How should I evaluate and manage a patient with eosinophilia?

Evaluation and Management of Eosinophilia

Begin by calculating the absolute eosinophil count (AEC) and immediately assess for end-organ damage, as any patient with eosinophilia presenting with cardiac symptoms (chest pain, dyspnea, heart failure), pulmonary symptoms (persistent cough, wheezing, infiltrates), or neurological symptoms (altered mental status, focal deficits, neuropathy) requires urgent medical evaluation and consideration of emergency treatment. 1, 2

Immediate Assessment for Life-Threatening Complications

• Check for signs of end-organ damage first, as persistent eosinophilia can cause irreversible damage to the heart, lungs, and central nervous system even before symptoms develop 1, 2
• Obtain ECG, cardiac troponin, and NT-proBNP in all patients with hypereosinophilia (≥1.5 × 10⁹/L) to screen for myocardial injury 2
• Perform echocardiography if troponin is elevated or cardiac symptoms are present 2
• Order chest X-ray if any respiratory symptoms exist 2
• Critical warning: If eosinophilia ≥1.5 × 10⁹/L persists for >3 months, or if AEC exceeds 5.0 × 10⁹/L at any time, the risk of morbidity and mortality is significantly elevated 2

Systematic Diagnostic Approach Based on AEC Level

Mild Eosinophilia (0.5-1.5 × 10⁹/L)

In non-travelers, allergic disorders and medications account for 80% of cases 1, 2, 3:

• Review all medications, particularly NSAIDs, beta-lactam antibiotics, nitrofurantoin, olmesartan, mycophenolate, and azathioprine 2, 3, 4
• Assess for atopic conditions: 50-80% of adults with mild eosinophilia have concurrent asthma, allergic rhinitis, atopic dermatitis, or eczema 2
• Consider aeroallergen sensitivity testing (skin-prick or specific IgE) to identify trigger allergens 2
• Important caveat: Seasonal pollen exposure can transiently increase eosinophil counts, so timing of testing matters 2

In returning travelers or migrants, helminth infections account for 19-80% of cases 1, 2, 3:

• Obtain detailed travel history: geographic regions visited, freshwater exposure in Africa/tropical areas, consumption of raw or undercooked meat, and timing relative to eosinophilia onset 1, 3
• Order three separate concentrated stool specimens for ova and parasites 1, 3
• Send Strongyloides serology and culture immediately 1, 3
• Add Schistosomiasis serology if freshwater exposure in endemic areas 1, 3
• Critical warning: Strongyloides can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients, so this must be excluded even in asymptomatic patients 1, 2, 3

Moderate to Severe Eosinophilia (≥1.5 × 10⁹/L)

This level rarely results from allergy alone and always requires comprehensive workup 5, 6:

• First, exclude helminth infections as described above, since tissue-invasive parasites during migration phase are the most common identifiable cause in travelers 3
• If travel history is positive and parasitic workup is pending, consider empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg as single doses (covers most tissue-invasive helminths) 1, 3, 4
• Critical warning for Loa loa: Do NOT use diethylcarbamazine if microfilariae are seen on blood film, as it may cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilarial load to <1000/mL before definitive treatment 2, 3

If infectious causes are excluded or treated and eosinophilia persists >3 months, refer to hematology for evaluation of primary eosinophilic disorders 1, 2, 4:

• Obtain peripheral blood smear, bone marrow biopsy, standard cytogenetics, FISH, and molecular testing for tyrosine kinase gene fusions (PDGFRA, PDGFRB, FGFR1) 7
• Flow immunophenotyping to detect aberrant T-cell clones (lymphocyte-variant hypereosinophilia) 7
• Key point: Identification of PDGFRA or PDGFRB rearrangements is critical because these respond exquisitely to imatinib 7

Organ-Specific Evaluation When Symptoms Present

Gastrointestinal Symptoms (Dysphagia, Food Impaction, Abdominal Pain)

Perform upper endoscopy with multiple biopsies (minimum 6: 2-3 from proximal and 2-3 from distal esophagus) to evaluate for eosinophilic esophagitis 1, 2:

