Peter D. Mooney

Neurological Dysfunction in Coeliac Disease and Non-Coeliac Gluten Sensitivity

Objectives:Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefit from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS.Methods:We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years.Results:Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confirm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identified no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%).Conclusions:The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms.

Cost and availability of gluten-free food in the UK: in store and online

Objective Coeliac disease (CD) is a lifelong condition requiring strict adherence to a gluten-free (GF) diet and good availability of GF foods is critical to this. Patients with CD from lower socioeconomic groups are recognised to have higher treatment burden and higher food costs may impact this. Therefore, we aimed to assess the availability and cost of GF food in supermarkets and via the internet. Design Supermarkets and internet shops delivering to homes in a single city (UK) were analysed between February and March 2014. Stores were identified with comprehensive internet searches. Ten commonly purchased items were analysed for cost and compared with standard non-GF alternatives. Direct measurement of the number of GF foods available was compared between stores which were categorised according to previously published work. Setting Supermarkets covering the whole of Sheffield, UK. Results None of the budget supermarkets surveyed stocked any GF foods. Quality and regular supermarkets stocked the greatest range, each stocking a median of 22 (IQR 39) items (p<0.0001). All GF foods were at least four times more expensive than non-GF alternatives (p<0.0001). GF products are prevalent online, but 5/10 of the surveyed products were significantly more expensive than equivalents in supermarkets. Conclusions There is good availability of GF food in regular and quality supermarkets as well as online, but it remains significantly more expensive. Budget supermarkets which tend to be frequented by patients from lower socioeconomic classes stocked no GF foods. This poor availability and added cost is likely to impact on adherence in deprived groups.

Increased Detection of Celiac Disease With Measurement of Deamidated Gliadin Peptide Antibody Before Endoscopy

BACKGROUND & AIMS Celiac disease is underdiagnosed. Many patients are examined by endoscopy, but celiac disease is missed or not detected. We evaluated the accuracy of finger prick-based point-of-care tests in the detection of celiac disease and developed an algorithm for diagnosis. METHODS We performed a prospective study of 2 groups of patients with celiac disease evaluated at the Royal Hallamshire Hospital in Sheffield (United Kingdom) from March 2013 through February 2014. In group 1, patients at high risk of celiac disease who tested positive for endomysial antibody (n = 55) were evaluated using the Biocard test (BHR Pharmaceuticals, Nuneaton, UK) and the Celiac Quick Test (Biohit Healthcare UK, Ellesmere Port, UK), which measure antibodies to tissue transglutaminase (anti-tTG), and the Simtomax test (Tillotts Pharma, Rheinfelden, Switzerland), which measures deamidated gliadin peptide antibodies (DGP). Patients in group 2 (508 consecutive patients who underwent an endoscopy examination for any indication) received the DGP test, and also were evaluated using a diagnostic algorithm that incorporated results from the DGP test and data on symptoms. In both groups, point-of-care tests were taken at the time of endoscopy and results were compared with results from histologic analyses of duodenal biopsy specimens from all patients. RESULTS In group 1, the DGP test identified patients with celiac disease with 94.4% sensitivity, the Celiac Quick Test identified patients with 77.8% sensitivity (P = .03 vs the DGP test), and the Biocard test identified patients with 72.2% sensitivity (P = .008 vs the DGP test). In group 2, the DGP test identified patients with celiac disease with 92.7% sensitivity (95% confidence interval, 83.0-97.3), 85.2% specificity (95% confidence interval, 81.5-88.3), a positive predictive value of 49.2% (95% confidence interval, 40.3-58.2), and a negative predictive value of 98.7% (95% confidence interval, 96.8-99.5). Measurement of serum anti-tTG identified patients with celiac disease with 91.2% sensitivity (95% confidence interval, 81.1-96.4), 87.5% specificity (95% confidence interval, 84.0-90.4), a positive predictive value of 53.0% (95% confidence interval, 43.6-62.2), and a negative predictive value of 98.5% (95% confidence interval, 96.5-99.4). The algorithm identified patients with celiac disease with 98.5% sensitivity; its use could reduce duodenal biopsies by 35%. CONCLUSIONS In a prospective study, a test for DGP identified patients with celiac disease with similar levels of sensitivity and specificity as standard serologic analysis of anti-tTG. Use of the DGP test before endoscopy could increase the accuracy of the diagnosis of celiac disease. Further studies, in lower-prevalence populations, are required to assess the impact of the test in clinical practice.

