Ileitis In Patients Research Articles

Isolated nonspecific terminal ileitis: prevalence, clinical evolution and correlation with metachronous diagnosis of Crohn's disease: a retrospective study and review of the literature.

The existing literature does not provide adequate guidance on the diagnosis and management of patients with nonspecific terminal ileitis, while data regarding the percentage of patients who ultimately develop Crohn's disease (CD) are scarce. We evaluated the prevalence and natural course of nonspecific terminal ileitis in patients who underwent colonoscopy during a 11-year period. All patients with endoscopic findings of terminal ileitis and nonspecific histological findings were included. Exclusion criteria were a clinical history of CD or any other disease that can cause terminal ileitis, or a recent history of using drugs implicated in lesions of the terminal ileum. From 5353 colonoscopies, 92 patients with nonspecific terminal ileitis were identified (prevalence: 1.7%). Among these patients, 56 (61%) had available follow up for ≥6 months after the initial endoscopy. Main indications for endoscopy were chronic diarrhea (37.5%), screening endoscopy (23%), and abdominal pain (20%). Sixteen (29%) patients received medical treatment, while recession of symptoms was recorded in 19 of 43 symptomatic patients (44.1%). Twenty-three (41%) of the 56 patients underwent a second endoscopy and 15 (65.2%) cases had persistent endoscopic findings. Eleven (19.6%) of the 56 patients were eventually diagnosed with CD. The probability of CD diagnosis was significantly higher in patients with persistent symptoms (P=0.002) and endoscopic findings at follow up (P=0.038). Nonspecific terminal ileitis generally has a benign clinical course. However, patients with persistent symptoms and endoscopic lesions are at increased risk for subsequent development of CD.

Bile acid conditioned Dendritic cells through FXR and specialize T cell function in the ileum

Abstract The accumulation of locally-reabsorbed bile acids (BAs) is suggested to contribute to the development of terminal ileitis. Our previous data showed nuclear receptor Constitutive Androstane Receptor (CAR) can directs T cell adaptation to BAs in the ileum by promoting the IL-10 producing Tr1 cells to prevent ileitis. Still, the mechanisms by which BA activate CAR in ileal T cells is not known. As CAR is not recognized as a BA sensor, its activation in ileal T cells may involves indirect pathways, such as dendritic cells (DCs). Farnesoid X receptor (FXR), a direct primary BA sensor, is highly expressed in both human and mouse DCs. Therefore, we hypothesized that BA-sensing by mucosal DCs through FXR may condition mucosal T cells in the ileum to upregulate CAR and to enforce anti-inflammatory T cell functions. Our result indicated WT DCs exposed to direct FXR agonist, chenodeoxycholic acid (CDCA), displayed increased production of IL-23a and decreased IL-6. While, CD4 +T cells cocultured with CDCA-treated DCs displayed increased CAR/Nr1i3, and its targets, cMyc and MDR1. Importantly, these observations were diminished in DCs from FXR −/−mice. In addition, when FXR is depleted in DC (CD11cCreFXR fl/fl, FXR ΔDC), the DC migration in the intestine is deficient, with low expressions of CCL19, CCR9 and less CD11c +CD11b −CD103 +MHCII +migratory DC population in the mesenteric lymph nodes. Meanwhile, the FXR ΔDCmice failed to promote CAR/Nr1i3as well as IL10in T cells. Furthermore, FXR −/−RAG2 −/−mice developed severe ileitis after engrafted with WT naïve T cell. These results suggest that FXR specializes intestinal DC and T cell function in the ileum. Collectively, these studies will shed new light on the understanding and treatment of ileitis in patients.

