Churg-Strauss Research Articles

Disease Overlap, Healthcare Resource Utilization, and Costs in Patients with Eosinophilic Granulomatosis with Polyangiitis: A REVEAL Sub-study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophil-associated disease (EAD) characterized by inflammation in small- to medium-sized blood vessels. Inthe REal-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study, overlap among 11 EADswas assessed. In the present sub-study, we evaluated EGPA overlapwith other EADs, all-cause EAD- and EGPA-related healthcare resource utilization (HCRU) and costs, and their relationship with blood eosinophil count and treatments received. REVEAL, a retrospective study, used Optum's de-identified Clinformatics® Data Mart Database. In this sub-study, eligibility criteria included an age of ≥ 12years, ≥ 1 EAD, continuous health-plan eligibility, and compliance with the EGPA/GPA case definition per International Classification of Diseases Ninth/Tenth Revision diagnosticcodes between 1 January 2015 and 30 June 2018. Patients were grouped based on whether they had received immunomodulators/cyclophosphamide/mepolizumab (ICM) or not (non-ICM). Of 701 patients with EGPA, 29.5% were in the ICM group. Overall, 72.2% had ≥ 1 overlapping EAD. The number of overlaps was similar for the ICM and non-ICM groups. In patients with blood eosinophil counts ≥ 300 cells/µL, 22.8% had ≥ 1 overlapping EAD. The mean annual all-cause cost was $98,644, 54.1% of which was from outpatients and 33.6% from inpatients. The mean annual EAD- and EGPA-related costs were $23,820 and $9,306, respectively. Patients in the non-ICM groupversus the ICM group had higher all-cause ($101,560 vs $91,684) but lower EAD-related ($22,733 vs $26,412) and EGPA-related ($6,171 vs $16,786) costs. All-cause HCRU and costs increased with increasing overlap. EGPA was associated with substantial HCRU and costs, driven by outpatient and inpatient settings. More overlapping EADs were associated with higher HCRU and costs, highlighting the need for treatment to reduce healthcare expenditure in these patients. Infographic available for this article.

Eosinophilic granulomatosis with polyangiitis associated with malignant arrhythmias: a case report

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis associated with significant cardiac morbidity and mortality. This case report presents the diagnostic and management challenges of EGPA-related arrhythmias in a remote general hospital setting. Case summary A 64-year-old Caucasian male presented with an indolent prodrome of fatigue, shortness of breath and anorexia, that culminated in an acute presentation with pulmonary embolism. His complicated clinical course included intracranial haemorrhage and refractory ventricular arrhythmias. Eosinophilia and subendocardial hypoattenuation observed on chest computed tomography were key findings that led to the diagnosis of EGPA. Multiple antiarrhythmic therapies were required as temporary measures whilst control of the underlying eosinophilic inflammation was achieved. Once stable, the patient was transferred to a tertiary cardiac centre for further investigation and cardioverter-defibrillator implantation. With EGPA now well controlled, he has experienced no further ventricular arrhythmias and has fully recovered. Conclusion Cardiac complications of EGPA, including ventricular arrhythmias, are difficult to manage without concurrent immunosuppression, which may itself further destabilise cardiac electrophysiology. The role of multiple imaging modalities in the diagnosis and monitoring of EGPA is emphasised, with cardiac magnetic resonance imaging playing a crucial role in detecting subendocardial fibrosis.

Dupilumab for refractory chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with refractory chronic rhinosinusitis with nasal polyps (CRSwNP), despite current treatments. Dupilumab demonstrated efficacy in the treatment of severe and uncontrolled CRSwNP, with improvements in patient-reported outcome measures and in objective measurements. This study aims to evaluate efficacy and safety of dupilumab in refractory CRSwNP in EGPA patients. A prospective observational study was conducted on EGPA patients treated with dupilumab between 2021 and 2023. Patients in a phase of prolonged remission of vasculitis manifestations but still experiencing active CRSwNP were included. Clinical, biological, and rhinologic evaluations were performed, alongside with patient-reported outcomes measures (PROMs) and nasal cytology. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤ 4 mg/day, while partial response by BVAS = 0 and prednisone dose >4 mg/day. Nine EGPA patients were included. After 3 months, 55.6% achieved complete response, increasing to 83.3% at 12 months. Nasal symptoms and patient-reported outcomes improved significantly, with sustained efficacy over 12 months. An improvement in quality of life was also observed, with a significant reduction of the AAV-PRO score. Nasal cytology revealed reductions in eosinophils and neutrophils counts. Adverse events occurred in 44.4%, including hypereosinophilia in 2 cases, which led to dupilumab discontinuation. Dupilumab is an effective treatment option for severe and refractory ENT manifestations in EGPA, as it improves symptoms, reduces inflammation, and leads to better a quality of life. However, careful patient selection and monitoring are necessary to minimize adverse events and optimize outcomes.

