Microscopic Polyangiitis Research Articles

#886 Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis

Abstract Background and Aims Cardiovascular disease (CVD) is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). However, in current clinical guidelines, limited evidence is available to support the recommendation of AAV-specific screening for cardiovascular comorbidities. This study reported the prevalence of electrocardiogram (ECG) abnormalities and investigated associations between ECG abnormalities and fatal CVD in a validated cohort of patients with AAV compared to matched controls. Method Based on a retrospective matched cohort design, patients with granulomatosis with polyangiitis [ICD-10: DM31.3] or microscopic polyangiitis [ICD-10: DM3.17] and accessible ECGs were identified in nationwide Danish health care registers from 2000 to 2021. Patients with AAV were matched 1:3 on age, sex, and calendar year of ECG measurement with controls without AAV. Index date was defined as the date of ECG measurement. ECGs were hierarchically categorized as either no, minor, or major ECG abnormalities according to contemporary literature. The associations between ECG abnormalities and fatal CVD were assessed in multiple Cox regression models adjusted for age, sex, and comorbidities. Counterfactual G-estimation of hazard ratios (HRs) standardized to age and sex was performed to estimate the 5-year absolute risk (AR) of fatal CVD according to ECG-abnormalities. Results A total of 1431 patients with AAV were matched to 4293 controls. The median age of patients with AAV and matched controls was 69 (IQR 58-77) years, and 52.3% were males. Median study follow-up time was 4.8 (IQR, 2.7-7.8) years. AAV was associated with increased prevalence of left ventricular hypertrophy (17.5% vs. 12.5%, p < 0.001), ST-T deviations (10.1% vs. 7.1%, p < 0.001), atrial fibrillation (9.6% vs. 7.5%, p = 0.017) and corrected QT prolongation (5.9% vs. 3.6%, p < 0.001) compared to controls. When examining associations of fatal CVD across no, minor or major ECG abnormalities, only the patients with AAV and major ECG abnormalities had a higher risk of fatal CVD [HR 1.99 (95% CI, 1.49-2.65)], compared to matched controls. This corresponded to a significantly higher standardized 5-year AR of fatal CVD compared to controls: 19.14% (95% CI, 16-22%) vs. 9.41% (95% CI, 8-11%). Conclusion AAV was associated with a higher prevalence of major ECG abnormalities such as left ventricular hypertrophy, atrial fibrillation, and ST-T deviations compared to matched controls. Moreover, the patients with AAV demonstrating major ECG abnormalities had a particularly elevated risk of fatal CVD. This indicates that AAV patients with major ECG abnormalities are a distinct high-risk group within AAV patients prone to cardiovascular-related mortality.

#1770 Clinical characteristics and outcomes in patients with ANCA-associated vasculitis (AAV) and kidney involvement—a Swedish single-center cohort

Abstract Background and Aims Poor patient outcomes in ANCA-associated vasculitis (AAV) with kidney involvement is attributed to multiple factors such as delay in diagnosis, inadequate efficacy of treatments and long-term complications due to the disease as well as the toxic effects of immunosuppressive therapy. The aim of the present study was to evaluate the clinical characteristics of a Swedish cohort of patients with AAV (granulomatosis with polyangiitis; GPA and microscopic polyangiitis; MPA) and kidney involvement to study causes of death and predictors of all-cause mortality. Method This retrospective single-centre cohort study included 93 patients from the Uppsala region in mid-Sweden, diagnosed with AAV and kidney involvement between 1993 and 2023. Clinical and laboratory variables were obtained from review of electronic medical records as well as patient follow-up visits. Differences between groups were assessed using independent t-test and Chi-square test. Multivariable logistic regression analyses were performed to evaluate the influence of risk factors of interest on all-cause mortality. Results 93 patients, 71 (76%) were clinically diagnosed with MPA, and 22 (24%) with GPA. The median age at diagnosis was 66.5 ± 13 years. eGFR at diagnosis was 29 ± 23.5 ml/min/1.73 m2 and 15% of patients were dialysis-dependent AAV at diagnosis. Patients with MPA and GPA received comparable induction therapy except for PLEX which was significantly more frequent in patients with GPA (52% vs 26% respectively, p = 0.041). 56 (60%) of patients died during follow up and survival time was 7.1 ± 6.9 years. Baseline clinical and biochemical characteristics are shown in Table 1. A multivariate logistic regression showed that older age at diagnosis (OR 95% CI 1.012-1.110; p = 0.013) and being dialysis-dependent at diagnosis (OR 95% CI 1.343-16.079; p = 0.015) significantly predicted all-cause mortality (Table 2). Causes of death are presented in Fig. 1. Infections was the most common cause of death (30%). Conclusion Long-term prognosis and patient survival were significantly associated with age and dialysis-dependency at diagnosis in this cohort of patients diagnosed with AAV and kidney involvement. Infections was the most common cause of death.

