Recent advances in understanding eosinophilia

Abstract

Hypereosinophilia occurs commonly in clinical practice and is usually secondary to some underlying disorder, such as parasitic disease or allergic drug reaction. Less common causes include haematological malignancies, and connective tissue or cutaneous disorders. In cases where diagnostic assessment reveals no underlying disease associated with hypereosinophilia, consideration is given to the hypereosinophilic syndrome (HES), a heterogenous group of eosinophilic disorders associated with high-grade peripheral eosinophilia (≥1500 eosinophils/mm3) usually accompanied by end organ damage/dysfunction. Advances in our understanding of the complex pathobiology of eosinophilic disorders have led to insights into the molecular basis of HES variants that make up the syndrome. These insights have led to treatment breakthroughs including molecularly targeted therapies for FIP1L1/PDGFRα-positive HES. Other specific molecular associations are now also recognised. Advances in our understanding of the pathobiology of HES have also led to increasing recognition of the pivotal role that the cytokine IL-5 plays in eosinophilopoiesis, eosinophil activation and eosinophil survival. First line treatments (i.e., corticosteroids, hydroxyurea, IFN-α, imatinib) have demonstrated efficacy in the different types of HES. The emergence of new anti-IL-5 monoclonal antibodies (reslizumab, mepolizumab) with the ability to directly target IL-5 represent a promising approach to HES treatment and these new therapies mark an important step in targeted therapy to prevent eosinophil organ tissue infiltration and damage. The full potential of these agents and their respective place needs to be further assessed. Hypereosinophilia occurs commonly in clinical practice and is usually secondary to some underlying disorder, such as parasitic disease or allergic drug reaction. Less common causes include haematological malignancies, and connective tissue or cutaneous disorders. In cases where diagnostic assessment reveals no underlying disease associated with hypereosinophilia, consideration is given to the hypereosinophilic syndrome (HES), a heterogenous group of eosinophilic disorders associated with high-grade peripheral eosinophilia (≥1500 eosinophils/mm3) usually accompanied by end organ damage/dysfunction. Advances in our understanding of the complex pathobiology of eosinophilic disorders have led to insights into the molecular basis of HES variants that make up the syndrome. These insights have led to treatment breakthroughs including molecularly targeted therapies for FIP1L1/PDGFRα-positive HES. Other specific molecular associations are now also recognised. Advances in our understanding of the pathobiology of HES have also led to increasing recognition of the pivotal role that the cytokine IL-5 plays in eosinophilopoiesis, eosinophil activation and eosinophil survival. First line treatments (i.e., corticosteroids, hydroxyurea, IFN-α, imatinib) have demonstrated efficacy in the different types of HES. The emergence of new anti-IL-5 monoclonal antibodies (reslizumab, mepolizumab) with the ability to directly target IL-5 represent a promising approach to HES treatment and these new therapies mark an important step in targeted therapy to prevent eosinophil organ tissue infiltration and damage. The full potential of these agents and their respective place needs to be further assessed.