The criteria for the diagnosis of hypereosinophilic syndrome (HES) are:
- blood eosinophilia equal to or exceeding 1.5 × 109/L, usually for a period of greater than 6 consecutive months
- no underlying cause of eosinophilia, such as parasitic infection
- evidence of eosinophil-mediated organ damage
The principal target organs in HIES are the heart, skin, and nervous system. Intracavitary thrombi might develop on damaged endocardium and disseminate throughout the circulatory system. Prognosis in HES is variable; it can be asymptomatic or progress rapidly to heart failure or acute leukemia.
A group of patients have a mutation involving the PDGFRA and FIP1L1 genes leading to a tyrosine kinase fusion protein. PDGFRA (Platelet-derived growth factor receptor, alpha polypeptide) gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family.
The presence FIP1L1/PDGFRA mutation of indicates response to imatinib (Gleevec), a tyrosine kinase inhibitor.
Imatinib. Image source: Wikipedia, public domain.
In this case report published in JACI, a 56-year-old woman with FIP1L1/PDGFRA-negative hypereosinophilic syndrome was treated with alemtuzumab, an anti-CD52 antibody. The patient had aortic valve vegetations and microinfarcts throughout the brain. Imatinib mesylate (Gleevec) for 3 weeks was associated with increased eosinophil levels. Prednisone and hydroxyurea decreased eosinophilia; she was later switched to IFN-α. Mepolizumab (humanized anti–IL-5) was also associated with increased eosinophil levels.
Because of the side effects from IFN-α and the incomplete control of eosinophilia, alemtuzumab (CamPath), a humanized anti-CD52 antibody, was started.
Structure of the therapeutic antibody Alemtuzumab in complex with a synthetic peptide antigen. Image source: Wikipedia, public domain.
Alemtuzumab sharply reduced eosinophil counts to normal levels. Lymphopenia developed as a result of alemtuzumab treatment,
Infusion reactions were treated successfully with Benadryl and Decadron. The patient died after 2 years.
CD52 is a glycosylphosphatidylinositol-anchored molecule expressed on human eosinophils, lymphocytes, macrophages, and monocytes but not on neutrophils. Alemtuzumab is approved for the treatment of B-cell chronic lymphocytic leukemia (CLL) and is also used to treat small lymphocytic lymphoma and mantle cell lymphoma in conjunction with other treatments.
Treatment of FIP1L1/PDGFRA-negative hypereosinophilic syndrome with alemtuzumab, an anti-CD52 antibody. Lori A. Wagner et al. JACI, Volume 123, Issue 6, Pages 1407-1408 (June 2009).
Images source: Eosinophil, Wikipedia, a free GNU license.