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Bifidobacterium infantis NLS super strain (B. infantis NLS-SS) was previously shown to alleviate gastrointestinal symptoms in newly diagnosed coeliac disease (CD) patients consuming gluten. A high proportion of patients following a gluten-free diet experiences symptoms despite dietary compliance. The role of B. infantis in persistently symptomatic CD patients has not been explored. The aim of the study was to evaluate the effect of B. infantis NLS-SS on persistent gastrointestinal symptoms in patients with CD following a long-term GFD. We conducted a randomised, cross-over, double-blind, placebo-controlled trial in symptomatic adult CD patients on a GFD for at least two years. After one-week run-in, patients were randomised to B. infantis NLS-SS or placebo for 3 weeks with cross-over after a 2-week wash-out period. We estimated changes (Δ) in celiac symptom index (CSI) before and after treatment. Stool samples were collected for faecal microbiota analysis (16S rRNA sequencing). Gluten immunogenic peptide (GIP) excretion in stool and urine samples was measured at each study period. Eighteen patients were enrolled; six patients were excluded due violations in protocol. For patients with the highest clinical burden, CD symptoms were lower in probiotic than in placebo treatment (P=0.046). B. infantis and placebo treated groups had different microbiota profiles as assessed by beta diversity clustering. In probiotic treated groups, we observed an increase in abundance of B. infantis. Treatment with B. infantis was associated with decreased abundance of Ruminococcus sp. and Bifidobacterium adolescentis. GIP excretion in stools and urine was similar at each treatment period. There were no differences in adverse effects between the two groups. B. infantis NLS-SS improves specific CD symptoms in a subset of highly symptomatic treated patients (GFD). This is associated with a shift in stool microbiota profile. Larger studies are needed to confirm these findings. ClinicalTrials.gov: NCT03271138

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Background Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established. Aim To assess the performance of enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (PoCTs) for GIP excretion in CeD patients on gluten-free diet (GFD). Methods We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion (by ELISA in stool and PoCTs (commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period. Results Forty-four patients were enrolled, of which 19 (43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected. Eleven out of 44 patients (25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases (Cohen´s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant (concomitantly positive or negative) in 67 out of 74 (90.5%) samples. Excretion of GIP was detected in 7 (8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports. Conclusion GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple home-based method for self-assessment of dietary indiscretions.

Currently, the only effective treatment for celiac disease is complete removal of gluten from the diet. However, patients need to follow a strict gluten-free diet that results in symptomatic, serologic, and histologic remission in most patients. Histologic remission is usually complete in children, but recovery is slower and more frequently incomplete in adults. When remission has been achieved, yearly follow-up is recommended for adults, children, and adolescents. This article deals with conventional strategies used in order to follow-up patients on treatment and aiming to obtain the best clinical outcome.

BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk. AIM To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception. METHODS We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs) RESULTS A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001). CONCLUSION Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual's pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections.(1-3) However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19.

