What is the appropriate management for an elevated eosinophil (white blood cell) differential?

Management of Elevated Eosinophil Differential

For any patient with eosinophilia, immediately assess for end-organ damage (cardiac, pulmonary, neurological symptoms) and determine the absolute eosinophil count (AEC) to guide urgency of workup and treatment. 1, 2

Immediate Red Flags Requiring Emergency Evaluation

• Cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias) demand urgent assessment with ECG, echocardiogram, and troponin, as endomyocardial involvement can be fatal 1, 3
• Neurological deficits (altered mental status, focal weakness, peripheral neuropathy) require immediate imaging and treatment 1, 3
• Pulmonary involvement (persistent cough, wheezing, infiltrates on imaging) necessitates urgent evaluation 1
• Any AEC ≥5.0 × 10⁹/L requires immediate evaluation regardless of duration 1, 2

Severity Classification and Initial Approach

Mild Eosinophilia (0.5-1.5 × 10⁹/L)

• Most commonly caused by allergic disorders or medications in non-endemic areas 1, 2
• In returning travelers or migrants, helminth infections account for 19-80% of cases 1, 2
• Obtain detailed travel history focusing on fresh water exposure in Africa/tropical regions, raw/undercooked meat consumption, and timing of travel relative to eosinophilia onset 4, 3
• Review all medications started within the past 6 months, as drug reactions are a common cause 2

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

• Requires hematology referral if persisting >3 months after infectious causes are excluded or treated 1, 2
• Carries significant risk of morbidity and mortality, particularly with end-organ damage 1

Essential Diagnostic Workup

First-Line Testing

• Stool microscopy for ova and parasites (3 separate concentrated specimens) 4, 2
• Serology for Strongyloides and other parasites based on travel history (schistosomiasis if fresh water exposure in endemic areas) 4, 2, 3
• Complete blood count with differential to calculate AEC and assess eosinophil morphology 2, 5
• Serum tryptase and vitamin B12 levels to screen for myeloproliferative variants (elevated in PDGFRA-associated neoplasms) 2
• Total IgE level (elevated in allergic conditions and lymphocytic variant hypereosinophilic syndrome) 2

Cardiac Evaluation for AEC ≥1.5 × 10⁹/L

• ECG, echocardiogram, and troponin are necessary to detect subclinical endomyocardial involvement 3

Gastrointestinal Symptoms

• Dysphagia or food impaction warrants endoscopy with multiple biopsies to evaluate for eosinophilic esophagitis 1
• Note that peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis is essential 1

Treatment Algorithm

Empiric Treatment for Returning Travelers

Albendazole 400 mg single dose PLUS ivermectin 200 μg/kg single dose is reasonable for returning travelers with asymptomatic eosinophilia while awaiting test results 2, 3

Confirmed Parasitic Infections

• Strongyloidiasis: Ivermectin 200 μg/kg daily for 1-2 days 3
• Schistosomiasis (Katayama syndrome): Praziquantel 40 mg/kg single dose, repeated at 6-8 weeks, PLUS prednisone 20 mg daily for 5 days 3
• Critical warning for Loa loa: Do NOT use diethylcarbamazine (DEC) if microfilariae are seen in blood, as it may cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilaria load to <1000/ml before definitive treatment 4

Eosinophilic Esophagitis

• Proton pump inhibitor therapy twice daily for 8-12 weeks is first-line treatment 2

Persistent Idiopathic Eosinophilia

• If no secondary cause identified after thorough workup, repeat CBC with differential in 4 weeks to determine persistence 2
• Corticosteroids are first-line therapy for idiopathic hypereosinophilic syndrome (diagnosis of exclusion) 2, 5
• If PDGFRA or PDGFRB rearrangement identified, imatinib is the treatment of choice with excellent response rates 2, 5

Hematology Referral Indications

Immediate referral required if:

• Eosinophilia persists >1500 cells/μL for more than 3 months despite treatment 1, 2
• Signs of end-organ damage present (cardiac, pulmonary, neurologic, or skin involvement) 2
• AEC >5.0 × 10⁹/L at any time 1

Hematology workup includes:

• Bone marrow biopsy with cytogenetics and FISH for PDGFRA, PDGFRB, FGFR1 rearrangements 2, 5
• Flow cytometry to evaluate for aberrant T-cell populations 2, 5
• Molecular testing for clonal hematopoiesis 2

Critical Pitfalls to Avoid

• Do not assume normal eosinophil count excludes helminth infection, as many infected patients have normal counts 1, 3
• Do not delay cardiac evaluation in patients with moderate-to-severe eosinophilia, as endomyocardial damage can be subclinical initially 1, 3
• Do not miss Strongyloides in immunocompromised patients, as it can persist lifelong and cause fatal hyperinfection syndrome 1, 3
• Do not rely solely on peripheral eosinophil counts to assess tissue eosinophilia in conditions like eosinophilic esophagitis 1
• Do not attribute all eosinophilia to allergies without excluding parasitic and hematologic causes 3
• Hypereosinophilia (≥1.5 × 10⁹/L) is rarely explained by allergy alone and should always prompt further workup 6

Special Populations

Immunocompromised Patients

• Require urgent evaluation for Strongyloides due to high mortality risk of hyperinfection syndrome 1, 3
• Strongyloides can persist lifelong and reactivate with immunosuppression 1

Chronic Schistosomiasis

• Can cause spinal cord compression presenting as back pain with neurological symptoms 3
• Can result in portal hypertension with esophageal varices and hepatosplenic disease 4
• Schistosoma haematobium is associated with squamous cell bladder carcinoma 1