HES and EGPA: Two Sides of the Same Coin

Elevated eosinophil counts are implicated in multiple diseases, from relatively prevalent organ-specific disorders such as severe eosinophilic asthma, to rare multisystem disorders such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA). Patients with these multisystem diseases, often associated with markedly elevated eosinophil counts, have a substantial risk of morbidity and mortality due to delayed diagnosis or inadequate treatment. A thorough workup of symptomatic patients presenting with elevated eosinophil counts is essential, although in some cases the differential diagnosis may remain difficult because of overlapping presentations between HES and EGPA. Notably, first- and second-line treatment options and response to therapy may differ for specific HES and EGPA variants. Oral corticosteroids are the first line of treatment for HES and EGPA, except when HES is the result of specific mutations driving clonal eosinophilia that are amenable to targeted treatment with a kinase inhibitor. Cytotoxic or immunomodulatory agents may be required for those with severe disease. Novel eosinophil-depleting therapies, such as those targeting interleukin 5 or its receptor, have shown great promise in reducing blood eosinophil counts, and reducing disease flares and relapses in patients with HES and EGPA. Such therapies could reduce the side effects associated with long-term oral corticosteroids or immunosuppressant use. This review provides a pragmatic guide to approaching the diagnosis and clinical management of patients with systemic hypereosinophilic disorders. We highlight practical considerations for clinicians and present cases from real-world clinical practice to show the complexity and challenges associated with diagnosing and treating patients with HES and EGPA. & COPY; 2023 THE AUTHORS. Published by Elsevier Inc on behalf of Mayo Foundation for Medical Education and Research. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) & BULL; Mayo Clin Proc. 2023;98(7):1054-1070

Automated summary

Elevated eosinophil counts are associated with various diseases, including severe eosinophilic asthma, hypereosinophilic syndrome (HES), and eosinophilic granulomatosis with polyangiitis (EGPA). Patients with these diseases have a high risk of morbidity and mortality. A comprehensive workup is essential for symptomatic patients, although differential diagnosis between HES and EGPA can be challenging. Treatment options vary for different variants of HES and EGPA, with oral corticosteroids being the first line of treatment. Novel eosinophil-depleting therapies show promise in reducing blood eosinophil counts and disease flares. This review provides a practical guide for diagnosing and managing systemic hypereosinophilic disorders.