Inflammatory Bowel Disease Unclassified Patients Research Articles

Clinical features of inflammatory bowel disease unclassified: a case-control study

BackgroundApproximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification.MethodsThe clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated.Results60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification.ConclusionsIBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Short noncoding RNAs as predictive biomarkers for the development from inflammatory bowel disease unclassified to Crohn's disease or ulcerative colitis.

Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60-97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

SHORT NONCODING RNAS AS PREDICTIVE BIOMARKERS FOR THE DEVELOPMENT FROM INFLAMMATORY BOWEL DISEASE UNCLASSIFIED TO CROHN’S DISEASE OR ULCERATIVE COLITIS

Abstract BACKGROUND Numerous pathogenic processes are mediated by short noncoding RNAs (ncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether short ncRNAs can predict CD or UC among IBDU patients. METHODS Of 35 IBDU patients initially diagnosed with IBDU, 12, 15, and eight were reclassified into CD(IBDU-CD), UC(IBDU-UC), or remained as IBDU(IBDU-IBDU) respectively. Eight IBD patients, were included as references. Short ncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. RESULTS Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95 % CI: 60 - 97) in discriminating IBDU-CD from IBDU-UC. CONCLUSIONS Based on the three-short ncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

P1174 The disease course of elderly patients with Inflammatory Bowel Disease two years prior to their death

Abstract Background The number of elderly patients with inflammatory bowel disease (IBD) is increasing. Hence, more patients will be dying with their IBD. Limited research has examined the disease course of IBD in the aging body, particularly in the period preceding their death. The purpose of this study was to investigate the disease course of elderly IBD patients leading up to the end of their lives. Methods This was a nationwide population-based study using the national Danish registries. We used a validated algorithm to identify patients that were diagnosed with Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) in a period between 1976-2018 from the Danish National Patient Registry. This information was linked with other national Danish registers which provided data on dates of death, cancer, hospitalisations, and corticosteroid usage. We included 6,183 IBD patients aged 65 and above at death, with no cancer or palliative treatment at the time of death. We analysed IBD-related hospitalisations, corticosteroid usage, and disease relapses (defined as a combined endpoint of corticosteroid prescription and/or hospitalisation, or both), in the two-year period before death. Results We analysed CD, UC and IBDU patients separately, and observed a noticeable spike in hospitalisations, prescription rates of corticosteroids and disease relapses in the last two months before the IBD patients’ death. Out of 6,183 IBD patients, 954 (15.43%) were hospitalised in the last two years before their death (see Table 1 for key characteristics). In the last two months, hospitalisation rates were 139 (28.66%) for CD patients, 155 (23.96%) for UC patients and 83 (34.87%) for IBDU patients. Corticosteroids were prescribed to 1,054 (17.05%) out of 6,183 IBD patients, and in the last two months 90 (20.45%) CD patients, 149 (20.13%) UC patients, and 67 (19.36%) IBDU patients received a corticosteroid treatment. Overall, 1,652 (26.72%) IBD patients experienced a disease relapse two years preceding their death, and during the last two months, 553 (22.45%) CD patients, 194 (24.01%) UC patients and 228 (20.25%) IBDU patients experienced relapses. Conclusion During the two-year period prior to death, we observed that hospitalisation, prescription, and relapse rates were highest during the final two months of life. For better understanding of the disease course of elderly IBD patients, further research should investigate the cause of death and differences between early- and late disease-onset patients as well as establish a cohort for comparison.

Crohn's Disease of the Ileoanal Pouch: A High Rate of Potential Overdiagnoses.

