Visceral hypersensitivity is together with psychological distress and female gender associated with severity of IBS-like symptoms in quiescent ulcerative colitis.

BACKGROUND: A subset of ulcerative colitis (UC) patients in remission demonstrate IBS-like symptoms. Visceral hypersensitivity is a key pathophysiological mechanism in IBS, but its relevance to IBS-like symptoms in inactive UC remains unclear. METHODS: UC patients in remission (UCR) were screened for IBS-like symptoms. Rectal sensitivity was assessed with rectal balloon distensions, with determination of sensory thresholds and unpleasantness/pain intensity ratings. Patients completed questionnaires evaluating gastrointestinal (GI) and psychological symptoms. Age- and gender-matched IBS subjects and healthy controls (HC) also underwent a rectal sensitivity test. KEY RESULTS: We included 36 UCR patients (18 with IBS-like symptoms (UCR + IBS) and 18 without (UCR - IBS)), 36 IBS subjects, and 14 HC. UCR and IBS patients were more sensitive to rectal balloon distensions than HC, but no differences between UCR and IBS patients were observed. UCR + IBS patients had lower sensory thresholds and higher unpleasantness ratings than UCR - IBS. In UCR patients, the overall GI symptom severity, pain, and bloating, but not diarrhea, constipation or satiety, were associated with rectal sensitivity. In multivariate analyses, rectal sensitivity, psychological distress, and female gender were identified as factors independently associated with GI symptom severity. 61% of UCR patients demonstrated rectal hypersensitivity, and these patients more commonly reported at least mild bloating and pain, and overall GI symptoms, compared to those with normal rectal sensitivity. CONCLUSION & INFERENCES: Visceral hypersensitivity was associated with IBS-like symptoms, in particular pain and bloating, in inactive UC. Together with psychological factors and female gender, visceral hypersensitivity seems to be involved in GI symptom generation in quiescent UC.

The diagnostic value of a change in bowel habit for colorectal cancer within different age groups.

BACKGROUND: Change in bowel habit as a sole alarm symptom for colorectal cancer is disputed. OBJECTIVE: We investigated the diagnostic value of change in bowel habit for colorectal cancer, particularly as a single symptom and within different age groups. METHODS: This retrospective cohort study examined colorectal cancer fast track referrals and outcomes across four Swedish hospitals (April 2016-May 2017). Entry criteria constituted one or more of three alarm features: anaemia, visible rectal bleeding, or change in bowel habit for more than 4 weeks in patients over 40 years of age. Patients were grouped as having only change in bowel habit, change in bowel habit plus anaemia/bleeding or anaemia/bleeding only. RESULTS: Of 628 patients, 22% were diagnosed with colorectal cancer. There were no cases of colorectal cancer in the only change in bowel habit group under 55 years, while this was 6% for 55-64 years, 8% for 65-74 years and 14% for 75 years and older. Among subjects under 55 years, 2% with anaemia/bleeding had colorectal cancer, this increased to 34% for 55 years and older (P < 0.0001). Change in bowel habit plus anaemia/bleeding gave a colorectal cancer prevalence of 16% in under 55 years and increased to 30% for 55 years and older (P = 0.07). CONCLUSION: Change in bowel habit as the only alarm feature has a low diagnostic yield for colorectal cancer in patients under 55 years.

Systemic Inflammatory Protein Profiles Distinguish Irritable Bowel Syndrome (IBS) and Ulcerative Colitis, Irrespective of Inflammation or IBS-Like Symptoms.

BACKGROUND: Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients. METHODS: Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR + IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins. RESULTS: The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR + IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR + IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor-α characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR + IBS, n = 9; IBS, n = 14). CONCLUSIONS: SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.

Symptoms compatible with functional bowel disorders are common in patients with quiescent ulcerative colitis and influence the quality of life but not the course of the disease.

BACKGROUND: Whether patients with inactive ulcerative colitis (UC) have symptoms compatible with functional bowel disorders (FBDs) other than irritable bowel syndrome (IBS) is unclear. Our aim was to investigate the prevalence and burden of these symptoms and determine impact on the UC course. METHODS: We used Mayo score, sigmoidoscopy and calprotectin (f-cal) to define remission in 293 UC patients. Presence of symptoms compatible with FBD, severity of gastrointestinal, extraintestinal and psychological symptoms, stress levels and quality of life (QoL) were measured with validated questionnaires. At 1 year later, remission was determined by modified Mayo score and f-cal in 171 of these patients. They completed the same questionnaires again. RESULTS: A total of 18% of remission patients had symptoms compatible with FBD other than IBS, and 45% subthreshold symptoms compatible with FBD. The total burden of gastrointestinal symptoms in patients with symptoms compatible with FBD was higher than in patients without FBD (p < 0.001), which had negative impact on QoL (p = 0.02). These symptoms were not correlated with psychological distress, systemic immune activity or subclinical colonic inflammation and were not a risk factor for UC relapse during follow up. CONCLUSION: Symptoms compatible with FBD other than IBS are common during UC remission influencing patients' QoL but not the UC course.

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

BACKGROUND: Patients with ulcerative colitis often report fatigue. OBJECTIVES: To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. METHODS: In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n = 133) or being in deep remission (n = 155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. RESULTS: The prevalence of high fatigue (general fatigue ≥ 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1-12.2)), iron deficiency (OR 2.5 (1.2-5.1)), active disease (OR 2.2 (1.2-3.9)) and female gender (OR 2.1 (1.1-3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. CONCLUSIONS: Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission.

IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being.

BACKGROUND: Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission. METHODS: We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined. RESULTS: The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 µg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1ß, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03). CONCLUSIONS: IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission.

BACKGROUND AND AIMS: Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. METHODS: In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR-IBS). RESULTS: Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. CONCLUSION: The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients.