Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field

Abstract

Eosinophils and their products play an essential role in the pathogenesis of various reactive and neoplastic disorders. Depending on the underlying disease, molecular defect and involved cytokines, hypereosinophilia may develop and may lead to organ damage. In other patients, persistent eosinophilia is accompanied by typical clinical findings, but the causative role and impact of eosinophilia remain uncertain. For patients with eosinophil-mediated organ pathology, early therapeutic intervention with agents reducing eosinophil counts can be effective in limiting or preventing irreversible organ damage. Therefore, it is important to approach eosinophil disorders and related syndromes early by using established criteria, to perform all appropriate staging investigations, and to search for molecular targets of therapy. In this article, we review current concepts in the pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in neoplastic and non-neoplastic conditions. In addition, we discuss classifications of eosinophil disorders and related syndromes as well as diagnostic algorithms and standard treatment for various eosinophil-related disorders.

Keywords::

• classification
• eosinophilic leukemia
• FIP1L1-PDGFRA
• hypereosinophilia
• hypereosinophilic syndromes
• targeted therapy

Financial & competing interests disclosure

P Valent has received a Research Grant from Novartis and a Research Grant from BMS, as well as honoraria from Novartis and BMS. AD Klein is supported by the Intramural Program of the NIAID, NIH. KM Leiferman, HU Simon and GJ Gleich have been supported by grants from GSK. M Arock received honorarium from Novartis. P Vandenberghe is a Senior Clinical Investigator of FWO-Vlaanderen. T Haferlach is part owner of the Munich Leukemia Laboratory. A Reiter received Honoraria from Novartis and BMS. BS Bochner is a co-author on existing and pending Siglec-8-related patents. If Siglec-8-related products are developed in the future, BS Bochner may be entitled to a share of royalties received by Johns Hopkins University on the potential sales of such products. The terms of this arrangement are being managed by Johns Hopkins University in accordance with its conflict of interest policies. This study was supported by a research grant of the Medical University of Vienna and by the Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

^† In most cases, eosinophilia may be triggered by eosinopoietic cytokines.

^‡ In most patients, eosinophils are clonal cells (neoplastic eosinophils).

^§ Eosinophilia often develops in patients with ASM, but may also occur in patients with indolent systemic mastocytosis.

AML: Acute myeloid leukemia; ASM: Aggressive systemic mastocytosis; CML: Chronic myeloid leukemia; HE: Hypereosinophilia; HEUS: Hypereosinophilia of undetermined (unknown) significance; IBD: Inflammatory bowel disease; L-HES: Lymphoid variant of hypereosinophilic syndrome; MDS: Myelodysplastic syndrome; MPN: Myeloproliferative neoplasm; NOS: Not otherwise specified.