P191 Non-specific terminal ileitis: prevalence, clinical course and association with later diagnosis of Crohn’s disease

Abstract Background The existing literature does not provide adequate guidance on the diagnosis and management of patients with non-specific terminal ileitis, while the data regarding the percentage of patients that finally develop Crohn’s disease are scarce. Methods The aim of this study was to evaluate the prevalence and natural course of non-specific terminal ileitis in patients who underwent colonoscopy in our department during the last decade. All patients with endoscopic findings of terminal ileitis and non-specific histological findings between 2008 and 2018 were included in the study. Patient characteristics, initial symptoms, biopsy findings, and the patients’ clinical and endoscopic course were recorded. Patients with a history of Crohn’s disease or histological findings related to specific diseases were excluded. Results Out of 5.353 colonoscopies in total, 92 patients (mean age: 50 years, men: 56.5%, asymptomatic: 72.5%) with non-specific terminal ileitis were identified (prevalence: 1.7%). Among 92 patients, 56 (61%) had available follow-up information for at least 6 months after initial endoscopy. In these patients, the reasons for performing endoscopy were chronic diarrhea (21/56, 37.5%), screening (16/56, 28.6%), abdominal pain (12/56, 21.4%), iron deficiency (5/56, 9%) and visible blood in stool (2/56, 3.5%). Endoscopic findings included erosions/ulcerations (62.5%), mucosal edema (23.2%), mucosal erythema (10.7%) and ileal valve stenosis (3.6%). Among 56 patients, 16 (28.6%) received medical treatment that included aminosalicylates (25%), budesonide (62.5%) and antibiotics (12.5%). Recession of symptoms was recorded in 20 out of 40 symptomatic patients (50%). Interestingly, symptomatic relief was more frequent in patients who did not receive any treatment (75%) comparing to those who received medications (26.3%), (p=0.02). In total, 23/56 (41%) patients underwent 2nd endoscopy with persisting endoscopic findings in 15/23 (65.2%). Eleven out of 56 (19.6%) patients were eventually diagnosed with Crohn’s disease. The probability of Crohn’s disease diagnosis was significantly higher in symptomatic patients (27.5%) comparing to asymptomatic (0%) (p=0.019). The majority of patients with Crohn’s disease (9/11, 81.8%) remained symptomatic after initial endoscopy (p= 0.002), while 90% of them had persisting endoscopic findings in follow-up endoscopy (p=0.019). Conclusion Non-specific terminal ileitis has a generally benign clinical course regardless of the administered treatment. However, patients with persisting symptoms and endoscopic findings should be followed closely to monitor later development of Crohn’s disease.

Post Colectomy Ileitis in patients with Ulcerative Colitis: A Diagnostic Challenge

Aims: Post-colectomy ileitis is a common yet challenging disease entity. We present our management approach in these complex patients. Methods: We present a case series of four patients with post-colectomy ileitis in patients with Ulcerative Colitis (UC). Results: Despite optimal medical therapy, these patients underwent subtotal colectomy with end ileostomy and were discharged with tapering steroid regimen. They represented acutely (2-4 weeks) or chronically (months to years) with severe abdominal pain and/or problematic stoma output. Three patients required re-laparotomies, with two requiring further small bowel resection. Histology revealed necrosis and perforation but no granulomas. Diagnosis of post-colectomy ileitis was made. Both patients who underwent further bowel resection responded well to steroid therapy with Total Parenteral Nutrition (TPN) and remain on endoscopic surveillance. Symptomatic control was achieved with systematic/local steroid therapy in the remaining two patients.

Can microscopic ileitis in patients with clinically suspected inflammatory bowel disease predict the future?

