Churg-Strauss Research Articles

Genetic and Non-Genetic Contributions to Eosinophilic Granulomatosis with Polyangiitis: Current Knowledge and Future Perspectives.

In this work, we present a comprehensive overview of the genetic and non-genetic complexity of eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare complex systemic disease that occurs in people presenting with severe asthma and high eosinophilia. After briefly introducing EGPA and its relationship with the anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAVs), we delve into the complexity of this disease. At first, the two main biological actors, ANCA and eosinophils, are presented. Biological and clinical phenotypes related to ANCA positivity or negativity are explained, as well as the role of eosinophils and their pathological subtypes, pointing out their intricate relations with EGPA. Then, the genetics of EGPA are described, providing an overview of the research effort to unravel them. Candidate gene studies have investigated biologically relevant candidate genes; the more recent genome-wide association studies and meta-analyses, able to analyze the whole genome, have confirmed previous associations and discovered novel risk loci; in the end, family-based studies have dissected the contribution of rare variants and the heritability of EGPA. Then, we briefly present the environmental contribution to EGPA, reporting seasonal events and pollutants as triggering factors. In the end, the latest omic research is discussed and the most recent epigenomic, transcriptomic and microbiome studies are presented, highlighting the current challenges, open questions and suggesting approaches to unraveling this complex disease.

Eosinophilic granulomatosis with polyangiitis: a review article

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a poorer prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.

The role of tobacco smoking in antineutrophil cytoplasmic antibody-associated vasculitis: a systematic review.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

Hypertrophic Pachymeningitis, Associated with Eosinophilic Granulomatosis with Polyangiitis, and ANCA-Negative Serology.

Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement. Hypertrophic pachymeningitis (HP) has several aetiologies; if the systemic investigation is not contributory to a diagnosis, a meningeal biopsy is necessary.This is the first case report of HP, associated with eosinophilic granulomatosis with polyangiitis (EGPA), and ANCA-negative serology.EGPA is probably a spectrum of diseases with predominant systemic involvement, but there may be cases where there is histological evidence, without the systemic context or positive serology.

Pulmonary function in patients with ANCA-associated vasculitis.

Although pulmonary manifestations occur frequently in ANCA-associated vasculitis (AAV), empirical evidence of their impact on pulmonary function is scarce. This study analyzed pulmonary function test (PFT) data from a large cohort of patients with AVV. Results were correlated with findings from diagnostic imaging and disease activity. Data from AAV patients with PFTs performed between 2008 and 2018 were extracted retrospectively from the database of a tertiary vasculitis center. Demographic and disease characteristics, imaging data and follow-up results were assessed and compared to PFT results. The final analysis encompassed 147 patients. The mean time between first PFT and follow-up was 7.0 ± 11.0 months. In Granulomatosis with Polyangiitis (GPA), forced expiratory vital capacity (FVCex, p<0.001), residual volume (RV, p<0.001) and the diffusion capacity of carbon oxide (TLCO, p=0.003) were significantly reduced compared to the reference value of 100% predicted. There was no significant difference between patients with or without pulmonary manifestations. In Microscopic Polyangiitis (MPA), reductions of FVCex (p<0.001), TLC (p=0.005), and TLCO (p=0.003) were observed. In Eosinophilic Granulomatosis with Polyangiitis (EGPA), total airway resistance (RAWtot, p=0.024) and RV (p=0.009) were significantly elevated and TLCO was reduced (p=0.014). Interstitial lung disease (ILD) is associated with a decline of FVCex (-15.7%, p=0.0028), TLC (-26.5%, p<0.001), RV (-38.9%, p=0.023) and TLCO (-29.1%, p=0.007). Significant differences were neither detected between first PFT and follow-up examination, nor between patients with active versus inactive disease. AAV patients presented with characteristic alterations in PFTs according to their respective pulmonary and/or airway manifestations. These results did not change over time and were independent from vasculitis activity.

A hybrid case of eosinophilic folliculitis and eosinophilic cellulitis associated with hypereosinophilic syndrome

AbstractEosinophilic cellulitis or Wells syndrome encompasses distinct histopathological features but can also be associated with eosinophilic related conditions like hyper eosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss syndrome). We report a case of a Turkish 41‐year‐old female who presented in clinic with pruritus and tenderness on her chest and breasts, having received several courses of antibiotics for recurrent abscess formation. A year before she had been diagnosed with HES with multiorgan involvement that included biopsy proven eosinophilic folliculitis, and prompted further investigation including bone marrow aspiration that revealed T cell clonality. Biopsy of her rash revealed eosinophilic infiltration of the dermis with flame figures. Ongoing respiratory symptoms and a history of childhood asthma were suggestive of EGPA. This case highlights important associations that should be considered in the investigation of Wells syndrome.

The Evaluation of Changing the Eponym Churg-Strauss Syndrome Due to the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

Background: Eponyms do not describe any pathogenesis of a disease. So, there is no other way than to memorize the disease or anatomical area. Over the years, new nomenclatures have been suggested for some diseases due to a better understanding of the pathogenesis. In this article, the changes in the use of Churg-Strauss syndrome were investigated. Methods: In the study, a computerized search was performed using the PubMed database. Books and documents, clinical trials, editorials, meta-analyses, reviews, and case reports were included in the study. Data were obtained from the title of the database, and the variations or distribution by year for the nomenclature of the most related studies were evaluated. Results: Overall, 68.3% of the articles included CSS, 25.7% included eosinophilic granulomatous polyangiitis (EGPA), and 6.0% included both nomenclatures. When evaluated in terms of the distribution according to years, it was determined that there was a statistically significant increase in use in terms of EGPA. When evaluated among specific section journals, the highest rate was in Rheumatology (29.4%). The highest rate of using CSS was in the Rheumatology (25.1%) journals, followed by Pulmonary/Respiratory (17%), Cardiovascular (12%), and Allergy/Immunology/Biology (9.8%). The use of EGPA combined with CSS decreased in all the specific journals from 2012 to the present. Conclusions: The findings of the study revealed that the number of articles with the eponym of EGPA showed an increased frequency in contrast to a decreasing frequency for those with CSS during recent years. Today, with the elaboration of the disease pathogenesis and the increase in knowledge, the trend has shifted in this direction.

Eosinophilic Granulomatosis with Polyangiitis with ophthalmic involvement: A Case report and Literature Review

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic necrotizing vasculitis primarily affecting small blood vessels. It is characterized by extravascular eosinophilic granulomas, peripheral eosinophilia, and often coexists with asthma. This rare condition can affect individuals of any gender and age, presenting with a variety of multisystemic symptoms. Prognosis is largely influenced by cardiac involvement, evaluated using the Five-Factor Score (FFS) to guide treatment decisions. Respiratory manifestations, particularly severe and corticosteroid-dependent asthma, are common in EGPA and may aid in its early diagnosis. In this case report, we describe a patient with an uncontrolled asthma admitted for moderate asthma exacerbation. Clinical examination revealed ocular redness and skin lesions, along with hypereosinophilia on assessment and reticulo-micronodular infiltrates on chest CT scan. EGPA diagnosis was confirmed based on the ACR 1990 criteria, wich have been updated and substituted with more objective criteria in 2022. According to the FFS score, the patient underwent systemic corticosteroid therapy in conjunction with azathioprine, leading to an overall favorable outcome over a 3-year follow-up period.

#3140 Investigating the impact of Anti-IL5 therapy in eosinophilic granulomatosis with polyangiitis (EGPA): a three year longitudinal perspective

