Antineutrophil cytoplasmic antibody-associated vasculitis classification by cluster analysis based on clinical phenotypes: a single-center retrospective cohort study

Abstract

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a group of small vessel inflammatory disorders. Overlapping clinical phenotypes of AAV subgroups continually provoke controversies over their diagnostic and classification criteria.

Methods Using the agglomerative hierarchical clustering method, we classified 210 Korean patients diagnosed with AAV into mutually exclusive clusters according to Birmingham Vasculitis Activity Score items, ANCA specificity, sex, and age. We analyzed the resulting clusters’ outcomes to investigate the clinical significance of the classification. We proposed a distance-based algorithm of patient assignment and explored its clinically relevant modification.

Results In total, 116 patients (55%) had microscopic polyangiitis, 53 (25%) had granulomatosis with polyangiitis, and 42 (20%) had eosinophilic granulomatosis with polyangiitis. Our model grouped the patients into five clusters, namely, “limited proteinase 3 (PR3)-ANCA vasculitis,” “generalized PR3-ANCA vasculitis,” “ANCA-negative vasculitis,” “renal-limited vasculitis,” and “myeloperoxidase-ANCA vasculitis.” Patients clustered under “generalized PR3-ANCA vasculitis” had a higher relapse rate (hazard ratio [HR] = 2.12, P = 0.067). The incidence of end-stage renal disease was higher in patients belonging to the “renal-limited vasculitis” cluster (HR=1.50, P=0.03), and those in the “ANCA-negative vasculitis” cluster experienced a relatively milder clinical course of AAV (mortality = 0).

Conclusion Because the clusters were naturally derived from their distinguished phenotypes and have different clinical courses, our clustering method may be a more clinically relevant classification system for AAV, revealing its phenotypic diversity. We also proposed a simple and intuitive distance-based assignment algorithm, which can be easily modified according to specific clinical needs.