What is the workup for eosinophilia?

Workup for Eosinophilia

The workup for eosinophilia should begin with determining the absolute eosinophil count (AEC), followed by a systematic evaluation for secondary causes, and if these are excluded, proceed to testing for primary hematologic disorders with specialized testing including bone marrow examination and genetic studies. 1

Initial Assessment

Definition and Classification

• Eosinophilia: AEC >0.5 × 10⁹/L
• Hypereosinophilia: AEC ≥1.5 × 10⁹/L
• Severe hypereosinophilia: AEC >5.0 × 10⁹/L

First-Line Laboratory Testing

• Complete blood count with differential
• Comprehensive metabolic panel with uric acid
• Lactate dehydrogenase and liver function tests
• Serum tryptase levels
• Vitamin B12 levels
• Peripheral blood smear review 1

Evaluation for Secondary (Reactive) Causes

Detailed History Elements

• Travel history (particularly to areas endemic for parasitic infections)
• New medications (complete medication review)
• Allergic conditions (asthma, eczema, hay fever)
• Recurrent infections
• Family history of eosinophilia
• Dietary exposures (raw or undercooked meat/fish)
• Occupational exposures 1

Physical Examination Focus

• Skin evaluation (rashes, urticaria)
• Hepatosplenomegaly
• Lymphadenopathy
• Signs of immunodeficiency
• Respiratory findings (wheezing)
• Neurological assessment 1

Secondary Cause Testing

1. Parasitic infections:

   • Concentrated stool microscopy (3 samples)
   • Strongyloides serology
   • Schistosomiasis serology (if travel to endemic areas)
   • Filarial serology (if travel to/residence in West Africa)
   • Toxocara serology (if suspected visceral larva migrans) 1

2. Allergic/atopic disorders:

   • Serum IgE levels
   • Aspergillus-specific IgE (if suspected ABPA)
   • Skin prick testing (when clinically indicated) 1

3. Autoimmune evaluation:

   • Antineutrophil cytoplasmic antibodies (ANCA)
   • Antinuclear antibodies (ANA)
   • Erythrocyte sedimentation rate
   • C-reactive protein 1

4. Medication review:

   • Discontinue suspected medications if possible
   • Common culprits: antibiotics, NSAIDs, anticonvulsants 1

Evaluation for Primary (Clonal) Causes

If secondary causes are excluded or eosinophilia persists despite treatment:

Bone Marrow Evaluation

• Bone marrow aspirate and biopsy with:
  • Immunohistochemistry for CD117, CD25, tryptase
  • Reticulin/collagen stains for fibrosis
  • Conventional cytogenetics
  • Fluorescence in situ hybridization (FISH) 1

Molecular and Genetic Testing

• Testing for TK fusion gene rearrangements:
  • PDGFRA, PDGFRB, FGFR1 rearrangements
  • PCM1-JAK2 fusion
  • Nested reverse transcription PCR (RT-PCR)
  • Next-generation sequencing (NGS) via myeloid mutation panels 1

T-cell Clonality Assessment

• Flow cytometry for aberrant T-cell populations
• T-cell receptor gene rearrangement studies
• Evaluation for lymphocyte-variant hypereosinophilia 1

Organ-Specific Evaluation

For patients with suspected end-organ damage:

1. Cardiac evaluation:

   • Echocardiogram
   • Troponin levels
   • BNP/NT-proBNP

2. Pulmonary evaluation:

   • Chest radiograph
   • Pulmonary function tests
   • High-resolution CT scan (if indicated)

3. Gastrointestinal evaluation:

   • Endoscopy with biopsies (if GI symptoms present)
   • Consider eosinophilic esophagitis/gastroenteritis 1

4. Neurological evaluation:

   • MRI brain/spine (if neurological symptoms)
   • CSF analysis (if meningitis/encephalitis suspected)

Special Considerations

Returning Travelers/Migrants

• Focus on parasitic infections based on geographic exposure
• Consider empiric treatment with albendazole (400 mg single dose) plus ivermectin (200 μg/kg single dose) for those >24 months with persistent unexplained eosinophilia 1

Persistent Unexplained Eosinophilia

• If AEC ≥1.5 × 10⁹/L persists for >3 months without identified cause, refer to hematology for evaluation of idiopathic hypereosinophilia 1

Warning Signs Requiring Urgent Assessment

• Evidence of end-organ damage (cardiac, pulmonary, neurological)
• Very high eosinophil counts (>5.0 × 10⁹/L)
• Associated cytopenias or blasts on peripheral smear 1

Diagnostic Algorithm

1. Confirm persistent eosinophilia (AEC >0.5 × 10⁹/L on multiple occasions)
2. Evaluate for secondary causes (most common)
3. If secondary causes excluded or eosinophilia persists despite treatment:
   • Perform bone marrow examination with cytogenetics
   • Test for myeloid/lymphoid neoplasms with specific genetic abnormalities
4. If all tests negative, diagnose as idiopathic hypereosinophilia syndrome (if organ damage present) or idiopathic hypereosinophilia (if no organ damage) 1

Pitfalls to Avoid

• Failing to calculate the absolute eosinophil count (not just percentage)
• Overlooking medication-induced eosinophilia
• Premature diagnosis of idiopathic hypereosinophilia without thorough evaluation
• Missing parasitic infections due to inadequate stool sampling
• Failing to recognize potentially life-threatening hypereosinophilic syndromes with organ involvement
• Neglecting to evaluate for clonal disorders in persistent unexplained eosinophilia 1