Abstract Background and Aims In the randomized, placebo-controlled MIRRA trial [1] for relapsing and refractory eosinophilic granulomatosis with polyangiitis (EGPA), adjuvant therapy with 300 mg anti-IL5 mAB Mepolizumab [MEPO] for 12 months (M), accrued longer times in remission, reduced steroid exposure and reduced relapse rates [1]. The aim of this study is to analyze the outcome of 100 mg MEPO monthly s/c for a minimum of 36 months. Changes to adjuvant immunosuppression and indications for anti-IL5 class switch from MEPO 100 mg s/c to Benralizumab (BRZ) or Reslizumab (Res) were assessed. Method In this observational study, 20 EGPA patients received anti-IL5 therapy for a minimum of 36M (range 49-68M). All commenced on 100 mg s/c MEPO every four weeks. Anti-IL5 therapy switched to BRZ or Res due to partial response or intolerance. Assessment time points included MEPO commencement, 6, 12, 18, 24 and 36 months. Results Overall, there was a 50% reduction in steroid dose by 12 months. This continued to reduce to 24M, by which time 2 were off steroids and a further 10/20 (50%) on weaning dose ≤ prednisolone 5 mg/day. Mean steroid dose continued to decrease to 36 months. The number on adjuvant conventional immunosuppressants (ACIS), reduced over time from 10/20 (50%) at M0 to 4/20 (20%) by M24. Clinical benefits included ANCA serology normalized in all four positive patients by 12 months. Mean eosinophil count reduced from 0.42 mg ± 0.33 × 109/L at M0 to 0.04 ± 0.03 × 109/L at 12 and 24M. BVAS reduced from median 5 [3-7], to 0 [0-1] by 24M. The change in mean FEV1 over 12 months was from (M0) 2.11 ± 0.66 to (M12) 2.39 ± 0.62 and FVC (M0) 3.42 ± 0.87 to (M12) 3.67 ± 0.93/105.60 ± 20.47 respectively. All 20 EGPA patients receiving anti -IL5 therapy, ranging from 49-68M remain on therapy. At 36M, 9 have remained on 100 mg s/c MEPO. 10 (50%) have switched to an alternative anti-IL5 agent—10 switched to benralizumab, 1 initially on benralizumab to reslizumab. 9/10 had achieved partial response prior to switch (reduction in steroids / relapse rate), 1/10 had no response.. During the duration of the study, 3 patients had a break of therapy, but all resumed anti-IL5 treatment with good response. Hence, all 20 remain on anti-IL5 beyond 24M. After 36M, one patient required cyclophosphamide along with anti-IL5 therapy for myocarditis. A further patient had Rituximab for EGPA/ Rheumatoid arthritis overlap between anti-IL5 agents. Conclusion In this study, there was a 50% reduction in steroid dosage by 12 months and steroid requirements continue to decrease to 36M. By 24 months 2 are steroid free and a further 10 on weaning dose ≤5 mg. Furthermore, the number on adjuvant conventional immunosuppression reduced over the 24M (n = 4 at 24M). This study demonstrates that anti-IL5 therapy serves as a favorable model for steroid and conventional immunosuppressant minimization in EGPA. Clinical benefits of reduction in BVAS, improved pulmonary function tests and reduced serum eosinophilia were recorded. The relapsing nature of EGPA places a dependency of therapy on steroids and this study demonstrated sustained and ongoing improvement annually with continued anti-IL5 therapy. Some participants required a switch in anti-IL5 agent.

#1739 Combination rituximab &amp; low-dose IV cyclophosphamide induction therapy for severe multi-system eosinophilic granulomatosis with polyangiitis

Abstract Background and Aims Current guidelines advise rituximab (RTX) or cyclophosphamide treatment for organ-threatening disease in eosinophilic granulomatosis with polyangiitis (EGPA). However, conventional treatment is often limited by partial efficacy, toxicity, high relapse rate and steroid dependency. We investigate the use of a combined RTX, low-dose cyclophosphamide, and steroid regimen for treatment of severe EGPA. Method Single-centre retrospective cohort study of patients treated with a combination induction regimen for severe EGPA (with kidney, cardiac or neurological involvement) between 2012-23. Data reported as median (±IQR) Results Eighteen patients (10 male; age 56 years [52-62]) are included. At treatment, BVAS was 16.3 [14-20], peak eosinophil count 9.3 × 109/L [5-13], C-reactive protein (CRP) 122 mg/L [80-193]. Eleven cases were ANCA positive (10 MPO-, 1 PR3-ANCA.) The proportions of patients affected by active/new respiratory, ENT, neurological, and gastrointestinal disease were 18/18 (100%), 14/18 (78%), 11/18 (61%), and 1/18 (6%), respectively. 11/18 (61%) had cardiac involvement (troponin 10345 ng/L [1240-7621]) and 6/18 (33%) had necrotising glomerulonephritis confirmed by renal biopsy (creatinine 123 µmol/L [83-167]). Cumulative cyclophosphamide dose was 3.5g [3.0-3.5] and total RTX dose was 2g. Initial prednisolone dose was 0.5-1.0 mg/kg/day, and this was rapidly weaned to 5 mg daily at a median time of 6.1 months [3.9-7.2], and 9/18 (50%) had steroids withdrawn completely by 11.7 months [4.6-20.6]. First-line maintenance treatment was azathioprine or MMF. By 6 months, all achieved disease remission as assessed by BVAS (all 0) and improved laboratory parameters: CRP 1 mg/L, eosinophil count 0.1 × 109/L, and ANCA testing negative. In those with renal disease, kidney function improved or stabilised in all (creatinine 95 µmol/L). In those with cardiac disease (11/18), magnetic resonance imaging was performed at baseline and at follow up (median time of 3.7 months) in all patients. Of these, 9/11 (82%) had oedema on initial scan and this improved in all cases; 10/11 (91%) had late gadolinium enhancement at baseline, which persisted in every case, though with significantly lower burden. The median follow-up period was 38 months [14-55]. At 1, 3 and 5 years, 100%, 92% and 76% of patients were in sustained remission (Fig. 1A). Three patients experienced relapse; one patient had major relapse with skin involvement requiring reinduction treatment; two patients had minor ENT relapse requiring retreatment with glucocorticoids. Infection-free survival at 1, 3 and 5 years was 94%, 78%, 62%, respectively (Fig. 1B). There were no deaths. Conclusion This regimen provided rapid disease control in patients with severe multi-system EGPA, including those with life-threatening cardiac manifestations, and enabled rapid glucocorticoid tapering and withdrawal. Disease-free remission was sustained during long-term follow up. Combination induction regimens may have a role in the treatment of organ-threatening disease in EGPA.

