Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

Shimodate, Yuichi; Takanashi, Kunihiro; Waga, Eriko; Fujita, Toshio; Katsuki, Shinichi; Nomura, Masafumi

doi:10.1159/000326931

Cited by 27 publications

(19 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There have been previous case studies reported of mesalazine worsening diarrhoea in colitis. 29 30 This may represent an allergic response to the drug as we did find an increase in T lymphocytes.…”

Section: Discussionmentioning

confidence: 61%

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D)

Lam

Tan

Leighton

et al. 2015

Gut

View full text Add to dashboard Cite

IntroductionImmune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11–12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms.MethodsParticipants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’.Results136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (−0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up.ConclusionsThis study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS.Trial registration numberNCT01316718.

show abstract

Section: Discussionmentioning

confidence: 61%

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D)

Lam

Tan

Leighton

et al. 2015

Gut

View full text Add to dashboard Cite

show abstract

“…There have been previous case studies reporting treatment with mesalazine worsening diarrhoea in colitis. 50,51 This may represent an allergic response to the drug, as we did find an increase in T lymphocytes.…”

Section: Postinfectious Irritable Bowel Syndromementioning

confidence: 55%

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

et al. 2015

View full text Add to dashboard Cite

BackgroundDiarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2 g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.ObjectivesOur primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.Design/participants/interventionWe performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.SettingsParticipants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.ResultsA total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53);p = 0.66.ConclusionsMesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.Trial registrationCurrent Controlled Trials ISRCTN76612274.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

show abstract

“…Colitis-like symptoms had been described in the treatment of ulcerative colitis using sulphasalazine, but also similar presentations had been reported with mesalamine in adults with ulcerative colitis [ 2 , 3 , 4 ]. There are a few reports on mesalamine-related colitis in children with ulcerative colitis [ 8 , 9 ], while it is scarce in children and adults with CD [ 5 ]. In both children and adult cases, abdominal pain, diarrhoea (may be bloody), fever and arthralgias were reported within 24–48 h of starting mesalamine treatment, and these symptoms resolve within 24–48 h of stopping the drug which were similar to our 3 cases.…”

Section: Discussionmentioning

confidence: 99%

Mesalamine Intolerance in Three Children with Crohn's Disease

Kırşaçlıoğlu

Kuloğlu²,

Üstündağ³

et al. 2015

Med Princ Pract

View full text Add to dashboard Cite

Objective: To present the mesalamine-induced acute exacerbation of symptoms and inflammatory markers in children with Crohn's disease (CD). Clinical Presentation and Intervention: Three children who presented with CD had acute exacerbation of colitis symptoms or elevated inflammatory markers when mesalamine was added to treatment while tapering/ceasing steroid treatment. While on steroid treatment, the patients maintained clinical and laboratory remission, but with the initiation of mesalamine treatment, they had abdominal pain and bloody mucoid diarrhoea and/or elevation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. Bacterial pathogens were excluded from the urine, throat and blood cultures, parasites with stool examination, viral pathogens with serology. Within 3-7 days after the mesalamine treatment had been stopped, the patients showed improvement of colitis symptoms and normalisation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. Conclusion: In this study mesalamine mimicked CD relapse in children with CD while tapering or after stopping steroid treatment. Awareness of this side effect of mesalamine could prevent a misdiagnosis of steroid dependency.

show abstract

Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

Cited by 27 publications

References 13 publications

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D)

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D)

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

Mesalamine Intolerance in Three Children with Crohn's Disease

Contact Info

Product

Resources

About