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.     

Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation

Background.Although an accurate diagnosis of inflammatory bowel disease (IBD) and differentiation between ulcerative colitis (UC) and Crohn's disease (CD) can be made in most patients, it is sometimes impossible to distinguish UC from CD even after thorough pathological study. Recently, clinicians have used the term indeterminate colitis (IC) for patients with features of both diseases that overlap temporarily or persistently. The frequency, reasons, and outcome of patients with a clinical diagnosis of IC based on radiological, endoscopic, and histopathological findings were investigated retrospectively. Methods. Based on records of 735 patients with IBD, IC was defined as having features of both UC and CD, with differentiation from each other impossible at least once during the observation period (average 6.8 years) based on diagnostic criteria using endoscopic, radiological, and histological findings. Results. Twenty-three patients were identified as having IC. They were classified into three patterns according to the clinical cource and the final diagnosis: (1) UC changing to CD (n = 8); (2) CD changing to UC (n = 5); and (3) UC or CD (n = 10). The frequency of IC was 24.5%–43.4% of colitis-type CD (n = 53), 2.3%–6.5% of all CD (n = 352), and 3.1% of IBD (n = 735). The reasons for the indetermination were temporary (56.5%) or persistent (43.5%) overlapping of UC-like and CD-like presentations. Treatment of IC was inappropriate in only two patients, and the prognoses of all patients except one were fairly good. Conclusions. Overlapping of UC-like presentations (persistent bloody stool and diffuse colitis) was frequently observed with Crohn's colitis but less so in CD patients during their clinical course. The basis of differentiation and treatment of IC needs more attention.     

Expression profiles of matrix metalloproteinases and their inhibitors in colonic inflammation related to pediatric inflammatory bowel disease

Abstract

Objective. The differential diagnosis of chronic colitis in inflammatory bowel disease (IBD) is challenging and a distinction between Crohn's disease (CD) and ulcerative colitis (UC) is not always possible. Matrix metalloproteinases (MMPs) cleave components of the extracellular matrix and their dysregulation leads to damage to the mucosa. They are involved in inflammation in IBD, as well as in eventual tissue repair. We aimed to examine putative differences in the profiles of MMPs and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)] in pediatric IBD to find better tools for differential diagnosis of various IBD subgroups at the tissue level in the colon. Material and methods. Expression of MMPs -1, -7, -8, -9, -10, -12 and -26 and TIMPs -1 and -3 was studied by immunohistochemistry in colonic tissue samples of 32 pediatric patients with IBD and 11 non-IBD cases. Results. In the colon, expression of MMP-7 in epithelium was greater in CD samples compared to UC samples (1.09 versus 0.33; P = 0.010). Furthermore, epithelial MMP-10 expression was elevated in CD and UC samples compared to non-IBD samples (1.55 versus 1.00; P = 0.041 and 1.58 versus 1.00; P = 0.025, respectively). TIMP-3 expression in the stroma was higher in both the CD and UC groups when compared to non-IBD samples (2.18 versus 1.36; P = 0.026 and 2.50 versus 1.36; P = 0.002, respectively), but differences between UC and CD could not be observed. Conclusions. Increased expression of epithelial MMP-10 and stromal TIMP-3 could serve as histological indicators of IBD etiology. Epithelial MMP-7 expression, on the other hand, could help to differentiate between CD-related colitis and UC.     

Microscopic colitis in patients with ulcerative colitis or Crohn’s disease: a retrospective observational study and review of the literature

Objectives: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn’s disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature.

Methods: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed.

Results: We identified 31 patients with onset of MC after a median (range) of 20 (2–52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n?=?16) or lymphocytic colitis (LC) (n?=?5); nine CD patients developed CC (n?=?5) or LC (n?=?4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients.

Conclusions: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.     

Serological markers in diagnosis of pediatric inflammatory bowel disease and as predictors for early tumor necrosis factor blocker therapy

Objective: To describe the prevalence of serological markers in newly diagnosed treatment-naïve pediatric inflammatory bowel disease (IBD), their utility in differentiating Crohn’s disease (CD), ulcerative colitis (UC) and symptomatic non-IBD patients and whether serological markers are associated with early TNF blocker treatment.

