Multiple sources were used to identify 325 systemic lupus erythematosus (SLE) patients within the city of Oslo during 1999-2009 who met ≥ 4 of the American College of Rheumatology (ACR) criteria. The survival, standard mortality rate (SMR), years of potential life loss before 60 years of age (YPLL60) and causes of death of these patients were examined and compared to a matched control population. Only inception cases (127) were studied in the calculation of survival. The analysis includes underlying, immediate and contributing causes of death. The five- and 10-year survival was 95% and 90%, respectively, which was significantly reduced when compared to the general population. A total of 50 SLE patients died during the study period. Overall SMR was 3.0 (95% confidence interval (CI) 2.2-3.8) with the highest SMR found for female patients aged 16-39 years old. SLE patients had a 10 times higher rate of YPLL60 compared to the control group. YPLL emphasizes active disease and reduces the importance of cancer as a cause of death in SLE. This study demonstrates that YPLL gives additional and useful information for the prognosis of SLE, supplementing traditional methods of measuring mortality.

Our aim was to identify all patients with systemic lupus erythematosus (SLE) within the city of Oslo from 1999-2008 and to estimate the incidence and prevalence of SLE according to age, sex and ethnicity. Adults (16 years and over) with SLE were identified from five different sources. Only patients fulfilling four or more of the updated 1997 American College of Rheumatology (ACR) criteria were included. The incidence was stable during the nine year study period, with a mean annual incidence rate of 3.0 per 100,000 at risk (95% confidence interval (CI) 2.4-3.5). Females exhibited a bimodal pattern in age specific incidence with the first peak at 16-29 years of age and the second at 50-59 years of age. The overall prevalence was 51.8 per 100,000 population (95% CI 45.2-58.4), with 91.0 (95% CI 78.8-103.1) for females and 10.7 (95% CI 6.4-15.0) for males. The prevalence proportions for European descendants were similar to those for Asians but statistically significant lower than those for individuals adopted from non-European countries. The findings indicate a higher prevalence in Norwegians compared to Caucasians in Denmark and England. The higher prevalence of SLE in foreign adopted individuals warrants further examination.

Objectives. Studies assessing relative mortality risks across the spectrum of systemic inflammatory rheumatic diseases are largely missing. In this study, we wanted to estimate standard mortality ratios (SMRs) and causes of death in an ethnically homogeneous cohort covering all major CTDs and primary systemic vasculitides (PSVs). Methods. We prospectively followed all incident CTD and PSV cases included in the Norwegian CTD and vasculitis registry (NOSVAR) between 1999 and 2015. Fifteen controls for each patient matched for sex and age were randomly drawn from the Norwegian National Population Registry. Causes of death were obtained from the National Cause of Death Register, death certificates and hospital charts.Results. The cohort included 2140 patients (1534 with CTD, 606 with PSV). During a mean follow-up time of 9 years, 279 of the patients (13%) died, compared with 2864 of 32 086 (9%) controls (P < 0.001). Ten years after diagnosis, the lowest survival was 60% in dcSSc, 73% in anti-synthetase syndrome (ASS) and 75% in lcSSc. In the CTD group, the highest SMRs were observed in dcSSc (SMR 5.8) and ASS (SMR 4.1). In the PSV group, Takayasu arteritis (SMR 2.5) and ANCAassociated vasculitis (SMR 1.5) had the highest SMRs. Major causes of death were cardiovascular disease (CTD 27%, PSV 28%), neoplasms (CTD 25%, PSV 27%), chronic respiratory disease (CTD 20%, PSV10%) and infections (CTD 9%, PSV 16%). Conclusion.We observed premature deaths across the spectrum of CTDs and PSVs, with highest SMRs in dcSSc and ASS. The overall mortality was highest in the CTD group.

ObjectivesSystemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE.MethodsWe undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS).ResultsWe identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes.ConclusionsOur results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.