Mobile Health technology in pediatric esophagogastroduodenoscopy quality indicators assessment: results from a national program of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND AND AIMS: Upper endoscopy procedures (UEP, esophagogastroduodenoscopy [EGDS] and retrograde endoscopic retrograde cholangiography [ERCP]) are an established standard of care in pediatric gastroenterology. The Pediatric endoscopy quality improvement network (PEnQuIN) recently published its pediatric-specific endoscopy quality guidelines. This study, initiated by the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP), aims to evaluate the adherence of Italian Pediatric Endoscopy Centers to these established quality standards. METHODS: Conducted between April 2019 and March 2021, this nationwide study utilized a smartphone app-based approach. Data encompassing pediatric endoscopy facilities, patient profiles, endoscopy indications, 17 procedure-related PEnQuIN indicators, and a GHAA-9m patient satisfaction questionnaire were systematically collected. RESULTS: A comprehensive analysis of 3582 procedures from 24 PECs revealed that 2654 (76%) were UEP. The majority of centers (75%) involved more than one operator, with 9 PEC incorporating adult endoscopists, responsible for 5% of UEPs. Overall, adherence to quality standards was good; however, areas of improvement include sub-optimal reporting of sedation details, adherence to disease-specific guidelines, and patient satisfaction questionnaire completeness (56%). The complication rate aligned with literature standards (1%), and patient satisfaction was generally high. A noteworthy observation was a 30% decrease monthly reporting rate and a shift in disease-specific patterns following the COVID-19 outbreak. CONCLUSIONS: Pediatric UEP practices in Italy adhere well to established quality standards. Emphasizing the adoption of disease-specific guidelines is crucial for optimizing resources, enhancing diagnostic accuracy, and minimizing unnecessary procedures. Prioritizing patient satisfaction is important for immediate enhancements in practice as well as for future research endeavors.

Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study.

BACKGROUND AND AIMS: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming. IMPACT: Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

INTRODUCTION: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. METHODS: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). RESULTS: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. DISCUSSION: Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study.

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (-308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.

Venous outflow obstruction in pediatric left lateral segment split liver transplantation.

BACKGROUND: Venous outflow obstruction (VOO) is a known cause of graft and patient loss after pediatric liver transplantation (LT). We analyzed the incidence, risk factors, diagnosis, management, and outcome of VOO in a large, consecutive series of left lateral segment (LLS) split LT with end-to-side triangular venous anastomosis. METHODS: We evaluated data collected in our prospective databases relative to all consecutive pediatric liver transplants performed from January 2006 to December 2021. We included in this study children undergoing LLS split liver transplant with end-to-side triangular anastomosis. Diagnosis of VOO was based on clinical suspicion and radiological confirmation. RESULTS: VOO occurred in 24/279 transplants (8.6%), and it was associated with lower graft weight (p = .04), re-transplantation (p = .008), and presence of two hepatic veins (p < .0001). In presence of two segmental veins' orifices, the type of reconstruction (single anastomosis after venoplasty or double anastomosis) was not significantly related to VOO (p = .87). Multivariable analysis indicated VOO as a risk factor for graft lost (hazard ratio 3.21, 95% confidence interval 1.22-8.46; p = .01). Percutaneous Transluminal Angioplasty (PTA) was effective in 17/22 (77%) transplants. Surgical anastomosis was redone in one case. Overall six grafts (25%) were lost. CONCLUSION: VOO after LLS split LT with end-to-side triangular anastomosis is an unusual but critical complication leading to graft loss in a quarter of cases. The occurrence of VOO was associated with lower graft weight, re-transplantation, and presence of two hepatic veins. PTA was safe and effective to restore proper venous outflow in most cases.

Gastrointestinal coronavirus disease 2019 manifestations in childhood.

PURPOSE OF THE REVIEW: The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged and caused a massive global health crisis. The aim of this review is first, to provide the latest evidence on what is known about the pathophysiology and the transmission of SARS-CoV-2 and then to focus on the manifestations of the gastrointestinal (GI) tract in children with COVID-19. Lastly, we summarise the impact of COVID-19 on patients with preexisting GI diseases. RECENT FINDINGS: Even though the virus is mostly transmitted from human to human via respiratory droplets, ACE2 is known to be expressed throughout the GI tract, and SARS-CoV-2 ribonucleic acid has been isolated from patients' stools. GI symptoms including abdominal pain, diarrhoea and vomiting are frequently reported in paediatric patients. Interestingly, a small number of patients seem to exhibit solely GI symptoms. In addition, a multisystem inflammatory syndrome in children (MIS-C) related to SARS-COV-2 described in children, has a high rate of GI involvement. Several etiopathogenetic mechanisms have been postulated to explain the GI involvement of COVID-19. SUMMARY: Clinicians should not underestimate or disregard these early or mild GI symptoms, because the patients may be infected and transmit the virus, or develop a more severe condition such as MIS-C.

