Symptoms in Inflammatory Bowel Disease: pathophysiologic aspects and their relation with disease activity

Abstract

Symptoms in Inflammatory Bowel Disease: pathophysiologic aspects and their relation with disease activity Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn's disease (CD). IBD patients frequently complain of fatigue, and a substantial proportion of the patients have gastrointestinal symptoms, resembling irritable bowel syndrome (IBS). These symptoms are not always related to disease activity, and the pathogenesis of the systemic symptoms in IBD is incompletely understood. 41% of the IBD patients in remission suffer from fatigue. We found mean fatigue scores comparable to the scores reported in cancer patients. We postulated that a disturbance in the hypothalamic-pituitary-adrenal axis would contribute to the generation of fatigue in these patients, but we could not confirm this hypothesis. As fatigue seems not to be the result of hypocortisolism, questions can be raised regarding other possible causes of this symptom. Cytokines (e.g. tumor necrosis factor (TNF)-α) play an important role in IBD, especially in active disease. Studies in patients with the chronic fatigue syndrome suggest an immunological basis for fatigue, mediated by cytokines. We found a clear reduction of fatigue following administration of infliximab (TNF-α antibody), although a placebo response was observed as well. A clear role of cytokines in the pathogenesis of fatigue could not be substantiated. Besides fatigue, symptoms resembling IBS symptoms are experienced by IBD patients in remission. One-third of UC patients and 40% of CD patients in remission suffer from IBS-like symptoms according to the Rome II criteria. The presence of these symptoms is not caused by a difference in coping strategies. In IBS patients visceral hypersensitivity is seen throughout the whole gastrointestinal tract. We addressed the question whether IBD patients with prior disease activity restricted to the colon, also develop visceral hypersensitivity throughout the whole gastrointestinal tract. Subtle differences in duodenal motor responses to lipids and acid were observed in IBD patients in remission. In our opinion these changes are indicative for changes at the level of chemoreceptors in the duodenal wall in this group of patients. However, the clinical relevance of these findings can be questioned, since none of the infusions induced altered perception of nausea, abdominal pain, bloating, urgency or fullness. At last, we studied the role of serotonin (5-HT) in the generation of IBS-like symptoms in CD patients in remission. Our data suggest that upregulated 5-HT synthesis in the colon might contribute to IBS-like symptom generation in CD patients in remission. Overall, our data suggest that the effect of inflammation on the ENS seems to play an important role in the generation of IBS-like symptoms in IBD patients. Assessing disease activity in CD is cumbersome and the tools used to measure inflammatory activity are not adequate. Mucosal healing is presently considered the ultimate goal of treatment in CD, but this can only be assessed by endoscopy. We developed a new activity index, including cheap, widely available, and easy-to-collect parameters that proved to accurately predict the severity of mucosal inflammation in CD patients. We feel that this index, after validation, will provide a better endpoint in clinical trials, and contribute importantly to clinical decision making in daily practice.