Many past studies of organ damage in SLE had limitations, such as retrospective assessment [7
], short disease duration [8
], cross-sectional study design rather than prospective [5
] or having relatively small numbers of patients [7
]. In this study, we report the result from the largest ongoing prospective study of SLE patients followed by protocol, comprising 2054 patients in the Hopkins Lupus Cohort.
The most important demographic predictors of progression in damage were high age at diagnosis race/ethnicity, and low income. Previous studies have showed divergent results between ethnicity and damage; some found that non-Caucasians were at greater risk [6
], specifically that African-Americans had greater damage [12
], while others did not [9
]. We observed significantly faster rates of progression among African-Americans in our univariate analysis, but not in our multivariate analysis. This suggests that the faster rate of progression in African-Americans is explained by other variables in the model such as income, hypertension, and proteinuria.
Lower income was associated with a higher rate of damage accrual. Some studies [11
] also concluded that low socioeconomic status was associated with greater degree of damage. Low income is also associated with malnutrition, limited access to quality care and poor compliance with medication.
Disease activity (SELENA-SLEDAI) was associated with increased the rate of progression. Other studies, using other measures of disease activity [6
], reached the same conclusion. In our analysis, the association between disease activity and damage largely disappears after adjustment for corticosteroid use, suggesting that the association between disease activity and damage is mediated by increased use of corticosteroids.
The most predictive serologic test was the lupus anticoagulant, not anti-dsDNA as found in one study [9
] or other antiphospholipid antibodies. We have previously emphasized that the lupus anticoagulant is the antiphospholipid antibody most associated with thrombosis in SLE [15
]. These data clearly point to the need for effective prophylactic therapy for the lupus anticoagulant.
The most striking finding was the strong association between corticosteroid use and damage accrual. This persisted even after adjusting for levels of SLE disease activity, suggesting that the association is not simply due to confounding by indication. In previous studies we have noted the association between corticosteroid use and specific forms of damage including osteoporotic fractures, coronary artery disease, cataracts, avascular necrosis and stroke [16
Previously, an analysis of the Hopkins Lupus Cohort suggested that hydroxychloroquine might have a long-term protective effect on the SLE-related organ damage on the SDI [17
]. Another study has found that hydroxychloroquine may protect against renal and neurologic damage, in particular. The current study confirmed that hydroxychloroquine use was associated with lower rates of damage accrual.
The cohort is unique, in that all patients are seen by one rheumatologist at least quarterly, and, thus, the results are not generalizable to all SLE patients. In addition, the analyses focused on the total damage score and not on individual items (which would likely have unique predictors). However, given these limitations, clear messages resulted.. Rates of damage differ significantly between demographic subgroups. The most important predictor of damage appears to be corticosteroid use. Prophylactic therapy for the lupus anticoagulant and better control of disease activity, without reliance on corticosteroids, may limit future damage.