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.