Inflammatory bowel disease in an underdeveloped region of Northeastern Brazil

AIM: To evaluate the demographic characteristics and clinical phenotypes of inflammatory bowel disease(IBD) in a geographic area in Northeastern Brazil.METHODS: This retrospective study was conducted at the Hospital of the Federal University of Piauí in Northeastern Brazil. Demographic characteristics and clinical phenotypes of IBD were analyzed in relation to the time of diagnostic confirmation, which was defined as the date of disease onset. Data were collected between January 2011 and December 2012 and included all census patients 18 years of age or older during that period for whom there was diagnostic confirmation of Crohn's disease(CD), ulcerative colitis(UC), or unclassified colitis according to the Montreal criteria. We also analyzed the period of time between the onset of clinical manifestations and the diagnosis of IBD(delay in the diagnosis). Statistical analyses included means and standard deviations for numeric variables and the Pearson χ2 adherence test for nominal variables. The annual index occurrence and overall prevalence of IBD at our institution were also calculated, with P values 0.05 indicating statistical significance. This study was approved by the Institutional Ethics and Research Committee.RESULTS: A total of 252 patients with IBD were included, including 152(60.3%) UC patients and 100(39.7%) CD patients. The clinical and demographic characteristics of all patients with IBD showed a female to male ratio of 1.3:1.0 and a mean age of35.2(SD = 14.5) years. In addition, the majority of patients were miscegenated(171, 67.9%), had received higher education(157, 62.4%), lived in urban areas(217, 86.1%), and were under the age of 40 years(97, 62.5%). For patients with CD, according to the Montreal classification, the predominant features present from the onset of disease were an age between 17 and 40 years(A2); colonic disease location(L2); and nonstricturing, nonfistulizing disease behavior(B1). However, approximately one-quarter of all CD patients demonstrated perineal involvement. We also observed considerable delay in the diagnosis of IBD throughout the entire study period(mean = 35.5 mo). In addition, the annual index occurrence rose from 0.08 to 1.53 cases/105 inhabitants/year during the study period, and the prevalence rate was 12.8 cases/105 inhabitants in 2012. Over the last two decades, there was a noted increase in the frequency of IBD in the study area.CONCLUSION: In this study, there was a predominance of patients with UC, young people under 40 years of age, individuals with racial miscegenation, and low annual incomes.     

Serum adipokines in inflammatory bowel disease

AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adiponectin,leptin,chemerin,resistin,and visfatin)were studied in 40 subjects with active IBD[24 subjects with Crohn’s disease(CD)and in 16 subjects with ulcerative colitis(UC)]before and after three months of therapy with corticosteroids and/or azathioprine.Clinical diagnoses were based on ileocolonoscopy,computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy.Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay.The control group was comprised of 16 age-and sex-matched healthyvolunteers.RESULTS:Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls(8.0±9.1 in CD and 8.6±6.3 in UC vs 16.5±10.1 ng/mL in controls;P<0.05),and significantly increased after treatment only in subjects with CD(14.9±15.1 ng/mL;P<0.05).Baseline serum resistin concentrations were significantly higher in CD(19.3±12.5ng/mL;P<0.05)and UC subjects(23.2±11.0 ng/mL;P<0.05)than in healthy controls(10.7±1.1 ng/mL).Treatment induced a decrease in the serum resistin concentration only in UC subjects(14.5±4.0 ng/mL;P<0.05).Baseline serum concentrations of visfatin were significantly higher in subjects with CD(23.2±3.2ng/mL;P<0.05)and UC(18.8±5.3 ng/mL;P<0.05)than in healthy controls(14.1±5.3 ng/mL).Treatment induced a decrease in the serum visfatin concentrations only in CD subjects(20.4±4.8 ng/mL;P<0.05).Serum levels of adiponectin,chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy.Clinical indices of IBD activity did not correlate with adipokine levels.CONCLUSION:IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.     