Biliary complications in pediatric liver transplantation: findings of percutaneous transhepatic cholangiography in a large single-center cohort.

BACKGROUND: Although biliary complications after orthotopic liver transplantation represent a common source of morbidity and mortality, decreasing graft survival, consensus is lacking on their management in the pediatric population. OBJECTIVE: The aim of this study was to present the prevalence of such biliary complications and their interventional radiologic management with representative images. MATERIALS AND METHODS: This retrospective study reports our experience with percutaneous transhepatic cholangiography in the management of biliary complications after orthotopic liver transplantation in pediatric patients. This study enrolled all pediatric patients (<18 years old) who underwent percutaneous transhepatic cholangiography for the management of biliary complications after orthotopic liver transplantation at a tertiary care center between January 2010 and December 2020. Diagnosis of biliary complications and indication to perform percutaneous transhepatic cholangiography were based on clinical, laboratory or radiologic data. RESULTS: Among the 301 orthotopic liver transplantations, 78 (26%) developed biliary complications that were managed by interventional radiology: these included 52 (17.3%) biliary strictures, 19 (6.3%) bile leaks, 5 (1.7%) biliary stones, 1 (0.3%) iatrogenic biliary obstruction and 1 (0.3%) vanishing syndrome. The median time interval between orthotopic liver transplantation and the diagnosis of biliary complications was 6.0 years (interquartile range [IQR] 8.2 years). Percutaneous transhepatic cholangiography and biliary duct catheterization were successful in all cases, with low rates of complications that were variable among subgroups. CONCLUSION: A wide spectrum of biliary complications can occur after pediatric orthotopic liver transplantation. In this large single-center experience, we highlight the value of percutaneous transhepatic cholangiography in their diagnosis and management. Percutaneous treatments in pediatric patients are safe and effective, providing resolution or serving as a bridge to surgery, including re-transplantation.

Subclinical biliary strictures as a cause of long-term allograft dysfunction in children who underwent liver transplantation.

We aimed to evaluate the role of liver biopsy to predict subclinical biliary strictures (BS) and assess the impact of BS on long-term allograft dysfunction following liver transplantation in children (LT). We reviewed all liver biopsies performed from 2012-2018. Percutaneous transhepatic cholangiography (PTC) was performed in patients presenting cholangiolar proliferation on cytokeratin-7 stained sections. We performed 271 biopsies in 161 children (86% with a left lateral segment); 44/161 (27%) presented with diffuse or multifocal cholangiolar proliferation. Among them, a tight BS was confirmed in 38/44 (86%, 24% of total) and it was managed by balloon dilatation. Cholangiolar proliferation showed a positive predictive value (PPV) for BS of 86.4%. Levels of alkaline phosphatase >325 IU/L predicted BS (P = .007). Dilatation of intrahepatic bile ducts on ultrasound was found only in 44% of patients with BS. Following a median follow-up of 9.2 years, only 15/38 (39%) patients resolved the BS. In conclusion subclinical BS is very common and probably underdiagnosed in these patients. Histological evidence of cholangiolar proliferation detectable by cytokeratin-7 immunostain should be preferred to liver function tests and ultrasound to suspect BS. BS in this setting should be regarded as a main cause of long-term allograft dysfunction.

Remote support by multidisciplinary teams: A crucial means to cope with the psychological impact of the SARS-COV-2 pandemic on patients with cystic fibrosis and inflammatory bowel disease in Lombardia.

