Clinical and epidemiological Studies in ANCA-associated vasculitis

Abstract: Objectives:This thesis aims to provide an overview of the epidemiology of AAV in southern Sweden, to evaluate different classification criteria in AAV. In addition we study if infection is a risk factor for later development of AAV comparing patients with AAV with a matched population cohort and to examine the occurrence of severe infections as an outcome in AAV. Methods:All adult patients diagnosed with AAV between 1997 and 2019 in the study area of 14 municipalities in Southern Sweden were identified and classified according to EMA algorithm and to the recently published ACR/EULAR classification criteria. Changes in the incidence and prevalence of AAV were studied over 23 years. Using a non-AAV age, sex and place of residence matched population the association of prior infections and later development of AAV was analysed with a logistic regression model. Events of severe infections after AAV diagnosis were identified and studied, incidence rate of severe infections was calculated. Results:Stable incidence with 30 cases per million inhabitants and rising prevalence are observed under the study period. Incidences are rising with age. The prevalence of 469/million in 2015 is the highest ever reported. Classification with the new ACR/EULAR criteria shows good agreement with earlier criteria (96% EGPA, 85% GPA, 75% MPA) but even with a classification based on ANCA serology alone (PR3 99%, MPO 84%). Infection, especially in the respiratory tract, is associated with later development of AAV. A history of prior infections is more likely in MPO-positive cases. In patients with AAV, severe infection occurs in 40% of cases after the onset of AAV. The incidence rate of severe infection is 9.1 per 100 person-years of follow-up but significantly higher during the first year with 22.1 per 100 person-years. High age and high diesaese activity independently predict the occurrence of severe infection. Conclusion:The incidence of AAV is stable in our area. The prevalence has increased substantially during the last decades, which can be attributed to better treatment and management and therefore increased survival. An ANCA based classification of AAV produces similar results as the new ACR/EULAR classification criteria. MPO-positive AAV is associated with prior infection. Severe infections are common problem in AAV especially in the first year, they are among the leading causes of death in vasculitis patients.