Mark E. McAlindon

Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care

BACKGROUND Irritable bowel syndrome has a high prevalence. Consensus diagnostic criteria (ROME II) based on symptoms have been established to aid diagnosis. Although coeliac disease can be misdiagnosed as irritable bowel syndrome, no prospective study has been published in which patients with this disorder are investigated for coeliac disease. We aimed to assess the association of coeliac disease with irritable bowel syndrome in patients fulfilling ROME II criteria. METHODS We undertook a case-control study at a university hospital. 300 consecutive new patients who fulfilled Rome II criteria for irritable bowel syndrome, and 300 healthy controls (age and sex matched) were investigated for coeliac disease by analysis of serum IgA antigliadin, IgG antigliadin, and endomysial antibodies (EMA). Patients and controls with positive antibody results were offered duodenal biopsy to confirm the possibility of coeliac disease. FINDINGS 66 patients with irritable bowel syndrome had positive antibody results, of whom 14 had coeliac disease (11 EMA positive, three EMA negative). Nine patients with positive antibody results were lost to follow-up or refused biopsy (only one EMA-positive patient refused biopsy), and 43 had normal duodenal mucosa. Two controls, both of whom were EMA positive, had coeliac disease. Compared with matched controls, irritable bowel syndrome was significantly associated with coeliac disease (p=0.004, odds ratio=7.0 [95% CI 1.7-28.0]). INTERPRETATION Patients with irritable bowel syndrome referred to secondary care should be investigated routinely for coeliac disease. With only EMA, three of 14 cases would have been missed.

Guidelines on small bowel enteroscopy and capsule endoscopy in adults

1.0 Introduction 2.0 Formulation of guidelines 2.1 Grading of recommendations 2.2 Scheduled review 3.0 Summary of recommendations 4.0 Types of small bowel enteroscopy 4.1 Enteroscopy using a colonoscope 4.2 Sonde enteroscopy 4.3 Push enteroscopy 4.4 Intraoperative enteroscopy 4.5 Double balloon (push and pull) enteroscopy 5.0 Capsule endoscopy 5.1. Technique 5.2 Indications for capsule endoscopy 5.3 Complications of capsule endoscopy 5.4 Patency capsule 6.0 Service provision and training References The small bowel has historically been a difficult area to examine due to its anatomy, location and relative tortuosity. Examination beyond the duodenojejunal flexure is of importance in a number of small bowel disorders. Before the advent of enteroscopy or capsule endoscopy, radiographic studies had been the main investigative modality of the small bowel. Barium follow-through and enteroclysis permits indirect examination of the small bowel but has a low diagnostic yield particularly in the context of obscure gastrointestinal bleeding.1–3 Capsule endoscopy and enteroscopy are now the preferred methods to examine the small bowel in most situations. These guidelines are intended to provide an evidence based document describing endoscopic investigation of small bowel disorders. These guidelines were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) and have been produced by the small bowel and endoscopy sections of the BSG. The guidelines have been produced to conform to the North of England evidence based guidelines development project.4 5 They have been drawn up from a Medline, Embase and Ovid literature search using terms “enteroscopy”, “push enteroscopy”, “intraoperative enteroscopy”, “double balloon enteroscopy” and “capsule endoscopy”. There have been 180 peer review studies, seven review articles, 58 case reports and letters, and one set of American guidelines on enteroscopy.6 The literature search for capsule endoscopy includes 100 peer review studies, 51 review articles, 74 …

Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel disease

Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD). Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa. Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay). Results—Normal colonic macrophages synthesised only the precursor form of IL-1β whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β released by isolated IBD macrophages (from a median of 1.2 (range 0.78–4.42) ng/ml to 0.43 (0.21–1.6) ng/ml; p<0.01). Conclusions—Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1β, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1β in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.

What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis.

BACKGROUND & AIMS The optimal serologic tests for the detection of celiac disease and follow-up assessment remains controversial. Our aim was to evaluate all current immunologic assays for diagnosing celiac disease using the gold standard of duodenal biopsy. We also assessed whether tissue transglutaminase (tTG) antibody is a quantitative marker for histologic severity. METHODS Consecutive adult patients referred for gastroscopy without a previous known diagnosis of celiac disease were recruited (group 1). Concurrently, patients with a known diagnosis of celiac disease on a gluten-free diet for more than 1 year undergoing repeat duodenal biopsy were identified (group 2). All patients had duodenal biopsies and serologic analysis performed for immunoglobulin(Ig) A and antibodies to human immunoglobulin (Ig)A-tTG, IgA-gliadin, IgG-gliadin, and IgA-endomysial antibody. RESULTS Two thousand patients were recruited in the first group. Seventy-seven (3.9%) patients were diagnosed with new celiac disease. The sensitivity, specificity, positive predictive value, and negative predictive value for IgA tTG were 90.9%, 90.9%, 28.6%, and 99.6%. When adopting a 2-step approach using tTG first and then EMA the sensitivity, specificity, positive predictive value, and negative predictive value was 85.7%, 98.6%, 71.7%, and 99.7%, respectively. The use of nondeamidated IgA/IgG gliadin antibodies conferred no additional diagnostic benefit when considering the detection of adult celiac disease. In the second group 48 patients with celiac disease on a gluten-free diet were identified. Sixteen of 48 of these patients had persisting villous atrophy, but 7 of 16 (44%) had a normal tTG level. CONCLUSIONS IgA tTG alone is a sensitive marker for celiac disease. A normal tTG level does not predict recovery of villous atrophy in patients with celiac disease on a gluten-free diet.