Approximately 1 in 10 patients with an ileal pouch-anal anastomosis is diagnosed with Crohn's disease of the pouch (CDP). However, this diagnosis may be established inappropriately, as alternative underlying causes necessitating an alternative treatment approach, such as long-term surgical sequelae, may mimic CDP. In this study, we aimed to identify patients diagnosed with and treated for CDP with a (concurrent) alternative diagnosis. Ulcerative colitis and inflammatory bowel disease unclassified patients who underwent ileal pouch-anal anastomosis surgery in a tertiary center between 1990 and 2017 were retrospectively reviewed. Patients with a postoperative diagnosis of CDP for which medical treatment was initiated were identified. Presence of pouchitis, prepouch ileitis, stricture, and fistulas was assessed and histopathological reports were evaluated. Thereafter, cross-sectional images of the pouch in CDP patients were re-evaluated to identify potential long-term surgical sequelae (ie, chronic presacral sinus or perianastomotic fistulas). After a median postoperative follow-up of 6.2 (interquartile range, 2.3-13.5) years, 47 (10%) of 481 patients were diagnosed with CDP. CDP patients had pouchitis (n = 38 [81%]), prepouch ileitis (n = 34 [74%]), strictures (n = 17 [36%]), fistulas (n = 15 [32%]), or a combination. Multiple granulomas were found in 1 pouch resection specimen. Re-evaluation of 40 (85%) patients who underwent magnetic resonance imaging revealed presence of long-term surgical sequelae in 17 (43%) patients. Six (15%) patients demonstrated isolated nonanastomotic fistulas. Re-evaluation of cross-sectional imaging of the pouch revealed that potential alternative causes were found in nearly half of CDP patients. Cross-sectional imaging is therefore recommended early in the diagnostic pathway to exclude an alternative diagnosis.

P003 MicroRNAs as biomarkers in Inflammatory Bowel Disease unclassified (IBDU) patient samples may predict the development from IBDU to Crohn’s Disease or Ulcerative Colitis

Abstract Background Differential diagnosis in Inflammatory Bowel Disease (IBD) is challenging; typically, discriminating Crohn’s Disease (CD) from Ulcerative Colitis (UC) among IBD unclassified (IBDU) patients is a diagnostic encounter in cases where the inflammatory lesions are restricted to the colon. MicroRNAs are found to be involved in the pathogenesis and are also evaluated as diagnostic biomarkers and therapeutic targets in IBD. Methods We obtained formalin fixed paraffin embedded (FFPE) colonic mucosal biopsies of 35 IBDU patients (including adults and children), and 8 IBD (4 CD and 4 UC) patients who were classified into CD or UC collected from the diagnostic endoscopy. Based on the patient charts, The IBDU samples were reclassified into CDs or UC or remained as IBDU after minimum 3 years clinical follow up, ie. 12 IBDU patients were reclassified as CD (IBDU-CD) and 15 IBDU patients as UC (IBDU-UC). Eight IBDU patients remained as IBDU. MicroRNA profiling was performed on all samples using Affymatrix GeneChip miRNA Arrays. Arrays were processed using pd.mirna.4.0 and oligo packages in R and were analysed using LIMMA package. Results We found that miR-3176 and miR-182-5p were upregulated in IBDU-CD and miR-671-5p, miR-668-5p, miR-4793-3p, and mir-6776 were upregulated in IBDU-UC with p values of less than 0.05 and 1< log [fold change] <-1 for all 6 microRNAs. Higher mucosal expression levels of miR-3176 and miR-182-5p in IBDU-CD samples compared to IBDU-UC samples, resulted in an area under the curve (AUC) of 0.87 (95% confidence interval (CI), 0.71 – 1.00) and 0.81 (CI, 0.63 – 1.00), respectively, in discriminating IBDU-CD from IBDU-UC. On the other hand, miR-3176 and miR-182-5p had AUCs of 0.69 (CI, 0.25-1.00) and 0.69 (CI, 0.21-1.00), respectively, in discriminating CD and UC. MicroRNA miR-671-5p had a higher AUC of 0.81 (CI, 0.48 - 1.00) for discriminating CDs and UCs, whereas in discriminating IBDU-CD and IBDU-UC, the AUC was only 0.64 (CI, 0.42 – 0.87). Conclusion We conclude that differential microRNA expression among IBDU patients can predict the development of IBDU to CD and IBDU to UC, and that the microRNA expression profile of IBDU patients differ from patients classified as CD or UC at time of diagnosis. Our findings suggest that IBDUs may have different pathogenic mechanisms for IBDU-CDs and IBDU-UCs.

