Mortality in systemic lupus erythematosus: causes, predictors and interventions

Background and aims We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan–Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. Results We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point). Conclusions Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.

The changing pattern of mortality in systemic lupus erythematosus (SLE) led to an examination of the deaths in a long-term systematic analysis of 81 patients followed for five years at the University of Toronto Rheumatic Disease Unit. During the follow-up 11 patients died; six patients died within the first year after diagnosis (group I) and five patients died an average of 8.6 years (from 2.5 to 19.5 years) after diagnosis (group II). In those who died early, the SLE was active clinically and serologically, and nephritis was present in four. Their mean prednisone dose was 53.3 mg/day. In four patients a major septic episode contributed to their death. In those who died late in the course of the disease, only one patient had active lupus and none had active lupus nephritis. Their mean prednisone dose was 10.1 mg/day taken for a mean of 7.2 years. In none was sepsis a contributing factor to their death. All five of these patients had had a recent myocardial infarction at the time of death; in four, ti was the primary cause of death. Mortality in SLE follows a bimodal pattern. Patients who die early in the course of their disease, die with active lupus, receive large doses of steroids and have a remarkable incidence of infection. In those who die late in the course of the disease, death is associated with inactive lupus, long duration of steroid therapy and a striking incidence of myocardial infarction due to atherosclerotic heart disease.

To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort.