What are the causes of pleural effusion in patients with various medical histories, such as heart failure, cancer, or autoimmune disorders?

Causes of Pleural Effusion

The most common causes of pleural effusion are heart failure (29%), malignancy (26%), pneumonia (16%), tuberculosis (6%), post-surgery (4%), pericardial diseases (4%), and cirrhosis (3%). 1

Transudative Causes

Heart failure dominates transudative effusions, accounting for more than 80% of all transudates. 1, 2 This represents the single most important cause to consider when evaluating bilateral effusions in patients with known cardiac disease. 1

• Liver cirrhosis accounts for approximately 10% of transudates 1
• End-stage renal failure causes pleural effusions in 24.7% of ESRF patients, typically from fluid overload, heart failure, or uremic pleuritis 1, 3
• Other transudative causes include hypoalbuminemia, nephrotic syndrome, and atelectasis 1

Clinical Approach to Transudates

Small bilateral effusions in patients with decompensated heart failure, cirrhosis, or kidney failure are likely transudative and do not require diagnostic thoracentesis. 4 Most transudative effusions can be successfully treated with diuretics addressing the underlying cause. 2

Exudative Causes

Malignancy

Lung cancer is the leading cause of malignant pleural effusion, followed by breast cancer, with lymphoma accounting for approximately 10% of malignant effusions. 1, 5 Malignancy represents 26% of all pleural effusions and is a critical diagnosis not to miss. 1

• Lung cancer accounts for 25-52% of malignant effusions based on cytology reviews 5
• Breast cancer represents 3-27% of malignant effusions 5
• Lymphoma comprises 12-22% of malignant effusions 5
• Ovarian and gastrointestinal carcinomas are less common causes 5
• In 5-10% of malignant effusions, no primary tumor is identified 5

Dyspnea is the most common presenting symptom in patients with malignant effusions, occurring in more than half of cases. 5, 1 The pathogenesis involves decreased chest wall compliance, mediastinal shifting, decreased ipsilateral lung volume, and reflex stimulation. 5, 1

Infectious Causes

Parapneumonic effusions are the most common cause of exudative effusions. 4 A pH level less than 7.2 indicates complicated parapneumonic effusion and warrants prompt consultation for catheter or chest tube drainage, possible tissue plasminogen activator/deoxyribonuclease therapy, or thoracoscopy. 4

Tuberculosis accounts for approximately 6% of pleural effusions and should always be reconsidered in undiagnosed cases. 1, 3 Pleural fluid smears for acid-fast bacilli are only positive in 10-20% of tuberculous effusions, with culture positive in only 25-50%. 3 Adding pleural biopsy histology and culture improves diagnostic sensitivity to about 90%. 3 A positive tuberculin skin test with an exudative lymphocytic effusion may justify empirical antituberculous therapy. 5, 3, 2

Vascular Causes

Pulmonary embolism is associated with pleural effusions in up to 40% of cases; 80% are exudates and 80% are bloodstained. 3 This diagnosis must be reconsidered in persistently undiagnosed effusions as it is amenable to specific treatment. 5, 3

Autoimmune and Rheumatologic Causes

Rheumatoid arthritis affects the pleura in approximately 5% of patients, with effusions being more common in men despite the disease generally affecting more women. 5, 3 Rheumatoid arthritis is unlikely to be the cause if pleural fluid glucose is above 1.6 mmol/l (29 mg/dl). 5 The effusion can appear serous, turbid, yellow-green, milky, or hemorrhagic. 5, 3

Systemic lupus erythematosus (SLE) causes pleural disease in up to 50% of patients during their illness. 5, 3 The presence of LE cells in pleural fluid is diagnostic of SLE. 5, 3 However, pleural fluid ANA testing is not helpful as it mirrors serum levels and should not be measured. 5, 2

Occupational Causes

Benign asbestos pleural effusion typically occurs within the first two decades after asbestos exposure, with prevalence related to exposure dose. 5, 3 These effusions are usually small and asymptomatic with a propensity to be hemorrhagic, may resolve within 6 months, but often leave residual diffuse pleural thickening. 5, 3

Special Populations

HIV Patients

In HIV patients, the leading causes of pleural effusion are Kaposi's sarcoma (33%), parapneumonic effusions (28%), and tuberculosis (14%). 5, 1, 2 Pneumocystis carinii pneumonia accounts for 10% and lymphoma for 7%. 5

Approach to Persistent Undiagnosed Effusions

In persistently undiagnosed effusions, pulmonary embolism and tuberculosis should be reconsidered as they are amenable to specific treatment. 5, 1, 3 Approximately 15% of pleural effusions remain undiagnosed despite repeated cytology and pleural biopsy. 5, 3 Many "undiagnosed" effusions ultimately prove to be malignant with continued observation. 3

Critical Diagnostic Pitfalls

• Misclassification of cardiac and liver transudates as exudates occurs in 25-30% of cases when using Light's criteria alone 1, 3, 2
• Diagnostic bronchoscopy is not indicated unless the patient has hemoptysis or features of bronchial obstruction 5
• Pleural fluid ANA should not be routinely measured for SLE diagnosis 5, 2