What is the cause of elevated eosinophils (eosinophilia) in this patient?

Causes of Elevated Eosinophils

The most common causes of elevated eosinophils are allergic disorders (approximately 80% of cases), followed by parasitic infections, with tissue-invasive helminths being the primary parasitic culprits. 1, 2

Primary Diagnostic Framework

The evaluation must distinguish between secondary (reactive) eosinophilia and primary (neoplastic) eosinophilia based on the degree of elevation and clinical context. 2, 3

Mild Eosinophilia (500-1500 cells/μL)

For mild elevations, focus on common secondary causes: 2

• Allergic conditions including allergic asthma, food allergy, atopic dermatitis, and drug reactions account for the vast majority of cases 1, 4
• Parasitic infections, particularly Strongyloides stercoralis, represent the second most common cause and require stool examination for ova and parasites plus serology if gastrointestinal symptoms or travel history is present 1, 2, 4
• Medication reactions should be evaluated through comprehensive medication review, including recent additions or changes 4
• Immune checkpoint inhibitor therapy can cause eosinophilia as part of immune-related adverse events 4

Hypereosinophilia (≥1500 cells/μL)

For persistent elevations ≥1500 cells/μL lasting more than 3 months, refer to hematology immediately and assess for organ damage. 2, 4

This threshold triggers evaluation for:

• Myeloid/lymphoid neoplasms with tyrosine kinase fusion genes (PDGFRA, PDGFRB, FGFR1, JAK2) which require bone marrow biopsy, cytogenetics, FISH, and RT-PCR 1, 2, 3
• Hypereosinophilic syndrome (HES) affecting skin, lungs, gastrointestinal tract, heart, and nervous system, with endomyocardial involvement particularly concerning 1
• Eosinophilic granulomatosis with polyangiitis (EGPA) presenting with asthma, nasal polyposis, and systemic vasculitis, though only 30-40% are ANCA-positive 1

Tissue-Specific Eosinophilic Disorders

Gastrointestinal Eosinophilia

Eosinophilic esophagitis (EoE) causes tissue eosinophilia (≥15 eos/hpf) but peripheral blood eosinophilia occurs in only 10-50% of adults and 20-100% of children, typically with modest 2-fold elevations. 1

• EoE requires symptoms of esophageal dysfunction plus exclusion of GERD, hypereosinophilic syndrome, Crohn's disease, infections, connective tissue disorders, and drug hypersensitivity 1
• 50-80% of EoE patients have concurrent atopic conditions (allergic rhinitis, asthma, atopic dermatitis) which may independently contribute to peripheral eosinophilia 1
• The presence of peripheral eosinophilia in EoE correlates with concurrent allergic sensitization rather than EoE severity alone 1

Systemic Conditions with Esophageal Involvement

HES can mimic EoE but is distinguished by peripheral eosinophilia (AEC >1500 cells/μL) and multisystem organ involvement. 1

Essential Diagnostic Testing

Initial Laboratory Evaluation

Obtain these tests for all patients with confirmed eosinophilia: 2

• Complete blood count with differential to assess for dysplasia, monocytosis, and circulating blasts 2
• Serum chemistries including liver function tests, lactate dehydrogenase, and uric acid 2
• Vitamin B12 levels (elevated in myeloproliferative variants) 2, 4
• Serum immunoglobulin levels (IgG, IgA, IgM, IgE) noting that normal IgE with elevated eosinophils suggests non-allergic causes 2, 4, 5
• Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) 2, 4
• Urinalysis with protein assessment 2

Parasitic Infection Screening

For any patient with travel history or gastrointestinal symptoms, perform Strongyloides serology and stool examination for ova and parasites. 2, 4

• Only tissue-invasive helminths cause eosinophilia; protozoa typically do not 6
• Eosinophilia may resolve spontaneously over time depending on parasite life cycle, requiring repeated testing 6
• Empiric treatment with albendazole 400 mg plus ivermectin 200 μg/kg (single doses) is appropriate for returning travelers with suspected parasitic infection 4

Critical Pitfalls to Avoid

Do not assume peripheral eosinophilia equals tissue eosinophilia or vice versa. 1, 5

• Eosinophilic esophagitis frequently presents with normal peripheral eosinophil counts 1, 5
• Conversely, peripheral eosinophilia without tissue involvement may not require aggressive intervention 2

Do not overlook drug-induced eosinophilia, including DRESS syndrome (drug rash with eosinophilia and systemic symptoms). 7

• Spironolactone and numerous other medications can cause DRESS with eosinophilia 7

Do not delay hematology referral for persistent hypereosinophilia ≥1500 cells/μL. 2, 4

• Identification of PDGFRA or PDGFRB rearrangements is critical as these respond exquisitely to imatinib 3, 8
• Delayed diagnosis risks irreversible organ damage, particularly cardiac fibrosis 1

Organ Damage Assessment

For hypereosinophilia, systematically evaluate for end-organ involvement: 2

• Echocardiography or cardiac MRI for cardiac assessment 2
• Pulmonary function tests and chest imaging for respiratory involvement 2
• Endoscopy with biopsies for gastrointestinal symptoms 2
• Skin biopsy for cutaneous manifestations 2
• Neurological evaluation with imaging if nervous system symptoms present 2