Causes of Eosinophilic Pleural Effusion
The most common causes of eosinophilic pleural effusion include pneumothorax, hemothorax, malignancy, infections (particularly tuberculosis and parasitic infections), pulmonary embolism, drug reactions, and asbestos exposure, with approximately one-third of cases remaining idiopathic despite thorough investigation.
Definition and Prevalence
Eosinophilic pleural effusion (EPE) is defined as a pleural effusion containing at least 10% eosinophils in the pleural fluid 1. These effusions represent approximately 5-16% of all exudative pleural effusions 2.
Major Causes
1. Air or Blood in the Pleural Space
- Pneumothorax: Introduction of air into the pleural space is a potent stimulus for eosinophil recruitment
- Hemothorax: Blood in the pleural space can trigger eosinophilic inflammation
- Post-thoracentesis: Previous pleural procedures can cause EPE
2. Malignancy
- Lung cancer: Most common neoplastic cause of EPE 3
- Breast cancer: Second most common malignancy associated with EPE
- Lymphomas: Both Hodgkin's and non-Hodgkin's lymphoma
- Mesothelioma: Incidence varies by geographic location
3. Infections
- Tuberculosis: A significant cause worldwide
- Parasitic infections:
4. Drug-Induced
- Cardiovascular drugs: Including angiotensin-converting enzyme inhibitors like lisinopril 4
- Neuropsychiatric medications
- Other medications: Methotrexate, procarbazine, cyclophosphamide, and bleomycin 3
5. Other Causes
- Pulmonary embolism: Can present with EPE
- Benign asbestos pleural effusion: Important occupational cause
- Hypereosinophilic syndrome: Rare but reported cause 5
- Autoimmune diseases: Including rheumatoid arthritis and lupus
- Post-radiation therapy: Following treatment for malignancy 3
- Idiopathic: No identifiable cause in 14-25% of cases 6
Pathophysiology
The pathogenesis of EPE involves multiple mechanisms:
- IL-5 production: A key cytokine driving eosinophil recruitment and activation in the pleural space 2
- Chemokines and adhesion molecules: Facilitate eosinophil migration
- Local inflammatory response: Increased capillary permeability in response to various stimuli
- Lymphatic obstruction: Particularly in malignancy-associated EPE 3
Diagnostic Approach
When evaluating a patient with EPE, consider the following diagnostic algorithm:
Thorough history:
- Medication use (focus on cardiovascular and neuropsychiatric drugs)
- Travel history (for parasitic infections)
- Asbestos exposure
- Previous thoracentesis or chest procedures
- History of malignancy
Pleural fluid analysis:
- Confirm eosinophil percentage ≥10%
- Apply Light's criteria to determine if exudate or transudate
- Cytology for malignant cells
- Cultures for bacteria, mycobacteria, and fungi
- Consider specialized tests for parasites in appropriate settings
Blood tests:
- Complete blood count with peripheral eosinophil count
- Inflammatory markers (ESR, CRP)
- Serological tests for parasites when indicated
Imaging:
- Chest radiography and CT scan
- Ultrasound can help characterize effusions and guide procedures
Consider pleural biopsy:
- When malignancy is suspected but cytology is negative
- For diagnosis of tuberculosis or other granulomatous diseases
Clinical Pearls and Pitfalls
- EPE is often associated with better prognosis in malignant effusions compared to non-eosinophilic effusions
- The presence of air or blood in the pleural space is a potent stimulus for eosinophil recruitment, so iatrogenic causes should always be considered
- Idiopathic EPE may respond to corticosteroid therapy 6
- In cases of drug-induced EPE, improvement typically occurs after discontinuation of the offending agent 4
- Always consider parasitic infections in patients with travel history to endemic areas, even with negative initial testing 3