Version July 2025
| Clinical history and examination |
| Does the patient have a past medical history of a disorder known to be associated with PFE (eg, malignancy, parapneumonic effusion, eosinophilic pneumonia, rheumatoid arthritis, EGPA, IgG4-related disease)? |
| Does the patient have risk factors for cancer (eg, hemoptysis, weight loss, fatigue, night sweats, smoking, change in bowel habit, breast lumps, recent mammography, skin abnormalities)? |
| Does the patient have a history or signs of infection (eg, fever, sweats, or chills; recent upper or lower respiratory tract symptoms) or travel to or reside in endemic areas of fungi? |
| What is the patient's list of medications including dietary supplements, herbal preparations, and vitamins? How long have they been on these medications? |
| Is there a history of asbestos exposure? |
| Is there evidence on examination of rheumatoid arthritis or skin lesions to suggest fungal or parasitic infection? Are there gastrointestinal symptoms suggestive of parasitic infection? |
| Is the effusion unilateral or bilateral (the latter might suggest a systemic etiology)? |
| Laboratory |
| Perform complete blood count with differential, serum chemistries including liver function tests, and stool for ova and parasites. |
| Perform microbe-specific serology when fungal and parasitic infections are suspected. |
| Perform disorder-specific serology when collagen vascular/inflammatory disorder is suspected (eg, rheumatoid arthritis, EGPA, or IgG4-related disease). |
| Pleural fluid analysis* |
| Perform pleural fluid cytology (malignant cells and microbe staining). |
| Perform Gram stain, bacterial, fungal, and mycobacterial culture. |
| Perform additional studies, as needed, to target suspected etiologies (eg, antibodies for fungus, parasites, or collagen vascular disorders; refer to related UpToDate content). |
| Imaging |
| Chest CT may identify pleuroparenchymal pathology that explains the PFE finding. |
| Pleural biopsy¶ |
| Useful when etiology is unknown and a diagnosis that can be made on histopathology or immunohistopathology is suspected or needs exclusion (eg, cancer, tuberculosis or other infection, autoimmune/collagen vascular disease). |
CT: computed tomography; EGPA: eosinophilic granulomatosis with polyangiitis; Ig: immunoglobulin; PFA: pleural fluid analysis; PFE: pleural fluid eosinophilia.
* Routine PFA has usually been performed (eg, cell count, lactate dehydrogenase, glucose, total protein, glucose, cholesterol). Additional testing is targeted at the suspected etiology of the pleural effusion. Further details on this analysis are found in related UpToDate content.
¶ In most cases, a preliminary or clinical diagnosis can be made without additional studies.