Exclusion Of Coeliac Disease Research Articles

DQA1*0102 DQB1*0602 haplotype distinguishes coeliac disease and its complications from gluten unrelated enteropathies.

Duodenal villous atrophy is due not only to coeliac disease and its complications but also to other rare enteropathies unrelated to gluten consumption, defined as noncoeliac enteropathies. The diagnosis of noncoeliac enteropathies remains challenging, and HLA typing has been widely used to exclude coeliac disease if DQ2 and DQ8 alleles are absent. However, the frequency of the various HLA alleles in noncoeliac enteropathies is still unknown. To describe the HLA genetic profile of patients affected by noncoeliac enteropathies who have been evaluated at our centres between 2000 and 2021, and to investigate the diagnostic role of HLA typing. Genomic DNA was collected from 44 Italian and 19 British adult patients with noncoeliac enteropathies. Patient genotypes were compared with those of healthy Italian and British populations obtained from HLA bone marrow donors' banks. In addition, genotypes were also compared with those of patients with coeliac disease and complicated coeliac disease. Both in the Italian and in the British group, the DQA1*0102 DQB1*0602 haplotype and related alleles occurred significantly more frequently in patients with noncoeliac enteropathies compared to coeliac disease and complicated coeliac disease. Together with negative HLA-DQ2 and DQ8 haplotypes, the DQA1*0102 DQB1*0602 haplotype can be used to guide the differential diagnosis between coeliac disease and noncoeliac enteropathies.

Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity

ObjectiveNon-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers...

Noncoeliac wheat sensitivity and diet.

Noncoeliac gluten sensitivity (NCGS) can be suspected after exclusion of coeliac disease and wheat allergy. However, poorly understood pathogenesis of the NCGS, lack of gold standard for diagnosis and agreement in the definition for the NCGS condition, open the space for future investigation. This review aims to give an overview on the diagnosis and effective diet composition in the treatment of NCGS symptoms. It appears that a diet low in fermentable oligo, di, and monosaccharides and polyols (FODMAPs) and gluten-free diet play a prominent role in the strategy of NCGS management. Considering available evidence with respect to diagnostic tools, it is challenging to prepare a standard guideline for NCGS diagnosis and treatment with clear cut-offs for symptom reduction/improvement that could directly be translated into test results. Nutritional support, including the use of pre/probiotics, has to be tailored to the individual situation of NCGS patients. The exclusion of such components of wheat as amylase/trypsin inhibitors, wheat-germ agglutinins, or free of FODMAPs diet can reduce clinical symptoms of NCGS. The further investigation on microbiota changes may strengthen the knowledge in this area, where the major challenge is to develop biomarkers for NCGS investigation.

Associations between migraine, celiac disease, non-celiac gluten sensitivity and activity of diamine oxidase

Background and pilot studyRecent reports reveal a close relationship between migraine and gastrointestinal disorders (GI), such as celiac disease (CD) and non-celiac gluten sensitivity (NCGS). CD is a genetic autoimmune disorder, which affects the mucosa of the small intestine. Gluten, found in various grains, not only plays a major role in the pathophysiology of CD and NCGS, but also aggravates migraine attacks. Another common food component, which can induce migraine headaches, is histamine. Diamine oxidase (DAO) is an enzyme, which degrades histamine. Reduced activity of DAO means reduced histamine degradation, which can cause histamine build-up and lead to various symptoms, including headaches and migraine. In this paper we propose a hypothesis, that in pathogenesis of migraine, low serum DAO activity is related to CD and NCGS. We also conducted our own pilot study of 44 patients with severe migraine in efforts to evaluate the co-presence of decreased serum DAO activity and celiac disease/NCGS in patients. 44 consecutive migraine patients were divided into 2 groups: decreased DAO activity (group 1; n = 26) and normal DAO activity (group 2; n = 18). All patients were screened for celiac disease. The diagnosis of NCGS was made after exclusion of CD, food allergies and other GI disorders in the presence of gluten sensitivity symptoms. Furthermore, dietary recommendations were given to all participants and their effects were assessed 3 months after the initial evaluation via the MIDAS (Migraine Disability Assessment) questionnaire. Results and conclusionsOnly 1 patient fit the criteria for celiac disease, rendering this result inconclusive. Pathological findings of the remainder of patients were attributed to NCGS (n = 10). 9 of 10 patients with NCGS belonged to the decreased serum DAO activity group (group 1; n = 26), suggesting a strong relationship between reduced serum DAO activity and NCGS. MIDAS questionnaire revealed, that patients with decreased serum DAO activity were more severely impacted by migraine than those with normal DAO activity, and this remained so after our interventions. Dietary adjustments significantly reduced the impact of migraine on patients’ daily activities after 3 months in both groups. We argue, that migraine, celiac disease and NCGS may benefit from treatment with a multidisciplinary approach, involving neurologists, gastroenterologists and dietitians.

Diseases Producing Malabsorption and Maldigestion

Malabsorption refers to the impaired intestinal absorption of nutrients. It can result from congenital defects in absorption and the transport of ions and nutrients, defects in hydrolysis within the intestinal lumen, acquired defects in the intestinal absorptive cells that line the surface of the intestine, impaired bile production, or interruption of enterohepatic circulation or secondary to pancreatic insufficiency. Maldigestion, another factor in nutrient absorption, refers to the impaired digestion of nutrients within the intestinal lumen or at the terminal digestive site of the brush border membrane of mucosal epithelial cells. Although malabsorption and maldigestion are pathophysiologically distinct, they are interdependent, and in clinical practice, malabsorption has come to signify derangements in either or both processes. This chapter discusses the clinical manifestations of malabsorption and tests for suspected malabsorption. The diseases that can cause malabsorption, their diagnosis, and treatment recommendations are included. Figures illustrate the diagnosis and management of celiac disease; an approach to gluten challenge for the diagnosis or exclusion of celiac disease in patients maintained on a gluten-free diet without previous definitive diagnostic testing; and the histologic features of celiac disease, Crohn disease, collagenous sprue, autoimmune enteropathy, eosinophilic gastritis, and intestinal lymphangiectasia. This review contains 9 figures, 25 tables, and 116 references. Keywords: Malabsorption, maldigestion, Crohn disease, celiac disease, tropical sprue, diarrhea, endoscopy, short bowel syndrome, bacterial overgrowth

Diseases Producing Malabsorption and Maldigestion

Malabsorption refers to the impaired intestinal absorption of nutrients. It can result from congenital defects in absorption and the transport of ions and nutrients, defects in hydrolysis within the intestinal lumen, acquired defects in the intestinal absorptive cells that line the surface of the intestine, impaired bile production, or interruption of enterohepatic circulation or secondary to pancreatic insufficiency. Maldigestion, another factor in nutrient absorption, refers to the impaired digestion of nutrients within the intestinal lumen or at the terminal digestive site of the brush border membrane of mucosal epithelial cells. Although malabsorption and maldigestion are pathophysiologically distinct, they are interdependent, and in clinical practice, malabsorption has come to signify derangements in either or both processes. This chapter discusses the clinical manifestations of malabsorption and tests for suspected malabsorption. The diseases that can cause malabsorption, their diagnosis, and treatment recommendations are included. Figures illustrate the diagnosis and management of celiac disease; an approach to gluten challenge for the diagnosis or exclusion of celiac disease in patients maintained on a gluten-free diet without previous definitive diagnostic testing; and the histologic features of celiac disease, Crohn disease, collagenous sprue, autoimmune enteropathy, eosinophilic gastritis, and intestinal lymphangiectasia. This review contains 9 figures, 25 tables, and 116 references. Keywords: Malabsorption, maldigestion, Crohn disease, celiac disease, tropical sprue, diarrhea, endoscopy, short bowel syndrome, bacterial overgrowth

Non celiac gluten sensitivity and diagnostic challenges.