#1700 Clinical presentation and prognosis in ANCA-associated vasculitis with occupational exposure to silica: a monocentric retrospective study

Abstract Background and Aims Exposure to silica is associated with an increased risk of autoimmune diseases, including ANCA-associated vasculitis (AAV) [1–3]. It remains unclear whether silica exposure modifies clinical presentation of AAV, and it is not known whether it affects prognosis. The aim of this work is to address these questions. Method This is a retrospective, monocentric observational study comparing clinical and prognostic features between two groups of patients with ANCA-positive AAV: cases with a well-documented history of occupational exposure to silica (confirmed by industrial hygienists) and controls with no exposure. Each case was matched to 2 controls based on time of diagnosis (± 1 year relative to the case). Clinical features were compared across the two groups using Student's t test or chi-squared test, as appropriate. Clinical outcomes were compared across groups with the log-rank test and Cox proportional hazards regression. Results We identified 25 patients with AAV and a clear-cut history of occupational exposure to silica and 50 controls with no exposure, diagnosed between 2000 and 2023. Compared to controls, patients exposed to silica were more frequently males and smokers (Table). Average age at presentation was 66 ± 14 years and most patients had microscopic polyangiitis and MPO-ANCAs, with no significant differences according to silica exposure (Table). Patterns of organ involvement were also comparable across the two groups (Table). Renal vasculitis was present in almost all patients, probably reflecting a referral bias. Severity of renal impairment at diagnosis (Table) and evolution to end stage renal disease (Figure) were similar between exposed and unexposed individuals. There was a trend for lower survival in patients with exposure to silica (median survival from AAV diagnosis: 172 months in cases and 111 months in controls, log-rank test p = 0.065, Figure). In multivariate Cox regression, the risk of death was independently associated with age at diagnosis (HR 1.09 per year, 95% CI 1.04-1.14, p < 0.001) and not with silica exposure (HR 0.96, 95% CI 0.39-2.41, p = 0.936) or smoking history (HR 2.06, 95% CI 0.80-5.33, p = 0.135). Conclusion Patients with AAV and exposure to silica were more frequently males and smokers, likely reflecting socio-economic factors. We did not identify otherwise distinct clinical features in exposed patients, similarly to other Authors such as Hogan et al [2]. Exposure to silica did not seem to significantly affect renal prognosis or survival either, despite a trend in univariate analysis for higher mortality in individuals with silica exposure. The limited sample size and lack of quantification of silica exposure must be acknowledged and may have reduced statistical power.

#1337 Evolution of ANCA-associated vasculitis in a population with confirmed renal involvement. Myeloperoxidase and proteinase 3 antibodies, which is worse?

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare but potentially serious diseases with high mortality. Renal involvement is frequent in AAV with patients developing end-stage renal disease (ESRD) or becoming dependent on dialysis in up to 23% of patients. Several studies suggest the presence of clinical factors as predictors of survival in these diseases. The objective of this study was to analyze clinical evolution of AAV and to identify potential risk factors for developing renal events (ESRD or dialysis) and death in patients with AAV, with special attention to the implications that the presence of myeloperoxidase (MPO) or proteinase 3 (PR3) antibodies at diagnosis may have on the disease progression. Method We conducted a retrospective observational study of patients under follow-up for AAV. We considered only those with a confirmed diagnosis of AAV through renal biopsy for the present study. We collected clinical and laboratory variables at the time of disease presentation. We divided the patients based on the presence of MPO or PR3. Subsequently, we analyzed the patients' progression towards the occurrence of renal events (ESRD or dialysis) and mortality. Results Out of the 42 studied patients, 29 were MPO-positive and 13 were PR3-positive. We observed statistically significant differences in age and the frequency of hypertension, with the MPO group being older and more hypertensive than the PR3 group. On the contrary, PR3-positive patients exhibited a higher percentage of diabetes and increased severity of vasculitis at diagnosis as measured by the Birmingham Vasculitis Activity Score (BVAS). While most MPO-positive patients met criteria for microscopic polyangiitis (MPA), all PR3-positive patients met criteria for granulomatosis with polyangiitis (GPA) according to the ACR/EULAR 2022 guidelines. There were no statistically significant differences regarding clinical or laboratory variables analyzed, neither with induction nor maintenance treatment. We did not observe differences in the progression towards renal events or mortality between groups. However, we did observe a higher percentage of disease recurrence among PR3-positive patients (Table 1). Conclusion There were no statistically significant differences observed in the progression towards renal events (ESRD and dialysis) or mortality regardless of MPO or PR3 antibodies.