P118 Inflammatory Bowel Disease Unclassified and Ulcerative Colitis: different outcomes? Multicenter case-control study (Spanish ENEIDA registry)

Abstract Background Patients with inflammatory bowel disease (IBD) are often classified as ulcerative colitis (UC) and Crohn’s disease (CD). However, in some cases this categorization is not possible and these patients are labelled as inflammatory bowel disease unclassified (IBDU) -or indeterminate colitis if histologic analysis of surgical specimens is possible-.The aims of this study were to compare the prognosis and therapeutic requirements in patients with IBDU and UC, and to identify potential predictive factors of reclassification as UC or CD. Methods Retrospective, observational, multicenter and case-control study of Spanish ENEIDA registry promoted by GETECCU. IBDU patients were identified from 18 centers. Every case of IBDU was matched with 2 patients of ulcerative colitis of the same hospital by sex, age at diagnosis and disease extent (in the patchy colitis subgroup, every case was matched with 1 extensive colitis and 1 left colitis). Results 231 IBDU patients and 469 UC patients were included. Only 15 IBDU patients met current criteria of indeterminate colitis. In the IBDU group 59.7% patients were males and the mean of age at diagnosis was 43.3 years. Disease extent was distributed in 14 proctitis, 59 left-sided colitis, 87 extensive colitis and 53 patchy colitis. 13.9% had rectal sparing and 31.9% presented ileitis. Thirteen percent were smokers at diagnosis, 5.6% had perianal disease and 15.9% had extraintestinal manifestations. Table 1: baseline characteristics of IBDU and UC group. When comparing IBDU to UC patients, there were no statistical differences between proportion of patients that needed immunosuppressants (35.7% vs 37.7%, p=0.558) and biological therapy (27.3% vs 24.3%, p=0.415). Regarding surgery for medically refractory disease, UC patients had higher surgical rates, although these differences did not reach statistical significance (2.6% vs 0.5%, p= 0.062). Figure 1: immunosuppressants, biological and surgery rates. Overall mortality rates were similar in both groups (5.1% in IBDU vs 2.6% in UC); with only one case related to IBD in IBDU group. During follow-up, 67 IBDU patients (31%) were reclassified (32 UC, 34 CD, 1 indeterminate colitis). 25% of patients were reclassified within 46 months of follow-up (Figure 2: Kaplan-Meier curve of reclassification). Neither clinical, biochemical (C- reactive protein, albumin, hemoglobin) nor endoscopic variable (rectal sparing, ileitis) was associated with change in diagnosis. Conclusion In clinical practice, there were no statistical differences in prognosis, therapeutic requirements and surgical treatment between IBDU and UC patients. Two thirds of patients remained classified as IBDU during the follow-up. No predictive factors of reclassification have been identified.

Impact of obesity on disease activity and disease outcome in inflammatory bowel disease: Results from the Swiss inflammatory bowel disease cohort.