Non-celiac gluten sensitivity (NCGS), also referred to as non-celiac wheat sensitivity (NCWS), is a clinical syndrome characterized by both intestinal and extra-intestinal symptoms responsive to the withdrawal of gluten-containing food from the diet. The aim of this review is to summarize recent advances in research and provide a brief overview of the history of the condition for the benefit of professionals working in gastroenterology. Academic databases such as PubMed and Google Scholar were searched using key words such as "non-celiac gluten sensitivity", "gluten related disorders", and the studies outlined in reference page were selected and analysed. Most of the analysed studiers agree that NCGS would need to be diagnosed only after exclusion of celiac disease and wheat allergy, and that a reliable serological marker is not available presently. The mechanisms causing symptoms in NCGS after gluten ingestion are largely unknown, but recent advances have begun to offer novel insights. The estimated prevalence of NCGS, at present, varies between 0.6 and 6%. There is an overlap between irritable bowel syndrome and NCGS with regard to the similarity of gastrointestinal symptoms. The histologic characteristics of NCGS are still under investigation, ranging from normal histology to slight increase in the number of T lymphocytes in the superficial epithelium of villi. Positive response to gluten free diet for a limited period (e.g., 6 weeks), followed by the reappearance of symptoms after gluten challenge appears, at this moment, to be the best approach for confirming diagnosis. The Salerno expert criteria may help to diagnose NCGS accurately in particular for research purposes but it has limited applicability in clinical practice.

Random duodenal biopsy to exclude coeliac disease as a cause of anaemia is not cost-efective and should be replaced with universally performed pre-endoscopy serology in patients on a suspected cancer pathway

BackgroundRandom duodenal biopsy to exclude coeliac disease during upper gastrointestinal endoscopy for the investigation of iron deficiency anaemia remains a common procedure, but is expensive and time-consuming. Serological investigation for coeliac disease is also recommended, having excellent accuracy with the added benefit of lower cost. This study sought to examine the utility of duodenal biopsy and coeliac serology in the diagnosis of coeliac disease.MethodsA prospectively maintained database was interrogated to identify all patients having upper gastrointestinal endoscopy for the investigation of anaemia between January 01, 2016, and December 31, 2016.ResultsOf the 1131 patients having an endoscopy, coeliac serology was measured in only 412 (36%) and was positive in 9 cases (2%), leading to 6 histological diagnoses of coeliac disease and 3 false positives. Two-hundred and seventy-four patients with negative serology had biopsies taken which were all negative. Only 2/451 (0.4%) patients who had biopsies performed in the absence of a serology test were histologically positive for coeliac disease. The cost per diagnosis of a case of coeliac disease in those with either negative or absent coeliac serology was £18,839 (US$25,244, €21,196).ConclusionsRandom duodenal biopsy is not a cost-effective method of diagnosing coeliac disease and should be replaced with pre-endoscopy coeliac serology.

Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of celiac disease in difficult cases

Diagnosis of celiac disease is difficult when the combined results of serology and histology are inconclusive. Studies using flow cytometry of intraepithelial lymphocytes (IELs) have found that celiac patients have increased numbers of γδ IELs, along with a decrease in CD3-CD103 + IELs. The objective of this article is to assess the role of flow cytometric analysis of IELs in the diagnosis of celiac disease in difficult cases. A total of 312 patients with suspicion of celiac disease were included in the study. Duodenal biopsy samples were used for histological assessment and for flow cytometric analysis of IELs. In 46 out of 312 cases (14.7%) the combination of serology and histology did not allow the confirmation or exclusion of celiac disease. HLA typing had been performed in 42 of these difficult cases. Taking into account HLA typing and the response to a gluten-free diet, celiac disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease in this setting. Flow cytometric analysis of IELs is useful for the diagnosis of celiac disease in difficult cases.

Non-coeliac gluten sensitivity.

Irritable bowel syndrome-like symptoms in response to wheat ingestion is common and well described, but whether the reaction is due to gluten (i.e., non-coeliac gluten sensitivity), other wheat proteins, or FODMAPs (mostly fructans) alone or in combinations has not been clearly defined. Exclusion of coeliac disease in the presence of negative serology, and normal villous architecture but increased density of intraepithelial lymphocytes on duodenal biopsies, is difficult. Furthermore, the confidence by which a positive diagnosis is made or non-coeliac gluten sensitivity is excluded by blinded placebo-controlled rechallenge with wheat protein is reduced by strong nocebo responses generally found in patients with self-reported non-coeliac gluten sensitivity. The absence of a clear biological mechanism of action and difficulties with the design and interpretation of research studies have plunged this entity into even deeper controversy. In the absence of clarity in its diagnosis, the epidemiology, prognosis, and therapeutic approaches to a patient who may be gluten sensitive remain to be determined. Adequate understanding of the issues surrounding the controversy and further research will slowly unravel the truth behind the problem.

Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet.

OBJECTIVES:Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS.METHODS:The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluorescence-activated cell sorting analysis for intracellular cytokines and surface markers.RESULTS:Rectal biopsies from wheat-challenged NCWS patients showed that a significant mucosal CD45+ infiltrate consisted of CD3+ and CD3− lymphocytes, with the latter spontaneously producing more interferon (IFN)-γ than IBS controls. About 30% of IFN-γ-producing CD45+ cells were T-bet+, CD56−, NKP44−, and CD117−, defining them as a type-1 innate lymphoid cells (ILC1). IFN-γ-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet.CONCLUSIONS:These data indicate that, in patients with active NCWS, IFN-γ-producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cell population in the pathogenesis of NCWS.

OC-024 Does the Point of Care Test, Simtomax, Distinguish between Coeliac Disease and Non-Coeliac Gluten Sensitivity?: Abstract OC-024 Table 1

Introduction Non coeliac gluten sensitivity (NCGS) is an emerging clinical entity with a prevalence of 0.5–13%. It is characterised by gluten related symptoms with a negative coeliac serology and no villous atrophy (VA). It is currently a diagnosis based on exclusion of coeliac disease (CD). We aimed to assess the role of Simtomax, an IgA/G deamidated gliadin peptide (DGP) based point of care test (POCT), in differentiating between NCGS and CD. Methods Group 1: we compared the sensitivities of 3 POCTs: Simtomax, Biocard [IgA-tissue transglutaminase (TTG)] and Celiac Quick Test (IgA/G/M-TTG). We prospectively recruited 100 patients referred with a positive endomysial antibody (EMA) attending for a gastroscopy. All patients undertook the 3 POCTs, EMA, TTG, and all underwent a gastroscopy with 5 duodenal biopsies. Sensitivities were measured based on their histology. Group 2: the sensitivity of Simtomax in the general population was evaluated by prospectively recruiting 667 patients with gastrointestinal symptoms or ataxia attending for a gastroscopy. To reduce positive ascertainment bias, we excluded patients referred with a positive EMA, previous VA, known CD, self-reported gluten sensitivity, and those on a gluten free diet. All patients undertook Simtomax, EMA, TTG and a gastroscopy with 5 duodenal biopsies. Sensitivities were measured based on their histology. Group 3: we demonstrated the sensitivities of Simtomax in a gluten sensitive population. 35 patients with self-reported gluten sensitivity attending for a gastroscopy were prospectively recruited. All patients undertook Simtomax, EMA, TTG and a gastroscopy with 5 duodenal biopsies. Sensitivities were measured based on their histology. Results Group 1 showed that Simtomax was the best POCT in detecting CD. The CD prevalence was 85%. In group 2, the sensitivity and negative predictive value (NPV) of Simtomax were comparable to that of EMA and TTG. The prevalence of CD was 4.95%. In group 3, Simtomax had 100% sensitivity and NPV in differentiating between CD and NCGS. 4 patients (11.4%) were diagnosed with CD, 4 (11.4%) with potential CD (positive serology but no VA) and 27 (77.1%) with NCGS (negative serology and no VA). Conclusion Simtomax was the most accurate POCT for detecting CD. In a lower CD prevalence group 2 cohort, its sensitivity remained comparable to TTG and EMA. Simtomax had 100% sensitivity in detecting CD in patients with self-reported gluten sensitivity, and 100% NPV in identifying patients with NCGS. Disclosure of Interest M. Lau: None Declared, P. Mooney: None Declared, W. White: None Declared, M. Burden: None Declared, S. Wong: None Declared, M. Kurien: None Declared, D. Sanders Grant/research support from: Tillotts Pharma for investigator led studies in coeliac disease. None of the funding sources had any input in the study design, access to study data, interpretation of the findings or drafting of the abstract.