Long-term efficacy of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: a propensity score matching analysis in the multicenter REVEAL cohort study.

Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings. This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients.

Clinical Significance of Overlap Syndrome of Histologically Confirmed Lupus Nephritis with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Objectives: We applied the 2022 American College of Rheumatology/ European Alliance of Association for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients histologically diagnosed with lupus nephritis (LN) to investigate the overall rate of and initial contributing factors to the reclassification of overlap syndrome of LN with AAV (OS-LN-AAV). Methods: We retrospectively reviewed the medical records of 1292 patients with systemic lupus erythematosus (SLE) and included 164 patients with LN in this study. Patient demographics, SLE manifestations, LN classes, and laboratory data, including ANCA levels, were recorded. All-cause mortality and end-stage kidney disease (ESKD) were evaluated as poor outcomes. Results: The median age of the 164 patients was 37.0 years, and 12.2% were men. The overall reclassification rate was 37.8%, of which 34.1% and 3.7% of the patients were reclassified as having OS-LN-microscopic polyangiitis and OS-LN-granulomatosis with polyangiitis (GPA), respectively, but none as having eosinophilic GPA. ANCA positivity and AAV-suggesting lung lesions were major contributors to OS-LN-AAV reclassification. When patients were compared based on OS-LN AAV reclassification, ANCA positivity and myeloperoxidase-ANCA (or P-ANCA) positivity favoured for OS-LN-AAV reclassification, whereas oral ulcers did not. However, OS-LN-AAV reclassification did not affect all-cause mortality or ESKD. Conclusions: This is the first study demonstrating a 37.8% reclassification rate in patients histologically diagnosed with LN using the 2022 ACR/EULAR criteria for AAV. Furthermore, it was also the first to reveal ANCA positivity and AAV-suggesting lung lesions as major contributors to OS-LN-AAV reclassification.

Long-term efficacy of mepolizumab on eosinophilic granulomatosis with polyangiitis: a retrospective study

Aim: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Patients with EGPA are treated with systemic glucocorticoids and immunosuppressive drugs to induce and maintain remission. However, most patients relapse after tapering glucocorticoids, and there are refractory cases with inadequate response to glucocorticoids. Mepolizumab, a humanized anti-IL-5 antibody, is approved for relapsing or refractory EGPA. Furthermore, recent studies have reported the efficacy of benralizumab, a humanized anti-IL-5 receptor α antibody, in EGPA. Here, we investigate the efficacy of biologics on consecutive cases of EGPA. Methods: We retrospectively collected patients with EGPA treated with mepolizumab in addition to glucocorticoids at the Department of Pulmonary Medicine in Kagoshima University Hospital and Imakiire General Hospital. In this study, we compared the effects of biologics on inflammatory parameters between pre- and post-treatment of biologics in patients with EGPA. Results: Ten patients were included in the study. All patients were treated with mepolizumab, and one was switched to benralizumab later. Treatment with biologics markedly reduced EGPA relapse from 70% (pre-treatment) to 20% (post-treatment), Birmingham Vasculitis Activity Score from 8.4 to 4.0, peripheral blood eosinophil counts from 470.3 /µL to 40.5 /µL, and glucocorticoid doses from 7.3 mg/dL to 1.6 mg/dL. In contrast, lung function and fractional exhaled nitric oxide levels were not affected by treatment with biologics. Furthermore, the duration of biologics was positively correlated with symptom improvement. Conclusions: Treatment with mepolizumab for EGPA was effective in glucocorticoid sparing, symptom reduction, and relapse prevention. Mepolizumab is expected to reduce the risk of glucocorticoid-related adverse events. Therefore, continued administration as well as early intervention with mepolizumab for EGPA might be important to conserve future medical resources and control the disease.

Tense blisters and hemorrhagic bullae as the first manifestation of eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) poses a significant diagnostic challenge due to its varied clinical presentation. Here, we present a case of a 59-year-old female with a history of asthma and sinusitis, who manifested with an extremely rare presentation of drastic tense blisters and hemorrhagic bullae alongside purpuric lesions and peripheral neuropathy. Examinations revealed eosinophilia, positive anti-neutrophil cytoplasmic antibody, and characteristic pathological findings with small vessel vasculitis in the purpura. Treatment with glucocorticoids and cyclophosphamide led to rapid improvement in peripheral eosinophilia, skin manifestations and motor neuron deficits. Although rare, our case underscores that bullous skin lesions should be recognized as a potential cutaneous hallmark of EGPA to aid timely diagnosis, since prompt treatment initiation is crucial given the potential irreversible organ damage and poor prognosis of EGPA.