The role of high-magnification-chromoscopic colonoscopy in hereditary nonpolyposis colorectal cancer screening: a prospective "back-to-back" endoscopic study.

BACKGROUND:In hereditary nonpolyposis colorectal cancer flat and diminutive adenomas occur, particularly in the right colon. Such lesions may assume a high risk of malignant transformation. Interval cancers are known to occur in this group. Chromoscopic colonoscopy enhances detection in patients assuming a moderate to high lifetime risk of colorectal cancer.AIM:To prospectively assess the efficacy of high-magnification-chromoscopic colonoscopy for the detection of neoplastic lesions in patients undergoing hereditary nonpolyposis colorectal cancer screening.METHODS:Twenty-five asymptomatic patients fulfilling modified Amsterdam criteria underwent “back-to-back” colonoscopy. Conventional colonoscopy with targeted chromoscopy was performed initially followed by pan-colonic chromoscopic colonoscopy. Diagnostic extubation times and volumes of normal saline and indigo carmine (IC) were controlled.RESULTS:Using conventional colonoscopy and targeted chromoscopy 24 lesions were detected in 13 patients (20 exophytic/4 flat). Pan-colonic chromoscopy identified a further 52 lesions in 16 patients (17 exophytic/35 flat). Pan-chromoscopy identified significantly more adenomas than conventional colonoscopy (p = 0.001) and a significantly high number of flat adenomas (p = 0.004).CONCLUSIONS:Pan-colonic chromoscopic colonoscopy improves detection of significant neoplastic lesions in hereditary nonpolyposis colorectal cancer screening. Pan-chromoscopy may help better stratify colorectal cancer “risk” in this cohort and aid planning of surveillance colonoscopic follow-up.

Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls

Objective. The relationship between coeliac disease and inflammatory bowel disease (IBD) is controversial. The aim of this study was to determine the prevalence of coeliac disease in IBD and the prevalence of IBD in coeliac disease. Material and methods. Patients were enrolled from specialist IBD and coeliac clinics. Antigliadins, endomysial, tissue transglutaminase antibody and total IgA levels were measured in IBD patients. Patients with positive antibodies were offered a duodenal biopsy. The notes on coeliac patients were reviewed for colonoscopic and biopsy findings. Controls were recruited from the local population. Results. The study included 305 patients with coeliac disease, 354 with IBD and 601 healthy controls. The IBD group comprised 154 ulcerative colitis (UC) cases, 173 Crohns disease, 18 indeterminate colitis and 9 cases of microscopic colitis. Forty-seven patients had positive antibodies and 3 had villous atrophy on biopsy. All three patients had positive anti-tissue transglutaminase antibodies but only two were endomysial antibody (EMA) positive. Ten coeliac patients had IBD (5 UC and 5 lymphocytic colitis). Five controls had coeliac disease and 2 had IBD (1 Crohns disease and 1 UC). Stepwise multiple logistic regression showed only antibody positivity as being significant (p<0.0001). Conclusions. The prevalence of IBD in coeliac disease was increased 10-fold compared with that in controls (odds ratio 9.98, 95% CI 2.8–45.9, p=0.0006), while the prevalence of coeliac disease in IBD was comparable with that in controls (odds ratio 1.02, 95% CI, 0.24–4.29, p=1.0).

