Ileocolonic Biopsies Research Articles

Mucin Expression Profiles in Ulcerative Colitis: New Insights on the Histological Mucosal Healing.

A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC.

DOP01 Definitions of histological abnormalities in inflammatory bowel disease: an ECCO position paper

Abstract Background High quality histological examination of ileocolonic biopsies in inflammatory bowel disease (IBD) plays a critical role in optimising clinical management, investigative studies, and clinical trials. The correct assessment of histological features can confirm the diagnosis of IBD, assist with its subclassification (as ulcerative colitis or Crohn’s disease), facilitate the estimation of disease activity and disease extent, and aid the detection of mimics and complication. However, there are surprisingly few universal definitions of each histological abnormalities and the existing definitions are often inconsistent. The main practical concern is that histological scoring schemes, or guidelines on histological diagnosis, include detailed features, and many of these features have, paradoxically, no, or vague definitions. Furthermore, interobserver variability for many histological features in IBD is significantly high, possibly reflecting lack of precision. The aim of this paper is to review and assess any existing histologcal definitions and criteria, selecting the most appropriate where possible, and modifying them or writing new definitions where necessary. Methods The European Crohn's and Colitis Organisation (ECCO) and the project leaders formed a panel of experts in the IBD field, composed of pathologists and gastroenterologists to explore inconsistencies in the definitions of histological abnormalities using the best resources and evidence available. The panel examined existing definitions, peer reviews publications, scoring schemes, guidelines and textbooks. An important contribution was also given by their professional experience and knowledge. Results The literature review process confirmed that most current existing definitions often have no evidence base and vary between sources. The panel of experts developed 40 statements on histological definitions in IBD with accompanying supporting text for each statement. Conclusion The statements represent expert consensus with the support of evidence where available. Further possible development of this process will include attempts to grade histological changes, aiming to improve the consistency of pathological diagnosis, a reduction in currently high rates of interobserver variability, more precision in clinical trial work and research, and to facilitate development of new guidelines and scoring schemes for IBD.

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.

Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT. We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3-V4) from ileocolonic biopsies. Intraindividual microbial diversity was reduced in both PSC and PSC-LT versus HCs. An expansion of Proteobacteria was more pronounced in PSC-LT (up to 19% relative abundance) than in PSC (up to 11%) and HCs (up to 8%; Q FDR < 0.05). When investigating PSC before (PSC vs. HC) and after LT (rPSC vs. no-rPSC), increased variability (dispersion) in the PSC group was found. Five genera were associated with PSC before and after LT. A dysbiosis index calculated from the five genera, and the presence of the potential pathobiont, Klebsiella , were associated with reduced LT-free survival. Concomitant IBD was associated with reduced Akkermansia . Consistent mucosal microbiota features associated with PSC, PSC-IBD, and disease severity, irrespective of LT status, highlight the usefulness of investigating PSC and rPSC in parallel, and suggest that the impact of gut microbiota on posttransplant liver health should be investigated further.

Immunohistochemical Detection of Tumor Necrosis Factor Alpha in Ileocolonic Biopsies of Patients with Inflammatory Bowel Disease

Background: Tumor necrosis factor alpha (TNF-α) is a major proinflammatory cytokine playing paramount role in the pathophysiology of inflammatory bowel disease (IBD). The identification of predictive biomarkers to establish response to treatment is intuitive and still unresolved need. A biomarker of TNF-α sensitivity would avoid unnecessary exposure of the patient to the drug and to its side effects. Objective: To investigate the relationship between immunohistochemical expression of TNF-α in the biopsies of ileocolonic segments in patients with activity of both ulcerative colitis (UC) and Crohn's disease (CD) and the clinicopathologic parameters and the response to treatment. Patients and methods: The study was conducted on 41 naive patients diagnosed as IBD (UC and CD) and 15 normal subjects as a control group. All patients and control underwent full history taking (age, gender and clinical data as weight loss, diarrhea, bleeding, and duration of the disease), complete physical examination, laboratory investigation (Complete blood count (CBC), ESR, C-reactive protein (CRP), fecal calprotectin (FC)), colonoscopy disease localization, upper endoscope with upper GIT symptoms. Biopsies from the terminal ileum and different colon segments were taken for histopathological evaluation and immunohistochemistry was done according to published protocols to all cases and control. Results: Percentage and H-score for TNF-α significantly correlated with clinical severity and need to give additional treatment besides conventional therapy as anti-TNF therapy. Increased TNF-α expression is significantly associated with better response to anti-TNF treatment. Conclusion: Increased expression of TNF-α in the tissues is associated with the need to give additional treatment besides conventional therapy as anti-TNF therapy and also increased TNF expression is associated with better response to anti-TNF treatment.

S2909 Granulomatous Appendicitis: Idiopathic or Prospective Crohn’s Disease?

INTRODUCTION: Isolated granulomatous inflammation of the appendix is a rare entity, identified histologically in < 2% of specimens, and typed into idiopathic granulomatous appendicitis (GA) and appendiceal Crohn’s disease (CD). Less than 10% of GA cases develop CD. CASE DESCRIPTION/METHODS: A healthy 26-year-old male was advised to seek care for computed tomography (CT) suggesting acute appendicitis, ordered to assess dysuria and right testicular and abdominal pain of 1-month duration. CT measured a dilated appendix extending to the seminal vesicle, with fecolith and fat stranding. Vitals were stable, abdomen benign, and labs normal. During appendectomy, an inflamed appendix was seen adherent to the bladder. An uneventful post-op period was followed by discharge home. Despite interval recovery, readmission for pain, vomiting, and diarrhea occurred on POD 10. Tachycardia was noted without fever. Abdomen was distended and generally tender. There was leukocytosis. CT found thickened jejunum with proximal dilation and air-fluid-levels. Jejunitis and obstruction resolved with conservative care, but evidence of GA (granuloma with giant cell, negative AFB and GMS stains) on recent pathology prompted testing for a broadened differential. There was denial of travel, ill contacts, personal and family history of CD, but admittance to colonoscopy a decade prior with findings of proctitis. Blood, urine, and stool cultures, as well as C. difficile and O&P were negative. CD, tuberculosis, fungal, and Coccidioides serologies were negative. Ileocolonoscopy found post-op cecal changes. Random ileocolonic biopsies resulted normal mucosa. With clinical stabilization, discharge home was planned. During follow-up visit, the patient declared return to normalcy, and thus declined investigations for CD. DISCUSSION: Causes of GA include infectious, systemic, and local reactions, but often remains elusive, as does a uniform approach to diagnosis and management. Omitted tests limit confidence in diagnosing idiopathic GA, and uncertainty in proper follow-up delays diagnosis of related conditions. Despite idiopathic labeling, we remain vigilant to alternate causes. The patient at first lacked acute infectious features, but as Yersenia is linked to ¼ of cases, serologic testing would be ideal to exclude infection and support idiopathic nature. Sub-acuity lends support to interval appendectomy as a cause. Lastly, a remote history of proctitis, in concert with enteritis on readmit, may hint at chronicity, and begs close follow-up for CD.Figure 1.: Histology showing presence of non-caseating granulomas in a background of lymphocytic inflammation in the appendiceal wall (x10).Figure 2.: Histology showing a giant cell in a granuloma in the appendiceal wall (x10).Figure 3.: Computed tomography of the abdomen and pelvis with IV contrast showing diffuse circumferential thickening of multiple distal jejunal loops.

Sa1901 – Expression of Integrin A4B7 and Madcam1 in Ileocolonic Biopsies from Patients with Inflammatory Bowel Disease

Sa1901 – Expression of Integrin A4B7 and Madcam1 in Ileocolonic Biopsies from Patients with Inflammatory Bowel Disease

Localization of TNF alpha in ileocolonic biopsies of patients with inflammatory bowel disease

BackgroundAlthough antitumor necrosis factor alfa (TNFα) agents are widely used to treat patients with inflammatory bowel diseases (IBD) - both Crohn's disease (CD) and ulcerative colitis (UC) - there is still some uncertainty in the cell type expressing TNFα in human ileo-colonic segments. AimsWe investigated the immunohistochemical (IHC) expression of TNFα in the ileo-colonic segments of patients with both active CD and UC, to establish its anatomic and cellular localization in the inflamed sites. Our aim was to identify patients potentially resistant to anti TNFα agents. Patients and methodsIleo-colonic slides of complete histological mapping of patients with CD and UC before any treatment was started were obtained, and serial sections assessed for TNFα expression, together with IHC markers for lymphocytes, macrophages, and plasma cells. ResultsTNFα was expressed in almost all inflamed segments of IBD patients, albeit with different strength, and was present, in addition to lymphocytes and, to a lesser extent, to macrophages, in plasma cells, where it had a strong positivity, as also demonstrated by colocalization of specific IHC staining. The expression of TNFα was mostly focal in CD patients and more diffuse in UC patients, likely due to the different patterns of inflammation (transmural and mucosal) of the two entities. ConclusionsIn IBD, TNFα is strongly expressed also in plasma cells, and it is easily evidenced by conventional IHC techniques. It remains to be established whether this observation might be useful in future to establish in routine biopsy samples whether patients may be responsive to treatments toward this cytokine.

