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Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been made in recent years, there are substantial gaps in our understanding of the pathologic mechanisms involved in these diseases, as well as numerous unmet needs relating to both diagnosis and patient management. For example, in most cases of HES, the underlying cause of hypereosinophilia is unknown, while in EGPA, although a polygenic genetic susceptibility has been found, understanding of the pathogenic mechanisms remains largely elusive. Delineating differences between certain disease variants may be challenging, and there are no reliable predictive markers of disease course. In addition, the current diagnostic criteria for HES and classification criteria for EGPA are not easy to implement in a nonspecialist setting, and specialist referral pathways need to be signposted more clearly. Furthermore, disease-specific activity scores need to be developed to aid the assessment of treatment effects, and improved biomarkers are needed to aid with treatment stratification. In this review, we outline the limitations of our current understanding of HES and EGPA and highlight areas for future work, which ultimately should help improve patient management and outcomes., SCOPUS: re.j, info:eu-repo/semantics/published

Background: Hypereosinophilic syndrome (HES) is characterized by persistent elevated blood and/or tissue eosinophil levels and eosinophil-mediated organ damage. Presentation is highly heterogenous; patients may experience symptoms affecting multiple organ systems.Objectives: To assess the effects of mepolizumab, which targets interleukin-5, on HES-related symptom burden, based on HES daily symptoms (HES-DS) questionnaire data collected during the Phase III (ClinicalTrials.gov ID: NCT02836496) study of mepolizumab in patients with HES.Methods: Each of the six HES-related symptoms were rated (0-10) daily by patients, recalling worst symptom experience in the prior 24 hours; change from baseline at Week 32 was also calculated for mepolizumab versus placebo.Results: Mepolizumab versus placebo reduced HES-related symptom burden severity in patients with HES at Week 32. Improvements in the median change from baseline scores were seen across all symptom groups except skin for patients treated with mepolizumab; greatest improvement from baseline was observed for breathing symptoms.Conclusion: These data highlight the considerable symptom burden associated with HES and further support the clinical benefits of mepolizumab treatment for these patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Eosinophil-associated diseases (EADs) are a group of conditions in which eosinophils (a type of white blood cell) are thought to play a key role in the disease and how it develops. Some EADs are common, such as atopic dermatitis (also called eczema) and a subtype of asthma called eosinophilic asthma, while others are rare, such as hypereosinophilic syndrome (a condition in which a person has a very high number of eosinophils in both the blood and one or more organs). People with EADs face many problems related to their conditions. Symptoms such as severe abdominal pain, itch, or shortness of breath impact both the patient as well as their friends and family. Patients with EADs also experience delays to diagnosis and treatment as well as financial barriers. Healthcare professionals sometimes fail to recognize the complex set of symptoms that characterize an EAD, and this may cause delays in reaching a correct diagnosis. As a result, it may take longer for a patient to get the best care and the most effective treatments, which may contribute to poor health. The goal of this charter is to describe the key elements of good quality care, which all people with EADs deserve, as well as to present an action plan to improve health and overall well-being for people with EADs. Proposed use of this patient charter: The principles described in this charter (a written guide to achieve an outcome) show the core elements of quality care that people with EADs must receive. They also describe clear steps to reduce the burden on patients and their caregivers and to improve patient health outcomes. We urge healthcare professionals, hospitals, and policymakers around the world to adopt these principles quickly. By doing this, people with EADs will be more likely to receive an accurate and timely diagnosis and have access to quality care and treatment in the right setting., info:eu-repo/semantics/published

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non-clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials., SCOPUS: re.j, info:eu-repo/semantics/published

Eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) are driven by persistently high eosinophil numbers, causing damage to tissues and organs. As rare diseases, they are often underappreciated by healthcare professionals. Using a social listening analysis, we collected patient and caregiver comments relating to EGPA and HES made on online social platforms between 1 January 2019 and 31 May 2020, in English, French, and German. Results were classified into key areas of interest. In total, 746 comments with consent to publish were collected mentioning EGPA, and 39 were identified mentioning HES. The most common theme was sharing of personal experiences (EGPA: 77%; HES: 100%). Diagnosis, including diagnosis delays and misdiagnosis, was mentioned in 33% of comments for EGPA, and 82% for HES. Other common themes included seeking and giving advice, symptoms, and treatments. These insights highlight the views and unmet needs of people living with EGPA and HES. Further work should improve disease awareness and effective communications among healthcare professionals and patients with these conditions., SCOPUS: ar.j, info:eu-repo/semantics/published

Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown., SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Eosinophil-associated diseases (EADs) are a range of heterogeneous conditions in which eosinophils are believed to play a critical pathological role. EADs include common illnesses such as eosinophilic asthma and chronic rhinosinusitis and rare conditions such as hypereosinophilic syndromes (HES) and eosinophilic gastrointestinal disorders (EGIDs). EADs are associated with substantial burdens for the patient, including chronic, debilitating symptoms, increased financial burden, decreased health-related quality of life, and the need for repeated visits to multiple different healthcare professionals (HCPs), emergency departments, and/or hospitals. Poor EAD recognition by HCPs often contributes to delayed diagnoses, which further delays patient access to appropriate care and effective treatments, contributing to poor health outcomes. The objective of this charter is to outline key patient rights and expectations with respect to the management of their condition(s) and to set forth an ambitious action plan to improve health outcomes for patients with EADs: (1) people with EADs, their caretakers, HCPs, and the public must have greater awareness and education about EADs; (2) people with EADs must receive a timely, accurate diagnosis; (3) all people with EADs must have access to an appropriate multidisciplinary team, when necessary; and (4) people with EADs must have access to safe and effective treatment options without unnecessary regulatory delays. The principles described in this charter demonstrate the core elements of quality care that people with EADs must receive, and they represent clear steps by which to reduce patient and caregiver burden and improve patient outcomes. We urge HCPs, healthcare systems, and policymakers worldwide to swiftly adopt these principles to ensure patients with EADs have an accurate diagnosis in a timely manner and access to high-level care and treatment in an appropriate setting., SCOPUS: no.j, info:eu-repo/semantics/published

