Guidelines For Celiac Disease Research Articles

Celiac disease prevalence and predisposing-HLA in a cohort of 93 Williams-Beuren syndrome patients.

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p> .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.

Update on celiac disease

Celiac disease is a T-cell-mediated autoimmune disorder. It is relevant to us for two very different reasons. Firstly, it has a prevalence of 1 % in the European population. Thus, a huge number of celiac patients remains undiagnosed. Secondly, the celiac trigger, gluten, functions as a "switch", that has the potential to selectively activate celiac immune pathology, thereby allowing us to uncover previously unknown immune conditions. This again contributes to new celiac treatment modalities that will presumably alleviate the future fate of celiac disease patients. In 2022, the German guidelines for celiac disease are published by the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS). We have summarized some of the recommendations published therein.

IgA Deficiency Is Not Systematically Ruled Out in Patients Undergoing Celiac Disease Testing

Guidelines for celiac disease (CD) testing recommend total serum IgA determination alongside anti-transglutaminase IgA antibodies. It is not well known if lack of serum IgA determination is a common finding in clinical practice. To determine the prevalence of lack of serum IgA determination among patients screened for celiac disease. We identified all subjects who underwent serum anti-transglutaminase IgA and/or other CD-related antibodies determination at a single teaching hospital in Buenos Aires from October 2019 to February 2020. Medical records were reviewed to select adult patients who were tested for celiac disease. The primary outcome was the proportion of patients with inadequate testing for celiac disease due to lack of serum IgA determination. We retrieved the following variables from each patient's record: age, gender, body mass index, symptoms present at screening, first-grade family history of CD, history of type-1 diabetes mellitus, autoimmune hypothyroidism, Down's syndrome. Overall, 1122 patients were included for analysis. Lack of serum IgA determination prevalence was 20.49%. Among patients who did have serum IgA determination, the prevalence of IgA deficiency was 5.16%. The following variables were independently associated with a significantly increased odds of serum IgA determination: diarrhea [OR 1.55 (1.01-2.34)] and abdominal pain [OR 2.28 (1.44-3.63)]; higher body mass index [OR 0.91 (0.85-0.98)], osteoporosis [OR 0.49 (0.28-0.89)], hypothyroidism [OR 0.18 (0.07-0.45)], arthralgia/arthritis [OR 0.47 (0.27-0.85)], or testing by endocrinologist [OR 0.46 (0.23-0.91)] and gynecologist [OR 0.14 (0.06-0.31)] were inversely associated. IgA deficiency is not systematically ruled out in a relatively high proportion of patients undergoing serological screening of celiac disease.

ESPGHAN 'biopsy-sparing' guidelines for celiac disease in children with low antitransglutaminase during COVID-19.

Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.

Current Espghan Guidelines for Celiac Disease in Pediatric Age, Tertiary Care Center Experience: A Proposal for Further Simplification.

This is a retrospective study conducted on all patients diagnosed CD from 2012 to 2018 in our Center. For all patients enrolled were analyzed: data of family history, symptoms, serology, genetics, Marsh grade and follow-up. A total of 481 children [mean age 6,4 yrs; F:M= 1.8:1] were included in the study. The mean age of patients who were not subject to DB was lower (4.51 yrs) comparing with patients that received DB (6.48 yrs). Out of the 256 patients with anti-tTG2 ≥ 10 fold, 121 underwent DB because of mild symptoms (84/121) or no symptoms (37/121). In all cases Marsh type 3 was found and HLA haplotypes was compatible with CD diagnosis. Our study confirms that the serology has a primary importance to diagnose CD, regardless of the symptoms. These data suggest that biopsy and HLA haplotypes search, in presence of anti-tTG2 IgA ≥ 10x the cut-off, are wasteful and unhelpful for the patients.

Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease.

Current diagnostic guidelines for celiac disease (CD) in pediatric patients require a duodenal biopsy if the IgA anti-tissue transglutaminase (tTG) is below 10x the upper limit of normal (ULN). Additional markers may enable a noninvasive diagnosis in this group. Serum intestinal-fatty acid-binding protein (I-FABP), a marker for intestinal epithelial damage, could be useful in this respect. A total of 95 children with a clinical suspicion of CD and tTG 1-10x ULN were investigated. All had a duodenal biopsy and analysis of serum I-FABP. A control group of 161 children with familial short stature and normal tTG was included. I-FABP levels in the 71 patients with tTG 1-10x ULN and biopsy-proven CD (median 725pg/mL) were not significantly different (p=0.13) from the levels in the 24 patients with a tTG 1-10x ULN but a normal biopsy (median 497pg/mL). However, when combining tTG and I-FABP levels, 11/24 patients could have been diagnosed noninvasively if tTG is ≥ 50 U/mL and I-FABP ≥880pg/mL or in 12/19 patients if tTG is ≥ 60 U/mL and I-FABP ≥ 620pg/mL. Therefore, addition of I-FABP to the diagnostic procedure of CD may provide a noninvasive diagnosis in patients with a tTG ≥ 50 U/mL.

Management of celiac disease: from evidence to clinical practice

Celiac disease (CD) is a complex polygenic disorder, which involves genetic factors human leukocyte complex (HLA) and non-HLA genes, environmental factors, innate and adoptive immunity, and a robust chronic T-mediated autoimmune component. The main goal of the present monograph is to define a methodological approach for the disease, characterized by frequent late diagnosis, in order for the physician to become aware of the disease management, the diversity of the clinical presentation itself and in different patients. A unique attention is payed to the specific diagnostic tests to define a correct and accurate application of them, and in addition, to disease follow-up and possible complications. Moreover, a dedicated space is assigned to refractory CD, to potential CD and non-celiac gluten sensitivity. Legislative aspects of the celiac disease in Italy are addressed, too. The celiac disease guidelines and their evaluation by means of Appraisal of Guidelines, Research and Evaluation II instrument allow us to classify the different recommendations and to apply them according to the stakeholders’ involvement, pertinence, methodological accuracy, clarity and publishing independence. Finally, the most current scientific evidence is taken into account to create a complete updated monograph.

Adherence to Endoscopy Biopsy Guidelines for Celiac Disease.

Histologic changes in celiac disease (CD) may be patchy or confined to the bulb. Present guidelines recommend obtaining multiple biopsies from the bulb and distal duodenum when evaluating for CD. Adherence to these recommendations among adult gastroenterologists is low. There are no such data for pediatric gastroenterologists. This study compared endoscopic biopsy practices among pediatric gastroenterologists in histologically confirmed patients with CD to those without histologically confirmed CD. Retrospective review of esophagogastroduodenoscopies (EGDs) during a 13-month period was performed. Children with histologically confirmed CD and a random sample of age-matched children without CD were identified. Endoscopy and histology reports were reviewed. The site and number of biopsy samples obtained was recorded. The groups were compared for number of biopsies. A total of 98 children with CD were compared with 103 controls without CD. The number of biopsies obtained in the group with CD was higher than the group without CD (5.9 ± 1.6 vs 3.6 ± 1.2) (P < 0.0001). In children with CD, 80.5% had ≥5 biopsies compared with 11.7% in the group without CD (P < 0.0001). Only 10% of the children in the group with CD had bulb biopsies documented compared with none in the group without CD. Pediatric gastroenterologists at our center generally obtain the recommended number of biopsies in children with histologically confirmed CD but seldom document biopsies from the bulb. In those without histologic evidence of CD, fewer biopsies are obtained with none documented from the bulb. Failure to take the recommended number of biopsies could result in some missed cases of CD.

Are ESPGHAN "biopsy-sparing" guidelines for celiac disease also suitable for asymptomatic patients?

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. 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. 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). 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.

Are ESPGHAN 2011 guidelines for celiac disease also suitable for asymptomatic patients?

of age (CDA: 16% versus 7%, P=0.002; overt CD: 12% versus 5%, P=0.01). However, this difference resolved at age five years (CDA: 21% in group A and 20% in group B, P=0.59; overt CD: 17% in group A and 17% in group B, P=0.78). Children with a high-risk HLA had a significantly higher risk of developing CDA and overt CD than did those with standard-risk HLA (CDA: 38% versus 19%; P=0.001; overt CD: 29% versus 16%; P=0.05). Other variables, including breast-feeding, were not associated with CD development. We did not observe any adverse events. Conclusions:Neither delayed introduction of gluten nor breastfeeding protects or increases the risk of CD in at-risk infants. Having a high-risk-HLA allele is an important disease predictor.

Prudence is necessary in the application of the new ESPGHAN criteria for celiac disease omitting duodenal biopsy

New guidelines for celiac disease (CD) diagnosis from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) propose the option to omit the duodenal biopsy in the diagnosis of CD. For this option, all four of the following criteria have to apply in children and adolescents: signs and symptoms suggestive of CD, anti-transglutaminase type 2 antibody (anti-TG2) levels more than 10 times the upper limit of normal, positive confirmation tests of anti-endomysium-IgA antibodies (EMA), and at-risk HLA-DQ2 or HLA-DQ8. Here, we report the case of a female patient, 2 years old, with chronic diarrhea that started after an acute viral gastroenteritis. The patient had anti-TG2 levels of more than 10 times the upper limit of normal, positivity for EMA, antigliadin IgA, and IgG (AGA-IgA, AGA-IgG, respectively), and the at-risk HLA-DRB1*0301, DQB1*0201/DRB1*10, DQB1*0501 genotype, thus fulfilling all criteria for the diagnosis of CD. Although the diarrhea disappeared after about 5 weeks, anti-TG2, EMA, and AGA-IgG remained positive. Therefore, a duodenal biopsy was performed and evidenced a normal mucosa (Marsh 0). After about 18 months, the antibody titer for AGA-IgG, anti-TG2, and EMA became negative. The patient was all the time on a normal, gluten-containing diet. This clinical case represents an exception to the new ESPGHAN guidelines for CD diagnosis. During 5 weeks, the new ESPGHAN criteria were all fulfilled, allowing to propose for this patient the diagnosis of CD without performing a duodenal biopsy. Therefore, a prudent approach is suggested when the pediatric gastroenterologist makes a diagnosis of CD without duodenal biopsy.

Tu1134 Are ESPGHAN 2011 Guidelines for Celiac Disease Also Suitable for Asymptomatic Patients?

positive scores on ASD screening questionnaires. Although only a small number meet criteria for a classic ASD, the majority meets criteria for other DSM-IV diagnoses. Further studies are needed to determine whether particular autistic-like behaviors, such as disruptive behaviors, are associated with particular phenotypes of FDDs or different outcomes. Physicians dealing with children with FDD need to be vigilant to uncover possible associated behavioral disturbances.

Procedure volume influences adherence to celiac disease guidelines

Although the prevalence of celiac disease in the USA approaches 1%, most cases are undiagnosed, in part, because of low adherence to the recommendation of submitting at least four specimens during duodenal biopsy. We aimed to determine whether physician and practice characteristics are associated with adherence to this recommendation. We used a large national pathology database to identify all adult patients who underwent duodenal biopsy during 2006-2009. Hierarchical modeling was used to determine whether procedure volume, the number of gastroenterologists per endoscopy suite, and the number of gastroenterologists per capita of the zip code of the practice were associated with adherence. We identified 92 580 patients (67% female, mean age 53.5 years) who met our inclusion/exclusion criteria. Specimens were submitted by 669 gastroenterologists from 200 endoscopy suites, located in 191 zip codes, with a mean of 3.4 gastroenterologists per suite. On multivariate analysis, a higher procedure volume was associated with a decreased adherence [odds ratio (OR) for each additional 100 procedures, 0.92; 95% confidence interval (CI), 0.88-0.97; P=0.002]. An increased adherence was reported for gastroenterologists working at suites with higher numbers of gastroenterologists (OR for each additional gastroenterologist, 1.08; 95% CI, 1.04-1.13; P<0.001) but not for a higher gastroenterologist density in the zip code of the practice (OR for each additional gastroenterologist per capita, 1.01; 95% CI, 0.99-1.03; P=0.21). High-volume physicians exhibit lower rates of adherence to biopsy guidelines, possibly because of the additional time required to submit at least four specimens. In contrast, a greater number of endoscopists working in an endoscopy suite are associated with an increased adherence, possibly because of peer education.

68 A Multicenter Review of the New Espghan Guidelines for Celiac Disease: How Many Biopsies Can We Really Skip?

68 A Multicenter Review of the New Espghan Guidelines for Celiac Disease: How Many Biopsies Can We Really Skip?

Do Gastroenterologists Adhere to Diagnostic and Treatment Guidelines for Celiac Disease?

Our group hypothesized that significant variation exists between suggested clinical guidelines, the clinical practices of practicing gastroenterologists and academic experts in celiac disease (CD). We designed 4 CD vignettes comparing experts and practicing gastroenterologists. Practicing gastroenterologists (n=169) were surveyed during Digestive Disease Week 2009 and experts (n=22) answered e-mail surveys. Ratings for answers in each vignette was done using a 9-point RAND Appropriateness Scale (RAS) with endorsement defined as RAS score of 7 to 9. We also calculated the RAND "Disagreement Index" (DI) was calculated, with DI>1.0 indicated extreme variation. A total of 169 practicing gastroenterologists and 22 experts were included. Differences in all vignette answers were present. Differences were seen for use of IgA anti-endomysial antibodies (P=0.0241), human leukocyte antigen DQ2/8 testing (P=0.0325), gluten challenge (P<0.0001), and oat consumption (P<0.0001). There were differences in recommendations for biopsy review (P=0.0479) and management of dermatitis herpetiformis (P=0.0025). Experts consistently endorsed CD screening in patients with type 1 diabetes, Down and Turner syndromes, and relatives of CD patients compared with practicing physicians (P=0.0054, 0.0003, <0.0001, 0.0304). Experts endorsed CD screening for atypical presentations (delayed puberty, elevated transaminases, primary biliary cirrhosis, autoimmune hepatitis, and infertility). There is significant disagreement between nonexperts and experts in diagnosis and management of CD. Promotion of existing guidelines and further research is advised.

Capsule Endoscopy: A Valuable Tool in the Follow-Up of People With Celiac Disease on a Gluten-Free Diet

OBJECTIVES:Traditional celiac disease guidelines recommend follow-up endoscopy and duodenal biopsies at 6–12 months after commencing a gluten-free diet (GFD). However, histology may remain abnormal even 1–2 years later. We evaluated the role of capsule endoscopy in patients with celiac disease after treatment with a GFD.METHODS:Twelve adult patients with newly diagnosed celiac disease were prospectively enrolled. All patients had baseline symptom assessment, celiac serology (tissue transglutaminase antibody, tTG), and capsule endoscopy. Twelve months after commencing a GFD, patients underwent repeat symptom assessment, celiac serology, upper gastrointestinal endoscopy, and capsule endoscopy.RESULTS:At baseline, capsule endoscopy detected endoscopic markers of villous atrophy in the duodenum and extending to a variable distance along the small intestine. On the basis of small bowel transit time, the mean±s.e.m. percentage of small intestine with villous atrophy was 18.2±3.7%. After 12 months on a GFD, repeat capsule endoscopy demonstrated mucosal healing from a distal to proximal direction, and the percentage of small intestine with villous atrophy was significantly reduced to 3.4±1.2% (P=0.0014) and this correlated with improvement in the symptom score (correlation 0.69, P=0.01). There was a significant improvement in symptom score (5.2±1.0 vs. 1.7±0.4, P=0.0012) and reduction in immunoglobulin A–tTG levels (81.5±10.6 vs. 17.5±8.2, P=0.0005). However, 42% of subjects demonstrated persistent villous abnormality as assessed by duodenal histology.CONCLUSIONS:After 12 months on a GFD, patients with celiac disease demonstrate an improvement in symptoms, celiac serology, and the extent of disease as measured by capsule endoscopy. Mucosal healing occurs in a distal to proximal direction. The extent of mucosal healing correlates with improvement in symptoms. Duodenal histology does not reflect the healing that has occurred more distally.

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report

Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report

Clinical Guidelines for Celiac Disease in Children: What Does It Mean to the Pediatrician/Family Practitioner?

Clinical Guidelines for Celiac Disease in Children: What Does It Mean to the Pediatrician/Family Practitioner?