Utility of Routine Colonic Biopsies in Pediatric Colonoscopic Polypectomy for Benign Juvenile Hamartomatous Polyps.

Benign juvenile hamartomatous polyps are common in pediatric gastrointestinal practice. We hypothesize that in the absence of gross mucosal abnormalities, the likelihood of histologic abnormalities from routine random colonic biopsies is low. We performed a retrospective chart review identifying patients ages 1 to 18 years who underwent complete colonoscopy and polypectomy for suspected colorectal polyps from January 1, 2004 to July 1, 2014. Indication, age, number of polyps, gross and histologic findings, and any management changes resulting from endoscopy were recorded. Exclusion criteria included history of polyposis syndrome, >5 polyps on colonoscopy, inflammatory bowel disease, and incomplete documentation. Practice patterns were assessed by online survey distributed via Pediatric Gastroenterology listserv. A total of 141 patients underwent colonoscopy with anticipated polypectomy. Seventy-two (63% male) were included. Mean age was 6.5 years. Indication was hematochezia in 71. Findings other than polyps were found in 7 (10%). Juvenile hamartomatous polyps were documented by histologic examination in 68 patients (94%). Routine colonic biopsies were performed in 55 patients (76%). In 8 (15%), histologic abnormalities were seen that did not result in management changes. Seventy-three providers responded to the online survey; 56% reported not taking ileocolonic biopsies in the absence of other mucosal abnormalities; 45% routinely biopsied from the terminal ileum and/or colon. None would biopsy the terminal ileum only. In children with benign juvenile hamartomatous polyps, routine colonic biopsies are not required in the absence of mucosal abnormalities. Overuse of pathology services, increased procedural time, risk, and cost can be avoided.

High Prevalence of Inflammatory Bowel Disease in United States Residents of Indian Ancestry

It is unclear whether the reported low prevalence of inflammatory bowel disease (IBD) in Southern and Eastern Asia is real (caused by genetic or environmental factors) or spurious (because of differences in awareness of the condition among physicians or different interpretations of endoscopic and histologic features). We aimed to estimate the prevalence of IBD in patients of different ethnicities who underwent endoscopy in the United States, with ileocolonic biopsies evaluated by a single group of gastrointestinal pathologists. We used a national pathology database to collect data on 1,027,977 subjects who underwent colonoscopy with ileocolonic biopsies from January 2008 through December 2013 throughout the United States; mucosal biopsy specimens were evaluated and reported by 1 group of 35 histopathologists. Patients were stratified into the following ancestries: Indian (persons with ancestry in the Indian subcontinent), East Asian (China, Korea, Japan, and Vietnam), Hispanic, Jewish, and Other. The prevalence of ulcerative colitis (UC), Crohn's disease (CD), and indeterminate colitis was determined for each ethnic group. In the study population, 30,812 patients were diagnosed with IBD (20,308 with UC, 7706 with CD, and 2798 with indeterminate colitis). UC was more commonly associated with Indian and Jewish ethnicity and less commonly associated with East Asian and Hispanic ethnicity. Similar patterns also applied to CD and to all types of IBD analyzed jointly. Among Indian patients, 11.7% of those of Gujarati origins had IBD, compared with 7.9% of other Indians (odds ratio, 1.5; 95% confidence interval, 1.14-2.11). Patients of Indian origin living in the United States have a greater risk for all types of IBD than other American populations. East Asians and Hispanics have a lower risk, possibly similar to that of the populations still living in their original countries. These findings may have relevance to the practice of gastroenterology in countries where there are sizable portions of the population with roots in the Indian subcontinent.

Su1460 Low Prevalence of Microscopic Colitis and Inflammatory Bowel in Americans of East Asian Ancestry

Background: East Asian countries have historically reported low incidences of microscopic colitis and inflammatory bowel disease. (Ahuja & Tandon, J Dig Dis, 2010). However, it is unclear whether these data reflect genetic or environmental factors or are the result of different diagnostic criteria among physicians and pathologists. To address this question, we have designed a study to estimate the prevalence of these conditions among adult patients of East Asian ancestry who live in the U.S., have had colonoscopies in the U.S., and had their biopsies evaluated by a single group of U.S. gastrointestinal pathologists. Methods: From a large national pathology database of subjects who had colonoscopy with ileocolonic biopsies between 1.2008 and 8.2013 in endoscopy centers through the U.S., we extracted all adult patients identified as Korean, Chinese, Japanese, or Vietnamese (collectively referred to as East Asians). Controls were all other adults. We then recorded the histopathologic diagnoses of Crohn's Disease, Ulcerative Colitis, Lymphocytic Colitis, and Collagenous Colitis, and compared their prevalence in East Asian patients to that of controls using unadjusted odds ratios. If a patient had multiple procedures during the study period, only the first chronological procedure was selected. Results: There were 14,209 unique East Asian patients (median age 59 years; 53.2% men) and 1,254,986 unique controls (median age 60 years; 48.9% men). Figure 1 shows the relative prevalence of the four types of colitis in each group. Conclusions: In our series, patients of East Asian descent living in the U.S. were affected by microscopic colitis and inflammatory bowel disease to a much lesser extent that those of other ancestries. The two groups of patients were similar in age and sex distribution, had their endoscopic procedures in similar U.S. settings, and their histopathologic diagnoses were made by a single pathology group whose members adhere to common criteria. Therefore, the remarkably low prevalence of non-infectious colitides detected in this analysis is likely to reflect, at least in part, genetic factors. Determining the relative risk in several generations of Asians in the U.S. might help determine whether environmental factors play a significant role in the development of these conditions.

Su1461 Lymphocytic Colitis-Related Diarrhea Is Caused by Both, ERK1/2-Dependent Inhibition of the Epithelial Sodium Channel (ENac) and a Claudin-Induced Barrier Defect

Background: East Asian countries have historically reported low incidences of microscopic colitis and inflammatory bowel disease. (Ahuja & Tandon, J Dig Dis, 2010). However, it is unclear whether these data reflect genetic or environmental factors or are the result of different diagnostic criteria among physicians and pathologists. To address this question, we have designed a study to estimate the prevalence of these conditions among adult patients of East Asian ancestry who live in the U.S., have had colonoscopies in the U.S., and had their biopsies evaluated by a single group of U.S. gastrointestinal pathologists. Methods: From a large national pathology database of subjects who had colonoscopy with ileocolonic biopsies between 1.2008 and 8.2013 in endoscopy centers through the U.S., we extracted all adult patients identified as Korean, Chinese, Japanese, or Vietnamese (collectively referred to as East Asians). Controls were all other adults. We then recorded the histopathologic diagnoses of Crohn's Disease, Ulcerative Colitis, Lymphocytic Colitis, and Collagenous Colitis, and compared their prevalence in East Asian patients to that of controls using unadjusted odds ratios. If a patient had multiple procedures during the study period, only the first chronological procedure was selected. Results: There were 14,209 unique East Asian patients (median age 59 years; 53.2% men) and 1,254,986 unique controls (median age 60 years; 48.9% men). Figure 1 shows the relative prevalence of the four types of colitis in each group. Conclusions: In our series, patients of East Asian descent living in the U.S. were affected by microscopic colitis and inflammatory bowel disease to a much lesser extent that those of other ancestries. The two groups of patients were similar in age and sex distribution, had their endoscopic procedures in similar U.S. settings, and their histopathologic diagnoses were made by a single pathology group whose members adhere to common criteria. Therefore, the remarkably low prevalence of non-infectious colitides detected in this analysis is likely to reflect, at least in part, genetic factors. Determining the relative risk in several generations of Asians in the U.S. might help determine whether environmental factors play a significant role in the development of these conditions.

