Cutaneous Lupus Erythematosus: Epidemiology, Association with SLE and Comorbidity

Lupus erythematosus (LE) is a disease that includes a broad spectrum of symptoms, from localized cutaneous LE (CLE) to severe systemic LE (SLE). Based on histopathological changes, the skin manifestations of LE can be divided into LE-specific (=CLE) and LE-non-specific manifestations. CLE is a chronic, inflammatory skin disease with a wide range of manifestations that can be seen in patients with or without SLE. As defined by clinical symptoms, average duration of symptoms, histological and serological findings, CLE can be further divided into three main subsets (acute CLE [ACLE], subacute CLE [SCLE] and chronic CLE [CCLE]). All four studies in this thesis focused on CLE and different comorbidities: the classification of cutaneous manifestations in SLE patients, the risk for progression to SLE, risk for cancer among CLE patients and the association between drug exposure and the development of subacute CLE. In study I we investigated the frequency of cutaneous manifestations in a cohort of 260 SLE patients. We compared clinical and serological manifestations in SLE patients with and without CLE. LE-non-specific skin manifestations (43 %) were almost twice as frequent as CLE (23 %). Raynaud’s phenomenon was significantly more common but arthritis and serositis were less common in the CLE group than in the non-CLE group. Of the SLE patients, 42 % had symptoms consistent with polymorphic light eruption. In study II a cohort study of 1,088 CLE patients from the National Patient Register was undertaken to calculate the incidence of CLE in Sweden. The incidence rate was estimated to 4.0/100,000 inhabitants. We also calculated age- and gender-specific incidence rates for different CLE subsets (i.e. discoid LE, SCLE and other local LE). We estimated the probability of also being diagnosed with SLE during the first 3 years after diagnosis of CLE. We found the cumulative probability of receiving an additional diagnosis of SLE to be 18 %, highest for women and the SCLE subset. In study III we evaluated the overall and specific cancer risks in CLE patients. In a cohort of 3,663 CLE patients we found increased risks for cancer overall (hazard ratio 1.8 (95 % confidence interval 1.5-2.2) and about a fourfold increased risk for buccal cancer, lymphomas, respiratory cancer and non-melanoma skin cancer. The elevated risks remained when we excluded patients also diagnosed with SLE. In study IV, we performed a case-control study to examine the association between previously dispensed drugs and a subsequent development of SCLE in a group of 234 incident SCLE patients. We found increased relative risks for exposure to terbinafine, TNF-α inhibitors, antiepileptics, proton pump inhibitors, thrombocyte inhibitors, ACE -inhibitors and NSAIDs 0-6 months before the diagnosis of SCLE. About one third of all SCLE cases could be attributed to previous drug exposure. This thesis adds to previous knowledge about epidemiology, prognosis, disease progression to SLE, comorbidity and the association with certain drugs in CLE. Swedish population-based epidemiological data on CLE will potentially be useful in the planning of health care as well as clinical trials. For prospective studies, especially of the intermediate group between CLE and SLE, population-based quality registers will be needed to further improve the health care for CLE patients

Incidence of End-Stage Renal Disease in Patients With Type 1 Diabetes

Peer reviewe

Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation

Background. Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy. Methods. 2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years). Results. In patients starting treatment with fluvastatin 6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (120 months) (P = 0.033). Conclusions. Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart diseas

Factors associating with differences in the incidence of renal replacement therapy among elderly : data from the ERA-EDTA Registry

Background. The incidence of renal replacement therapy (RRT) in the general population >= 75 years of age varies considerably between countries and regions in Europe. Our aim was to study characteristics and survival of elderly RRT patients and to find explanations for differences in RRT incidence. Methods. Patients >= 75 years of age at the onset of RRT in 2010-2013 from 29 national or regional registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry were included. Chi-square and Mann-Whitney U tests were used to assess variation in patient characteristics and linear regression was used to study the association between RRT incidence and various factors. Kaplan-Meier curves and Cox regression were employed for survival analyses. Results. The mean annual incidence of RRT in the age group >= 75 years of age ranged from 157 to 924 per million age-related population. The median age at the start of RRT was higher and comorbidities were less common in areas with higher RRT incidence, but overall the association between patient characteristics and RRT incidence was weak. The unadjusted survival was lower in high-incidence areas due to an older age at onset of RRT, but the adjusted survival was similar [relative risk 1.00 (95% confidence interval, 0.97-1.03)] in patients from low- and high-incidence areas. Conclusions. Variation in the incidence of RRT among the elderly across European countries and regions is remarkable and could not be explained by the available data. However, the survival of patients in low-and high-incidence areas was remarkably similar.Peer reviewe

One- and 2-Year Mortality Prediction for Patients Starting Chronic Dialysis

Introduction Mortality risk of patients with end-stage renal disease (ESRD) is highly elevated. Methods to estimate individual mortality risk are needed to provide individualized care and manage expanding ESRD populations. Many mortality prediction models exist but have shown deficiencies in model development (data comprehensiveness, validation) and in practicality. Therefore, our aim was to design 2 easy-to-apply prediction models for 1- and 2-year all-cause mortality in patients starting long-term renal replacement therapy (RRT). Methods We used data from the Finnish Registry for Kidney Diseases with complete national coverage of RRT patients. Model training group included all incident adult patients who started long-term dialysis in Finland in 2000 to 2008 (n = 4335). The external validation cohort consisted of those who entered dialysis in 2009 to 2012 (n = 1768). Logistic regression with stepwise variable selection was used for model building. Results We developed 2 prognostic models, both of which only included 6 to 7 variables (age at RRT start, ESRD diagnosis, albumin, phosphorus, C-reactive protein, heart failure, and peripheral vascular disease) and showed sufficient discrimination (c-statistic 0.77 and 0.74 for 1- and 2-year mortality, respectively). Due to a significantly lower mortality in the newer cohort, the models, to a degree, overestimated mortality risk. Discussion Mortality prediction algorithms could be more widely implemented into management of ESRD patients. The presented models are practical with only a limited number of variables and fairly good performance.Peer reviewe