Supported by Ministerio de Ciencia e Innovacion, No. DI-16-08943 and No. DI-17-09627., BACKGROUND Gluten is a complex mixture of proteins with immunogenic peptide sequences triggering the autoimmune activity in patients with celiac disease (CeD). Gluten immunogenic peptides (GIP) are resistant to gastrointestinal digestion and are then excreted via the stool and urine. Most common detection methods applied in the follow-up visits for CeD patients such as serology tests, dietetic interviews, questionnaires, and duodenal biopsy have been proved to be inefficient, invasive, or inaccurate for evaluating gluten-free diet (GFD) compliance. Determination of excreted GIP in stool and urine has been developed as a non-invasive, direct, and specific test for GFD monitoring. AIM To summarize published literature about the clinical utility of GIP determination in comparison to the tools employed for GFD monitoring. METHODS PubMed and Web of Science searches were performed using the keywords “gluten immunogenic peptides” or “gluten immunogenic peptide” and a combination of the previous terms with “feces”, “stools”, “urine”, “celiac disease”, “gluten-free diet”, and “adherence” to identify relevant clinical studies published in English and Spanish between 2012 to January 2021. Reference lists from the articles were reviewed to identify additional pertinent articles. Published articles and abstracts reporting the clinical use of GIP determination in stool and/or urine for the follow-up of patients with CeD in comparison with other tools in use were included. Case reports, commentaries, reviews, conference papers, letters, and publications that did not focus on the aims of this review were excluded. RESULTS Total of 15 publications were found that involved the use of GIP determination in stool and/or urine to monitor the adherence to the GFD in comparison to other tools. Studies included both children and adults diagnosed with CeD and healthy volunteers. Overall, these preliminary studies indicated that this novel technique was highly sensitive for the detection of GFD transgressions and therefore could facilitate the follow-up of patients with CeD. Tools identified in this work included the CeD-specific serology, dietetic questionnaires, symptomatology, and the duodenal biopsy. Review of the literature revealed that the rates of GFD adherence may vary between 30%-93% using either stool or urine GIP determination, 49%-96% by the serology, 59%-94% using the dietetic questionnaires, 56%- 95% by the reported symptoms and 44%-76% with the duodenal biopsy. In addition, the association between the different methods and histological abnormalities (Marsh II-III) was found to be 33%-100% for GIP determination (stool and urine), 25%-39% for CeD-specific serology, 3%-50% for dietetic questionnaires, and 22%-28% for the symptomatology. CONCLUSION Excreted GIP detection is the precise approach for determining voluntary or involuntary gluten consumption in CeD patients preventing future complications arising from gluten exposure., Instituto de Salud Carlos III Spanish Government European Commission DI-16-08943 DI-17-09627

Introduction Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms and quality of life (QOL) in patients with CD. Methods We searched EMBASE, MEDLINE, CINAHL, Web of Science, CENTRAL, and DARE databases up to February 2019 for randomized controlled trials (RCTs) evaluating probiotics compared with placebo for treating CD. We collected data on GI symptoms, QOL, adverse events, serum tumor necrosis factor-α, intestinal permeability, and microbiota composition. Results We screened 2,831 records and found that 7 articles describing 6 RCTs (n = 279 participants) were eligible for quantitative analysis. Probiotics improved GI symptoms when assessed by the GI Symptoms Rating Scale (mean difference symptom reduction: -28.7%; 95% confidence interval [CI] -43.96 to -13.52; P = 0.0002). There was no difference in GI symptoms after probiotics when different questionnaires were pooled. The levels of Bifidobacteria increased after probiotics (mean difference: 0.85 log colony-forming units (CFU) per gram; 95% CI 0.38-1.32 log CFU per gram; P = 0.0003). There were insufficient data on tumor necrosis factor-a levels or QOL for probiotics compared with placebo. No difference in adverse events was observed between probiotics and placebo. The overall certainty of the evidence ranged from very low to low. Discussion Probiotics may improve GI symptoms in patients with CD. High-quality clinical trials are needed to improve the certainty in the evidence (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B595).

