Explore the vast range of titles available.

Benralizumab, an interleukin-5 receptor blocker, significantly reduced absolute eosinophil counts and relieved symptoms in a small group of patients with hypereosinophilic syndrome. Adverse events were similar in the benralizumab group and the placebo group.

The hypereosinophilic syndrome, although uncommon, is difficult to treat, and the treatment has substantial toxic effects. This proof-of concept trial shows that treatment of patients with the hypereosinophilic syndrome with an anti–interleukin-5 monoclonal antibody, mepolizumab, improves clinical and laboratory outcomes. This proof-of concept trial shows that treatment of patients with the hypereosinophilic syndrome with an anti–interleukin-5 monoclonal antibody, mepolizumab, improves clinical and laboratory outcomes. The hypereosinophilic syndrome consists of several heterogeneous disorders characterized by sustained blood eosinophilia and eosinophil-related end-organ damage, with no identifiable cause, such as parasitic infection. 1 The objective of treatment is long-term reduction of blood and tissue eosinophil levels to prevent end-organ damage and thromboembolic events. Except for the myeloproliferative variant of the hypereosinophilic syndrome (associated with the Fip1-like 1–platelet-derived growth factor receptor α fusion gene [ FIP1L1–PDGFRA ]), for which imatinib mesylate is considered first-line therapy, current management is based on long-term systemic corticosteroids. 1 – 4 Eosinophil development from hematopoietic progenitors is regulated mainly by interleukin-5, 5 which has a selective role . . .

Current standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496). In the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/μL at screening and ≥4 weeks' stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This , descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo. Mepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32-96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3-31.4%) than placebo (35.7-74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22-0.68 vs 1.14-1.62). The proportion of patients who experienced ≥1 flare during Weeks 20-32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55-85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group. Patients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy. (https://clinicaltrials.gov/ct2/show/NCT02836496).

Hypereosinophilic syndromes are rare in children. Sporadic, mild-severity FIP1L1-platelet-derived growth factor receptor α (PDGFRα) rearrangement cases have been reported, mainly in boys. We present the case of a 5-year-old girl referred from her African country of birth, due to severe constitutional symptoms, multifocal bone pain, headache, gastrointestinal complaints, cardiomyopathy and unexplained hypereosinophilia. She presented multiple end-organ diseases and striking bone involvement. Although she had a positive serology for Strongyloides stercoralis, extensive evaluation detected a FIP1L1-PDGFRA fusion gene. Systemic corticosteroids and low-dose imatinib were started and the child became asymptomatic. After 9 months of treatment, FIP1L1-PDGFRA was no longer detected.

With cell-by-cell mapping, we charted immune cells in lymphocytic-variant hypereosinophilic syndrome, found drug targets, and showed targeted therapy removed disease-causing cells and eased symptoms.With cell-by-cell mapping, we charted immune cells in lymphocytic-variant hypereosinophilic syndrome, found drug targets, and showed targeted therapy removed disease-causing cells and eased symptoms.

Overlap between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (\"rhupus\") is recognized, but coexistence with a severe eosinophilic asthma syndrome is exceptionally rare. We describe a triple autoimmune overlap of RA, SLE, and hypereosinophilic asthma with systemic manifestations (HASM), initially managed as ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) and subsequently re-classified in light of evolving concepts. A 44-year-old woman with a 10-year history of seropositive RA developed alopecia, Coombs-positive hemolytic anemia, hypocomplementemia, and ANA and anti-Sm positivity, fulfilling SLE criteria. While receiving prednisone, hydroxychloroquine and conventional DMARDs, she subsequently developed adult-onset asthma, chronic rhinosinusitis with nasal polyps, and marked hypereosinophilia (>3.5×10 /L). Secondary causes were excluded; bone marrow showed reactive eosinophilia and ANCA (indirect immunofluorescence and ELISA for MPO/PR3) remained negative. She was diagnosed and treated as ANCA-negative EGPA with high-dose glucocorticoids plus methotrexate and hydroxychloroquine, leading to rapid normalization of eosinophils and durable remission of asthma and sinus disease. In retrospect, and according to the ERS/GERM'O'P proposal, this eosinophilic disorder is best classified as HASM within the EGPA-hypereosinophilic spectrum because ANCA and biopsy-proven vasculitis were absent. The case illustrates the evolving boundary between EGPA and hypereosinophilic syndromes and extends the concept of rhupus to include an EGPA-spectrum eosinophilic asthma syndrome. New-onset eosinophilic asthma in patients with established rheumatic disease should prompt evaluation for EGPA-spectrum or hypereosinophilic disorders. Even when the final label is HASM rather than definite EGPA, timely institution of EGPA-type immunosuppression may avert organ damage.

Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients’ association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges.

Hypereosinophilic syndrome (HES) is a rare condition characterized by elevated eosinophil levels and related symptoms of eosinophil-mediated organ damage. We reviewed the effectiveness and safety of mepolizumab for the treatment of HES. A scoping review was conducted following the PRISMA Scoping Reviews Checklist to identify real-world evidence of mepolizumab use in HES. In total, 36 references were identified as relevant and selected for review. Overall, 105 patients previously treated with glucocorticoids received mepolizumab at different dosages (range: 100–750 mg), routes of administration (subcutaneous/intravenous), and schedules (every 2–12 weeks). Remission rates were 57.1–76.0%. Most studies reported a range of 71.4–99.1% reduction in mean blood eosinophil counts with mepolizumab treatment. In addition, a glucocorticoid-sparing effect was observed; 85.7% of patients discontinued glucocorticoids after 12 months of mepolizumab administration. Mepolizumab was considered safe and well-tolerated and severe adverse events were rare. Mepolizumab provided clinically significant benefits in patients with HES in a real-world setting.

Idiopathic hypereosinophilia (IHE) and hypereosinophilic syndrome (HES) are benign haematological disorders. Studies have suggested that venous thromboembolism (VTE) is a rare but sometimes fatal complication of hypereosinophilia; however, data are limited. We retrospectively analysed clinical features and short-term outcomes of 63 consecutive patients (82.5% men; mean age, 40.92 ± 10.89 years) with IHE or HES with concurrent VTE from January 1998 through December 2018. Risk factors for pulmonary embolism (PE) were explored by multivariate logistic analysis. DVT and/or PE was detected by imaging in all patients. Independent risk factors for PE were a body mass index of >24.1 kg/m 2 (odds ratio [OR]: 5.62, 95% confidence interval [CI]: 1.21–26.13, P = 0.028), peak absolute eosinophil count of >6.3 × 10 9 /L (OR: 5.55, 95% CI: 1.292–23.875, P = 0.021), and >13.9-month duration of hypereosinophilia (OR: 4.51, 95% CI: 1.123–18.09, P = 0.034). All patients were treated with corticosteroids and anticoagulants. The short-term hypereosinophilia remission rate was 100%; no recurrent VTE or major bleeding was observed. Hypereosinophilia is a potential risk factor for VTE. PE in patients with IHE/HES and DVT is associated with a higher body mass index, higher peak absolute eosinophil count, and longer duration of hypereosinophilia. Corticosteroids and anticoagulants provided effective short-term control of hypereosinophilia and VTE.

Interleukin-5 (IL-5) is a central regulator of eosinophil differentiation, maturation, survival, activation, and mobilization, and it contributes to eosinophil recruitment to inflamed tissues. These biological functions have made the IL-5/IL-5 receptor alpha (IL-5Rα) pathway a key therapeutic target in eosinophil-associated diseases. Four biologics currently target this pathway in clinical practice: mepolizumab, reslizumab, and depemokimab bind soluble IL-5, whereas benralizumab targets IL-5Rα and induces antibody-dependent cellular cytotoxicity. Clinical development has been successful in severe eosinophilic asthma (SEA), where targeting the IL-5/IL-5Rα pathway reduces exacerbation risk and can lower the need for long-term oral corticosteroid use. The therapeutic scope has since expanded to chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and idiopathic hypereosinophilic syndrome (iHES). Mepolizumab has shown efficacy across these eosinophilia-associated diseases, reducing asthma exacerbations, nasal polyp burden, EGPA relapse activity, HES flares, and eosinophils in peripheral blood. Mepolizumab is approved by both FDA and EMA for SEA, CRSwNP, EGPA, and HES. Reslizumab improves exacerbation rates and lung function in SEA and is approved by FDA and EMA for this indication. Benralizumab produces rapid and near-complete blood and tissue eosinophil depletion, reduces exacerbation rates and oral corticosteroid use in SEA, and has demonstrated sustained remissions and corticosteroid-sparing efficacy in EGPA; it is approved by FDA and EMA for SEA and EGPA. Depemokimab extends IL-5 inhibition through a long-acting, twice-yearly dosing strategy, reduces exacerbation rates in SEA, and improves nasal polyp burden in CRSwNP; it is approved by FDA and EMA for SEA and by EMA for CRSwNP. Safety data from randomized trials, extension studies, real-world cohorts, and meta-analyses are generally reassuring, with most adverse events being mild to moderate and no consistent major safety signal. This review synthesizes current understanding of IL-5 biology, critically evaluates the clinical trial evidence for IL-5/IL-5Ra-targeted biologics across major eosinophilia-associated diseases, and highlights remaining evidence gaps and future directions.