Material and methods: Ninety-six children and adolescents <18 years, 58 with IBD and 38 symptomatic non-IBD controls were included. At diagnosis and after 1–2 years, serological antibodies (anti-Saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), flagellin expressed by Clostridial phylum (anti-CBir1), outer membrane porin of Escherichia coli (anti-OmpC), Pseudomonas fluorescens-associated sequence (anti-I2), CRP, ESR and fecal calprotectin were analyzed. The choice of treatment was made at the discretion of the treating pediatrician.

Results: Of the IBD patients, 20 (36%) and 26 (47%) were positive for ASCA and pANCA compared to 3(8%), p?<?.01 and 10 (27%), p?=?.04 of the controls. Thirteen (72%) of UC patients were pANCA positive, versus 13 (35%) of CD patients (p?<?.01). None of the UC patients was ASCA positive versus 20 (54%) of CD patients (p?<?.0001). Compared to conventionally treated patients, the 18 (49%) TNF blocker treated CD patients had higher presence of ASCA (p?<?.01), lower presence of pANCA (p?=?.02) and higher levels of fecal calprotectin, CRP and ESR at diagnosis. In multivariate analyses ASCA and pANCA status, but not CRP, ESR or calprotectin, were independently associated with early TNF blocker treatment.

Conclusions: ASCA and pANCA status were associated with having IBD and with early TNF blocker treatment in CD.     

Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study

Objective: Fatigue is a major concern for patients with ulcerative colitis (UC) and Crohn’s disease (CD), but evidence from population-based studies regarding fatigue in long-standing inflammatory bowel disease (IBD) patients is scarce. Our aims were to assess fatigue scores and the prevalence of chronic fatigue in IBD patients 20 years after diagnosis and to identify variables associated with fatigue in this cohort.

Methods: Twenty years after diagnosis, patients from a cohort with incident IBD were invited to a follow-up visit that included a structured interview, a clinical examination, laboratory tests and the Fatigue Questionnaire (FQ). Fatigue scores were obtained, and factors associated with fatigue were assessed via linear and logistic regression analyses.

Results: Of the 599 invited patients, 440 (73.5%) completed the FQ. Among those with active disease, we found significantly higher fatigue scores than among those with quiescent disease (fatigue scores: UC 17.1 versus 12.4, p?<?.001, and CD 17.5 versus 13.3, p?<?.001). The fatigue scores of those with quiescent disease were comparable with those of the reference population. Chronic fatigue was more frequent among IBD patients than in the reference population. Factors associated with fatigue included self-perceived disease activity, poor sleep quality, anxiety and depression.

Conclusion: At 20 years after IBD diagnosis, fatigue scores were higher and chronic fatigue was more frequent among IBD patients with active disease than in the reference population and among those with quiescent IBD. Subjectively perceived disease activity, sleep quality, anxiety and depression were associated with fatigue in IBD patients.     

The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis

Background: The pathogenesis of inflammatory bowel diseases (IBD) involves complex interactions between the microbiome and the immune system. We evaluated the association between the gut microbiota and disease activity in IBD patients.

Methods: Systematic review of clinical studies based on a published protocol. Included patients had ulcerative colitis (UC) or Crohn’s disease (CD) classified as active or in remission. We selected bacteria assessed in at least three studies identified through electronic and manual searches (November 2015). Bias control was evaluated with the Newcastle Ottawa scale (NOS). Results of random-effects meta-analyses were presented as mean differences (MD).

Results: Three prospective and seven cross-sectional studies (NOS score 6–8) were included. Five studies included patients with CD (231 patients) and eight included patients with UC (392 patients). Compared to patients in remission, patients with active IBD had lower abundance of Clostridium coccoides (MD?=??0.49, 95% CI: ?0.79 to ?0.19), Clostridium leptum (MD?=??0.44, 95% CI: ?0.74 to ?0.14), Faecalibacterium prausnitzii (MD?=??0.81, 95% CI: ?1.23 to ?0.39) and Bifidobacterium (MD?=??0.37, 95% CI: ?0.56 to ?0.17). Subgroup analyses showed a difference in all four bacteria between patients with UC classified as active or in remission. Patients with active CD had fewer C. leptum, F. prausnitzii and Bifidobacterium, but not C. coccoides.

