What to order next if eosinophils are elevated?

Diagnostic Approach for Elevated Eosinophils

When eosinophil levels are elevated, a systematic diagnostic workup should be performed starting with comprehensive laboratory testing to identify the underlying cause, followed by targeted testing for specific conditions based on initial findings.

Initial Evaluation

• Obtain a complete blood count with differential to confirm eosinophilia and assess for other blood count abnormalities (dysplasia, monocytosis, circulating blasts) 1
• Perform routine serum chemistries including liver function tests, lactate dehydrogenase, and uric acid 1
• Check vitamin B12 levels, as they may be elevated in myeloproliferative variants 2
• Measure serum immunoglobulin levels (IgG, IgA, IgM, IgE) as there may be an inverse relationship between IgE levels and blood eosinophil counts in certain conditions 1, 2
• Order inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate 1
• Perform urinalysis and assess for proteinuria (24-hour collection or protein-to-creatinine ratio) 1

Classification-Based Approach

For Mild Eosinophilia (500-1500 cells/μL)

• Evaluate for common causes such as allergies, atopy, drug reactions, and autoimmune disorders 1, 3
• Review medication history for potential drug reactions 4
• Consider parasitic infection screening, especially with relevant travel history 4, 5

For Hypereosinophilia (≥1500 cells/μL)

• Refer to hematology for further investigation, especially if persistent for more than 3 months 1, 6
• Assess for symptoms of organ damage (cardiac, pulmonary, neurologic, gastrointestinal) 1, 7
• Evaluate for hypereosinophilic syndrome (HES) using criteria from Table 2 classification 7

Advanced Testing Based on Initial Findings

For Suspected Secondary (Reactive) Causes

• Perform serology testing for parasitic infections, particularly Strongyloides 1, 2
• Order stool examination for ova and parasites if gastrointestinal symptoms are present 1, 4
• Test for autoimmune markers (ANA, ANCA) if autoimmune disease is suspected 1, 4
• Consider allergic bronchopulmonary aspergillosis testing (Aspergillus IgE) 2

For Suspected Primary (Neoplastic) Causes

• Perform bone marrow aspirate and biopsy with immunohistochemistry 2
• Order conventional cytogenetics 2
• Conduct fluorescence in situ hybridization (FISH) and/or nested RT-PCR to detect tyrosine kinase fusion gene rearrangements (PDGFRA, PDGFRB, FGFR1, JAK2) 7, 2
• Consider next-generation sequencing via myeloid mutation panels to establish clonality 2
• Test for KIT D816V mutation, which occurs in most patients with systemic mastocytosis 2

For Suspected Lymphocytic Variant HES

• Perform flow cytometry to identify aberrant T-cell populations 2
• Consider molecular analysis to confirm T-cell clonality when flow cytometry results are equivocal 2

Organ-Specific Evaluation

• Echocardiography and/or cardiac MRI if cardiac involvement is suspected 7
• Pulmonary function tests and chest imaging for suspected respiratory involvement 1
• Endoscopy with biopsies for suspected gastrointestinal involvement 7
• Skin biopsy for cutaneous manifestations 7
• Neurological evaluation including imaging for suspected nervous system involvement 7

Common Pitfalls to Avoid

• Failing to evaluate for parasitic infections in patients with relevant travel history 4, 5
• Not recognizing that normal IgE levels with elevated eosinophils may suggest non-allergic causes 4
• Overlooking potential organ damage in patients with persistent eosinophilia 1, 6
• Not testing for specific genetic abnormalities that may predict response to targeted therapies 1, 7
• Premature closure of diagnosis without comprehensive genetic testing, as rare mutations may be present 2

When to Refer to Specialists

• Eosinophilia ≥1500 cells/μL persisting for more than 3 months requires hematology evaluation 1, 6
• Any evidence of end-organ damage potentially related to eosinophilia requires urgent medical assessment 1, 7
• Suspected myeloid/lymphoid neoplasms with eosinophilia should be referred to hematology 7
• Suspected eosinophilic esophagitis or gastrointestinal involvement warrants gastroenterology consultation 7, 8