BackgroundThe implication of microscopic ileitis finding in patients referred for ileocolonoscopy for clinically suspected inflammatory bowel disease (IBD) is not well defined, and its correlation with clinical outcome has not been fully studied. The current study aims to determine the prognostic yield of biopsies in this setting, and to evaluate the correlation of microscopic ileitis with long-term clinical outcome.MethodsWe reviewed endoscopic reports of patients referred to our department for ileocolonoscopy in the years 2010–2016, as part of a diagnostic work-up for suspected IBD. Patients whose ileocolonoscopies proved normal were included, provided that terminal ileum biopsies had been performed. Accordingly, patients were divided into groups classified as normal (normal or reactive changes) and microscopic ileitis (inflammation or ileitis of any severity). Both groups were followed prospectively to determine clinical outcome.ResultsA total of 439 patients met the inclusion criteria. Sixty-four (14.6%) showed inflammation on biopsy and were included in the microscopic ileitis group. Age range and gender figures did not differ significantly between the groups. Overall follow-up period was 6.1 ± 2.3 years. Patients in the microscopic ileitis group were significantly associated with Crohn’s diagnosis during the follow-up period compared with the normal group (19% vs 2%, OR = 11.98, 95%CI = 4.48–32.01; p < 0.01). Patients with granuloma or moderate-severe ileitis on biopsy were significantly associated with Crohn’s development (100% vs 11%; P < 0.01) compared with mild or nonspecific inflammation.ConclusionThe discovery of microscopic ileitis in clinically suspected IBD is associated with increased risk of future diagnosis of Crohn’s disease.

DOP86 An IFN-STAT1-MLKL axis drives programmed necrosis of Paneth cells in Crohn’s ileitis

Abstract Background Interferons (IFNs) are immune-modulatory cytokines expressed by epithelial and mucosal cells in response to viral and bacterial infection. Just recently, we discovered a correlation between IFN-λ expression and disease activity, including small intestinal inflammation and Paneth cell dysfunction, in human Crohn’s disease patients. On a molecular level, we uncovered that IFN-λ mediates epithelial cell death, in particular, Paneth cell death by a programmed necrosis, dependent on STAT1 activation and controlled by caspase-8. These results suggested that IFN-λ can be considered as a pathogenic cytokine in Crohn′s ileitis and should be considered as a new and promising target for future therapeutic intervention for this particular subtype of IBD. Our central question is now by which pathways interferon-regulated programmed necrosis of epithelial cells contributes to intestinal inflammation and how these mechanisms could be targeted for future therapeutic intervention. Methods We use a mouse model for Crohn’s Disease like inflammation and Paneth cell death that has a specific deletion of Caspase-8 in intestinal epithelial cells (Casp8∆IEC). We stimulate small intestinal organoids derived from Casp8∆IEC mice with IFNs in vitro and we overexpress IFN-λ in these mice in vivo by hydrodynamic tail vein injection of an IFN-λ expression vector. Furthermore, we use JAK-inhibitors to impede pharmacologically cell death pathways in the pathogenesis of intestinal inflammation in vitro and in vivo. Results We uncovered that gene expression of the cell death mediators Mlkl and Caspase-8 is dependent on IFN-λ-mediated JAK-STAT1 signalling. The non-specific pan JAK-inhibitor Tofacitinib is able to attenuate gene expression of Mlkl and Caspase-8 in vitro as well as in vivo. It prevents non-apoptotic as well as apoptotic cell death of small intestinal organoids stimulated with IFN-λ and is sufficient to prevent small intestinal tissue destruction in Casp8∆IEC mice challenged with IFN-λ. Additionally, we use the selective JAK1-inhibitor Filgotinib to limit the targeted JAK-STAT signalling pathways to only JAK1-STAT1 signalling and thus reduce side effects of the inhibitor on other signalling pathways. This had a similar effect as Tofacitinib suggesting that IFN controls MLKL-mediated cell death via JAK1. Conclusion In summary, our results indicate that targeting IFN-λ-mediated JAK-STAT1 signalling by the small-molecules Tofacitinib and Filgotinib impedes induction of Mlkl and Caspase-8-mediated cell death pathways. Therefore, JAK1 inhibitors such as Filgotinib might represent a promising novel therapy that may be sufficient to achieve efficacy particularly in Crohn′s ileitis patients who display elevated IFN-l serum levels.

Diffusion-weighted imaging and apparent diffusion coefficient values for evaluating terminal ileitis in patients with Crohn's disease.

