ICON: Eosinophil Disorders The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Valent, P., A. D. Klion, L. J. Rosenwasser, M. Arock, B. S. Bochner, J. H. Butterfield, J. Gotlib, et al. 2012. “ICON: Eosinophil Disorders.” The World Allergy Organization Journal 5 (12): 174-181. doi:10.1097/WOX.0b013e31827f4192. http://dx.doi.org/10.1097/ WOX.0b013e31827f4192. Published Version doi:10.1097/WOX.0b013e31827f4192 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717517 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA CONSENSUS DOCUMENT ICON: Eosinophil Disorders Peter Valent, MD,1 Amy D. Klion, MD,2 Lanny J. Rosenwasser, MD,3 Michel Arock, PharmD, PhD,4 Bruce S. Bochner, MD,5 Joseph H. Butterfield, MD,6 Jason Gotlib, MD,7 Torsten Haferlach, MD,8 Andrzej Hellmann, MD,9 Hans-Peter Horny, MD,10 Kristin M. Leiferman, MD,11 Georgia Metzgeroth, MD,12 Kenji Matsumoto, MD, PhD,13 Andreas Reiter, MD,12 Florence Roufosse, MD, PhD,14 Marc E. Rothenberg, MD, PhD,15 Hans-Uwe Simon, MD, PhD,16 Karl Sotlar, MD,9 Peter Vandenberghe, MD, PhD,17 Peter F. Weller, MD,18 and Gerald J. Gleich, MD11,19 Key Words: eosinophil disorders, hypereosinophilic syndrome Several different neoplastic, paraneoplastic, infectious, and aller- (HES), global consensus, classification gic disorders may underlie HE. Eosinophil-induced organ dam- age with more or less typical symptoms may develop in these (WAO Journal 2012; 5:174–181) patients. The final diagnosis is based on clinical, molecular, and histopathologic criteria, and the presence of signs and symptoms indicative of HE-induced organ damage, the latter often mani- SUMMARY festing as hypereosinophilic syndrome. The clinical course, Eosinophil disorders and related syndromes are a hetero- prognosis, and response to certain drugs vary greatly among geneous group of conditions characterized by marked persistent patients and among disease variants. During the last few years, blood eosinophilia and involvement of one or more organ several new markers and targets have been identified, improving systems. The hypereosinophilic (HE) state is defined by diagnosis, prognostication, and therapy for patients with HE- a persistent eosinophil count exceeding 1.5 · 109/L blood. related disorders. Moreover, several attempts have been made to establish robust disease-related criteria and a global classi- From the 1Department of Medicine I, Division of Hematology & Hemos- fication for HE-related diseases. However, the pathogenesis taseology, Medical University of Vienna, Austria; 2Eosinophil Pathol- ogy Unit, Laboratory of Parasitic Diseases, NIH/NIAID, Bethesda, and mechanisms of HE and of HE-induced organ damage MD; 3Children’s Mercy Hospital, Kansas City, MO; 4LBPA CNRS are complex, and expert opinions remain divided. UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France; In light of the increasing burden of allergic diseases, the 5Department of Medicine, Division of Allergy and Clinical Immunol- World Allergy Organization; the American Academy of ogy, Johns Hopkins University School of Medicine, Baltimore, MD; 6 7 Allergy, Asthma & Immunology; the European Academy of Division of Allergic Diseases, Mayo Clinic, Rochester, MN; Division of Hematology, Stanford Cancer Center, Stanford, CA; 8MLL Münchner Allergy and Clinical Immunology; and the American College Leukämielabor, Munich, Germany; 9Department of Hematology, Medical of Allergy, Asthma & Immunology have come together to University School of Gdansk, Gdansk, Poland; 10Institute of Pathology, increase the communication of information about allergies Ludwig-Maximilians-University, Munich, Germany; 11Department of Der- matology, University of Utah Health Sciences Center, Salt Lake City, UT; and asthma at a global level. Within the framework of this 12III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Hei- collaboration, termed the International Collaboration in delberg, Mannheim, Germany; 13Department of Allergy and Immunology, Asthma, Allergy and Immunology, a series of consensus National Research Institute for Children’s Health and Development, Tokyo, documents called International Consensus ON (ICON) are Japan; 14Department of Internal Medicine, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium; 15Division of Allergy and Immunology, being developed to serve as an important resource and sup- Cincinnati Children’s Hospital, Medical Center, Cincinnati, OH; 16Institute port physicians in managing different allergic diseases. of Pharmacology, University of Bern, Bern, Switzerland; 17Center for This ICON provides an updated proposal for a global Human