BACKGROUND: During Coronavirus Disease 2019 (COVID-19) outbreak in Lombardia, people were recommended to avoid visiting emergency departments and attending routine clinic visits. In this context, it was necessary to understand the psychological reactions of patients with chronic diseases. We evaluated the psychological effects on patients with chronic respiratory conditions and inflammatory bowel disease (IBD) through the analysis of their spontaneous contacts with their referral centres. METHODS: Cross-sectional study was conducted from February 23 to April 27, 2020 in patients, or their parents, who contacted their multidisciplinary teams (MDT). E-mails and phone calls directed to the MDT of the centre for cystic fibrosis (CF) in Milano and for paediatric IBD in Bergamo, were categorised according to their contents as information on routine disease management, updates on the patient's health status, COVID-19 news monitoring, empathy towards health professionals, positive feedback and concern of contagion during the emergency. RESULTS: One thousand eight hundred and sixteen contacts were collected during the study period. In Milano, where the majority of patients were affected by CF, 88.7% contacted health professionals by e-mail, with paediatricians receiving the largest volume of emails and phone calls compared with other professionals (P< .001). Compared with Milano, the centre for IBD in Bergamo recorded more expression of empathy towards health professionals and thanks for their activity in the COVID-19 emergency (52.4% vs 12.7%, P< .001), as well as positive feedback (64.3% vs 2.7%, P = .003). CONCLUSION: One of the most important lessons we can learn from COVID-19 is that it is not the trauma itself that can cause psychological consequences but rather the level of balance, or imbalance, between fragility and resources. To feel safe, people need to be able to count on the help of those who represent a bulwark against the threat. This is the role played, even remotely, by health professionals.

Trend of Antitissue Transglutaminase Antibody Normalization in Children With Celiac Disease Started on Gluten-free Diet: A Comparative Study Between Chemiluminescence and ELISA Serum Assays.

BACKGROUND: The aim of this study is to compare the performance of antitissue transglutaminase (atTG) chemiluminescence immunoassay (CLIA) with the standard enzyme-linked immunosorbent assay (ELISA) methods in monitoring celiac children after the start of gluten-free diet (GFD). METHODS: Celiac children diagnosed between 2005 and 2016 at our centre were classified into 2 groups based on serum assay (ELISA vs CLIA) used for atTG monitoring, and were compared on percentage of decrease and time to normalization of atTG on GFD. RESULTS: Among 260 included children, the rate of normalization of atTG levels at 30 months' follow-up was 86% and 70% in ELISA and CLIA group, respectively (P < 0.01). Median time to normalization was 11.7 and 14.7 months in ELISA and CLIA group respectively (P = 0.003). Marsh score at diagnosis was not associated with time to atTG normalization (P = 0.770), whereas older age at diagnosis and higher baseline atTG predicted longer time to atTG normalization (P = 0.01, P < 0.01). CONCLUSIONS: The percentage and the time of the atTG normalization in celiac children on GFD should be interpreted according to the utilized assay: at 30 months' follow-up children tested by CLIA are less likely to normalize atTG levels compared to those tested by ELISA. Younger age at diagnosis and lower baseline atTG are predictors of earlier atTG normalization, regardless of the adopted assay.

Longitudinal Immune Phenotype Assessment and Serological Outcome in Foreign-born Children With Chronic Hepatitis B.

OBJECTIVES: The aim of the study was to assess changes in clinical phenotype, and identify determinants of outcome in children with chronic hepatitis B virus (HBV) infection born in HBV-endemic countries followed in 2 Italian tertiary care centers after immigration or adoption. METHODS: A prospective observational study on hepatitis B e-antibodies-negative chronic hepatitis B children started on 2002. Patients with liver fibrosis, or those needing antiviral treatment were excluded. Immune active patients were defined those with raised transaminases (alanine aminotransferase > 40 IU/L), immune tolerants those having normal alanine aminotransferase, both exhibiting substantial viral replication (HBV DNA >2000 IU/mL). RESULTS: Sixty-nine patients (44 boys, median age 4.7 years) had a median follow-up of 53 months. At entry, 18 (26%) children were immune tolerant, 47 (68%) immune active, and 4 had indeterminant immune status. At last follow-up, 14 (78%) of the immune-tolerant patients remained so, whereas only 23 (49%) of the immune active children maintained their initial immune phenotype. Seroconversion to hepatitis B e antibodies (SCHBe) occurred in only 2 (11%) immune tolerants, whereas 13 (28%) immune active patients achieved SCHBe.Ethnicity was the only feature independently correlated to SCHBe: Asian origin reduced by 4.1 times the probability of SCHBe (Asian vs other; odds ratio = 0.24 [95% confidence interval = 0.07-0.76]; P = 0.016) compared to other ethnicities, whereas viral genotype did not influence the outcome. CONCLUSIONS: Ethnicity and immune status phenotype against HBV, rather than HBV genotype, are the main determinants of SCHBe in foreign-born children with chronic HBV infection.

