eosinophilia in pleural effusion suggests BAPE, air, PE, or cancer

Both air and blood have been reported to cause EPE, and because both frequently coexist, it is difficult to determine which is primarily responsible. Spontaneous pneumothorax has been reported to be associated with EPE. Air in the pleural space can stimulate eosinophilic pleural inflammation relatively quickly, perhaps related to the cytokine interleukin-5 (IL-5). Blood in the pleural space following trauma, chest surgery, and pulmonary infarction can also be associated with EPE. In particular, bloody pleural effusions that develop within the first 30 days in patients who undergo coronary artery bypass graft (CABG) surgery often have a high percentage of eosinophils (especially when a pleurotomy is performed), possibly as a result of IL-5 and vascular cell adhesion molecule-1. In general, however, pleural blood often does not have an elevated eosinophil count, with one institution reporting a 20% incidence in patients who had a pleural fluid red blood cell count ≥100,000/mm3.

Asbestos exposure is associated with benign asbestos pleural effusions (BAPE), where 25 to 50% of cases are associated with pleural fluid eosinophilia. The latency period between initial exposure and the onset of BAPE ranges from 15 to 48 years (choice A is incorrect).

Malignancy is one of the more common conditions associated with EPE (though few malignant effusions have eosinophilia). One study reported up to 40% of patients with EPE were due to malignancy, most commonly solid tumors, with lung cancer being the most common. Interestingly, there may be an inverse relationship between the percentage of eosinophils in pleural fluid and the proportion of patients with a malignant effusion. While this patient is at increased risk for lung cancer based on his smoking and suspected exposure to asbestos, this usually occurs 20 years after exposure (choice C is incorrect).

Several drugs can cause EPE, including warfarin, propylthiouracil, and nitrofurantoin. Morphine, however, has not been reported to cause EPE (choice D is incorrect). Further, onset of drug-induced EPE is usually months after initiation of the drug, though can vary widely. Peripheral blood eosinophilia is sometimes seen. Diagnosis is made after excluding all known causes. Treatment involves discontinuing the drug and occasionally corticosteroids.

Other causes of EPE include infections due to bacteria, fungi, mycobacteria, parasites and viruses, pulmonary embolism, and collagen vascular diseases. Many however are idiopathic.1

Presumably, the development of pleural fluid eosinophilia requires production of a cytokine milieu that favors the recruitment of circulating eosinophils to the pleural space and prolongation of their life span through inhibition of eosinophil apoptosis. It is believed that nonspecific injury or irritation of pleural mesothelial cells (as occurs with trauma or introduction of air or blood into the pleura) increases the production of cytokines, chemokines, and adhesion molecules that result in the observed pleural fluid eosinophilia. Important mediators in this process include eotaxin-1 (CCL11); eotaxin-2 (CCL24); eotaxin-3 (CCL26); IL-3; IL-5; granulocyte-macrophage colony-stimulating factor; and regulated on activation, normal T cell expressed and secreted.

The most common causes of pleural fluid eosinophilia include trauma or surgery to the pleura (including thoracoscopy and thoracentesis) and/or pneumothorax or hemothorax. Other processes in the differential diagnosis of eosinophilic pleural effusion include drug reactions (eg, warfarin, sulfasalazine, antipsychotics, valproic acid, nitrofurantoin, fluoxetine, dantrolene); inflammatory conditions (eg, acute or chronic eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis, rheumatoid arthritis); infections (eg, mycobacteria, Histoplasma capsulatum, Paragonimus, Strongyloides); benign asbestos pleural effusions; and, more rarely, malignancy. Some cases are idiopathic, and these are generally self-limited.

While Hodgkin lymphoma has rarely been associated with pleural eosinophilia, the presence of pneumothorax in this patient and the absence of features suggestive of Hodgkin lymphoma makes this a much less likely explanation (choice A is incorrect). Exposure to high concentrations of inhaled oxygen has been associated with consequences such as absorption atelectasis; exacerbation of preexisting hypercapnia; injury of airways and lung parenchyma; and extrapulmonary toxicity to the heart, brain, and retina. However, it has not been linked to pleural fluid eosinophilia (choice B is incorrect). Pneumocystis infection, which can develop in patients with significant impairment of cell-mediated immunity, typically does not cause pleural effusions of any type (choice D is incorrect).1

Footnotes

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