What are the causes and treatment options for elevated eosinophils in a patient with a history of allergies or asthma?

Causes of High Eosinophils in Patients with Allergies or Asthma

In patients with allergies or asthma presenting with elevated eosinophils, allergic/atopic disorders account for approximately 80% of cases, but helminth infections must be systematically excluded—especially in travelers or migrants—before attributing eosinophilia solely to the known allergic condition. 1, 2

Primary Causes by Category

Allergic and Atopic Disorders (Most Common in Non-Endemic Areas)

• Asthma, allergic rhinitis, atopic dermatitis, and food allergies constitute the vast majority (80%) of secondary reactive eosinophilia cases in patients without travel to endemic regions 2, 3
• The majority of patients with eosinophilic esophagitis (50-80%) are atopic, with coexisting asthma, allergic rhinitis, or atopic dermatitis 4
• Peripheral eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis via endoscopy remains essential if dysphagia or food impaction is present 4, 1

Drug-Induced Eosinophilia

• Non-steroidal anti-inflammatory drugs, beta-lactam antibiotics, and nitrofurantoin are the most common medication culprits 2, 3
• Antileukotriene antagonists (zafirlukast, montelukast) may unmask eosinophilic granulomatosis with polyangiitis (EGPA) in asthma patients, though these drugs can still be used if needed 4

Parasitic Infections (Critical to Exclude)

• Helminth infections account for 19-80% of eosinophilia cases in returning travelers or migrants, making them the most common identifiable cause in this population 1, 2
• Strongyloides stercoralis can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients, requiring urgent exclusion 1, 2
• Hookworm (Ancylostoma duodenale, Necator americanus), Ascaris lumbricoides, and Schistosomiasis are other major helminth causes 2, 3
• Many helminth-infected patients do not have eosinophilia, so normal eosinophil counts do not exclude parasitic infection 1, 2

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• EGPA requires four of six criteria: history of asthma, eosinophilia >10%, mono/polyneuropathy, nonfixed pulmonary infiltrates, paranasal sinus abnormalities, and biopsy showing eosinophils in extravascular tissue 4
• The prodromal stage is characterized by allergic rhinitis, chronic rhinosinusitis with/without polyps, and asthma, which may predate overt vasculitis by years (mean 8 years) 4

Hematologic and Neoplastic Causes

• Myeloid/lymphoid neoplasms with tyrosine kinase fusion genes (PDGFRA, PDGFRB) require bone marrow evaluation with cytogenetics and molecular testing 4
• Elevated serum tryptase and vitamin B12 levels are commonly observed in myeloproliferative variants, particularly with PDGFRA fusion genes 4

Severity-Based Diagnostic Approach

Mild Eosinophilia (0.5-1.5 × 10⁹/L)

• Most commonly caused by allergic disorders or medications in non-endemic areas 1
• In returning travelers or migrants, obtain three separate concentrated stool specimens for ova and parasites plus Strongyloides serology immediately 1, 2

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

• Refer to hematology if persisting >3 months after infectious causes excluded or treated 1, 2
• Obtain CBC with differential, comprehensive metabolic panel, LDH, liver function tests, serum tryptase, and vitamin B12 levels 4
• Perform bone marrow aspirate and biopsy with immunohistochemistry for CD117, CD25, tryptase, and cytogenetics/FISH to detect tyrosine kinase fusion gene rearrangements 4

Critical Thresholds Requiring Urgent Assessment

• Any eosinophilia with end-organ damage symptoms (chest pain, dyspnea, heart failure, arrhythmias, altered mental status, focal neurologic deficits, peripheral neuropathy) requires emergency evaluation 1
• Absolute eosinophil count ≥5.0 × 10⁹/L at any time carries significant risk of morbidity and mortality 1

Essential Diagnostic Workup

History and Physical Examination

• Detailed travel history focusing on freshwater exposure in Africa/tropical regions, raw/undercooked meat consumption, and timing of travel relative to eosinophilia onset 1, 2
• Assessment of new medications, recurrent infections, family history of eosinophilia, and seasonal symptom variations 4
• Skin evaluation, palpation of liver and spleen, and signs of immunodeficiency syndrome 4

Laboratory Testing

• Strongyloides serology and culture (high diagnostic yield across all regions) 1, 2
• Schistosomiasis serology if freshwater exposure in endemic areas 1, 2
• Elevated IgE is nonspecific but found in allergies, infections, and lymphocytic-variant hypereosinophilic syndrome 4
• Aspergillus-specific immunoglobulins and increased serum IgE are characteristic of allergic bronchopulmonary aspergillosis 4

Organ Damage Screening (for ≥1.5 × 10⁹/L)

• Cardiac: ECG, cardiac troponin, NT-proBNP; echocardiography if troponin elevated or cardiac symptoms present 1
• Pulmonary: Chest X-ray, pulmonary function tests if respiratory symptoms present 1
• Neurologic: Electromyography if sensory/motor deficits present 1
• Gastrointestinal: Endoscopy with multiple biopsies (minimum 6: 2-3 proximal, 2-3 distal esophagus) if dysphagia or food impaction present 1

Treatment Approach

For Allergic/Atopic Eosinophilia

• Topical swallowed corticosteroids (fluticasone or budesonide) for eosinophilic esophagitis, which decrease blood eosinophil counts in 88% of patients 4, 1
• Systemic corticosteroids for severe allergic conditions intractable to conventional treatment 5
• Maintenance therapy is mandatory after achieving remission in eosinophilic esophagitis, as clinical relapse rates are high after topical steroid withdrawal 1

For Helminth Infections

• Ivermectin 200 μg/kg daily for 2 days for Strongyloidiasis 1
• Albendazole 400 mg as single dose for hookworm 2
• For asymptomatic eosinophilia with suspected helminth infection: empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg as single doses 1, 2
• Critical warning for Loa loa: Do not use diethylcarbamazine if microfilariae seen on blood film, as it may cause fatal encephalopathy; use corticosteroids with albendazole first 1, 2

For Hypereosinophilic Syndrome

• Corticosteroids as first-line treatment after excluding helminth infections 1
• Imatinib for myeloid neoplasms with PDGFRA/PDGFRB rearrangements 1

Critical Pitfalls to Avoid

• Do not assume eosinophilia alone is adequate screening for helminth infection, as many infected patients have normal eosinophil counts 1, 2
• Do not attribute persistent eosinophilia solely to known asthma/allergies without excluding helminth infections, especially in travelers or migrants 1, 2
• Do not rely solely on peripheral eosinophil counts to assess eosinophilic esophagitis, as tissue biopsy is the gold standard (≥15 eosinophils per high-power field required for diagnosis) 4, 1
• Serological tests for helminths may not become positive until 4-12 weeks after infection, and stool microscopy may be negative during tissue migration phase when eosinophilia is present 2, 3
• Do not initiate corticosteroid therapy before excluding Strongyloides, as immunosuppression can trigger fatal hyperinfection syndrome 1, 2