Diagnosis of Preclinical Crohn’s Disease: Hurdles, Challenges, and Hopes

We read with interest the paper by Taylor et al.1Taylor K.M. al.Clin Gastroenterol Hepatol. 2020; 18: 908-916Abstract Full Text PDF PubMed Scopus (12) Google Scholar The authors calculated a risk score for asymptomatic first-degree relatives (FDR) of patients Crohn's disease (CD) combining genetic (a synthesis 72 CD variants) and smoking status. Such was used to identify FDRs in lowest highest quartiles risk. were then invited undergo video capsule endoscopy (VCE). They built model predict inflammation at VCE that included several variables. Variable selection regularization carried out using different methods. best predictive according elastic net family history, score, fecal calprotectin (area under curve, 0.8; confidence interval, 0.62–0.98); random forest, 5 most important predictors (1) calprotectin, (2) (3) high-sensitivity C-reactive protein, (4) interleukin-6, (5) history 0.87; 0.75–1.00). As today, diagnosis clinical occurs late time when has already caused extensive mucosal damage appearance symptoms. is often associated complications or poor response medical therapy. have shown single reported long-term follow-up case patient preclinical interval between biologic onset symptoms years.2Sorrentino D. al.J Crohns Colitis. 2014; 8: 702-707Abstract (9) long period offers an excellent opportunity prevent symptomatic better understand causes pathogenesis. For example, aggressive therapy seems capable healing intestinal mucosa.2Sorrentino Testing individuals also raised possibility dysbiosis (widely considered key factor etiology/pathogenesis) could be consequence rather than cause disease.3Kuballa A. al.Inflamm Bowel Dis. (Epub ahead print)PubMed This nice study al1Taylor consistent our early findings FDR underwent ileocolonoscopy older, unrelated studies showing mild increase stool markers large proportion them.4Sorrentino 20: 1049-1056Crossref (25) Scholar,5Thjodleifsson B. al.Gastroenterology. 2003; 124: 1728-1737Abstract (139) However, one wonders how applicable al's1Taylor proposed strategy screen Multiple-relatives well-known CD. Fecal other blood are not sensitive enough even detect small bowel disease.6Sorrentino 2018; 24: 1566-1574Crossref (20) certainly potentially helpful tool but it only minimally improve accuracy prediction model, notwithstanding its inherent uncertainty might make cost ineffective generate undue expectations (as commercial “genetic” tests done). Finally, investigate inflammation. can affect colon considerable patients. Furthermore, scoring should developed validated this particular indication. currently conducting similar whereby evaluated new panenteric ("Crohn's”) reflex colonoscopy performed positive cases obtain tissue confirm diagnosis. Biomarker, genetic, gene expression investigations run parallel.7Sorrentino al.Cells. 2019; E548Crossref Others chosen retrospective effective approach indicators disease.8Torres J. print)Google Ideally, future accurate noninvasive marker trigger execution diagnostic tests, such as VCE, general population. before completely change current dismal algorithms propose strategies block evolution much data need gathered on natural rate progression, intervene. There road journey just begun. there little doubt we moving right direction. Genetic Inflammatory Biomarkers Classify Small Intestine Inflammation Asymptomatic First-degree Relatives Patients With Crohn’s DiseaseClinical Gastroenterology HepatologyVol. 18Issue 4PreviewRelatives carry CD-associated variants exposed environmental factors their disease. aimed estimate utility genotype, status, biomarkers calculate Full-Text ReplyClinical 19Issue 4PreviewWe thank colleagues Sorrentino al letter editor concerning study.1 raise legitimate concerns about testing risk, intention validity informative capacity translate practice stage. believe work provides platform refining comprehensive (whole-genome) information, which longitudinal data, underway group.