Diagnostic and therapeutic management in patients with hypereosinophilic syndromes

The hypereosinophilic syndromes (HES) are rare disorders characterized by sustained, nonreactive hypereosinophilia with eosinophilia-associated organ damage/dysfunction. The most frequent clinical manifestations include skin abnormalities, cardiac failure, and neurological deficits, but disease presentations differ between patients and every organ may be affected. HES patients are currently categorized according to 2 classifications: World Health Organization 2008 and Working Classification 2006, but both have several limitations in daily practice. Despite advances in our understanding of HES pathogenesis, more than 50% of patients are still diagnosed with idiopathic disease, while the remaining subset has myeloproliferative (M-HES) or lymphocytic (L-HES) variants. In 10% to 20% of patients with M-HES, a unique genetic marker, fip1-like1/platelet-derived growth factor receptor α (FIP1L1-PDGFRA), was identified. It has dramatically changed disease management since imatinib, a tyrosine kinase inhibitor, appeared to be highly effective in these patients with up to 100% of long-term hematological response. L-HES is associated with abnormal T-cell populations secreting excessive amounts of eosinophilopoietic cytokines, mainly interleukin 5 (IL-5). Recently, encouraging results of treatment with monoclonal antibody neutralizing IL-5, mepolizumab, have been published. Corticosteroids remain the first-line therapeutic option for patients who do not have FIP1L1-PDGFRA fusion transcript, but treatment discontinuation leads to the recurrence of eosinophilia. This review reflects the current state of knowledge on the pathogenesis and therapy of HES. The shortcomings of current definitions and classifications are also discussed.