Background Celiac disease is a chronic autoimmune disorder triggered by dietary gluten. The only available treatment for celiac disease is strict compliance to the gluten-free diet. Despite adherence to a gluten-free diet, many celiac patients still experience symptoms which may be mediated by the gut microbiota. Different studies have assessed the use of probiotics as an adjuvant treatment for celiac disease. Aims We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal symptoms and quality of life in patients with celiac disease. Methods We searched MEDLINE (1966 to February 2019), EMBASE (1974 to February 2019), CINAHL, Web of Science, CENTRAL, DARE, and Sigle up to February 2019 for randomized controlled trials (RCTs) assessing the effects of probiotics on celiac disease. We collected data on gastrointestinal symptoms, quality of life, adverse events, serum tumor necrosis factor α (TNF-α), intestinal permeability, and microbiota composition. Results Out of 2831 records screened, 7 articles from 6 RCTs with a total of 279 participants were eligible for quantitative analysis. Probiotic supplementation for a minimum of 2 weeks improved gastrointestinal symptoms when assessed by the Gastrointestinal Symptoms Rating Scale (GSRS) (2 studies; 131 participants; mean difference (MD) symptom reduction: -28.7%; 95% CI -43.96 to -13.52; P=0.0002). No differences in gastrointestinal symptoms after probiotics were observed when pooling data from the GSRS, Celiac Symptoms Index (CSI), and the Celiac Disease Questionnaire (CDQ) (4 studies; 197 participants; standardized mean difference (SMD) symptom reduction: -0.48; 95% CI -1.21 to +0.25; P=0.20). TNF-α levels did not change after probiotics (SMD: -0.52; 95% CI -1.08 to +0.04; P=0.07). Levels of Bifidobacteria species increased (MD: increase by 0.85 log CFU/g; 95% CI +0.38 to +1.32 log CFU/g; P=0.0003) but there was no difference in Lactobacilli species (MD: change of 1.13 log CFU/g; 95% CI -0.67 to +2.93 log CFU/g; P=0.22) after probiotic supplementation. No difference in quality of life or adverse events was observed after probiotics. There was insufficient evidence to assess the effects of probiotics on intestinal permeability. The overall quality of the evidence ranged from very low to low. Conclusions Probiotics may improve gastrointestinal symptoms in patients with celiac disease; however, our confidence in these results is limited by the low quality of the evidence. Further large clinical trials with a more rigorous design are needed to improve the quality of the evidence. Funding Agencies None

Background & Aims Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. Methods We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. Results There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P = .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16–1427.8; P = .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. Conclusions Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333 .

We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity. To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD). Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies. We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P

ObjectiveWe aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.DesignThe study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.ResultsCohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.ConclusionOur results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Gluten free diet is the only available treatment for celiac disease (CeD). Patients with CeD who do not adhere to a strict gluten-free diet (GFD) have been found to have complications involving nutritional deficiencies, increased risk of bone fractures, increased risk of mortality, and certain types of cancers. Complete removal of gluten from the diet in a patient with CeD often results in symptomatic, serologic, and histologic remission. However, strict compliance with the diet is challenging. Long-term follow-up care is needed to assure treatment compliance and positive health outcomes. Monitoring celiac specific serology, nutrient deficiencies, bone mineral density, and assessment of GFD compliance have been recommended in clinical practice. However, there is no consensus on which specific tests and how often they should be performed during the follow up. Here, we have performed a review of the literature on current strategies to follow up patients with CeD. There are new tools for monitoring adherence to the GFD which could change some paradigms in following up treated patients.

It is not clear how often patients who are on gluten-free diets (GFDs) for treatment of celiac disease still are exposed to gluten. We studied levels of gluten immunogenic peptides (GIP) in fecal and urine samples, collected over 4 weeks, from patients with celiac disease on a long-term GFD.We performed a prospective study of 53 adults with celiac disease who had been on a GFD for more than 2 years (median duration, 8 y; interquartile range, 5-12 y) in Argentina. At baseline, symptoms were assessed by the celiac symptom index questionnaire. Patients collected stool each Friday and Saturday and urine samples each Sunday for 4 weeks. We used a commercial enzyme-linked immunosorbent assay to measure GIP in stool and point-of-care tests to measure GIP in urine samples.Overall, 159 of 420 stool and urine samples (37.9%) were positive for GIP; 88.7% of patients had at least 1 fecal or urine sample that was positive for GIP (median, 3 excretions). On weekends (urine samples), 69.8% of patients excreted GIP at least once, compared with 62.3% during weekdays (stool). The number of patients with a sample that was positive for GIP increased over the 4-week study period (urine samples in week 1 vs week 4: P.05). Patients with symptoms had more weeks in which GIP was detected in stool than patients without symptoms (P.05). The number of samples that were positive for GIP correlated with titers of deamidated gliadin peptide IgA in patients' blood samples, but not with levels of tissue transglutaminase.Patients with celiac disease on a long-term GFD still frequently are exposed to gluten. Assays to detect GIP in stool and urine might be used to assist dietitians in assessment of GFD compliance.