Objective:To determine the accuracy of diffusion-weighted imaging (DWI) in identifying terminal ileitis in patients with Crohn’s disease.Materials and Methods:This was a retrospective study of 38 consecutive patients with Crohn’s disease who underwent magnetic resonance enterography with DWI in a 3.0 T scanner. The patients were divided into two groups, on the basis of colonoscopy and biopsy findings: active inflammation; and inactive disease. Apparent diffusion coefficient (ADC) values were determined, as were the magnetic resonance index of activity (MaRIA) and the Clermont score.Results:Of the 38 patients evaluated, 18 (47%) had active inflammation. The patients with active inflammation showed greater restricted diffusion, more pronounced mucosal edema, greater wall thickening, a higher MaRIA, and a higher Clermont score than did those with inactive disease. The level of interobserver agreement (intraclass correlation coefficient) was excellent for the MaRIA and the Clermont score, whereas it was substantial for the ADC values. For identifying colonoscopy-proven inflammation, the best ADC cut-off point was 2.1 × 10−3 mm2/s, which had a sensitivity of 88.8% and a specificity of 95.0%, whereas DWI presented an overall accuracy of 89.4%, with a sensitivity of 88.9% and a specificity of 90.0%.Conclusion:Visual analysis of the DWI sequence has good accuracy in detecting terminal ileitis in patients with Crohn’s disease. In addition, low ADC values have good sensitivity for detecting colonoscopy-proven inflammation.

Backwash ileitis in ulcerative colitis: Are there MR enterographic features that distinguish it from Crohn disease?

ObjectiveTo reveal the MR enterography (MRE) findings that distinguish backwash ileitis (BWI) from terminal ileitis due to Crohn's disease (CD) and to determine the usability of barium studies manifestations (ileocecal valve (ICV) gaping, terminal ileum dilatation) in MRE for the diagnosis of BWI in ulcerative colitis (UC) patients by pointing at the diagnostic performance of these imaging findings. Subjects-methodsThe study population consisted of patients who were diagnosed as ulcerative colitis (UC), and underwent 1.5 T MRI between August 2011 and November 2017 to rule out small bowel involvement. The matched controls were comprised of Crohn’s patients examined at the same period. Ileocolonoscopic/ histopathologic findings were accepted as reference standard. Mural/extramural changes in bowel segments, ileocecal valve (ICV) gaping, terminal ileum dilatation, restricted diffusion and anatomical extent of involvement were evaluated. In UC patients, the association between ICV gaping and terminal ileum dilatation and BWI was assessed by χ2 test. The diagnostic accuracy of these two findings in BWI was determined. ResultsSixty patients were included in the study (30 UC; 30 CD; mean age, 43 years in both groups). Ileocecal valve gaping and terminal ileum dilatation were significantly more frequent among BWI patients (p < 0.001) in UC. Patients with BWI showed a higher rate of pancolitis (88.9%). Median terminal ileum wall thickness was found to be significantly greater in patients with CD (p < 0.001). ConclusionIn patients with definite diagnosis of UC, ileocecal valve gaping and terminal ileum dilatation suggest the development of BWI. However, these findings cannot be use to differentiate cause of terminal ileitis in patients with unconfirmed diagnosis and do not give reliable information about the causative factor of ileitis.

Alpha-defensins (α-Defs) in Crohn's disease: decrease of ileal α-Def 5 via permanent methylation and increase in plasma α-Def 1-3 concentrations offering biomarker utility.

