Birmingham Vasculitis Activity Score Research Articles

ANCA Kidney Risk Score (AKRiS) performance in a German Cohort of Patients with Histologically Confirmed ANCA-Associated Renal Vasculitis.

Predicting the outcome of ANCA-associated vasculitis (AAV) is a difficult task. One of the most promising prognostic scores, the ANCA Renal Risk Score (ARRS), has recently been updated and renamed to ANCA Kidney Risk Score (AKRiS). We wanted to test its performance in our population. 164 patients were included and categorized in subgroups analogous to that of both scores. Multivariable logistic regression analysis was applied to assess the risk of renal failure. Additionally, baseline data and outcome were compared between the subgroups of each score to retrieve useful clinical information. Stratified by AKRiS risk category, the proportions of patients who developed end-stage kidney disease (ESKD) at 36 months were 9.8%, 29.1%, 63.0%, and 83.3%, respectively (p < 0.001).Those belonging to the higher risk groups showed more pronounced proteinuria and anemia at diagnosis (p=0.001, p<0.001, respectively). Although our patients exhibited a more severe disease phenotype than those of AARS and AKRiS, both scores performed equally well: The Harrell´s C Index was similar (0.8381 vs. 0.8337). Beyond that, we found differences and similarities in the risk associations between the subgroups of both scores and disease activity or patient outcome, with some of them being described for the first time. For example, there was a higher risk of renal failure with anemia but not with C-reactive protein and the Birmingham Vasculitis Activity Score (BVAS) and an increased incidence of relapsing disease in the lower risk categories of ARRS. Here, we present the first external AKRiS validation confirming the improved ESKD prediction of the revised score in our cohort. Furthermore, we highlighted associations between risc score categories and patient mortality or vasculitis relapse.

A case of rapid avacopan-induced liver injury in pediatric granulomatosis with polyangiitis.

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered.

Patient-Reported Sinonasal Symptoms and Risk of Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Relapses are frequent and difficult to predict in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), resulting in long-term use of immunosuppression. Although sinonasal disease is associated with relapse of AAV, detailed characterization of sinonasal symptoms is lacking. Using a patient-reported outcome, the 22-item SinoNasal Outcome Test (SNOT-22), we investigated the relationship between sinonasal symptoms and disease activity in AAV. This was a prospective, longitudinal study of individual with AAV and healthy individuals. Relapse was defined as a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis score >0. Higher SNOT-22 scores indicate worse symptoms. Generalized estimating equation and Cox proportional hazard models evaluated the association between SNOT-22 and relapse. There were 773 visits (106 active disease visits) from 168 patients with AAV and 51 controls. Median SNOT-22 at remission was higher in AAV versus controls (20 vs 5; P < 0.001) and higher during active disease versus remission (P < 0.001). In all AAV, and particularly within granulomatosis with polyangiitis, higher SNOT-22 scores were observed months to years before relapse and were associated with increased risk of relapse (hazard ratio 2.7, 95% confidence interval 1.2-6.2; P = 0.02). Similar findings were seen when examining patients with versus without sinonasal disease and after removing relapses limited to the ear, nose, and throat. A patient-reported outcome measure of sinonasal disease, the SNOT-22, not only changes with disease activity in AAV, but also is associated with a higher risk of relapse within two years. These findings support the possibility that the SNOT-22 score may enhance prediction of relapse and that persistent sinonasal disease may be important in the pathophysiology of relapse.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA

Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients’ clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the “dominant” phenotype in idiopathic double-positive AAV.

Computable phenotype for real-world, data-driven retrospective identification of relapse in ANCA-associated vasculitis

ObjectiveANCA-associated vasculitis (AAV) is a relapsing-remitting disease, resulting in incremental tissue injury. The gold-standard relapse definition (Birmingham Vasculitis Activity Score, BVAS>0) is often missing or inaccurate in registry settings, leading...

Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group (P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission (P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV.

Von Willebrand factor: a possible biomarker for disease activity in vasculitis

Objective Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature. Method Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment. Results Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active. Conclusion vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Patient-reported outcomes in large vessel vasculitis: insights from a retrospective analysis of disease activity and associated factors

BackgroundPatient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA).MethodsWe retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0–10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors.ResultsThe study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14–0.24, p < 0.001). Higher patient G-DAS correlated with younger age (CI -3.4 - -1.5, p < 0.001), increased pain (CI 3.5-4, p < 0.001), functional limitations (HAQ, CI 0.5–0.6, p < 0.001), reduced physical (CI 2.3–2.7, p ≤ 0.001) and psychological well-being (CI 2.1–2.5, p < 0.001), and higher BMI (CI 1.3–2.4, p < 0.001). Physician G-DAS correlated with Birmingham Vasculitis Activity Score (V3.0; R 0.42, p 0.046) and were significantly linked to serum CRP elevations (β = 0.04, CI 0.0-0.08, p 0.028).ConclusionsThese findings underscore the need to integrate PRO measures into vasculitis disease management strategies, enhancing the understanding of disease activity from the patient’s perspective.

