Hypereosinophilic Syndrome: Diagnosis and Treatment
Purpose of review: Hypereosinophilic syndrome is increasingly recognized as a heterogeneous group of disorders, in some cases with precisely defined pathogenesis, which has led to changes in diagnostic approaches and therapeutic strategies. An update on causes and modern therapy is presented here.
Recent findings: Clonal eosinophilias belong to the group of myeloid malignancies. Karyotypically occult FIP1L1- platelet-derived growth factor receptor alpha and beta rearranged eosinophilic disorders respond to imatinib mesylate with almost 100% efficacy. If standard therapies fail, the FIP1L1- platelet-derived growth factor receptor-negative cases of hypereosinophilic syndrome should also be considered for treatment with imatinib. The recognition of acquired resistance to imatinib has aroused interest in developing new tyrosine kinase inhibitors. Other subgroups of clonal eosinophilias have been molecularly defined, but the curative verification of pathogenetic relevance has not been certified. Hypereosinophilic syndrome patients with abnormal T-cell populations have benefited from treatment with anti IL-5 monoclonal antibodies.
Summary: The FIP1L1- platelet-derived growth factor receptor alpha and beta-positive patients, and those with abnormal T-cell populations are currently the only clearly defined treatable subgroups of hypereosinophilic syndrome. The FIP1L1- platelet-derived growth factor receptor alpha-negative responders to imatinib pose a question as to the existence of subentities with unrecognized tyrosine kinases-based mutation. The search for such cases and other treatable subgroups of hypereosinophilic syndrome has already begun.

The term hypereosinophilic syndrome (HES) was first introduced in 1968 by Hardy and Anderson. Inclusion criteria for idiopathic HES were defined by Chusid et al. 1975. HES has since been characterized by persistently elevated eosinophil count (≥1.5 x 10/L) in the peripheral blood for at least 6 months, with evidence of damage to the organs involved and a lack of known causes. Our perception of HES has changed significantly over the past few years. Recent achievements in the comprehension of pathogenesis and the necessary diagnostic procedures are presented, with direct influence on therapy decisions.

Acquired hypereosinophilias are currently classified into primary and secondary, and primary further into clonal or idiopathic.