Large-vessel involvement in ANCA-associated vasculitis: A multicenter case-control study

ObjectiveAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. MethodsThis multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. ResultsWe included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11–10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23–2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70–5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). ConclusionRegardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.

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.

The predictive performance of the ANCA renal risk score in patients over 65 years of age with renal ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden and prevalent microscopic polyangiitis. We retrospectively studied a cohort of 192 patients over 65 years of age [median (interquartile range) age: 73 (68-78) years], including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres in northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event. The median serum creatinine concentration at diagnosis was 300 (202-502) µmol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%) and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% (interquartile range 7.6-20.0) in the medium-risk group and 44.0% (29.0-58.0) in the high-risk group (P<.001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 (0.58-0.74) for the prediction of ESKD at 12 months; this rose to 0.86 (0.80-0.90) when dialysis status at diagnosis was included. The ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement-especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the predictive performance of the ARRS.

Evolution of therapeutic management of patients with ANCA associated vasculitis in France after licensing Rituximab use

IntroductionIn 2013, rituximab was approved in France for the treatment of ANCA-associated vasculitis (AAV). The aim of the study was to compare the treatment and health events of adult incident patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), included before rituximab approval (over 2010–2012, Group 1) and those included after rituximab approval (over 2014–2017, Group 2).MethodData were extracted from the French National Health Insurance database (SNDS) including outpatient health care consumption and hospital discharge forms. Comparisons between inclusion periods were performed using Wilcoxon and χ² tests. Kaplan-Meier method was used to model the duration of treatment induction, maintenance, and off-drug periods. Fine and Gray tests were used to compare treatment phase durations.ResultsA total of 694 GPA and 283 MPA patients were included in Group 1, while 668 GPA and 463 MPA patients were included in Group 2. Between the two inclusion periods, the proportions of patients treated with rituximab increased in the induction and maintenance phases whereas treatment with azathioprine declined. These proportions remained stable in the case of methotrexate, cyclophosphamide, and glucocorticoid-treated patients. Frequency of first-time hospitalized infections, diabetes and renal failure during the first year after inclusion increased for both groups.Limitations of the studyThis is a retrospective study based on claims data including only 76% of people covered by health insurance in France. The period studied includes the learning phase of using rituximab. This study lacks biological data and precise quantitative analysis for the use of steroids, therefore the criteria for establishing diagnosis and therapeutic choice were unknown.ConclusionsIntroduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids or cyclophosphamide.

Investigating the concomitance of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides and inflammatory bowel disease (IBD)

ObjectiveTo assess relationship between Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and inflammatory bowel disease (IBD). MethodsThis is a retrospective study design. The patients were identified using a preset criteria of patients who have the diagnosis of ANCA associated vasculitis including a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) with overlapping inflammatory bowel disease (Crohn's disease or ulcerative colitis) in the time period from 01/01/2020 to 08/03/2023. Subsequently data from each patient was collected that will include baseline demographics, disease characteristics, disease activity, treatment information, multiorgan involvement, and pathology findings which were then analyzed. Results39 patients were identified that met criteria. 20 patients carried a diagnosis of GPA, 6 had MPA and 4 patients had EGPA. 20 patients with GPA had inflammatory bowel disease, 13 with ulcerative colitis and 6 with Crohn's disease while 1 GPA patient had unspecified inflammatory bowel disease. 4 patients with EGPA had inflammatory bowel disease, 2 with ulcerative colitis and 2 with Crohn's disease. 6 patients with MPA had inflammatory bowel disease, 4 with ulcerative colitis and 2 with Crohn's disease. IBD diagnosis preceded the diagnosis of ANCA vasculitis in 77.8 % of the cases. ConclusionObjective observation and deductions from this study raise the concern for a possible pathogenic association of ANCA associated vasculitis and inflammatory bowel disease and more research is needed to identify any causal association or influence of the two systemic disease on each other.