Conclusion: This systematic review suggests that dysbiosis may be involved in the activity of IBD and that there may be differences between patients with CD and UC.     

Pancreatic Autoantibodies in Greek Patients with Inflammatory Bowel Disease

Pancreatic autoantibodies (PAbs) have been suggested as a specific but not sensitive marker for Crohn's disease (CD). The aim of this study was to assess the value of detecting PAbs in Greek patients with ulcerative colitis (UC) and CD. Sera were collected from 150 patients with IBD (73 with UC and 77 with CD), 31 cases with non-IBD intestinal inflammation, 16 cases with other autoimmune diseases, and 104 healthy controls. Determination of PAbs was performed by a standard indirect immunofluorescence technique. PAbs were detected in 18 of 73 (24.7%) samples from UC patients and in 32 of 77 (41.6%) samples from CD patients. The prevalence of positive PAbs was significantly higher in CD than in UC (P= 0.04). None of the 104 samples from healthy controls and the 31 cases with non-IBD intestinal inflammation had detectable PAbs. One patient with Sjogren's syndrome was PAbs positive. No association of PAbs with IBD activity, IBD localization, or medical treatment was found. Patients with stenotic CD had a significantly higher prevalence of PAbs positivity (60%) compared with patients with inflammatory (28.6%) and fistulizing (41.2%) disease (P= 0.02). The prevalence of PAbs in Greek CD patients was found to be similar to that in previous reports. In contrast to these studies we found also increased prevalence of PAbs in UC patients. These findings suggest that PAbs should be considered as a specific marker for IBD rather than for CD.     

Incidencia e historia natural de la enfermedad inflamatoria intestinal en Castilla y León: estudio prospectivo,multicéntrico y poblacional

IntroductionThe incidence of inflammatory bowel disease (IBD) is increasing worldwide.ObjectivesTo evaluate the incidence of IBD in Castilla y León describing clinical characteristics of the patients at diagnosis, the type of treatment received and their clinical course during the first year.Materials and methodsProspective, multicenter and population-based incidence cohort study. Patients aged >18 years diagnosed during 2017 with IBD (Crohn's disease [CD], ulcerative colitis [UC] and indeterminate colitis [IC]) were included from 8 hospitals in Castilla y León. Epidemiological, clinical, and therapeutic variables were registered. The global incidence and disease incidence were calculated.Results290 patients were diagnosed with IBD (54.5% UC, 45.2% CD, and 0.3% IC), with a median follow-up of 9 months (range 8?11). The incidence rate of IBD in Castilla y Leon in 2017 was 16.6 cases per 10,000 inhabitants-year (9/10⁵ UC cases and 7.5/10⁵ CD cases), with a UC/CD ratio of 1.2:1. Use of systemic corticosteroids (47% vs 30%; P = .002), immunomodulatory therapy (81% vs 19%; P = .000), biological therapy (29% vs 8%; P = .000), and surgery (11% vs 2%; p = .000) were significatively higher among patients with CD comparing with those with UC.ConclusionsThe incidence of patients with UC in our population increases while the incidence of patients with CD remains stable. Patients with CD present a worse natural history of the disease (use of corticosteroids, immunomodulatory therapy, biological therapy and surgery) compared to patients with UC in the first year of follow-up.     

The diagnostic value of colonoscopy compared with rectosigmoidoscopy in children and adolescents with symptoms of chronic inflammatory bowel disease of the colon

Seventy-eight young patients with symptoms of chronic inflammatory bowel disease (IBD) of the colon have been investigated to determine to what degree colonoscopy adds important information for the diagnosis of IBD in addition to results of the routine procedures, including rectosigmoidoscopy carried out at the same time. After colonoscopy IBD was established in 4 of 12 patients classified as non-IBD after the routine procedures. Eleven of 18 patients with the routine diagnosis indeterminate colitis (IC) could after colonoscopy be differentiated into UC or probable CC. In 30 of 31 cases classified as UC the routine diagnosis was confirmed by colonoscopy. Routine diagnosis as probable CC was changed to definite CC in 3 of 10 cases. In all cases but one with previously established IBD it was possible to confirm the diagnosis. Thirty-seven of 70 patients with established IBD of the colon had no radiologic evidence of colitis.     

