What are the next steps for a patient with elevated eosinophils (eosinophilia)?

Management of Elevated Eosinophils

Begin with a systematic evaluation prioritizing the most common causes: parasitic infections (especially in travelers), drug reactions, and gastrointestinal eosinophilic disorders, before considering hematologic causes. 1

Immediate Assessment

Critical Red Flags Requiring Urgent Evaluation

• Any patient with eosinophilia presenting with chest pain, dyspnea, heart failure symptoms, or arrhythmias needs immediate cardiac evaluation for potential eosinophilic myocarditis 2
• Neurological symptoms (altered mental status, focal deficits, peripheral neuropathy) demand prompt assessment for eosinophil-mediated CNS or peripheral nerve damage 2
• Pulmonary symptoms (persistent cough, wheezing, infiltrates on imaging) require urgent evaluation for eosinophilic pneumonia 2
• Absolute eosinophil count >5.0 × 10⁹/L at any time carries significant risk and warrants immediate workup 2

Severity Stratification

• Mild eosinophilia (0.5-1.5 × 10⁹/L): Most commonly caused by allergic disorders or medications in non-endemic areas; helminth infections account for 19-80% in returning travelers 1, 2
• Moderate-to-severe eosinophilia (≥1.5 × 10⁹/L): Requires hematology referral if persisting >3 months after infectious causes excluded or if any end-organ damage present 1, 2

Essential History Elements

Travel and Exposure History

• Document travel to tropical/subtropical regions where helminth infections are endemic, particularly fresh water exposure in Africa (schistosomiasis risk) 1, 2
• Raw or undercooked meat consumption (trichinosis, toxocariasis) 1
• Timing of travel relative to eosinophilia onset 2

Medication Review

• Review all medications started within the past 6 months, as drug reactions are a common cause of eosinophilia 1

Symptom Assessment

• Dysphagia or food impaction: Strongly suggests eosinophilic esophagitis and warrants endoscopy 1, 2
• Abdominal pain, nausea, diarrhea: May indicate parasitic infection or gastrointestinal eosinophilic disorders 1
• Fever, weight loss, night sweats: Raise concern for malignancy or systemic vasculitis 2

Initial Diagnostic Testing

First-Line Laboratory Studies

• Stool microscopy for ova and parasites (3 separate concentrated specimens) to evaluate for helminth infections 1, 2
• Strongyloides serology (critical because this parasite can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients) 1, 2
• Schistosomiasis serology if fresh water exposure in endemic areas 1, 2
• Serum tryptase and vitamin B12 levels to screen for myeloproliferative variants (elevated in PDGFRA-associated neoplasms) 1
• Total IgE level (elevated in allergic conditions and lymphocytic variant hypereosinophilic syndrome) 1

Gastrointestinal Evaluation

• For patients with dysphagia or food impaction, perform upper endoscopy with multiple biopsies (minimum 6 biopsies: 2-3 from proximal and 2-3 from distal esophagus) 3, 2
• Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis remains essential 3, 2
• Eosinophilic esophagitis is diagnosed when >15 eosinophils per high-power field are present on esophageal biopsy 3

Treatment Approach

For Parasitic Infections

• Empiric treatment with albendazole 400 mg single dose PLUS ivermectin 200 μg/kg single dose is reasonable for returning travelers with asymptomatic eosinophilia while awaiting test results 1
• 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 2

For Eosinophilic Esophagitis

• First-line treatment is proton pump inhibitor therapy twice daily for 8-12 weeks 1
• Topical swallowed corticosteroids (fluticasone or budesonide) decrease blood eosinophil counts in 88% of patients 3, 2
• Maintenance therapy is mandatory after achieving remission, as clinical relapse rates are high after withdrawal 2

For Persistent Idiopathic Eosinophilia

• If no clear secondary cause is identified, repeat CBC with differential in 4 weeks to determine if eosinophilia persists 1
• Corticosteroids are first-line therapy for idiopathic hypereosinophilic syndrome (diagnosis of exclusion) 1
• If PDGFRA or PDGFRB rearrangement is identified, imatinib is the treatment of choice with excellent response rates 1, 4, 5

Hematology Referral Criteria

Immediate hematology referral is indicated if:

• Eosinophilia persists >1500 cells/μL for more than 3 months despite treatment 1
• Any signs of end-organ damage (cardiac, pulmonary, neurologic, or skin involvement) 1, 2

Hematology workup will include:

• Bone marrow biopsy with cytogenetics and FISH for PDGFRA, PDGFRB, FGFR1 rearrangements 1
• Flow cytometry to evaluate for aberrant T-cell populations 1
• Molecular testing for clonal hematopoiesis 1

Monitoring Strategy

For Treated Patients

• Repeat eosinophil counts after treatment to assess response 6
• For eosinophilic esophagitis, repeat endoscopy with biopsies if symptoms recur during treatment 2, 6
• Histological remission is defined as <15 eosinophils per 0.3 mm²; deep remission as <5 eosinophils per 0.3 mm² 2, 6

For Asymptomatic Patients with Persistent Eosinophilia

• Regular clinic visits to assess for development of symptoms or end-organ damage 3
• Consider repeat upper endoscopy and/or barium swallow every 2-3 years to evaluate for progressive disease, weighing risks against unknown benefits 3

Common Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection, as many infected patients have normal eosinophil counts 2
• 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 rely solely on peripheral eosinophil counts to assess tissue eosinophilia in conditions like eosinophilic esophagitis, as tissue biopsy is the gold standard 3, 2
• Do not use allergy testing to foods for choosing dietary restriction therapy for eosinophilic esophagitis 6