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Background Systemic lupus erythematosus (SLE) shows marked heterogeneity in epidemiology across regions and over time. Understanding temporal changes in incidence, prevalence and patient characteristics is important to interpreting disease burden and assessing the performance of care systems.Objectives To evaluate changes after 12 years (2010 vs 2022) in epidemiology, demographic, clinical and therapeutic features of SLE in a general practitioner (GP)-based cohort in Tuscany, Italy.Methods We conducted two cross-sectional surveys among GPs in the Florence District (Tuscany, Italy) to identify SLE cases. We assessed temporal variations in incidence and prevalence rates, as well as in sociodemographic, clinical and treatment variables.Results SLE incidence doubled from 2010 to 2022, from 5.4 to 10.9 per 100 000 person-years; prevalence increased from 75 to 120 per 100 000 persons. Most diagnoses remained in adults aged 18–60, though non-negligible proportions had paediatric or late onset. Joint, skin and haematological involvement were most frequent, while renal involvement declined from 22% to 16%. Use of biologic therapies grew substantially over time, while glucocorticoids remained pivotal in management. Notably, the proportion of patients not receiving any treatment (glucocorticoids included) increased, indicating a shift towards glucocorticoid-sparing strategies. Furthermore, despite 12 years of demographic change in the general population, the ethnic composition of the SLE cohort remained largely stable, with most patients of Caucasian origin.Conclusions Over a decade, this GP-based study shows an increase in SLE prevalence and incidence within participating practices, accompanied by evolving therapeutic strategies and an increasing proportion of patients off treatment, including glucocorticoids. These findings have implications for health planning and support the value of GP-based epidemiologic studies.