What is the recommended evaluation and management for a patient with eosinophilia?

Evaluation and Management of Eosinophilia

Initial Assessment and Risk Stratification

For any patient with eosinophilia, immediately assess for end-organ damage (cardiac, pulmonary, neurologic) and obtain a detailed travel/exposure history, as helminth infections account for 19-80% of cases in returning travelers and require empiric treatment, while hypereosinophilic syndrome with organ damage requires urgent corticosteroid therapy. 1, 2

Urgent Red Flags Requiring Immediate Evaluation

• Cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias) demand immediate ECG, troponin, NT-proBNP, and echocardiography, as eosinophil-mediated myocardial damage can progress to irreversible fibrosis 2
• Pulmonary involvement (persistent cough, wheezing, infiltrates on imaging) requires urgent chest X-ray and pulmonary function tests 2
• Neurologic symptoms (altered mental status, focal deficits, peripheral neuropathy) necessitate prompt EMG and consideration of nerve biopsy 2
• Absolute eosinophil count ≥5.0 × 10⁹/L at any time or ≥1.5 × 10⁹/L persisting >3 months carries significant morbidity/mortality risk 2

Severity Classification

• Mild eosinophilia (0.5-1.5 × 10⁹/L): Most commonly caused by allergic disorders (50-80% have concurrent atopic conditions) or medications in non-endemic areas; helminth infections in travelers 2, 3
• Moderate-to-severe eosinophilia (≥1.5 × 10⁹/L): Requires hematology referral if persisting >3 months after infectious causes excluded or treated 2, 3

Diagnostic Evaluation

Essential Travel and Exposure History

Obtain detailed geographic history including exact timing of freshwater swimming in Africa/tropical regions, barefoot walking, and raw/undercooked meat consumption, as this determines parasitic workup. 1, 4, 3

First-Line Diagnostic Tests

• Three separate concentrated stool specimens for ova and parasites 1, 4
• Strongyloides serology and culture (higher sensitivity than stool microscopy) 1, 4
• Schistosomiasis serology if freshwater exposure in endemic areas 1, 4
• CRITICAL: Check for Loa loa microfilariae on blood film in patients from Central/West Africa BEFORE administering ivermectin, as it can cause fatal encephalopathy 1, 2, 4

Additional Testing Based on Clinical Context

• For gastrointestinal symptoms (dysphagia, food impaction): Upper endoscopy with minimum 6 biopsies (2-3 from proximal, 2-3 from distal esophagus) to evaluate for eosinophilic esophagitis, as peripheral eosinophilia occurs in only 10-50% of adults with this condition 1, 2, 3
• For suspected primary eosinophilia: Bone marrow biopsy, cytogenetics, FISH for PDGFRA/PDGFRB/FGFR1 rearrangements, flow cytometry, T-cell clonality assessment 5, 6, 7
• Allergy testing (skin prick, specific IgE) for aeroallergen sensitivity in patients with atopic features 1, 2

Organ Damage Assessment

When eosinophilia is moderate-to-severe or symptomatic:

• Cardiac: ECG, troponin, NT-proBNP; if elevated, proceed to echocardiography and cardiac MRI 2
• Pulmonary: Chest X-ray, pulmonary function tests; if abnormal, consider bronchoscopy with bronchoalveolar lavage 2
• Neurologic: EMG for peripheral neuropathy; nerve biopsy if EMG abnormal 2
• Gastrointestinal: Endoscopy with mucosal biopsy and immunohistochemistry 2
• Dermatologic: Deep skin biopsy including fascia; MRI for suspected eosinophilic fasciitis 2

Treatment Approach

Helminth Infections (Most Common in Travelers)

For asymptomatic eosinophilia with travel history to endemic areas and negative stool microscopy, initiate empiric treatment with albendazole 400 mg single dose PLUS ivermectin 200 μg/kg single dose (for patients >24 months), but ONLY after excluding Loa loa. 1, 4, 3

• Repeat treatment at 8 weeks to treat residual worms that have matured, as eggs and immature schistosomulae are relatively resistant 1, 4
• Confirmed Strongyloidiasis: Ivermectin 200 μg/kg daily for 2 days 4, 3
• Schistosomiasis: Praziquantel 40 mg/kg single dose, repeated at 6-8 weeks; add prednisolone 20 mg/day for 5 days in acute Katayama syndrome 2
• Tropical pulmonary eosinophilia: Diethylcarbamazine (DEC) promptly to prevent irreversible pulmonary fibrosis, AFTER excluding Loa loa and Onchocerca volvulus; add prednisolone 20 mg/day for 5 days for ongoing alveolitis 2

Eosinophilic Esophagitis

First-line treatment is topical swallowed corticosteroids (fluticasone or budesonide), which decrease blood eosinophil counts in 88% of patients; maintenance therapy is mandatory after achieving remission due to high relapse rates. 1, 2, 4, 3

• Proton pump inhibitor therapy twice daily for 8-12 weeks is effective in inducing histological and clinical remission 1
• Histological remission defined as <15 eosinophils per 0.3 mm² 1, 2
• Endoscopic dilation is safe and effective for fibrostenotic disease but must be combined with anti-inflammatory therapy 2, 4
• Repeat endoscopy with biopsies while on treatment to assess response, as symptoms may not correlate with histological activity 1, 2

Primary Eosinophilia/Hypereosinophilic Syndrome

For patients with PDGFRA or PDGFRB rearrangements, imatinib is the treatment of choice due to exquisite responsiveness; for idiopathic hypereosinophilic syndrome or lymphocyte-variant hypereosinophilia, corticosteroids are first-line therapy. 4, 5, 6, 7

• Imatinib for myeloid/lymphoid neoplasms with PDGFRA/PDGFRB rearrangements 5, 6, 7
• Corticosteroids (prednisone) for symptomatic hypereosinophilic syndrome and lymphocyte-variant hypereosinophilia 8, 5, 6, 7
• Hydroxyurea or interferon-α for steroid-refractory cases 5, 6, 7
• Mepolizumab (anti-IL-5 antibody) approved for idiopathic hypereosinophilic syndrome 6

Watch-and-Wait Approach

For mild eosinophilia (<1.5 × 10⁹/L) without symptoms or signs of organ involvement, close follow-up without immediate treatment is appropriate. 5, 6, 7, 9

Common Pitfalls to Avoid

• Do not assume normal eosinophil counts exclude helminth infection, as many infected patients have normal counts 2
• Do not rely solely on peripheral eosinophil counts to diagnose eosinophilic esophagitis, as tissue biopsy is the gold standard 1, 2, 3
• Do not administer ivermectin or diethylcarbamazine without first excluding Loa loa in patients from endemic regions, as fatal encephalopathy can occur 1, 2, 4
• Do not wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 2
• Do not use allergy testing (skin prick, specific IgE, patch testing) to guide dietary restriction therapy for eosinophilic esophagitis 1

Follow-Up and Monitoring

• Repeat eosinophil counts after treatment to assess response 3
• For eosinophilic esophagitis: Repeat endoscopy with biopsies if symptoms recur during treatment 2, 3
• Monitor for treatment-related complications: Corticosteroid side effects (bone mineral density, adrenal suppression), imatinib hepatotoxicity 2, 3
• For hypereosinophilic syndrome: Regular clinic visits to assess for end-organ damage development 2