Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
Prevalence, symptoms and risk factor profile of rumination syndrome and functional dyspepsia: a population‐based study
SummaryBackgroundRumination syndrome is a functional gastroduodenal disorder characterised by effortless regurgitation of recently ingested food. Emerging evidence reports duodenal eosinophilic inflammation in a subset, suggesting a shared pathophysiology with functional dyspepsia (FD).AimTo assess the clinical features of rumination syndrome and FD in a community‐based study.MethodsWe mailed a survey assessing gastrointestinal symptoms, diet and psychological symptoms to 9835 residents of Olmsted County, MN, USA in 2017‐2018; diagnostic codes were obtained from linked clinical records. The two disorders were assessed as mutually exclusive in ‘pure’ forms with a separate overlap group, all compared to a control group not meeting criteria for either. Prevalence of associations, and univariate and independent associations with predictors were assessed by logistic regression.ResultsPrevalence of rumination syndrome and FD were 5.8% and 7.1%, respectively; the overlap was 3.83‐times more likely than expected by chance. Independent predictors for rumination (odds ratio (OR), 95% confidence interval (CI)) were female gender (1.79, 1.21‐2.63), smoking (1.89, 1.28‐2.78), gluten‐free diet (1.58, 1.14‐2.19), allergic rhinitis (1.45, 1.01‐2.08) and depression (1.10, 1.05‐1.16). FD was independently associated with female gender, depression, non‐coeliac wheat sensitivity, migraine, irritable bowel syndrome and somatic symptoms. A similar reported efficacy (≥54%) of low fat or dairy‐free diets was found with both disorders (P = 0.53 andP = 1.00, respectively). The strongest independent associations with overlapping FD and rumination syndrome were a history of rheumatoid arthritis (3.93, 1.28‐12.06) and asthma (3.02, 1.44‐6.34).ConclusionRumination syndrome overlaps with FD with a shared risk factor profile, suggesting a common pathophysiology.
Outcome measures in coeliac disease trials: the Tampere recommendations
Objective A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures. Design Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed. Results We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease. Conclusion Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.
Transition from childhood to adulthood in coeliac disease: the Prague consensus report
The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.
Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.