Abstract
Hypereosinophilia (HE) can be caused by a wide variety of non-hematologic (secondary
or reactive) and hematologic (primary, clonal) disorders. Diagnosing hypereosinophilia/hypereosinophilic
syndrome (HE/HES) is challenging due to the complex nature of disease manifestations
and numerous underlying etiologies. Knowing that only rare cases are clonal, it is
wise to rule out reactive conditions and proceed with molecular and other advanced
tools. The exclusion of secondary causes needs a detailed clinical evaluation followed
by a wide range of serological and imaging investigations. Once reactive eosinophilia
has been ruled out, the diagnosis of primary HE/HES is made using a combination of
morphologic examination of the blood and bone marrow, conventional cytogenetics, fluorescent
in situ hybridization, flow-cytometry, and T-cell clonality evaluation to look for
histopathologic or clonal evidence of an underlying hematological disorder. The accurate
diagnosis of clonal eosinophilia-causing myeloid and lymphoid neoplasms and the identification
of numerous gene rearrangements significantly enhance patient outcomes, because a
proportion of these patients (such as PDGFRA and PDGFRB rearrangements) responds well to tyrosine kinase inhibitors. Considering the complex
etiopathologies, the cost of testing, and the time involved, the workup needs to be
tailored according to the urgency of the situation and the resources available. In
urgent situations with organ damage, it is crucial to initiate appropriate management
without waiting for the results of investigations. In contrast, in a resource-limited
situation, it is acceptable to employ step-by-step rather than comprehensive testing
to rule out the most common causes first. Here, we discuss various laboratory investigations
employed in diagnosing HE/HES, highlighting their importance in different situations.
Keywords
hypereosinophilia - hypereosinophilic syndrome - mastocytosis - tyrosine kinase domain
fusions - myelodysplastic syndromes - myeloproliferative neoplasms
