Impact of Chronic Rhinosinusitis on Granulomatosis with Polyangiitis Exacerbations

<b>Background/Objectives:</b> Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis, often presenting first with sinonasal symptoms diagnosed as vasculitis chronic rhinosinusitis (CRS). Patients with limited (L) GPA do not have renal involvement and often have more local sinonasal disease. Few studies have examined systemic progression in LGPA patients presenting with local sinonasal disease. Our objective was to compare GPA disease progression and activity in LGPA patients with and without CRS. <b>Methods:</b> Using the US Collaborative Network of the TriNetX platform, we conducted a retrospective study of adults with LGPA and CRS versus those without CRS. Outcomes were measured 1 month-5 years after patients met inclusion criteria. Primary outcomes were acute sinusitis, end-organ damage, and major GPA disease activity. Secondary outcomes were end-organ damage and major disease activity for each organ system and mortality. <b>Results:</b> There were <i>n</i> = 1097 in the LGPA with CRS cohort and n = 3331 in the LGPA without CRS cohort, with n = 1023 in each cohort after 1:1 propensity matching on age, gender, ethnicity, and race. We found a significantly greater risk of acute sinusitis (risk ratio: 4.80, 95% confidence interval: [2.89,7.99]), end-organ damage (2.99 [2.41, 3.70]), and major disease activity (2.41 [1.73, 3.35]) comparing patients with CRS to those without. LGPA patients with CRS had no significant difference in mortality compared to those without CRS (0.94, [0.64,1.38]). <b>Conclusions:</b> Patients with LGPA and CRS have greater risk of developing disease progression and increased organ system disease activity compared to LGPA without CRS.