The purpose of this study was to investigate the impact of obesity on disease activity and disease outcome in patients with inflammatory bowel disease. The impact of obesity on inflammatory bowel disease disease activity and outcome was retrospectively assessed in 3075 patients enrolled in the prospective nation-wide Swiss inflammatory bowel disease cohort between July 2006 and September 2018. Baseline characteristics, disease activity and disease course in 325 obese inflammatory bowel disease patients (body mass index ≥30 kg/m2) were compared to 1725 normal weight inflammatory bowel disease individuals (body mass index 18.5-24.9). Among 3075 patients in the prospective Swiss inflammatory bowel disease cohort, 325 patients (10.6%) were obese, namely, 194 Crohn's disease patients, 131 ulcerative colitis, and inflammatory bowel disease-unclassified patients. Disease activity scores were elevated in obese Crohn's disease (Crohn's Disease Activity Index 33 vs 20, p = 0.001), but not ulcerative colitis patients. Obese Crohn's disease, but not ulcerative colitis patients were less likely to be in remission based on a Crohn's Disease Activity Index less than 100 and a calprotectin less than 100 ug/g. In a multivariate regression model, obesity was negatively associated with disease remission in Crohn's disease (odds ratio 0.610, 95% confidence interval 0.402-0.926, p = 0.020), but not ulcerative colitis. Increased soft stool frequency was observed in both obese Crohn's disease and ulcerative colitis patients. Adjusted Cox regression models revealed increased risk of complicated disease course in obese Crohn's disease patients (hazard ratio 1.197, 95% confidence interval 1.046-1.370, p = 0.009). No association between obesity and disease progression, index treatment failure was seen neither in Crohn's disease nor ulcerative colitis. Obesity is associated with decreased rates of disease remission and increased risk of complicated disease course in Crohn's disease over a six-year follow-up period. No effects were seen on disease progression and index treatment failure neither in Crohn's disease nor ulcerative colitis.

Disease course of inflammatory bowel disease unclassified in a European population‐based inception cohort: An Epi‐IBD study

A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5years. The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period. Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n=20, 71%) or CD (n=8, 29%) after a median of 6months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n=6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n=107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.

Long-term Outcome of Inflammatory Bowel Disease-Unclassified in Children.

To document the frequency at diagnosis and evolution over time of inflammatory bowel disease-unclassified in children. Analysis of case records (2004-2011) of patients diagnosed with inflammatory bowel disease-unclassified following upper-gastrointestinal endoscopy, ileocolonoscopy and small bowel imaging. Any subsequent diagnostic reclassification by 2016 was recorded. 344 children diagnosed as inflammatory bowel disease: 58% Crohn's disease, 34.5% ulcerative colitis, and 7.5% (n=26) inflammatory bowel disease-unclassified. 25/26 inflammatory bowel disease-unclassified patients were followed for 4.5-11.5 years. 17 of these patients needed endoscopic re-evaluation leading to changed diagnosis in ten (Crohn's disease 7, ulcerative colitis 3). 7.5% (25/344) of inflammatory bowel disease children had inflammatory bowel disease-unclassified at diagnosis; 10 (40%) evolved into Crohn's disease or ulcerative colitis.

The natural history of pediatric-onset IBD-unclassified and prediction of Crohn’s disease reclassification: a 27-year study

Objectives: A definitive diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) in patients who were initially diagnosed as inflammatory bowel disease-unclassified (IBDU) remains challenging. Our aims were to describe the natural history of pediatric-onset IBDU patients during prolonged period of follow up and to identify associated predictors for CD reclassification among them.Materials and methods: In this retrospective single center study, out of 723 patients with pediatric onset IBD, we identified 53 patients (7.3%) diagnosed with IBDU at the Schneider Children’s Medical Center of Israel between 1986 and 2013. Potential predictors for CD reclassification including age at diagnosis, gender, clinical manifestations, disease extent and laboratory findings were assessed.Results: The median follow-up was 6.8 (± 6.7) years. Reclassification to CD was observed in 24/53 (45%) of patients. The median interval from diagnosis to CD reclassification was 9.4 years. In 58% of these patients, CD reclassification occurred within 5 years from diagnosis. Multivariate Cox models showed that familial history of CD and hypoalbuminemia at diagnosis were significantly associated with CD reclassification (HR 11.3, p = .02 and HR 5.3, p = .03, respectively). All other assessed clinical, laboratory and endoscopic parameters did not serve as predictors for CD reclassification later on.Conclusions: In our cohort, a substantial high proportion of pediatric onset IBDU patients were later re-diagnosed as CD. Only a family history of CD and hypoalbuminemia could predict reclassification among IBDU patients.

