Eosinophilic Granulomatosis Research Articles

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.

Radioclinical Profile of Eosinophilic Lung: A Case Series.

In this study, we present findings from an analysis of 17 patients diagnosed with eosinophilic lung disease, with a majority (64.70%) being male. The average age of the patients was 54±13.22 years. A history of uncontrolled asthma was noted in nine cases. The clinical picture was characterized by persistent dyspnea and cough. Blood hypereosinophilia was present in all cases, with a median of 1770 cells/ul. Two patients had a pulmonary eosinophilia greater than 25%.Radiological findings were consistent with diffuse bilateral ground-glass opacities or areas of consolidation in the majority of cases. The main etiologies identified were chronic eosinophilic pneumonia (12 cases), followed by eosinophilic granulomatosis with polyangiitis(3 cases), idiopathic hypereosinophilic syndrome (1 case) and drug-induced hypereosinophilia (1 case). All patients were treated with systemic corticosteroids, with the addition of immunosuppressive therapy necessary in three cases. Notably, five relapses were recorded after corticosteroid therapy was stopped.

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.

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.

Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan.

Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration(FDA) and the European Medicines Agency (EMA)also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.

The role of radiological imaging in the management of severe and difficult-to-treat asthma.

Radiological imaging has proven to be a useful tool in the assessment of asthma, its comorbidities and potential complications. Characteristic chest radiograph and computed tomography scan findings can be seen in asthma and in other conditions that can coexist with or be misdiagnosed as asthma, including chronic rhinosinusitis, inducible laryngeal obstruction, excessive dynamic airway collapse, tracheobronchomalacia, concomitant COPD, bronchiectasis, allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, and eosinophilic pneumonia. The identification of the characteristic radiological findings of these conditions is often essential in making the correct diagnosis and provision of appropriate management and treatment. Furthermore, radiological imaging modalities can be used to monitor response to therapy.

#1828 Venous thromboembolic events in ANCA associated vasculitis patients—data from Croatian referral center

Abstract Background and Aims Our aim was to investigate the prevalence of venous thromboembolic events (VTE) in a cohort of patients with ANCA-associated vasculitis (AAV) and define factors associated with the frequency of VTE considering there is data on high incidence of VTE in AAV patients. In these cohorts VTE occurred mostly early in the course of disease. Method This study included 114 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Patients were classified according to clinical: granulomatosis with poliangitis (GPA), microscopic polingitis (MPA) and eosinophilic granulomatosis with poliangitis (EGPA) and serological phenotype: MPO-ANCA positive, PR3-ANCA positive, MPO- and PR3-ANCA positive and ANCA-negative. Ordinal variables were analysed using logistical regression test. Statistical analysis was done in MedCalc Statistical Software version 18.11.6 (MedCalc Software Bvba, Ostend, Belgium). Results In the cohort there were 64 (56%) females, mean age was 58 (IQR 16-84) with mean follow up time 46.9 months (IQR 1-127). Clinically there were 84 (73%) patients with MPA, 26 (22%) with GPA and 4 (5%) with EGPA. Serologically there were 20% PR3-ANCA, 54% MPO-ANCA, 8% MPO- and PR-3 ANCA positive patients and 18% ANCA-negative patients. Mean serum creatinine levels (SCr) was 380.9 μmol/l (IQR 65-1402). Mean BVAS (Brimingham vasculitis score) at the time of diagnosis of AAV was 17 (IQR 5-50) and at the time of VTE 0, 9 (0-22). Mean body weight was 71kg (IQR 48-110) and mean CRP was 84 mg/ml (IQR 0, 3-256). During the follow up 7 (6.14%) of the patients had VTE, with 4 having VTE in first month after the diagnosis and other two at month 14 and 19. Logistic regression showed the connection of weight (P = 0.0052) and CRP (0.0138) with VTE with odds ratio of 1,0829 for CRP (1.003-1.027) and 1.0150 for weight (1.0284-1.1736) respectively. There was no statistical significance for clinical or serological phenotype being associated with VTE nor for other clinical or laboratory parameters. Conclusion In our cohort patients with AAV were at risk of VTE, particularly within the first year following onset of disease. In this cohort the frequency of VTE did not depend of clinical or serological AAV phenotype, age or gender. Only CRP and body weight were associated significantly with VTE occurrence. Despite VTE rates in AAV patients, routine anticoagulation is not recommended in AAV patients, given the potential risk of bleeding complications. Prospective studies are needed to assess VTE risk stratification in AAV patients and to evaluate the both benefits and potential risks ratio of prophylactic anticoagulation in AAV patients.

#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.

Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

EOSINOPHILIC MYOPERICARDITIS: A CASE SERIES

Abstract Background Eosinophilic myocarditis is characterized by acute myocardial inflammation due to eosinophilic tissue infiltration. Methods Diagnosis was based on laboratory tests, Echo and CMR; EMB was performed in uncertain cases. Treatment was performed according to the etiology of EM. All patients underwent regular follow–up at our Center. Results This study includes 9 patients (89% Caucasian, 78% women, mean age 48.2±13.6 years), admitted in our Center from February 2021 to November 2023. 66.67% cases occurred in the setting of eosinophilic granulomatosis with polyangiitis, 11% was secondary to B–cell lymphoblastic leukemia, and 22% were labelled as idiopathic EM. All patients presented with high eosinophil count (6133±4893/mcL), elevated CRP (57±66 mg/L) and hs–troponin I (3610±5166 ng/L) levels, and 67% cases NT–proBNP (10751±4038 ng/L) was elevated. 67% patients presented with dyspnea, 56% with chest pain, and 56% with fever. On ECG, sinus tachycardia, low QRS voltages and ST segment depression with negative T–waves were common. Thickening of the myocardial walls with reduction of GLS was seen in all cases; in 44% cases, the EF was below 50%; 56% cases had mild pericardial effusion. 1 patient had intraventricular thrombi at CMR, another one had bilateral pulmonary embolism. On CMR, all patients had areas of hypokinesia, myocardial edema, and myo–pericardial late gadolinium enhancement. EMB was performed in 5 cases, confirming the presence of intramyocardial eosinophilic infiltrates. 7 patients required CICU, and 1 needed inotrope (dobutamine) use. The patient with ALL was treated with combined chemotherapy. The other EM cases were treated with immunosuppressive therapy consisting of corticosteroids and either cyclophosphamide or rituximab or mepolizumab. All patients received cardioprotective therapy with BBs and ACE–inhibitors; in patients with pericardial involvement, colchicine was administered. All patients showed rapid clinical improvement following immunosuppressive therapy initiation, with prompt reduction of circulating eosinophils and hs–troponin I values and normalization of the ejection fraction. On CMR imaging, edema disappeared at follow–up, with LGE replacement in one case. All patients were alive and in good conditions at the last follow–up. Conclusions EM is an underdiagnosed life–threatening disease. A careful assessment of the etiology, as prompt therapy, is mandatory to achieve clinical amelioration and good mid–term prognosis.

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.

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.

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.

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.

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.

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.