American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease.

This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.

Single-Center Analysis of Essential Laboratory Testing in Patients with Newly Diagnosed Celiac Disease.

OBJECTIVE: To analyze laboratory testing results from pediatric patients newly diagnosed with celiac disease to determine the usefulness of each test derived from recommended guidelines. METHODS: Serological testing at the time of diagnosis from patients enrolled in our celiac disease registry from January 2018 through December 2021 was reviewed. The incidence of abnormal laboratory results, routinely obtained as per the recommendations of Snyder et al and our institution's Celiac Care Index, was assessed. Rates of abnormal laboratory values and estimated costs associated with these screening measures were analyzed. RESULTS: Our data demonstrated abnormalities in all serological testing obtained at celiac diagnosis. Hemoglobin, alanine aminotransferase, ferritin, iron, and vitamin D screening were found to be abnormal with notable frequency. Only 7% of patients had an abnormal thyroid-stimulating hormone and <0.1% had an abnormal free T4. Nonresponse to hepatitis B vaccination was prominent, with 69% of patients considered nonimmune. Screening protocols as currently outlined in our Celiac Care Index resulted in an estimated cost of approximately $320 000 during our study. CONCLUSIONS: Review of screening laboratory results at our center reveals that abnormal values for several recommended measures are uncommon. Thyroid screening was infrequently abnormal and the usefulness of screening for hepatitis B at diagnosis is uncertain. Similarly, our data suggest that iron deficiency screening may be condensed effectively into hemoglobin and ferritin testing, eliminating the need for initial iron studies. Decreasing baseline screening measures could safely decrease the burden of testing on patients and overall healthcare expenditures.

The Diagnostic Error Index: A Quality Improvement Initiative to Identify and Measure Diagnostic Errors.

OBJECTIVE: To develop a diagnostic error index (DEI) aimed at providing a practical method to identify and measure serious diagnostic errors. STUDY DESIGN: A quality improvement (QI) study at a quaternary pediatric medical center. Five well-defined domains identified cases of potential diagnostic errors. Identified cases underwent an adjudication process by a multidisciplinary QI team to determine if a diagnostic error occurred. Confirmed diagnostic errors were then aggregated on the DEI. The primary outcome measure was the number of monthly diagnostic errors. RESULTS: From January 2017 through June 2019, 105 cases of diagnostic error were identified. Morbidity and mortality conferences, institutional root cause analyses, and an abdominal pain trigger tool were the most frequent domains for detecting diagnostic errors. Appendicitis, fractures, and nonaccidental trauma were the 3 most common diagnoses that were missed or had delayed identification. CONCLUSIONS: A QI initiative successfully created a pragmatic approach to identify and measure diagnostic errors by utilizing a DEI. The DEI established a framework to help guide future initiatives to reduce diagnostic errors.

A Celiac Care Index Improves Care of Pediatric Patients Newly Diagnosed with Celiac Disease.

OBJECTIVES: To describe quality improvement efforts to reduce variability in the care of children diagnosed with celiac disease through use of an institutional patient registry and a chronic care index. STUDY DESIGN: An institutional patient registry tracked rates of follow-up visits and repeat serologic testing. A Celiac Care Index that included anthropometrics, biopsy expectations, dietician consultation, and baseline laboratory evaluation was developed to standardize evaluation at diagnosis. Provider education sessions communicated expectations for this standard of care and order sets within the electronic medical record simplified test collection. Data was recorded and reviewed weekly and structured communications with providers were provided biweekly. RESULTS: Adherence with follow-up expectations (77%-89% P = .03) and repeat serologic testing (50%-90% P < .0001) significantly increased during the study period. Adherence with completion of the Celiac Care Index resulted in significant improvement in obtaining complete blood count (80%-98% P < .0001), iron (25%-78% P < .0001), ferritin (34%-80% P < .0001), alanine aminotransferase/aspartate aminotransferase (74%-96% P < .0001), thyroid-stimulating hormone (64%-90% P < .0001), vitamin D (36%-83% P < .0001), and hepatitis B immune status (30%-80% P < .0001). Iron deficiency demonstrated by low ferritin levels was common (41%) and a high rate of nonimmunity to hepatitis B (70%) was detected. CONCLUSIONS: The Celiac Care Index improved adherence with published care recommendations and reduced variability in baseline evaluation at diagnosis. Laboratory test results indicate further studies are needed to evaluate these recommendations.

The Utility of IgA-Based Serologic Markers in Diagnosing Celiac Disease in Children 24 Months of Age or Younger.

Current screening guidelines in North America for celiac disease recommend additional IgG based testing for younger children. Our multicenter retrospective study showed that the anti-tissue transglutaminase IgA antibody test should be the recommended initial test in all children, including those ≤24 months of age.

Assessment of Exocrine Pancreatic Function During Endoscopy in Children.

This article will review briefly the physiology of pancreatic enzyme secretion and the role of stimulated endoscopic testing for assessing exocrine pancreatic function. Published studies in both the pediatric and adult literature are reviewed. The technique and utility of endoscopic pancreatic function testing as the method of choice in the differential diagnosis of pancreatic disorders in childhood is described. Finally, emerging, clinically useful markers that can be measured in the pancreatic fluid will be described.

