K E Evans

A prospective study into the aetiology of lymphocytic duodenosis

Aliment Pharmacol Ther 2010; 32: 1392–1397

Bile acid malabsorption: An under-investigated differential diagnosis in patients presenting with diarrhea predominant irritable bowel syndrome type symptoms

Abstract Objective. Bile acid malabsorption (BAM) has been reported as a possible cause of diarrhea predominant irritable bowel syndrome (D-IBS) type symptoms. We aimed to determine how commonly patients with D-IBS type symptoms had a diagnosis of BAM as demonstrated by a positive SeHCAT (75 Selenium-homocholic acid taurine) test (retention <10% at seven days). Materials and methods. A retrospective analysis was undertaken of patients records for all patients who underwent a SeHCAT test between 2001 and 2009 in a tertiary hospital (Group A). Concurrently, a cohort of patients with Rome II D-IBS type symptoms was examined to determine the potential utility of SeHCAT test (Group B). Results. In Group A 39.2% (n = 107/273) of patients had a positive SeHCAT result. The median time from first hospital visit to SeHCAT result was 30 weeks. Predictive factors for BAM: terminal ileal Crohns disease (p < 0.01), terminal ileal resection (p < 0.01), and previous cholecystectomy (p < 0.01). 33.6% of patients who had a positive SeHCAT also had Rome II D-IBS. In Group B the D-IBS control cohort only 1.9% of patients had undergone a SeHCAT scan (p < 0.001 compared to Group A). Conclusion. BAM is common and should be considered earlier when investigating unselected patients with D-IBS type symptoms.

Capsule endoscopy in adult celiac disease: a potential role in equivocal cases of celiac disease?

BACKGROUND There have been limited studies evaluating capsule endoscopy (CE) in equivocal celiac disease (CD). OBJECTIVE To determine the role CE may have in equivocal CD cases, compared with patients with biopsy-proven and serology-proven CD who have persisting symptoms. DESIGN Prospective cohort study. SETTING University hospital. PATIENTS A total of 62 patients with equivocal CD and 69 patients with nonresponsive CD. INTERVENTION CE. MAIN OUTCOME MEASUREMENTS Diagnostic yield of CE in equivocal cases and accuracy of mucosal abnormality detection in patients with nonresponsive CD. RESULTS Equivocal cases (n = 62) were divided into two subgroups: group A (antibody-negative villous atrophy, n = 32) and group B (Marsh 1-2 changes, n = 30). In group A, CE secured a diagnosis of CD or Crohns disease in 28% (9/32), significantly higher than the diagnostic yield in group B (7%; P = .044). In patients with CD with persisting symptoms, significant CE findings were identified in 12% (8/69), including 2 cases of enteropathy-associated lymphoma, 4 type 1 refractory disease cases, 1 polypoidal mass histologically confirmed to be a fibroepithelial polyp, and 1 case of ulcerative jejunitis. This outcome was significantly lower than the diagnostic yield of CE in antibody-negative villous atrophy (P = .048). LIMITATIONS Single center. CONCLUSION There have been no previous reports systematically evaluating equivocal CD by using CE. The diagnostic yield of CE in patients with antibody-negative villous atrophy is better than that of CE in patients with CD with persisting symptoms. We advocate the use of CE in equivocal cases, particularly in patients with antibody-negative villous atrophy.

Is it time to screen for adult coeliac disease

To meet the principles of screening as described by Wilson and Jungner a disease must be common, a significant health burden, detectable and treatable. The key lies in the early detection and alteration of the natural history of disease. Coeliac disease affects 1 in 100 people. Despite this patients frequently have delays in diagnosis or may remain undetected. There is an associated morbidity and mortality which can be effectively treated by simple means of a gluten-free diet. For these reasons coeliac disease has been suggested as appropriate for mass screening. However, there are caveats to this: a complex clinical spectrum, a natural history that is imperfectly understood, overestimation of morbidity and mortality, poor adherence to treatment, and costs of service provision may argue against the time being right for mass screening. This review article provides the most contemporary overview and reference base to allow any clinician to understand the benefits or limitations of a screening programme for adult coeliac disease.

Point-of-care testing for celiac disease has a low sensitivity in endoscopy

BACKGROUND Celiac disease (CD) is a common but underdiagnosed condition. A rapid point-of-care test (POCT) could reduce lead times and missed diagnoses. OBJECTIVE To assess the utility of an immunoglobulin (Ig) A tissue transglutaminase (TTG) antibody POCT in an endoscopic setting. DESIGN Prospective observational study. SETTING A single UK university hospital. PATIENTS Patients presenting with suspected CD, known CD, and routine endoscopy for upper GI symptoms. INTERVENTIONS All patients were tested with POCT, serum TTG, endomysial antibody (EMA), and upper GI endoscopy with duodenal biopsies at the same visit. MAIN OUTCOME MEASUREMENTS Comparison was made with histology in all cases, with villous atrophy regarded as diagnostic of CD. RESULTS A total of 576 patients (63.5% female, mean [± standard deviation] age 49.7 years [± 17.6 years]) were recruited. A total of 523 patients had no prior diagnosis of CD, and 53 patients had known CD coming for reassessment. A total of 117 patients were newly diagnosed with CD, and 82 were positively identified by the POCT. Sensitivity, specificity, positive predictive value, and negative predictive value were 70.1%, 96.6%, 85.4%, and 91.8%, respectively. In comparison, TTG and EMA both performed significantly better than the POCT. Sensitivity and specificity of TTG were 91.0% and 83.5%, respectively, and EMA were 83.8% and 97.5%, respectively. Of patients with known CD coming for reassessment, 26 had villous atrophy, and POCT results were positive in 16 (61.5%). There was poor agreement between POCT and standard serology. LIMITATIONS High pre-test probability of CD. CONCLUSION The performance of this POCT was disappointing compared with standard serology and cannot at present be recommended within the context of an endoscopy unit.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

BACKGROUND Coeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics. METHODS Unselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors. RESULTS 4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk. CONCLUSIONS Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted.

