The Journal of Allergy and Clinical Immunology
Volume 124, Issue 6 , Pages 1319-1325.e3 , December 2009

Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy

  • Princess U. Ogbogu, MD

      Affiliations

    • National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Md
    • ,
  • Bruce S. Bochner, MD

      Affiliations

    • Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
    • ,
  • Joseph H. Butterfield, MD

      Affiliations

    • Division of Allergic Diseases, Mayo Clinic, Rochester, Minn
    • ,
  • Gerald J. Gleich, MD

      Affiliations

    • Department of Medicine, University of Utah, Salt Lake City, Utah
    • ,
  • Johannes Huss-Marp, MD

      Affiliations

    • ZAUM—Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Center Munich/Technische Universität München, Munich, Germany
    • Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany
    • ,
  • Jean Emmanuel Kahn, MD

      Affiliations

    • Department of Internal Medicine, Hôpital Foch, Suresnes, France
    • French Eosinophil Network, Department of Immunology, CHRU de Lille, Lille, France
    • ,
  • Kristin M. Leiferman, MD

      Affiliations

    • Department of Dermatology, University of Utah, Salt Lake City, Utah
    • ,
  • Thomas B. Nutman, MD

      Affiliations

    • National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Md
    • ,
  • Florian Pfab, MD

      Affiliations

    • ZAUM—Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Center Munich/Technische Universität München, Munich, Germany
    • Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany
    • ,
  • Johannes Ring, MD

      Affiliations

    • Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany
    • ,
  • Marc E. Rothenberg, MD, PhD

      Affiliations

    • Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    • ,
  • Florence Roufosse, MD

      Affiliations

    • Département de Médecine Interne, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
    • Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium
    • ,
  • Marie-Helene Sajous, MD

      Affiliations

    • Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
    • ,
  • Javed Sheikh, MD

      Affiliations

    • Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
    • ,
  • Dagmar Simon, MD

      Affiliations

    • Department of Dermatology, Inselspital, Bern, Switzerland
    • ,
  • Hans-Uwe Simon, MD, PhD

      Affiliations

    • Institute of Pharmacology, University of Bern, Bern, Switzerland
    • ,
  • Miguel L. Stein, MD

      Affiliations

    • Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    • ,
  • Andrew Wardlaw, MD

      Affiliations

    • Institute for Lung Health, University of Leicester, Leicester, United Kingdom
    • ,
  • Peter F. Weller, MD

      Affiliations

    • Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
    • ,
  • Amy D. Klion, MD

      Affiliations

    • National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Md
    • Corresponding Author InformationReprint requests: Amy D. Klion, MD, Bldg 50, Rm 6351, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD 20892.

Received 13 May 2009 ,Revised 26 August 2009 ,Accepted 3 September 2009.