Prolonged QT dispersion in inflammatory bowel disease

AIM:To investigate the frequency and factors of prolonged QT dispersion that may lead to severe ventricular arrhythmias in patients with inflammatory bowel disease(IBD).METHODS:This study included 63 ulcerative colitis(UC) and 41 Crohn’s disease(CD) patients.Forty-seven healthy patients were included as the control group.Heart rate was calculated using electrocardiography,corrected QT dispersion(QTcd) and the Bazett’s formula.Homeostasis model assessment(HOMA) was used to determine insulin resistance(IR).HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR.RESULTS:Prolonged QTcd was found in 12.2% of UC patients,and in 14.5% of CD patients compared with the control group(P < 0.05).A significant difference was found between the insulin values(CD:10.95 ± 6.10 vs 6.44 ± 3.28,P < 0.05;UC:10.88 ± 7.19 vs 7.20 ± 4.54,P < 0.05) and HOMA(CD:2.56 ± 1.43 vs 1.42 ± 0.75,P < 0.05;UC:2.94 ± 1.88 vs 1.90 ± 1.09,P < 0.05) in UC and CD patients with and without prolonged QTcd.Disease behavior types were determined in CD patients with prolonged QTcd.Increased systolic arterial pressure(125 ± 13.81 vs 114.09 ± 8.73,P < 0.01) and age(48.67 ± 13.93 vs 39.57 ± 11.58,P < 0.05) in UC patients were significantly associated with prolonged QTcd.CONCLUSION:Our data show that IBD patients have prolonged QTcd in relation to controls.The routine followup of IBD patients should include determination of HOMA,insulin values and electrocardiogram examination.     

Similar clinical characteristics of familial and sporadic inflammatory bowel disease in South Korea

AIM:To investigate differences of clinical characteristics and disease courses between familial and sporadic inflammatory bowel disease(IBD)patients.METHODS:We obtained clinical data on Crohn’s disease(CD)(n=691)and ulcerative colitis(n=1113)from a tertiary referral medical center between 2005and 2012.Seventeen patients(2.5%)with CD and27 patients(2.4%)with ulcerative colitis(UC)were identified as having a familial history of IBD,including the first and second degree relatives.For each control case,three times the number of age-,sex-,and diagnosis year-matched CD and UC patients,without a family history of IBD,were randomly selected in this case control study.RESULTS:There were no significant differences in age or main symptom at diagnosis,extraintestinal manifestation,location/extent,behavior of disease activity,number of hospitalizations,number of operations,operation type,number of relapses,or oral medical treatment between familial and sporadic CD and UC patients.Median(min-max)follow-up periods after diagnosis of familial CD and sporadic CD patients were 84(24-312)and 36(8-240)mo,respectively(P=0.008).Familial CD patients more frequently used anti-tumor necrosis factor(TNF)antibodies compared to sporadic CD patients(17.6%vs 0%,P=0.014).CONCLUSION:In conclusion,a family history of IBD does not seem to be an important predictive factor affecting clinical characteristics or disease course even if there is a more frequent use of anti-TNF antibodies in familial CD patients compared to sporadic CD patients.     

Colorectal cancer in patients with inflammatory bowel disease:Can we predict risk?

The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.     

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

AIM:To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride(PLC) in colonic inflammatory bowel disease.METHODS:Patients suffering from mild to moderate ulcerative colitis(UC) or Crohn's disease(CD) colitis,with disease activity index(DAI) between 3 and 10 and under stable therapy with oral aminosalicylates,mercaptopurine or azathioprine,for at least 8 wk prior to baseline assessments,were considered suitable for enrollment.Fourteen patients were enrolled to assume PLC 2 g/d(two active tablets twice daily) orally.Clinical-endoscopic and histological activity were assessed by DAI and histological index(HI),respectively,following a colonoscopy performed immediately before and after 4 wk treatment.Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2.Histological response was defined as an improvement of HI of at least 1 point.We used median values for the analysis.Differences pre-and post-treatment were analyzed by Wilcoxon signed rank test.RESULTS:All patients enrolled completed the study.One patient,despite medical advice,took deflazacort 5 d before follow-up colonoscopy examination.No side effects were reported by patients during the trial.After treatment,71%(SE 12%) of patients achieved clinical response,while 64%(SE 13%) obtained remission.Separating UC from CD patients,we observed a clinical response in 60%(SE 16%) and 100%,respectively.Furthermore 60%(SE 16%) of UC patients and 75%(SE 25%) of CD patients were in clinical remission after therapy.The median DAI was 7 [interquartile range(IQR):4-8] before treatment and decreased to 2(IQR:1-3)(P 0.01) after treatment.Only patients with UC showed a significant reduction of DAI,from a median 6.5(IQR:4-9) before treatment to 2(IQR:1-3) after treatment(P 0.01).Conversely,in CD patients,although displaying a clear reduction of DAI from 7(IQR:5.5-7.5) before therapy to 1.5(IQR:0.5-2.5) after therapy,differences observed were not significant(P = 0.06).Seventy-nine percent(SE 11%) of patients showed improvement of HI of at least 1 point,while only one CD and two UC patients showed HI stability;none showed HI worsening.Median HI decreased from 1(IQR:1-2),to 0.5(IQR:0-1) at the endoscopic control in the whole population(P 0.01),while it changed from 1(IQR:1-2) to 0.5(IQR:0-1) in UC patients(P 0.01) and from 1.5(IQR:1-2) to 0.5(IQR:0-1) in CD patients(P = not significant).The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients.No side effects were reported during treatment or at 4 wk follow-up visit.CONCLUSION:PLC improves endoscopic and histological activity of mild to moderate UC.Further studies are required to evaluate PLC efficacy in colonic CD patients.     