Symposium 1: Joint BAPEN and British Society of Gastroenterology Symposium on 'Coeliac disease: basics and controversies' Coeliac disease: optimising the management of patients with persisting symptoms?

The vast majority of patients with coeliac disease will derive benefit from a gluten-free diet. However, some patients will not improve on the gluten-free diet or they will have a relapse of their symptoms. The present review will focus on this group of patients. Definitions for non-responsive coeliac disease and refractory coeliac disease will be provided. The most common reason for recurrent symptoms is continued gluten exposure. Other causes of persisting symptoms are discussed, including alternative causes of villous atrophy or co-existent pathology. Current literature is reviewed, including an initial investigation strategy for patients with persisting symptoms. A pragmatic management plan is described that can be initiated by any clinician. Finally, the current optimal investigational pathway for patients with refractory (or suspected refractory) coeliac disease is discussed and the reported effects of a number of therapeutic options are summarised. The aim of the present article is to provide clinicians with an up-to-date review of the literature in this clinical field and allow them to determine the most appropriate management strategy.

Letter: coeliac disease and small intestinal bacterial overgrowth ‐ is dysmotility the missing link?

cation breath test) and that the prevalence of the intolerances is similar across all major FGIDs. Most importantly, we demonstrate that in excess of 80% of patients with FGIDs identified as fructose and/or lactose intolerant with the described testing protocol achieve adequate symptom relief with dietary modification. This clearly supports the usefulness of the test protocol chosen and invalidates the presumption of ‘virtual intolerance’ due to a ‘high sugar dose’. These high response rates to dietary modification provide the most effective symptom relief currently available to FGID patients, even if the mechanisms involved are likely to include cognition, the microbiome, immune activation and sensation (‘braingut-microbiome axis’), among others. Future research should clarify the interactions between these interdependent underlying mechanisms in FGID. The breath tests, while requiring further refining, are clearly an interim phase until our mechanistic understanding is clearer.

Gastro-oesophageal reflux symptoms and coeliac disease: no role for routine duodenal biopsy.

Background Coeliac disease (CD) has been linked to gastro-oesophageal reflux disease (GORD). Previous studies have demonstrated an increased prevalence of reflux in patients with CD. However data on the risk for CD in patients presenting with reflux are conflicting. Aims The aim of this study was to establish the prevalence of CD in patients with GORD and to elucidate the mechanisms for reflux symptoms in newly diagnosed CD patients. Methods Group A: patients who had undergone routine duodenal biopsy were prospectively recruited between 2004 and 2014. Diagnostic yield was compared with that of a screening cohort. Group B: 32 patients with newly diagnosed CD who had undergone oesophageal manometry and 24-h pH studies were prospectively recruited. Results Group A: 3368 patients (58.7% female, mean age 53.4 years) underwent routine duodenal biopsy. Of these patients, 850 (25.2%) presented with GORD. The prevalence of CD among GORD patients was 1.3% (0.7–2.4%), which was not significantly higher than that in the general population (P=0.53). Within the context of routine duodenal biopsy at endoscopy (when corrected for concurrent symptoms, age and sex), reflux was found to be negatively associated with CD [adjusted odds ratio 0.12 (0.07–0.23), P<0.0001]. In group B, 34% of patients complained of reflux. On manometry, 9% had a hypotensive lower oesophageal sphincter and 40.6% had oesophageal motor abnormalities, with 25% significantly hypocontractile. On pH studies, 33% demonstrated reflux episodes. Conclusion The prevalence of undiagnosed CD among GORD patients is similar to that in the general population, and routine duodenal biopsy cannot be recommended. A significant number of patients with newly diagnosed CD were found to have reflux and/or oesophageal dysmotility on pH/manometry studies; this may explain the high prevalence of reflux symptoms in CD.

Re: “Decreased Risk of CEliac Disease in Patients With Helicobacter Pylori Colonization”

Although their fascinating work supports this model, there may be other models to consider. It is not clear whether patientshave CD from birth, but we do knowthat the mostcommon age for presentation is during the fourth or fifth decade of life (4). Could infection play another role? Our group conducted a 2-part study that may provide evidence to support the “second hit” hypothesis. This hypothesis postulates that, in addition to a genetic predisposition, an environmental trigger is required to initiate the autoimmune process (5). In the first part of the study, we investigated 101 patients (48 men; median age, 57 years) with stool culture– proven bacterial gastroenteritis (95% Campylobacter species) for CD. All patients underwent tissue transglutaminase and endomysial antibody testing, and if either test was positive, we performed a small-bowel biopsy. The prevalence of CD was higher in this group of patients than in a healthy control group (2.97% vs. 1%, P = 0.10). In the second part of our study, we used a validated questionnaire (6) to assess patients with CD or inflammatory bowel disease, as well as healthy controls. A total of 69 of 233 (29.6%) patients with CD and 53 of 196 (27.1%) patients with inflammatory bowel disease self-reported having a gastrointestinal infection within the 12 months prior to diagnosis. In both diseases, this rate was significantly greater than in healthy controls (15 of 219 (6.8%) patients) (P < 0.0001). The role of infection in the development of CD and other autoimmune conditions is complex (3). Circumstantial evidence exists for both the protective and deleterious consequences of gastrointestinal infection, and further work is required to delineate more clearly the role of different pathogens in the development of CD. ACKNOWLEDGMENTS