Genetics, University Hospitals Leuven and Katholieke Universiteit nomenclature and classification of HE-related disorders and Leuven, Leuven, Belgium; 18Department of Medicine, Beth Israel Deaconess 19 conditions. The proposal is based on the currently available Medical Center, Harvard Medical School, Boston, MA; Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT. literature and merges previously published proposals and the Supported in part by the Division of Intramural Research, NIAID, NIH. classification proposal of the World Health Organization. The authors have no conflicts of interest to disclose. The International Collaboration in Asthma and Allergy This article is a product on eosinophil disorders by the iCAALL, an international initiated an international coalition among the American coalition between the World Allergy Organization; American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Academy of Allergy, Asthma & Immunology; European Immunology; and American College of Allergy, Asthma & Immunology. Academy of Allergy and Clinical Immunology; World Correspondence to: Peter Valent, MD, Department of Medicine I, Division of Allergy Organization; and American College of Allergy, Hematology & Hemostaseology, Medical University of Vienna, Austria, Asthma and Immunology on eosinophilic disorders. An Wahringer Gurtel 18-20, Wien A-1090 Austria.Telephone: 143 1 40400 6085. Fax: 143 1 40400 4030. E-mail: [email protected]. author group was formed and then divided into individual Copyright Ó 2012 by World Allergy Organization committees. Within the committee, teams of authors were 174 WAO Journal December 2012 WAO Journal December 2012 ICON: Eosinophil Disorders created to generate content for specific sections of the article. (not just idiopathic) associated with organ damage. Thus, Content was derived from literature searches, relevant pub- HESs can be divided into primary (neoplastic) HES, second- lished guidelines, and clinical experience. After a draft of the ary (reactive) HES, and idiopathic HES.4–9 The ICOG-EO document was assembled, it was collectively reviewed and group recommends that the term HES be reserved for such revised by the authors. Where evidence was lacking or con- clinical syndromes but not for underlying malignancy or auto- flicting, the information presented represents the consensus immune disease associated with eosinophilia.9 In primary expert opinion of the group. (neoplastic) HES or secondary HES, an underlying disease is identified and is included in the final diagnosis, for exam- ple, chronic eosinophilic leukemia (CEL) with primary HES. PROPOSED NOMENCLATURE AND REVIEW OF In contrast, a diagnosis of idiopathic HES implies the absence THE LITERATURE of a known etiology. The published literature was screened for terminolo- Using this nosology, the term HES should be applied to gies, nomenclatures, criteria, classification proposals, and key document and describe syndromes with eosinophil-induced information concerning incidence, prevalence, and prognos- organ damage, irrespective of the presence of an underlying tication of eosinophil disorders. Key publications are refer- etiology. In fact, the diagnosis of HES should prompt fi physicians to investigate and search for underlying mecha- enced. Whenever found, controversies and dif culties in 8,9 nomenclatures and classifications were reviewed and dis- nisms and disorders. In previous WHO classifications, HES cussed. In this way, the current International Consensus ON was sometimes employed as a synonym of CEL and some- (ICON) article attempts to adhere to the principles of previous times to discriminate CEL from other hematologic conditions/ 10–13 (traditional) classifications, including World Health Organi- neoplasms. In the latest edition of the “WHO mono- 12 zation (WHO) criteria for eosinophilia-associated hematopoi- graph,” the term “HES” is not recommended as a synonym etic neoplasms. In addition, a recent proposal of the of WHO-defined neoplasms. This distinction between HES “International Cooperative Working Group on Eosinophil and the underlying disorder is in agreement with the proposal 9 Disorders” (ICOG-EO) was used as the basis for the formu- of the ICON group. lation of the ICON document. The ICOG-EO was established The spectrum of nonneoplastic and neoplastic disorders that can underlie HES is broad, and allergic disorders are often in 2011 as an interdisciplinary network, including representa- – tives from the fields of allergy, immunology, pathology, important considerations in the differential diagnosis.14 23 hematology, infectious