An impaired expression of α-defensins (α-Defs) in the ileal mucosa and, conversely, increased levels in plasma, have been reported in Crohn's disease (CD). However, the specificity and correlation of these findings with the degree of inflammation are unclear. We aimed to characterize the concentration and utility of ileal and plasma α-Defs in CD and to analyse a potential epigenetic mechanism of α-Def expression. Peripheral blood samples and ileal biopsies were obtained from patients at disease onset (aCD), from those who achieved remission (iCD) and from two control groups (healthy controls and non-CD-aetiology ileitis patients). Plasma α-Defs 1-3 and 4 were detected by enzyme-linked immunosorbent assay (ELISA); α-Def 5 by immunolocalization. Methylation analysis of the α-Def 5 gene was performed using the MassARRAY EpiTYPER system. Plasma α-Defs 1-3 concentrations were significantly higher in aCD with ileal involvement (L1, L3) versus iCD or the control groups. The α-Defs 1-3 concentrations were also similar to healthy controls in patients with non-CD ileitis. There was a significant positive correlation between plasma α-Defs 1-3 levels in aCD and the endoscopic index, as well as with C-reactive protein (CRP) levels. The immunopositivity scoring showed significantly reduced α-Def 5 expression in ileal inflamed (aCD) versus non-inflamed mucosa (iCD and healthy controls). The α-Def 5 gene showed a higher methylation status in CD patients than controls, regardless of the inflammation. Plasma α-Defs 1-3 concentrations correlate with the degree of inflammation and appear to be specific biomarkers of ileal-CD at diagnosis. Ileal α-Def 5 expression is down-regulated permanently by methylation.

Prospective Evaluation of Terminal Ileitis in a Surveillance Population of Patients with Ulcerative Colitis.

Ulcerative colitis (UC) is a disease that is normally limited to involvement of the colon. Terminal ileitis in patients with UC with only inactive or mildly active disease has never been investigated. The aim of this prospective study was to determine the prevalence and significance of ileitis among patients with UC enrolled in an endoscopic surveillance program. The study consisted of 72 patients with UC and 90 healthy controls who underwent surveillance and screening colonoscopy, respectively. The endoscopic and histologic features of the terminal ileum (both groups) and colon (UC group only) were evaluated in a standardized fashion. Extensive clinical and endoscopic information was obtained from the subjects, and these data were compared between patients with UC either with or without ileitis. Sixteen of 72 patients with UC (22%) had ileitis compared to only 4 of 90 (4%) of the non-UC controls (P < 0.001). None of the patients had features of backwash. Among patients with UC, the presence of ileitis showed a trend towards correlation with extent of disease, but a significant association with involvement of the colonic side of the ileocecal valve (P = 0.02) was noted. Alcohol use in the week before the colonoscopy was also significant (P = 0.02). There were no other features that were significantly related to ileitis in the patients with UC. Only one UC case with ileitis developed Crohn's disease on follow-up. Ileitis in patients with UC may represent a primary extracolonic manifestation of UC in patients with inactive or mild disease and is not due to backwash.

Sa1927 Natural History of Isolated Terminal Ileitis in Patients Without an Existing Diagnosis of Inflammatory Bowel Disease

Sa1927 Natural History of Isolated Terminal Ileitis in Patients Without an Existing Diagnosis of Inflammatory Bowel Disease

Histological evaluation in ulcerative colitis.

This review summarizes diagnostic problems, challenges and advances in ulcerative colitis (UC). It emphasizes that, although histopathological examination plays a major role in the diagnosis and management of UC, it should always be interpreted in the context of clinical, endoscopic, and radiological findings. Accurate diagnosis requires knowledge of the classic morphological features of UC, as well as a number of atypical pathological presentations that may cause mis-classification of the disease process, either in resection or biopsy specimens. These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC, cecal or ascending colon inflammation in left-sided UC, and backwash ileitis in patients with severe ulcerative pancolitis. Loosely formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt or eroded surface, should not be interpreted as evidence of Crohn’s disease. Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis. Patients with UC are at risk for the development of dysplasia and carcinoma; optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy. Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities. Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic correlation. Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis, or adenoma-like dysplasia if occurring in the diseased segment. Recent data suggest that such lesions may be treated adequately by polypectomy in the absence of flat dysplasia in the patient. UC patients with DALM or flat high-grade dysplasia should be treated by colectomy because of the high probability of adenocarcinoma. The natural history of low-grade dysplasia (LGD) is more controversial: while multifocal LGD, particularly if detected at the time of initial endoscopic examination, is treated with colectomy, unifocal flat LGD detected during surveillance may be managed by close follow-up with increased surveillance. The surveillance interval and treatment options for UC patients with dysplasia are reviewed in detail.

