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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.

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 & 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 .

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.

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.

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.

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.

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/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.

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.

OBJECTIVE: Serological screening for celiac disease (CD) can detect a large number of otherwise undiagnosed patients based on the sequential evaluation of serological tests and intestinal biopsy. The aim of this study was to compare the screening value for CD of two different protocols for the same community-based population. METHODS: We screened 1000 consecutive subjects (497 women, age range 16–71 yr) attending a centralized laboratory for obligatory prenuptial blood tests. Serum samples obtained from all subjects were processed using two different protocols: 1) a three-level classic screening consisting of the parallel use of IgG and IgA antigliadin antibodies as first level, followed by endomysial antibodies and total serum IgA for positive patients, and finally, intestinal biopsy of positive patients; and 2) a study screening protocol consisting of the parallel use of a commercial guinea pig antitissue transglutaminase antibody and total serum IgA as first line, endomysial antibodies (type IgA and/or IgG) for positive patients, and finally, intestinal biopsy. RESULTS: The classic screening protocol identified five subjects who were eligible for intestinal biopsy, which confirmed the presence of CD in all (prevalence 5.0 × 1000, 95% CI = 1.6–11.6). Using the study algorithm, we detected seven new patients including the five patients detected by the first protocol (prevalence 7.0 × 1000, 95% CI = 2.8–14.4). The two additional patients diagnosed using the proposed algorithm had positive IgG antigliadin antibodies and normal total serum IgA and were not detected by the classic protocol. Both patients were endomysial antibodies positive. The comparative analysis showed that the classic approach was more expensive (U.S. $4687 per new patient detected) compared with the proposed study algorithm (U.S. $3006). CONCLUSIONS: Our data showed that a new screening protocol using antitissue transglutaminase as first line followed by endomysial antibodies is a cost-effective screening and yielded more realistic figures of prevalence for CD in a community setting than the classic three-level sequential evaluation using antigliadin antibodies.

Background: Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon-like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis. Aim: To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole. Materials and methods: Twenty-six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score ≥ 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double-blind, double-dummy, 6-week, controlled trial. Results: Based on the intention-to-treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P

Objectives: It has been suggested that environmental factors other than gliadin might play a role in pathogenesis of celiac disease. Cigarette smoking was reported to exert a protective effect against the development of symptomatic celiac disease; however, this relationship was not confirmed. The aim of this study was to determine the effect of cigarette smoking on celiac disease. Methods: A cohort of 87 consecutive celiac disease patients attending the clinic of Malabsorption and 174 age- and sex-matched individuals diagnosed with functional GI disorder were included in the study. Clinical information was obtained both at the time of diagnosis and at follow-up by reviewing the clinical history. Smoking information was obtained through an in-person interview using a questionnaire. Results: Although 33% of controls were current smokers at the time of the study, only 16% of celiac patients were smokers at diagnosis (odds ratio, 0.39; 95% confidence interval 0.19–0.79; p < 0.006). The proportion of nonsmokers among patients (84%) was significantly greater than that among controls (67%; odds ratio, 2.54; 95% confidence interval 1.27–5.16; p < 0.007). Current smoker patients had a lower baseline BMI (p < 0.05) and body weight (p < 0.05) compared to former smokers. Compared with nonsmokers, control individuals who were active smokers at entry in the study were younger (p < 0.02) and had lower body weight (p < 0.03) and BMI (p < 0.03). Interestingly, positive lineal correlation was observed between age at diagnosis and daily cigarette consumption (r = 0.72; p < 0.004) in active smokers. We did not detect any relationship either between causes for cessation of smoking and clinical symptoms or between differences in the proportions of smoking habits when patients were stratified according to their clinical status at diagnosis (symptomatic vs subclinical/asymptomatic cases). Conclusions: This study provides evidence that, compared with control subjects, a significantly lower proportion of patients with celiac disease were current smokers at the time of diagnosis, and that cigarette smoking delayed diagnosis of celiac disease. Our study suggests that the nutritional compromise of patients with celiac disease who smoked resulted from the summation of the effect of celiac disease per se and that produced by the smoking habit. Further studies are necessary to identify whether the relationship between smoking and celiac disease is causal or incidental.

Objective: To investigate serum levels of transforming growth factor-β1 and interferon-γ in active ulcerative colitis and to assess changes during treatment. Methods: We prospectively evaluated serum from 25 patients with untreated active ulcerative colitis and 19 healthy controls. Disease activity score (DAI), serum transforming growth factor-β1 and interferon-γ levels were measured at baseline and after 7 days of conventional treatment. Disease activity score and transforming growth factor-β1 were also assessed at 42 days. Results: Baseline transforming growth factor-β1 levels were significantly higher in patients than in controls (P