Chromogranin A as a biomarker of disease activity and biologic therapy in inflammatory bowel disease: a prospective observational study

Abstract

Objective. To access the correlation of Chromogranin A (CgA) with inflammatory bowel disease (IBD) activity and responsiveness to medical therapy. Material and methods. A prospective observational study was conducted in 56 patients with moderate ulcerative colitis (UC) or Crohn’s disease (CD) (UC, n = 29, CD, n = 27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D) and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate and steroids) and were classified according to their treatment in two groups. Serum CgA was measured at baseline and 4-week posttreatment period. Results. Serum CgA was significantly higher in IBD patients than in those with IBS-D or healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in CD patients than in UC patients (p < 0.01). CgA value was significantly reduced in ‘biologic’ group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week posttreatment period (p < 0.01), while 18/24 (72%) patients were already in remission during that time. In contrast, CgA value was significantly increased in the ‘conventional’ treatment group (32 IBD patients, UC, n = 14, CD, n = 18) between the two visits (p < 0.01), although 22/32 (69%) patients were in remission during the 4-week posttreatment period. Conclusion. CgA appears to be a reliable marker of disease activity in IBD patients and especially in those who received biologic therapy. IBS-D patients presented normal CgA values.     

Prevalence and risk factors for venous thromboembolic complications in the Swiss Inflammatory Bowel Disease Cohort

Objective: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is associated with the occurrence of venous thromboembolism (VTE) such as deep vein thrombosis (DVT) and pulmonary embolism (PE). We aimed to assess the prevalence and associated risk factors for VTE in a large national cohort of IBD patients.

Material and methods: Data from patients of the Swiss IBD Cohort Study (SIBDCS) enrolled between 2006 and 2013 were analyzed.

Results: A total of 2284 IBD patients were analyzed of which 1324 suffered from CD and 960 from UC. VTE prevalence was 3.9% (90/2284) overall and 3.4% (45/1324) in CD patients (whereof 2.4% suffered from DVT and 1.5% from PE) and 4.7% (45/960) in UC patients (whereof 3.2% suffered from DVT and 2.4% from PE). Median disease duration in CD patients with VTE was 12 years [IQR 8–23] compared to eight years [3–16] in CD patients without VTE (p?=?0.001). Disease duration in UC patients with VTE was seven years [4–18] compared to six years [2–13] in UC patients without VTE (p?=?0.051). Age at CD diagnosis ≥40 years (OR 1.851, p?=?0.073) and disease duration >10 years (OR 1.771, p?=?0.088) showed a trend to be associated with VTE. In UC patients, IBD-related surgery (OR 3.396, p?=?0.004) and pancolitis (OR 1.927, p?=?0.050) were significantly associated with VTE.

Conclusions: VTE are prevalent in CD and UC patients. Pancolitis and UC-related surgery are significantly associated with VTE in UC patients.     

Subnormal alanine aminotransferase values in blood of patients with Crohn disease

Background: It was observed that several patients from the outpatient clinic with Crohn disease (CD) occasionally had subnormal values of alanine aminotransferase (ALAT) in blood. Subnormal ALAT values have previously been reported only in renal failure. Methods: A retrospective study of clinical chemistry values going back 10 years was conducted in all patients from the outpatient clinic with CD or ulcerative colitis (UC). Exclusion criteria were age >50 years, a daily alcohol consumption, known liver disease or other chronic diseases with a possible effect on liver function (n?=?42). The remaining patients (n?=?123) were classified as UC, CD or indeterminate colitis (ID). Eight patients with microscopic colitis (MC) were also included. Results: It was found that 49/50 CD patients had subnormal ALAT on one or several occasions (mean 7?U/L, range 5–9). Only 1/67 patients with UC had subnormal ALAT values. The mean ALAT value in UC was 20?U/L, range 10–40. In IC, 5/6 patients had subnormal ALAT. None of the 8 patients with MC had subnormal ALAT. Conclusions: The demonstration that subnormal ALAT values are almost entirely seen in CD as compared with UC may have clinical importance and adds to the information on the pathophysiological differences between these two diseases.     