The good bugs: the use of probiotics in pediatrics.

PURPOSE OF REVIEW: There is growing evidence encouraging the use of probiotics in many conditions in children. However, given the wide number of probiotics available and contradictory data in the literature, the health-care provider is often faced with uncertainness about whether or not to use probiotics and which one(s) to choose. We here review current hypotheses regarding the efficacy and safety of probiotics and evaluate the available data on the use of probiotics in most common diseases in children. Considering that probiotics have strain-specific effects, we will focus on individual probiotic strains rather than on probiotics in general. RECENT FINDINGS: Strain-specific efficacy was clearly demonstrated with Lactobacillus rhamnosus GG and Saccharomyces boulardii I-745 in the treatment of acute infectious diarrhea, Lactobacillus reuteri DSM 17938 in infantile colics, Lactobacillus rhamnosus GG, and VSL#3 in irritable bowel syndrome. In addition, encouraging results are seen for use of probiotics in necrotizing enterocolitis, food allergy, and nonalcoholic fatty liver disease. However, the data available for constipation are to be considered somewhat equivocal. SUMMARY: The clinical relevance of these findings indicates that healthcare providers need to take strain-specificity and disease specificity of probiotics into consideration when recommending probiotic for their patients.

Effects of the Gluten-free Diet on Body Mass Indexes in Pediatric Celiac Patients.

OBJECTIVE: The aim of the study was to determine the effects of the gluten-free diet (GFD) on body mass indexes (BMIs) in children with celiac disease at University of Chicago before and after 2011, when processed gluten-free foods became readily available on the market. METHODS: We conducted a retrospective chart review of children seen at University of Chicago Celiac Center from January 2002 to May 2016. BMI was recorded upon GFD initiation in addition to at least 1 other timepoint: 6 months, 1 year, 2 years, 3 years, and 4+ years. We compared the rate of BMI increase in children who were diagnosed before versus after 2011. RESULTS: A total of 147 children (66% girls) with biopsy-confirmed celiac disease were included in the study. The mean BMI at diagnosis was 17.8 (standard deviation 3.9) for those diagnosed before 2011 and 17.1 (standard deviation 2.7) for those diagnosed after 2011. Based on a mixed-effects random-intercept random-slope regression model, there was no evidence for significant difference in BMI change over time between the 2 groups (P value = 0.36). BMI values overall were noted to increase after starting the GFD, even at the first appointment. Serologies were monitored after patients started the GFD and approached normal values, allowing us to conclude that patients were adherent to the GFD. CONCLUSIONS: Although overall we observed no significant changes in BMI before and after 2011, we did notice that in adolescent celiac patients there was a trend toward a higher postdiagnosis BMI in the years after 2011. We speculate that teenagers may be especially vulnerable to choosing quick and easy processed gluten-free options over more healthy, natural alternatives leading to a rise in their BMIs after the 2011 surge in production of processed gluten-free foods on the market. Therefore, special attention must be paid to this population to insure ongoing healthy food choices even after many years on the GFD.

Probiotics in the Treatment of Inflammatory Bowel Disease.

While considerable progress has been made in the treatment of inflammatory bowel diseases (IBD), alternative options are constantly sought by adult patients as well as frustrated parents of young patients. These include dietary modifications, food supplements, and, more recently, probiotics.Their potential use is based on the demonstrated role of the altered mucosal immune response to bacterial agents that eventually leads to the chronic intestinal inflammation that characterized IBD. In fact, probiotics might conceivably be beneficial due to multiple mechanisms: stimulation of anti-inflammatory cytokines, inhibition of inflammatory cytokines, strengthening of intestinal barrier, and antagonistic action on pathogens. Such mechanisms have been largely extensively investigated in animal models both in vitro and in vivo.Despite such premise, a relatively scarce number of clinical trials are available, and of them only a handful in pediatric age. Overall, available evidence is very disappointing in the treatment of Crohn's disease (CD), where no recommendation for probiotic use can be made. In ulcerative colitis (UC), on the other hand, there is clinical evidence of efficacy for some specific strains and especially for multi-strain preparations.In summary, more data are needed very likely to yield a better understanding on what strains and in what doses should be used in different specific clinical settings.

Celiac Disease Symptom Resolution: Effectiveness of the Gluten-free Diet.