Non‐celiac gluten sensitivity: clinical relevance and recommendations for future research

There has been increasing interest in the entity of Non‐Celiac Gluten Sensitivity (NCGS) in recent years; however, it still remains a controversial topic and its pathogenesis is not well understood. Celiac Disease, in contrast, is a well‐studied condition that has become increasingly recognized as a prevalent condition arising from a heightened immunological response to gluten. Wheat allergy is an IgE‐mediated condition capable of causing a variety of gastrointestinal symptoms. However, the number of patients who have neither celiac disease nor wheat allergy, but appear to derive benefit from a gluten‐free diet, is also increasing substantially. The use of the term NCGS as a way of describing this condition has become increasingly prevalent in recent years.

Prevalence, investigational pathways and diagnostic outcomes in differing irritable bowel syndrome subtypes.

Background There has been increasing interest in subclassifying irritable bowel syndrome (IBS) to make a positive diagnosis. Aim The aim of this study was to assess the population prevalence of differing subtypes, investigational pathways and diagnostic outcomes. Materials and methods Data were prospectively collected from three groups between 2005 and 2012. Group 1 [n=1002, 55% female, mean age 39 years (range 16–93 years)] comprised healthy volunteers who were interviewed using the Rome III diagnostic questionnaire. In secondary care, group 2 [n=64, 80% female, mean age 44 years (range 23–79 years)] comprised patients with constipation-predominant IBS (IBS-C) and group 3 [n=333, 66% female, mean age 51 years (range 23–92 years)] comprised patients with diarrhoea-predominant IBS (IBS-D). In groups 2 and 3, demographic data and diagnostic yield of investigations were evaluated as per normal clinical practice. Results IBS prevalence in group 1 was 6% (60/1002). IBS-C patients were significantly older than those with IBS-D (mean age 45 vs. 30 years, P=0.027). In groups 2 and 3, patients with IBS-C underwent a total of 56 additional investigations (mean 0.88 per patient), which was significantly lower than the number of investigations undertaken in the IBS-D group of 734 (mean 2.2 per patient, P<0.001). Further investigations in group 3 (IBS-D) identified an alternative diagnosis in 22%, whereas in group 2 (IBS-C) this was 0% (P<0.0001). Conclusion This is the first study to evaluate the population prevalence of different IBS subtypes within a UK population. Although further investigations in IBS-D patients have led to alternative diagnoses, none were identified in the IBS-C population. The merits of investigating IBS-C patients should be questioned.

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.

Simtomax, a novel point of care test for coeliac disease

INTRODUCTION Coeliac disease is an autoimmune condition resulting from an abnormal reaction to dietary gluten leading to small bowel villous atrophy. International prevalence studies suggest that coeliac disease affects 1% of the adult population. However, despite its high prevalence, large numbers of patients go undiagnosed. One method of increasing detection rates would be to introduce a quick screening test in the form of a finger-prick blood test. AREAS COVERED There are currently four available point-of-care tests (POCTs) available for use by health professionals. This diagnostic evaluation will review the evidence for the use of POCTs in coeliac disease including Simtomax a novel test for deamidated gliadin peptides and total IgA level. EXPERT OPINION An accurate POCT has the potential to increase the rates of diagnosis of coeliac disease if used effectively as part of a case finding approach in primary or secondary care. Evidence for the use of Simtomax is currently fairly limited only drawing comparison with laboratory serology rather than the gold standard of histology and it has only been trialled in high-risk populations. However, results to date are encouraging and further research into this area is required.

Emerging drugs for coeliac disease

Introduction: Coeliac disease is an autoimmune gluten sensitive enteropathy and is now known to affect 1% of the adult population. A gluten-free diet (GFD) should be curative; however, up to 30% of patients have persistent symptoms and many patients find the diet difficult to fully adhere to. Currently, there are no licensed therapeutic options for patients with coeliac disease outside of a GFD. Areas covered: This review will outline the case for alternative treatments and discuss the potential therapeutic targets. The products in the most advanced stage of development will be discussed in detail. Expert opinion: There is clearly an unmet need for alternatives to a GFD for the treatment of coeliac disease. Oral glutenase supplements to improve the degradation of gluten into non-toxic peptides appear to be the most likely to provide a breakthrough in the treatment of coeliac disease; however, other modalities such as a therapeutic vaccine or zonulin inhibitors to reduce intestinal permeability have shown promising results.

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.