A case of eosinophilic granulomatosis with polyangiitis combined with pulmonary tuberculosis: A case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune disease that can affect multiple organ systems. The standard treatment mainly relies on glucocorticoids and immunosuppressive agents. In our study, we present an EGPA patient who had pulmonary tuberculous mycobacteria infection, such cases are rarely reported. A 71-year-old male patient was diagnosed with EGPA (systemic type) and pulmonary tuberculosis simultaneously. The Five-Factor score indicated that the patient required glucocorticoids combined with immunosuppressive agents for induction therapy, however, the use of immunosuppressive agents would significantly inhibit antituberculosis treatment. Nowadays, treating active autoimmune disease in patients with infections remains a clinical challenge. Considering the patient did not show life-threatening or severe organ involvement and reduced the effect of antituberculosis immunity, we used glucocorticoids alone. Finally, the patient had no adverse events, the eosinophil counts were markedly decreased and symptoms of EGPA were relieved. The patient of EGPA combined with pulmonary tuberculosis successfully treated with glucocorticoids alone may provide significant support in selecting the appropriate treatments for similar cases in the future.

The coincidence of multiple sclerosis and primary vasculitis; from the bench of pathology to the bedside of treatment: a systematic review of case reports.

Multiple sclerosis (MS) is a chronic, disabling neurodegenerative disease, leads to reduced quality of life. The increasing prevalence of MS around the world and its comorbidities increase its burden. Primary vasculitis subtypes, one of autoimmune diseases with different prevalence in different ages and genders, should be considered one of the important differential diagnosis in patients with MS. This study aims to verify the relationship between MS and primary vasculitis by conducting a systematic review. We searched PubMed, Scopus, EMBASE, Web of Science, and Google Scholar, from January 1974 to July 2023. We included original articles that reported characteristics of patients involved with any type of Primary Vasculitis with MS. From an initial 816 publications, 18 studies consisting of 18 individual patients from 14 countries with confirmed MS and one of different subtypes of primary vasculitis met the inclusion criteria. The female/male ratio was 0.38:1, the mean (SD) age was 40.44 (14.37) years with the range of 16 to 70 years old, and the relapsing/progressive ratio was 1.57:1. Most of them, 14 (77%) experienced MS before vasculitis, and mostly received Corticosteroids, interferon, cyclophosphamide, Glatiramer acetate as MS treatment. The concurrence of Takayasu Arteritis (2 cases), Polyarteritis Nodosa (2 cases), Churg-Strauss Syndrome (1 case), Wegener's Granulomatosis (2 cases), Microscopic Polyangiitis (1 case), Cutaneous leukocytoclastic vasculitis (5 cases), Good pasture's disease (5 cases) were reported with MS. Our study suggested that different primary vasculitis can be an important comorbidity of MS and can mimic its symptoms and MRI. Any atypical syndrome for PwMS, whether clinical or radiological, must be evaluated in terms of other differential diagnoses including vasculitis.

Ocular manifestations in ANCA-associated vasculitis: a comprehensive analysis from Chinese medical centers.

This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes.

Efficacy and Safety of Mepolizumab in Patients With Eosinophilic Granulomatosis With Polyangiitis: A Single-Center Experience.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic vasculitis characterized by eosinophil-rich, necrotizing granulomatous inflammation primarily affecting the respiratory tract with necrotizing vasculitis of small- to medium-sized arteries. In this case series, we retrospectively evaluated the efficacy and safety of mepolizumab in seven patients diagnosed with EGPA who presented to the Department of Allergy and Clinical Immunology at Cleveland Clinic Abu Dhabi.The variables assessed before and after mepolizumab treatment included Birmingham Vasculitis Activity Score (BVAS), prednisolone dose, Asthma Control Test (ACT) score, and blood eosinophil count (BEC).We found a significant reduction in BVAS and prednisolone dosage with clinical improvements in asthma symptoms after treatment with mepolizumab.Our case series, the first from the Middle East on the use of mepolizumab in EGPA, demonstrates that mepolizumab is a safe and effective treatment for patients with EGPA.

