What is the appropriate management for an increase in eosinophil (white blood cell) count?

Management of Elevated Eosinophil Count

Initial Risk Stratification

The first priority is determining whether urgent intervention is needed based on eosinophil count severity and presence of end-organ damage. 1

Immediate Red Flags Requiring Emergency Evaluation

• Any patient with eosinophilia plus symptoms of end-organ damage requires urgent medical evaluation and consideration of emergency treatment. 1
• Cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias) demand immediate assessment due to risk of eosinophil-mediated myocardial damage 1
• Pulmonary involvement (persistent cough, wheezing, infiltrates on imaging) necessitates urgent evaluation 1
• Neurological symptoms (altered mental status, focal deficits, peripheral neuropathy) require prompt assessment 1
• Absolute eosinophil count ≥5.0 × 10⁹/L at any time carries significant morbidity/mortality risk regardless of symptoms 1

Severity Classification

• Mild eosinophilia (0.5-1.5 × 10⁹/L): Most commonly caused by allergic disorders or medications in non-endemic areas 1
• Moderate to severe eosinophilia (≥1.5 × 10⁹/L): Requires hematology referral if persisting >3 months after infectious causes excluded or treated 1
• Persistent eosinophilia ≥1.5 × 10⁹/L for >3 months: Carries significant risk of morbidity and mortality 1

Diagnostic Workup Algorithm

Step 1: Travel and Exposure History

Obtain detailed travel history focusing on fresh water exposure in Africa/tropical regions, raw/undercooked meat consumption, and timing relative to eosinophilia onset, as helminth infections account for 19-80% of cases in returning travelers. 1

• Helminth infections are the most common identifiable cause of mild eosinophilia in returning travelers or migrants (19-80% of cases) 1
• Strongyloides stercoralis can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 1
• Schistosoma haematobium is associated with squamous cell bladder carcinoma 1

Step 2: Parasitic Infection Evaluation

• Stool microscopy for ova and parasites (3 separate concentrated specimens) is first-line testing, particularly with travel history to endemic areas 1
• Serology for Strongyloides and other parasites based on travel history (schistosomiasis if fresh water exposure in endemic areas) 1
• Critical warning for Loa loa: Do not use diethylcarbamazine if microfilariae seen in blood, as it may cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilaria load to <1000/ml before definitive treatment 1

Step 3: Organ-Specific Symptom Assessment

For gastrointestinal symptoms (dysphagia, food impaction):

• Perform endoscopy with multiple biopsies (six biopsies from at least two different sites) to evaluate for eosinophilic esophagitis 2, 1
• Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis remains essential 1
• Histological remission defined as <15 eosinophils per 0.3 mm² in tissue biopsies 2

For respiratory symptoms:

• Assess for allergic conditions including allergic rhinitis, atopic dermatitis, and asthma 2
• Evaluate for aeroallergen sensitivity, given high rates (50-80%) of allergic diatheses in eosinophilic conditions 2

For fever, weight loss, or night sweats:

• These symptoms raise concern for malignancy or systemic vasculitis 1

Step 4: Hematologic Evaluation (if no secondary cause identified)

After excluding secondary causes, evaluation for primary eosinophilia includes:

• Morphologic review of blood and marrow 3, 4
• Standard cytogenetics and fluorescence in situ hybridization 3, 4
• Flow immunophenotyping 3, 4
• T-cell clonality assessment 3, 4
• Identification of rearranged PDGFRA or PDGFRB is critical because of exquisite responsiveness to imatinib 3, 4

Treatment Approach

For Parasitic Infections

• Albendazole 400 mg as a single dose for most helminth infections 2
• Ivermectin 200 μg/kg as a single dose for strongyloidiasis 2
• For returning travelers with asymptomatic eosinophilia, empiric treatment with albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose may be considered 2

For Eosinophilic Esophagitis

• Topical steroids decrease blood eosinophil counts in 88% of patients with eosinophilic esophagitis 2
• Support from an experienced dietitian is recommended for patients on elimination diets (two-food elimination diet for 8-12 weeks) 2
• Allergy testing to foods is not recommended for choosing dietary restriction therapy 2

For Primary Eosinophilia

• Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and idiopathic hypereosinophilic syndrome 3, 4
• Imatinib is the treatment of choice for patients with rearranged PDGFRA or PDGFRB 3, 4
• Hydroxyurea and interferon-alfa have demonstrated efficacy as initial treatment and in steroid-refractory cases 3, 4

For Mild Eosinophilia Without Symptoms

• For patients with eosinophilia <1.5 × 10⁹/L without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken 3, 4

Monitoring and Follow-Up

• Follow-up eosinophil counts should be obtained after treatment to assess response 2
• If symptoms recur while on treatment, repeat endoscopy for assessment and obtain further histology 2
• Patients with refractory eosinophilia and/or significant concomitant atopic disease should have joint management by a gastroenterologist and specialist allergy clinic 2

Critical Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection, as many infected patients have normal eosinophil counts 1
• Do not wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia, as end-organ damage can be subclinical initially 1
• Do not rely solely on peripheral eosinophil counts to assess tissue eosinophilia in conditions like eosinophilic esophagitis, as tissue biopsy is the gold standard 1
• Immunocompromised patients with eosinophilia and potential helminth exposure require urgent evaluation for Strongyloides due to high mortality risk of hyperinfection syndrome 1

Referral Criteria

• Patients without diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department 5
• Moderate to severe eosinophilia (≥1.5 × 10⁹/L) persisting >3 months after infectious causes excluded requires hematology referral 1