Eosinophil-Related Disorders - Eosinophilia

Indications for Testing

Peripheral blood eosinophilia may be discovered during a screening evaluation or workup for specific symptoms. Patient history (eg, medical or travel history, environmental exposure, drugs) should guide further evaluation. 

The presence of eosinophilia in skin biopsy or other tissue biopsy should prompt further evaluation. Cutaneous involvement is a common presenting clinical manifestation. ^, 

Laboratory Testing

Diagnosis

Initial Testing

First-level characterization of a possible eosinophil-related disorder involves a CBC with differential to determine AEC and the percentage of eosinophils within the WBC population. Repeat testing may be indicated for eosinophilia (typically considered >500 cells/µL) but may not be required if absolute counts exceed 1,500 cells/µL, especially in a symptomatic patient (anemia and thrombocytopenia detected on CBC may indicate a neoplasm). ^, 

A peripheral blood smear analysis by a hematopathologist can be used to assess eosinophils for abnormal granulation, nuclear segmentation, or size.  Abnormal eosinophils may indicate a neoplasm, although abnormalities also can be observed in reactive processes. Abnormalities in other cell lines may contribute to diagnosis.

To identify eosinophil involvement in tissue, especially when eosinophil degranulation may have occurred and intact eosinophils are not identifiable, consider staining for eosinophil granule major basic protein 1 (eMBP1) or another eosinophil-specific marker.  Eosinophil granule proteins, including eMBP1, have various and numerous toxic effects on tissues and organs, and their detection has important pathophysiologic and treatment implications.

Testing for Secondary/Reactive Eosinophilia

A broad range of conditions can result in secondary/reactive eosinophilia, and a clinically driven workup is needed to determine cause. Conditions commonly associated with eosinophilia include drug reactions, allergy/asthma, hypersensitivity conditions, pulmonary eosinophilic diseases, skin diseases,  metabolic conditions, and infections (especially parasitic). ^, ,  Nonmyeloid leukemias also can be implicated.  Additional rare conditions include Gleich syndrome and familial eosinophilia. ^,  Due to risks associated with hyperinfection syndrome, consider testing all patients for Strongyloides (Strongyloides immunoglobulin G [IgG] antibody testing) before glucocorticoid administration. ^, 

See Additional Testing below.

Hematopathologic Assessment

Once secondary causes have been ruled out, consider a tissue and/or bone marrow biopsy, as applicable. Assessment for a possible acute or chronic myeloid or lymphoproliferative disorder may involve the following ^{, , , , ,} :

• Morphologic examination of the blood and bone marrow by histopathology and immunohistochemistry
• Cytogenetics
• Fluorescence in situ hybridization (FISH)
• Flow immunocytometry
• T-cell clonality evaluation

Additional Testing

A workup for a patient with eosinophilia may involve a range of other tests, based on history and physical findings. These might include:

• Inflammatory, infectious, and immunologic marker tests, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), antiproteinase 3 and antimyeloperoxidase (c-ANCA and p-ANCA), IgE level, other parasite serologies (in addition to Strongyloides), fungal or viral serologies (HIV, human T-cell leukemia-lymphoma virus), interleukin-5
• Metabolic marker tests, such as liver function tests (including aspartate aminotransferase and alanine aminotransferase), renal function tests (including creatinine, blood urea nitrogen [BUN], and urinalysis for protein and sediment), B₁₂ serum level, mast cell/basophil tryptase level, Beta-2 (β₂) microglobulin, lactate dehydrogenase, coagulation factors, troponin (before imatinib treatment), angiotensin-converting enzyme, thyroid and adrenal function tests
• Serum protein analyses, such as serum protein electrophoresis, quantitative immunoglobulins, IgG4 subclass level, and immunofixation electrophoresis for monoclonal proteins
• Cytogenetic testing (see Hematopathologic Assessment above) to assess for specific chromosomal abnormalities such as FIP1L1-PDGFRA deletion or BCR-ABL1, JAK2 V617F, KIT D816V, or FGFR1 mutations, PDGFRA/PDGFRB rearrangements
• Assessment for T-cell receptor gene rearrangement

Monitoring

Monitoring should include assessment for possible end-organ damage because any organ system can be affected by persistent eosinophilia. ^{, , , , ,}  Physical examination as part of monitoring should include assessment for lymphadenopathy and organomegaly, observation for splinter hemorrhages and nail fold infarcts as indicators of thromboembolic phenomenon, and cardiac auscultation to detect murmurs associated with endomyocardial disease. Test selection is clinically driven and also may include imaging and other testing (such as electrocardiogram or pulmonary function tests).