References 

  1. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). 1975;54:1–27
  2. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. 1994;83:2759–2779
  3. Simon HU, Plotz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med. 1999;341:1112–1120
  4. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, et al. A novel tyrosine kinase created by the fusion of the PDGFRA and FIP1L1 genes is a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201–1214
  5. Klion AD, Noel P, Akin C, Law MA, Gilliland DG, Cools J, et al. Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis and imatinib-responsiveness. Blood. 2003;101:4660–4666
  6. Klion AD, Bochner BS, Gleich GJ, Nutman TB, Rothenberg ME, Simon HU, et al. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol. 2006;117:1292–1302
  7. Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008;358:1215–1228
  8. Roufosse F, Cogan E, Goldman M. Lymphocytic variant hypereosinophilic syndromes. Immunol Allergy Clin North Am. 2007;27:389–413
  9. Simon HU, Cools J. Novel approaches to therapy of hypereosinophilic syndromes. Immunol Allergy Clin North Am. 2007;27:519–527
  10. Bush RK, Geller M, Busse WW, Flaherty DK, Dickie HA. Response to corticosteroids in the hypereosinophilic syndrome: association with increased serum IgE levels. Arch Intern Med. 1978;138:1244–1246
  11. de Lavareille A, Roufosse F, Schmid-Grendelmeier P, Roumier AS, Schandene L, Cogan E, et al. High serum thymus and activation-regulated chemokine levels in the lymphocytic variant of the hypereosinophilic syndrome. J Allergy Clin Immunol. 2002;110:476–479
  12. Simon D, Salemi S, Yousefi S, Simon HU. Primary resistance to imatinib in Fip1-like 1-platelet-derived growth factor receptor alpha-positive eosinophilic leukemia. J Allergy Clin Immunol. 2008;121:1054–1056
  13. Stein ML, Villanueva JM, Buckmeier BK, Yamada Y, Filipovich AH, Assa'ad AH, et al. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008;121:1473–1483
  14. Pardanani A, Brockman SR, Paternoster SF, Flynn HC, Ketterling RP, Lasho TL, et al. FIP1L1/PDGFRA fusion: prevalence and clinicopathologic correlates in 89 patients with moderate to severe eosinophilia. Blood. 2004;104:3038–3045
  15. Vaklavas C, Tefferi A, Butterfield J, Ketterling RP, Vertovsek S, Kantarjian H, et al. Idiopathic" eosinophilia with an Occult T-cell clone: prevalence and clinical course. Leuk Res. 2007;31:691–694
  16. Roche-Lestienne C, Lepers S, Soenen-Cornu V, Kahn JE, Lai JL, Hachulla E, et al. Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics. Leukemia. 2005;19:792–798
  17. Klion AD, Law MA, Noel P, Haverty TP, Nutman TB. Safety and efficacy of the monoclonal anti-interleukin 5 antibody, SCH55700, in the treatment of patients with the hypereosinophilic syndrome. Blood. 2004;103:2939–2941

 Supported by the Division of Intramural Research of the NIAID/NIH (A.D.K., P.U.O., T.B.N.), grants AI41472 and AI72265 from the NIH (B.S.B.), grant AI061097 from the NIH (G.J.G.), the Human Immunology grant program of the Dana Foundation (B.S.B.), the Swiss National Science Foundation (H.-U.S.), the Belgian National Fund for Scientific Research (F.R.), and the Campaign Urging Research for Eosinophilic Disorders (M.E.R.). B.S.B. is a Cosner Scholar in Translational Research from Johns Hopkins University. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation or review of the manuscript. The manuscript was approved by the Division of Intramural Research, NIAID/NIH.

 Disclosure of potential conflict of interest: G. J. Gleich and K. M. Leiferman have equity in Ception, have received research support from GlaxoSmithKline, and are on the advisory board for APFE. J. E. Kahn has received consulting fees and research support from GlaxoSmithKline. T. B. Nutman is a stockholder in Johnson & Johnson and is employed by the National Institutes of Health. J. Ring has received research support from Novartis, Schering-Plough, Fujisawa, GlaxoSmithKline, Bencard, Stallergenes, ALK-Abelló, Allergopharma, Pharmacia, DPC Biermann, Aventis, Almirall, Leo, Galderma, and Switch Biotech. M. E. Rothenberg is a speaker and consultant for Merck; is a consultant for Ception Therapeutics, Novartis, Nycomed, and Centocor; has received research support from the National Institutes of Health, FAAN, and the Dana Foundation; is on the Medical Advisory Board for APFED; and is on the Executive Council for the International Eosinophil Society. F. Roufosse has received consulting fees from GlaxoSmithKline. J. Sheikh is on the speakers' bureau for Alcon, Meda, Sanofi-Aventis, and UBC; is a consultant for and is on the Advisory Board for Zeer.com; has received research support from GlaxoSmithKline; has been a legal consultant on the topics of allergy/immunology medical malpractice and latex allergy; is a member of the ACAAI; and is on the Executive Board of the Massachusetts Allergy Society (Secretary) and the New England Society of Allergy (CME Director). H.-U. Simon has received consulting fees from Pfizer, has received honoraria from Merck, and has received research support from the Swiss National Science Foundation, GlaxoSmithKline, and AstraZeneca. A. Wardlaw has received honoraria and research support from GlaxoSmithKline. P. F. Weller has served as a consultant for GlaxoSmithKline and has received research support from Merck. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)01410-9

doi: 10.1016/j.jaci.2009.09.022

The Journal of Allergy and Clinical Immunology
Volume 124, Issue 6 , Pages 1319-1325.e3 , December 2009

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