Clinical characteristics of hypertrophic cranial pachymeningitis in granulomatosis with polyangiitis: a retrospective single-center study in China.

Hypertrophic cranial pachymeningitis (HCP) is uncommon but a poorly understood complication of granulomatosis with polyangiitis (GPA). We conducted this retrospective study to elucidate the clinical characteristics and factors independently associated with granulomatosis with polyangiitis (GPA) complicated by hypertrophic cranial pachymeningitis (HCP) in China. We collected the medical records of 78 patients diagnosed with GPA who were admitted to the inpatient department of Peking Union Medical College Hospital between January 2003 and September 2021. Clinical features, laboratory and radiological findings, and Birmingham Vasculitis Activity Scores (excluding meningitis score) were recorded. A binary logistic regression analysis was performed to analyze factors independently associated with GPA-related HCP. Headache (100%) and cranial nerve palsy (61.5%) were common manifestations of HCP. Compared to 52 GPA patients without HCP, 26 patients with HCP required more time from initial symptoms to diagnosis, with a lower ratio of pulmonary and renal involvement, a higher ratio of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity, conductive or sensorineural hearing loss, mastoiditis, and decreased vision or sudden visual loss. Binary logistic regression analysis indicated that proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) negativity (OR 10.698, p = 0.001), conductive or sensorineural hearing loss (OR 10.855, p = 0.005), and decreased vision or sudden visual loss (OR 8.647, p = 0.015) were significantly associated with GPA-related HCP. Of the 26 patients, 18 received methylprednisolone pulse treatment, and 18 received intrathecal injections of dexamethasone and methotrexate. HCP was a severe manifestation of GPA in our study. Independent factors associated with the occurrence of HCP in patients with GPA included PR3-ANCA negativity, conductive or sensorineural hearing loss, and decreased vision or sudden visual loss. Furthermore, GPA-related HCP was associated with higher disease activity, requiring more intensive treatments.

Clinical Manifestations of Wegener Granulomatosis in Iranian Ethnicities Using the K-Means Algorithm: A Descriptive Study.

Introduction Wegener granulomatosis (WG) appears with clinical symptoms, including recurrent respiratory infection, renal manifestations, and nonspecific systemic symptoms. Objective To study the clinical manifestations of WG in Iranian ethnicities, and data on 164 patients were recorded from 2013 to 2018. Methods The data included demographics, symptoms, and the Birmingham Vasculitis Activity Score (BVAS). The symptoms involved the following sites: the nose, sinus, glottis, ears, lungs, kidneys, eyes, central nervous system, mucous membranes, skin, heart, stomach, intestine, as well as general symptoms. The clinical manifestations of nine ethnicities were analyzed. Results In total, 48% of the patients were male and 51% were female, with a median age of 51 years. The BVAS was of 15.4, the sites most involved were the sinus ( n = 155), nose ( n = 126), lungs ( n = 125), and ears ( n = 107). Gastrointestinal ( n = 14) and cardiac ( n = 7) involvement were less common. Among the patients, 48.17% were Persian, 13.41% were Azari, 11.17% were Gilaki, 11.17% were Kurd, and 10.9% were Lor. Conclusion Our findings indicated that the sinus, nose, lungs, and ears were the sites most involved, and gastrointestinal and cardiac involvement were less common. In the present study, involvement of the upper and lower respiratory tract was higher than that reported in Western and Asian case series. Moreover, we report for the first time that, in all patients with ear involvement, the left ear was the first to be affected. The clinical manifestations among Iranian ethnicities were not different, and the Gilaki ethnicity had the highest BVAS, mostly because the weather was humid; therefore, in Iran, in areas with humidity, the rate of the disease was higher.