More Than the Significance of Conventional Urinalysis

It is nowadays well established that a urinalysis is one of the most essential and useful diagnostic modalities in the field of urology. On many occasions, however, its key elements are neglected and omitted and the inaccurate results are produced and then misinterpreted accordingly. This occurs when the investigators collect inappropriate samples, perform the test incompletely during short periods of time, possess a lower level of technical expertise, and neglect the significance of results. Currently, there is a widespread recognition that a microscopic urinalysis would be unnecessary so long as if there are normal results on dip-strip test that is routinely performed as a macroscopic one. But if there are any chances that specific markers, such as protein, hemoglobin, leukocyte esterase or nitrate, are detected on dip-strip test, it would be mandatory to perform a complete urinalysis including a microscopic one. A macroscopic urinalysis is routinely performed to examine the color and appearance, specific gravity, chemical composition test for pH, protein, glucose, hemoglobin, bacteria (nitrate), and leukocyte esterase. On the other hand, a microscopic urinalysis is performed to detect bacteria, leukocyte, erythrocytes, epithelial cells, and casts. Moreover, it may also be used to make a diagnosis of colon cancer, diverticulitis, and regional ileitis in patients with fistula beyond urothelial cancer, prostate cancer, hormone, and stone constituents on urinalysis. But I do assume that various types of qualitative and quantitative test regimens might be clinically useful only in a limited scope because of their sensitivity, specificity and high cost. In an actual clinical setting, bladder tumor antigen, nuclear matrix protein 22, immunCyt, and uroVysion fluorescence in situ hybridization are also currently available as adjunct to cytology in making a diagnosis of urothelial cancer. In addition, prostate cancer antigen 3, also known as differential display code 3, has been of increasing interest as a novel biomarker for prostate cancer, and ongoing studies are conducted to examine its clinical significance. Current efforts are made to identify and to examine the clinical application of novel urine markers in making a diagnosis of lower urinary tract dysfunction (LUTD) and other related diseases. But this is greatly dependent on the discovery of novel target markers rather than the simple application of new technology. It would be both complex and time-consuming to screen and to establish a diagnosis of many conditions associated with LUTD. This is because underlying diseases pose challenging problems for clinicians. It is therefore imperative that efficient biomarkers be discovered and then applied to an actual clinical setting. In the review of this issue [1], as a follow-up review of the article Recent progress in lab-on-a-chip technology and Its potential application to clinical diagnoses published in the first issue of this year [2], the authors describe that a quantitative, microfluidic paper-based bio-analysis is a novel technology and it is also one of the most relevant applications that have overcome the disadvantages of conventional macroscopic urinalysis using a dip strip. This puts an emphasis on the emergence of new technology that has undergone great advancements. Henceforth, we'll make every effort to identify neuro-urologic target markers and to assess their feasibility from medical, scientific and economic perspectives rather than to develop new technologies.

