What is the appropriate diagnosis and treatment approach for a patient with elevated eosinophils (eosinophilia)?

Elevated Eosinophils: Diagnostic and Treatment Approach

The management of elevated eosinophils requires immediate risk stratification based on absolute eosinophil count (AEC) and assessment for end-organ damage, with helminth infections being the most common identifiable cause (19-80% of cases) in travelers or migrants, followed by allergic disorders in non-endemic populations, and urgent hematology referral for persistent moderate-to-severe eosinophilia (≥1.5 × 10⁹/L) after excluding infectious causes. 1

Immediate Risk Stratification

Critical Red Flags Requiring Emergency Evaluation

• Any patient with eosinophilia presenting with cardiac symptoms (chest pain, dyspnea, heart failure, arrhythmias) requires immediate evaluation for endomyocardial thrombosis/fibrosis, as this represents life-threatening end-organ damage. 1

• Neurological involvement (altered mental status, focal deficits, peripheral neuropathy) demands urgent assessment for CNS/spinal cord involvement. 1

• Pulmonary symptoms (persistent cough, wheezing, infiltrates on imaging) necessitate immediate evaluation for eosinophilic pulmonary disease. 1

• Absolute eosinophil count ≥5.0 × 10⁹/L at any time, or ≥1.5 × 10⁹/L persisting >3 months, or any level with evidence of end-organ damage carries significant mortality risk and requires urgent intervention. 1

Severity-Based Classification

• 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

• Moderate-to-severe eosinophilia (≥1.5 × 10⁹/L): Requires hematology referral if persisting >3 months after infectious causes excluded or treated. 1

• Hypereosinophilia (≥1.5 × 10⁹/L on two occasions ≥4 weeks apart): Mandates systematic evaluation for hypereosinophilic syndrome and organ damage assessment. 1, 2

Systematic Diagnostic Approach

Step 1: Detailed History - Critical Elements

• Travel history: Specifically document fresh water exposure in Africa/tropical regions, raw/undercooked meat consumption, and timing relative to eosinophilia onset, as helminth infections are the leading cause in endemic-exposed patients. 1

• Medication review: All current and recent medications, as drug reactions are a common reversible cause. 1

• Gastrointestinal symptoms: Dysphagia or food impaction warrants endoscopy with multiple biopsies (minimum 6: 2-3 proximal, 2-3 distal esophagus) to evaluate for eosinophilic esophagitis. 1

• Respiratory symptoms: Chronic cough, wheezing, or dyspnea suggests asthma or eosinophilic lung disease. 1

• Constitutional symptoms: Fever, weight loss, night sweats raise concern for malignancy or systemic vasculitis. 1

Step 2: First-Line Laboratory Evaluation

For any eosinophilia >0.5 × 10⁹/L with travel history to endemic areas:

• Stool microscopy for ova and parasites (3 separate concentrated specimens) - first-line test for helminth detection. 1

• Strongyloides serology and culture - critical because Strongyloides can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients. 1

• Schistosomiasis serology if fresh water exposure in endemic areas documented. 1

Critical caveat: Many helminth-infected patients do not have eosinophilia, so normal eosinophil counts do not exclude parasitic infection; only tissue-invasive helminths cause eosinophilia. 1

Step 3: Organ Damage Assessment (for AEC ≥1.5 × 10⁹/L)

Cardiac evaluation (highest priority due to mortality risk):

• Electrocardiogram, cardiac troponin, NT-proBNP in all patients with hypereosinophilia. 1

• Echocardiography when troponin elevated or clinical features suggest cardiac injury. 1

• Cardiac MRI indicated when elevated troponin or clinical cardiac features present. 1

Pulmonary evaluation:

• Pulmonary function tests for all patients with respiratory symptoms. 1

• Chest X-ray to identify infiltrates (migratory infiltrates suggest Loeffler's syndrome; interstitial/reticulonodular patterns suggest tropical pulmonary eosinophilia). 1

• Bronchoscopy with bronchoalveolar lavage when imaging suggests parenchymal disease. 1

Neurologic evaluation:

• Electromyography to confirm eosinophil-induced peripheral neuropathy in patients with sensory/motor deficits. 1

• Nerve biopsy confirms eosinophilic infiltration when EMG consistent with neuropathy. 1

Gastrointestinal evaluation:

• Endoscopy with mucosal biopsy for patients with GI symptoms. 1

• For eosinophilic esophagitis diagnosis: >15 eosinophils per high-power field (0.3 mm²) on esophageal biopsy. 3, 1

Dermatologic evaluation:

• Deep skin biopsy including fascia to confirm cutaneous involvement. 1

• MRI for eosinophilic fasciitis when clinical suspicion high. 1

Treatment Algorithm

For Helminth Infections (Most Common Identifiable Cause)

Strongyloidiasis:

• Ivermectin 200 μg/kg daily for 2 days is the treatment of choice. 1

• Critical warning for immunocompromised patients: Urgent evaluation required due to high mortality risk of hyperinfection syndrome. 1

Schistosomiasis:

• Praziquantel 40 mg/kg single dose, repeated at 6-8 weeks. 1

• Add prednisolone 20 mg/day for 5 days in acute Katayama syndrome. 1

Loeffler's syndrome (Ascaris, hookworm):

• Albendazole 400 mg twice daily for 3 days. 1

Tropical pulmonary eosinophilia (typically AEC >3 × 10⁹/L):

• CRITICAL: First exclude Loa loa co-infection before initiating treatment. 1

• DO NOT use diethylcarbamazine (DEC) if Loa loa microfilariae seen on blood film - can cause fatal encephalopathy. 1

• If Loa loa excluded: Initiate DEC promptly to prevent irreversible pulmonary fibrosis. 1

• Adjunctive corticosteroids (prednisolone 20 mg/day for 5 days) for ongoing alveolitis. 1

• 20% of patients relapse and require second DEC course. 1

For Eosinophilic Esophagitis

First-line treatment:

• Topical swallowed corticosteroids (fluticasone or budesonide) decrease blood eosinophil counts in 88% of patients. 1

• Maintenance therapy mandatory after achieving remission due to high relapse rates after steroid withdrawal. 1

Monitoring:

• Histological remission defined as <15 eosinophils per 0.3 mm²; deep remission as <5 eosinophils per 0.3 mm². 1

• Repeat endoscopy with biopsies if symptoms recur during treatment. 1

• Critical caveat: Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis remains essential. 1

For fibrostenotic disease:

• Endoscopic dilation safe and effective but must be combined with anti-inflammatory therapy. 1

For Hypereosinophilic Syndrome

Myeloproliferative variants with PDGFRA/PDGFRB rearrangements:

• Imatinib 100-400 mg daily is the treatment of choice for FIP1L1-PDGFRA-positive cases. 1, 4

Other HES variants:

• Oral corticosteroids (prednisone 1 mg/kg/day initially) are first-line treatment except for clonal eosinophilia amenable to targeted therapy. 1, 4

• Novel eosinophil-depleting therapies targeting IL-5 or IL-5 receptor (mepolizumab, reslizumab, benralizumab) reduce exacerbations by approximately 50% and may reduce long-term corticosteroid side effects. 4

For Allergic Disorders (Most Common Cause of Mild Eosinophilia in Non-Endemic Areas)

Asthma with eosinophilia:

• Sputum eosinophil count <3% has 100% negative predictive value for significant FEV1 improvement with inhaled corticosteroids. 1

• Management strategies targeting eosinophil normalization reduce severe asthma exacerbations by up to 60%. 1

• For persistent eosinophilia despite maximal inhaled therapy: Consider biologics targeting IL-5 pathway. 1

Critical Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection - many infected patients have normal eosinophil counts. 1

• Do not wait for symptoms before investigating persistent moderate-to-severe eosinophilia - 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 - tissue biopsy is the gold standard. 1

• Do not use diethylcarbamazine if Loa loa microfilariae present - can cause fatal encephalopathy; use corticosteroids with albendazole first to reduce microfilarial load. 1

• Do not overlook cardiac evaluation in hypereosinophilia - endomyocardial damage is a leading cause of mortality. 1