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Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use., (© 2023. Springer Nature Limited.)

Hypereosinophilic syndrome (HES) is defined as a peripheral eosinophil count of > 1500/μl (assessed twice at an interval of ≥ 2 weeks) and an eosinophil-induced organ damage. Idiopathic HES is differentiated from primary (clonal or neoplastic) HES and secondary (reactive) HES, depending on the etiology. Eosinophilic granulomatosis with polyangiitis (EGPA) is categorized as a secondary form of HES and is characterized by hypereosinophilia and vasculitis of small to medium-sized vessels and can be associated with an antineutrophil cytoplasmic antibody (ANCA). The treatment of HES is dependent on the etiology. Clonal HES is treated according to the respective genetic aberration, e.g. with tyrosine kinase inhibitors or chemotherapy and allogenic stem cell transplantation. Secondary forms should be treated according to the underlying cause (e.g. parasitic infection). The treatment of EGPA is carried out with immunosuppressants depending on the disease stage and disease activity. Conventional drugs, such as glucocorticoids (GC), cyclophosphamide (CYC) and methotrexate (MTX) or biologics, such as the monoclonal anti-IL5 antibody mepolizumab are commonly used. Mepolizumab is also a good option for the treatment of idiopathic HES., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rheumatic diseases characterized by small-to-medium vessel vasculitis. Three different entities can be distinguished: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). While lung and renal involvement are typical manifestations of both GPA and MPA, EGPA usually shows paranasal sinus and lung involvement as well as a history of bronchial asthma. Furthermore, EGPA is frequently associated with cardiac disease and peripheral neuropathy. Cyclophosphamide or rituximab, combined with glucocorticoids, are used to induce remission of severe disease. Maintenance therapy options include rituximab as the first-line treatment, as well as methotrexate or azathioprine plus low-dose glucocorticoids., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare chronic inflammatory systemic disease that occurs in patients with bronchial asthma and is associated with significant blood and tissue eosinophilia. Another characteristic is vasculitis of small and/or medium-sized vessels, which may be absent in prodromal stages of the disease and is therefore no longer an obligatory part of the disease definition. Antineutrophil cytoplasmic antibodies (ANCA) can be detected in approximately one third of patients. The ANCA-positive and ANCA-negative EGPA are genetically distinct diseases with common clinical manifestations, which, however, occur with different frequencies. Cardiac involvement is associated with a poor prognosis. Permanent organ damage often occurs as a result of the underlying disease or treatment, especially with glucocorticoids (GC). The standard treatment of EGPA consists of GC in combination with cyclophosphamide for severe organ involvement or medium potency immunosuppressants for more prognostically favorable manifestations. Biologics are increasingly being used in the treatment of EGPA. The interleukin (IL) 5 antagonist mepolizumab reduces the risk of relapses and decreases the demand for GC in patients with relapsing EGPA without severe organ involvement. In analogy to the approach to other ANCA-associated vasculitides, the use of rituximab in ANCA-positive EGPA patients with severe vasculitis recurrence is a possible option, even though formal evidence for such an approach is currently low and formal approval is lacking., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Glucocorticoids (GC) still represent an essential pillar of treatment in the phase of remission induction of vasculitides, which are often organ or life-threatening; however, they entail a significant potential for side effects. In the phase of remission maintenance prednisolone should be reduced to 7.5 mg/day or less. Whether a discontinuation can alway be achieved for any form of vasculitis without increasing relapse rates, is unclear. By the use of biologics, e.g. tocilizumab in giant cell arteritis (GCA), a fast tapering and discontinuation of GC seems to be more easily achievable compared to using a GC monotherapy regimen. Avacopan could in the future be an efficient agent to spare GC in the phase of remission induction in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), e.g. granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Mepolizumab is a promising option to reduce the use of GC in eosinophilic granulomatosis with polyangiitis (EGPA).

