New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Infection and inflammation stimulate expansion of a CD74+ Paneth cell subset to regulate disease progression.

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 2015.

OBJECTIVES: To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation. DESIGN: Nationwide population-based cohort study 1990-2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum. RESULTS: We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002-2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males).Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa. CONCLUSIONS: In Sweden, the incidence of CD increased until 2002-2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.

Navigating celiac disease and the gluten-free diet in China.

BACKGROUND: Little is known about celiac disease (CeD) diagnosis and management in China. AIM: This pilot aimed to be the first study to describe, quantitatively and qualitatively, how individuals living in China navigate CeD and the gluten-free diet (GFD). METHODS: Participants were 13 adults and four parents of children with reported CeD, recruited from 11 mainland China cities via an online GFD support group. CeD-specific quality of life (CD-QOL and CD-PQOL) and diet adherence (CDAT) were assessed. In-depth interviews addressed experiences with CeD and the GFD. RESULTS: Six of 17 participants reported biopsy- or serology-confirmed CeD. The mean (SD) adult CDAT score was 15.2 (3.6), > 13 indicating inadequate GFD adherence. The mean adult CD-QOL score was 62.1 (24.1) out of 100, in the "medium" to "good" range. Results were similar in children. Major interview themes included: (1) a challenging journey to obtain diagnosis; (2) social and structural barriers to maintaining the GFD; and (3) reliance on self in management of CeD. CONCLUSION: Obtaining a diagnosis, maintaining a GFD, and living with CeD can be extremely challenging in mainland China. Results suggest an urgent need for CeD-specific education and Asian-adapted GFD guidance for both healthcare practitioners and patients.

Mucosal healing and the risk of serious infections in patients with celiac disease.

BACKGROUND: Patients with celiac disease (CD) are at increased risk of certain infections, but it is unknown if mucosal healing influences this risk. METHODS: We collected data on 29,096 individuals with CD (equal to villous atrophy) through Sweden's 28 pathology departments undergoing biopsy 1969-2008. Through the Swedish Patient Register we obtained information on any infection and specifically sepsis, streptococcal infection, influenza, Clostridium difficile, herpes zoster and pneumococcal infection up until December 2009. We used Cox regression to calculate hazard ratios (HRs) for the risk of future diagnosis of infection according to mucosal healing on follow-up biopsy (persistent villous atrophy vs mucosal healing). RESULTS: Of 5598 CD individuals with no record of any infections before follow-up biopsy, 45% had persistent villous atrophy, 619 (24%) of them had a later infection, compared to 579 (19%) in those with mucosal healing (p < 0.01); the yearly incidence was 2.1% in both groups. Adjusting for age, sex, calendar period, time between biopsies and education, persistent villous atrophy was however not associated with later infection overall (HR = 0.99; 95% CI = 0.88-1.11) or with any of the specific infections. CONCLUSIONS: In CD, mucosal healing does not influence the risk of serious infection requiring hospital-based medical attention.

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.

Outcome of breath tests in adult patients with suspected small intestinal bacterial overgrowth.

AIM: The aim was to investigate breath test outcomes in patients with suspected SIBO and indicative symptoms of SIBO, diagnosed by breath testing. BACKGROUND: Breath testing is used to detect small intestinal bacterial overgrowth (SIBO) by measuring hydrogen and methane produced by intestinal bacteria. METHODS: This retrospective cross sectional study included 311 patients with gastrointestinal symptoms who underwent the breath test for evaluation of SIBO at Celiac Disease Center at Columbia University, New York, in 2014-2015. The patients were divided into two groups based on the physician's choice: lactulose breath test group (72%) and glucose breath test group (28%). Among them, 38% had a history of celiac disease or non-celiac gluten sensitivity. RESULTS: In total, 46% had a positive breath test: 18% were positive for methane, 24 % positive for hydrogen and 4% positive for both gases (p=0.014). Also, 50% had a positive lactulose breath result and 37% had a positive glucose breath result (p=0.036). The most common symptom for performing the breath test was bloating and the only clinical symptom that significantly showed a positive glucose breath test was increased gas (p=0.028). CONCLUSION: Lactulose breath test was more often positive than glucose breath test. Positivity for hydrogen was more common than methane. Bloating was the most frequently perceived symptom of the patients undergoing the breath test but the only statistically significant clinical symptom for a positive glucose breath test was increased gas. Furthermore, the results showed that there was no significant association between positive breath test result and gender, age, non-celiac gluten sensitivity or celiac disease.

