Quiescent Crohn's Disease Research Articles

Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

Inflammation is involved in the pathogenesis of cardiovascular diseases that includes reduced response to pharmacotherapy due to altered pharmacokinetics and pharmacodynamics. It is not known if these effects exist in general in all inflammatory conditions. It also remains unknown whether in a given population the effect is a function of disease severity. We investigated whether pharmacokinetics and pharmacodynamics of a typical calcium channel inhibitor are influenced by Crohn's disease (CD), a disease for which the disease severity can be readily ranked. We administered 80 mg verapamil orally to (i) healthy control subjects (n= 9), (ii) patients with clinically quiescent CD (n= 22) and (iii) patients with clinically active CD (n= 14). Serial analysis of verapamil enantiomers (total and plasma unbound), blood pressure and electrocardiograms were recorded over 8 h post dose. The severity of CD was measured using the Harvey-Bradshaw Index. CD substantially and significantly increased plasma verapamil concentration and in a stereoselective fashion (S, 9-fold; R, 2-fold). The elevated verapamil concentration, however, failed to result in an increased verapamil pharmacodynamic effect so that the patients with elevated verapamil concentration demonstrated no significant increase in response measured as PR interval and blood pressure. Instead, the greater the disease severity, the lower was the drug potency to prolong PR interval (r= 0.86, P < 0.0006), CD patients with severe disease may not respond to cardiovascular therapy with calcium channel blockers. Reducing the severity increases response despite reduced drug concentration. This observation may have therapeutic implication beyond the disease and the drug studies herein.

Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease

Background TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease. Aims To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment. Methods Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR. Results We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti-inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement. Conclusions TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities.

Effects of Dairy Products on Crohn's Disease Symptoms Are Influenced by Fat Content and Disease Location but not Lactose Content or Disease Activity Status in a New Zealand Population

Background Dairy products have been perceived as having the potential to cause adverse effects in individuals with Crohn's disease (CD) and are often avoided, potentially increasing the risk of osteoporosis and related morbidity associated with inadequate dietary calcium intake. Objective To evaluate the self-reported effects of dairy products on CD symptoms and to determine whether these effects differed between types of dairy products consumed and disease state or location. Design Secondary analysis of dietary survey and clinical data from participants in the Genes and Diet in Inflammatory Bowel Disease study based in Auckland, New Zealand. Subjects/setting One hundred and sixty-five men and women diagnosed with CD for which both dietary survey data and clinical information were available. Statistical analyses performed χ 2 analysis was conducted to assess whether significant differences in the proportions of responses relating to a worsening of CD symptoms from individual dairy products were evident between individuals with active or quiescent CD, or ileal or colonic disease locations. Odds ratios with confidence interval were calculated to determine whether CD location was associated with risk of any type of adverse reaction to milk products. Logit scales were utilized to depict self-reported CD symptoms associated with individual dairy product consumption for ileal and colonic CD patients. Results Dairy products had no effect on self-reported CD symptoms for most people. Dairy products with a high fat content were most frequently reported to worsen perceived CD symptoms. Clinically, self-reported CD activity status did not influence responses to dairy products; however, colonic inflammation was more frequently associated with adverse CD effects in comparison to ileal CD involvement. Conclusions Research outcomes question the necessity of dairy product avoidance in CD patients and illustrate the highly individual nature of dairy product tolerance in this clinical population.

Solution focused therapy: A promising new tool in the management of fatigue in Crohn's disease patients: Psychological interventions for the management of fatigue in Crohn's disease

