Psychological stress has long been reported anecdotally to increase disease activity in inflammatory bowel disease (IBD), and recent well designed studies have confirmed that adverse life events, ...chronic stress, and depression increase the likelihood of relapse in patients with quiescent IBD. This evidence is increasingly supported by studies of experimental stress in animal models of colitis. With the evolving concept of psychoneuroimmunology, the mechanisms by which the nervous system can affect immune function at both systemic and gut mucosal levels are gradually becoming apparent. Recent data suggest that stress induced alterations in gastrointestinal inflammation may be mediated through changes in hypothalamic-pituitary-adrenal (HPA) axis function and alterations in bacterial-mucosal interactions, and via mucosal mast cells and mediators such as corticotrophin releasing factor (CRF). To date, the therapeutic opportunities offered by stress reduction therapy remain largely unexplored, in part because of methodological difficulties of such studies. This paper reviews recent advances in our understanding of the pathogenic role of psychological stress in IBD and emphasises the need for controlled studies of the therapeutic potential of stress reduction.
Summary
Background There is increasing concern about the apparently rising incidence and worsening outcome of Clostridium difficile infection (CDI) associated with inflammatory bowel disease (IBD). ...We have systematically reviewed the literature to evaluate the incidence, risk factors, endoscopic features, treatment and outcome of CDI complicating IBD.
Aim To systematically review: clostridium difficile & inflammatory bowel disease.
Methods Structured searches of Pubmed up to September 2010 for original, cross‐sectional, cohort and case‐controlled studies were undertaken.
Results Of 407 studies, 42 met the inclusion criteria: their heterogeneity precluded formal meta‐analysis. CDI is commoner in active IBD, particularly ulcerative colitis, than in controls. Certainty about a temporal trend to its increasing incidence in IBD is compromised by possible detection bias and miscoding. Risk factors include immunosuppressants and antibiotics, the latter less commonly than in controls. Endoscopy rarely shows pseudomembranes and is unhelpful for diagnosing CDI in IBD. There are no controlled therapeutic trials of CDI in IBD. In large studies, outcome of CDI in hospitalised IBD patients appears worse than in controls.
Conclusions The complication of IBD by Clostridium difficile infection has received increasing attention in the past decade, but whether its incidence is really increasing or its outcome worsening remains unproven. Therapeutic trials of Clostridium difficile infection in IBD are lacking and are needed urgently.
Interleukin 17 (IL17) is now known to be involved in a number of chronic inflammatory disorders. However, the mechanisms regulating its production in inflammatory bowel disease (IBD) are still ...unclear.
Endoscopic biopsies or surgical specimens were taken from inflamed and uninflamed colonic mucosa of 72 patients with IBD (38 with Crohn's disease and 34 with ulcerative colitis), and normal colon of 38 control subjects. IL17 and interferon gamma (IFNgamma) were detected by ELISA in the supernatants of biopsies cultured ex vivo, and anti-CD3/CD28-stimulated lamina propria mononuclear cells (LPMCs) incubated with IL12, IL23, IL1beta plus IL6, transforming growth factor beta1 (TGFbeta1), or anti-IL21 neutralising antibody. Intracellular flow cytometry was performed to analyse mucosal Th17 and Th1/Th17 cells.
IL17 production by organ culture biopsies was higher in IBD inflamed mucosa than IBD uninflamed mucosa and controls, and was equivalent in amount to IFNgamma. Anti-CD3/CD28-stimulated IBD LPMCs produced higher IL17 amounts compared to controls. The percentages of Th17 and Th1/Th17 cells were increased in patients with IBD. IL23 and IL1beta plus IL6 had no effect on IBD LPMC production of IL17; however, IL12 markedly increased IFNgamma production and decreased IL17 production. TGFbeta1 dose-dependently decreased IFNgamma, but had no significant inhibitory effect on IL17 production. Blocking IL21 significantly downregulated IL17 production.
Our findings support a role for IL12, TGFbeta and IL21 in modulating IL17/IFNgamma production in IBD. The abundant IL17 in inflamed IBD mucosa may help explain the relative lack of efficacy of anti-IFNgamma antibodies in clinical trials of Crohn's disease.
Background:
Anxiety and depression are common in patients with inflammatory bowel disease (IBD); however, the factors associated with mood disorders in patients with ulcerative colitis (UC) and ...Crohn's disease (CD) are poorly defined.