Lack of correlation between Treg quantification assays in inflammatory bowel disease patients

AIM:To compare the number of regulatory T-cells( Tregs) measured by flow cytometry with those obtained using a real-time quantitative PCR(q PCR) method in patients suffering from inflammatory bowel disease(IBD).METHODS:Tregs percentages obtained by both flow cytometry and q PCR methods in 35 adult IBD patients,18 out of them with Crohn′s disease(CD)and 17 with ulcerative colitis(UC)were compared to each other as well as to scores on two IBD activity questionnaires using the Harvey Bradshaw Index(HBI)for CD patients and the Simple Colitis Clinical Activity Index(SCCAI)for UC patients.The Treg percentages by flow cytometry were defined as CD4+CD25highCD127lowFOXP3+cells in peripheral blood mononuclear cells,whereas the Treg percentages by q PCR method were determined as FOXP3 promoter demethylation in genomic DNA.RESULTS:We found an average of 1.56%±0.78%Tregs by using flow cytometry,compared to 1.07%±0.53%Tregs by using q PCR in adult IBD patients.There were no significant correlations between either the percentages of Tregs measured by flow cytometry or q PCR and the HBI or SCCAI questionnaire scores in CD or UC patients,respectively.In addition,there was no correlation between Treg percentages measured by q PCR and those measured by flow cytometry(r=-0.06,P=0.73;Spearman Rho).These data suggest that,either Treg-related immune function or the clinical scores in these IBD patients did not accurately reflect actual disease activity.Until the cause(s)for these differences are more clearly defined,the resultssuggest caution in interpreting studies of Tregs in various inflammatory disorders.CONCLUSION:The two methods did not produce equivalent measures of the percentage of total Tregs in the IBD patients studied which is consistent with the conclusion that Tregs subtypes are not equally detected by these two assays.     

Laboratory markers in ulcerative colitis: Current insights and future advances

Ulcerative colitis(UC)and Crohn’s disease(CD)are the major forms of inflammatory bowel diseases(IBD)in man.Despite some common features,these forms can be distinguished by different genetic predisposition,risk factors and clinical,endoscopic and histological characteristics.The aetiology of both CD and UC remains unknown,but several evidences suggest that CD and perhaps UC are due to an excessive immuneresponse directed against normal constituents of the intestinal bacterial flora.Tests sometimes invasive are routine for the diagnosis and care of patients with IBD.Diagnosis of UC is based on clinical symptoms combined with radiological and endoscopic investigations.The employment of non-invasive biomarkers is needed.These biomarkers have the potential to avoid invasive diagnostic tests that may result in discomfort and potential complications.The ability to determine the type,severity,prognosis and response to therapy of UC,using biomarkers has long been a goal of clinical researchers.We describe the biomarkers assessed in UC,with special reference to acute-phase proteins and serologic markers and thereafter,we describe the new biological markers and the biological markers could be developed in the future:(1)serum markers of acute phase response:The laboratory tests most used to measure the acute-phase proteins in clinical practice are the serum concentration of C-reactive protein and the erythrocyte sedimentation rate.Other biomarkers of inflammation in UC include platelet count,leukocyte count,and serum albumin and serum orosomucoid concentrations;(2)serologic markers/antibodies:In the last decades serological and immunologic biomarkers have been studied extensively in immunology and have been used in clinical practice to detect specific pathologies.In UC,the presence of these antibodies can aid as surrogate markers for the aberrant host immune response;and(3)future biomarkers:The development of biomarkers in UC will be very important in the future.The progress of molecular biology tools(microarrays,proteomics and nanotechnology)have revolutionised the field of the biomarker discovery.The advances in bioinformatics coupled with cross-disciplinary collaborations have greatly enhanced our ability to retrieve,characterize and analyse large amounts of data generated by the technological advances.The techniques available for biomarkers development are genomics(single nucleotide polymorphism genotyping,pharmacogenetics and gene expression analyses)and proteomics.In the future,the additionof new serological markers will add significant benefit.Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of pathophysiology of UC.     

Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility

Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals.Genetic markers are associated with disease phenotype and long-term evolution,but their value in everyday clinical practice is limited at the moment.IBD has a clear immunological background and interleukins play key role in the process.Almost130 original papers were revised including meta-analysis.It is clear these data are very important for understanding the base of the disease,especially in terms of clinical utility and validity,but text often do not available for the doctors use these in the clinical practice nowadays.We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD,performing an electronic search of PubMed Database from publications of the last 10 years,and used the following medical subject heading terms and/or text words:IBD,CD,UC,interleukins and polymorphisms.     

Inflammatory bowel disease in pediatric and adolescent patients:A biomolecular and histopathological review

Crohn’s disease(CD)and ulcerative colitis(UC)are the two main forms of inflammatory bowel disease(IBD)with both overlapping and distinct clinical,pathological and biomolecular features.It has been suggested that pediatric IBD is a distinct disease entity,with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD.The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities.For clinicians and pathologists convenience,practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.     

Real-world treatment patterns and disease control over one year in patients with inflammatory bowel disease in Brazil

BACKGROUNDCrohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD.AIMTo describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil.METHODSThis was a prospective, noninterventional study of adult patients with active Crohn’s disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control (i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined.RESULTSThe study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease.CONCLUSIONAlthough a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting.     

Arterial Stiffness in Inflammatory Bowel Disease: An Updated Systematic Review and Meta-Analysis

BackgroundThis systematic review and meta-analysis were carried out on well-conducted and adequately powered studies to explore whether arterial stiffness was associated with inflammatory bowel disease (IBD).MethodsThe search for potential literature was conducted on PubMed, MEDLINE, Cochrane Library, and Embase from inception to February 15, 2020. The studies assessing arterial stiffness in IBD were reviewed and included.ResultsConclusively, 17 eligible trials with a total of 2188 participants were in compliance with the inclusion criteria. Of the included 2188 participants, the cases for ulcerative colitis (UC) and Crohn’s disease (CD) were 558 and 693, respectively. Altogether 10 studies were conducted to evaluate the carotid-femoral pulse wave velocity (CPWV) in overall IBD patients, which was significantly increased with the mean difference (MD) and 95% CI as 0.70 (0.48-0.92, P < .01). The pooled results for CPWV in patients with CD and UC were also faster than that of control groups with MD and 95% CI as 1.09 (0.45-1.72) and 0.57 (0.57-1.24), respectively. The CPWV in CD and UC groups was comparable with a MD of 0.07 (P = .74, 95% CI: −0.32 to 0.45).ConclusionArterial stiffness had associations with the overall IBD, UC, and CD with a similar strength of association between UC and CD.     

Case-control study of factors that trigger inflammatory bowel disease flares

AIM:To explore the association between inflammatory bowel diseases(IBD)flares and potential triggers.METHODS:Patients evaluated for an acute flare of IBD by a gastroenterologist at the Dallas VA Medical Center were invited to participate,as were a control group of patients with IBD in remission.Patients were systematically queried about nonsteroidal anti-inflammatory drug use,antibiotic use,stressful life events,cigarette smoking,medication adherence,infections,and travel in the preceding 3 mo.Disease activity scores were calculated for each patient at the time of enrollment and each patient’s chart was reviewed.Multivariate regression analysis was performed.RESULTS:A total of 134 patients with IBD(63 with Crohn’s disease,70 with ulcerative colitis,and 1 with indeterminate colitis)were enrolled;66 patients had flares of their IBD and 68 were controls with IBD in remission(for Crohn’s patients,average Crohn’s disease activity index was 350 for flares vs 69 in the controls;for UC patients,Mayo score was 7.6 for flares vs 1 for controls in those with full Mayo available and 5.4p for flares vs 0.1p for controls in those with partial Mayo score).Only medication non-adherence was significantly more frequent in the flare group than in the control group(48.5%vs 29.4%,P=0.03)and remained significant on multivariate analysis(OR=2.86,95%CI:1.33-6.18).On multivariate regression analysis,immunomodulator use was found to be associated with significantly lower rates of flare(OR=0.40,95%CI:0.19-0.86).CONCLUSION:In a study of potential triggers for IBD flares,medication non-adherence was significantly associated with flares.These findings are incentive to improve medication adherence.     

Crohn��s disease genotypes of patients in remission vs relapses after infliximab discontinuation

AIM:To investigate genetic differences between Crohn's disease(CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission.METHODS:Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response,were identified by review of an electronic database and charts.Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index(CDAI) 150] during follow-up visits based on physician global assessments.A CD relapse(loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity(CDAI 220) and a therapeutic intervention with CD medication(s),or a hospitalization with complications related to active CD.Genetic analyses were performed on samples from 14 patients(n = 6 who had a sustained long term remission after stopping infliximab,n = 8 who rapidly relapsed after stopping infliximab).Nucleotide-binding oligomerization domain 2(NOD2)/caspase activation recruitment domain 15(CARD15) polymorphisms(R702W,G908R and L1007fs) and the inflammatory bowel disease 5(IBD5) polymorphisms(IGR2060a1 and IGR3081a1) were analyzed in each group.RESULTS:Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects.There was no significant increase in frequency of the NOD2/CARD15 polymorphisms(R702W,G908R and L1007fs) and the IBD5 polymorphisms(IGR2060a1 and IGR3081a1) in either group of patients;those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab.Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission,while two-thirds relapsed rapidly.There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups.The patients who lost remission did so after 1.0 years ± 0.6 years,while those still in remission were at the time of this study,8.1 years ± 2.6 years post-discontinuation of infliximab,P 0.001.The 8 patients who had lost remission after discontinuing infliximab had a mean number of 5 infusions(range 3-7),with a mean treatment time of 7.2 mo(range 1.5 mo-15 mo).The mean duration of time from the last infusion of infliximab to the time of loss of remission was 382 d(range 20 d-701 d).The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions(range 3-12),with a mean treatment duration of 12 mo(range 3.6 mo-32 mo)(P = 0.45 relative to those who lost remission).CONCLUSION:There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sustained remission and which will relapse rapidly after stopping infliximab.     

Clinical, serological and genetic predictors of inflammatory bowel disease course

Patients with extensive or complicated Crohn's disease (CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines. In patients with localized and uncomplicated CD at diagnosis, early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact. In this context, there is a need for predictors of benign or unfavourable subsequent clinical course, in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions. At diagnosis, an age below 40 years, the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course. The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts. Consequently, the use of these predictors can be integrated into the elements that influence individual decisions. In the CD postoperative context, keeping smoking and history of prior resection are the strongest predictors of disease symptomatic recurrence. However, these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice. In ulcerative colitis (UC), extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease, and also with long-term colectomy and colorectal inflammation-associated colorectal cancer. In patients with extensive UC at diagnosis, a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered. At the moment, no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.     

Ethnic variation in the annual rates of adult inflammatory bowel disease in hospitalized patients in Vancouver, British Columbia

BACKGROUND:

There is currently little available information regarding the impact of ethnicity on the clinical features of inflammatory bowel disease (IBD). Migrating populations and changing demographics in Vancouver, British Columbia (BC) provide a unique opportunity to examine the role of ethnicity in the prevalence, expression and complications of IBD.

OBJECTIVES:

To determine the demographics of IBD and its subtypes leading to hospitalization in the adult population of BC.

METHODS:

A one-year retrospective study was performed for all patients who presented acutely with IBD to Vancouver General Hospital from January 1, 2006 to December 31, 2006. Data regarding sex, age, ethnicity, IBD type and extent of disease, complications and management strategies were collected. Clinical data were confirmed by pathology and radiology reports.

RESULTS:

There were 186 cases of IBD comprising Crohn’s disease (CD) 56%, ulcerative colitis (UC) 43% and indeterminate colitis (1%) 1%. The annual rate of IBD cases warranting hospitalization in Caucasians was 12.9 per 100,000 persons (7.9 per 100,000 persons for CD and 5.0 per 100,000 persons for UC). This was in contrast to the annual rate of IBD in South Asians at 7.7 per 100,000 persons (1.0 per 100,000 persons for CD and 6.8 per 100,000 persons for UC) and in Pacific Asians at 2.1 per 100,000 persons (1.3 per 100,000 persons for CD, 0.8 per 100,000 persons for UC). The male to female ratio was higher in South Asians and Pacific Asians than in Caucasians. The extent of disease was significantly different across racial groups, as was the rate of complications.

CONCLUSIONS:

These early results suggest that there are ethnic disparities in the annual rates of IBD warranting hospitalization in the adult population of BC. There was a significantly higher rate of CD in the Caucasian population than in South Asian and Pacific Asian populations. The South Asian population had a higher rate of UC, with an increased rate of complications and male predominance. Interestingly, the rate of CD and UC was lowest in the Pacific Asian population. These racial differences – which were statistically significant – suggest a role for ethnodiversity and environmental changes in the prevalence of IBD in Vancouver.     

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease

There is currently no gold standard test for the diagnosis of inflammatory bowel disease(IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis(UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Noninvasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.     

Change of diagnosis during the first five years after onset of inflammatory bowel disease: Results of a prospective follow-up study (the IBSEN Study)

Objective. An exact diagnosis of inflammatory bowel disease (IBD) and further subclassification may be difficult even after clinical, radiological and histological examinations. A correct subclassification is important for the success of both medical and surgical therapeutic strategies, but there is a dearth of information available on the frequency of changes in diagnosis in population-based studies. The objective of this work was prospectively to re-evaluate the diagnosis in an unselected cohort of IBD patients during the first five years after the initial diagnosis. Material and methods. Patients classified as IBD or possible IBD in the period 1990–94 (the IBSEN cohort) had their diagnosis re-evaluated after 1 and 5 years. Initially, the patients were classified as ulcerative colitis (UC), Crohn's disease (CD), indeterminate colitis (IC) or possible IBD. At the 5-year visit, patients were classified as UC, CD or non-IBD. Results. A total of 843 patients (518 UC, 221 CD, 40 IC and 64 possible IBD) were identified. Clinical information was available for 94% of the patients who survived after 5 years. A change in diagnosis was found in 9% of the patients initially classified as UC or CD. A change to non-IBD was more frequent than a change between UC and CD. A large proportion of patients initially classified as IC or possible IBD were diagnosed as non-IBD after 5 years (22.5% versus 50%). When IBD was confirmed in these groups, UC was more frequent than CD. Two changes in diagnosis during follow-up were observed in 2.8% of the patients; this was more frequent in patients initially classified as IC or possible IBD. Conclusions. There are obvious diagnostic problems in a minority of patients with IBD; a systematic follow-up is therefore important in these patients.     

Assessment of disease specific knowledge and health-related quality of life among United States military veterans with inflammatory bowel disease

AIM: To evaluate the association between patient disease knowledge of inflammatory bowel disease(IBD)and health related quality of life(HRQoL) and identify patient and disease related predictors of patient knowledge of IBD.METHODS: We performed a cross-sectional study of IBD patients with an established diagnosis of IBD longer than 3 mo prior to enrollment. The Crohn's and colitis knowledge score(CCKNOW) and short inflammatory bowel disease questionnaire(SIBDQ) were selfadministered to assess patient knowledge of IBD and HRQoL, respectively. Demographic and disease characteristics were abstracted from the electronic medical record. The correlation between CCKNOW and SIBDQ scores was assessed by a linear regression model. Associations of patient knowledge and the variables of interest were calculated using ANOVA.RESULTS: A total of 101 patients were recruited.Caucasian race, younger age at diagnosis, and havinga college or post-graduate degree were significantly associated with higher CCKNOW scores. Patients with CD had higher CCKNOW scores compared to patients with ulcerative colitis and inflammatory bowel disease type unclassified, P 0.01. There was no significant correlation between overall CCKNOW and SIBDQ scores(r 2 = 0.34, P = 0.13). The knowledge sub-domain of diet in CCKNOW was negatively correlated with HRQoL(r 2 = 0.69, P 0.01).CONCLUSION: IBD diagnosis at a younger age in addition to Caucasian race and higher education were significantly associated with higher knowledge about IBD. However, patient knowledge of IBD was not correlated with HRQoL. Further studies are required to study the effect of patient knowledge of IBD on other clinical outcomes.