Serial fecal calprotectin as a screening tool for subclinical ileitis in patients with idiopathic uveitis or scleritis: a prospective cohort study

Idiopathic uveitis accounts for 27%–51% of uveitis cases in Europe and the United States. Subclinical inflammatory bowel disease (IBD) may remain undiagnosed in patients with idiopathic uveitis or scleritis despite shared immunopathogenic mechanisms and the absence of digestive symptoms. Early identification may enable intervention within the inflammatory window of opportunity, yet subclinical ileitis has not been systematically explored in this population. We evaluated the diagnostic performance of serial fecal calprotectin for identifying subclinical inflammatory bowel disease in a prospective cohort of 69 patients with idiopathic uveitis or scleritis, using a baseline measurement repeated at 6–12 months if negative or at three months if positive, defining four longitudinal patterns (A–D). Subclinical ileitis was confirmed by capsule endoscopy and/or colonoscopy in 5 of the 62 patients with an evaluable outcome (8.1%). Baseline fecal calprotectin was significantly higher in patients with confirmed ileitis ( p = 0.024), a difference that became more pronounced at the second determination ( p = 0.002). The pattern of persistent elevation (subgroup D) showed the best diagnostic balance: sensitivity 100% (exact 95% CI: 47.8–100.0), specificity 82.5% (95% CI: 70.1–91.3), negative predictive value 100% (95% CI: 92.5–100.0), and positive likelihood ratio 5.7 (95% CI: 3.25–10.01). ROC curve analysis showed a numerically higher discriminative capacity for the second calprotectin determination (AUC: 0.932; 95% CI: 0.850–1.000) than for the baseline measurement (AUC: 0.809; 95% CI: 0.652–0.966), although a formal DeLong comparison between both c-statistics found no statistically significant difference ( p = 0.242). This exploratory, hypothesis-generating cohort suggests that a persistently elevated fecal calprotectin trajectory identifies a subgroup of patients with idiopathic uveitis or scleritis who may warrant digestive evaluation; because subgroups A and C were not endoscopically verified, the reported sensitivity and negative predictive value are estimates conditioned on this verification scheme and on only five events, not validated evidence that a negative trajectory excludes subclinical ileitis. Confirmation in larger, prospectively verified, multicenter cohorts is required before any screening recommendation can be made.