Clinical Factors Associated with the Development of Crohn's Disease in Inflammatory Bowel Disease-unclassified Patients Undergoing Ileal Pouch-anal Anastomosis.

Patients with inflammatory bowel disease-unclassified (IBDU) undergoing ileal pouch-anal anastomosis (IPAA) are at the risk of developing Crohn's disease (CD) after surgical procedure. In these patients, a clinically centered set of preoperative risk factors has not been prospectively defined. We report a single-center analysis of clinical factors associated with the development of CD after IPAA. Consecutive IBDU patients undergoing IPAA were identified. The diagnosis of IBDU was based on the presence of atypical disease distribution, presence of granulomas on endoscopic biopsy, and/or perianal disease. The diagnosis of CD after IPAA included the presence of afferent limb inflammation on pouchoscopy in the absence of nonsteroidal anti-inflammatory drug use and/or the development of pouch fistulizing disease more than 3 months after ileostomy closure. Of the 149 study patients, 33 (22%) were diagnosed with CD after IPAA at a median of 37 months (interquartile range, 11-83 mo) after ileostomy closure. CD was diagnosed by mucosal inflammation above the pouch (n = 23; 70%), pouch fistulizing disease (n = 4; 12%), anorectal septic complications (n = 2; 6%), or the presence of ≥2 of the above complications (n = 4; 12%). The sole clinical predictor for the development of CD after IPAA was younger age at disease onset even after controlling for relevant clinical factors in a multivariate analysis. The odds of developing CD increased by 4% for each year that IBDU was diagnosed at a younger age. Younger age at disease onset is the only clinical factor associated with the development of CD after IPAA for IBDU. Patients with IBDU undergoing IPAA with young age at disease onset should be counseled about the potentially higher risk of developing CD.

Pediatric IBD-unclassified Is Less Common than Previously Reported; Results of an 8-Year Audit of the EUROKIDS Registry.

Inflammatory bowel disease-unclassified (IBD-U) is diagnosed in ∼10% of pediatric and adolescent onset IBD patients. The EUROKIDS registry (2004) initiated by the Porto IBD working group of ESPGHAN prospectively monitors diagnostic workup of newly diagnosed pediatric and adolescent onset IBD patients. We aimed to describe diagnostic workup, phenotype, and change of diagnosis over time in pediatric IBD-U patients. Data were collected on children from 52 centers across 20 European countries and Israel, diagnosed with IBD from May 2005 through November 2013. Full endoscopy plus small bowel radiology was considered complete diagnostic workup. Participating centers reporting IBD-U patients were queried in 2014 for follow-up data. IBD-U was the provisional first diagnosis in 265 of 3461 children (7.7%) (91/158 [58%] with pancolitis; 140 [53%] male), diagnosed more frequently under the age of 10 (median age 12.3 years, 89 [34%] under 10 years). Half (48%) had undergone complete diagnostic workup. Lack of small bowel radiology was the prevailing reason for incomplete workup. As a result of reinvestigations (endoscopy in 54%, radiology in 38%) during a median follow-up of 5.7 years (interquartile range, 2.5-7.8), a change in diagnosis from IBD-U to Crohn's disease (12%) or ulcerative colitis (20%) was reported. Only half of patients reported as IBD-U in EUROKIDS had undergone complete diagnostic workup. Follow-up with reinvestigations resulted in a reduction of IBD-U rate to 5.6%. A diagnosis of IBD-U becomes less likely in case of complete diagnostic workup. Implementation of clear diagnostic criteria will further reduce the rate of IBD-U in the future.

Initial Disease Course and Treatment in an Inflammatory Bowel Disease Inception Cohort in Europe

The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

East–West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort

ObjectiveThe incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West...

Concurrent Erythema Nodosum and Pyoderma Gangrenosum in a Patient with Inflammatory Bowel Disease Unclassified

Purpose: Previous studies have shown that up to 40% of patients with Inflammatory Bowel Disease (IBD) may develop extraintestinal manifestations (EIMs) with skin manifestations being one of the most common. Although erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two most common skin EIMs of IBD, there have been few studies documenting the presence of both EN and PG in the same patient, and no studies documenting the presence of EN, PG and psoriasis in the same patient. Multivariable analyses have shown significant predictive associations between EN and PG. IBD has traditionally been classified into either CD or ulcerative colitis (UC), but a 3rd subgroup of patients, eventually labeled as IBD Unclassified (IBDU), was defined as those who could not be classified as having either CD or UC despite comprehensive diagnostic tests. We report a Caucasian male with IBDU complicated by numerous EIMs including psoriasis, PG, and deep venous thrombi who presented with new indurated plaques and nodules over his upper and lower extremities. These erythematous lesions were purple, tender, and more prominent on the anterior shins. Of note, seven months prior to this rash, he had PG of the left shin that improved with intravenous infliximab treatment. Regarding the patient's IBD history, he was initially diagnosed with ulcerative colitis (UC). However, because he had atypical features including aphthous ulcerations, anorectal strictures, and an indeterminate IBD serology panel, his diagnosis was changed to IBDU. The patient was admitted for further work up of this new skin rash. The dermatology service performed a skin biopsy that was consistent with EN. He was started on steroids and his lesions improved. To our knowledge, the occurrence of both EN and PG has not been described among IBDU patients. Furthermore, our case report may be the first describing an IBD patient with three types of inflammatory skin lesions - EN, PG, and psoriasis.Figure: [1571] Figure A. EN of the lower extremity. Figure B. Healing PG of the lower extremity.

Auto-antibodies in patients with inflammatory bowel disease unclassified.

Inflammatory bowel disease unclassified (IBDU) is considered to be an aberrant immune response with loss of tolerance to many antigens. This paper tries to address whether there is any value to test for auto-antibodies in such patients. 60 patients with inflammatory bowel disease unclassified participated in the study. Auto-antibodies to nuclear antigen, intestinal goblet cell, exocrine part of pancreatic acinar cells, perinuclear antineutrophil cytoplasmic, cytoplasmic antineutrophil cytoplasmic and Saccharomyces cerevisiae were tested and compared to 20 ulcerative colitis (UC) patients and 30 healthy controls matched for age and sex. There was a significant difference (p=0.000) between patients and control group in anti-exocrine part of pancreatic acinar cells, perinuclear antineutrophil cytoplasmic and Saccharomyces cerevisiae auto-antibodies. There was also a significant difference between IBDU and UC patients in the auto-antibodies directed against intestinal goblet cells, (p=0.000) exocrine part of pancreas (p=0.000) and anti Saccharomyces cerevisiae antibody (p=0.000). Due to the autoimmune nature of indeterminate colitis, involvement of some antigens from gastrointestinal tract or the bile system in the initiation of this disease is likely.

Aplicación de los criterios de Oporto para el diagnóstico de enfermedad inflamatoria intestinal pediátrica en un centro pediátrico de referencia