255 Clinical Implications of Histologic Abnormalities in Ileocolonic Biopsy of Crohn's Patients in Clinical Remission

setting. Methods: Patients were recruited from 6 centers (3 US, 3 Europe) globally based on their pre-specified levels of disease according to a prospectively conducted CDAI (Remission: 225, respectively). Within a 2 week period each patient underwent an ileocolonoscopy and a pair of MREs with and without colonic distention with each procedure separated by at least 24 hours. MRE scans and ileocolonoscopy videos were scored by central readers using the MaRIA index and CDEIS, respectively. A MaRIA subsegment score > 11 and CDEIS > 8 were used as selection criteria demonstrating active disease for inclusion into a study of moderate to severely active CD. Results: A total of 19 patients were enrolled across the six centers. Using ileocolonoscopy as the standard reference, MRE without enema identified deep ulcers in the colon with 58% sensitivity, 73% specificity; MRE with enema had similar sensitivity, 58% but better specificity, 80%. For enrollment into a trial for moderate to severely active CD, the CDAI identified 6 patients. Of these, only 3 patients had active disease confirmed by either MRE or Ileocolonoscopy. One of these three patients had an abscess identified by MRE. The remaining three patients had no objective evidence of disease by MRE or ileocolonoscopy. Using MRE, 12 subjects were identified for inclusion into a trial of which 3 would have been excluded from a clinical trial due to presence of an abscess or abdominal extramedullary hematopoeisis. Two of the remaining 9 subjects did not have identifiable disease on ileocolonoscopy. Using ileocolonoscopy, 6 subjects were identified of whom 2 patients would have been excluded by MRE due to an abscess. Overall, MRE selected 7 patients with active disease compared with 4 and 2 patients by CDEIS and CDAI who would be appropriate to include in a CD clinical trial Conclusions: In comparison to endoscopy and the CDAI, MRE better enriches for patients with more appropriate levels of disease for inclusion in a clinical trial with therapeutic intervention.

Additional Value of Upper GI Tract Endoscopy in the Diagnostic Assessment of Childhood IBD

For the choice of treatment in children with inflammatory bowel disease (IBD), it is important to make a distinction between Crohn disease (CD) and ulcerative colitis (UC). To look for pathognomonic features of CD, upper gastrointestinal tract (UGT) endoscopy has become part of the routine evaluation of children with suspected IBD; however, pathological changes can also be found in the UGT in patients with UC. The aims of the present study were to establish the role of UGT involvement in the diagnostic assessment of suspected IBD in children and to detect histopathological changes in the UGT mucosa, which can distinguish CD from non-CD (UC and non-IBD). Biopsies (colon, ileum, duodenum, stomach, esophagus) from children suspected of having IBD who underwent endoscopy between 2003 and 2008 were reassessed by a blinded, expert pathologist. The histological findings of the UGT were compared with the diagnosis based on ileocolonic biopsies and the final diagnosis. In 11% of the children with CD, the diagnosis was based solely on the finding of granulomatous inflammation in the UGT. Focal cryptitis of the duodenum and focally enhanced gastritis were found significantly more frequently in children with CD compared with children with UC and non-IBD, with a specificity and positive predictive value of 99% and 93% and 87.1% and 78.6%, respectively. Histology on ileocolonic biopsies alone is insufficient for a correct diagnosis of CD or UC in children. UGT endoscopy should, therefore, be performed in the diagnostic assessment of all children suspected of having IBD.

La tuberculose intestinale : à propos de 11 observations

IntroductionIn recent years, the incidence of intestinal tuberculosis has been increasing. This is, in part, due to the pandemic of HIV. Intestinal tuberculosis can be difficult to diagnose and needs a high index of suspicion. The aim of our study is to describe epidemiological, clinical and therapeutic aspects of intestinal tuberculosis in Tunisian adults.Material and methodsRetrospective study of all intestinal tuberculosis recorded from January 1996 to December 2007 in gastroenterology B department of Rabta Hospital in Tunis.ResultsEleven patients were included: five males and six females. Mean age was 35. Clinical manifestations were dominated by abdominal pain. Biologic signs of inflammation were constant. The intradermal tuberculin reaction was positive in 27% of the cases. Mycobacterium tuberculosiswas identified in sputum or urine in two patients. HIV serology was negative in all cases. Lesions were more frequently localized in the ileo-caecal area (36%). Ulcerations were present in 72% of the cases. In histology reports, a granuloma with caseating necrosis was present in three cases (27%). M. tuberculosis was isolated on ileo-colonic biopsies in three patients (27%). Morphologic studies showed ileo-caecal valve or ileal stenosis in six patients (54.5%). Extraintestinal tuberculosis was associated in 45% of the cases. Antituberculous therapy was given in seven patients for a mean duration of nine months (four patients were lost). Clinical and endoscopic outcome was favourable in 86% of the cases.ConclusionAlthough Tunisia is a high endemic country for tuberculosis, intestinal tuberculosis is rare. However, it should be suspected mainly in patient having history of tuberculosis or in case of characteristic clinical or radiological signs.

