[Diagnosis of non-parasitic hypereosinophilia]

Diagnosis of major hypereosinophilia (>1500 x 10(9)/L) is complex because the possible causes cover the entire range of medical specialties. History and clinical condition will usually suggest parasitic or allergic diseases or drug reactions. When workups for them are negative, rarer causes must be suspected: specific organ diseases (chronic eosinophilic pneumonia, bullous pemphigoid, etc.), solid tumor, clonal blood disorders, or vasculitis. When the condition is prolonged and unexplained, hypereosinophilic syndrome is diagnosed. A rare disorder, its prognosis depends on largely on its cardiac effects. It is usually associated with heterogeneous hematologic conditions, mainly myeloproliferative and lymphocytic disease. The myeloproliferative or primary variant sometimes follows chromosomal deletions that cause a fusion between the Fip1-like1 (FIP1L1) and platelet-derived growth factor receptor (PDGFR) genes, thus increasing the tyrosine kinase activity of the latter. Imatinib mesylate, a tyrosine kinase inhibitor, is usually effective in this situation. In the lymphocytic variant, hypereosinophilia is secondary to a primitive Th2 lymphocyte expansion that causes overproduction of interleukin 5 (IL-5). Corticosteroids are the first-line therapy. Mepolizumab, an anti-IL-5 monoclonal antibody, currently being evaluated, seems promising. Despite recent progress, about 40% of the cases of hypereosinophilic syndrome remain unexplained.