Abstract
BACKGROUND: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a type of necrotizing vasculitis with poor prognosis, which is more severe in children. Classifying AAV patients may be helpful for diagnosis and management. However, present classification criteria for pediatric AAV are developed mainly based on adults, which have limitations in clinical practice. In this study, we introduced an updated algorithm based on the European Medicines Agency (EMA) algorithm in conjunction with the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria. This new approach aims to resolve the issue of duplicate classification present in the 2022 ACR/EULAR criteria and to refine the existing EMA algorithm. METHODS: This study included 179 pediatric patients diagnosed with AAV across 17 centers in China. Patients were classified using the EMA algorithm, the ACR/EULAR criteria, and the EMA-ACR/EULAR algorithm. The Kappa value and Net Reclassification Index (NRI) were used to evaluate the classification performance of these criteria. RESULTS: According to the EMA algorithm, 136 (76.0%) patients were classified with microscopic polyangiitis (MPA) and 14 (7.8%) with granulomatosis with polyangiitis (GPA), while 29 (16.2%) remained unclassifiable. According to the ACR/EULAR criteria, 145 (81.0%) patients were classified with MPA, 14 (7.8%) with GPA, 2 (1.1%) with eosinophilic granulomatosis with polyangiitis (EGPA), and 4 (2.2%) with both MPA and GPA, while 14 (7.8%) remained unclassifiable. The EMA-ACR/EULAR algorithm classified 124 patients (69.3%) as MPA, 26 (14.5%) as GPA, and 2 (1.1%) as EGPA, while 27 (15.1%) were unclassified. The Kappa values between the EMA algorithm and ACR/EULAR criteria for GPA and MPA were 0.225 [95% confidence interval (CI) 0.000-0.456, P = 0.003] and 0.357 (95% CI 0.196-0.518, P < 0.001). Compared to these two criteria, the EMA-ACR/EULAR algorithm demonstrated positive NRIs in the classification of both GPA (0.702, 95% CI 0.258-1.146, P = 0.002; 0.547 95% CI 0.150-0.944, P = 0.007) and MPA (0.425, 95% CI 0.209-0.642, P < 0.001; 0.519, 95% CI 0.305-0.733, P < 0.001). CONCLUSIONS: The EMA-ACR/EULAR algorithm addresses the limitations of the 1990 ACR criteria within the EMA framework and resolves the issue of duplicate classification in the 2022 ACR/EULAR criteria. However, further research is necessary to validate the superiority of the EMA-ACR/EULAR algorithm in the clinical classification of pediatric AAV patients.