We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p

SummaryBackground Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. Aim To create a prognostic model to estimate survival of patients with refractory coeliac disease. Methods We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. Results The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11–63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38–3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22–6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61–0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Conclusions Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

More than 50% of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.

AIMS Our objectives were to: (1) determine whether celiac disease (CD) patients have cognitive impairment at diagnosis; and (2) compare their cognitive performance with nonceliac subjects who have similar chronic symptoms and healthy controls. MATERIALS AND METHODS Fifty adults (age range: 18 to 50 y) with symptoms and signs compatible with CD were enrolled in a prospective cohort irrespective of the final diagnosis. At baseline, all individuals underwent cognitive functional and psychological evaluation. CD patients were compared with subjects in whom CD was ruled out and with healthy controls matched by sex, age, and years of schooling. RESULTS Thirty-three subjects (66%) were diagnosed with CD. Compared with the healthy controls (n=26), CD cases and disease controls (n=17; mostly irritable bowel syndrome) had impaired cognitive performance (P=0.02 and P=0.04, respectively), functional impairment (P

Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p

Celiac disease is an autoimmune disorder that is induced by dietary gluten in genetically predisposed individuals. It has a prevalence of approximately 1% in many populations worldwide. New diagnoses have increased substantially, owing to increased awareness, better diagnostic tools, and probable real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA-DQ2 and HLA-DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsy specimens. However, according to recent controversial guidelines, a diagnosis can be made without a biopsy in certain circumstances, especially in children. Symptoms, mortality, and risk for malignancy each can be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, because the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing nondietary therapies.

Celiac disease affects 1% of the North American population, with an estimated 350,000 Canadians diagnosed with this condition. The disease is triggered by the ingestion of gluten, and a lifelong, strict gluten-free diet (GFD) is the only currently available treatment. Compliance with a strict GFD is essential not only for intestinal mucosal recovery and alleviation of symptoms, but also for the prevention of complications such as anemia, osteoporotic fractures and small bowel lymphoma. However, a GFD is difficult to follow, socially inconvenient and expensive. Different approaches, such as tax reduction, cash transfer, food provision, prescription and subsidy, have been used to reduce the additional costs of the GFD to patients with celiac disease. The current review showed that the systems in place exhibit particular advantages and disadvantages in relation to promoting uptake and compliance with GFD. The tax offset system used in Canada for GFD coverage takes the form of a reimbursement of a cost previously incurred. Hence, the program does not help celiac patients meet the incremental cost of the GFD – it simply provides some future refund of that cost. An ideal balanced approach would involve subsidizing gluten-free products through controlled vouchers or direct food provision to those who most need it, independently of ‘ability or willingness to pay’. Moreover, if the cost of such a program is inhibitive, the value of the benefits could be made taxable to ensure that any patient contribution, in terms of additional taxation, is directly related to ability to pay. The limited coverage of GFD in Canada is concerning. There is an unmet need for GFD among celiac patients in Canada. More efforts are required by the Canadian medical community and the Canadian Celiac Association to act as agents in identifying ways of improving resource allocation in celiac disease.

BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD.OBJECTIVE: To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission.METHODS: An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies.RESULTS: A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors’ laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype.CONCLUSION: The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.

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.

Background and Aim: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia-Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia. Methods: A working group consisting of members from Asia-Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia-Pacific region both in terms of what exists and what needs to be done. Results: The working group identified the gaps in epidemiology, diagnosis, and manage- ment of CD in Asian-Pacific region and recommended the following: to establish preva- lence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized. Conclusions: Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia-Pacific region define extent of problem and get prepared to handle impending epidemic of CD.