Inflammatory bowel disease in Tuzla Canton,Bosnia-Herzegovina: A prospective 10-year follow-up

BACKGROUNDThe incidence and prevalence of inflammatory bowel disease (IBD) vary between regions but have risen globally in recent decades. A lack of data from developing nations limits the understanding of IBD epidemiology.AIMTo perform a follow-up review of IBD epidemiology in the Tuzla Canton of Bosnia-Herzegovina during a 10-year period (2009-2019).METHODSWe prospectively evaluated the hospital records of both IBD inpatients and outpatients residing in Tuzla Canton for the specified period of time between January 1, 2009 and December 31, 2019. Since all our patients had undergone proximal and distal endoscopic evaluations at the hospital endoscopy unit, we used the hospital’s database as a primary data source, alongside an additional cross-relational search of the database. Both adult and pediatric patients were included in the study. Patients were grouped by IBD type, phenotype, age, and gender. Incidence rates were calculated with age standardization using the European standard population. Trends in incidence and prevalence were evaluated as a 3-year moving average and average annual percentage change rates.RESULTSDuring the 10-year follow-up period, 651 patients diagnosed with IBD were monitored (of whom 334, or 51.3%, were males, and 317, or 48.7%, were females). Of all the patients, 346 (53.1%) had been diagnosed with ulcerative colitis (UC), 292 (44.9%) with Crohn’s disease (CD), and 13 (2%) with indeterminate colitis (IC). We observed 440 newly diagnosed patients with IBD: 240 (54.5%) with UC, 190 (43.2%) with CD, and 10 (2.3%) with IC. The mean annual crude incidence rates were found to be 9.01/100000 population for IBD [95% confidence interval (CI): 8.17-9.85], with 4.91/100000 (95%CI: 4.29-5.54) for UC and 3.89/100000 (95%CI: 3.34-4.44) for CD. Calculated IBD prevalence in 2019 was 146.64/100000 (95%CI: 128.09-165.19), with 77.94/100000 (95%CI: 68.08-87.70) for UC and 65.77/100000 (95%CI: 54.45-74.1) for CD. The average annual IBD percentage change was 0.79% (95%CI: 0.60-0.88), with -2.82% (95%CI: -2.67 to -2.97) for UC and 6.92% (95%CI: 6.64-7.20) for CD. During the study period, 24,509 distal endoscopic procedures were performed. The incidence of IBD was 3.16/100 examinations (95%CI: 2.86-3.45) or 1.72/100 examinations (95%CI: 1.5-1.94) for UC and 1.36/100 examinations (95%CI: 1.17-1.56) for CD.CONCLUSIONTrends in the incidence and prevalence of IBD in Tuzla Canton are similar to Eastern European averages, although there are significant epidemiological differences within geographically close and demographically similar areas.     

G protein-coupled receptor 55 (GPR55) expresses differently in patients with Crohn’s disease and ulcerative colitis

Aim: To investigate the levels of G protein-coupled receptor 55 (GPR55) expression in colonic tissue of inflammatory bowel disease (IBD) patients and healthy controls, and its potential implication in IBD treatment.

Methods: Fifty patients were enrolled in our prospective study: n?=?21 with Crohn’s disease (CD) and n?=?16 with ulcerative colitis (UC); 19 women and 18 men. Control consisted of 13 non-IBD patients. In each subject, two biopsies were taken from different colonic locations. In IBD patients, biopsies both from endoscopically inflamed and non-inflamed areas were drawn and the development of inflammation confirmed in histopathological examination. GPR55 mRNA and protein expression were measured using real-time PCR and Western blot, respectively.

Results: GPR55 expression at mRNA and protein level was detected in all samples tested. The level of GPR55 mRNA expression in non-inflamed colonic areas was comparable in all analyzed groups (p?=?.2438). However, in the inflamed tissues GPR55 mRNA expression was statistically significantly (p?<?.0001) higher (6.9 fold) in CD patients compared to UC. Moreover, CD patients manifested higher (12.5 fold) GPR55 mRNA expression in inflamed compared with non-inflamed colonic tissues (p?<?.0001). Although no significant differences were stated, GPR55 protein level tends to decrease in IBD as compared to control.

Conclusions: Different patterns of GPR55 expression at mRNA level were observed in IBD patients. We speculate that GPR55 is crucial for the mucosal inflammatory processes in IBD, particularly in CD and its expression may affect disease severity, and response to treatment. The GPR55 receptors may become an attractive target for novel therapeutic strategies in IBD.     

