What are the causes of pleural effusions?

Causes of Pleural Effusions

Pleural effusions are commonly caused by heart failure (29%), malignancy (26%), pneumonia (16%), tuberculosis (6%), post-surgery (4%), pericardial diseases (4%), and cirrhosis (3%). 1

Classification of Pleural Effusions

Pleural effusions are classified into two main categories:

Transudative Pleural Effusions

• Heart failure accounts for more than 80% of transudative pleural effusions 1, 2
• Liver cirrhosis (hepatic hydrothorax) accounts for approximately 10% of transudative effusions 1, 2
• Other causes include hypoalbuminemia, nephrotic syndrome, and atelectasis 3
• End-stage renal failure is associated with pleural effusions due to fluid overload 1
• Most transudates can be successfully treated with diuretics 3

Exudative Pleural Effusions

• Malignancy is a leading cause of exudative effusions 3
  • Lung cancer is the most common neoplasm (approximately one-third of all malignant effusions) 3
  • Breast cancer is the second most common cause 3
  • Lymphomas (both Hodgkin's and non-Hodgkin's) are also important causes 3
  • In 5-10% of malignant effusions, no primary tumor is identified 3
• Parapneumonic effusions (associated with pneumonia) 1, 4
• Tuberculosis (accounts for 6% of pleural effusions) 1, 2
• Pulmonary embolism 1, 4
• Rheumatoid arthritis (occurs in 5% of patients) 1
• Systemic lupus erythematosus (affects up to 50% of patients during disease course) 1

Pathophysiological Mechanisms

Malignant Pleural Effusions

• Most pleural metastases arise from tumor emboli to the visceral pleural surface 3
• Other mechanisms include:
  • Direct tumor invasion (lung cancers, chest wall neoplasms, breast carcinoma) 3
  • Hematogenous spread to parietal pleura 3
  • Lymphatic involvement 3
  • Interference with lymphatic drainage 3
  • Local inflammatory changes causing increased capillary permeability 3

Paramalignant Effusions

• Not direct results of neoplastic involvement but related to primary tumor 3
• Examples include:
  • Postobstructive pneumonia with parapneumonic effusion 3
  • Obstruction of thoracic duct (chylothorax) 3
  • Pulmonary embolism 3
  • Transudative effusions due to atelectasis or low plasma oncotic pressure 3
  • Treatment-related (radiation therapy, drugs like methotrexate, procarbazine) 3

Diagnostic Approach

• Light's criteria are effective at identifying exudates (high sensitivity 98%) but have moderate specificity (70%), leading to misclassification of transudates as exudates in about 25% of cases 3, 1
• When heart failure is suspected but Light's criteria suggest an exudate, a serum-effusion albumin gradient >1.2 g/dL can reclassify the effusion as a transudate 3, 2
• N-terminal pro-brain natriuretic peptide (NT-BNP) levels >1500 μg/mL in serum or pleural fluid accurately diagnose heart failure as the cause 3, 2
• For suspected hepatic hydrothorax with ambiguous Light's criteria, a pleural fluid to serum albumin ratio <0.6 confirms the diagnosis 3

Special Considerations

• In HIV patients, the leading causes of pleural effusion are Kaposi's sarcoma, parapneumonic effusions, and tuberculosis 1
• Reconsider pulmonary embolism and tuberculosis in cases of persistent undiagnosed effusions as they are amenable to specific treatment 1, 2
• Thoracoscopy may be necessary if malignancy is suspected after routine tests have failed 1
• Diagnostic bronchoscopy is not indicated unless the patient has hemoptysis or features of bronchial obstruction 1

Clinical Manifestations

• Dyspnea is the most common presenting symptom in patients with malignant effusions, occurring in more than half of cases 3
• Patients with advanced malignancy may also present with generalized symptoms such as weight loss, anorexia, and malaise 3
• The pathogenesis of dyspnea from large pleural effusions involves decreased chest wall compliance, mediastinal shifting, decreased ipsilateral lung volume, and reflex stimulation from the lungs and chest wall 3