A Wegner's Granulomatosis Risk Prediction Model Based on Machine Learning Algorithms

Introduction: Prediction of Wegener's granulomatosis diagnosis and relapse is a complex process. In this study, we applied machine learning algorithms to predict Wegener's granulomatosis relapse.&#x0D; Methods: In this research, 189 patients admitted to Amiralam Hospital were studied and followed for approximately 2 years. Patient features included demographics, organ involvement, symptoms, and other clinical data. Different popular machine learning algorithms were applied for predicting Wegener's granulomatosis relapse, including Support Vector Machines, Random Forest, Gradient Boosting, and XGBoost algorithms. The prediction model performance was measured for the different candidate prediction algorithms using accuracy, precision, recall, and F1-measure. The selected prediction model performance was calculated based on different relapse rates and major relapse occurrence according to Birmingham Vasculitis Activity Score (BVAS) fields.&#x0D; Results: Applying different machine learning algorithms, the XGBoost algorithm performed the best. The results indicated that the prediction model's performance increased when calculating higher relapse rate possibilities. The XGBoost model had 82% accuracy while predicting more than one relapse rate and 92% accuracy in predicting more than twice the relapse rate. We also calculated the SHAP value for the prediction model. The results indicated that Cr, BVAS, lymphocyte percentage, vitamin D, nose involvement, alkaline phosphatase, diagnosis age, white blood cell count, erythrocyte sedimentation rate, and initial nose presentation are the 10 most important features according to SHAP value.&#x0D; Conclusion: In this study, we have developed Wegener's granulomatosis relapse prediction model using machine learning algorithms. We achieved reasonable precision and recall for early prediction and decision- making regarding Wegener's granulomatosis relapse.

Clinical association of health-related quality of life and mortality in an antineutrophil cytoplasmic antibody-associated vasculitis cohort

ObjectivesTo evaluate the association between health-related quality of life (HRQoL) and mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). MethodsWe searched patients with AAV assessed for HRQoL at initial diagnosis using Short Form 36 (SF-36). Relationships between SF-36 physical component summary (PCS) and mental component summary (MCS) scales and variables were estimated using Pearson's correlation analysis. Contal's and O'Quigley's methods were used to determine optimal SF-36 PCS cut-off for predicting all-cause mortality. The Cox proportional hazards model and inverse probability of treatment weighting (IPTW) analysis were used to ascertain prognostic implications of SF-36 scales and mortality. ResultsThe median SF-36 PCS and MCS values of the 189 patients were 47.5 and 53.3, respectively, and 21 (11.1%) patients (microscopic polyangiitis [MPA], n=15; granulomatosis with polyangiitis [GPA], n=6) died during follow-up. SF-36 PCS was significantly but weakly associated with Birmingham Vasculitis Activity Score, Five-factor score, erythrocyte sedimentation rate (ESR), and C-reactive protein. However, SF-36 MCS was not associated with ESR. In the multivariable Cox analysis, a decrease of SF-36 PCS score by one unit indicated a higher death risk (hazard ratio [HR]: 1.030; 95% confidence interval [CI]: 1.007, 1.052; p=0.041), which was not for SF-36 MCS. IPTW analysis in a subgroup of MPA and GPA patients revealed increased patient mortality with SF-36 PCS <53.75 independently (HR: 3.249; 95% CI: 1.169, 9.033; p=0.024). ConclusionPoor baseline physical functioning associated with premature death in patients with MPA and GPA. HRQoL assessment during initial diagnosis may provide clinical insights for this population.

Clinical implications of peripheral eosinophil count at diagnosis in patients newly diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis

BackgroundThis study investigated the clinical implications of peripheral eosinophil count at diagnosis in estimating cross-sectional antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity and predicting all-cause mortality during follow-up in patients newly diagnosed with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsThis study included 224 immunosuppressive drug-naïve patients with peripheral eosinophil count at diagnosis < 1,000/mm3. The Birmingham Vasculitis Activity Score (BVAS), the Five-Factor Score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were assessed.ResultsThe median age of the 224 patients (152 MPA and 72 GPA) was 62.0 years; 35.3% of them were men. At diagnosis, peripheral eosinophil count was significantly correlated with BVAS (P = 0.001), FFS (P = 0.046), ESR (P < 0.001), and CRP (P < 0.001). Deceased patients had a significantly higher median peripheral eosinophil count at diagnosis than surviving patients (310.0/mm3 vs. 170.0/mm3, P = 0.004). In addition, patients with MPA and those with cardiovascular and renal manifestations at diagnosis exhibited significantly higher peripheral eosinophil counts than those without. When the optimal cut-off of peripheral eosinophil count at diagnosis for all-cause mortality during follow-up was set at 175.0/mm3, Patients with peripheral eosinophil count at diagnosis ≥ 175.0/mm3 exhibited a significantly lower cumulative patients’ survival rate than those with peripheral eosinophil count at diagnosis < 175.0/mm3 (P = 0.008).ConclusionsThis study was the first to demonstrate that peripheral eosinophil count at diagnosis could estimate cross-sectional AAV activity at diagnosis and contribute to predicting all-cause mortality during follow-up in MPA and GPA patients.