Chemokine expression in sera of patients with microscopic polyangiitis and granulomatosis with polyangiitis

We evaluated chemokine expression and its correlation with disease activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) (MPA/GPA). Serum CCL2, CCL4, CCL19, CXCL1, CXCL2, and CX3CL1 level in 80 patients were analysed using multiple enzyme-linked immunosorbent assays. Correlations between variables were investigated using Pearson’s correlation analysis, and receiver operator curve analysis was performed to identify optimal CX3CL1 values in determining active disease. Multivariate logistic regression analysis was done to evaluate predictors of active disease. CCL4 (r = 0.251, p = 0.025), CXCL1 (r = 0.270, p = 0.015), and CX3CL1 (r = 0.295, p = 0.008) significantly correlated with BVAS, while CX3CL1 was associated with five-factor score (r = − 0.290, p = 0.009). Correlations were revealed between CCL2 and CCL4 (r = 0.267, p = 0.017), CCL4 and CXCL1 (r = 0.368, p < 0.001), CCL4 and CXCL2 (r = 0.436, p < 0.001), and CXCL1 and CXCL2 (r = 0.518, p < 0.001). Multivariate analysis revealed serum CX3CL1 levels > 2408.92 pg/mL could predict active disease (odds ratio, 27.401, p < 0.001). Serum chemokine levels of CCL4, CXCL1, and CX3CL1 showed association with disease activity and especially, CX3CL1 > 2408.92 pg/mL showed potential in predicting active MPA/GPA.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomized into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day and IVMP 1.0 g/day. The primary outcome was all-cause mortality, and the secondary outcomes were composite all-cause mortality and kidney failure, severe relapse and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (3%) died, 4 (2.0%) had kidney failure, 11 (5.5%) had severe relapse, and 40 (19.9%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause mortality 0.46 (95% CI: 0.07, 2.81) and 0.07 (95% CI: 0.01, 0.41), respectively; all-cause mortality/kidney failure 1.18 (95% CI: 0.26, 5.31) and 0.59 (95% CI: 0.08, 4.52), respectively; subdistribution HRs for severe relapse were 1.26 (95% CI: 0.12, 13.70) and 3.36 (95% CI: 0.49, 23.29), respectively; and for serious infection 1.88 (95% CI: 0.76, 4.65) and 0.94 (95% CI: 0.28, 3.13), respectively. IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

Risk factors for serious infections and infection-related mortality in patients with microscopic polyangiitis: Multicentre REVEAL cohort study.

Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

Avacopan's potential to decrease MPO-ANCA titres concurrent with ameliorated activity in ANCA-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, is effective in microscopic polyangiitis via the inhibition of neutrophil priming induced by C5a. However, the exact effect of avacopan on the production of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is yet to be clearly established. This report presents a microscopic polyangiitis patient without major organ damage where high levels of MPO-ANCA persisted with high-dose steroid therapy and azathioprine, but the addition of avacopan led to a reduction in MPO-ANCA titres. The present case implies that avacopan-mediated inhibition of C5a may lead to a reduction in MPO-ANCA levels, thereby potentially ameliorating the pathophysiology of ANCA-associated vasculitis. Nevertheless, the impact of avacopan on MPO-ANCA production cannot be asserted solely based on this report; therefore, further examination is necessary through subgroup analysis using data from larger-scale studies.

Latent class analysis of chest CT abnormalities to define subphenotypes in patients with MPO-ANCA-positive microscopic polyangiitis