Background Crohn's disease patients have a decreased Quality of Life (QoL) which is in part due to extreme fatigue. In a pilot study we prospectively assessed the feasibility and effect of psychological interventions in the management of fatigue. Methods Patients with quiescent Crohn's disease and a high fatigue score according to the Checklist Individual Strength were randomized to Problem Solving Therapy (PST), Solution Focused Therapy (SFT) or to a control group (treatment as usual, TAU). Patients completed the Inflammatory Bowel Disease Questionnaire, the EuroQol-5D, and the Trimbos questionnaire for Costs. Results Twenty-nine patients were included (12 TAU, 9 PST, 8 SFT), of these 72% were female, mean age was 31 years (range 20–50). The SFT group improved on the fatigue scale in 85.7% of the patients, in the PST group 60% showed improved fatigue scores and in the TAU group 45.5%. Although not significant, in both intervention groups the QoL increased. Medical costs lowered in 57.1% of the patients in the SFT group, in the TAU 45.5% and the in PST group 20%. The drop out rate was highest in the PST group (44%; SFT 12.5%; TAU 8.3%). Conclusions PST and SFT both positively affect the fatigue and QoL scores in patients with Crohn's disease. SFT seems most feasible with fewer dropouts and is therefore a promising new tool in the management of fatigue in Crohn's disease patients.

Efficacy of Immunosuppressive Therapy for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

There remains controversy regarding the efficacy of thiopurine analogs (azathioprine (AZA) and 6-mercaptopurine (6-MP)), methotrexate (MTX), and cyclosporine for the treatment of inflammatory bowel disease (IBD). We performed an updated systematic review of the literature to clarify the efficacy of immunosuppressive therapy at inducing remission and preventing relapse in ulcerative colitis (UC) and Crohn's disease (CD). Only parallel group randomized controlled trials (RCTs) were considered eligible. Studies with adult IBD patients receiving immunosuppressive therapy compared with placebo for at least 14 days and up to 17 weeks for active disease, or at least 6 months in quiescent disease were analyzed. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat analysis. The data were summarized using relative risk (RR) and pooled using a random effects model. Data on MTX and cyclosporine in IBD were limited although there were some data to support the use of intramuscular MTX in CD but not UC. There were five trials of AZA/6-MP in 380 active CD patients and there was no significant effect of therapy inducing remission (RR=0.87; 95% confidence interval (CI)=0.71-1.06). In quiescent CD, there were two trials involving 198 patients with no significant benefit of active therapy preventing relapse compared with placebo (RR=0.64; 95% CI=0.34-1.23). There were, however, three additional AZA withdrawal trials in 163 patients that indicated continuing medication did prevent relapse (RR=0.39; 95% CI=0.21-0.74). There were two AZA RCTs in 130 active UC patients that suggested a trend for benefit of therapy, but this did not reach statistical significance (RR=0.85; 95% CI=0.71-1.01). In quiescent UC, there were three trials involving 127 patients and there was a statistically significant benefit of AZA preventing relapse (RR=0.60; 95% CI=0.37-0.95). Most evidence relates to AZA/6-MP where there is no statistically significant benefit at inducing remission in active CD and UC. Thiopurine analogs may prevent relapse in quiescent UC and CD. However, there is a paucity of data for immunosuppressive therapy in IBD and more research is needed.

Efficacy of 5-Aminosalicylates in Crohn's Disease: Systematic Review and Meta-Analysis

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Evidence for treatment with 5-aminosalicylic acid (5-ASA) drugs is conflicting. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine this issue. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Authors of studies were contacted to provide additional information on trials where required, and experts in the field were contacted to identify unpublished studies. Eligible trials recruited adults with active or quiescent CD and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active CD, and RR of relapse of disease activity in quiescent CD, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. The search identified 3,061 citations. Twenty-two RCTs were eligible. Six RCTs compared 5-ASA with placebo in active CD remission. There was a trend towards a benefit with sulfasalazine over placebo (two RCTs, RR of failure to achieve remission=0.83; 95% CI=0.69-1.00), but no definite benefit of mesalamine over placebo (four RCTs, RR=0.91; 95% CI=0.77-1.06). Neither sulfasalazine nor mesalamine were effective in preventing quiescent CD relapse, but in a per protocol analysis mesalamine appeared to reduce risk of relapse (RR=0.79; 95% CI=0.66-0.95, NNT=13). The role of 5-ASAs in inducing remission of active CD and preventing relapse of quiescent CD remains uncertain, and more RCTs are required.