• Diagnosis requires ≥15 eosinophils per 0.3 mm² (high-power field) on esophageal biopsy 1, 2
• Important caveat: Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so normal blood counts do NOT exclude the diagnosis 1, 2
• First-line treatment is topical swallowed corticosteroids (fluticasone or budesonide), which decrease blood eosinophil counts in 88% of patients 1, 2
• Maintenance therapy is mandatory after achieving remission, as relapse rates are high after steroid withdrawal 1
• Endoscopic dilation is safe for fibrostenotic disease but must be combined with anti-inflammatory therapy 1

Pulmonary Symptoms (Cough, Wheezing, Infiltrates)

• Obtain pulmonary function tests in all patients with respiratory symptoms 2
• Chest X-ray to identify infiltrates: migratory infiltrates suggest Loeffler's syndrome (Ascaris, hookworm), while interstitial/reticulonodular patterns suggest tropical pulmonary eosinophilia 3
• For tropical pulmonary eosinophilia (typically AEC >3 × 10⁹/L): Initiate diethylcarbamazine promptly to prevent irreversible pulmonary fibrosis, but first exclude Loa loa co-infection 3
• Add adjunctive corticosteroids (prednisolone 20 mg/day for 5 days) for ongoing alveolitis 3
• Important: 20% of tropical pulmonary eosinophilia patients relapse and require re-treatment 3

Acute Presentations in Travelers

Schistosomiasis (acute Katayama syndrome) presents 2-8 weeks post-freshwater exposure with fever, urticaria, hepatosplenomegaly, and marked eosinophilia 3:

• Treat with praziquantel 40 mg/kg single dose, repeated at 6-8 weeks 3
• Add prednisolone 20 mg/day for 5 days in acute Katayama syndrome 3
• Long-term risk: Schistosoma haematobium is associated with squamous cell bladder carcinoma and spinal cord compression 1, 2

Hookworm causes marked eosinophilia with "ground itch" at skin penetration, followed by Loeffler's syndrome during lung migration 3:

• Treat with albendazole 400 mg twice daily for 3 days 3

Management Algorithm for Asymptomatic Eosinophilia

If AEC <1.5 × 10⁹/L and No Organ Involvement

• Address secondary causes (optimize atopic disease control, discontinue offending medications) 2, 4
• Watch-and-wait approach with eosinophil monitoring every 3-6 months 2
• Reassess if counts rise or symptoms develop 2

If AEC ≥1.5 × 10⁹/L Without Organ Damage

• Complete infectious workup as above 1, 3
• If helminth infection suspected based on travel history, treat empirically with albendazole 400 mg plus ivermectin 200 μg/kg as single doses 1, 3, 4
• If eosinophilia persists >3 months after infectious causes excluded/treated, refer to hematology 1, 2, 4
• Consider idiopathic hypereosinophilic syndrome (diagnosis of exclusion) 1, 7

If AEC ≥5.0 × 10⁹/L at Any Time

• Urgent hematology referral regardless of symptoms 2
• Assess for end-organ damage with cardiac biomarkers, echocardiography, chest imaging, and neurologic examination 2

Common Pitfalls to Avoid

• Do NOT assume eosinophilia alone is adequate screening for helminth infection, as many infected patients have normal eosinophil counts 1, 2
• Do NOT rely solely on peripheral eosinophil counts to diagnose eosinophilic esophagitis; tissue biopsy is the gold standard 1, 2
• Do NOT wait for symptoms before investigating persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 1, 2
• Do NOT miss medication-induced enteropathy (especially olmesartan), which can mimic refractory celiac disease 4
• Do NOT use diethylcarbamazine if Loa loa microfilariae are present, as this can cause fatal encephalopathy 2, 3
• Do NOT forget that only tissue-invasive helminthic parasites cause eosinophilia, limiting its application as a general screening tool for all parasitic infections 2

Monitoring and Follow-Up

• Regular clinic visits to assess symptoms, compliance, and adverse effects 1, 2
• For treated eosinophilic esophagitis, repeat endoscopy with biopsies if symptoms recur during treatment 1, 2
• For asymptomatic patients with persistent esophageal eosinophilia, consider repeat endoscopy every 2-3 years to evaluate for progressive disease, weighing risks against unknown benefits 1
• Monitor for treatment-related complications (corticosteroid side effects, imatinib hepatotoxicity) 1, 2