is another major metabolic cause 1.
Cardiovascular Causes
Heart failure causes transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 1. Pericardial effusion occurs in 25-30% of pulmonary arterial hypertension patients, typically small and rarely causing hemodynamic compromise 1. Aortic dissection with hemopericardium occurs in 17-45% of ascending aortic dissection cases 1.
Iatrogenic and Traumatic Causes
Direct injuries include penetrating thoracic trauma and esophageal perforation 1. Post-procedural causes include cardiac surgery, percutaneous coronary intervention, pacemaker insertion, and radiofrequency ablation 1. Radiation therapy causes pericardial effusion and/or constriction in 6-30% of patients 1. Chemotherapy agents including anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, and osimertinib can cause effusions 1.
Drug-Related Causes
Lupus-like syndrome drugs (procainamide, hydralazine, methyldopa, isoniazid, phenytoin) and various other medications including amiodarone, methysergide, mesalazine, clozapine, minoxidil, anti-TNF agents, and immune checkpoint inhibitors can cause pericardial effusion 1, 3.
Idiopathic
Up to 50% of cases remain idiopathic in developed countries despite comprehensive evaluation 1, 4.
Pleural Effusion Causes
Transudative Effusions
Congestive heart failure is the most common cause of transudative pleural effusions, resulting from increased hydrostatic pressure 5. Cirrhosis with hepatic hydrothorax and nephrotic syndrome are other major transudative causes 5.
Exudative Effusions - Infectious
Parapneumonic effusions and empyema from bacterial pneumonia are common infectious causes 6, 5. Tuberculosis is a major cause globally, particularly in endemic areas, diagnosed through elevated adenosine deaminase levels in pleural fluid 6, 5.
Exudative Effusions - Malignant
Malignant pleural effusions occur commonly with lung cancer, breast cancer, and lymphoma, often representing disseminated or advanced disease 7, 6. These may be the presenting sign of cancer or indicate recurrence 7. Mesothelioma can be diagnosed using mesothelin biomarkers 6.
Exudative Effusions - Autoimmune
Lupus erythematosus and rheumatoid disease cause pleural effusions through inflammatory mechanisms 5. Rheumatoid effusions characteristically have low glucose and pH 5.
Other Causes
Chylothorax results from thoracic duct injury or obstruction due to trauma, surgery, malignancy, or lymphangiomatosis 1. Pulmonary embolism, pancreatitis, and post-cardiac injury syndrome are additional causes 5.
Diagnostic Approach
Pericardial Effusion
Serosanguinous or hemorrhagic fluid appearance cannot determine etiology alone, as it occurs in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions 2, 1. Bacterial cultures are diagnostic in sepsis, TB, and HIV-positive patients 2. Fluid cytology separates malignant from non-malignant effusions, though tumor markers in pericardial fluid remain controversial 2. Histological/immunohistological evaluation of pericardioscopically-guided biopsies (7-10 samples) provides the highest diagnostic yield 2.
Pleural Effusion
First determine if the effusion is transudative or exudative using Light's criteria 5. Specific biomarkers include natriuretic peptides for heart failure, adenosine deaminase for tuberculosis, and mesothelin for mesothelioma 6. Image-guided biopsies should be attempted first when parietal pleural nodularity or thickening exists; pleuroscopic biopsies are reserved for persistently symptomatic undiagnosed effusions after fluid analysis 6.
Management Principles
Pericardial Effusion
Pericardiocentesis is the Class I indication for cardiac tamponade to provide immediate relief and establish diagnosis 2, 8. For large suspected neoplastic effusions without tamponade: (1) systemic antineoplastic treatment as baseline therapy, (2) pericardiocentesis for symptom relief and diagnosis, and (3) intrapericardial instillation of cytostatic/sclerosing agents to prevent recurrences (40-70% recurrence rate) 2. Intrapericardial cisplatin is most effective for lung cancer involvement; thiotepa for breast cancer metastases 2.
Surgical pericardiotomy does not improve outcomes over pericardiocentesis and has higher complication rates (myocardial laceration, pneumothorax, mortality) 8. Pericardial window via left minithoracotomy is safe and effective for malignant tamponade but is palliative 2, 8. Pericardiectomy is rarely indicated, mainly for constriction or complications of previous procedures 2, 8.
For uremic effusions, intensified hemodialysis plus intrapericardial triamcinolone (300 mg/m² body surface) should be considered 2. Immune checkpoint inhibitor-related effusions typically respond to corticosteroid therapy 3.
Pleural Effusion
Treatment goals prioritize symptom reduction and quality of life improvement, particularly in malignant effusions with poor prognosis 7. Permanent drainage and/or obliteration of the pleural space are crucial for effective management and long-term palliation 7. Management requires coordination between interventional radiology, cardiology, thoracic surgery, and medical/radiation oncology 7.