Health-related Quality of Life in Newly Diagnosed Pediatric Patients With Celiac Disease.

OBJECTIVES: Celiac disease (CD) is a common chronic condition with potential adverse physical and psychosocial implications for affected children. The study purpose was to characterize health-related quality of life (HRQOL) in a large sample of pediatric patients with newly diagnosed CD using the PedsQL 4.0 Generic Core Scales, and compare it to that of healthy children and children with nonceliac gastrointestinal (GI) conditions using historic data. METHODS: The PedsQL was administered to 159 children with newly diagnosed CD and their parents at either the time of diagnostic esophagogastroduodenoscopy or before their initial dietitian appointment for gluten-free diet teaching. Mean parent-report and self-report PedsQL summary and subscale scores were calculated, then compared to published means from a sample of healthy children and a sample of children with nonceliac GI symptoms using 1-sample t tests. RESULTS: Compared to the healthy children, those with newly diagnosed CD had lower Total Scores, Physical Health, Psychosocial Health, Emotional Functioning, and School Functioning on parent report (P < 0.008) with similar findings on self-report. Within the CD sample, clinically significant scores were found in 55.9% for School Functioning, 62.7% for Physical Health, 54.4% for Emotional Functioning, 43.7% for Social Functioning, and 49% for Total Score. CONCLUSIONS: Children and adolescents with newly diagnosed CD had lower HRQOL than healthy children and similar HRQOL to that of patients with nonceliac GI conditions. Patients with deficits in domains such as school or emotional functioning may benefit from early interventions including a Section 504 plan or meeting with a psychologist or social worker.

PEG 3350 Administration Is Not Associated with Sustained Elevation of Glycol Levels.

OBJECTIVE: To determine whether trace amounts of ethylene glycol (EG), diethylene glycol (DEG), or triethylene glycol (TEG) in PEG 3350 are associated with increased blood levels of EG, DEG, or TEG in children receiving daily PEG 3350 therapy. STUDY DESIGN: Blood samples were drawn from 9 children who were being treated for constipation with PEG 3350 (6-12 years old) before and every 30 minutes for 3 hours after receiving 17 g of PEG 3350. PEG 3350, tap water, and blood samples from 18 age- and sex-matched controls also were analyzed. RESULTS: Baseline blood levels of EG and TEG did not differ between control and treated groups. DEG levels (median [IQR]) were lower in the PEG 3350 group (40.13 ng/mL [36.69, 63.94] vs 92.83 ng/mL [51.06, 128.93], P = .008). After PEG 3350 dose, levels of EG (390.51 ng/mL [326.06, 624.55]) and TEG (2.21 ng/mL [0, 4.5]) peaked at 90 minutes at 1032.81 ng/mL (826.84, 1486.13) (P = .009) and 35.17 ng/mL (15.81, 45.13) (P = .0005), respectively. DEG levels did not significantly change. Standard 17-g doses of PEG 3350 in 8 oz (237 mL) of water resulted in concentrations (mean ± SD) of EG, DEG, and TEG of 1.32 ± 0.23 µg/mL, 0.18 ± 0.03 µg/mL, and 0.12 ± 0.01 µg/mL, respectively. EG, DEG, and TEG levels in public water supply were 0.07 µg/mL, 0.21 µg/mL, and 0.02 µg/mL, respectively. CONCLUSIONS: Daily PEG 3350 therapy in children was not associated with sustained elevation of EG, DEG, or TEG blood levels over levels in matched controls. Although EG and TEG levels increased after a standard dose of PEG 3350, their peak values remained well below toxic levels.

Creatively Improving Care Delivery.

The medical community has been challenged to improve upon deficiencies in the delivery of patient care. Quality improvement methods are therefore increasingly used in everyday clinical practice. As demonstrated in this review, creative and impactful improvement projects within pediatric gastroenterology can be successfully achieved as either multicenter projects or single-center efforts. Through our willingness to accept the challenge to improve, practitioners within the pediatric gastroenterology community have become leaders in using quality improvement to change practice and improve clinical outcomes.

Using Serum IgE Antibodies to Predict Esophageal Eosinophilia in Children.

OBJECTIVES: Symptoms of eosinophilic esophagitis are variable and can be nonspecific. Food-specific serum immunoglobulin E (IgE) antibodies are frequently found in patients with eosinophilic esophagitis and are obtained using a widely available blood test. Our objective was to evaluate the ability of food-specific IgE antibodies to predict the presence of esophageal eosinophilia. METHODS: We reviewed 144 medical records for pediatric patients having esophageal biopsy and serum analysis for IgE antibodies to food (exploratory group). We performed logistic regression using sex and number of positive food-specific IgE tests to develop a model that predicts ≥15 eosinophils/high-power field (hpf) in the esophagus. We tested the model using 142 additional patients (validation group). RESULTS: The probability of having ≥15 eosinophils/hpf in the esophagus was higher in boys and increased with the number of positive food-specific IgE tests from 12% (95% confidence interval 4.8-26) in girls with 0 foods positive to 86% (95% confidence interval 71-94) for boys with 4 or 5 foods positive. The statistical model using sex and number of positive IgE tests to predict patients having ≥15 eosinophils/hpf showed acceptable discriminative ability (area under the receiver operating characteristic curve 0.80). The performance metrics for the model to predict ≥15 eosinophils/hpf in the validation group were similar (area under the receiver operating characteristic curve 0.75). CONCLUSIONS: Requiring only a blood test and a simple algorithm, analysis for IgE antibodies to food may expedite an esophagogastroduodenoscopy and decrease delays in the diagnosis and treatment of patients with nonspecific gastrointestinal symptoms who have increased eosinophils in the esophagus.

