The hypereosinophilic syndromes: current concepts and treatments.
The hypereosinophilic syndromes (HES) encompass a spectrum of diseases that have increased blood eosinophils and tissue damage in common. The clinical manifestations are protean and may involve any organ system, but especially the skin. Our understanding of these diseases has drastically changed over the past 15 years, along with new classifications that characterize patients with marked eosinophilia. One HES variant, myeloproliferative, is actually chronic eosinophilic leukaemia with a unique genetic marker, FIP1L1-PDGFRA. Such patients are well-controlled by administration of the kinase inhibitor, imatinib, and remissions appear durable with continued imatinib therapy. FIP1L1-PDGFRA is expressed in several cell lineages, thus explaining increases in neutrophils and mast cells in HES. The lymphocytic HES variant is associated with T-cell clones producing interleukin-5 (IL-5) and can evolve into lymphoma. While myeloproliferative and lymphocytic HES are well established and permit elimination of the term, idiopathic, to these varieties, most HES patients do not fall into these categories and are classified as complex (using the 2006 Workshop Report). A recent study showed that a monoclonal antibody to IL-5, mepolizumab, reduced glucocorticoid therapy in HES patients who did not possess the FIP1L1-PDGFRA mutation while controlling eosinophilia and preventing recurrence or progression of tissue damage. These advances augur well for continued progress in the understanding and treatment of HES.
Gleich
Gerald J
GJ
Departments of Dermatology and Medicine, The Health Sciences Center, School of Medicine, University of Utah, Salt Lake City, UT 84103, USA. gerald.gleich@hsc.utah.edu
Leiferman
Kristin M
KM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002999:Clone Cells; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy; D000068877:Imatinib Mesylate; D008297:Male; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
D000970:Antineoplastic Agents; D001549:Benzamides; D005938:Glucocorticoids; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha