The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented.
Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, HLA genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations.
Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. HLA DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely.
CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

Celiac disease (CD) is a lifelong condition with significant morbidity and requires an accurate diagnosis. Guidelines for pediatric CD were revised by the European and British Societies of Paediatric Gastroenterology Hepatology and Nutrition in 2012 and 2013, respectively. New recommendations introduced non-biopsy pathway (NBP) of diagnosis for a selective group of symptomatic children whose anti-tissue transglutaminase (anti-tTG) antibody titer is greater than ten times upper limit of normal. A clear understanding of the guidelines amongst consultant pediatricians will ensure all children with suspected CD receive a prompt and secure diagnosis. The aim of this study was to establish the interpretation and implementation of the revised guideline for CD amongst consultant general pediatricians in Southwest England (SWE) during the study period.
Telephone/email survey was conducted amongst consultant general pediatricians (n ≈ 140) working in 12 secondary care hospitals across SWE. The survey included eight questions incorporating three main themes: understanding of diagnostic pathway particularly for non-biopsy diagnosis, awareness of laboratory tests involved, and variations in practice in relation to the revised guidelines.
Responses were available from 101/140 (72%). One hundred respondents were aware of the revised guidelines for diagnosing CD. However, only 17 respondents stated all the criteria of the guideline required for diagnosis by NBP, with further 17 seeking immediate advice from a specialist. Forty-four listed both the criteria for HLA-DQ2/DQ8 testing applicable to pediatricians. Forty-nine out of 100 pediatricians would commence gluten-free diet only after all the results were available. Thirty-three pediatricians also considered asymptomatic children with high anti-tTG titer eligible for diagnosis of CD by NBP.
There is a need for improved understanding of revised CD guidelines amongst consultant general pediatricians especially while using the NBP and requesting HLA-DQ2/DQ8 testing.

The 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline for diagnosis of celiac disease (CD) questioned the requirement for intestinal biopsy to confirm the diagnosis. The guideline recommends that in symptomatic patients with consistent human leukocyte antigen (HLA) subtypes, the diagnostic accuracy of strongly positive serology is sufficient to confirm the diagnosis. We prospectively assessed these guidelines in a \"real-life\" clinical setting.
One hundred and four children referred for evaluation of possible CD were prospectively recruited. Following informed consent, blood was drawn for serological testing and HLA analysis at upper gastrointestinal endoscopy. Histological findings according to Marsh criteria were correlated with blood results and the accuracy of the guideline analyzed.The study also examined the role of deamidated gliadin peptide (DGP) in the diagnosis of CD.
For symptomatic patients with consistent HLA subtypes, strongly positive serology (as described in the ESPGHAN guidelines) accurately predicted biopsy-proven CD in >95% of cases. DGP was positive in fewer patients than anti-TG2 or EMA. Incorporation of DGP as a second confirmatory serological test in place of EMA was associated with maintained predictive value of guideline, but fewer patients fulfilling criteria for biopsy-free diagnosis.
The ESPGHAN guideline performs well in our population. Adoption of the guideline would reduce the number of patients requiring endoscopy without compromise in diagnostic accuracy. The involvement of pediatric gastroenterological expertise, however, remains key to diagnosis of CD.

OBJECTIVE: Coeliac disease (CD) is more common in those with type 1 diabetes mellitus (T1DM) and may be asymptomatic despite the presence of intestinal histological changes. Optimal screening practice guidelines differ internationally. We undertook a retrospective audit to determine the efficacy of current screening practice for CD in T1DM in our centre.
METHODS: All children and adolescents < 16 years, diagnosed with T1DM in our service and continuing to attend the service in January 2017 were included. Data on CD screening was collected and compared to current NICE, NASPGHAN and ESPGHAN guidelines.
RESULTS: Of the 355 patients attending our service, 253 attended from T1DM diagnosis and all had CD screening performed in our centre. In 37 of 253 patients, IgA-TTG was positive, providing a cumulative prevalence of 14.6%. Of these, 31(83.78%) with an elevated TTG on screening had no recorded gastrointestinal symptoms or CD-related clinical signs. Of the 35 TTG plus EMA-positive patients, 22/35 (59.46%) had diagnostic endoscopic biopsy. Nineteen (83.4%) had CD confirmed, 1 (4.54%) had negative biopsy and 2 (9%) had equivocal, non-diagnostic changes.
CONCLUSIONS: Timely diagnosis of CD can prevent chronic ill health in affected individuals, and in patients with T1DM, CD is an independent risk factor for increased morbidity and mortality. Given the high prevalence of atypical symptoms and silent CD in those with T1DM, in this and other studies, and the benefits of detection and treatment of CD, screening is essential. Large-scale data collection allowing for the development of evidence-based guidelines is required.

BACKGROUND: We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources.
METHODS: A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities.
RESULTS: There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94-97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD.
CONCLUSIONS: The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies.

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OBJECTIVE: In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients.
METHODS: We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers.
RESULTS: A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD (\"high-titer\" symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic (\"high-titer\" asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between \"high-titer\" symptomatic and \"high-titer\" asymptomatic children (Fisher exact test, P=1.000).
CONCLUSIONS: If confirmed in large multicenter prospective studies, the \"biopsy-sparing\" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

OBJECTIVE: We retrospectively examined the performance of the tissue transglutaminase (TTG), endomysial antibody (EMA) tests, and the ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition) nonbiopsy criteria in a pediatric population.
METHODS: Consecutive celiac serologies and corresponding intestinal biopsy results were obtained on children <18 years old over 3.5 years. Patients were classified into three categories: positive TTG, negative TTG, and IgA deficiency.
RESULTS: Of the 17,505 patients with celiac serology performed, 775 had a positive TTG, 574 with a negative TTG were biopsied, and 25 were IgA deficient. Of the patients with a TTG ≥10 × upper limit of normal (ULN), positive EMA, and symptoms, 98.2% had biopsies consistent with celiac disease (CD). Four human leukocyte antigen (HLA) DQ2/DQ8-positive patients who met the ESPGHAN nonbiopsy criteria did not have CD. In the group with a TTG 3-10 × ULN, 75.7% EMA-positive patients and only 40% EMA-negative patients had CD (P<0.001). Of those with a TTG 1-3 × ULN, 52.2% EMA-positive patients vs. only 13.3% EMA-negative patients had CD (P<0.01). Of the patients with bulbar and duodenal biopsies, 9.8% had CD confined only in the bulb, especially those with a low titer TTG (P<0.01). CD prevalence in our cohort was 34.6%. Sensitivity, specificity, and positive predictive value of the TTG were 98.7%, 86.4%, and 79.4%, respectively.
CONCLUSIONS: The TTG is a very sensitive screen for CD, but positive predictive value improves with a positive EMA titer. To apply the new ESPGHAN guidelines, clinicians must understand the performance of their celiac serology tests.

Celiac disease is a relatively common immunological systemic disease triggered by the protein gluten in genetically predisposed individuals. Classical symptoms like chronic diarrhea, steatorrhea, weight loss and growth retardation are nowadays relatively uncommon. Diagnostic workup includes serological tests for IgA antibodies against tissue transglutaminase 2 (anti-TG2-IgA) and total IgA and histology of duodenal biopsies. Histomorphological classification should be done according to the modified Marsh-Oberhuber classification. Diagnosis of celiac disease should be based on serological, clinical, and histological findings. The only treatment is a life-long gluten-free diet. Unchanged or recurrent symptoms under gluten-free diet may indicate refractory celiac disease. Enteropathy-associated T-cell lymphoma and adenocarcinomas of the small intestine are known complications of celiac disease.

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.