Objective \ud The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten.\ud \ud Design \ud A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies.\ud \ud Results \ud CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper.\ud \ud Conclusion \ud This paper presents the Oslo definitions for CD-related terms.\ud

Deterioration of quality of life in the long term has been suggested for celiac disease patients on a gluten-free diet.To determine long-term quality of life of celiac disease patients and to assess the benefits of gluten-free diet compliance.We prospectively evaluated 53 newly diagnosed adult celiac disease patients.The Short Form 36 Health Survey, the Gastrointestinal Symptoms Rating Scale and the Beck Depression Inventory were employed at the time of diagnosis, 1 year, and beyond 4 years (median: 53 months) on treatment.At 1 year, a significant improvement from baseline in quality of life indicators was observed (p0.001 to p0.0001) with comparable scores to healthy subjects. At 4 years, the Short Form 36 Health Survey scores (p0.002 to p0.0002) and Beck Depression Inventory score (p0.002) show significant deterioration compare with 1 year. Most scores remained significantly better than those at diagnosis (p0.03 to p0.0005). No changes were detected in the Gastrointestinal Symptoms Rating Scale scores. The long-term impairment of quality of life was attributable to the deterioration of most dimensions in patients who were not strictly compliant with the gluten-free diet (p0.05 to p0.001).Long-term deterioration of quality of life outcomes after the first year of gluten-free diet was associated with the lack of strict compliance with the diet.

The usefulness of celiac disease-related serology in monitoring patients on a gluten-free diet has been debated.To describe serologic changes over time and assess whether serology tests can predict compliance with the gluten-free diet.Sera obtained at baseline and every 3 months thereafter for 1 year in 82 adult celiac disease patients were assayed for: (1) IgA antigliadin, (2) IgA anti-tissue transglutaminase, (3) IgA endomysial, (4) IgA, and (5) IgG anti-deamidated gliadin peptides, (6) dual detection of IgA and IgG anti-deamidated gliadin peptides, (7) a single assay for IgA and IgG of both anti-deamidated gliadin peptide and anti-tissue transglutaminase, and (8) IgA antiactin antibodies.At 3 months after diagnosis, most antibody assays significant decrease in mean concentrations (p0.0001) and the percentage of positive samples (p0.0001) with further improvement in subsequent determinations. Strictly adherents had significantly lower concentrations of antibodies (p0.01 to p0.00001) and smaller proportion of positive samples for IgA endomysial, IgA antiactin antibodies and IgA antigliadin (15.6%, 17.4% and 23.9%, respectively) than partially compliant. At 1 year, IgA endomysial (p0.02), IgA antiactin antibodies (p0.05) and anti-tissue transglutaminase (p0.02) predicted the degree of compliance.Gluten-free diet treatment produced rapid and significant qualitative and quantitative changes in celiac disease-related antibodies which may be useful for monitoring dietary compliance.

Background: Some patients with celiac disease (CD) may be seronegative with the commonly used test for IgA anti–tissue transglutaminase (anti-tTG) antibodies. Our aim was to explore whether newer assays incorporating synthetic deamidated gliadin-related peptides (DGPs) or other TG isoenzymes as antigen are useful for detecting gluten sensitivity in IgA anti-tTG–seronegative patients. Methods: We assayed serum samples obtained at diagnosis from (a) anti-tTG–seronegative patients with a CD-like enteropathy (n = 12), (b) skin biopsy–proven dermatitis herpetiformis (DH) patients (n = 26), and (c) IgA anti-tTG–positive CD patients (n = 26). All patients had typical total IgA concentrations. All patients underwent intestinal biopsy and serum testing for (a) detection of IgA and IgG isotypes of both anti-DGP and anti-tTG in a single assay (tTG/DGP Screen; INOVA Diagnostics), (b) simultaneous detection of both IgA and IgG anti-DGP antibody isotypes (DGP Dual; INOVA Diagnostics), and (c) detection of antibodies to transglutaminase 3 (TG3) or transglutaminase 6 (TG6). Results: All anti-tTG–seropositive patients also tested positive in anti-DGP assays. Overall, tTG/DGP Screen detected 6 (31.6%) of the 19 anti-tTG seronegatives, and anti-DGP Dual produced positive results in 5 (26.3%) of these cases. Whereas both assays detected 2 anti-tTG–negative DH patients with partial villous atrophy, they were positive in only 2 of the 5 cases with no histologically discernible mucosal damage. Testing for antibodies to TG3 and TG6 identified 7 (36.8%) of the 19 anti-tTG–negative patients, 5 of which were also positive for anti-DGP. Conclusions: Detection of anti-DGP with tTG/DGP Screen or anti-DGP Dual, or detection of antibodies to other TG isoenzymes, enhances the sensitivity for detecting gluten sensitivity among non–IgA- deficient, anti-tTG–seronegative patients with CD-like enteropathy.