Update on treatment of ANCA-associated vasculitis

This article summarizes the current guidelines and recommendations published by the European Alliance of Associations for Rheumatology (EULAR), the Kidney Disease Improving Global Outcomes (KDIGO) and the American College of Rheumatology (ACR). In addition to glucocorticoids (GC), treatment with biologics is nowadays an established option to treat Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV). Rituximab (RTX) is used for remission induction and maintenance in organ-threatening and non-organ-threatening granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). For eosinophilic GPA (EGPA) anti-interleukin 5 (IL5) strategies are an important component of treatment for remission induction and maintenance of refractory or relapsing non-organ-threatening diseases in conjunction with GC. The dosing of GC for remission induction in GPA and MPA is now lower than was previously used and additionally, avacopan is approved as anew GC-sparing medication for GPA and MPA over 52weeks. Conventional strategies, such as cyclophosphamide (CYC) are important for remission induction in severe or refractory organ-threatening disease for all AAVs. The use of methotrexate (MTX) and azathioprine (AZA) is becoming less prominent. The most important unanswered questions in the treatment of AAVs are with respect to the duration of remission maintenance treatment and the individualized treatment guidance based on biomarkers.

Superiority of Avacopan and Mepolizumab to Glucocorticoid Tapering in the Treatment of Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Systematic Review.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a spectrum of autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have shown that avacopan and mepolizumab are promising therapeutics for partial or complete replacement of glucocorticoids (GC), with sustained remission while completely weaning off GC. Avacopan inhibits C5aR in the complement pathway, preventing neutrophil migration, while mepolizumab targets IL-5R, reducing eosinophil activity. Additionally, complement inhibition has not only contributed to the recovery of renal function and alleviation of physical symptoms but has also enhanced patients' overall quality of life and mental well-being. This systematic review explores the pathogenesis of AAV, traditional treatments, and the potential of emerging complement and interleukin antagonist therapies such as avacopan and mepolizumab in revolutionizing AAV management.

Epidemiology of ANCA vasculitis in Northern Spain.

The incidence of anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) shows disparate results due to variable classification criteria and heterogeneous-population series. We aimed to estimate the incidence of AAV in a well-defined population with standardized classification criteria. Population-based study of AAV patients diagnosed from January 2000 to December 2023 in Cantabria, Northern Spain. Patients were classified according to ACR/EULAR 2022 into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or unclassified vasculitis if the criteria were not met. Eosinophilic granulomatosis with polyangiitis (EGPA) patients were not included. The annual incidence rates were estimated by cases over 1,000 000 (106) (95% CI) including overall AVV, type of AAV, sex, and year of diagnosis. A literature review was also performed. We included 152 (80/72 men; mean age; 70.6 ± 13.18 years) patients. They were classified as MPA (67; 44%), GPA (64; 42.2%), and unclassified vasculitis (21; 13.8%). Annual incidence was 13.4 (10-16.8)/106 [male 14.5 (10.5-18.5); female 12.1 (8.7-15.6)]. The Annual incidence of MPA was 5.9 (4-7.8)/106 and GPA 5.6 (3.9-7.3)/106. The mean Annual incidence increased from 6.1 (4.5-7.7)/106-16.5 (5.6-27.4)/106 in the last three years, particularly, in GPA from 2.3 (0.3-4.9)/106-8.2 (2-14.5)/106. The prevalence of AAV was 184.7 (181-188)/106. During a 20-year period we found that the incidence of AAV (GPA and MPA) in Northern Spain is higher than Southern Spain, but lower than Northern European countries. An increase in the incidence was observed in the last years.

Severe Eosinophilic Asthma or Eosinophilic Granulomatosis With Polyangiitis: Potential Biomarkers for Novel Diagnostic Strategies

BackgroundSevere Eosinophilic Asthma (SEA) may be the prodromal phase of Eosinophilic Granulomatosis with Polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease. ObjectivesTo identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making. Methods30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose and Throat (ENT) and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein-ECP, IL5, IL4, total-IgE, IgG4, anti-neutrophil cytoplasmic antibody (ANCA), sputum (eosinophils count, periostin, IL8 and GMCSF) and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used. ResultsSEA patients had poorer asthma control (p<0.001) and higher level of sputum eosinophils (p<0.002) while EGPA patients reported higher levels of blood eosinophils in the past. Sputum GMCSF was the only biomarker significantly increased in EGPA patients compared with SEA (p<0.0001). Among SEA patients, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GMCSF (p<0.0005), blood and sputum eosinophils (p<0.0006, p<0.011) in comparison with the other patients. ConclusionSputum GMCSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in SEA patients, suspected of having EGPA

Myeloperoxidase-ANCA IgG induces different forms of small vessel vasculitis based on type of synergistic immune stimuli

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA-IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

Relapse in patients with ANCA-associated vasculitis: A cohort study from a centre for rheumatic diseases in Colombia

