What are the other causes of pleural effusion beyond the commonly recognized ones?

Less Common Causes of Pleural Effusion

Beyond the common causes of pleural effusion (heart failure, malignancy, pneumonia), there are numerous other important etiologies that should be considered in the diagnostic workup of patients with unexplained pleural effusions. 1

Autoimmune and Rheumatologic Causes

• Rheumatoid arthritis affects the pleura in approximately 5% of patients, with pleural effusions being more common in men despite the disease generally affecting more women 2
• Rheumatoid pleural effusions can appear serous, turbid, yellow-green, milky, or hemorrhagic; a pleural fluid glucose level below 1.6 mmol/L (29 mg/dL) strongly suggests rheumatoid etiology 2
• Systemic lupus erythematosus (SLE) causes pleural disease in up to 50% of patients during the course of their illness; the presence of LE cells in pleural fluid is diagnostic 2
• Pleural fluid ANA testing is not helpful in diagnosing SLE-related effusions as it mirrors serum levels and may be positive in other conditions, including malignancy 2, 3

Infectious Causes Beyond Pneumonia

• Tuberculosis accounts for approximately 6% of pleural effusions and should always be considered in undiagnosed cases 1, 4
• Pleural fluid smears for acid-fast bacilli are only positive in 10-20% of tuberculous effusions, with culture positive in only 25-50%; adding pleural biopsy histology and culture improves diagnostic sensitivity to about 90% 2
• HIV-associated effusions have a different differential diagnosis, with the three leading causes being Kaposi's sarcoma (33%), parapneumonic effusions (28%), and tuberculosis (14%) 2, 3
• Empyema requires prompt recognition and treatment with appropriate antibiotics and drainage; bench centrifugation can distinguish empyema from chylothorax, as empyema will leave a clear supernatant 2

Vascular Causes

• Pulmonary embolism is associated with pleural effusions in up to 40% of cases; 80% are exudates and 80% are bloodstained 2
• Effusions associated with pulmonary embolism have no specific characteristics, requiring diagnosis based on clinical suspicion 2
• A pleural fluid red blood cell count exceeding 100,000/mm³ suggests malignancy, pulmonary infarction, or trauma 2

Occupational and Environmental Causes

• Benign asbestos pleural effusion typically occurs within the first two decades after asbestos exposure, with prevalence related to exposure dose 2
• These effusions are usually small and asymptomatic with a propensity to be hemorrhagic; they may resolve within 6 months but often leave residual diffuse pleural thickening 2
• Diagnosis requires a prolonged period of follow-up as there are no definitive tests 2

Urologic Causes

• Urinothorax is a rare complication of obstructed kidneys where urine moves through the retroperitoneum into the pleural space 2
• The effusion typically occurs on the same side as the obstruction, smells like urine, and resolves when the obstruction is relieved 2
• Diagnosis is confirmed when pleural fluid creatinine level exceeds serum creatinine; the fluid is typically a transudate with low pH 2

Other Uncommon Causes

• Chylothorax appears milky and remains so after centrifugation, unlike empyema which clears 2
• End-stage renal failure causes pleural effusions in approximately 24.7% of patients, typically due to fluid overload, heart failure, or uremic pleuritis 1
• Post-surgical effusions account for approximately 4% of all pleural effusions 1
• Pericardial diseases are responsible for about 4% of pleural effusions 1

Approach to Persistent Undiagnosed Effusions

• In persistently undiagnosed effusions, pulmonary embolism and tuberculosis should be reconsidered as they are amenable to specific treatment 2, 4
• Many "undiagnosed" effusions ultimately prove to be malignant with continued observation 2
• Approximately 15% of pleural effusions remain undiagnosed despite repeated cytology and pleural biopsy 2
• Consider thoracoscopy if malignancy is suspected after routine tests have failed 4

Diagnostic Pitfalls

• Misclassification of cardiac and liver transudates as exudates occurs in 25-30% of cases 3, 4
• Diagnostic bronchoscopy is not indicated in the assessment of an undiagnosed effusion unless the patient has hemoptysis or features suggestive of bronchial obstruction 2
• A positive tuberculin skin test with an exudative lymphocytic effusion may justify empirical antituberculous therapy 3