Validation of the Red Flags Index for Early Diagnosis of Crohn’s Disease: A Prospective Observational IG-IBD Study Among General Practitioners

Abstract

Introduction Diagnostic delay >12 months is frequent in Crohn’s disease [CD]. Recently, the International Organization for Inflammatory Bowel Disease [IO-IBD] developed a tool to identify early CD and reduce diagnostic delay. Subjects with an index ≥8 are more likely to have suspected CD (odds ratio [OR] 205, p <0.0001). We aimed to validate this questionnaire at the community level in patients seen by the general practitioners [GPs] in two large areas of Lombardy, Italy. Methods Consecutive adult patients referring to the GP were screened. The GPs administered the Red Flags [RF] questionnaire to the eligible patients. All patients were referred to the nearest participating centre to confirm or exclude the diagnosis of CD. Sensitivity, specificity, and positive and negative predictive values [PPV, NPV] of the RF index [RFI] were calculated. Patients lost to follow-up after the first gastroenterological visit were analysed using a non-responder imputation, assuming they were negative for CD diagnosis. Results From November 2016 to November 2019, 112 patients were included. A total of 66 subjects [59%] completed the study after the first gastroenterological visit. The prevalence of CD was 3.6% in the study population [4/112]. The RF index had 50% sensitivity, 58% specificity, 4% PPV, and 97% NPV. A combined diagnostic strategy with faecal calprotectin [FC] [RFI ≥8 and/or FC >250 ng/g] resulted in significantly improved accuracy: sensitivity 100% [29–100%], specificity 72% [55–85%], PPV = 21% [5–51%], NPV = 100% [88–100%]. Conclusions The RF Index combined with FC is a valid tool to identify patients with high probability of having CD at early stage.

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2022

“…A cutoff of 100 μg/g has demonstrated high sensitivity and specificity and appears to be the optimal cutoff value to be used as a screening tool for SB CD 118 121 . Moreover, in a prospective validation study, a combined diagnostic strategy based on clinical presentation with Red Flags index score ≥ 8 and/or fecal calprotectin > 250 ng/g showed average values (ranges) of sensitivity 100 % (29 %–100 %), specificity 72 % (55%–85 %), PPV 21 % (5 %–51 %), and NPV 100 % (88–100 %) for the diagnosis of CD 123 . Evidence also shows that a combination of biomarkers can further enhance patient selection.…”

“…based on clinical presentation with Red Flags index score ≥ 8 and/or fecal calprotectin > 250 ng/g showed average values (ranges) of sensitivity 100 % (29 %-100 %), specificity 72 % (55%-85 %), PPV 21 % (5 %-51 %), and NPV 100 % (88-100 %) for the diagnosis of CD [123]. Evidence also shows that a combination of biomarkers can further enhance patient selection.…”

Approach to the Management of Recently Diagnosed Inflammatory Bowel Disease Patients: A User’s Guide for Adult and Pediatric Gastroenterologists

“…35 Similarly, in the Red Flags Index validation study, combining the index with FC (Red Flags Index !8 and/ or FC >250 mg/g) increased the positive predictive value from 4% to 21% and negative predictive value from 97% to 100%. 36 Diagnostic criteria for IBD involve a composite of clinical symptoms, endoscopic, biomarker, and cross-sectional imaging features, which are beyond the scope of this review. We refer readers to the excellent guidelines laid out by the American College of Gastroenterology, European Crohn's and Colitis Organization, and British Society of Gastroenterology.…”

Early Diagnosis, Early Stratification, and Early Intervention to Deliver Precision Medicine in IBD

“… 16 Accordingly, one solution to overcome these delays in diagnosis is likely to be through increasing awareness in the medical community and encouraging use of tools to identify red flags, which allow more timely referrals to specialist clinics and greater pickup for cases of early IBD. 17 , 18 …”