Coeliac Disease Case-Control Study: Has the Time Come to Explore beyond Patients at Risk?

The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

Encephalopathy in short bowel syndrome: a diagnostic challenge.

A 15-year-old boy was admitted to the hospital due to ataxia, drowsiness and bradypsychia. He was known to have a short bowel syndrome Initial venous blood gases revealed a metabolic acidosis with a high anion gap of 24 mmol/L and normal L-lactate. He improved with fasting and fluids and was discharged with oral metronidazole. 2 weeks later he was admitted again with similar symptoms. A specific study of D-Lactic acidosis was carried out, confirming the diagnosis. D-lactic acidosis is an uncommon complication of short bowel syndrome. It occurs as a consequence of the metabolism of unabsorbed carbohydrates. The symptoms are mainly neurological. Limiting the dietary carbohydrates is useful to avoid recurrences. Poorly absorbable antibiotics are used but with varying results. Surgery may be an option if medical treatment fails. Probiotics might be useful to avoid symthoms recurrence.

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain.

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections. CONCLUSION: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective. WHAT IS KNOWN: • The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain. • Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease. WHAT IS NEW: • A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone. • Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

Correlation of Anti-Tissue Transglutaminase Antibodies With the Mucosal Changes and IgA Status of Children With Celiac Disease.

OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.

Intestinal anti-tissue transglutaminase IgA deposits as a complementary method for the diagnostic evaluation of celiac disease in patients with low-grade histological lesions.

Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2-3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2-3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.

The Use of Fecal Calprotectin Testing in Paediatric Disorders: A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee.

OBJECTIVES: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. METHODS: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. RESULTS: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. CONCLUSIONS: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schönlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

Screening-detected positive serology for celiac disease: a real clinical challenge.

According to European Society for Paediatric Gastroenterology, Hepatology, and Nutrition 2020 criteria for celiac disease diagnosis, the small bowel biopsy (SBB) can be omitted in selected circumstances, even in asymptomatic patients. Hence, we have conducted a retrospective study to identify the histological findings of the asymptomatic patients with antitransglutaminase IgA antibodies 10 times above the upper limit of normal and positive antiendomisium antibodies; 5/24 patients fulfilling these criteria had, however, a nonconclusive SBB and were diagnosed with potential celiac disease. The nonbiopsy approach in these cases needs to be carefully evaluated and the risk of overdiagnosis pondered as the management and evolution of potential celiac disease cases is still a matter of study.

Analysis of gluten immunogenic peptides in feces to assess adherence to the gluten-free diet in pediatric celiac patients.

PURPOSE: In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. METHODS: A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. RESULTS: Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p < 0.001) in a non-linear way (p = 0.028) after starting a GFD and were below the detection limit on the third day in most individuals. CONCLUSION: GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated.

Fecal calprotectin in healthy children aged 4-16 years.

Reference values of fecal calprotectin (fCP) have not been convincingly established in children. We aimed to investigate fCP concentrations in a larger population of healthy children aged 4-16 years to analyze more in depth the behavior of fCP in this age range and to determine if cut-off levels could be conclusively recommended. A prospective study was conducted to investigate fCP concentrations of healthy children aged 4-16 years. In 212 healthy children, the median and 95th percentile for fCP were 18.8 mg/kg and 104.5 mg/kg, respectively. We found a statistically significant association between the 95th percentile of fCP concentrations and age (p < 0.001). We propose a nomogram to facilitate the interpretation of fCP results in children aged 4-16 years. Further studies are required to validate the proposed values in clinical practice.

Recurrent Metabolic Alkalosis in a Cystic Fibrosis Patient: Coexistence with Congenital Chloride Diarrhea.

Metabolic alkalosis is uncommon in infancy. Cystic fibrosis (CF) patients can develop dehydration because of sweat salt or gastrointestinal losses; with the correct salt supplementation, the electrolyte alterations can be reversed. Here, we present a CF patient with recurrent metabolic alkalosis, initially oriented as pseudo-Bartter's syndrome. However, despite accurate treatment, patient needed daily intravenous fluids to maintain homeostasis. An extended study was made, including a urine study that could rule out Bartter's diagnosis. Finally, after a complementary test that included electrolyte stools study and genetic analysis, congenital chloride diarrhea could be diagnosed.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population.

The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children.

Common Problems Found in the Methodological Approach to Small Bowel Biopsies in the Diagnosis of Celiac Disease.

Small bowel biopsy (SBB) is not always helpful to establish celiac disease diagnosis. Hence we have conducted a retrospective study to know the amount of SBB in our center that was not optimal for this purpose. Histological findings were not appropriate for diagnosis in 3.56% (34 out of 955). The main problem encountered was inadequate sample cutting, although this could be solved by a new recut in almost 30% of cases.

Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned.

AIM: to evaluate the influence of gluten consumption on celiac disease development and to describe its natural history in the Spanish cohort of the European PreventCD study. METHODS: prospective multi-center double blind study of 225 children that were followed up from birth. All cases were HLA-DQ2/HLA-DQ8 positive with a 1st degree relative with celiac disease and were followed up in three centers from Madrid, Reus and Valencia. Gluten intake was determined between four and ten months according to the protocol. Gluten intake was ad libitum between eleven and 36 months and was prospectively quantified by means of dietary records. Clinical visits and specific antibody analysis for celiac disease were performed periodically. RESULTS: twenty-six cases were diagnosed, all had a positive biopsy and serology; 21 had gastrointestinal symptoms and five were asymptomatic. In addition, 2,565 food records were analyzed and statistically significant differences (p < 0.001) were found with regard to gluten consumption among the three centers, although not between celiac and non-celiac children (p = 0.025). The HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes had a relative risk of 4.7 (95% CI: 0.80-27.55; p = 0.08), which was higher than for the rest of genotypes. Female gender also had a relative risk that was five times higher than that for males. CONCLUSIONS: the amount of gluten intake between 11 and 36 months or the duration of breast feeding were not risk factors for the development of CD in the Spanish population. The HLA genotype and gender were the most relevant associated factors. In this at-risk group, the disease presented before two years of age in the majority of the cases with a weak clinical expression.

Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.

BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study.

OBJECTIVES: A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). METHODS: The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. RESULTS: CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. CONCLUSIONS: Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

Guideline for wireless capsule endoscopy in children and adolescents: A consensus document by the SEGHNP (Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition) and the SEPD (Spanish Society for Digestive Diseases).

INTRODUCTION: Capsule Endoscopy (CE) in children has limitations based mainly on age. The objective of this consensus was reviewing the scientific evidence. MATERIAL AND METHODS: Some experts from the Spanish Society of Gastroenterology (SEPD) and Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP) were invited to answer different issues about CE in children. These sections were: a) Indications, contraindications and limitations; b) efficacy of CE in different clinical scenarios; c) CE performance; d) CE-related complications; e) Patency Capsule; and f) colon capsule endoscopy. They reviewed relevant questions on each topic. RESULTS: The main indication is Crohn's disease (CD). There is no contraindication for the age and in the event that the patient not to swallow it, it should be administered under deep sedation with endoscopy and specific device. The CE is useful in CD, for the management of OGIB in children and in Peutz-Jeghers syndrome (in this indication has the most effectiveness). The main complication is retention, which should be specially taken into account in cases of CD already diagnosed with malnutrition. A preparation regimen based on a low volume of polyethylene glycol (PEG) the day before plus simethicone on the same day is the best one in terms of cleanliness although does not improve the results of the CE procedure. CONCLUSIONS: CE is safe and useful in children. Indications are similar to those of adults, the main one is CD to establish both a diagnosis and disease extension. Moreover, only few limitations are detected in children.

Duodenal-mucosal bacteria associated with celiac disease in children.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of cereal gluten proteins. This disorder is associated with imbalances in the gut microbiota composition that could be involved in the pathogenesis of CD. The aim of this study was to characterize the composition and diversity of the cultivable duodenal mucosa-associated bacteria of CD patients and control children. Duodenal biopsy specimens from patients with active disease on a gluten-containing diet (n = 32), patients with nonactive disease after adherence to a gluten-free diet (n = 17), and controls (n = 8) were homogenized and plated on plate count agar, Wilkins-Chalgren agar, brain heart agar, or yeast, Casitone, and fatty acid agar. The isolates were identified by partial 16S rRNA gene sequencing. Renyi diversity profiles showed the highest diversity values for active CD patients, followed by nonactive CD patients and control individuals. Members of the phylum Proteobacteria were more abundant in patients with active CD than in the other child groups, while those of the phylum Firmicutes were less abundant. Members of the families Enterobacteriaceae and Staphylococcaceae, particularly the species Klebsiella oxytoca, Staphylococcus epidermidis, and Staphylococcus pasteuri, were more abundant in patients with active disease than in controls. In contrast, members of the family Streptococcaceae were less abundant in patients with active CD than in controls. Furthermore, isolates of the Streptococcus anginosus and Streptococcus mutans groups were more abundant in controls than in both CD patient groups, regardless of inflammatory status. The findings indicated that the disease is associated with the overgrowth of possible pathobionts that exclude symbionts or commensals that are characteristic of the healthy small intestinal microbiota.

