The Importance of Demographic and Geographical Factors on the Incidence and Outcome of Systemic Small Vessel Vasculitis Associated with Anti-Neutrophil Cytoplasmic Antibodies

Abstract: The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) comprise microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Two serotypes are recognized: myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA. Renal involvement is a common and severe manifestation associated with increased mortality. The incidence varies geographically, but studies are difficult to compare due to heterogeneous methodology and inclusion criteria. AAV is commonly found in the elderly, but there are little data on outcome and optimal treatment in the highest age groups. This thesis focuses on the epidemiology of AAV: incidence, geographical distribution, and outcome.In Paper I annual incidence rates and outcome were compared between nephritis in AAV and nephritis in systemic lupus erythematosus (SLE) in two geographically defined populations in Sweden. Even though SLE is twice as common as AAV, ANCA-associated nephritis outnumbered lupus nephritis by three to one, and was significantly more severe in terms of mortality and development of end stage renal disease.In Paper II associations between ANCA serotype and geographical and demographic factors were investigated in a large multi-centre study of 1408 patients with renal biopsy-proven AAV. PR3-ANCA was associated with male gender, younger age and higher glomerular filtration rate. PR3-ANCA was also associated with higher latitude and lower ultraviolet radiation levels, but analyses of subgroups suggested that genetic rather than environmental explanations might be more important for this geographical gradient.In Paper III a consecutive cohort of 151 elderly patients with MPA and GPA was studied with a focus on treatment, mortality and renal survival. Patients who had received immunosuppressive treatment with cyclophosphamide or rituximab had better survival rates compared to less intensively treated or untreated patients. Severely impaired renal function at diagnosis was associated with worse outcome in terms of both patient and renal survival.In Paper IV the elderly cohort was extended to 202 patients. In this study we found that treatment with cyclophosphamide or rituximab was associated with the development of less permanent organ damage, and not with higher utilization of in-hospital care. However, high doses of glucocorticoids were associated with fatal infections and treatment-related damage.