Methods:
In all, 103 patients with UC, 101 with CD, and 124 healthy controls completed the Hospital Anxiety and Depression Scale (HADS). Disease activity was defined both from symptom scores and in UC endoscopically, and in CD by fecal calprotectin and/or serum C‐reactive protein. Multivariate regression analyses were used to identify factors associated with anxiety and depression.
Results:
In both UC and CD, anxiety (HADS‐A) and depression (HADS‐D) scores were higher than in controls (HADS‐A: 8.5 ± 4.1 mean ± SD, 8.6 ± 3.9, 3.2 ± 1.8, P < 0.001; and HADS‐D: 4.1 ± 3.3, 4.7 ± 3.3, 1.7 ± 1.4, P < 0.001, respectively). There were no differences in the prevalence of mild, moderate, and severe anxiety and depression in UC and CD. In UC, anxiety scores were associated with perceived stress and a new diagnosis of IBD; depression was associated with stress, inpatient status, and active disease. In CD, anxiety was associated with perceived stress, abdominal pain, and lower socioeconomic status, and depression with perceived stress and increasing age.
Conclusions:
Anxiety and depression are common in IBD. Perceived stress is associated with mood disturbances in both UC and CD, but the other associated factors differ in the two diseases. Gastroenterologists should look for mood disorders in IBD and consider stress management and psychotherapy in affected patients. (Inflamm Bowel Dis 2012;)
Measurements of luminal pH in the normal gastrointestinal tract have shown a progressive increase in pH from the duodenum to the terminal ileum, a decrease in the caecum, and then a slow rise along ...the colon to the rectum. Some data in patients with ulcerative colitis suggest a substantial reduction below normal values in the right colon, while limited results in Crohn's disease have been contradictory. Determinants of luminal pH in the colon include mucosal bicarbonate and lactate production, bacterial fermentation of carbohydrates and mucosal absorption of short chain fatty acids, and possibly intestinal transit. Alterations in these factors, as a result of mucosal disease and changes in diet, are likely to explain abnormal pH measurements in inflammatory bowel disease (IBD). It is conceivable that reduced intracolonic pH in active ulcerative colitis impairs bioavailability of 5-aminosalicylic acid from pH dependent release formulations (Asacol, Salofalk) and those requiring cleavage by bacterial azo reductase (sulphasalazine, olsalazine, balsalazide), but further pharmacokinetic studies are needed to confirm this possibility. Reports that balsalazide and olsalazine may be more efficacious in active and quiescent ulcerative colitis, respectively, than Asacol suggest that low pH may be a more critical factor in patients taking directly pH dependent release than azo bonded preparations. Reduced intracolonic pH also needs to be considered in the development of pH dependent colonic release formulations of budesonide and azathioprine for use in ulcerative and Crohn's colitis. This paper reviews methods for measuring gut pH, its changes in IBD, and how these may influence current and future therapies.
Evidence that psychological stress can increase inflammation and worsen the course of immune-mediated inflammatory disease (IMID) is steadily accumulating. The majority of data supporting this ...hypothesis come from studies in patients with inflammatory bowel disease (IBD). While there is no evidence to suggest that stress is a primary cause of IBD, many, although not all, studies have found that patients with IBD experience increased stress and stressful life events before disease exacerbations. Further, the disease itself can cause psychological stress, creating a vicious cycle. In addition to reviewing the epidemiological evidence supporting a stress-IMID relationship, this article also briefly discusses how stress-related changes in neural, endocrine, and immune functioning may contribute to the pathogenesis of immune diseases, IBD in particular. The effects of different pharmacological and nonpharmacological interventions, including stress management and behavioral therapy, on stress, mood, quality of life (QOL), and activity of the underlying IMID are also summarized.
Summary
Complementary and alternative medicine includes a wide range of practices and therapies outside the realms of conventional western medicine. Despite a lack of scientific data in the form of ...controlled trials for either efficacy or safety of complementary and alternative medicine, use by patients with inflammatory bowel disease, particularly of herbal therapies, is widespread and increasing.
There is limited controlled evidence indicating efficacy of traditional Chinese medicines, aloe vera gel, wheat grass juice, Boswellia serrata and bovine colostrum enemas in ulcerative colitis. Encouraging results have also been reported in small studies of acupuncture for Crohn's disease and ulcerative colitis. Contrary to popular belief, natural therapies are not necessarily safe: fatal hepatic and irreversible renal failure have occurred with some preparations and interactions with conventional drugs are potentially dangerous.