Non-celiac disease non-wheat allergy wheat sensitivity

Non-celiac non-wheat allergy wheat sensitivity is regarded as discrete glutensensitivity diagnosed after the exclusion of celiac disease and wheat allergy. Due to the absence of reliable biomarkers no exact prevalence rates are known and estimations range between 0,5-6 %. Soon after ingestion of wheat, patients complain of intestinal symptoms mainly bloating, abdominal pain, diarrhea or nausea which improve fast under glutenfree diet. Often extraintestinal manifestation as tiredness, muscle or joint pain, headache and depression are reported. Actually, there are no serological markers and no intestinal mucosal damage was found in patients. The underlying mechanism of the disease is completely unknown and beside of gluten other wheat proteins as well as amylase-trypsin-inhibitor or short chain sugars are discussed as triggers. In addition, the involvement of the intestinal microbiome in pathology of glutensensitivity must be considered.

PTU-162 “coeliac disease screening in ‘2 week wait’ patients: biopsy or serology?”

<h3>Introduction</h3> Patients with iron deficiency anaemia (IDA) or weight loss are usually referred to gastroenterology services through the 2 week wait (2ww) referral pathway. When these patients undergo an oesophagogastroduodenoscopy (OGD) it is common practice to take biopsies from the second part of the duodenum (D2) to exclude coeliac disease. Both BSG (British Society of Gastroenterology) and NICE (National Institute for Health and care Excellence) guidelines recommend that patients with suspected coeliac disease should be screened with serology initially. If coeliac serology is negative then small bowel biopsies are generally not necessary. Despite this D2 are routinely taken which results in an increased workload and cost. <h3>Method</h3> The aim of this study was to determine if D2 biopsies were necessary and cost effective in patients with IDA or weight loss referred on the 2ww pathway. We analysed retrospective data collected from the endoscopy database (Adam) at Queen Elizabeth Hospital for 400 patients referred through 2ww pathway (200 for IDA and 200 for weight loss) who underwent an OGD. Demographic data, histological findings and cost of analysing histology were evaluated. <h3>Results</h3> Of the 200 IDA patients who had D2 biopsy during the study period, 2 patients were excluded (1 had a prior diagnosis of coeliac and 1 did not have histology results on our system). 3 patients had villous atrophy (serology was not checked in 1 patient, 2 had positive serology). The overall pick up rate for significant pathology on D2 biopsies for IDA was 1.5% With D2 biopsy for weight loss, 2 patients were excluded (no histology results was available), 2 patients had villous atrophy (serology was not checked in 1 patient and was negative in 1 patient who had a low IgA), 1 patient had Crohn’s disease on histology. The overall pick up rate for significant pathology on D2 biopsies for weight loss was 1.0%. The cumulative cost of analysing these biopsies was £ 13,440 (£33.6/biopsy). <h3>Conclusion</h3> Overall only a single patient with villous atrophy would have been missed if celiac serology was used in place of D2 biopsies. The cost of performing these biopsies is considerable and burdens the histopathology with large numbers of specimens that have to be processed urgently. Coeliac serology should therefore be done in place of D2 biopsies in 2ww patients undergoing OGD. <h3>Disclosure of interest</h3> None Declared.

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective.

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results.

Gluten Sensitivity in Pediatrics: A Clinical Conundrum

Non-celiac gluten sensitivity (NCGS) is a condition in which symptoms are triggered by gluten ingestion, in which both allergic and autoimmune mechanisms have been ruled out. The “classical” presentation of NCGS is a combination of gastrointestinal symptoms (including abdominal pain, bloating, and bowel habit abnormalities) and extra-intestinal manifestations. So far, NCGS has been described extensively in adults, and few data are available for the pediatric population. Due to lack of a serological or histological marker, the diagnosis of NCGS remains clinical and it is based on the exclusion of celiac disease and wheat allergy and on gluten challenge. G is a 2.5-year-old child referred to our Center for chronic diarrhea, diurnal abdominal pain, and mild failure to thrive. His mother reported that symptoms were related to wheat ingestion and that resolved on a gluten-free diet; therefore, she was worried about Celiac Disease. However, blood tests did support neither celiac disease because of anti-transglutaminase-IgA, anti-endomysium, and anti-gliadin-IgA negativity nor wheat allergy for the absence of specific IgE for wheat or gluten. G was positive just to anti-gliadin-IgG. We reassured the mother and concluded for a chronic unspecific diarrhea to be treated conservatively without elimination diets. On the follow-up visit, G was still complaining with same symptoms, and his growth was further slowing; we ,therefore, decided to repeat the blood tests (with similar results), to define the HLA status (DQ1/7), and to perform intestinal duodenal biopsies. These showed normal villous architecture and a modest increase of intraepithelial lymphocytes. Based on the clear association between clinical symptoms and wheat ingestion, the final diagnosis was “non IgE-mediated adverse reaction to wheat,” although G had no other clue to support this diagnosis such as personal or family history of atopy and/or eczema. G was started on a gluten-free diet with resolution of symptoms. This diagnosis was confirmed 6 months later with a double-blind placebo-controlled challenge that resulted in the onset of diarrhea and abdominal pain 30 h after wheat ingestion. This was happening in 2006 and 2 years later a “new” disease entity might have better explained the symptoms of this child: NCGS.

Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis

Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging. We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (P<0.0001). In addition, CD subjects were significantly more likely to have a family history of CD (P=0.004), personal history of autoimmune diseases (P=0.002), or nutrient deficiencies (P<0.0001). The positive likelihood ratio for diagnosis of CD of a >2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5-918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5-16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9. On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.

A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care

Reports suggest that gluten sensitivity (GS) exists in the absence of coeliac disease (CD). This clinical entity has been termed noncoeliac gluten sensitivity (NCGS). To determine the population prevalence of self-reported GS and referral characteristics to secondary care. A UK population-based questionnaire screened for GS and related symptoms. Diagnostic outcomes were also analyzed in patients referred to secondary care with GS. CD diagnosis entailed a positive coeliac serology (endomysial and/or tissue transglutaminase antibodies) plus Marsh 1-3 on duodenal biopsies. NCGS diagnosis was based on exclusion of CD. Clinical comparisons were made between NCGS and CD. A total of 1002 adults in the population (female 55%, mean age 39 years). The self-reported prevalence for GS was 13% (female 79%, mean age 39.5 years, P<0.0001), with 3.7% consuming a gluten-free diet and 0.8% known to have a doctor diagnosis of CD. Individuals with GS had an increased prevalence of fulfilling the Rome III criteria for irritable bowel syndrome, in comparison with those without GS (20 vs. 3.89%, odds ratio 6.23, P<0.0001).In secondary care 200 GS patients (female 84%, mean age 39.6 years) were investigated, in whom 7% were found to have CD and 93% to have NCGS. All CD patients were human leucocyte antigen DQ2 or DQ8 positive compared with 53% of NCGS cases (P=0.0003). Nutritional deficiencies (P≤0.003), autoimmune disorders (23.1 vs. 9.7%, P=0.0001) and a lower mean BMI (23.7 vs. 25.8, P=0.001) were significantly associated with CD compared with NCGS. GS is commonly self-reported with symptoms suggesting an association with irritable bowel syndrome. The majority of patients have NCGS, an entity which demonstrates clinical and immunologic difference to CD.

Reactivity to dietary gluten: new insights into differential diagnosis among gluten‑related gastrointestinal disorders

The ingestion of dietary gluten sometimes may trigger allergic, autoimmune or nonallergic and nonautoimmune response. The typical gluten‑related allergic disorder is the wheat allergy (WA). Celiac disease (CD) is a well‑known gluten‑related autoimmune condition. The clinical expression of a gluten‑related nonallergic and nonautoimmune response is nonceliac gluten sensitivity (NCGS), an emerging condition whose framework is yet unclear and whose diagnosis is suggested only by demonstration of gluten‑dependency in patient' symptoms after exclusion of WA and CD. This review discusses the current tools to identify patients suffering from WA, CD, and NCGS, as well as the most recent insights in the differential diagnosis among these gluten‑related gastrointestinal disorders .

PTU-181 The Low Diagnostic Yield of Non-Targeted Duodenal Biopsies

IntroductionDuodenal mucosa of normal endoscopic appearance is often biopsied (non-targeted biopsy) to exclude coeliac disease (CD) as the cause of iron deficiency anaemia or other symptoms. Our aim was to...