Eosinophil disorders: an update on diagnosis and management

Abstract

Eosinophilia can be seen in almost all medical subspecialty patients. Delay in diagnostic workup and treatment is associated with significant morbidity and mortality. Clinical vigilance and timely referral for diagnostic evaluation are critical. Causes of hypereosinophilia (HE) are diverse and can be grouped under 3 categories: primary (neoplastic), secondary (reactive), and idiopathic. Advances in molecular genetic diagnostics have led to elucidation of the genetic basis for many neoplastic hypereosinophilic disorders. One common molecular feature is formation of a fusion gene, resulting in the expression of an aberrantly activated tyrosine kinase (TK). The World Health Organization endorsed a biologically oriented classification scheme and created a new major disease category, namely, myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions. Rearrangement of other TK genes and activating somatic mutation(s) in TK genes have also been reported in eosinophilic neoplasms. Diagnostic evaluation of HE involves a combination of clinical, histopathologic, and immunophenotypic analyses, as well as molecular genetic testing, including next-generation sequencing–based mutation panels. The management of primary HE is largely guided by the underlying molecular genetic abnormalities. Good knowledge of recent advances in HE is necessary to ensure timely and accurate diagnosis and to help optimize patient care.