Objective: To develop disease-specific recommendations for the diagnosis and management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (EGPA)., Methods: The EGPA Consensus Task Force experts comprised 8 pulmonologists, 6 internists, 4 rheumatologists, 3 nephrologists, 1 pathologist and 1 allergist from 5 European countries and the USA. Using a modified Delphi process, a list of 40 questions was elaborated by 2 members and sent to all participants prior to the meeting. Concurrently, an extensive literature search was undertaken with publications assigned with a level of evidence according to accepted criteria. Drafts of the recommendations were circulated for review to all members until final consensus was reached., Results: Twenty-two recommendations concerning the diagnosis, initial evaluation, treatment and monitoring of EGPA patients were established. The relevant published information on EGPA, antineutrophil-cytoplasm antibody-associated vasculitides, hypereosinophilic syndromes and eosinophilic asthma supporting these recommendations was also reviewed., Discussion: These recommendations aim to give physicians tools for effective and individual management of EGPA patients, and to provide guidance for further targeted research., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate a vasculitis centre based management strategy for eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA)., Methods: A retrospective cohort study at a vasculitis referral centre was performed. All EGPA patients admitted from 1990 to 2009 were included. A structured interdisciplinary work-up for proof of diagnosis, Disease Extent Index and Birmingham Vasculitis Activity Score was performed. Immunosuppressive therapy was initiated and regularly adapted. Treatment targets were induction and maintenance of remission according to definitions given by the European League Against Rheumatism and the European Vasculitis Study Group. Outcomes were mortality, rate of remission, relapses, adverse events and prednisolone-dose., Results: Out of 269 patients with suspected EGPA 150 fulfilled the inclusion criteria. Of those, 104 had more than one follow-up visit resulting in a mean follow up of 53±4.9 months. By using additional data sources the follow-up concerning survival was extended to 92±5 month. Severe organ manifestations occurred at heart (46%), kidney (18%) and lungs (10%). Cyclophosphamide was used in 107 patients (71%). The prednisolone-doses of all patients were within the targeted range (i.e. ≤7.5 mg) in 69% of the total follow-up time; the median dose at end of follow-up was 5mg/d. The 10-year survival rate was 89% resulting in mortality comparable to the general population (SMR 1.29). Only patients with cardiac failure associated with EGPA had an increased mortality (SMR 3.06)., Conclusions: Regular re-evaluation and target-orientated adaption of therapy may lead to normalization of life expectancy and attenuation of disease progression. Continued centre based interdisciplinary treatment should be standard of care.

Objective: There is evidence that the leptin/ghrelin system is involved in T-cell regulation and plays a role in (auto)immune disorders such as SLE, RA and ANCA-associated vasculitides (AAVs). Here, we evaluate the genetic background of this system in WG., Methods: We screened variations in the genes encoding leptin, ghrelin and their receptors, the leptin receptor (LEPR) and the growth hormone secretagogue receptor (GHSR). Three single nucleotide polymorphisms (SNPs) in each gene region were analysed in 460 German WG cases and 878 ethnically matched healthy controls., Results: A three-SNP haplotype of GHSR was significantly associated with WG [P = 0.0067; corrected P-value (P(c)) = 0.026; odds ratio (OR) = 1.30; 95% CI 1.08, 1.57], as was one non-synonymous SNP in LEPR (Lys656Asn, P = 0.0034; P(c) = 0.013; OR = 0.72; 95% CI 0.58, 0.90). These four SNPs were re-analysed in independent cohorts of 226 German WG cases and 519 controls. While the GHSR association was not confirmed, allele frequencies of the LEPR SNP were virtually identical to those from the initial cohorts. Analysis of this SNP in the combined WG and control panels revealed a significant association of the LEPR 656Lys allele with WG (P = 0.00032; P(c) = 0.0013; OR = 0.72; 95% CI 0.60, 0.86). Remarkably, the Lys656Asn SNP showed contrasting allele distribution in two cohorts of 108 and 88 German cases diagnosed with Churg-Strauss syndrome (CSS, combined P = 0.0067; OR = 1.41; 95% CI 1.10, 1.81), whereas identical allele frequencies were revealed when comparing British WG and microscopic polyangiitis cases., Conclusions: While GHSR has to be further evaluated, these data provide profound evidence for an association of the LEPR Lys656Asn SNP with AAV, resulting in opposing effects in WG and CSS.

Objectives: The aim of this study was to analyse mPR3 expression on neutrophils in two Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), namely WG (localised vs. generalised) and Churg-Strauss syndrome (CSS) and other inflammatory disorders, in order to evaluate (i) whether the pattern of mPR3 expression is specific for AAV and (ii) to assess whether the mPR3high status is associated with clinically distinct disease stages of WG (localised vs. generalised)., Methods: Localised WG (n=15), generalised WG (n=55), Churg-Strauss Syndrome (CSS) (n=20), systemic lupus erythematosus (SLE) (n=15), Rheumatoid Arthritis (RA) (n=22) and healthy controls (n=30) were analysed. mPR3 and CD63 expression on surface of neutrophils were assessed by flow cytometric analysis on isolated neutrophils and whole blood., Results: In patients with genWG and SLE, an increased percentage of mPR3+ neutrophils and an elevated level of mPR3 expression compared to healthy controls were found (percentage: p=0.001, p=0.000; MFI ratio: p=0.038, p=0.019, respectively). There was no increased frequency of mPR3+ neutrophils in CSS. Within the group of WG, an elevated level of mPR3 expression was significantly associated with disease stage (genWG and not locWG), and in genWG with disease activity and the presence of ANCA., Conclusions: The mPR3high status is associated with generalised WG and correlates with disease activity and ANCA status in generalised WG. An increased proportion of mPR3-positive neutrophils is not specific for AAV.