Commercially available glutenases: a potential hazard in coeliac disease.

BACKGROUND: The only treatment for celiac disease (CD) is a gluten-free diet (GFD). However, there is interest among patients in a medical therapy to replace or help with a GFD. Therapies include gluten-degrading enzymes (glutenases). There are glutenases available marketed as dietary supplements that have not been demonstrated to digest the toxic epitopes of gluten. METHODS: We investigated the contents, claims, and disclaimers of glutenase products and assessed patient interest using Google AdWords to obtain Google search frequencies. RESULTS: Among 14 glutenase product, all contained proteases, eight contained X-prolyl exopeptidase dipeptidyl peptidase IV, two did not state the protease contents, and eight failed to specify the name or origin of all proteases. Eleven contained carbohydrases and lipases and three probiotics. One declared wheat and milk as allergens, two contained herbal products (type not stated) and one Carica papaya. Thirteen claimed to degrade immunogenic gluten fragments, four claimed to help alleviate gastrointestinal symptoms associated with eating gluten. Disclaimers included not being evaluated by the US Food and Drug Administration and products not intended to diagnose, treat, cure, or prevent any disease. On Google AdWords, the search frequency for the product names and the search terms was 3173 searches per month. CONCLUSIONS: The names of these products make implicit claims that appear to be supported by the claims on the labels and websites for which there is no scientific basis. Google search data suggest great interest and therefore possible use by patients with CD. There needs to be greater oversight of these 'drugs'.

Classification of videocapsule endoscopy image patterns: comparative analysis between patients with celiac disease and normal individuals.

BACKGROUND: Quantitative disease markers were developed to assess videocapsule images acquired from celiac disease patients with villous atrophy, and from control patients. METHOD: Capsule endoscopy videoclip images (576 x 576 pixels) were acquired at 2/second frame rate (11 celiacs, 10 controls) at regions: 1. bulb, 2. duodenum, 3. jejunum, 4. ileum and 5. distal ileum. Each of 200 images per videoclip (= 100s) were subdivided into 10 x 10 pixel subimages for which mean grayscale brightness level and its standard deviation (texture) were calculated. Pooled subimage values were grouped into low, intermediate, and high texture bands, and mean brightness, texture, and number of subimages in each band (nine features in all) were used for quantifying regions 1-5, and to determine the three best features for threshold and incremental learning classification. Classifiers were developed using 6 celiac and 5 control patients' data as exemplars, and tested on 5 celiacs and 5 controls. RESULTS: Pooled from all regions, the threshold classifier had 80% sensitivity and 96% specificity and the incremental classifier had 88% sensitivity and 80% specificity for predicting celiac versus control videoclips in the test set. Trends of increasing texture from regions 1 to 5 occurred in the low and high texture bands in celiacs, and the number of subimages in the low texture band diminished (r(2) > 0.5). No trends occurred in controls. CONCLUSIONS: Celiac videocapsule images have textural properties that vary linearly along the small intestine. Quantitative markers can assist in screening for celiac disease and localize extent and degree of pathology throughout the small intestine.

Celiac sprue (the great modern-day imposter).

PURPOSE OF REVIEW: To review the current epidemiological information on celiac disease and the various presentations and associated. RECENT FINDINGS: Epidemiologic studies reveal celiac disease to be common, occurring in approx. 1% of the population. It is being diagnosed worldwide, even in developing countries. The classic mode of presentation has become less common, with diarrhea or a malabsorption syndrome as the mode of presentation in fewer than 50% of individuals. The other major modes of presentation are iron-deficiency anemia, osteoporosis, screening of family members, or incidentally at endoscopy done for dyspepsia or reflux. Neurological presentations may include peripheral neuropathy or ataxia. Arthritis is commonly found in patients with celiac disease when systematically sought. Patients often have a previous diagnosis of irritable bowel syndrome. Autoimmune diseases occur more frequently (three to ten times more) in those with celiac disease than the general population. However, this increased incidence of autoimmune diseases is not prevented by early diagnosis of celiac disease. SUMMARY: We will review the various associated diseases/presentations of celiac disease. The heterogeneity of the symptoms can make the diagnosis challenging and certainly the great modern-day imposter.