Efficacy of Biological Therapies in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI). The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80-0.94 and RR=0.88; 95% CI 0.83-0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65-0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57-0.91). Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD.

Antibiotic Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn's disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73-0.99, P=0.03). There was moderate heterogeneity between results (I(2)=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66-0.98) with no heterogeneity (I(2)=0%) and an number needed to treat 5 (95% CI=3-20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46-0.84), with no heterogeneity (I(2)=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43-0.96). There was moderate heterogeneity (I(2)=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD.

Glucocorticosteroid Therapy in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis

The use of glucocorticosteroids to treat both Crohn's disease (CD) and ulcerative colitis (UC) is widespread, but no systematic review and meta-analysis has examined the issue of efficacy of these agents in its entirety. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through December 2010). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD comparing standard glucocorticosteroids or budesonide with placebo or each other, or comparing standard glucocorticosteroids with placebo in active UC, were eligible. Dichotomous data were extracted to obtain relative risk (RR) of failure to achieve remission in active disease, and RR of relapse of activity in quiescent disease, with a 95% confidence interval (CI). Adverse events data were extracted where reported. The search identified 3,061 citations, and 20 trials were eligible. Only one trial was at low risk of bias. Standard glucocorticosteroids were superior to placebo for UC remission (RR of no remission=0.65; 95% CI 0.45-0.93). Both trials of standard glucocorticosteroids in CD remission reported a statistically significant effect, but because of heterogeneity between studies, the overall effect was not significant (RR=0.46; 95% CI 0.17-1.28). Budesonide was superior to placebo for CD remission (RR=0.73; 95% CI 0.63-0.84), but not in preventing CD relapse (RR=0.93; 95% CI 0.83-1.04). Standard glucocorticosteroids were superior to budesonide for CD remission (RR=0.82; 95% CI 0.68-0.98), but glucocorticosteroid-related adverse events were commoner (RR=1.64; 95% CI 1.34-2.00). Standard glucocorticosteroids are probably effective in inducing remission in UC, and may be of benefit in CD. Budesonide induces remission in active CD, but is less effective than standard glucocorticosteroids, and is of no benefit in preventing CD relapse.

Optimizing management of Crohn's disease within a project management framework: results of a pilot study.

Psychotherapy for Crohn's disease (CD) has focused on patients with psychological distress. Another approach to optimize management of CD is to target patients who do not exhibit psychological distress but engage in behaviors that undermine treatment efficacy / increase risk for flare. We sought to determine the feasibility/acceptability and estimate the effects of a program framed around Project Management (PM) principles on CD outcomes. Twenty-eight adults with quiescent CD without a history of psychiatric disorder were randomized to PM (n = 16) or treatment as usual (TAU; n = 12). Baseline and follow-up measures were Inflammatory Bowel Disease Questionnaire (IBDQ), Medication Adherence Scale (MAS), Perceived Stress Questionnaire (PSQ), and IBD Self-Efficacy Scale (IBD-SES). There were significant group × time effects favoring PM on IBDQ-Total Score (F(1) = 15.2, P = 0.001), IBDQ-Bowel (F(1) = 6.5, P = 0.02), and IBDQ-Systemic (F(1) = 9.3, P = 0.007) but not IBDQ-Emotional (F(1) = 1.9, P = ns) or IBDQ-Social (F(1) = 2.4, P = ns). There was a significant interaction effect favoring PM with respect to PSQ (F(1) = 8.4, P = 0.01) and IBD-SES (F(1) = 12.2, P = 0.003). There was no immediate change in MAS (F(1) = 4.3, P = ns). Moderate effect sizes (d > 0.30) were observed for IBDQ total score (d = 0.45), IBDQ bowel health (d = 0.45), and systemic health (d = 0.37). Effect sizes for PSQ (d = 0.13) and IBDSES (d = 0.17) were smaller. Behavioral programs that appeal to patients who may not seek psychotherapy for negative health behaviors may improve quality of life and potentially disease course and outcomes.