Deficiency of Invariant NK T Cells in Crohn's Disease and Ulcerative Colitis

The aim of this study was to investigate whether immunoregulatory invariant NK T cells are deficient in Crohn's disease or ulcerative colitis. Blood was collected for flow cytometry from 106 Crohn's disease, 91 ulcerative colitis, and 155 control subjects. Invariant NK T cells were assessed by Valpha24 and (alpha-galactosylceramide/CD1d tetramer markers. Intracellular cytokine was measured after in vitro anti-CD3 antibody stimulation. Valpha24+ T cells were quantified in ileocolonic biopsies as mRNA by real-time PCR and by immunofluorescence. Circulating invariant NK T cells were 5.3% of the control levels in Crohn's (P < 0.001) and 7.9% of the control levels in ulcerative colitis (P < 0.001). Interleukin-4 production was impaired in Crohn's disease and ulcerative colitis. Intestinal Valpha24 mRNA expression was 7% in Crohn's disease (P < 0.05) and 9% in ulcerative colitis (P < 0.05). Intestinal Valpha24+ T cells were 23% in Crohn's disease but not reduced in ulcerative colitis. We conclude that invariant NK T cells are deficient in Crohn's disease and in ulcerative colitis.

A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease

The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.

Enterocolitis in children with developmental disorders

OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3–16; 53 male). Developmental diagnoses were autism (50 patients), Asperger’s syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0–3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2–13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely. RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls ( p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls ( p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls ( p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls ( p < 0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

Clinical pharmacokinetics of slow release mesalazine.

Slow release oral mesalazine (Pentasa) contains microgranules covered by a semipermeable ethylcellulose membrane. The microgranules continuously release their content from duodenum to ileum in a pH- and time-dependent way. About 75% of the microgranules pass into the colon, where further release is slower. This release pattern does not appear to be affected by food, diarrhoea or the simultaneous use of H2 antagonists. Rectal forms of mesalazine deliver active drug directly to the rectum and left colon. Plasma concentrations of mesalazine and its metabolite acetyl-5-aminosalicylic acid after oral or local administration are the result of systemic absorption and hepatic metabolism by N-acetyltransferase. Most studies report maximal plasma concentrations of less than 1 mg/L after oral administration of slow release mesalazine, much lower than those observed after uncoated mesalazine but generally higher than after azo-bound drugs such as sulfasalazine. Urinary recovery is an indicator of absorption and metabolism, and is lower after rectal administration (10 to 30%) than after oral administration (30 to 40%). Faecal recovery after oral administration of slow or delayed release mesalazine is lower than with azo-bound drugs. Mesalazine acts locally after absorption by colonic and ileal mucosa. Mean steady-state concentrations of 25.7+/-2.2 microg/kg wet weight are found in ileocolonic biopsy specimens from patients with irritable bowel syndrome treated for 1 week with slow release mesalazine 1.5 g/day. Intramucosal concentrations after slow release mesalazine differ little between healthy individuals and patients with inflammatory bowel disease. Although significant differences are found between the various aminosalicylates in release patterns and the resulting pharmacokinetic parameters, no differences in therapeutic effects have been found in comparative studies. High doses of oral mesalazine (2 to 4 g/day) are more effective than lower doses in the treatment of patients with mild to moderate active ulcerative colitis. High doses (4 g/day) are also effective in the treatment of Crohn's disease, predominantly in patients with ileitis. In contrast, no dose ranging effects were demonstrated with local treatment forms: mesalazine 1g enema seems sufficient for patients with distal colitis. Higher serum concentrations and urinary recoveries after the administration of slow or delayed release mesalazine compared with azo-bound drugs suggest a higher risk for renal adverse effects, although the reported occurrence is extremely low. Although preliminary data support an association between mucosal concentrations of mesalazine and its clinical activity, further studies are needed to correlate the effects of this drug with its pharmacokinetic parameters.