Provini Chiara, Minoia Francesca, Antonio Mastrangelo, Rossano Martina, Di Stasio Fabiana, Beretta Gisella, Lanni Stefano, La Bella Saverio, Nicolino Ruperto, Filocamo Giovanni, Vianello Federica, Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Associated Group of Milan Area (PRAGMA)
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in childhood is a rare but severe condition associated with significant morbidity and treatment-related toxicity. Current therapies mainly rely on high-dose glucocorticoids and conventional immunosuppressants, which may cause substantial long-term adverse effects in pediatric patients. Advances in the understanding of AAV pathogenesis have identified the alternative complement pathway, particularly the C5a-C5a receptor axis, as a key driver of inflammation and vascular injury, leading to the development of complement-targeting therapies. While these agents have shown efficacy and steroid-sparing effects in adults, pediatric evidence remains limited to case reports and small case series. Available data suggest that complement inhibitors may represent a promising option for selected children with refractory disease, although concerns remain regarding dosing, long-term safety, and accessibility. This review summarizes current evidence, discusses unmet clinical needs, and highlights the need for collaborative pediatric studies and dedicated clinical trials.