Celiac disease: the new proposed ESPGHAN diagnostic criteria do work well in a selected population.

BACKGROUND: The need for an early and accurate diagnosis in celiac disease (CD) has focused attention on new diagnostic approaches, based on the efficiency of serological markers and the high negative predictive value of human leukocyte antigen (HLA) non-DQ2/8. METHODS: We performed a retrospective review of all of the patients suspected of having CD who had undergone a small bowel biopsy in our gastroenterology unit. All symptomatic children with serological marker at time of biopsy (immunoglobulin A-tissue transglutaminase antibody, endomysial antibody, and HLA genotype) were included. The triple test (TT) was positive if immunoglobulin A-tissue transglutaminase antibody was 10 times the upper limit of normal, plus positive endomysial antibody plus human leukocyte antigen-DQ2/DQ8. RESULTS: A total of 150 patients met the inclusion criteria and were enrolled in the study. One hundred sixteen were positive for the TT; 113 of 116 (97.4%) had a Marsh 2/3 histological lesion and had been considered to have CD. Thus, positive predictive value of the TT was 97.4%. The other 3 cases (2.6%) had Marsh 0/1 lesion, so we consider them to be false-positives for the TT; however, on follow-up, all 3 children developed histological damage after a gluten challenge. Finally, the positive predictive value of the TT was 100%. Thirty-four patients were negative for the TT: 22 patients are celiac, 3 are celiac but challenge gluten diet is pending, and the 9 patients left have other gastrointestinal disorder. CONCLUSIONS: Our study supports the view that in selected children who are symptomatic and positive for the TT, CD diagnosis could be established independent of histological findings.

Intestinal Bacteroides species associated with coeliac disease.

AIMS: To characterise the predominant species of bacterial populations associated with duodenal biopsies of paediatric patients with active and treated coeliac disease. METHODS: 20 biopsy specimens from patients with active coeliac disease, 12 from patients with treated coeliac disease, and eight from age-matched controls were evaluated for comparative purposes. Bacteroides, Bifidobacterium and lactic acid bacteria (LAB) populations were analysed by PCR-denaturing gradient gel electrophoresis using group-specific primers. RESULTS: Bacteroides diversity was higher in biopsy specimens from controls than in those from patients with active and treated coeliac disease. Bacteroides distasonis, Bacteroides fragilis/Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides ovatus were more abundant in controls than in patients with coeliac disease (p<0.05). Bacteroides vulgatus was more frequently detected in controls than in patients with treated coeliac disease (p<0.01). Bacteroides dorei was more common in patients with active coeliac disease than in those with treated coeliac disease and control children (p<0.01). Bifidobacterium diversity was higher in patients with coeliac disease than in controls. Bifidobacterium adolescentis and Bifidobacterium animalis subsp lactis were more prevalent in patients with active coeliac disease than in patients with treated coeliac disease and control children. A higher LAB diversity was found in patients with treated coeliac disease and controls than in patients with active coeliac disease. Weissella spp and Lactobacillus fermentum were more frequently detected in patients with treated coeliac disease than in controls and patients with active coeliac disease. CONCLUSIONS: Bacteroides, Bifidobacterium and LAB populations in the duodenum of Spanish children with typical coeliac disease (active and treated) and controls differ in diversity and species composition; this could contribute to features of the disease.

Imbalances in faecal and duodenal Bifidobacterium species composition in active and non-active coeliac disease.

BACKGROUND: Gut bifidobacteria are believed to influence immune-related diseases. The objective of this study was to assess the possible relationships between the gut bifidobacteria composition and coeliac disease (CD) in children. A total of 48 faecal samples (30 and 18 samples from active and no active CD patients, respectively) and 33 duodenal biopsy specimens of CD patients (25 and 8 samples from active and non-active CD patients, respectively) were analysed. Samples (30 faecal samples and 8 biopsies) from a control age-matched group of children were also included for comparative purposes. Gut Bifidobacterium genus and species were analyzed by real-time PCR. RESULTS: Active and non-active CD patients showed lower numbers of total Bifidobacterium and B. longum species in faeces and duodenal biopsies than controls, and these differences were particularly remarkable between active CD patients and controls. B. catenulatum prevalence was higher in biopsies of controls than in those of active and non-active CD patients, whereas B. dentium prevalence was higher in faeces of non-active CD patients than in controls. Correlations between levels of Bifidobacterium and B. longum species in faecal and biopsy samples were detected in both CD patients and controls. CONCLUSION: Reductions in total Bifidobacterium and B. longum populations were associated with both active and non-active CD when compared to controls. These bacterial groups could constitute novel targets for adjuvant dietary therapies although the confirmation of this hypothesis would require further investigations.