Are Various Babesia Species a Missed Cause for Hypereosinophilia? A Follow-up on the First Reported Case of Imatinib Mesylate for Idiopathic Hypereosinophilia

James L. Schaller, MD, MAR; Glenn A. Burkland, DMD; PJ Langhoff


February 27, 2007


In 2001 we reported the first case of use of imatinib mesylate (Gleevec) for treatment of idiopathic hypereosinophilia syndrome (HES).[1]

After 5 years, new information is available about the patient's care. Specifically, it is possible that an emerging complex protozoa infection, babesiosis, is associated with his medical history. On the basis of our experience with this patient, it appears that a diagnosis of babesiosis is not always simple. For example, the number of Babesia species that infect humans has grown from 4 to 10 or more during the last 15 years.[2] Available laboratory testing does not offer species-specific antibody and polymerase chain reaction (PCR) testing for these emerging species. Diagnostic clues for active Babesia, such as anemia, are not actually present in at least one aggressive emerging species (B duncani)[3] (P.A. Conrad, oral communication, October 2006). Some Babesia experts caution that this intracellular parasite might be common.[4,5,6]

As a background, the patient was diagnosed repeatedly with idiopathic HES, an often fatal illness that can damage a wide range of possible organs, including the heart, nervous system, lungs, liver, and kidneys. It is often treated with interferon-alpha and hydroxyurea, and we believe that these medications saved his life. For example, a small cerebral infarction related to his idiopathic HES did not recur over 6 years and his eosinophil counts were moderately controlled (eg, 12% eosinophils) on this combination treatment. However, his eosinophil cationic protein (ECP) was not controlled. (His values were 30-140 ng/mL with < 24 as the reference range.)

His interferon-alpha/hydroxyurea treatment increased or did not remove a profound intractable headache, severe fatigue, irritability, and concentration difficulties. After years on hydroxyurea and interferon-alpha, the severity of this morbidity or side effects motivated us to try a trial of imatinib mesylate. Treatment involved compounded capsules of 25 mg, used in doses between 75 and 100 mg per day, and was followed by an abrupt remission of HES in a few weeks and a normalization of his ECP. He experienced no significant side effects. Over the course of a year, the patient's eosinophil count remained low-normal, and the patient decided on a trial of imatinib mesylate in 25-mg reductions over 3 months. He has not experienced a relapse during the past 5 years.

Since our initial publication, our findings have been repeatedly replicated.[7,8,9,10,11,12,13] In summary, these publications report many patients with HES have a dramatic positive response with imatinib treatment. Yet not all patients with HES respond to imatinib mesylate and not all retain positive responses. The cause of HES is unclear and heterogeneous. Causes for HES include dysregulation of interleukin 5, interleukin 3, and granulocyte-macrophage colony-stimulating factor. Of these cytokines, interleukin 5 appears to have the greatest role in the regulation of eosinophil maturation.[14] The positive effect of imatinib mesylate on HES has been attributed to many mechanisms. These include activated kinase such as Abl, platelet-derived growth factor receptor (PDGFR), KIT, and the novel fusion tyrosine kinase FIP1L1-PDGFRalpha, which is a consequence of an interstitial chromosomal deletion. All of these are inhibited by imatinib.[15] However, no single mechanism seems to explain all patients' positive response.[16]


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