Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis

Patients with ulcerative colitis often report fatigue

Fecal calprotectin - the usefulness in special clinical situations and issues on the sampling procedure

Fecal Calprotectin The usefulness in special clinical situations and issues on the sampling procedure Anders Lasson Department of Internal Medicine Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Sweden Ulcerative colitis and Crohnʼs disease are chronic inflammatory bowel diseases (IBD) of unknown etiology. In recent years, mucosal healing has emerged as the goal for therapy to achieve long-term remission and to change the natural course of IBD. Thus, it is essential to monitor thoroughly the disease activity. Fecal calprotectin is the best available biomarker of disease activity in IBD. The overall aim of this thesis was to study the clinical usefulness of fecal calprotectin. Four different patient cohorts were investigated. For patients with active ulcerative colitis, the fecal calprotectin levels varied considerably, even over a single day, and the variability was considered to be clinically important in up to one-third of the patients. However, the longer the time period between bowel movements, the higher were the concentrations of calprotectin. To reduce both the impact of the variability and the risk of false low calprotectin values, samples should be obtained from the first stool passed in the morning. In stool samples stored at room temperature, the concentrations of calprotectin were stable for 3 days, while the levels decreased significantly after 7 days. In a questionnaire, the patients declared that they did not find it burdensome to obtain stool samples, although suitable equipment was considered desirable. The levels of fecal calprotectin did not distinguish between patients with endoscopic recurrence 1 year after ileocaecal resection for Crohn’s disease and those without. However, in patients with low calprotectin values, endoscopic remission was commonly noted, suggesting that a colonoscopy might be avoided in these cases. In the group of patients with quiescent ulcerative colitis, dose escalation of 5-aminosalicylic acid (5-ASA) in those patients identified with increased levels of calprotectin significantly reduced the relapse rate. However, the overall relapse rate of the intervention group was not significantly lower than that of the control group. At cut-off values for calprotectin of 169 µg/g and 262 µg/g, the clinical course in patients with newly diagnosed ulcerative colitis could be predicted with good specificity and moderate sensitivity, for 1 and 3 years, respectively. Conclusions: These results facilitate standardization of the stool sampling procedure, which is necessary to improve the accuracy of this biomarker. Furthermore, fecal calprotectin might be used to select patients for ileocolonoscopy 1 year after ileocaecal resection for Crohnʼs disease. To treat patients with IBD in clinical remission, but with increased values of calprotectin suggesting subclinical disease activity, brings a new dimension to IBD care. In this context, dose escalation of 5-ASA may be appropriate in patients with ulcerative colitis. This therapeutic concept should be tested also in patients with new onset of ulcerative colitis

Faecal secretogranin and chromogranin levels persist over time and are unrelated to disease history and outcome in patients with ulcerative colitis

Objectives: Chromogranins (Cg) and secretogranins (Sg) are expressed by endocrine cells and may be important for the pathophysiology of ulcerative colitis (UC). We investigated dynamics of faecal granin expression in patients with UC during a period of 18 months, both during remission and relapse, and association to disease outcome the following 3 years. Materials and methods: Secretoneurin (SN), Sg3, CgA and CgB were measured in three to seven serial faecal samples from UC patients who did not (n = 20) or did (n = 20) relapse during study time. All patients were in remission at baseline and disease characteristic were monitored during sampling and 3 years after the final sample. Results: Faecal SN, Sg3, CgA and CgB levels showed no association to patient characteristic or disease history at baseline. Faecal granin levels showed low intra-patient variability and levels stayed constant during short and long intervals at remission, did not alter during or after clinical relapse and were not associated to medical therapy. In contrast, high inter-patient variability was detected and multivariate analysis revealed three distinct patient groups, where extensive disease was more common in patients with high levels of SN and CgA as compared to patients with low levels of all granins or patients with high levels of Sg3 and CgB. These patient subgroups did, however, not differ in patient characteristics, disease history or future disease course. Conclusions: Faecal granin levels are stable over time but are unrelated to disease history, activity and outcome and are thus not valuable markers for disease activity in UC patients

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study

Abstract Background: Targeted therapy, using biomarkers to assess disease activity in ulcerative colitis (UC), has been proposed. Objective: The objective of this study was to evaluate whether pharmacological intervention guided by fecal calprotectin (FC) prolongs remission in patients with UC. Methods: A total of 91 adults with UC in remission were randomized to an intervention group or a control group. Analysis of FC was performed monthly, during 18 months. A FC value of 300 mg/g was set as the cut-off for intervention, which was a dose escalation of the oral 5-aminosalicylate (5-ASA) agent. The primary study end-point was the number of patients to have relapsed by month 18. Results: There were relapses in 18 (35.3%) and 20 (50.0%) patients in the intervention and the control groups, respectively (p ¼ 0.23); and 28 (54.9%) patients in the intervention group and 28 (70.0%) patients in the control group had a FC > 300 mg/g, of which 8 (28.6%) and 16 (57.1%) relapsed, respectively (p < 0.05). Conclusion: Active intervention significantly reduced relapse rates, although no significant difference was reached between the groups overall. Thus, FC-levels might be used to identify patients with UC at risk for a flare, and a dose escalation of their 5-ASA agent is a therapeutic option for these patients

Faecal secretogranin and chromogranin levels persist over time and are unrelated to disease history and outcome in patients with ulcerative colitis

<p><b>Objectives</b>: Chromogranins (Cg) and secretogranins (Sg) are expressed by endocrine cells and may be important for the pathophysiology of ulcerative colitis (UC). We investigated dynamics of faecal granin expression in patients with UC during a period of 18 months, both during remission and relapse, and association to disease outcome the following 3 years.</p> <p><b>Materials and methods</b>: Secretoneurin (SN), Sg3, CgA and CgB were measured in three to seven serial faecal samples from UC patients who did not (n = 20) or did (n = 20) relapse during study time. All patients were in remission at baseline and disease characteristic were monitored during sampling and 3 years after the final sample.</p> <p><b>Results</b>: Faecal SN, Sg3, CgA and CgB levels showed no association to patient characteristic or disease history at baseline. Faecal granin levels showed low intra-patient variability and levels stayed constant during short and long intervals at remission, did not alter during or after clinical relapse and were not associated to medical therapy. In contrast, high inter-patient variability was detected and multivariate analysis revealed three distinct patient groups, where extensive disease was more common in patients with high levels of SN and CgA as compared to patients with low levels of all granins or patients with high levels of Sg3 and CgB. These patient subgroups did, however, not differ in patient characteristics, disease history or future disease course.</p> <p><b>Conclusions</b>: Faecal granin levels are stable over time but are unrelated to disease history, activity and outcome and are thus not valuable markers for disease activity in UC patients.</p