Beclomethasone dipropionate in Crohn's ileitis: A randomised, double-blind trial

Background Steroids, the mainstay of Crohn's disease treatment, have been associated with systemic side effects. Aim To evaluate the efficacy and tolerability of beclomethasone dipropionate for maintaining remission induced by a short course of systemic steroids in patients with Crohn's ileitis with or without right colonic involvement. Methods Patients ( n = 84) with active Crohn's disease who achieved remission during a 2-week prednisone run-in period were randomised to receive beclomethasone dipropionate for 24 weeks or continue prednisone for a further 2 weeks followed by placebo for 22 weeks. The primary outcome was relapse rate (Crohn's Disease Activity Index score > 150 and an increase of ≥60 points from baseline) or withdrawal due to disease deterioration. Results The relapse rate was 23.3% and 53.8% in beclomethasone dipropionate and placebo groups, respectively ( p = 0.027). According to Kaplan–Meier analysis, the cumulative relapse rate was 38.0% in the beclomethasone dipropionate group and 56.0% in the placebo group ( p = 0.025). Six percent and 1.7% of all adverse events in the beclomethasone dipropionate and placebo groups, respectively, were endocrine-related. Conclusion These results demonstrate that beclomethasone dipropionate significantly reduces the relapse rate in post-active Crohn's ileitis patients compared with placebo after induction of remission with a short course of systemic steroids, and is well tolerated.

Isolated Asymptomatic Ileitis Does Not Progress to Overt Crohn Disease on Long-term Follow-up Despite Features of Chronicity in Ileal Biopsies

Isolated ileal abnormalities may be detected during routine colonoscopy performed for polyp screening or surveillance. The significance of these abnormalities in asymptomatic patients without a prior diagnosis of inflammatory bowel disease is unknown. A critical clinical issue is whether isolated ileitis in asymptomatic patients is a manifestation of early Crohn disease (CD). We examined clinical, endoscopic, and pathologic data from 29 patients with isolated ileitis and no prior history of inflammatory bowel disease, and no colonic or upper gastrointestinal involvement. Only patients with at least 2 years of follow-up (range: 2.2 to 12.6 y) were included. Fifteen of 29 patients had colonoscopy for gastrointestinal symptoms whereas the remaining 14 were asymptomatic (screening colonoscopy). Seven of 15 (47%) of patients categorized as chronic active ileitis and 3 of 14 (21%) of those classified as focal active ileitis, on blinded histopathologic review, had a clinical diagnosis of CD at last follow-up. One or more features of chronicity were present in 11 of 14 (79%) of asymptomatic ileitis patients but none developed any manifestations of CD on long-term follow-up. In contrast, 8 of 10 (80%) of symptomatic patients with features of chronicity in ileal biopsies progressed to a diagnosis of CD, as did 2 of 5 (40%) symptomatic patients with focal active ileitis. Thus, the presence of symptoms seems to be the best predictor of likelihood of progression to CD in patients with isolated ileitis (P<0.001). Isolated ileitis detected in asymptomatic patients undergoing polyp screening or surveillance does not evolve into CD on follow-up, despite endoscopic and histologic overlap with findings typically seen in CD.

Lymphocytic Leiomyositis and Myenteric Ganglionitis Are Intrinsic Features of Cystic Fibrosis: Studies in Distal Intestinal Obstruction Syndrome and Meconium Ileus

Cystic fibrosis (CF) is a multisystem disorder intrinsically associated with inflammation of mucosal surfaces. Because inflammation can result in enteric neuromuscular dysfunction we hypothesized that terminal ileitis in patients with CF may predispose to distal ileal obstruction syndrome (DIOS). Full-thickness terminal ileal tissues from 6 children with CF and severe DIOS, 6 infants with complicated meconium ileus (MI), and 6 children with non-CF intestinal atresia were studied. Lymphocyte-predominant mucosal and transmural ileal inflammation was present in 6 of 6 patients with DIOS. Lymphocytic ganglionitis was present in 4 of 6 although numbers of myenteric neurons were not decreased (5/5). Myocyte proteins were preserved (6/6). Mild submucosal fibrosis was common in DIOS (5/6) and transformation of submucosal fibroblasts to a myofibroblastic phenotype was noted in 4 of 6. Inflammatory changes were distinct from those described in fibrosing colonopathy. Antroduodenal manometry in an individual who had experienced MI/DIOS was consistent with a neuropathic pseudo-obstructive process. Submucosal or transmural lymphocyte predominant inflammation was also present in 6 of 6 infants with complicated MI, which, when coupled with submucosal myofibroblast proliferation (5/6), appeared highly predictive of CF rather than non-CF atresia. Histological findings at birth were similar, although milder, than those seen in DIOS, suggesting that these changes are a primary abnormality in CF. Submucosal or transmural inflammation of the ileum is common in newborns with CF and MI and older children with DIOS. Severe recurrent DIOS should be investigated with seromuscular and mucosal biopsy of the ileum to seek a transmural ileitis potentially amenable to anti-inflammatory therapies.