Clinical course of Crohnʼs disease following treatment of lymphoma

Crohn's disease (CD) patients may be at increased risk for the development of Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), either through exposure to immunosuppressive medications or due to their underlying chronic inflammatory illness. There are limited data regarding the natural history of CD following treatment of lymphoma. We present a series of CD patients who were treated for lymphoma and describe the natural history of their CD following lymphoma treatment. Retrospective case series from three academic referral centers was used. All CD patients with a history of lymphoma were identified. Demographic data, CD medication exposure, and surgical procedures before and after lymphoma treatment were recorded. Nine CD patients with a history of lymphoma were identified. Eight individuals received chemotherapy, while one patient was observed without treatment. Eight patients remained free of lymphoma for a mean of 72.8 months (range 1-276 months). The ninth patient had recurrence of his HL 3 years after lymphoma diagnosis. Following lymphoma treatment, two patients had quiescent CD with no specific therapy. Three patients demonstrated significant clinical relapse of their CD and a fourth patient developed CD after treatment of her lymphoma, which ultimately required long-term immunomodulator therapy with 6-mercaptopurine or methotrexate in the first three patients, and azathioprine in the fourth. Four patients required CD surgery after lymphoma treatment. We report on the clinical course of CD in patients who develop lymphoma. Significant clinical relapse of CD following successful medical treatment of lymphoma occurred frequently in patients with a history of this neoplasm.

Changing shape of disease: Nonalcoholic fatty liver disease in Crohnʼs disease—A case series and review of the literature

With improvements in therapy for inflammatory bowel disease (IBD) and changes in the prevalence of obesity, the phenotype of Crohn's disease (CD) is changing. These changes may herald an increase in the incidence of nonalcoholic fatty liver disease (NAFLD) in this population. Over a 10-month period we identified seven patients with CD who required liver biopsy for elevated liver function tests (LFTs), with an ultimate diagnosis of NAFLD. We performed a retrospective chart review and literature search to identify relevant data on NAFLD and CD. Specifically, we abstracted prior and current IBD-related medication exposures, disease severity, and the presence of typical comorbidities associated with NAFLD. We describe seven patients with CD and biopsy-proven NAFLD. The majority of these patients were overweight or obese, had quiescent CD, and were more likely to be receiving a tumor necrosis factor-alpha inhibitor. Review of the literature produced a total of 29 articles describing NAFLD in IBD patients, primarily restricted to historical autopsy and surgical series. Limited contemporary studies highlight the rising prevalence of NAFLD in treated IBD populations. NAFLD is increasing in incidence and prevalence among the general population. With improvements in therapy, NAFLD is likely increasing among the CD population as well. When evaluating an IBD patient with abnormal LFTs, clinicians need to consider NAFLD. NAFLD may impact IBD management in the future if therapeutic modalities are limited due to elevated LFTs. Further, patients should be monitored for excessive weight gain and counseled regarding healthy dietary and exercise habits.

Use of a novel vitamin D bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent crohnʼs disease1,2,3

Vitamin D deficiency is a common problem in patients with Crohn's disease (CD). The aim of this study was to determine the ability of normal subjects and patients with quiescent CD to absorb vitamin D(2) using a novel vitamin D bioavailability test. In addition, we evaluated whether the location of disease or previous surgery had any influence on the bioavailability of vitamin D(2) in CD patients. Ten normal subjects (50% female) and 37 CD patients with quiescent disease (51% female) were included in this study. Subjects who recently received any vitamin D(2) were excluded. The vitamin D bioavailability test was performed in all subjects. After a baseline blood draw, all subjects were then given a single 50,000 IU oral dose of vitamin D(2) in a capsule formulation and had their blood drawn 12 hours later to determine serum vitamin D(2), which reflected their vitamin D(2) absorption capacity. Forty-two percent and 29% of CD patients were found to be either vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL] or insufficient [25(OH)D 21-29 ng/mL], respectively. Twelve hours after ingesting 50,000 IU vitamin D(2) , vitamin D(2) levels rose from a baseline of 0.7 ± 0.7 ng/mL (mean ± SEM) to 49.8 ± 3.0 ng/mL in normal subjects. In CD patients, baseline vitamin D(2) levels rose from 0 ng/mL to 34.8 ± 2.8 ng/mL. CD patients had on average a 30% decrease in their ability to absorb vitamin D(2) (P = 0.01). Moreover, we found a wide variability of vitamin D(2) bioavailability in CD patients. Analysis of variance (ANOVA) revealed no statistical difference of vitamin D(2) bioavailability between patients in the CD subgroup stratified by the location of disease, the type of surgery, and receiving or not receiving surgery. More than 70% of the patients with quiescent CD were vitamin D-deficient or insufficient. The ability to absorb vitamin D(2) in CD patients is unpredictable and the only way to determine this is to perform a vitamin D bioavailability test. Use of this test may guide clinicians in administering the appropriate therapeutic dose of vitamin D for treating vitamin D deficiency in patients with CD.

