Differential Diagnosis of Exudative Pleural Effusion
Exudative pleural effusions arise from increased pleural membrane permeability or altered local capillary permeability, and the most common causes are pneumonia/parapneumonic effusion, malignancy, tuberculosis, and pulmonary embolism. 1, 2
Major Categories of Exudative Effusions
Infectious Causes
- Parapneumonic effusion/empyema: The most common infectious cause, characterized by pleural fluid pH <7.2, elevated LDH (>200 IU/L), and nucleated cell count >5,000 cells/μL in complicated cases 3
- Tuberculosis: Typically presents with lymphocyte-predominant effusion and elevated adenosine deaminase levels; pleural biopsy confirms diagnosis in virtually 100% of cases 4, 5
- Other bacterial infections: Including anaerobic infections, which may produce foul-smelling fluid 4
Malignant Causes
- Metastatic malignancy: Accounts for a substantial proportion of exudative effusions; cytology combined with thoracoscopy achieves 97% diagnostic accuracy 5
- Malignant mesothelioma: Particularly important to diagnose efficiently, as 40% of needle incisions become invaded by tumor 1
- Primary lung cancer: With direct pleural involvement 2
Thromboembolic Disease
- Pulmonary embolism: Approximately 75% of patients with PE and pleural effusion have pleuritic pain; effusions typically occupy <1/3 of hemithorax with dyspnea disproportionate to effusion size 1, 2
Autoimmune/Inflammatory Causes
- Rheumatoid pleuritis: Characterized by very low pleural fluid glucose (<60 mg/dL) and low pH 3
- Systemic lupus erythematosus: Produces exudative effusion through autoimmune pleural inflammation 1
- Other connective tissue diseases: Including scleroderma and Sjögren's syndrome 1
Gastrointestinal Causes
- Esophageal rupture: Presents with very low pH (<7.0) and low glucose; consider with history of vomiting, chest pain, or recent instrumentation 3
- Pancreatitis: Elevated pleural fluid amylase is diagnostic 4
- Subphrenic abscess: Extension of intra-abdominal infection 1
Drug-Induced Causes
- Medication-related effusions: Multiple drugs can cause exudative effusions; obtain detailed drug history in all cases 1
Other Causes
- Post-cardiac injury syndrome: Following myocardial infarction or cardiac surgery 1
- Chylothorax: Milky appearance due to high lipid content from lymphatic obstruction 6
- Hemothorax: Bloody effusion requiring hematocrit measurement 6
Critical Diagnostic Approach
Initial Pleural Fluid Analysis
- Send all exudative effusions for: differential white cell count, cytology, bacterial cultures (including blood culture bottles), Gram stain, acid-fast bacilli stain and culture, protein, LDH, pH, glucose, and adenosine deaminase 1, 4
- Neutrophil-predominant effusions: Suggest parapneumonic effusion, empyema, or early-stage malignancy 7
- Lymphocyte-predominant effusions: Strongly suggest tuberculosis or malignancy; neutrophil-lymphocyte ratio significantly lower in TB compared to other causes 7
When Initial Testing Is Non-Diagnostic
- Pleural biopsy (blind needle): Achieves 40-70% diagnostic yield for both malignancy and inflammatory disease 5
- Medical thoracoscopy: Gold standard with ~95% diagnostic accuracy for exudative effusions; 97% for malignancy and virtually 100% for tuberculosis 5
Common Pitfalls to Avoid
- Missing pulmonary embolism: Pleural fluid tests are unhelpful for PE diagnosis; maintain high clinical suspicion based on presentation (pleuritic pain, small effusion, disproportionate dyspnea) 1
- Inadequate drug history: Always review medications, as drug-induced effusions are uncommon but important reversible causes 1
- Over-reliance on imaging: Ultrasound and CT cannot replace biochemical analysis for determining exudative nature or specific etiology 8, 6
- Delayed recognition of empyema: pH <7.2 mandates urgent chest tube drainage; delays worsen morbidity 3
- Insufficient sampling: Always send pleural fluid in both sterile vials and blood culture bottles to maximize microbiological yield 1