Timing of discoid lupus erythematosus onset impacts disease outcomes in systemic lupus erythematosus: A single-center and large, real-world retrospective cohort study

Summary: Abstract Body: Discoid lupus erythematosus (DLE) significantly affects a subset of systemic lupus erythematosus (SLE) patients. When DLE precedes SLE, severe systemic manifestations are less common. However, the effects of concurrent or late-onset DLE on long-term SLE outcomes remain underexplored. We conducted two retrospective cohort studies: one using deidentified data from 103 global healthcare organizations in TriNetX and another via chart review of DLE patients with SLE at Johns Hopkins Hospital (2014–2024). Three cohorts were defined: early DLE (>1 year before SLE), concurrent DLE (within 1 year before/after SLE), and late DLE (>1 year after SLE). In TriNetX, cohorts were propensity-matched and univariate regression was performed. At Hopkins, multivariate logistic regression adjusted for demographics, DLE onset timing, smoking, anti-dsDNA positivity, and metabolic syndrome. Risk of 10-year incident outcomes after SLE diagnosis was compared using early DLE as the reference group. We analyzed 3387 patients from TriNetX and 191 from Hopkins. Late DLE was linked to higher odds of CKD/ESRD (TriNetX: p<0.01; Hopkins: p=0.02) and major adverse cardiovascular events (TriNetX: p<0.01; Hopkins: p=0.02). In TriNetX, late and concurrent DLE were also associated with increased risk of lupus nephritis (p<0.01), malignant neoplasms (p=0.02) and hospitalization (p<0.01). Hopkins data showed late DLE had higher risk of fractures (p=0.04) and osteopenia (p<0.01). Among Hopkins patients, 31.3% of late DLE and 71.4% of concurrent DLE cases developed lupus nephritis after DLE, with median times to diagnosis of 8.0 months and 4.5 months, respectively. Our findings reveal worse outcomes in SLE patients with late or concurrent DLE compared to early DLE. Notably, the elevated 10-year incidence of CKD/ESRD and MACE in late DLE was validated in the Hopkins cohort. Late-onset DLE may involve distinct immune dysregulation, requiring vigilant monitoring to mitigate adverse outcomes. Saloni Patel¹, Ruchita Kothari¹, Maria Kaltchenko¹, Sara Khoshniyati¹, Anjana Srikumar¹, Elena Wei¹, Shirin Shahsavari¹, Jun Kang¹ 1. Dermatology, Johns Hopkins Medicine, Baltimore, MD, United States. Clinical Research: Epidemiology and Observational Research