Abstract: This study aimed to evaluate the standardized incidence ratios (SIRs) of non-Hodgkin lymphoma (NHL) in patients with Sjögren's disease (SjD) compared to the general population. Additionally, it sought to identify independent predictors of lymphoma and estimate both the relative risk (RR) and the etiologic fraction in exposed individuals (EFE) to assess the contribution of lymphoma to mortality in this population. This observational, multicenter, prospective study was conducted using data from a well-characterized Spanish cohort of patients with SjD. SIRs were calculated using data from the National Cancer Registry, and independent predictors of lymphoma were identified through multivariate Cox regression models. The RR was employed to assess the impact of lymphoma on mortality. A total of 314 patients with SjD were followed for a median of 9.5 years (range: 9.2-9.9). Eleven patients (3.5%) developed NHL, resulting in an SIR of 15.36 (95% CI: 15.32-15.40) compared to the general population. Cryoglobulinemia was identified as the strongest independent predictor of lymphoma (HR: 11.07; 95% CI: 1.18-103.75).Patients with SjD face a markedly elevated risk of NHL, primarily driven by cryoglobulinemia. These findings underscore the need for vigilant risk stratification, early detection, and tailored interventions to reduce lymphoma-related mortality in this population. Future studies should validate these results in diverse cohorts and explore targeted therapeutic strategies.