The diagnostic role and clinical association of serum proteinase 3 anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease

Abstract

Background and aim: Accurate differentiation of patients with ulcerative colitis (UC) or Crohn’s disease (CD) is important for appropriate therapy and prognosis. This study was designed to explore the utility of proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) in the diagnosis of Chinese patients with inflammatory bowel disease (IBD).

Methods: Blood samples were collected from 216 Chinese patients, including 175 IBD and 41 colorectal polyps (disease control). Clinical characteristics were extracted from electronic medical records.

Results: Serum PR3-ANCA were increased in UC patients compared to those with CD or colorectal polyps (p?<?.0001). PR3-ANCA was negative in colorectal polyps and there was no significant difference between CD and colorectal polyps (p?>?.05). Using the cut-off value of 20 chemiluminescent units (CU) provided by manufacturer, the positive rate of PR3-ANCA was higher in UC than CD (41.7% vs. 1.1%; p?<?.0001). Receiver operating characteristic (ROC) analysis demonstrated an area under the curve (AUC) of 0.89 (95% CI: 0.84–0.95; p?<?.0001) for differentiating UC from CD and suggested an optimized cutoff of 7.3 CU which improved sensitivity from 41.7% to 57.1%, while maintaining a specificity of 98.9%. PR3-ANCA in severe UC patients were higher than those with moderate UC (p?<?.05), no difference was found between those in remission or with mild or moderate activity (p?>?.05).

Conclusions: Serum PR3-ANCA is a potentially useful clinical biomarker in Chinese patients with IBD. A modified cut-off value of 7.3 CU improves the performance for distinguishing UC from CD.     

Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease

BACKGROUND AND AIM: Colorectal Paneth cell metaplasia (PCM) is known to be a sign of idiopathic inflammatory bowel disease (IBD), although its distribution and histogenesis are not fully understood. Objectives of this research were to investigate the spatial distribution of PCM in IBD and other forms of colitis (non-IBD), and to find stimuli causing PCM. METHODS: We studied multiple biopsy specimens from 181 patients with ulcerative colitis (UC), 159 with Crohn's disease (CD), 448 with non-IBD, and 78 normal controls. Paneth cell metaplasia frequency, at each colorectal site, was evaluated to find possible differences among diseases, phases of activity, and extents of disease. RESULTS: In non-IBD and controls, PCM was rarely (0-1.9%) seen at distal sites, but frequently (up to 48.7%) found at the ascending colon and cecum (P < 0.001). Paneth cell metaplasia frequency was significantly higher in IBD than in non-IBD patients and controls at distal sites (P < 0.001), but did not differ significantly between UC and CD, or among active, resolving, and quiescent phases. In UC, proctitis and left-sided colitis rarely displayed PCM at unaffected sites. Multiple logistic regression analysis revealed that PCM was positively associated with crypt distortion and mononuclear cell infiltration (P < 0.005), but negatively or not significantly associated with crypt atrophy, mucin depletion, acute inflammation, or phase of activity. CONCLUSIONS: Paneth cell metaplasia is a non-specific phenomenon in the proximal colon, but distal PCM, which occurs exclusively in affected mucosa, is a useful marker indicating IBD, even in the inactive phase. Regression analysis suggests that repair and regeneration may be the most potent stimuli causing PCM.     

Time-Dependent Changes in the Luminal Surface and Mass of the Rat Colon during Prolonged Systemic Treatment with Epidermal Growth Factor

Abstract

Background. In chronic inflammatory bowel disease (IBD) (Crohn’s disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. Methods. IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. Results. The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. Conclusion. In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.     

Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)

Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown.

Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn’s disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated.

Results: For cases with ≥2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87–97) for any IBD, 79% (66–88) for UC and 72% (60–82) for CD. In UC patients with ≥2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77–97). The PPV for CD in patients with ≥2?CD diagnoses but never a UC diagnosis was 81% (67–91)). Combining data from SWIBREG (≥1 record) and the NPR (≥1 record), the PPV was 99% for any IBD (97–100), 96% (89–99) for UC, and 90% (82–96) for CD.

Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.