Reply.

Abstract

We thank Hirten and Colombel1Hirten R. et al.Clin Gastroenterol Hepatol. 2017; 15: 1315Abstract Full Text Full Text PDF Scopus (3) Google Scholar for their erudite commentary on our recently published work.2Gracie D.J. et al.Clin Gastroenterol Hepatol. 2017; 15: 376-384.e5Abstract Full Text Full Text PDF Scopus (67) Google Scholar The findings of our study highlight the association between irritable bowel syndrome (IBS)–type symptoms in patients with quiescent inflammatory bowel disease (IBD) as well as psychological comorbidity and poor quality of life, and are in keeping with those of another large study from Sweden, reporting that 18% of patients with ulcerative colitis (UC) in deep remission report these symptoms.3Jonefjall B. et al.Inflamm Bowel Dis. 2016; 22: 2630-2640Google Scholar These studies highlight a hitherto poorly characterized cohort of patients with unmet needs, for which the therapeutic options are limited. In response to their specific comments, first we acknowledged that the use of fecal calprotectin (FC) as an objective measure of inflammatory disease activity is contentious, as is the cut-off used to define disease activity. However, the routine use of ileocolonoscopy and small bowel imaging in a cross-sectional study of 378 patients is impractical and potentially unethical, given that 60% of patients did not have clinically active disease at the time of participation. We used a FC cutoff of ≥250 μg/g to define active disease, based on previous studies in this field and expert consensus.4Rogler G. et al.J Crohns Colitis. 2013; 7: 670-677Google Scholar, 5Targownik L.E. et al.Am J Gastroenterol. 2015; 110: 1001-1012Google Scholar, 6Gracie D.J. et al.Am J Gastroenterol. 2016; 111: 541-551Google Scholar However, we conducted sensitivity analyses using a cutoff of ≥100 μg/g. In these analyses, the proportion of patients with IBS-type symptoms was reduced, but the association among symptoms, psychological comorbidity, and poor quality of life remained. In addition, the mean FC in those with IBS-type symptoms in our primary analysis was <100 μg/g in both Crohn's disease and UC. Second, we conceded that describing all patients as suffering from IBS may be misleading, particularly as similar symptoms secondary to other organic complaints such as bile acid malabsorption and small intestinal bacterial overgrowth may be the culprit,7Aziz I. et al.Clin Gastroenterol Hepatol. 2015; 13: 1650-1655.e2Abstract Full Text Full Text PDF Scopus (58) Google Scholar, 8Ford A.C. et al.Clin Gastroenterol Hepatol. 2009; 7: 1279-1286Google Scholar particularly in those with previous surgery, and that this may have inflated the prevalence of these symptoms. It may therefore be more accurate to describe these patients as reporting persistent gastrointestinal (GI) symptoms in the absence of inflammation, rather than IBS-type symptoms. Indeed, within the same cohort of patients, subsequent analysis of the prevalence and impact of persistent GI symptoms in the absence of inflammation on psychological comorbidity and quality of life demonstrated similar findings to those described in the present study, irrespective of whether these symptoms met Rome III criteria for IBS.9Gracie D.J. et al.Inflamm Bowel Dis. 2017; 23: E4-E5Google Scholar Third, Hirten and Colombel highlight the potential for misclassification of persistent symptoms in quiescent IBD as IBS, and that treatment of these patients should be tailored to the underlying cause, citing dysregulation of the enteric nervous system and enteric dysmotility, 2 of the cardinal features of the functional GI disorders, as potential targets to therapy. To the best of our knowledge, evidence-based management strategies for these patholophysiologies are lacking in IBD, and it is this exact group of patients that our study successfully seeks to identify and better characterize. Thus, our findings highlight the need for trials of novel therapeutic interventions in these patients, and the requirement of a paradigm shift in the approach toward their management. In the United Kingdom there has been a recent call from the Health Technology Assessment for a trial of therapies for ongoing diarrhea and abdominal pain in patients with stable UC, which may help to address this deficit in current knowledge.1017/33 Management of diarrhoea in patients with stable ulcerative colitis. Available at: http://www.nihr.ac.uk/funding-and-support/funding-opportunities/1733-management-of-diarrhoea-in-patients-with-stable-ulcerative-colitis/5984. Accessed April 20, 2017.Google Scholar Need for Caution in Diagnosis of Irritable Bowel Syndrome in Patients With Inflammatory Bowel DiseaseClinical Gastroenterology and HepatologyVol. 15Issue 8PreviewWe read with interest the article by Gracie et al,1 which reported the prevalence of irritable bowel syndrome (IBS)-type symptoms in patients with Crohn’s disease (CD) and ulcerative colitis (UC) in remission to be 27.7% and 19.8%, respectively. We would like to raise several concerns regarding the interpretation of their findings. Full-Text PDF