Rheumatoid arthritis (RA) is the most common systemic inflammatory arthritis, affecting close to 0.5% of the population. It is characterized by joint and systemic inflammation that are responsible for pain and increased morbidity and mortality if left untreated. Accurate diagnosis and timely treatment with anti-rheumatic drugs at an early stage can help prevent handicap. However, this is hindered by the fact that in roughly one third of RA patients, the commonly used diagnostic biomarkers, anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are absent. Antibodies against carbamylated proteins (Anti-CarPA) have been suggested as a third diagnostic and prognostic biomarker in RA. The established method for anti-CarPA detection is based on the use of an in vitro carbamylated fetal calf serum (CaFCS) as an antigen for ELISA assays. Antibodies detected in that manner (anti-CaFCS) have been shown to be present in approximately 40% of sera from RA patients, including a small subset of patients seronegative for RF and ACPA. Anti-CaFCS positivity predates the development of RA and predict structural joint damage. In the present research work, we set out to evaluate the presence of anti-CaFCS in Belgian RA patients, as well as in rheumatic disease controls and healthy individuals (PUBLICATION I). We demonstrated that anti-CaFCS are present in our RA cohort, including in a seronegative patient subset (4.4%). In that last subgroup, we found that anti-CaFCS antibodies were associated with higher disease activity measures. We also observed increased anti-CaFCS levels in patients with Sjögren’s syndrome (pSS), as well as in the sera of certain Juvenile Idiopathic arthritis (JIA) patients. In JIA, the RF+ polyarticular subgroup showed the highest anti-CaFCS levels, and a proportion of otherwise seronegative patients was also detected (PUBLICATION II). We then designed an experiment to examine whether the inherent heterogeneity of FCS batches could have an impact, La polyarthrite rhumatoïde (PR) est l’arthrite inflammatoire systémique la plus fréquente, touchant environ 0.5% de la population. La maladie est caractérisée par une inflammation articulaire et systémique responsables de douleurs et d’une morbidité et une mortalité accrues chez les patients non traités. Un diagnostic précoce et précis permet le traitement rapide par des agents antirhumatismaux, aidant à prévenir le handicap. Chez un tiers de patients atteints de PR, les biomarqueurs diagnostiques utilisés à ce jour (i.e. les autoanticorps ciblant les protéines citrullinées (ACPA) et le facteur rhumatoïde (FR)) sont absents, ce qui rend le diagnostic plus difficile. Les autoanticorps dirigés contre les protéines carbamylées (anti-CarPA) ont été proposés comme troisième biomarqueur de pronostic et diagnostic pour la PR. La méthode établie pour la détection des anti-CarPA est fondée sur l’utilisation d’un sérum fœtal bovin carbamylé in vitro (CaFCS) comme antigène pour le test ELISA. Les anticorps détectés ainsi (anti-CaFCS) sont présents dans le sérum d’environ 40% de patients PR, incluant une fraction des patients séronégatifs pour le FR et les ACPA. La positivité anti-CaFCS précède le développement de la PR et pourrait être un marqueur prédictif de lésions articulaires structurales. Dans le présent travail de recherche, nous avons évalué la présence des anti-CaFCS chez des sujets belges atteints de PR ou d’une autre maladie rhumatismale et chez des sujets sains (PUBLICATION I). Nous avons démontré que les anti-CaFCS sont présents dans notre cohorte de PR, y compris dans un sous-groupe séronégatif (4.4%). Dans ce sous-groupe, nous avons remarqué une association entre la présence des anti-CaFCS et des scores d’activité de la maladie plus élevés. Nous avons également observé des taux d’anti-CarPA élevés dans le sérum de patients souffrant du syndrome de Sjögren primaire (pSS) et de certains patients atteints d’arthrite juvénile idiopathique (JIA). Parmi ces derniers, Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished

The functions ascribed to eosinophils have classically been limited to host defence against certain parasitic infections and potentially deleterious effects in the setting of specific diseases that are associated with elevated eosinophil counts in blood and/or tissue. The ability to induce eosinophil depletion either experimentally in animal models or through targeted therapies in humans has extended our understanding of the roles played by eosinophils in health and homeostasis as well as in disease pathogenesis. When associated with human disease aetiology, the eosinophil takes on a pathogenic rather than a protective role. This maladaptive response, called "eosinophilic immune dysfunction" herein, appears central to exacerbation pathogenesis and disease control in severe asthma and may be involved in the aetiology of other eosinophil-related conditions ranging from organ-system-limited diseases such as phenotypic subsets of chronic obstructive pulmonary disease and chronic rhinosinusitis with nasal polyposis to more broadly systemic diseases such as eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. In this review, we describe the evidence supporting eosinophilic functions related to health and homeostasis and explore the contribution of eosinophilic immune dysfunction to human disease., SCOPUS: re.j, info:eu-repo/semantics/published