M1129 Primary Sclerosing Cholangitis Is Associated with Endoscopic and Histologic Backwash Ileitis in Patients with Ileal Pouch-Anal Anastomosis

M1129 Primary Sclerosing Cholangitis Is Associated with Endoscopic and Histologic Backwash Ileitis in Patients with Ileal Pouch-Anal Anastomosis

Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis

BackgroundOne of nine types of FABP, intestinal fatty acid binding protein (I-FABP) is primarily limited to the mature enterocytes of the small intestine, with only trace amounts identified in the stomach and large intestine. The aim of this study was to investigate the use of I-FABP as a possible plasma marker of intestinal injury in patients with ulcerative colitis (UC). Material and methodsThe study group consisted of 42 patients (11 females and 31 males) with active ulcerative colitis (UC), aged from 24 to 74 years (mean age: 41.8±3.5 years). Plasma I-FABP concentrations and hsCRP were compared using endoscopic pictures scored according to the system developed by Meyers et al., and analysed in the context of inflammatory process extension: pancolitis, or distal or left side colitis. ResultsThe mean serum I-FABP concentration in UC patients was 166.9±36.3 vs. 61.3±7.8 pg/mL in healthy individuals. The highest I-FABP concentrations were observed in the pancolitis group (249.89±54.84 pg/mL), whereas individuals with left-side colitis had a mean I-FABP concentration of 61.8±8.5 pg/mL. Significant serum I-FABP elevation was observed in UC patients with a severe form of the disease, in contrast to the serum I-FABP concentration in patients with the mild form (260.5±60.6 vs. 61.5±7.9 pg/mL). ConclusionThe elevated serum I-FABP concentration in patients with UC may indicate ileitis. I-FABP may be a useful marker of the extended inflammatory process.

Increased permeability of macroscopically normal small bowel in Crohn's disease

To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P = 0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P = 0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.

Pouch ileitis.

Pouch ileitis is the most poorly understood complication of ileal reservoir surgery. Variability in definition of this syndrome may account for differences in incidence rate, associated symptoms, and response rate to therapy present in the literature. Outcomes of 19 episodes of pouch ileitis in patients having undergone prior colectomy and continent ileostomy construction for presumed ulcerative colitis were analyzed. An episode of pouch ileitis was characterized by: (1) abdominal pain, (2) increased ileal output, (3) mucosal inflammation within the continent ileostomy, and (4) absence of other recognized concurrent postoperative complications. The mean time of occurrence after construction of the continent ileostomy was 25 months (range 3-54 months). The mean length of follow-up of patients included in this analysis was 49 months from the time of continent ileostomy construction (range 22-101 months). Associated clinical symptoms included bloody effluent (53%), nausea or emesis (47%), and fever (42%). Endoscopic features were often nonspecific, with mucosal erythema (84%), edema (79%), friability (58%), and mucosal ulceration (53%) the most common. In those episodes of pouch ileitis where ileoscopy revealed no evidence of mucosal ulceration, complete resolution of the episode occurred 89% of the time, with 78% treated with antibiotics alone. In those episodes where mucosal ulceration was described on ileoscopy, 40% of episodes completely resolved after medical treatment, 20% with antibiotics alone. The varied clinical symptoms, endoscopic findings, and response to treatment raises the possibility that what has previously been described in the literature as pouch ileitis may be a heterogeneous group not of single etiology.(ABSTRACT TRUNCATED AT 250 WORDS)