Immunologic links between cutaneous lupus and internal organ involvement in SLE: A systematic review and meta-analysis

Background: Cutaneous lupus erythematosus (CLE) represents one of the most frequent clinical manifestations of systemic lupus erythematosus (SLE), yet its relationship with internal organ involvement remains incompletely defined. Increasing evidence suggests that cutaneous inflammation may reflect systemic immune activation through dysregulated interferon signaling, immune complex deposition, and complement consumption. This systematic review and meta-analysis aimed to determine the association between CLE and major organ involvement in patients with SLE. Methods: , and publication bias evaluated with funnel plot and Egger's test. Results: Twenty-three studies met inclusion criteria for qualitative synthesis, and sixteen were eligible for quantitative pooling, comprising 8412 patients. Meta-analysis demonstrated that CLE was significantly associated with increased risk of lupus nephritis (OR 2.14, 95% CI 1.62-2.85), neuropsychiatric lupus (OR 1.78, 95% CI 1.29-2.46), and hematologic abnormalities (OR 1.95, 95% CI 1.40-2.71). A modest but significant association with cardiopulmonary involvement was also observed (OR 1.52, 95% CI 1.11-2.09). Subgroup analyses revealed stronger associations in acute CLE phenotypes and in patients with high interferon signatures. Sensitivity analyses confirmed robustness of findings, with no evidence of major publication bias. Conclusion: CLE is associated with significantly greater renal, neuropsychiatric, hematologic and cardiopulmonary involvement in patients with SLE compared with those without skin disease. These findings suggest that CLE is associated with increased systemic disease activity and a higher burden of internal organ involvement in SLE. CLE should therefore be considered an important clinical indicator of increased systemic risk in SLE.