What are the causes of unilateral pleural effusion?

Causes of Unilateral Pleural Effusion

Unilateral pleural effusions are most commonly caused by malignancy, parapneumonic effusion/empyema, pulmonary embolism, and tuberculosis, with the majority being exudative in nature. 1, 2

Transudative Causes

Heart failure is the dominant transudate etiology, accounting for over 80% of all transudates, though it typically presents bilaterally; when unilateral, it characteristically appears on the right side. 1, 2

• Hepatic hydrothorax represents approximately 10% of transudates and characteristically appears on the right side due to diaphragmatic defects. 1, 2
• End-stage renal failure causes pleural effusions in 24.7% of patients, typically from fluid overload, heart failure, or uremic pleuritis. 2, 3
• Urinothorax is a rare complication of obstructed kidneys where urine moves through the retroperitoneum into the pleural space; diagnosis is confirmed when pleural fluid creatinine exceeds serum creatinine. 3

Exudative Causes

Malignancy

Malignant effusions represent 26% of all pleural effusions and are a leading cause of unilateral presentations, frequently appearing ipsilateral to the primary tumor. 1, 2

• Lung cancer is the most common malignant cause, followed by breast cancer; lymphoma accounts for approximately 10% of malignant effusions. 2, 3
• Malignant effusions may present with circumferential pleural thickening that mimics tuberculosis but lacks chest wall invasion. 1

Infectious Causes

Parapneumonic effusion/empyema accounts for 16% of all pleural effusions and can be identified by CT features including lentiform configuration, split pleura sign, and adjacent consolidation. 1, 2

Tuberculosis represents 6% of effusions and should always be reconsidered in persistently undiagnosed cases as it is amenable to specific treatment. 4, 1, 2

• Pleural fluid smears for acid-fast bacilli are only positive in 10-20% of tuberculous effusions, with culture positive in 25-50%; adding pleural biopsy histology and culture improves diagnostic sensitivity to approximately 90%. 4, 3
• Adenosine deaminase (ADA) levels tend to be higher with tuberculosis than other exudates, though ADA is also elevated in empyema, rheumatoid pleurisy, and malignancy, limiting its utility in low-prevalence tuberculosis countries. 4

Vascular Causes

Pulmonary embolism is associated with effusions in up to 40% of cases, typically small, unilateral, and ipsilateral to the embolus, with approximately 75% presenting with pleuritic pain. 4, 1, 3

• Of these effusions, 80% are exudates and 20% are transudates; 80% are bloodstained. 4
• A pleural fluid red blood cell count exceeding 100,000/mm³ suggests malignancy, pulmonary infarction, or trauma. 4, 3
• There are no specific pleural fluid characteristics to distinguish pulmonary embolism-related effusions; the diagnosis should be pursued on clinical grounds with a high index of suspicion. 4

Autoimmune/Inflammatory Causes

Rheumatoid arthritis affects the pleura in approximately 5% of patients, more commonly in men despite the disease generally affecting more women. 4, 2, 3

• Pleural fluid glucose less than 1.6 mmol/L (29 mg/dL) strongly suggests rheumatoid etiology; rheumatoid arthritis is unlikely if glucose exceeds this threshold. 4, 3
• Pleural fluid can appear serous, turbid, yellow-green, milky, or hemorrhagic. 4, 3

Systemic lupus erythematosus (SLE) causes pleural disease in up to 50% of patients during their disease course. 4, 2, 3

• The presence of LE cells in pleural fluid is diagnostic of SLE. 4, 3
• Pleural fluid ANA testing should not be performed as it mirrors serum levels and is unhelpful; 10% of ANA-positive effusions without clinical SLE are actually due to malignancy. 4

Occupational/Environmental Causes

Benign asbestos pleural effusion typically occurs within the first two decades after asbestos exposure, with prevalence related to exposure dose and shorter latency than other asbestos-related disorders. 4, 3

• The effusion is usually small, asymptomatic, and has a propensity to be hemorrhagic. 4, 3
• The effusion may resolve within 6 months but often leaves residual diffuse pleural thickening; diagnosis can only be made with certainty after prolonged follow-up as there are no definitive tests. 4, 3

Special Populations

In HIV-infected patients, the differential diagnosis differs significantly from immunocompetent patients, with pleural effusions seen in 7-27% of hospitalized patients. 4

• The three leading causes are Kaposi's sarcoma (33% of cases), parapneumonic effusions (28%), and tuberculosis (14%). 4, 2
• Pneumocystis carinii pneumonia accounts for 10% and lymphoma for 7%. 4

Critical Diagnostic Pitfalls

In persistently undiagnosed effusions, pulmonary embolism and tuberculosis must be reconsidered as they are amenable to specific treatment. 4, 2, 3

• Many "undiagnosed" effusions ultimately prove to be malignant with sustained observation. 4, 2, 3
• Misclassification of cardiac and liver transudates as exudates occurs in 25-30% of cases when using Light's criteria alone. 2, 3
• NT-proBNP ≥1,500 pg/mL in serum or pleural fluid accurately diagnoses heart failure as the primary or contributory cause and predicts multiple etiologies. 1, 2