#1960 Incidence of cancer in ANCA associated vasculitis (AAV)

Abstract Background and Aims We investigated the incidence rate and type of cancer in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in our Institute. Method We retrospectively included 210 patients with AAV [106 patients with microscopic polyangiitis (MPA), 93 with granulomatosis with polyangiitis (GPA) and 11 patients with eosinophilic GPA (EGPA)], and reviewed their medical records. We collected demographic, clinical and laboratory data. We selected patients with history of cancer, patients diagnosed with paraneoplastic AAV and patients who developed malignant disease after AAV. We reviewed the use of glucocorticoid and immunosuppressive drugs. Results Between 1993-2024 there were 16 patients with AAV who had cancer during their life in our Department. There were eight patients with malignancy-associated AAV. Two patients were simultaneously diagnosed with kidney carcinoma and vasculitis. One patient's serum was positive for cytoplasmatic ANCA, the other patient's for pANCA. Complete resection of cancer and renal biopsy was performed, they got steroid monotherapy. Five patients were diagnosed with pANCA vasculitis a few months (1-5) after the diagnosis of malignancies (two pts with breast carcinoma, two pts with ovarium carcinoma, one patient with ventricular carcinoma). In one case the pAAV was established after 5 months of oropharyngeal tumor's resection. Two patients had history of malignancy (one pts had colon carcinoma 4 ys before the appearance of AAV, the other patient had breast carcinoma 10 ys before the AAV). In both cases there were examinations for malignancy with negative results. In these cases the vasculitis was not associated with carcinoma. The therapeutic approach included the use of corticosteroids, plasmapheresis, and cyclophosphamide or rituximab. Six patients were observed malignancy 0.5-10 years after the diagnosis of AAV. There was one pancreas, one ventricular, two lung and two bladder carcinoma. Conclusion In our study we focused on the relationship of malignancy and AAV. Between the 210 patients with AAV eight cases (3.8%) were malignancy-associated, in one case cANCA associated, the other cases pANCA was presented. Treating paraneoplastic vasculitis can be challenging. Individualized treatment strategy tailored to patients' needs is crucial. Six patients were diagnosed with solid tumor during the follow-up. The cumulative overall cancer incidence rates were 1.4% and 2.8% at 5 and 10 years, respectively. Only in one patient with bladder cancer was treated with the cumulative CYC doses ≥ 36 g. No leukemia or non melanotic skin cancer (NMSC) was represented contrary to other studies.

A COMPLEX POST CARDIAC–ARREST SYNDROME: FROM UNCERTAIN NEUROLOGICAL OUTCOME TO HEMORRHAGIC COMPLICATION

Abstract A 49–years–old woman with type II diabetes mellitus, hypothyroidism and Churg–Strauss syndrome experienced chest pain with loss of consciousness. Emergency service was called and CPR promptly started. Cardiac arrest with shockable rhythm was documented, DC–shock performed with sign of anterior STEMI after ROSC, then refractory cardiac arrest appeared. The patient was centralized in our hospital and VA–ECMO was positioned through a percutaneous femoral access in cath–lab. Coronary angiography showed acute occlusion of the mid–proximal LAD and subocclusive stenosis of the dominant Cx for which PCI with DES was performed, then intra–aortic balloon pump (IABP) was implanted. At ICCU admission the patient was supported by ECMO and IABP with MAP 65 mmHg and lactates 3.5 mmol/L. Echocardiography and chest X–ray showed severe biventricular dysfunction and pulmonary overload (Fig 1). She was ventilated via ECMO circuit and mechanical ventilation setting protective TV values of 6 ml/kg. Diuresis was good with low dose of furosemide, lactates progressively decreased. Temperature control was set within 36°C with the cooling system of the ECMO circuit. Cardioaspirin, ticagrelor and bivalirudin were administered. At early neurological stratification EEG documented absence of epileptiform anomalies, responsiveness to painful stimuli, SSPE showed normal and symmetrical morphology, NSE at 48 h was 59 ng/mL, she opened eyes and performed simple orders. Levosimendan was administered with partial recovery of the right ventricular dysfunction leading to ECMO removal on 5th day. Due to poor consciousness recovery despite sedation reduction, percutaneous tracheostomy was performed on 8th day, IABP removed and the following day all vasopressors suspended. Neurological improvement allowed transition to spontaneous breathing and weaning from mechanical ventilation; on 19th day tracheostomy was removed. Massive enterorrhagia appeared after ECMO removal (figure 2). The colonoscopy showed ischemic pancolitis, therefore ticagrelor was suspended. On 18th day clopidogrel was reintroduced based on hemoglobin stability and endoscopic improvement. She was discharged from the cardiology department after a total length of stay of thirty days, with normal neurological status, no motor deficits, recovery of left and right ventricular function, stable hemoglobin levels.

Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.

Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.

Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

Eosinophilic granulomatosis with polyangiitis and its association with montelukast: a case-based review.

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.

Burden of eosinophilic granulomatosis with polyangiitis in Europe.

Real-world evidence characterising the burden of eosinophilic granulomatosis with polyangiitis (EGPA) in Europe is limited. The aim of this study was to characterise patients in a large European EGPA cohort. This retrospective, non-interventional, longitudinal study (GSK ID: 214661) recruited cross-specialty physicians from France, Germany, Italy, Spain and the UK to conduct medical chart reviews for patients with a physician-confirmed diagnosis of EGPA. Patients were ≥12 years of age at diagnosis with ≥1 year of follow-up data from the first clinical visit with the physician (index date). Outcome measures collected from index date to end of follow-up included clinical manifestations and healthcare resource utilisation (HCRU). In total, 407 patient medical charts were reviewed by 204 physicians; median (interquartile range) duration of follow-up from index date was 2.2 (1.7-3.5) years. Most patients (73.5%) had asthma. Patients underwent multiple diagnostic assessments, and 74.9% received ≥3 different therapies between diagnosis and end of follow-up (98.8% oral corticosteroids, 63.9% immunosuppressive therapies, 45.5% biologics). During follow-up, 84.5% of patients experienced EGPA clinical manifestations; most were considered moderate or severe and commonly affected the lungs (55.8%; including lung infiltrates 25.8% and severe asthma 24.8%), ear, nose and throat (53.3%), and skin (41.8%). HCRU was substantial: 26.0% of patients made emergency department visits, 36.6% were hospitalised and 84.8% had outpatient visits. These real-world data show that EGPA presents a substantial burden to patients and the healthcare system. Earlier and better differential diagnosis and appropriate treatment may help reduce incidence of clinical manifestations and HCRU.

Severe heart failure and intracardiac thrombosis: going beyond the appearance for diagnosis and treatments.

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

Peripheral Neuropathy in Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic autoantibody-associated vasculitis secondary to inflammation of the small vessels. EGPA-induced neuropathy develops in approximately 90% of patients with peripheral blood eosinophilia and may lead to serious complications of the peripheral nervous system, necessitating emergency therapeutic intervention.

Unmasking of Churg–Strauss Syndrome in an Asthmatic

Abstract Churg–Strauss syndrome, also known as eosinophilic granulomatosis, is one of the antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis associated with asthma and peripheral eosinophilia. Here, we present a case of a 50-year-old male, known asthmatic presenting with cough, dyspnea, fever, and lower limb purpura. On evaluation found to have perinuclear ANCA positivity; a nerve conduction study showed mononeuritis multiplex, and he was diagnosed with Churg–Straus syndrome.

A case of eosinophilic granulomatosis with polyangiitis associated with diffuse alveolar haemorrhage: A case report and case-based review.

A 76-year-old man with bronchial asthma was admitted for respiratory failure and bloody sputum. A significant drop in haemoglobin and multiple consolidations supported clinical diagnosis of diffuse alveolar haemorrhage (AH). Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was positive and urinalysis suggested glomerulonephritis. Based on eosinophilia, sinusitis, peripheral nerve involvement, and leukocytoclastic vasculitis, he was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) associated with AH. Our case-based review suggested that male predominance (65%), high positivity for ANCA (88%), and a high frequency of renal involvement (45%) may be characteristic of AH in EGPA. Although AH is rare in EGPA, we should be aware of this life-threatening complication.