What are the causes and management of exudative pleural effusions?

Causes of Exudative Pleural Effusions

The most common causes of exudative pleural effusions are malignancy (particularly lung and breast cancer), pneumonia/parapneumonic effusions, tuberculosis, and pulmonary embolism. 1, 2

Primary Etiologies

Malignant Effusions

• Lung carcinoma accounts for approximately one-third of all malignant pleural effusions, making it the single most common malignant cause 1, 2
• Breast carcinoma is the second most common malignancy causing exudative effusions 1, 2, 3
• Lymphomas (both Hodgkin's and non-Hodgkin's) represent approximately 10% of malignant effusions 1, 2
• Ovarian and gastrointestinal carcinomas are less common causes 1
• In 5-10% of malignant effusions, no primary tumor is identified despite thorough investigation 1
• Studies demonstrate that 42-77% of all exudative effusions are secondary to malignancy 1

Infectious Causes

• Parapneumonic effusions from bacterial pneumonia account for approximately 16% of all pleural effusions 1, 2
• Tuberculosis causes approximately 6% of pleural effusions overall and is always exudative 1, 2
• In resource-limited settings, tuberculosis may be the most common cause, accounting for up to 54.57% of exudative effusions 4
• Empyema represents a complicated parapneumonic effusion requiring specific management 4

Pulmonary Embolism

• Pulmonary embolism is a critical exudative cause that must be reconsidered in persistent undiagnosed effusions because it is amenable to specific treatment 1, 2

Rheumatologic Causes

• Rheumatoid arthritis causes pleural effusion in approximately 5% of patients, typically presenting as an exudate with high rheumatoid factor titers 2, 5
• Systemic lupus erythematosus affects up to 50% of patients during their disease course with exudative effusions 2
• These effusions have characteristic features: exudative with high lipids and lactate dehydrogenase, very low glucose and pH levels 5

Pathophysiologic Mechanisms

Direct Pleural Involvement

• Most pleural metastases arise from tumor emboli to the visceral pleural surface with secondary seeding to the parietal pleura 1
• Direct tumor invasion occurs with lung cancers, chest wall neoplasms, and breast carcinoma 1
• Local inflammatory changes from tumor invasion increase capillary permeability, resulting in fluid accumulation 1

Lymphatic Obstruction

• Interference with lymphatic drainage anywhere between the parietal pleura and mediastinal lymph nodes results in pleural fluid formation 1

Paramalignant Effusions

• Post-obstructive pneumonia with parapneumonic effusion 1
• Thoracic duct obstruction causing chylothorax 1
• Pulmonary embolism in cancer patients 1
• Treatment-related: radiation therapy, methotrexate, procarbazine, cyclophosphamide, bleomycin 1
• Tyrosine kinase inhibitors are now the most common drug-related cause of exudative effusions 1

Special Population Considerations

HIV Patients

• The leading causes in HIV patients are Kaposi's sarcoma, parapneumonic effusions, and tuberculosis 2, 3

End-Stage Renal Failure

• While most effusions are transudative from fluid overload, uraemic pleuritis causes exudative effusions in ESRF patients 2

Critical Diagnostic Pitfalls

Misclassification Issues

• Cardiac and liver transudates are misclassified as exudates in approximately 25-30% of cases when using Light's criteria 1, 2, 3
• This occurs because Light's criteria were designed to maximize sensitivity for detecting exudates (98% sensitivity) at the expense of specificity (72% specificity) 1
• When heart failure is suspected but Light's criteria suggest an exudate, use a serum-effusion albumin gradient >1.2 g/dL to reclassify as transudate 2
• NT-BNP levels >1500 μg/mL in serum or pleural fluid can accurately diagnose heart failure as the cause 2, 3

Conditions Causing Either Transudate or Exudate

• Non-expansile lung, chylothorax, and superior vena cava syndrome may present as either transudate or exudate 1

Diagnostic Approach for Exudative Effusions

Initial Evaluation

• Obtain detailed drug history using resources like the Pneumotox app, as numerous medications cause exudative effusions 1
• Document complete occupational history, particularly asbestos exposure, for all pleural effusions 1
• Perform thoracic ultrasound on every patient at initial presentation to assess safety of aspiration and identify nodularity of diaphragm/parietal pleura suggesting malignancy 1

Laboratory Analysis

• Pleural fluid cytology provides diagnosis in approximately 55% of malignant effusions 4
• Blind pleural biopsy yields diagnosis in 62% of tuberculous effusions 4
• Lymph node FNAC has the highest yield (81.5%) for diagnosing tuberculous effusion 4
• Sputum smear for AFB is positive in only 27.4% of tuberculous cases 4

Advanced Procedures When Initial Tests Fail

• Bronchoscopic biopsy provides the highest yield (84.6%) for lung cancer, followed by CT-guided FNAC (77.6%) 4
• Thoracoscopy should be considered if malignancy is suspected after routine tests fail 2
• A positive tuberculin skin test with exudative lymphocytic effusion may justify empirical antituberculous therapy 2

Persistent Undiagnosed Effusions

• Reconsider pulmonary embolism and tuberculosis as they require specific treatment 1, 2
• Watchful waiting with interval CT scans is appropriate for small effusions too difficult to sample 1
• Even after comprehensive investigation, approximately 2% of cases remain undiagnosed 4