Challenges in the diagnosis, classification and prognosis of ANCA-associated vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses three rare yet interrelated diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Despite increasing recognition, the diagnosis of AAV remains challenging, even in specialized medical centres, owing to its clinical heterogeneity, overlap with mimicking conditions, and the variable performance of ANCA testing. The assessment of a patient suspected of AAV requires a timely synthesis of symptoms, physical examination, laboratory tests, histopathology and imaging data to substantiate the diagnosis, exclude alternative diagnoses, assess disease activity and extent, and enable rapid initiation of appropriate therapies. Classification is similarly complex, and evolving classification systems are based on clinical phenotype, ANCA specificity or a combination of both, each with implications for disease monitoring, therapeutic decisions and trial design. Assessing disease severity and predicting prognosis are fundamental but complicated by the diverse patterns of organ involvement, relapsing-remitting course and co-morbidities. Although validated tools exist for measuring disease activity, organ damage and prognosis, many limitations remain, particularly in identifying smouldering disease, irreversible damage and risk of relapse. Emerging therapies have improved outcomes, with recovery of kidney function, better overall survival and improved glucocorticoid-related toxicity, but patients with AAV continue to experience high risks of chronic morbidity and early mortality. This Review explores current challenges and opportunities in the diagnosis, classification and prognostic assessment of AAV, and outlines a structured framework to support personalized and outcome-focused care.