When should blood eosinophils be checked and what labs should be ordered in patients with suspected eosinophilic disorders?

When to Check Blood Eosinophils and Appropriate Laboratory Tests

Blood eosinophil testing should be performed in patients with suspected eosinophilic disorders, including those with unexplained persistent allergic symptoms, vasculitis features, organ-specific damage patterns, or treatment-refractory conditions like asthma or rhinosinusitis. The diagnostic approach should be guided by clinical presentation and suspected underlying condition.

Definition and Classification of Eosinophilia

• Eosinophilia is defined as a peripheral blood eosinophil count >0.5 × 10⁹/L 1
• Severity classification:
  • Mild: 0.5-1.5 × 10⁹/L
  • Moderate: 1.5-5.0 × 10⁹/L
  • Severe: >5.0 × 10⁹/L 1
• Hypereosinophilia is defined as >1.5 × 10⁹/L 2, 3

When to Check Blood Eosinophils

Suspected Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• In patients with asthma plus any of the following:
  • Peripheral neuropathy
  • Purpura
  • Renal function impairment
  • Cardiac involvement
  • Pulmonary infiltrates
  • Sino-nasal symptoms 4

Suspected Eosinophilic Esophagitis (EE)

• In patients with:
  • Dysphagia
  • Food bolus obstruction
  • Refractory GERD symptoms (especially in children)
  • Atopic conditions 4

Suspected Myeloid/Lymphoid Neoplasms with Eosinophilia

• In patients with:
  • Persistent unexplained eosinophilia
  • Signs of organ damage
  • Abnormal blood smear findings 4

Suspected Eosinophilic Rhinosinusitis

• In patients with:
  • Chronic rhinosinusitis with nasal polyps
  • Treatment-refractory sinus disease 4

Laboratory Tests to Order

Initial Workup for All Suspected Eosinophilic Disorders

1. Complete blood count with differential (to confirm eosinophilia)
2. Peripheral blood smear (to evaluate for dysplastic eosinophils or blasts)
3. Comprehensive metabolic panel with liver function tests
4. Urinalysis with protein-to-creatinine ratio
5. C-reactive protein
6. Serum tryptase and vitamin B12 levels 4, 1

Immunological and Allergic Tests

1. ANCA testing (especially MPO-ANCA) - critical for EGPA diagnosis 4
2. Immunoglobulin levels (IgG, IgA, IgM, IgE, IgG4)
3. Allergen-specific IgE testing in patients with suspected allergic etiology 4, 1

Infectious Disease Testing

1. Stool cultures for parasites (especially Strongyloides stercoralis)
2. HIV serology
3. Parasite serology for travelers/migrants 4, 1

Hematological Tests for Suspected Myeloid/Lymphoid Neoplasms

1. FIP1L1 fusion protein testing
2. FISH for CHIC2 deletion (to identify FIP1L1-PDGFRA rearrangement)
3. Cytogenetic studies
4. Flow cytometry (for T-cell immunophenotyping in suspected lymphocyte-variant hypereosinophilia)
5. Bone marrow biopsy and aspirate (for persistent unexplained eosinophilia) 4, 3

Disease-Specific Testing Algorithms

For EGPA Diagnosis 4

1. Initial labs: CBC with differential, CRP, ANCA testing
2. If ANCA positive (especially MPO-ANCA): Strongly supports EGPA diagnosis
3. If organ involvement suspected:
   • Cardiac: ECG, troponin, BNP, echocardiography, cardiac MRI
   • Pulmonary: Chest X-ray/HRCT, pulmonary function tests
   • Renal: 24-hour proteinuria, kidney biopsy if indicated
   • Neurological: EMG/ENG, nerve biopsy if indicated

For Eosinophilic Esophagitis 4

1. CBC with differential
2. Allergy testing (skin prick testing or food-specific IgE)
3. Endoscopy with esophageal biopsies (≥6 biopsies from different sites)
   • Diagnostic threshold: ≥15 eosinophils per 0.3 mm² in any biopsy specimen

For Myeloid/Lymphoid Neoplasms with Eosinophilia 4, 3

1. CBC with differential and peripheral blood smear
2. Molecular testing for tyrosine kinase gene fusions:
   • PDGFRA rearrangement (especially FIP1L1-PDGFRA)
   • PDGFRB rearrangement
   • FGFR1 rearrangement
   • PCM1-JAK2
3. Bone marrow examination with cytogenetics

Pitfalls and Caveats

1. False negatives in PDGFRA testing: Peripheral blood FISH may not detect FIP1L1-PDGFRA fusion due to low clone size; consider bone marrow testing if clinical suspicion is high 4

2. Transient eosinophilia: Single elevated eosinophil count may be transient; confirm persistence before extensive workup 1

3. Medication-induced eosinophilia: Always review medication history as drugs (especially NSAIDs and beta-lactams) can cause eosinophilia 1

4. ANCA-negative EGPA: 60-70% of EGPA patients are ANCA-negative; absence of ANCA doesn't exclude diagnosis 4

5. Proton pump inhibitor effect: For accurate diagnosis of eosinophilic esophagitis, PPIs should be withdrawn for at least 3 weeks prior to endoscopy and biopsy 4

6. Blood eosinophil count limitations: Normal blood eosinophil count doesn't exclude tissue eosinophilia; tissue biopsy may be necessary for diagnosis 4

By following this structured approach to eosinophil testing, clinicians can efficiently diagnose and manage patients with suspected eosinophilic disorders, leading to improved outcomes in terms of morbidity, mortality, and quality of life.