Severe Leukocytosis with Eosinophilia in Children

Differential Diagnosis

The American Society of Hematology recommends considering myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions as the most critical diagnosis given extreme leukocytosis, as these can present with clinical features similar to chronic eosinophilic leukemia, other myeloproliferative neoplasms, or acute leukemia 1, 2
Myeloid/lymphoid neoplasms with PDGFRA, PDGFRB, or ETV6::ABL1 rearrangements are particularly important because they respond to tyrosine kinase inhibitors and represent treatable causes, according to the American Society of Hematology 1, 2, 3
BCR::ABL1-positive chronic myeloid leukemia can present with marked leukocytosis and eosinophilia, with basophilia being an additional clue, as noted by the American Society of Hematology 1, 2

A complete blood count with manual differential is essential to determine absolute eosinophil count and percentage, presence of basophilia, blast percentage, and promyelocyte count, as recommended by the American Society of Hematology 4
Peripheral blood flow cytometry should be performed to define myeloid versus lymphoid phenotype and assess for aberrant immunophenotypes, according to the American Society of Hematology 4
Bone marrow aspiration and biopsy with morphology, conventional cytogenetics, FISH for CHIC2 deletion, RT-PCR for tyrosine kinase fusion genes, and immunohistochemistry are mandatory for diagnosis, as recommended by the American Society of Hematology 4, 7

Serum tryptase and vitamin B12 levels should be measured, as they are elevated in myeloproliferative neoplasms, according to the American Society of Hematology 7
Comprehensive metabolic panel and liver function tests should be performed to assess organ involvement, as recommended by the American Society of Hematology 7
Cardiac evaluation, including ECG, echocardiogram, and troponin, is critical for prognosis, as persistent high-grade eosinophilia can cause irreversible cardiac damage, according to the American Society of Hematology 7, 5, 6

Failing to test for PDGFRA/PDGFRB rearrangements can lead to missed opportunities for highly effective tyrosine kinase inhibitor therapy, as noted by the American Society of Hematology 7
Attributing severe leukocytosis to allergic disease can be misleading, as allergic disorders account for 80% of eosinophilia but cause only mild elevations, according to the American Society of Hematology 5
Not assessing cardiac involvement early can result in irreversible heart failure, as eosinophil-mediated cardiac damage occurs with persistent high-grade eosinophilia, as recommended by the American Society of Hematology 7