Impact of different ANCA serotypes on the long-term outcome of ANCA-associated vasculitis patients

Objectives To investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes. Methods Two hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared. Results In this study, the average follow-up was 46.4 months (range 0.3–188.4 months). One hundred and seventy-seven (79.0%) patients were MPO–ANCA-positive and 47 were PR3–ANCA-positive; the mean age of MPO–ANCA positive patients at diagnosis was elder than that of PR3–ANCA positive patients (67.0 vs. 60.0 years, p = .004). Among PR3–ANCA-positive patients, ear, nose and throat symptoms were more common (p = .014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p = .23). The ANCA serotype also had no effect on either disease relapse (p = .20) or remission rates (p = .10). In our study, PR3–ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3–ANCA patients were 60.7% and 76.9%, while that of MPO–ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis. Conclusions The likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores.

Risk prediction model for mortality in microscopic polyangiitis: multicentre REVEAL cohort study

BackgroundTo establish refined risk prediction models for mortality in patients with microscopic polyangiitis (MPA) by using comprehensive clinical characteristics.MethodsData from the multicentre Japanese registry of patients with vasculitis (REVEAL cohort) were used in our analysis. In total, 194 patients with newly diagnosed MPA were included, and baseline demographic, clinical, laboratory, and treatment details were collected. Univariate and multivariate analyses were conducted to identify the significant risk factors predictive of mortality.ResultsOver a median follow-up of 202.5 (84–352) weeks, 60 (30.9%) of 194 patients died. The causes of death included MPA-related vasculitis (18.3%), infection (50.0%), and others (31.7%). Deceased patients were older (median age 76.2 years) than survivors (72.3 years) (P < 0.0001). The death group had shorter observation periods (median 128.5 [35.3–248] weeks) than the survivor group (229 [112–392] weeks). Compared to survivors, the death group exhibited a higher smoking index, lower serum albumin levels, higher serum C-reactive protein levels, higher Birmingham Vasculitis Activity Score (BVAS), higher Five-Factor Score, and a more severe European Vasculitis Study Group (EUVAS) categorization system. Multivariate analysis revealed that higher BVAS and severe EUVAS independently predicted mortality. Kaplan–Meier survival curves demonstrated lower survival rates for BVAS ≥20 and severe EUVAS, and a risk prediction model (RPM) based on these stratified patients into low, moderate, and high-risk mortality groups.ConclusionsThe developed RPM is promising to predict mortality in patients with MPA and provides clinicians with a valuable tool for risk assessment and informed clinical decision-making.

IL-6 Receptor Expression on the Surface of T Cells and Serum Soluble IL-6 Receptor Levels in Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

We investigated the IL-6 receptor (IL-6R) expression on the surface of T cells isolated from peripheral blood mononuclear cells (PBMCs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and measured the serum soluble IL-6R (sIL-6R) levels in these patients. Sera and PBMCs were obtained from 51 patients with MPA (n = 32) and GPA (n = 19), with 25 patients having active disease (defined as a Birmingham Vasculitis Activity Score [BVAS] ≥ 5). The median age of patients was 67.0 years, and 52.9% were women. Serum IL-6 levels were significantly correlated with the BVAS (r = 0.384); however, IL-6R expression on the surface of T cells did not significantly differ based on disease activity. Meanwhile, IL-6R expression on the surface of stimulated CD4+ (median mean fluorescence intensity [MFI] 588.0 vs. 1314.8; p < 0.001), CD4+CD25+ (MFI 853.3 vs. 1527.3; p < 0.001), and CD4+CD45RO+ (MFI 679.5 vs. 1241.5; p < 0.001) T cells was significantly reduced compared with unstimulated conditions. Conversely, patients with active disease exhibited a significantly higher median serum sIL-6R level than those with inactive disease (38.1 ng/mL vs. 34.7 ng/mL; p = 0.029). These results imply that the trans-signalling IL-6 pathway may be more activated than the classical signalling pathway in patients with MPA and GPA, suggesting the therapeutic potential of targeting sIL-6R.

Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study

Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. None.

Clinical features and outcomes of small airway disease in ANCA-associated vasculitis.