Background/aims Celiac disease (CD) patients are affected in their quality of life (QoL). Our objectives were to assess differences in quality of life of patients according to the clinical presentation at diagnosis, and to determine the time–course impact of a gluten-free diet. Patients/methods We prospectively evaluated 132 newly diagnosed adult CD patients and 70 healthy controls using self-administered questionnaires: the Short Form-36 health survey, the Gastrointestinal Symptoms Rating Scale; the Beck Depression Inventory both, at diagnosis and at 3-, 6- and 12-months on treatment. Results At diagnosis, patients with classical symptoms ( n = 97) exhibited a significantly more pronounced alteration of all items of the three questionnaires than atypical/silent cases ( n = 35) ( p p Conclusions Atypical/silent celiac disease patients have a significantly better baseline quality of life than those with classical symptoms. Treatment induces a rapid and significant improvement in symptomatic cases but not in silent patients with all subgroups having similar 1-year scores comparable to healthy controls.

Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD.Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR.Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients.Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation.

Case finding for celiac disease (CD) is becoming increasingly common practice and is conducted in a wide range of clinical situations ranging from the presence of gastrointestinal symptoms to failure to thrive in children, prolonged fatigue, unexpected weight loss and anemia. Case finding is also performed in associated conditions, such as autoimmune thyroid disease, dermatitis herpetiformis and type 1 diabetes, as well as in patients with irritable bowel syndrome, unexplained neuropsychiatric disorders and first-degree relatives of patients with diagnosed CD. This aggressive active case finding has dramatically changed the clinical characteristics of newly diagnosed patients. For instance, higher numbers of patients who present with extraintestinal symptoms are now being diagnosed with CD. Current recommendations state that due to a high risk for complications if the disease remains undiagnosed, patients with extraintestinal symptoms due to CD require appropriate diagnosis and treatment. Despite criticism regarding the cost-effectiveness of case finding in CD, such an aggressive approach has been considered cost-effective for high-risk patients. The diagnosis of CD among patients with extraintestinal symptoms requires a high degree of awareness of the clinical conditions that carry a high risk for underlying CD. Also, understanding the correct use of specific serology and duodenal histology is key for an appropriate diagnostic approach. Both procedures combined are able to confirm diagnosis in the vast majority of cases. However, in certain circumstances, serology and even duodenal histology cannot confirm or rule out CD. A common cause of negative IgA serology is IgA deficiency. For such eventuality, IgG-based serological tests can help confirm the diagnosis. Importantly, some histologically diagnosed cases still remain seronegative despite exclusion of IgA deficiency. On the other hand, duodenal histology may be normal despite the presence of CD-specific antibodies and active CD. This has been clearly demonstrated in some cases of untreated dermatitis herpetiformis, but may also be due to the patchy condition of CD or lesions that are not adequately recognized by nonexpert endoscopists and/or pathologists. The effectiveness of agluten-free diet depends on the clinical end point addressed. A good example is the outcome of bone loss. While risk for fracture normalizes after the first year of dietary treatment, bone parameters measured by densitometry may not be normalized in the long-term follow-up. Moreover, it is still unclear how far an early gluten-free diet will positively affect associated autoimmune diseases like type 1 diabetes and autoimmune thyroiditis.

