In-Depth Analysis of Disease Manifestations in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides Identifies Distinct Clinical Phenotypes.

Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are heterogeneous disorders. The aim of this study was to identify and characterize subgroups of patients based on sex, ANCA, age at diagnosis, and organ involvement.

Methods: In total, 1,167 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were retrospectively recruited to the study. Data including cumulative involvement of 10 different organ systems, end-stage kidney disease (ESKD), sex, proteinase (PR) 3-ANCA, myeloperoxidase (MPO)-ANCA, age at diagnosis, disease duration, and relapse were obtained from medical records. Clinical variables were analyzed for associations with sex, age at diagnosis, and relapse using logistic regression analysis. Thirteen clinical variables were included in hierarchical cluster analyses using the Ward method.

Results: In patients with GPA, PR3-ANCA, renal and pulmonary involvement, and ESKD were significantly associated with male sex, whereas MPO-ANCA was associated with female sex. Patients with GPA who were younger than 32 years of age at diagnosis were significantly more often females and had more ear-nose-throat involvement than patients older than 32 years. In patients with MPA, female patients were significantly younger at diagnosis than male patients. Relapse was significantly associated with young age at diagnosis and pulmonary involvement in GPA and with musculoskeletal involvement in MPA. Hierarchical cluster analyses identified five and seven patient clusters among individuals with GPA and MPA, respectively. PR3-/MPO-ANCA defined the largest clusters, whereas heart, gastrointestinal, and central nervous system involvement were hallmarks for three clusters for both patients with GPA and MPA.

Conclusion: Sex, age at diagnosis, and specific organ involvements define clinically relevant subgroups among patients with ANCA-associated vasculitides.