To clarify the prevalence, features and outcomes of small airway disease (SAD) in a Chinese cohort with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) related pulmonary involvement. SAD was recorded when the manifestations of either centrilobular nodules or air trapping were observed according to CT scans, except for infection or other airway-related comorbidities. Baseline and follow-up data were collected retrospectively. Of the 359 newly diagnosed AAV patients with pulmonary involvement, 92 (25.6%) had SAD, including 79 (85.9%) cases of anti-MPO-ANCA positive, 9 (9.8%) cases of anti-PR3-ANCA positive and 2 (2.2%) cases of double positive. Patients with SAD were more likely to be younger, female, non-smokers, have more ear-nose-throat (ENT) involvement, and have higher baseline Birmingham Vasculitis Activity Score (BVAS) compared to patients without SAD. Several AAV-related SAD patients have improved lung function and CT scans after immunosuppressive therapy. Patients with SAD had a better prognosis compared to those without SAD. When dividing all patients into three groups: isolated SAD (only small airway involvements), SAD with other lower airway involvements, and non-SAD, patients in the SAD with other lower airway involvements group had the highest risk of infection, while patients in the non-SAD group had the worst long-term outcomes. Similar results were observed in anti-MPO-ANCA positive patients when performing subgroup analyses. SAD is a unique manifestation of AAV-related lung involvement and exhibits distinct clinical features. It is vital to focus on SAD because of its association with prognosis and infection in AAV patients, especially in anti-MPO-ANCA positive patients. Moreover, SAD might represent a better response to immunosuppressors.

Augmented thrombin formation is related to circulating levels of extracellular vesicles exposing tissue factor and citrullinated histone-3 in anti-neutrophil cytoplasmic antibody-associated vasculitides.

To study circulating myeloperoxidase (MPO)-positive extracellular vesicles (MPO+EVs) exposing citrullinated histone-3 (H3Cit), tissue factor (TF), and plasminogen (Plg) in association to thrombin generation in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). We have involved well-characterized patients with AAV together with population-based controls. Flow cytometry was used to assess the levels of MPO+EVs in citrated plasma. MPO+EVs were phenotyped by anti-MPO-antibodies together with anti-CD142 (anti-TF), anti-H3Cit, and anti-Plg antibodies. A modified Calibrated Automated Thrombogram (CAT) assay was utilized to measure thrombin generation in plasma initiated by EVs-enriched pellets. The activity of AAV was evaluated with the Birmingham Vasculitis Activity Score (BVAS). This study comprised 46 AAV patients, 23 in the active stage of the disease and 23 in remission, as well as 23 age- and sex matched population-based controls. Augmented levels of all investigated MPO+ EVs were found in active AAV patients in comparison to the subgroup of patients in remission and controls. Thrombin generation, measured by endogenous thrombin potential (ETP) and peak of thrombin formation, was higher in plasma when triggered by EVs-enriched pellet from AAV patients. ETP and peak were associated with the levels of MPO+TF+ and MPO+H3Cit+ EVs. Additionally, MPO+TF+ EVs correlated with the disease activity evaluated with BVAS. Augmented thrombin generation is found in AAV patients regardless of disease activity and is associated with higher exposure of TF and H3Cit on MPO+EVs. This may contribute to the increased risk of thrombosis seen in AAV patients.

Soluble triggering receptor expressed on myeloid cell-1 reflects the cross-sectional activity of microscopic polyangiitis and granulomatosis with polyangiitis

ObjectivesWe investigated whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflects cross-sectional activity of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). MethodsForty-seven MPA and 32 GPA patients with well-documented clinical records and stored sera were enrolled. sTREM-1 levels were evaluated using Magnetic Luminex® assay, and disease activity was assessed using Birmingham vasculitis activity score (BVAS). Patients were divided into two groups according to the upper and lower halves of BVAS. Receiver operator characteristic (ROC) curve analysis was used to identify cut-off for determining upper half of BVAS. Linear and binary logistic regression was performed to evaluate the association between sTREM-1 and disease activity and status. ResultsThe median age of patients was 67.0 years, and 58.2 % were women. The median BVAS and sTREM-1 were 12.0 and 467.1 pg/mL. sTREM-1 was significantly correlated with BVAS along with five-factor score, Short-Form 36-Item Health Surveys, and C-reactive protein. In multivariable linear regression analysis, erythrocyte sedimentation rate (standardised β 0.241), and sTREM-1 (standardised β 0.288) were correlated with BVAS. ROC analysis revealed that the cut-off of sTREM-1 for the upper half of BVAS was 474.1 pg/mL. MPA and GPA patients with sTREM-1 ≥474.1 pg/mL exhibited a significantly higher risk for the upper half of BVAS than those without (relative risk 5.932). Multivariable logistic regression analysis demonstrated sTREM-1 ≥474.1 pg/mL (odds ratio 5.662) was associated with the upper half of BVAS. ConclusionsTREM-1 reflects the activity of MPA and GPA, suggesting its role as a potential biomarker for assessing disease severity.