BackgroundPatients with microscopic polyangiitis (MPA) and positive myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) may present with various abnormalities in chest computed tomography (CT). This study aimed to identify subphenotypes using latent class analysis (LCA) and to explore the relationship between the subphenotypes and clinical patterns, as well as compare the clinical characteristics of these subphenotypes in patients with MPO-ANCA-positive MPA (MPO-MPA). MethodsThe study identified subphenotypes using LCA based on chest CT findings in 178 patients with MPO-MPA and pulmonary involvement from June 2014 to August 2022. ResultsLCA identified 27 participants (15.2%) in class 1, 43 (24.1%) in class 2, 35 (19.7%) in class 3, and 73 (41.0%) in class 4. Class 1 was characterized by prominent inflammatory exudation, class 2 by fibrosis and architectural distortion, class 3 by predominantly bronchiectasis, and class 4 by lesions mixed with inflammation and fibrosis. Class 1 had the highest level of extrapulmonary disease activity, with 77.8% of patients experiencing diffuse alveolar hemorrhage. Class 2 had the lowest level of extrapulmonary disease activity, with 41.9% of patients showing usual interstitial pneumonia. Class 3 patients were more likely to have complications involving the ear, nose, and throat, as well as pulmonary infections before treatment, and they exhibited the best outcomes. The characteristics and outcomes of class 4 were intermediate among the four classes. ConclusionsThese findings suggest that bronchiectasis may represent a unique pattern of pulmonary involvement in MPO-MPA, highlighting the importance of screening for bronchiectasis in MPO-MPA and identifying optimal management strategies.

Predictors of medications-free and long-term remission in anti-neutrophil cytoplasmic antibody-associated vasculitis: Real-world evidence.

In this study, we report the outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in daily practice based on Connective Tissue Diseases Research Center-Vasculitis Registry (CTDRC-VR) data. Patients were included if they were 18 years or older, had a diagnosis of the groups of AAV based on 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis, and were followed for a period longer than 2 years or were died. Complete clinical remission was defined as granulomatosis with polyangiitis (BVAS/GPA) of 0. Sustained remission was defined as a complete clinical remission for at least six months and tapering prednisolone dose to ≤ 7.5 mg/d. Long-term remission was defined as complete clinical remission for ≥ 5 years and tapering prednisolone dose to ≤ 7.5 mg/d. Medications-free remission was defined as complete clinical remission and discontinuation of glucocorticoids, cytotoxic medications and biologics. Sixty patients with AAV were enrolled in this study. Sustained and long-term remission were developed in 91.7 and 72.1 percent of patients, respectively. Relapse was developed in 27 (45%) patients. Medications-free remission was developed in 23 (33.3%) patients. Vasculitis induced damage was developed in 40 (66.7%) patients. Patients with damage had significantly lower age and higher BVAS at the baseline. Upper airway and renal involvement, and non-adherence in patients with damage was significantly more common. Induction therapy leads to long-term and medications-free remission in 72% and 38% of patients with AAV, respectively.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial

IntroductionSeveral studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis...

Performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for antineutrophil cytoplasmic antibody-associated vasculitis in previously diagnosed adult patients from Türkiye.

Objectives: This study aimed to evaluate the applicability of the new 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria in Turkish adult patients previously diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients and methods: One hundred sixty-four patients (96 males, 68 females; mean age: 49.6±14.4 years; range, 18 to 87 years) diagnosed with AAV by experienced rheumatologists between July 2016 and May 2022 were included in this retrospective cross-sectional study and reclassified based on the 1990 ACR criteria, the European Medicines Agency (EMEA) algorithm, and the 2022 ACR/EULAR criteria. For external validation, 83 patients (48 males, 35 females; mean age: 47.3±17.5 years; range, 19 to 81 years) diagnosed with immunoglobulin (Ig)A vasculitis were included. Results: One hundred twenty-six (76.8%) patients had granulomatosis with polyangiitis (GPA), 13 (7.9%) patients had eosinophilic granulomatosis with polyangiitis (EGPA), and 25 (15.2%) patients had microscopic polyangiitis (MPA). According to the criteria, the number of unclassified patients was nine (5.5%) for both the 2022 ACR/EULAR AAV classification criteria and the EMEA algorithm. The new criteria had an almost perfect agreement with the clinician's diagnosis (Cohen's kappa coefficient [κ]=0.858 for GPA, κ=0.820 for EGPA, and κ=0.847 for MPA). The kappa statistics for agreement of 2022 ACR/EULAR classification criteria with the EMEA algorithm were found 0.794 for GPA, 0.820 for EGPA, and 0.700 for MPA. None of the 83 patients diagnosed with IgA vasculitis could be classified as GPA, EGPA, or MPA using the new ACR/EULAR AAV classification criteria. Conclusion: The 2022 ACR/EULAR classification criteria for AAV showed substantial or perfect agreement with the clinical diagnosis and the EMEA algorithm.