What is the best approach to diagnose and treat a patient with eosinophilia (elevated eosinophil count) without a history of travel?

Approach to Eosinophilia Without Travel History

In patients with eosinophilia without travel history, prioritize identifying non-infectious causes—particularly medications (especially olmesartan, mycophenolate, azathioprine), allergic/atopic conditions (asthma, eczema, hay fever), and assess urgently for end-organ damage affecting the heart, lungs, or central nervous system. 1, 2

Immediate Assessment for Life-Threatening Complications

Any patient with eosinophilia presenting with cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias), pulmonary symptoms (persistent cough, wheezing, infiltrates), or neurological symptoms (altered mental status, focal deficits, peripheral neuropathy) requires urgent medical evaluation and consideration of emergency treatment. 1, 3

• Obtain electrocardiogram, cardiac troponin, and NT-proBNP in all patients with eosinophilia ≥1.5 × 10⁹/L to screen for myocardial injury 3
• Perform echocardiography if troponin is elevated or cardiac symptoms are present 3
• Order chest radiograph to identify pulmonary infiltrates 3
• Eosinophilia can cause significant end-organ damage to the heart, lungs, and central nervous system, particularly at levels ≥1.5 × 10⁹/L 1, 3

Comprehensive Medication and Allergy History

Obtain a detailed medication history as the first diagnostic step, as drugs are among the most common causes of eosinophilia in non-travelers. 1, 2

• Olmesartan and other angiotensin II receptor antagonists cause seronegative enteropathy with eosinophilia that mimics refractory celiac disease 2
• Mycophenolate mofetil and azathioprine cause enteropathy that resolves with drug discontinuation 2
• If medication-induced enteropathy is suspected, discontinue the offending medication as enteropathy typically resolves with cessation 2
• Assess for allergic and atopic conditions (asthma, eczema, hay fever), which represent approximately 80% of eosinophilia cases in non-exposed populations 4

Diagnostic Algorithm Based on Clinical Presentation

For Asymptomatic Eosinophilia:

First-line investigations include concentrated stool microscopy (three separate specimens) and Strongyloides serology, even without travel history, as parasitic infections can occur through contaminated food or contact with infected individuals. 1, 4

• Perform HIV testing where recommended by guidelines, as HIV infection has been associated with eosinophilia 1
• Check complete blood count with differential to quantify absolute eosinophil count 4
• Eosinophilia is defined as peripheral blood eosinophil count >0.5 × 10⁹/L 4, 3

For Gastrointestinal Symptoms (Dysphagia, Food Impaction, Abdominal Pain, Diarrhea):

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

• Eosinophilic esophagitis is diagnosed when >15 eosinophils per high-power field are present on esophageal biopsy 3
• Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis remains essential 4, 3
• Refer to gastroenterology if gastrointestinal symptoms are present with eosinophilia 2

For Respiratory Symptoms (Cough, Wheezing, Dyspnea):

• Perform pulmonary function tests in all patients with respiratory symptoms 3
• Obtain chest radiograph to document pulmonary infiltrates 3
• Consider bronchoscopy with bronchoalveolar lavage if imaging suggests parenchymal disease 3

Treatment Based on Etiology

Eosinophilic Esophagitis:

First-line treatment is topical swallowed corticosteroids (fluticasone or budesonide), which decrease blood eosinophil counts in 88% of patients. 3

• Maintenance therapy is mandatory after achieving remission, as clinical relapse rates are high after topical steroid withdrawal 3
• Histological remission is defined as <15 eosinophils per 0.3 mm² 3

Medication-Induced Eosinophilia:

Discontinue the offending medication immediately, as enteropathy typically resolves with cessation. 2

Allergic/Atopic Conditions:

• Nasal corticosteroids can reduce eosinophilia in both nasal tissue and peripheral blood for allergic rhinitis 4
• Montelukast is NOT recommended for managing eosinophilia, as it has no proven efficacy for reducing eosinophil counts (OR 0.48,95% CI 0.10-2.16, p=0.33) 4
• Anti-IgE therapy (omalizumab) is not recommended for eosinophilia management, as it showed no effect on eosinophil counts in controlled trials 4

Referral Criteria

If eosinophilia ≥1.5 × 10⁹/L persists for more than 3 months without evidence of end-organ damage, refer to hematology for further investigations after infectious causes have been excluded or treated. 1, 2, 3

• This evaluation is necessary to exclude idiopathic hypereosinophilia or idiopathic hypereosinophilic syndrome (if end-organ damage is present) 1
• Hematology workup includes bone marrow histology, cytogenetics, molecular markers for PDGFRA/PDGFRB rearrangements, and flow immunophenotyping 5, 6

Critical Pitfalls to Avoid

• Do not fail to obtain a comprehensive medication history, particularly for olmesartan, which can mimic refractory celiac disease 2
• Do not rely solely on peripheral eosinophil counts to assess tissue eosinophilia in conditions like eosinophilic esophagitis, as tissue biopsy is the gold standard 3
• Do not wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 3
• Do not assume eosinophilia alone is adequate screening for helminth infection, as many infected patients have normal eosinophil counts 3