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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies. [ABSTRACT FROM AUTHOR]

The authors discuss the article "Reclassification of Previously Diagnosed GPA Patients Using the 2022 ACR/EULAR Classification Criteria" by Jung Yoon Pyo et al. Topics include purpose of the Diagnostic and Classification Criteria in Vasculitis (DCVAS) study, reason that classification criteria for diagnosis should be avoided, and the American College of Rheumatology/European Alliance of Associations for Rheumatology ACR/EULAR classification criteria for granulomatosis with polyangiitis (GPA).

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting, or sino‐nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (+5); pulmonary nodules, mass, or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci‐immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (−1); and eosinophil count ≥1 × 109/liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% confidence interval [95% CI] 87–96%) and the specificity was 94% (95% CI 89–97%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research. [ABSTRACT FROM AUTHOR]

Objective To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Conclusion Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE. [ABSTRACT FROM AUTHOR]

Background. Studies in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) have revealed promising biomarkers. The aim of our study was to validate the most encouraging markers of granulomatosis with polyangiitis and microscopic polyangiitis identified by literature search and to create biomarker panels. Methods. A systematic literature review was performed and we identified 161 marker molecules that were ranked by their quantitative differential expression between active and inactive disease. Enzyme-linked immunosorbent assays were used to validate the results in a cross-sectional cohort of patients with renal involvement. Active vasculitis as assessed by the Birmingham Vasculitis Score version 3 (BVAS v3) was defined as BVAS v3 ≥1 and inactive disease as BVAS v3 = 0. Statistical analysis was performed with SPSS version 21 and the Salford Predictive Modeler 7.0 was used to generate a predictive biomarker panel. Results. The review indicated abundant expression of sC5bC9, C3a, C5a and monocyte chemotactic protein (MCP)-1 in urine, whereas granulocyte macrophage colony-stimulating factor, Creactive protein (CRP), soluble fms-like tyrosine kinase-1, interleukin-17A (IL-17A), C5a, hyaluronan, C3a and interleukin- 18 binding protein (IL-18BP) were identified to be highly diverse in active and inactive disease in blood samples. Our cross-sectional analysis revealed significant up-regulation of CRP, C5a, C3a, IL-18BP in blood and C5a and MCP-1 in urine samples during active AAV (all P < 0.05). Creation of a biomarker panel comprising CRP and urinary MCP-1 yielded a sensitivity and specificity of 76% (area under the curve 0.89). Conclusions. We identified promising biomarkers in a literature- based review that were in part corroborated as has been shown for CRP, C3a, C5a, IL-18BP in blood and MCP-1 and C5a in urine samples. Moreover, we propose a biomarker panel comprising CRP and urinary MCP-1 in patients with AAV and renal involvement. Further investigations to confirm our preliminary results are clearly warranted, including the reliability to predict disease relapses. [ABSTRACT FROM AUTHOR]