IntroductionRelapses are common in patients with ANCA-associated vasculitis (AAV), which results in a significant burden of morbidity, mortality, impact on quality of life, disability, and cost. However, evidence in the Colombian population is scarce. ObjectiveThe objective of this study was to estimate the relapse-free survival during the first year and describe clinical and serological variables of patients with AAV in a specialized centre for rheumatic diseases in Colombia. Materials and methodsA retrospective follow-up study was conducted on a cohort based on medical records of patients over 18 years old with confirmed diagnosis of AAV by the treating rheumatologist and who had achieved remission. Information on AAV relapse and clinical, immunoserological, and treatment-related characteristics was extracted. The relapse-free survival function during the first year was estimated. ResultsA total of 56 patients were included, 69.9% of whom were women, with a median age of 60 (IQR=48−63). According to the clinical phenotype, 64.3% were classified as granulomatosis with polyangiitis (GPA), 23.2% as microscopic polyangiitis (MPA), and 12.5% as eosinophilic granulomatosis with polyangiitis (EGPA). According to the European Vasculitis Study Group (EUVAS) classification, 39.3% had generalized AAV at debut, 23.2% had localized AAV, 21.4% had severe renal AAV, and 16.1% had systemic AAV. The median Five Factor Score (FFS) was 1 (IQR=0−2). The cumulative relapse-free survival at one year was 82.2%. ConclusionsThe relapse-free survival observed in this cohort was similar to other reports in clinical studies and AAV registries.

ST-Elevation Myocardial Infarction Due to Coronary Vasospasm Associated with Eosinophilic Granulomatosis with Polyangiitis: A Case Report.

ST-elevation myocardial infarction (STEMI) can be caused by underlying coronary artery vasospasm (CAV) with or without associated atherosclerotic disease. Coronary artery vasospasm is a rare but potentially devastating manifestation of eosinophilic granulomatosis with polyangiitis (EGPA). We describe a 54-year-old male with a known history of EGPA and coronary artery disease presenting to the emergency department with chest pain and an inferior STEMI on electrocardiogram. He was ultimately taken for coronary angiography and found to have a discrete vasospastic lesion in the right coronary artery that was treated with intra-coronary nitroglycerin and calcium channel blockers. He was continued on immunosuppressant agents (prednisone and mepolizumab) for management of EGPA and followed up with outpatient cardiology and rheumatology for vasospastic angina. This case highlights a rare cause of STEMI, discusses the nuances in treatment of STEMI due to CAV, and provides background on pathophysiology and treatment of EGPA.

Aural Manifestations of Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis-Diagnosis, Symptoms, Treatment.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitis sharing a common pathophysiology, which affects small and medium blood vessels. There are three categories of AAV: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). As a systemic disease, AAV can affect basically every organ. The goal of this publication is to sum up and underline the problem of the aural manifestation of AAV; it details the definition of Otitis Media with Antineutrophil Cytoplasmic Antibody Associated Vasculitis (OMAAV) and allows for a better understanding of the specific tasks of medical professionals taking part in the diagnostic and therapeutic process. Among others, this publication is directed to otolaryngologists who may encounter patients with AAV and often are the first specialists who see patients with early symptoms of AAV. This publication presents brief characteristics of AAV, descriptions of aural manifestations and symptoms, differential diagnosis, and both pharmacological and surgical treatment options, based on current recommendations and information found in the literature and clinical databases.

Causal relationship between immune cells and the risk of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: A Mendelian randomization study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease categorized as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The majority of patients are ANCA-positive, predominantly against myeloperoxidase (MPO). Previous studies have predominantly concentrated on the association between EGPA and neutrophils, but recent research has emphasized the role of lymphocytes in the development of EGPA. The objective of our research was to examine the causal association between immune cells and MPO + ANCA EGPA. A two-sample bidirectional Mendelian randomization (MR) analysis was performed, which included 159 MPO + ANCA EGPA cases and 6688 controls and utilizedGenome-Wind Associaton Studies (GWAS) summary statistics of immune traits from approximately 3757 individuals, encompassing around 22 millionsingle nucleotide polymorphisms (SNPs). Our findings revealed that 23 immunophenotypes were associated with MPO + ANCA EGPA. Furthermore, the reverse MR analysis showed that MPO + ANCA EGPA had significant causal effects on three immunophenotypes within the Treg panel. By integrating existing research, our study unveiled the contributions of Tregs, B cells, and monocytes to the development of EGPA. Subgroup analysis specifically examined the roles of lymphocyte subtypes, cytokines, and their surface molecules in the pathogenic mechanisms of the disease. This comprehensive approach provides a novel perspective on the biological mechanisms and early intervention strategies for MPO + ANCA EGPA by focusing on immune cells.