Influence of frailty syndrome on disease outcomes in systemic lupus erythematosus: a systematic review and narrative synthesis

To synthesize evidence on how frailty in adults with systemic lupus erythematosus (SLE) is measured and to evaluate its associations with major clinical and patient-centered outcomes. We conducted a PROSPERO-registered systematic review (CRD42024600473) following PRISMA guidelines. PubMed, Scopus, Web of Science, and EBSCO were searched from inception to July 2025. Observational studies assessing frailty in adults with SLE and reporting prevalence and/or associations with organ damage, healthcare utilization, mortality, disability, or health-related quality of life (HRQoL) were included. Owing to heterogeneity in definitions and outcomes, findings were synthesized narratively. Seventeen studies were included. Frailty was measured using deficit-accumulation indices (e.g. the SLICC-Frailty Index), phenotype-based definitions (e.g. the Fried Phenotype), and performance measures, with prevalence ranging from approximately 7% to 46%. Frailty predicted faster accrual of organ damage (per 0.05 increase in SLICC-FI, adjusted IRR 1.20, 95% CI 1.14–1.27) and higher healthcare utilization (adjusted IRR 1.21, 95% CI 1.13–1.30). In the largest cohort (n=1,566), frailty was associated with increased mortality (adjusted HR 4.37, 95% CI 2.67–7.17) and showed a dose–response relationship. Frailty was also consistently linked to worse physical function, greater disability, and poorer HRQoL. Frailty is common in SLE and independently identifies patients at higher risk of adverse outcomes. Standardized definitions and longitudinal studies are needed to support risk stratification and targeted interventions. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect many organs and often requires long-term treatment with medications such as corticosteroids and immunosuppressants. Although advances in therapy have improved survival, many people with SLE continue to experience health complications and reduced quality of life. This study reviewed the scientific evidence about frailty, a condition marked by decreased strength, energy, and stress resistance, and its impact on people living with SLE. The researchers examined 17 studies from different countries that assessed how frailty is measured and its relationship to outcomes, including organ damage, hospitalizations, and mortality. The findings show that frailty is common in SLE, and frailty prevalence varied widely across studies and instruments. People with SLE who are frail are more likely to be hospitalized, stay longer in the hospital, and have a higher risk of death compared to those who are not frail. Frailty is also linked to faster progression of organ damage, poorer physical function, more pain and fatigue, lower bone strength, and a greater likelihood of fractures. These associations remain even when age, disease activity, and medication use are considered. Recognizing frailty early in SLE care may help doctors identify patients at higher risk and design personalized interventions, such as exercise, nutrition, and medication adjustments, to improve resilience, quality of life, and long-term outcomes.