Whipple's disease is a rare multisystemic infectious disorder affecting predominantly middle-aged men. Clinical manifestations are very variable with a very long, insidious, prediagnostic course. Weight loss, chronic diarrhea, arthralgias, and low-grade fever are characteristic features in most patients. Although gastrointestinal compromise is very common, atypical clinical forms are being increasingly recognized. Although a bacterial cause was strongly suggested for many years, the infectious agent was elusive until recently. The bacillus that was classified as an actinomycete was named Tropheryma whipplei and has singular characteristics. It presents affinity for the periodic acid-Schiff stain, but it is negative for Ziehl-Neelsen staining and has a characteristic trilamellar cell wall. Its genetic material has been recently sequenced, and culture was finally performed on a human fibroblast cell line. Pathological specimens show macrophage infiltration with mostly intracellular invasion of live bacteria. Immunologic factors, such as a subtle defect of cellular immunity possibly specific for the Whipple's bacterium, are believed to play a role in pathogenesis. The diagnosis requires the histologic assessment of diseased tissue, showing the characteristic infiltration, as a first approach, and confirmatory tests such as electron microscopy and/or polymerase chain reaction. Antibiotic treatment is mandatory and leads to a rapid clinical improvement and remission in most patients. Although the rationale for treatment is largely empiric, current recommendations include a 2-week parenteral therapy (third generation cephalosporin) followed by a long-term therapy with trimethoprim-sulphamethoxazole. This approach has been shown to reduce the number of relapses and was effective for prevention and/or treatment of the neurologic compromise.

Our objective in this cross-sectional, case-control study was to gain insight into celiac osteopathy by examining a well-defined cohort of patients with a wide clinical spectrum of the disease.We studied 148 unselected celiac patients and 296 (1:2) age- and sex-matched controls diagnosed with functional gastrointestinal disorders. Based on the clinical history, 53% were classically symptomatic, 36% had subclinical celiac disease, and 11% were silent, detected by screening. The fracture information was obtained through an in-person interview using a pre-designed questionnaire.Classically symptomatic patients had an increased number of fractures in the peripheral skeleton (47%) compared with age- and sex-matched controls (15%; odds ratio, 5.2; 95% confidence interval, 2.8-9.8). However, fractures in subclinical/silent celiac cases (20%) were no different from those in controls (14%; odds ratio, 1.7, 0.7-4.4). Compared with the subclinical/silent group, a significantly greater prevalence of fractures was detected in classically symptomatic patients (odds ratio, 3.6, 1.7-7.5). Compared with controls, celiac disease patients had significantly more fractures produced by mild trauma (P0.01), but there were no differences in the severity of trauma events that induced fractures. Mean bone density femoral neck z score was higher for subclinical/silent cases compared with classically symptomatic patients (P0.05).Celiac patients show a very wide variation in fracture risk, with increased risk in classically symptomatic patients. Diagnostic and therapeutic strategies to prevent bone loss and fracture should be preferentially used in the subgroup of patients with classic clinical disease.

Summary Background: The screening and diagnosis of coeliac disease have been simplified by the advent of new serological tools. Aim: To assess the clinical utility of a newly developed kit for antibodies to human recombinant tissue transglutaminase (hu-anti-tTG) in a large population of patients undergoing intestinal biopsy for suspected intestinal disorders. Methods: We evaluated 426 serum samples from consecutive adult patients (250 from untreated coeliac disease patients and 176 from individuals in whom a diagnosis of coeliac disease had been excluded), obtained at the time of intestinal biopsy. Samples were tested for immunoglobulin A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples was also assessed for a guinea-pig-based anti-tissue transglutaminase. Results: According to the cut-off for hu-anti-tTG, the sensitivity, specificity and positive and negative predictive values were 91%, 96%, 97% and 87%, respectively. Simultaneous determination of EmA showed values of 86%, 100%, 100% and 83% for the same parameters. Although 19 coeliac disease patients (7.6%) were negative for EmA and hu-anti-tTG, both tests rendered superior statistical values to antigliadin antibody tests. At diagnosis, IgA deficiency was detected in 11 patients, but both assays were able to detect samples with mild to moderate deficiency. The comparison of hu-anti-tTG with EmA showed excellent concordance between the tests (κ statistic, 0.85). Discordance was observed in 20 samples from coeliac disease patients (8%) and in nine samples from controls (5%). Fifteen samples had an EmA-negative but hu-anti-tTG-positive serology, and five showed the converse pattern. Comparison of human recombinant and guinea-pig tests showed concordant results in 96% of cases. Conclusions: The quantitative determination of hu-anti-tTG type IgA using a commercial enzyme-linked immunoabsorbent assay kit was highly sensitive and specific for the detection of coeliac disease. Our results in a large population of patients with a clinical condition suggestive of the disorder demonstrated that the test can be used to detect a substantial number of patients otherwise unrecognized by IgA EmA.

