OBJECTIVE: This review aims to summarize the evolution and recent developments in the classification of ANCA associated vasculitis (AAV) and to summarize evaluations of the 2022 ACR/EULAR classification criteria of AAV in several cohorts.
RESULTS: The classification of AAV has been a field of controversy for some time. The parallel existence of classification criteria and disease definitions produced some overlap in classification, leading to challenges when comparing different cohorts. The 2022 ACR/EULAR classification criteria derived from the largest study ever conducted in vasculitis account for significant changes in vasculitis classification with the integration of ANCA and modern imaging. These criteria show good performance compared to previous ones but also raise questions as ANCA serotypes have substantial impact on classification. In addition, there are some discrepancies with earlier agreed histopathological features of AAV disease phenotypes. During the last 35 years, several sets of classification criteria have evolved to facilitate epidemiologic studies and clinical trials in AAV. While some of these criteria have been in use for many years, they were criticized due to either not using ANCA or not integrating surrogate markers for vasculitis but also due to overlapping when used in parallel. The long-awaited new ACR/EULAR criteria for AAV were published in 2022 and are the result of a large international study, introducing for the first time ANCA and modern imaging in the classification of AAV. Though the criteria show good performance, they bring several other challenges with practical application.

A 75-year-old woman, with hypertension and atrial fibrillation but no prior renal history, presented to the hospital for chest discomfort and dyspnea. She was found to be in acute renal failure, with a serum creatinine of 5.1, increased from a baseline of 0.9, and urine analysis revealing proteinuria and hematuria with dysmorphic red blood cells. Subsequent work up was significant for positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA) and myeloperoxidase antibodies. She underwent a renal biopsy, which revealed necrotizing crescents in 12 of 14 glomeruli, and she was diagnosed with rapidly progressive glomerulonephritis due to microscopic polyangiitis. Despite aggressive treatment with plasmapheresis, high-dose prednisone, and rituximab infusions, renal function worsened, and she required initiation of hemodialysis. She was ultimately discharged after a three-week admission, with plans to continue rituximab infusions and three times weekly hemodialysis in the outpatient setting. Due to her poor response to traditional therapies, initiation of a new targeted immunomodulator known as avacopan, a complement 5a receptor antagonist, was considered. Such targeted immunomodulators are also of particular interest as possible ways to reduce the risk of severe infection associated with current broad immunosuppressive modalities. In addition, when used in place of steroids, they reduce the morbidity associated with cumulative glucocorticoid toxicity. For patients with ANCA-associated vasculitis refractory to standard therapies, targeted immunomodulators such as avacopan should be considered as alternative or adjunct therapy.

BACKGROUND: Kidney and life outcomes remain unsatisfactory in patients with microscopic polyangiitis (MPA). Appropriate treatment intensity must be provided to the appropriate patients. To identify severe cases early, we investigated the factors related to kidney and life outcomes.
METHODS: We included patients diagnosed with MPA based on myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity and kidney histopathology results after kidney biopsies between January 1, 2021, and May 11, 2023, at 10 affiliated centers, including our hospital. Death, maintenance dialysis, and estimated glomerular filtration rate (eGFR) < 15 after 6 months of treatment were defined as poor prognosis groups, and factors associated with these conditions were investigated.
RESULTS: We included 84 (36 men and 48 women) patients in this study. Median age was 73.8 (interquartile range: 71-81) years. After 6 months of treatment, the proportion of patients in the poor prognosis group was 16.7 %, with a mortality of 7.1 % and a poor kidney prognosis rate of 9.5 %. Area under the receiver operating characteristic curve showed that eGFR at 2 weeks had a comparable prognostic performance equal as eGFR at 4 weeks (area under the curve: 0.875 and 0.896, respectively). After adjustment by various factors, eGFR at 2 weeks was related with prognosis significantly (p = 0.031).
CONCLUSIONS: Kidney function 2 weeks after the start of treatment for MPA can predict prognosis.

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

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.

To assess whether Casitas B-lineage lymphoma (CBL) gene polymorphism influences the risk of microscopic polyangiitis (MPA) in Chinese populations.
In total, 266 MPA patients and 297 healthy controls were recruited for a case-control study. Five CBL SNPs were genotyped using multiplex polymerase chain reaction and high-throughput sequencing. The relationship between SNPs and the risk of MPA under different genetic models was evaluated by SNPstats. SNP-SNP interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Finally, the association between CBL SNPs and treatment effects were assessed.
The results showed that CBL rs2276083 was associated with decreasing MPA risk under dominant (OR: 0.53; p = 0.014) and recessive models (OR: 0.52; p = 0.0034). Stratification analysis indicated that rs2276083 and rs2509671 in age < 60 years, rs2276083 in female or in Han population were protective factors for MPA. The CBL haplotype (A-A-G-C-T) was associated with an increased risk of MPA. GMDR suggested that CBL rs2276083, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) rs1607237, and autophagy-related gene 7 (ATG7) rs7549008 might interact with each other in MPA development (p = 0.0107). CBL rs1047417 with AG genotype and rs11217234 with AG genotype had better clinical treatment effects than other two genotypes (p = 0.048 and p = 0.025, respectively).
The genetic polymorphism of CBL had a potential association with the risk of MPA and clinical treatment effects in Guangxi population in China.

A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.

ANCA associated vasculitides are multi-system autoimmune diseases which are increasing in prevalence. In this review we will discuss the clinical manifestations and review the management options. We highlight the various trials of induction and maintenance therapy and discuss the areas of unmet need. These include understanding which patients are at highest risk of relapse, clinical adaptation of improved biomarkers of disease activity and tools to discuss long term prognosis.

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.

UNASSIGNED: Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that affects predominantly small- sized vessels. A causal relationship between viral infections and vasculitis has been postulated.Aim of the workTo present the concomitant association of coronavirus disease 2019 (COVID-19) infection with MPA in an elderly Iranian male.
UNASSIGNED: A 67 year old Iranian man with the history of COVID-19 infection and a positive polymerized chain reaction (PCR) test four weeks before admission to the neurology department with acute onset pain, numbness and progressive weakness in both hands grip, sudden left foot drop and paresthesia. Erythrocyte sedimentation rate (ESR) was 95 mm/hr, ferritin 912 ng/ml and C-reactive protein (CRP) positive, proteinuria 1.1 g/24 h and markedly elevated perinuclear (P-ANCA): 526 IU/ml. Diagnosis of MPA was held presenting with mononeuritis multiplex, glomerulonephritis followed by diffuse alveolar hemorrhage and infiltration of lymphocytes in muscle fibers and vessels wall in sural nerve biopsy. He was successfully treated by methylprednisolone (1 g/day for 3 days) followed by 1 mg/kg with gradual tapering along with cyclophosphamide (CYC) (2 mg/kg). Intravenous immunoglobulin (IVIG, 2 g/kg in four divided doses) started for the management of inflammatory mononeuritis multiplex with gradual improvement. During hospitalization, plasmapheresis was performed due to alveolar hemorrhage for 5 day. The patient returned home on day 32 and followed-up in the rheumatology clinic with improvement of muscle power and handgrip strength.
UNASSIGNED: Vasculitis is potentially one of COVID-19\'s presenting symptoms and prompt diagnosis and treatment is crucial in improving outcome of patients.