OBJECTIVE: Early studies revealed that up to 50% of nonatrophic, first-degree relatives of celiac disease patients exhibit features of gluten sensitivity. However, whether these features progress to a fully expressed celiac disease remain partially known. Our aim was to report two new patients resulting from a prospective, long-term surveillance of relatives who were nonatrophic at initial assessment. METHODS: After a median time of 86 months (range: 42–102 months) from the baseline assessment, we re-evaluated 44 first-degree relatives of propositi who had taken part in family studies and in whom baseline small intestinal biopsies were normal. At the baseline screening, 21 relatives had positive serum antigliadin antibodies and/or increased intraepithelial lymphocyte infiltration, and 23 did not. In addition, 11 of 18 had a celiac-like response to rectal gluten challenge and 16 of 34 possessed the characteristic HLA DQ2 haplotype (DQA1 0501 DQB1 0201). Re-evaluation was based on celiac-related serology antigliadin (AGA) and endomysial (EmA) antibodies. EmA-positive subjects underwent intestinal biopsy. RESULTS: At the end of the study, EmA was positive in only two subjects. Histological examination revealed flat small bowel mucosa in both. At baseline, both cases were EmA-negative and no minor histological changes were observed. One was a woman with positive baseline IgA and IgG AGA and a rectal gluten challenge with a celiac-like response; the other patient has presented only with a positive IgG AGA. In both cases, progression was detected in a clinically silent context. Both new patients had the characteristic HLA DQ2 haplotype. CONCLUSIONS: Our data suggest the need to re-evaluate relatives who have been negative on initial screening for celiac disease. Up to now, the progression to severe enteropathy was only observed in relatives who had presented some evidence of gluten sensitivity and the characteristic HLA DQ2 haplotype. Longer longitudinal studies are necessary to obtain definitive conclusions.

OBJECTIVES: Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients. METHODS: We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis. RESULTS: Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8–7.2; p < 0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7–11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p < 0.06) and remained undiagnosed for more prolonged periods (p < 0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures. CONCLUSIONS: This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.

Several studies have demonstrated that chronic exposure to gluten may damage the structure and function of the gastric mucosa in gluten-sensitive patients. However, until now, these abnormalities have been incompletely studied. Our purpose in the present study was to characterize, in a prospective controlled study, the endoscopic and histological appearance of the gastric mucosa in a large cohort of patients with celiac disease with and without Helicobacter pylori (H. pylori) infection.We evaluated biopsy specimens taken from the gastric body and antrum of 218 individuals who underwent upper endoscopy for small bowel biopsy. One hundred-four patients had celiac disease (80 of them at the time of diagnosis-untreated). In 114 subjects celiac disease was excluded.Endoscopic findings did not show a difference between the groups. The prevalence of cases with normal gastric mucosa, chronic superficial gastritis, and atrophic gastritis was similar in patients and controls. Similarly, presence of metaplasia, inflammatory activity, and lymphoid follicles and aggregates did not show differences between the groups. Histological or serological evidence of H. pylori infection was detected in 86% of patients (82% of untreated celiacs and 95% of those on those taking treatment). The infection was highly prevalent in patients (89%) and controls (97%) diagnosed with chronic gastritis. Untreated patients had a significant greater IEL count in the antrum and corpus than controls (p0.0001 and p0.001, respectively). A global analysis of the data on intraepithelial lymphocyte (IEL) counts in the different populations suggest that the inflammatory state may represent the cumulative effect of H. pylori infection and gluten sensitivity. Only three patients had IEL infiltration compatible with diagnosis of lymphocytic gastritis (count25%) and three other patients had borderline counts.According to our results, celiac disease patients presented a similar prevalence of gastric mucosal abnormalities compared with the control population. Evidence of H. pylori infection was very high compared with the prevalence in the general Argentine population. As a particular observation in our celiac population, the disease was rarely associated with lymphocytic gastritis. We suggest that the chronic inflammatory state evidenced by a gastric mucosal lymphocyte infiltration may be secondary to the combination of H. pylori infection and chronic gluten ingestion in gluten-sensitive subjects.

Should ESPGHAN Guidelines for Serologic Diagnosis of Celiac Disease be Used in Adults? A Prospective Analysis in an Adult Patient Cohort With High Pretest Probability

Retractile mesenteritis is a rare inflammatory mesenteric disorder that involves the intestine secondarily. The natural history of this process is diverse, but most patients require some empiric therapeutic measures. Up to now, pharmacological therapy has included corticosteroids, colchicine, and immunosuppressive drugs. Although these drugs are successful in most patients, some have been refractory to these therapies and, in others, the beneficial effects were counterbalanced by adverse reactions. Many patients require surgery, but most have poor results. This report describes a 42-year-old man with histologically proven retractile mesenteritis refractory to surgical intervention who had a good response to oral progesterone (10 mg/day for 6 months) with complete disappearance of tumor mass and clinical symptoms. No adverse effects were detected. Current knowledge about the mechanism by which progesterone affects fibrogenesis is scanty. It seems likely that progesterone down-regulates proliferation and metabolism of fibroblasts and fibrogenesis.

Objective Whereas celiac disease and primary biliary cirrhosis have been reported to coexist in the same patient, the frequency of this relationship has not been clarified. Nowadays, the concept of celiac disease has been extended from that of a severe enteropathy to a broader concept of gluten-driven intestinal immunological response. In this study we assessed features of gluten sensitivity in a cohort of patients with primary biliary cirrhosis. Methods: Ten patients with primary biliary cirrhosis were evaluated a mean of 2 yr after diagnosis. The following features of gluten sensitivity were assessed: serum antigliadin and endomysial antibodies, small bowel histology (degree of atrophy and quantitative histological parameters), the presence of the typical celiac HLA genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa after local gluten instillation (rectal gluten challenge). Results Overall, three patients presented evidence of gluten sensitivity. All three had abnormal titers of antigliadin antibody type IgA and one was positive for endomysial antibody. Two patients had partial villous atrophy. The rectal gluten challenge showed a celiac-like response, evidenced by an increase in intraepithelial lymphocyte infiltration after gluten exposure, in the three patients. The characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in three patients. One of them also exhibited other features of gluten sensitivity. However, despite evidence of gluten intolerance, patients had minimal or no symptoms characteristic of celiac disease. Conclusion We detected features of gluten sensitivity in a high proportion of patients with primary biliary cirrhosis. Further studies should be performed to elucidate the clinical significance of this association.