OBJECTIVE: The aim of this study was to gain insight into the pathogenesis of bone mass loss and weakening affecting patients with celiac disease, according to the new concepts of bone structure/strength and muscle/bone interrelationships. METHODS: We studied serum variables and tomographic indicators of bone structure and strength and regional muscle masses in a series of patients at diagnosis and after 1 yr on a gluten-free diet and in gender- and age-matched controls. RESULTS: At diagnosis, serum levels of calcium and vitamin D were low, and indicators of parathyroid hormone activity and bone formation and resorption were increased. All these parameters were normalized by treatment. Peripheral quantitative CT scans of the distal radius revealed that cortical bone was generally more affected than trabecular bone. The cross-sectional area (CSA) and the volumetric mineral content and density of cortical bone (indicators of cortical tissue mass and mechanical quality), and moments of inertia (CSMI, indicator of the bone architectural design) were in the lower end of normal range in men, and below that in 50% of women. In men, the CSMI/CSA ratio (indicator of the architectural efficiency of distribution of the available cortical tissue) was lower than expected and remained unchanged after treatment. In women, the baseline ratio was normal, but both the ratio and the CSMI were low at diagnosis and normalized after treatment. Both baseline values and the treatment-induced changes of cortical and trabecular bone in the radius and the axis (L3) correlated inversely with serum parathyroid hormone levels. Baseline values or changes in the mineral content of the vertebral bone correlated with the CSA of psoas and spine-extensor muscles. Multiple regression analyses showed that metabolic and mechanical parameters were independent determinants of different aspects of the vertebral bone weakening. CONCLUSIONS: Our results show that bone weakening in celiac disease might result from both 1) a metabolic disturbances of bone remodeling affecting trabecular and cortical bone masses and the mechanical quality of the bone material, and 2) a reduction of muscle strength impairing the modeling-dependent optimization of bone architectural design and mass of cortical bone. Dietary treatment seems to correct almost exclusively the metabolically induced disturbances, which were predominant in women.

BACKGROUND: Celiac disease (CD) occurs in approximately 1% of the Western population. It is a lifelong disorder that is associated with impaired quality of life (QOL) and an excessive risk of comorbidity and death. OBJECTIVES: To review the literature on screening for CD in relation to the current World Health Organization (WHO) criteria for mass screening. METHODS: We performed a PubMed search to identify indexed papers on CD screening with a publication date from 1900 until 1 June 2014. When we deemed an abstract relevant, we read the corresponding paper in detail. RESULTS: CD fulfills several WHO criteria for mass screening (high prevalence, available treatment and difficult clinical detection), but it has not yet been established that treatment of asymptomatic CD may reduce the excessive risk of severe complications, leading to higher QOL nor that it is cost-effective. CONCLUSIONS: Current evidence is not sufficient to support mass screening for CD, but active case-finding may be appropriate, as we recognize that most patients with CD will still be missed by this strategy. Although proof of benefit is still lacking, screening for CD may be appropriate in high-risk groups.

BACKGROUND: Celiac disease has been linked to decreased quality of life and certain mood disorders. The effect of the gluten free diet on these psychological aspects of the disease is still unclear. OBJECTIVES: The objective of this article is to review the literature on psychological morbidity of celiac disease. METHODS: We performed a PubMed search for the time period from 1900 until June 1, 2014, to identify papers on psychological aspects of celiac disease looking specifically at quality of life, anxiety, depression and fatigue. RESULTS: Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While aspects of these conditions may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity. Psychological symptoms may affect the quality of life and the dietary adherence. CONCLUSION: Health care professionals need to be aware of the ongoing psychological burden of celiac disease in order to support patients with this disease.