Abstract
Background
A diagnostic delay >12 months is frequent in Crohn’s disease (CD), and associated with lower therapeutic response rates and worse outcomes. The Red Flags index, a simple tool to help to identify early CD and reduce diagnostic delay, was recently developed. We aimed to assess its accuracy for early diagnosis of CD patients.
Methods
Consecutive adult patients, suffering from intestinal symptoms and having no medical history of any gastrointestinal disease, referring to the General Practitioner (GP) were screened. Patients should have at least one of the following symptoms: chronic abdominal pain, chronic diarrhoea, nocturnal diarrhoea, unexpected weight loss, or perianal lesions. The GPs administered the Red Flags questionnaire to each eligible patient. Then, all patients were referred to the nearest participating Centre to confirm or exclude the diagnosis of CD. IBD specialists were blinded to the results of the questionnaire. The first-line examination systematically included blood cell count, serum C-reactive protein, faecal calprotectin (FC) and abdominal ultrasound, according to routine practice. If required to confirm CD, second-line examinations were planned (i.e. colonoscopy and cross-sectional imaging). Sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) of the Red Flags index were estimated. Patients lost to follow-up were included in the analysis by a non-responder imputation assuming they were negative for CD.
Results
From 11/2016 to 11/2019, 64 GPs participated (Bergamo: 52, Pavia: 12, in charge of a population of 93,000 subjects) and 112 patients over a mean number of 53,568 subjects screened were included in the study (median age 35 years, range: 18–69, 37% males). Only 66 subjects (59%) completed the study. The prevalence of CD was 3.6% in the study population (4 of 112 subjects; 3 with B1, and 1 with B2 phenotype). The Red Flags index had Se=0.50 (95% CI: 0.07–0.93), Sp = 0.58 (0.49–0.68), PPV=0.04 (0.01–0.15), and NPV=0.97 (0.89–1.00). A combined diagnostic strategy with faecal calprotectin (in which a subject was considered ‘positive’ if having RFI ≥8 and/or FC >250) resulted in significantly improved diagnostic accuracy: Se=1.00 (0.29–1.00), Sp = 0.72 (0.55–0.85), PPV=0.21 (0.05–0.51), NPV=1.00 (0.88–1.00); however, only 42 subjects (with 3 confirmed cases of CD) were available for this analysis.
Conclusion
The diagnostic accuracy of the Red Flags questionnaire was moderate when applied alone to a primary care setting. However, the combined diagnostic strategy of the Red Flags index and faecal calprotectin has given promising results. Further research is warranted on how to best identify patients with early clinical onset of CD.
Diagnostic Delay in Crohn’s Disease: Time for Red Flags