Transition from childhood to adulthood in coeliac disease: the Prague consensus report.

The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.

Hypertransaminasemia in Newly Diagnosed Pediatric Patients With Celiac Disease.

OBJECTIVES: The aim of the present study was to determine the proportion of pediatric patients with celiac disease (CD) who had transaminases obtained at diagnosis and to determine the proportion with hypertransaminasemia. METHODS: Data from newly diagnosed patients with CD at Nationwide Children's Hospital from February 2007 to March 2014 were retrospectively reviewed. Alanine transaminase (ALT) and aspartate transaminase (AST) values at diagnosis and after initiation of a gluten-free diet (GFD) were assessed. RESULTS: Of 388 patients (mean age 10.1 ±â€Š4.4 years, 235 girls), 185 (47.7%) had transaminases obtained at the time of diagnosis. Twenty-eight of one hundred eighty-five (15.1%) had an elevated ALT and/or AST level with an average ALT 2.52 × upper limit of normal (ULN) and AST 1.87 × ULN. Those with hypertransaminasemia were younger than those with normal levels (6.31 ±â€Š4.75 vs 11.00 ±â€Š4.28 years, P < 0.0001). Sex, symptoms at diagnosis, and weight, height, and body mass index z scores were not predictive of elevated transaminases. Of the 21 patients with hypertransaminasemia at diagnosis who had repeat laboratory test results after starting the GFD, 15 (71.4%) normalized whereas 6 (28.6%) remained elevated. CONCLUSIONS: There is variation in practice among pediatric gastroenterologists in the assessment of transaminases in children with CD. Hypertransaminasemia is present at diagnosis in a significant proportion of children with CD although at a lower frequency than previously reported. Younger patients are more likely to have an elevation in transaminases. Abnormal transaminases normalize in the majority of patients within 1 year after initiation of a GFD.

NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders.

Dietary exclusion of gluten-containing products has become increasingly popular in the general population, and currently ∼30% of people in the United States are limiting gluten ingestion. Although celiac disease (CD), wheat allergy (WA), and nonceliac gluten sensitivity (NCGS) constitute a spectrum of gluten-related disorders that require exclusion of gluten from the diet, together these account for a relatively small percentage of those following a gluten-free diet, and the vast majority has no medical necessity for doing so. Differentiating between CD, WA, and NCGS has important prognostic and therapeutic implications. Because of the protean manifestations of gluten-related disorders, it is not possible to differentiate between them on clinical grounds alone. This clinical report will compare and contrast the manifestations of gluten-related disorders, emphasize the importance of differentiating between these conditions, discuss initial and subsequent tests needed to confirm the diagnosis, and provide recommendations on treatment and follow-up for each condition.

Adherence to Endoscopy Biopsy Guidelines for Celiac Disease.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 ±â€Š1.6 vs 3.6 ±â€Š1.2) (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. CONCLUSIONS: 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.

Esophageal eosinophilia in pediatric patients with celiac disease: is it a causal or an incidental association?

OBJECTIVES: Celiac disease (CD) and eosinophilic esophagitis (EoE) are 2 distinct disease entities affecting the gastrointestinal tract of pediatric patients. Recently it has been suggested that EoE is more prevalent in patients with celiac disease than in the general population. We studied the association between these 2 disease entities in our pediatric patients. METHODS: We reviewed our hospital files for suspected or confirmed cases of CD. Only cases with both duodenal and esophageal biopsies in pediatric patients were included. A total of 120 patients who met these criteria were included as the disease group. We also selected 100 patients with no clinical suspicion of CD and included them as a control group. Slides were reviewed using established criteria for diagnosis of both conditions. Duodenal biopsies were categorized as positive, negative, and suspicious for CD, whereas esophageal biopsies were classified as either positive or negative for esophageal eosinophilia (EE). Serologic and clinical data were additionally collected. RESULTS: Sixty-two (62) cases were considered positive for CD in the disease group; among those 4 (6.5%) showed EE. In the control group, 91 cases were negative for CD, histologically, and 7 of those had EE (7.7%). Although 6 patients in the control group were histologically suspicious for CD, none of them had evidence of EE. CONCLUSIONS: Our findings show that, in our patient population, patients with CD are not more likely to have EE than patients undergoing upper endoscopy for other reasons. Therefore, we suggest that the association between CD and EE is likely incidental and not causal.