Diagnostic Approach for Elevated Eosinophils

Initial Evaluation

Obtain a complete blood count with differential to confirm eosinophilia and assess for other blood count abnormalities, such as dysplasia, monocytosis, and circulating blasts, as recommended by the American College of Physicians 1
Perform routine serum chemistries, including liver function tests, lactate dehydrogenase, and uric acid, to identify potential underlying causes of eosinophilia 1
Check vitamin B12 levels, as they may be elevated in myeloproliferative variants, according to the American Society of Hematology 2
Measure serum immunoglobulin levels, including IgG, IgA, IgM, and IgE, as there may be an inverse relationship between IgE levels and blood eosinophil counts in certain conditions, as noted by the American Academy of Allergy, Asthma, and Immunology 1, 2
Order inflammatory markers, such as C-reactive protein and erythrocyte sedimentation rate, to assess for potential inflammatory causes of eosinophilia 1
Perform urinalysis and assess for proteinuria, using a 24-hour collection or protein-to-creatinine ratio, to evaluate for potential renal involvement 1

For mild eosinophilia (500-1500 cells/μL), evaluate for common causes, such as allergies, atopy, drug reactions, and autoimmune disorders, as recommended by the American College of Allergy, Asthma, and Immunology 1, 3
For hypereosinophilia (≥1500 cells/μL), refer to hematology for further investigation, especially if persistent for more than 3 months, and assess for symptoms of organ damage, such as cardiac, pulmonary, neurologic, and gastrointestinal involvement, according to the American Society of Hematology 1, 4
Evaluate for hypereosinophilic syndrome (HES) using criteria from the World Health Organization classification, as noted by the National Comprehensive Cancer Network 5

For suspected secondary (reactive) causes, perform serology testing for parasitic infections, particularly Strongyloides, and order stool examination for ova and parasites if gastrointestinal symptoms are present, as recommended by the Centers for Disease Control and Prevention 1, 2, 3
For suspected primary (neoplastic) causes, perform bone marrow aspirate and biopsy with immunohistochemistry, and order conventional cytogenetics and fluorescence in situ hybridization (FISH) and/or nested RT-PCR to detect tyrosine kinase fusion gene rearrangements, such as PDGFRA, PDGFRB, FGFR1, and JAK2, according to the National Comprehensive Cancer Network 2, 5, 6

Perform echocardiography and/or cardiac MRI if cardiac involvement is suspected, as recommended by the American Heart Association 4
Order pulmonary function tests and chest imaging for suspected respiratory involvement, according to the American Thoracic Society 1
Perform endoscopy with biopsies for suspected gastrointestinal involvement, as recommended by the American Gastroenterological Association 7
Conduct skin biopsy for cutaneous manifestations, according to the American Academy of Dermatology 6
Perform neurological evaluation, including imaging, for suspected nervous system involvement, as recommended by the American Academy of Neurology 4