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After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ\u2010hybridization, flow immunophenotyping, and T\u2010cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk stratification<\/jats:title><jats:p>Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi\u2010molecular classification scheme of disease subtypes. This includes the major category \u201cmyeloid\/lymphoid neoplasms with eosinophilia and rearrangement of <jats:italic>PDGFRA<\/jats:italic>, <jats:italic>PDGFRB<\/jats:italic>, or <jats:italic>FGFR1<\/jats:italic> or with <jats:italic>PCM1\u2010JAK2<\/jats:italic>\u201d, and the MPN subtype, \u201cchronic eosinophilic leukemia, not otherwise specified\u201d (CEL, NOS). Lymphocyte\u2010variant hypereosinophilia is an aberrant T\u2010cell clone\u2010driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk\u2010adapted therapy<\/jats:title><jats:p>The goal of therapy is to mitigate eosinophil\u2010mediated organ damage. For patients with milder forms of eosinophilia (eg, &lt;1.5\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L) without symptoms or signs of organ involvement, a watch and wait approach with close\u2010follow\u2010up may be undertaken. Identification of rearranged <jats:italic>PDGFRA<\/jats:italic> or <jats:italic>PDGFRB<\/jats:italic> is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first\u2010line therapy for patients with lymphocyte\u2010variant hypereosinophilia and HES. Hydroxyurea and interferon\u2010alfa have demonstrated efficacy as initial treatment and in steroid\u2010refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. The use of antibodies against interleukin\u20105 (IL\u20105) (mepolizumab), the IL\u20105 receptor (benralizumab), as well as other targets on eosinophils remains an active area of investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.25617","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:44:15Z","timestamp":1566197055000},"page":"1149-1167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":169,"title":["World Health Organization\u2010defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6500-350X","authenticated-orcid":false,"given":"William","family":"Shomali","sequence":"first","affiliation":[{"name":"Division of Hematology Stanford Cancer Institute\/Stanford University School of Medicine  Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gotlib","sequence":"additional","affiliation":[{"name":"Division of Hematology Stanford Cancer Institute\/Stanford University School of Medicine  Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.03.035"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-97-1-78"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.09.022"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.287"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-050054"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0787"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2005.11.011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(87)80352-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200301000-00017"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000193467.06938.77"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025217"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11420"},{"key":"e_1_2_8_14_1","first-page":"963","article-title":"Eosinophilia detected by automated blood cell counting in ambulatory North American outpatients. 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