Introduction Inflammatory bowel diseases (IBD) have classically included two entities: Crohn's disease (CD) and ulcerative colitis (UC). The correct differentiation between these two diseases has important implications. The term inflammatory bowel disease unclassified (IBDu) describes inflammatory changes of the colon that cannot be classified as ulcerative colitis or Crohn's disease. This situation has been described in 20-30% of paediatric IBD at diagnosis. In order to reach a definitive diagnosis of suspicion of inflammatory bowel disease in children, the ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) established the Porto criteria (PC) in July 2005. The recommendations include: 1) total colonoscopy with ileal intubation, 2) upper endoscopy, 3) multiple biopsies and 4) complete small bowel exploration. Aim To evaluate the diagnostic procedures used in our IBD patients regarding the PC. Patients and methods Retrospective review of the data of our IBD patients diagnosed in the last ten years (1999-2008) in a Spanish tertiary hospital, differentiating two periods: before and after the publication of the PC. Results A total of 108 IBD patients had been diagnosed (51 UC, 52 CD, 5 IBDu), 43 girls (39.81%), 65 boys (60.18%). According to the Montreal classification: 1) UC, 40 (78%) extensive colitis, 5 left-sided colitis (9.8%), 6 proctitis (11%), 2) CD: 44 ileo-colonic (84%), 13 ileal, 7 colonic. Median age at diagnosis: 13 years 1 month (p25-p75: 10 years 3 months- 14 years 9months). The Porto criteria were followed in 49% of the cases (33.3% before its publication, 64.8% after, P = .001). Upper endoscopy was performed in 62 patients (58%): 38.9% versus 72.2%, P < .001. Upper involvement was found in 51% of our CD patients. Total colonoscopy with ileoscopy was achieved in 85.2% of the cases. The mean number of ileo-colonic segments biopsied was 6.6 (7 different segments). Granulomas at biopsies were present in 38% of our CD patients. Up to 38% of the CD patients had microscopic inflammation in endoscopically normal appearing segments. During the follow-up, initial diagnosis among the IBDu patients, was changed to CD in 1, to UC in 2 and the other 3 remained with the same diagnosis. We did not observe other changes in diagnosis in the remaining 103 patients (median follow-up: 4y 8mo). Thirty patients were discharged when becoming adults. Conclusions Our clinical practice in IBD diagnosis has changed after the PC. Upper endoscopy is a useful tool to find upper involvement in CD. Total colonoscopy with ileoscopy and performance of multiple biopsies are essential to determine extension of the inflammatory changes. We have not observed changes in the final diagnosis in our CD and UC patients after a median follow-up of 4 years.

Rigorous Histopathological Assessment of the Colectomy Specimen in Patients With Inflammatory Bowel Disease Unclassified Does Not Predict Outcome After Ileal Pouch–Anal Anastomosis

Abdominal colectomy has been used in patients with inflammatory bowel disease unclassified (IBDU), requiring surgery to allow histopathological evaluation of the colectomy specimen to rule out Crohn's disease (CD). We evaluated whether any histopathological feature was associated with an adverse postoperative outcome. Patients with ulcerative colitis (UC) or IBDU undergoing ileal pouch-anal anastomosis (IPAA) were prospectively examined. A checklist of 17 histopathological features atypical for UC was developed. Outcomes of acute pouchitis (AP), chronic pouchitis (CP), and de novo CD were assessed. The 153 study patients included 119 (78%) UC and 34 (22%) IBDU patients. The following atypical features were identified (n; %): broad-based ulcer (99; 65%), appendiceal involvement (78; 51%), V-shaped ulcer (48; 31%), crypt-associated granuloma (42; 27%), isolated giant cells (39; 25%), discontinuous active inflammation (36; 24%), slit-like fissure (32; 21%), discontinuous chronic inflammation (16; 10%), ileal villous architectural distortion (12; 8%), neural hypertrophy (10; 7%), backwash ileitis (10; 7%), transmural inflammation (8; 5%), discontinuous ileitis (8; 5%), muscle hypertrophy (5; 3%), ileal ulcer (4; 3%), and ileal pyloric metaplasia (1; 1%). A total of 29 patients (19%) developed AP, 17 (11%) developed CP, and 13 patients (8%) developed de novo CD. On univariate analysis, de novo CD developed in 3 of the 10 patients (30%) with neural hypertrophy compared with only 10 of the 143 patients (7%) without neural hypertrophy (P=0.01). Multivariate regression did not show a single atypical histopathological feature, which predicted a worse outcome after IPAA. No single atypical histopathological feature of UC, or combination of features, was associated with any adverse pouch outcome after IPAA. There seems to be no value in performing a staged IPAA in IBDU patients.