What are the other causes of eosinophilic effusion in a patient, aside from Eosinophilic Granulomatosis with Polyangiitis (EGPA)?

Causes of Eosinophilic Effusion Beyond EGPA

Eosinophilic pleural effusions (≥10% eosinophils) can result from nearly any condition causing pleural disease, with the most common causes being blood or air in the pleural space, infections, and malignancy. 1

Primary Causes to Consider

Blood or Air in Pleural Space

• Hemothorax and pneumothorax are among the most frequent causes of eosinophilic pleural effusion, as the presence of blood or air in the pleural space triggers eosinophilic recruitment 1

Malignancy

• Cancer represents one of the commonest causes of eosinophilic pleural effusion and should be high on the differential diagnosis 1, 2
• Thorough evaluation for underlying malignancy is essential when eosinophilic effusion is identified 1

Infections

• Various infectious etiologies can produce eosinophilic pleural effusions, requiring consideration of bacterial, fungal, and parasitic causes 1
• Parasitic infections specifically should be excluded in the appropriate clinical context 3

Drug-Induced Pleural Disease

• Medication-related pleural effusions are a common cause of eosinophilic effusions and require careful medication history review 1
• Drug hypersensitivity should be ruled out when evaluating esophageal or systemic eosinophilia 3

Pulmonary Embolism

• Pleural effusions accompanying pulmonary embolism frequently demonstrate eosinophilic predominance 1

Asbestos Exposure

• Benign asbestos pleural effusions are among the common causes of eosinophilic pleural effusion 1

Systemic Eosinophilic Disorders

Hypereosinophilic Syndrome (HES)

• HES is characterized by peripheral blood eosinophilia (AEC >1500 cells/μL) with organ/tissue damage from eosinophilic infiltration, and up to 38% of HES patients have gastrointestinal symptoms 3
• HES can present with eosinophilic pleural effusion, though this is a rare manifestation 2
• The key distinguishing feature is marked peripheral eosinophilia (>1500 cells/μL), which is rare in isolated eosinophilic esophagitis 3
• Patients with HES and pleural effusions may continue to accumulate eosinophilic pleural fluid even after peripheral eosinophil counts normalize with treatment, indicating that peripheral counts alone may not adequately guide therapy 2
• When HES is suspected, screening for multi-organ involvement (skin, lung, heart, neurologic) is essential 3

Other Eosinophilic Gastrointestinal Diseases

• Eosinophilic gastritis and eosinophilic enteritis may be associated with peripheral eosinophilia and can have concurrent esophageal involvement 3
• Crohn's disease should be excluded as a cause of esophageal eosinophilia, particularly in patients with active intestinal disease 3

Autoimmune and Connective Tissue Disorders

Systemic Sclerosis and Mixed Connective Tissue Disease

• Esophageal involvement in systemic sclerosis and MCTD results from atrophy and fibrosis of esophageal smooth muscle, causing severe hypomotility 3
• These conditions affect esophageal function but are not typically associated with pleural eosinophilia 3

Other Autoimmune Conditions

• Systemic lupus erythematosus, Sjogren's disease, and myositis can cause esophageal dysfunction 3
• Vasculitis, pemphigoid, and graft-versus-host disease should be excluded as causes of esophageal eosinophilia 3

Idiopathic Eosinophilic Effusion

• No etiology is identified in approximately one-third of patients with eosinophilic pleural effusion, representing a significant proportion of cases 1
• When no cause is found after thorough evaluation, the diagnosis of idiopathic eosinophilic effusion is made by exclusion 1

Diagnostic Approach

The diagnostic workup should be tailored to clinical characteristics since studies evaluating different diagnostic approaches are lacking 1:

• Obtain detailed medication history to identify drug-induced causes 1
• Assess for recent trauma, procedures, or pneumothorax that could introduce blood or air 1
• Evaluate for malignancy with appropriate imaging and cytology 1, 2
• Check peripheral eosinophil count: AEC >1500 cells/μL suggests HES rather than isolated organ eosinophilia 3
• Screen for parasitic infections, particularly toxocariasis, and perform serologic testing as indicated 3
• Consider pulmonary embolism evaluation if clinically appropriate 1
• Assess occupational/environmental exposure history for asbestos 1

Critical Pitfall

The most important pitfall is assuming peripheral eosinophil counts alone guide adequacy of treatment in HES with pleural involvement—pleural fluid eosinophilia may persist despite normalized peripheral counts, requiring clinical reassessment rather than relying solely on laboratory values 2.