Histomorphometric Analysis Reveals Reduced Bone Mass and Bone Formation in Patients With Quiescent Crohn's Disease

Crohn's disease (CD) is associated with an increased prevalence of osteoporosis, but the pathogenesis of this bone loss is only partly understood. We assessed bone structure and remodeling at the tissue level in patients with quiescent CD. We also investigated the roles of osteocyte density and apoptosis in CD-associated bone loss. The study included 23 patients with quiescent CD; this was a subgroup of patients from a large randomized, double-blind, placebo-controlled, multicenter trial. We obtained transiliac bone biopsy samples and performed histomorphometric analysis. Results were compared with data from age- and sex-matched healthy individuals (controls). Trabecular bone volume was decreased among patients with CD compared with controls (18.90% vs 25.49%; P < .001). The low bone volume was characterized by decreased trabecular thickness (120.61 vs 151.42 μm; P < .01). Bone formation and resorption were reduced, as indicated by a decreased mineral apposition rate (0.671 vs 0.746 μm/day; P < .01) and a low osteoclast number and surface area compared with controls and published values, respectively. In trabecular bone of patients with CD, osteocyte density and apoptosis were normal. The percentage of empty lacunae among patients was higher than that of published values in controls. In adult patients with quiescent CD, bone histomorphometric analysis revealed a reduction in bone mass that was characterized by trabecular thinning. The CD-associated bone loss was caused by reduced bone formation, possibly as a consequence of decreased osteocyte viability in the patients' past.

Fecal calprotectin is a predictive marker of relapse in Crohn's disease involving the colon: a prospective study

Fecal calprotectin seems to have a diagnostic precision in predicting relapse in quiescent ulcerative colitis patients. However, the data remain controversial in Crohn's disease. The aim of this study was to prospectively evaluate the role of fecal calprotectin as a predictive marker for 1-year follow-up in patients with asymptomatic Crohn's disease. Fifty-three Crohn's disease patients in clinical remission were consecutively included providing at the beginning of the study a single stool sample as well as a blood sample and regularly followed-up for 12 months. Fecal calprotectin level was measured using a commercially available enzyme-linked immunoassay. Among 53 patients, 10 (18.9%) developed clinical relapse during the 12-month follow-up period. Median fecal calprotectin level was significantly higher in relapse group patients compared with that in nonrelapse group (380.5 vs. 155 microg/g, P<0.001). With a cutoff value of 340 microg/g fecal calprotectin gave sensitivity of 80% and specificity of 90.7% in predicting clinical relapse. Fecal calprotectin level greater that 340 microg/g gave an 18-fold higher risk to develop relapse (log rank P<0.001) and was found to be an independent predictive factor of relapse (P=0.02). Fecal calprotectin seems to be a reliable marker of relapse in quiescent Crohn's disease patients.