Purpose of Review: Recently, numerous studies have been performed to elucidate the genetic background of Wegener's granulomatosis and Churg-Strauss syndrome (CSS). Many of these investigations suffer from low statistical power, inconsistent case classification and other error-prone study designs. The majority of these findings has to be considered preliminary, if not spurious. We summarize the most important and robust findings., Recent Findings: HLA-DPB1, the association of which with Wegener's granulomatosis has been discovered some years ago, is still the strongest and best replicated risk locus for this condition. Yet, no association is demonstrable for CSS, in which another HLA locus, HLA-DR, seems to be more important. Vice versa, a strong association with IL10 promotor polymorphisms was detected in CSS but not in a large Wegener's granulomatosis panel. Numerous other associations, including CTLA4, CD226 and copy number polymorphisms of FCGR3B still need further investigation, before reliable conclusions can be drawn., Summary: In order to be able to evaluate critically the genetic background of Wegener's granulomatosis and CSS future projects should take into account several aspects of study design. These preconditions include sufficient numbers of cases (i.e. statistical power) and a clear-cut classification of these cases, thus allowing differentiated analyses of certain disease subgroups.

Objective. Assessment of disease activity in vasculitis can be achieved using the BVAS, a clinical checklist of relevant symptoms, signs and features of active disease. The aim of this study was to revalidate the BVAS version 3 (BVAS v. 3) in a cohort of patients with systemic vasculitis.Methods. A total of 238 patients with vasculitis from seven countries in Europe were evaluated at a single time point. Spearman’s correlation coefficients were calculated between BVAS v. 3 scores, vasculitis activity index (VAI), physician’s global assessment (PGA), the physician’s treatment decision, CRP and the vasculitis damage index (VDI) to demonstrate that the BVAS v. 3 measures disease activity.Results. WG (63%), Churg–Strauss syndrome (9%) and microscopic polyangiitis (9%) were the most common diagnoses. The BVAS v. 3 showed convergent validity with the VAI [ρ = 0.82 (95% CI 0.77, 0.85)], PGA [ρ = 0.85 (95% CI 0.81, 0.88)] and the physician’s treatment decision [ρ = 0.54 (95% CI 0.44, 0.62)]. There was little or no correlation between BVAS v. 3 and the CRP level [ρ = 0.18 (95% CI 0.05, 0.30)] or with the VDI [ρ = −0.10 (95% CI 0.22, 0.03)]. The inter-observer reliability was very high with an intra-class correlation coefficient (ICC) of 0.996 (95% CI 0.990, 0.998) for the total BVAS v. 3 score.Conclusion. The BVAS v. 3 has been evaluated in a large cohort of patients with vasculitis and the important properties of the tool revalidated. This study increases the utility of the BVAS v. 3 in different populations of patients with systemic vasculitis. [ABSTRACT FROM PUBLISHER]

Churg–Strauss syndrome is a rare small-vessel vasculitis that is associated with asthma, granulomatous inflammation, peripheral/tissue eosinophilia and a positive antineutrophil cytoplasmic antibody status (in approximately 40% of patients). The disease can be organ- and life-threatening, either due to tissue eosinophil infiltration such as myocarditis or due to vasculitis manifestations, for example glomerulonephritis. Furthermore, life-threatening disease can also occur due to the side effects of immunosuppression, for example, infection. A thorough diagnostic work-up should be performed in order to identify all organs involved and to rule out other disorders with similar features, such as hypereosinophilic syndrome. Therapeutic management is conducted according to disease stage and activity. Glucocorticoids remain the mainstay of therapy; however, further immunosuppressants (e.g., cyclophosphamide for lifethreatening disease) are usually required. Future promising therapy options target cytokines. involved in the disease process, such as IL-5. INSET: Key issues. [ABSTRACT FROM AUTHOR]