There is a need for further controlled clinical trials of the potential efficacy of complementary and alternative approaches in inflammatory bowel disease, together with enhanced legislation to maximize their quality and safety.
Summary
Background : Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition.
Aim : To assess the effects of aloe vera in ...vitro on the production of reactive oxygen metabolites, eicosanoids and interleukin‐8, all of which may be pathogenic in inflammatory bowel disease.
Methods : The anti‐oxidant activity of aloe vera was assessed in two cell‐free, radical‐generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. Eicosanoid production by biopsies and interleukin‐8 release by CaCo2 epithelial cells in the presence of aloe vera were measured by enzyme‐linked immunosorbent assay.
Results : Aloe vera gel had a dose‐dependent inhibitory effect on reactive oxygen metabolite production; 50% inhibition occurred at 1 in 1000 dilution in the phycoerythrin assay and at 1 in 10–50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30% at 1 in 50 dilution (P = 0.03), but had no effect on thromboxane B2 production. The release of interleukin‐8 by CaCo2 cells fell by 20% (P < 0.05) with aloe vera diluted at 1 in 100, but not at 1 in 10 or 1 in 1000 dilutions.
Conclusion : The anti‐inflammatory actions of aloe vera gel in vitro provide support for the proposal that it may have a therapeutic effect in inflammatory bowel disease.
Summary
Background
Medication non‐adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome.
Aims
To assess ...whether non‐adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co‐morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8‐item Adherence Scale (MMAS‐8) to detect non‐adherence.
Methods
Seventy young adults 51% (36) male and 74 62% (46) male adults were included. Psychological co‐morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self‐reported adherence using the MMAS‐8.
Results
Twelve percent (18/144) of the patients were non‐adherent. Multivariate analysis OR, (95% CI), P value confirmed that being young adult 6.1 (1.7–22.5), 0.001, of lower socio‐economic status 1.1 (1.0–1.1), <0.01 and reporting higher HADS‐D scores 1.2 (1.0–1.4), 0.01 were associated with non‐adherence. Receiver operator curve analysis of MMAS‐8 scores gave an area under the curve (95% CI) of 0.85 (0.77–0.92), (P < 0.0001): using a cut‐off of <6, the MMAS‐8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non‐adherence. Non‐adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up.
Conclusions
Non‐adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio‐economic status and depression. The high negative predictive value of MMAS‐8 scores <6 suggests that it could be a useful screen for thiopurine non‐adherence.
Summary
Background : The herbal preparation, aloe vera, has been claimed to have anti‐inflammatory effects and, despite a lack of evidence of its therapeutic efficacy, is widely used by patients with ...inflammatory bowel disease.
Aim : To perform a double‐blind, randomized, placebo‐controlled trial of the efficacy and safety of aloe vera gel for the treatment of mildly to moderately active ulcerative colitis.
Methods : Forty‐four evaluable hospital out‐patients were randomly given oral aloe vera gel or placebo, 100 mL twice daily for 4 weeks, in a 2 : 1 ratio. The primary outcome measures were clinical remission (Simple Clinical Colitis Activity Index ≤ 2), sigmoidoscopic remission (Baron score ≤ 1) and histological remission (Saverymuttu score ≤ 1). Secondary outcome measures included changes in the Simple Clinical Colitis Activity Index (improvement was defined as a decrease of ≥ 3 points; response was defined as remission or improvement), Baron score, histology score, haemoglobin, platelet count, erythrocyte sedimentation rate, C‐reactive protein and albumin.
Results : Clinical remission, improvement and response occurred in nine (30%), 11 (37%) and 14 (47%), respectively, of 30 patients given aloe vera, compared with one (7%) P = 0.09; odds ratio, 5.6 (0.6–49), one (7%) P = 0.06; odds ratio, 7.5 (0.9–66) and two (14%) P < 0.05; odds ratio, 5.3 (1.0–27), respectively, of 14 patients taking placebo. The Simple Clinical Colitis Activity Index and histological scores decreased significantly during treatment with aloe vera (P = 0.01 and P = 0.03, respectively), but not with placebo. Sigmoidoscopic scores and laboratory variables showed no significant differences between aloe vera and placebo. Adverse events were minor and similar in both groups of patients.
Conclusion : Oral aloe vera taken for 4 weeks produced a clinical response more often than placebo; it also reduced the histological disease activity and appeared to be safe. Further evaluation of the therapeutic potential of aloe vera gel in inflammatory bowel disease is needed.
PDF
