Causes of Pleural Effusion
Pleural effusion results from either transudative processes (heart failure, cirrhosis, renal failure) or exudative processes (infection, malignancy, autoimmune disorders), with heart failure being the single most common cause overall, accounting for 29% of all pleural effusions and over 80% of transudates. 1, 2
Transudative Causes
Heart failure dominates the transudative category, representing more than 80% of all transudates and 29% of all pleural effusions regardless of type 1. The mechanism involves increased pulmonary capillary pressure causing transudation of pulmonary interstitial fluid across the visceral pleura that overwhelms lymphatic drainage capacity 2, 3.
Cirrhosis with ascites accounts for approximately 10% of transudates and 3% of all pleural effusions 1. The fluid moves directly from the peritoneal cavity into the pleural space through diaphragmatic pores 3.
End-stage renal failure causes pleural effusion in 24.7% of ESRF patients through fluid overload, concurrent heart failure, and uremic pleuritis 1.
Other transudative causes include hypoalbuminemia, nephrotic syndrome, and atelectasis 1.
Exudative Causes
Malignancy (26% of all effusions)
Lung cancer is the leading malignant cause, accounting for 25-52% of all malignant pleural effusions based on cytology reviews 4, 2. Hemoptysis with pleural effusion is highly suggestive of bronchogenic carcinoma 4.
Breast cancer ranks second, representing 3-27% of malignant effusions on cytology, with 36-65% of patients with disseminated breast cancer developing pleural effusions 4, 2.
Lymphoma accounts for approximately 12-22% of malignant pleural effusions 4, 2. The main mechanism in Hodgkin's disease is obstruction of lymphatic drainage by enlarged mediastinal lymph nodes, while non-Hodgkin's lymphoma causes direct tumor infiltration of the pleura 2.
Mesothelioma characteristically presents with massive effusion and dull, aching chest pain rather than pleuritic pain 4. Critical diagnostic clue: absence of contralateral mediastinal shift despite large effusion volume indicates mediastinal fixation by tumor, mainstem bronchus occlusion, or extensive pleural involvement 4.
Infection (16% of all effusions)
Pneumonia accounts for 16% of all pleural effusions 1. Approximately 40% of patients with pneumonia develop parapneumonic effusions 3. These require chest tube drainage if the fluid is purulent, Gram stain positive, glucose <40 mg/dL, or pH <7.00 3.
Tuberculosis represents 6% of all pleural effusions and is the most common infectious cause of lymphocytic exudative effusions 1, 5. A positive tuberculin skin test with an exudative lymphocytic effusion may justify empirical antituberculous therapy 1, 5.
Autoimmune Disorders
Systemic lupus erythematosus affects up to 50% of patients during their disease course, producing lymphocytic exudates 5. However, pleural fluid ANA testing is not helpful as it merely mirrors serum levels 1, 5.
Rheumatoid arthritis causes pleural effusion in 5% of patients 1.
Other Exudative Causes
Pulmonary embolism is an important cause that must be reconsidered in persistent undiagnosed effusions as it is amenable to specific treatment 1, 5.
Post-surgical effusions account for 4% of cases 1.
Pericardial diseases represent 4% of cases 1.
Special Population Considerations
In HIV patients, the leading causes are Kaposi's sarcoma, parapneumonic effusions, and tuberculosis 1.
Drug-induced effusions are increasingly recognized, with tyrosine kinase inhibitors now being the most common drugs causing exudative pleural effusions 5. Other culprits include methotrexate, procarbazine, cyclophosphamide, and bleomycin 2.
Critical Diagnostic Pitfalls
Misclassification occurs in 25-30% of cases when cardiac and liver transudates are incorrectly labeled as exudates using Light's criteria 1, 5. 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 1.
NT-BNP levels >1500 μg/mL in serum or pleural fluid can accurately diagnose heart failure as the cause 1.
Always obtain detailed occupational history including asbestos exposure, as pleural plaques on CT should raise suspicion for mesothelioma 4, 5.
Do not assume bilateral effusions exclude malignancy—malignant effusions can be bilateral 4.