Impact of functional bowel symptoms on quality of life and fatigue in quiescent Crohn disease and irritable bowel syndrome

Patients with irritable bowel syndrome (IBS) and Crohn disease (CD) have impaired quality of life (Qol) associated with fatigue. Whether IBS-like symptoms have a similar impact on Qol and fatigue in quiescent CD than in IBS is currently unknown. Our aims were (i) to evaluate the prevalence of IBS-like symptoms in quiescent CD and (ii) to compare the impact of IBS-like symptoms on Qol and fatigue in both diseases. A total of 92 quiescent CD, 40 IBS and 20 healthy subjects similar in age were included prospectively in five French academic centers. IBS symptoms were evaluated through the Rome III criteria. The severity of IBS symptoms, Qol, fatigue, depression and anxiety was measured using questionnaires (Francis Score, Likert scales, Fatigue Impact Scale, short-form Beck and Hospital Anxiety and Depression Scale). Irritable bowel syndrome-like symptoms were found in 42/92 (45.6%) patients with quiescent CD. The presence of IBS-like symptoms was associated with significant more profound alterations of Qol, high scores of fatigue, depression, but similar levels of anxiety. Compared to CD patients with IBS-like symptoms, IBS patients had more severe gastrointestinal symptoms and alterations of Qol, but similar scores of fatigue, depression and anxiety. In quiescent CD patients, fatigue was independently associated with the presence of IBS-like symptoms (OR = 1.018, 95% CI: 1.002-1.034, P = 0.02). The prevalence of IBS-like symptoms is elevated in quiescent CD. The presence of IBS-like symptoms in quiescent CD is probably associated with the range of fatigue/depression disorders. The mechanism underlying the occurrence of IBS-like symptoms in quiescent CD needs to be further explored.

Assessment of activity of Crohn's disease by Doppler sonography of superior mesenteric artery flow

BackgroundEvaluation of activity of Crohn's disease is based on CDAI. Several other tools have been studied to assess disease activity with more accuracy. AimsTo assess the correlation between Doppler parameters of superior mesenteric artery and disease activity and to assess the accuracy of these parameters in discriminating between active and quiescent Crohn's disease. Material and methodsWe perform a prospective study including non-operated and non-complicated Crohn's disease patients involving terminal ileum and/or right colon and sex and age-matched controls. Doppler sonography of superior mesenteric artery was performed in all subjects. ResultsWe studied 41 patients and 15 controls. There was no statistical difference between patients and controls according to the studied US parameters. The difference in resistance index between the three groups using analysis of variance is not significant (p=0.064). Resistance index was significantly lower in patients with active disease compared to inactive disease patients (0.82+/−0.04 vs 0.85+/−0.03; p=0.01). Pulsatility index was also lower in patients with active disease compared to inactive disease patients (1.37+/−0.21 vs 1.53+/−0.15; p=0.01). A value of resistance index less than 0.79 predicted active disease with a sensitivity of 35.3% and specificity of 95.7%. A value of pulsatility index less than 1.56 predicted active disease with a sensitivity of 94.1% and specificity of 43.5%. In case of resistance index less than 0.79 and pulsatility index less than 1.56 in the same patient, the probability of active disease was 86%. However, in case of resistance index over than 0.79 and pulsatility index over than 1.56, this probability was only 9%. In Crohn's disease patients, correlation study showed that resistance index value was significantly correlated with CDAI (r=−0.46; p=0.003). Pulsatility index value was also correlated with CDAI (r=−0.39; p=0.01). ConclusionDoppler sonographic parameters of superior mesenteric artery are significantly correlated with disease activity in non-operated and non-complicated Crohn's disease.

