Molecular Pathogenesis and Treatment Perspectives for Hypereosinophilia and Hypereosinophilic Syndromes

Abstract

Hypereosinophilia (HE) is a heterogeneous condition with a persistent elevated eosinophil count of >350/mm3, which is reported in various (inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. HE may be associated with tissue or organ damage and, in this case, the disorder is classified as hypereosinophilic syndrome (HES). Different studies have allowed for the discovery of two major pathogenetic variants known as myeloid or lymphocytic HES. With the advent of molecular genetic analyses, such as T-cell receptor gene rearrangement assays and Next Generation Sequencing, it is possible to better characterize these syndromes and establish which patients will benefit from pharmacological targeted therapy. In this review, we highlight the molecular alterations that are involved in the pathogenesis of eosinophil disorders and revise possible therapeutic approaches, either implemented in clinical practice or currently under investigation in clinical trials.

Clinical analysis of hypereosinophilic syndrome first presenting with asthma-like symptoms

“…Regardless of the cause of HES, the purpose of therapy is to reduce the EOS count and EOS-mediated organ dysfunction. The main therapeutic options for HES patients can be divided into five groups: corticosteroids; cytotoxic agents; tyrosine kinase inhibitors (TKIs); monoclonal antibodies; and chemotherapy [ 25 ] .Corticosteroids can be used as first-line therapy in patients with strictly defined HES, and the recommended dose is prednisone 1 mg/kg/day [ 26 ] .With the control of symptoms and a decrease in EOS count <1.5 × 10 9 /L, the dose of prednisone can be gradually reduced [ 27 ]. However, secondary HES should be treated according to the primary aetiology, and individualised treatment should be provided for vital organ involvement.…”

“…Repeated symptoms, signs of organ damage, and/or a significant increase in EOS at prednisone >10 mg/day indicate that treatment should be combined with other immunosuppressive therapies [ 27 ]. Hydroxyurea can be used as a first-line drug or in combination in steroid-insensitive patients, while interferon-α is usually used as a second-line agent after steroid treatment failure [ 26 ]. In recent years, TKIs have been applied to treat HES, which mainly depends on the aetiology and subtype and has strict indications.…”

“…In addition, case reports have found that alemtuzumab (anti-CD52 monoclonal antibody) had a certain effect on refractory HES [ 31 ]. In addition, anti-IL-5 and anti-IL-5 receptors for HES treatment are still in the research stage, and several drugs have reached phase 2 and phase 3 trials [ 26 ]. Idiopathic HES is not only an exclusive but also a temporary diagnosis.…”

Mepolizumab in Hypereosinophilic Syndrome: A Systematic Review and Meta-analysis

“…These syndromes are associated with excessive production of cytokines, such as IL-3, IL-5, and the macrophage granulocyte colony-stimulating factor (GM-CSF), which in turn promote the maturation and survival of eosinophils, while inhibiting their apoptosis. IL-5 is the most important factor for this process; however, its binding and action can be inhibited by the use of anti-IL-5 to reduce eosinophilia (6).…”

Steroid resistant hypereosinophilic syndrome found to be Hodgkin’s Lymphoma

“…[2] Others simply define it as hypereosinophilia with tissue or organ damage or as hypereosinophilia (HE) present for six months with presumptive tissue damage. [2,3] HES is distinguished from simple HE, which is characterized by AEC greater than 1,500 cells/µl without end-organ damage. [4] The clinical manifestations of this condition are highly variable, ranging from asymptomatic eosinophilia to end-organ failure.…”