Less Small-Bowel Injury With Lumiracoxib Compared With Naproxen Plus Omeprazole

BACKGROUND & AIMS The selective cyclooxygenase-2 inhibitor lumiracoxib has been shown to reduce endoscopically detected ulcers and ulcer complications in the upper gastrointestinal tract compared with nonselective nonsteroidal anti-inflammatory drugs. We investigated whether lumiracoxib would reduce small-bowel injury compared with naproxen plus omeprazole. METHODS Healthy volunteers were randomized to receive lumiracoxib 100 mg once daily, naproxen 500 mg twice daily plus omeprazole 20 mg once daily, or placebo in a 16-day double-blind, parallel-group study. Small-bowel mucosal injury and inflammation were assessed by video capsule endoscopy, the lactulose:L-rhamnose permeability assessment, and the fecal calprotectin test. RESULTS Of 152 randomized subjects, 139 completed the study with valid video capsule endoscopies (lumiracoxib, n = 47; naproxen plus omeprazole, n = 45; placebo, n = 47). Compared with placebo, an increased number of subjects on naproxen plus omeprazole had small-bowel mucosal breaks (77.8% vs 40.4%, P < .001), with increased permeability (P = .023) and increased fecal calprotectin (increase, 96.8 vs 14.5 mg/kg for placebo; P < .001). With lumiracoxib, 27.7% of subjects had small-bowel mucosal breaks (P = .196 vs placebo; P < .001 vs naproxen), there was no increase in permeability (P = .157 vs placebo; P = .364 vs naproxen), and no increase in fecal calprotectin (-5.7 mg/kg; P = .377 vs placebo; P < .001 vs naproxen). CONCLUSIONS As assessed by 3 different measures, acute small-bowel injury on lumiracoxib treatment is less frequent than with naproxen plus omeprazole and similar to placebo.

Reflux and irritable bowel syndrome are negative predictors of quality of life in coeliac disease and inflammatory bowel disease.

Background and aim An increased prevalence of reflux and irritable bowel syndrome (IBS) symptoms is associated with coeliac disease and inflammatory bowel disease (IBD). We aimed to determine the prevalence of reflux and IBS symptoms in a cohort of patients with coeliac disease and IBD and their relationship with quality of life (QoL) and psychological distress. Methods Histologically proven coeliac disease (n=225), ulcerative colitis (UC) (n=228), Crohns disease (CD) (n=230) patients and age/sex-matched controls (n=348) completed the Short-Form 36 (SF-36)-Item Health Survey, Hospital Anxiety and Depression Scale (HADS), reflux screen and Rome II criteria. Results UC patients report higher SF-36 (QoL) scores than coeliac disease; CD fairing worse overall (P⩽0.0001). Reflux prevalence: coeliac disease 66%; UC 62%; CD 72%; controls 50%. Patients report reflux of a greater severity: coeliac disease odds ratio=6.8, 95% confidence interval=3.6–12.7, P⩽0.001; IBD odds ratio=2.2, 95% confidence interval=1.6–3.2, P⩽0.0001. Stepwise reductions in SF-36 scores in association with increasing reflux severity were found (P⩽0.0001). IBS prevalence: coeliac disease 22%; UC 16%; CD 24%; controls 6%. Concomitant IBS was associated with reduced SF-36 scores in patients (P⩽0.0001). Conclusion Reflux and IBS are more prevalent in coeliac disease and IBD in comparison with age-matched and sex-matched controls. These additional symptoms are associated with reduced QoL and increasing likelihood of anxiety and depression. QoL may be improved if coeliac disease and IBD patients were assessed for reflux and IBS.

Prospective analysis of percutaneous endoscopic colostomy at a tertiary referral centre.

Percutaneous endoscopic colostomy (PEC) is an alternative to surgery in selected patients with recurrent sigmoid volvulus, recurrent pseudo‐obstruction or severe slow‐transit constipation. A percutaneous tube acts as an irrigation or decompressant channel, or as a mode of sigmoidopexy. This prospective study evaluated the safety and efficacy of this procedure at a single tertiary referral centre.

Making the diagnosis of coeliac disease: is there a role for push enteroscopy?

Background Push enteroscopy is used in the assessment of refractory coeliac disease. However, its value in making the diagnosis of coeliac disease is still not defined. Methods Thirty-one patients (22 females, nine males) were recruited prospectively between September 2001 and October 2002; the age range was 20–80 years (mean age, 52.7 years). All patients had symptoms suggestive of coeliac disease and positive serology but duodenal biopsy was not diagnostic. Twenty-three patients had positive IgA or/and IgG antigliadin antibodies, eight patients had positive endomysial antibodies (EMA). All patients underwent enteroscopy with repeat quadrantic duodenal and additional jejunal biopsies. Results All samples were reviewed by a single, blinded, histopathologist. There were no cases of coeliac disease diagnosed on further biopsy in patients who had a positive gliadin antibody in isolation. In the eight EMA-positive cases repeat biopsy demonstrated coeliac disease in five patients. In 3/5 cases the changes were confined to the jejunal biopsies only. Conclusion EMA-positive patients with initially normal histology should have a further duodenal biopsy. In our series three of the five newly diagnosed coeliac disease patients only had villous atrophy demonstrable in the jejunum. There may be a role for push enteroscopy in making the diagnosis of coeliac disease. However, further prospective studies are needed.