Magnetic resonance follow-through imaging for evaluation of disease activity in ileal Crohnʼs disease

Magnetic resonance follow-through (MRFT) is a new cross-sectional imaging modality with the potential to accurately stage ileal Crohn's disease (CD), while avoiding ionizing radiation and the discomfort associated with enteroclysis. We aimed to assess the reliability of this technique in assessing the extent and activity of ileal CD, and to assess its influence on subsequent management. Out of a total of 342 patients undergoing MRFT between 2004 and 2008, 221 were performed in 191 patients with confirmed CD. Case notes were reviewed in detail with documentation of all investigations pre- and post-MRFT. Agreement between inflammatory markers, histopathology, and MRFT findings was determined. Overall, 116/221 (52.5%) of MRFTs showed active ileal CD, and 76/221 (34.4%) quiescent CD, while 29/221 (13.1%) were suboptimal. Overall, 66 strictures and 18 fistulae were identified. There was substantial agreement between active ileal CD on MRFT and histopathology (n = 59; kappa = 0.66; P = 0.0006; sensitivity 85.1%, specificity 85.7%) and fecal calprotectin (n = 14; kappa = 0.72; P = 0.047), while C-reactive protein (CRP) showed moderate agreement (n = 107; kappa = 0.402; P = 0.00028). Management was influenced by MRFT reports following active (52/84, 62% treated medically) or quiescent (48/62, 77.4% managed conservatively) disease. Fibrotic strictures were predominantly treated surgically (7/14, 50%). In all, 13/32 (40.6%) patients with inflammatory ileal strictures required surgery, mostly due to steroid-resistant disease. Overall, 75 MR findings were documented in 221 MRFTs, including 1 renal cancer. MRFT provides accurate information on ileal CD activity, with close agreement to inflammatory markers and histopathology. It represents a substantial advance in the staging of CD, while avoiding painful enteroclysis and radiation exposure in young patients.

Prospective clinical trial: enteral nutrition during maintenance infliximab in Crohn’s disease

Hitherto, the efficacy of enteral nutrition (EN) on clinical outcomes during biological maintenance therapy in Crohn's disease (CD) has not been investigated. This prospective study was to assess the efficacy of EN on the maintenance rate of clinical remission in patients with quiescent CD receiving infliximab as maintenance therapy. Fifty-six patients who achieved clinical remission with infliximab induction therapy received infliximab as maintenance therapy (5 mg/kg, every 8 weeks). Thirty-two of the 56 patients received concomitant EN: elemental diet infusion during night-time and a low fat diet during daytime (EN group), while the remaining 24 patients received neither nutritional therapy nor food restriction (non-EN group). All patients were followed for 56 weeks; CD activity index (CDAI) was assessed and CDAI < 150 was defined as clinical remission. During the 56-week observation, the mean CDAI was not significantly different between the 2 groups. Seven patients in the EN group ceased EN therapy because they maintained complete remission. On an intention-to-treat basis, 25 patients in the EN group (78%) and 16 patients in the non-EN group (67%) remained in clinical remission during the 56-week observation (P = 0.51). The outcomes of this prospective study showed that concomitant EN during infliximab maintenance therapy does not significantly increase the maintenance rate of clinical remission in patients with CD.

Coping strategy when patients with quiescent Crohn’s disease recognize that their conditions are worsening

Although self-management is important for Crohn's disease (CD), there is no research focusing on self-management, especially in worsening conditions. The purpose of this study was to investigate how quiescent CD patients cope with their conditions worsening. A questionnaire containing six types of coping strategy for worsening conditions was created based on a semi-structured interview. Seventy-six quiescent CD patients participated in this study. We also analyzed the related factors of each coping strategy for worsening conditions. The total percentage of subjects who adopt the strategy of "change contents of meals" 'always' or 'often' was approximately 70%. On the other hand, the strategy of "see a doctor immediately" was approximately 20% in total of 'always' or 'often'. When 'sometimes' was added, "take extra medicine" was approximately 42%. The subjects with experience of hospitalization within 3 years (Z = -2.352, P = 0.019), presence of supplemental elemental diet (Z = -5.182, P < 0.001), or 1 year or less interval since last relapse (Z = -3.352, P = 0.001) showed a significant tendency to adopt the coping strategy of "take (add to) elemental diet." The major coping strategy was "change contents of meals," and the minor coping strategy was "see a doctor immediately." The subjects with unstable disease state adopted the coping strategy of "take (add to) elemental diet." The coping strategies for worsening conditions vary according to patients' backgrounds. The coping type should be taken into account when treating CD patients.