OBJECTIVE: The aim of the study was to evaluate the efficacy of the gluten-free diet (GFD) on gastrointestinal (GI) and extra-intestinal (EI) symptom resolution and identify predictors for persistence of symptoms in all celiac patients at the University of Chicago. METHODS: We conducted a retrospective chart review from 2002 to 2015. GI symptoms included abdominal pain, bloating, constipation, diarrhea, failure to thrive/weight loss, nausea, reflux, and vomiting. EI symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgia, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. RESULTS: A total of 554 patients (227 children) with celiac disease (CeD) were included. Abdominal pain, diarrhea and failure to thrive were the most common GI symptoms in children whereas diarrhea, bloating, and abdominal pain were most common in adults. Short stature, fatigue, and headache were the most common EI symptoms in children whereas iron deficiency anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children had significantly higher rates of EI and GI symptom resolution as compared to adults, with greater rates of improvements in GI versus EI symptoms at more than 24 months. Long duration of symptoms, female sex, and non-adherence to a GFD were the most important significant predictors of failure to clinically improve. CONCLUSIONS: On a strict GFD, children report greater rates of both GI and EI symptom resolution as compared to adults with greater rates of improvement in GI over EI symptoms. Early recognition of CeD and close attention to diet adherence may help in symptom resolution.

Abdominal Pain-Associated Functional Gastrointestinal Disorder Prevalence in Children and Adolescents with Celiac Disease on Gluten-Free Diet: A Multinational Study.

OBJECTIVE: To test the hypothesis that children with celiac disease (CD) on gluten-free diet are at increased risk of abdominal pain (AP) associated-functional gastrointestinal disorders (FGIDs). STUDY DESIGN: This was a multinational cross-sectional study performed from 2014 to 2015. Patients 4-18 years of age with CD on gluten-free diet for longer than 6 months were recruited from pediatric CD clinics in US and Italy. Control groups included siblings of children with CD (with normal tissue transglutaminase levels) and unrelated controls. Subjects or parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III. RESULTS: Children (n = 289) were recruited (55% US, 45% Italy): 96 children with CD, 96 sibling controls, and 97 unrelated controls. Chronic AP was present in 30 (30.9%) subjects with CD, 22 (22.7%) sibling controls, and 21 (21.6%) unrelated controls (P = .26 patients with CD vs siblings; P = .18 patients with CD vs unrelated; P = .96 siblings vs unrelated). AP-FGIDs were present in 8 (8.2%) subjects with CD, 8 (8.2%) sibling controls, and 2 (2.1%) unrelated controls (P = 1.00 subjects with CD vs sibling controls; P = .06 subjects with CD vs unrelated controls; P = .06 sibling controls vs unrelated controls). CONCLUSION: This multinational study evaluated the prevalence of chronic abdominal pain and AP-FGIDs in the pediatric population with CD. We found that subjects with CD and controls have a similar prevalence of chronic AP and AP-FGIDs. This suggests that not all types of gastrointestinal inflammation result in AP-FGIDs in children.

Extraintestinal Manifestations of Celiac Disease: Effectiveness of the Gluten-Free Diet.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of the gluten-free diet (GFD) on extraintestinal symptoms in pediatric and adult celiac populations at the University of Chicago. METHODS: We conducted a retrospective chart review of the University of Chicago Celiac Center clinic charts from January 2002 to October 2014. Demographics, serologic testing, intestinal biopsies, and extraintestinal symptoms at presentation, 12, 24, and >24 months were recorded. Extraintestinal symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgias, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. RESULTS: A total of 737 patients with biopsy-confirmed celiac disease or skin biopsy-confirmed dermatitis herpetiformis were included. Patients lost to follow-up, or with insufficient data were excluded leaving 328 patients (157 pediatrics younger than 18 years). For pediatrics, the female to male ratio was 2:1 and the mean age at diagnosis was 8.9 years. For adults, 4:1 and 40.6 years old. Extraintestinal symptom rates were similar in children (60%) and adults (62%). Short stature (33%), fatigue (28%), and headache (20%) were most common in children. Iron deficiency anemia (48%), fatigue (37%), and headache/psychiatric disorders (24%) were common in adults. Children had faster/higher rates of symptom resolution compared with adults. Twenty-eight percent of children with unresolved short stature on a GFD were found to have other comorbidities. CONCLUSIONS: Children and adults with celiac disease have similar rates of extraintestinal manifestations. In children short stature, fatigue, and headache were most common, whereas anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children on a strict GFD showed faster and higher rates of symptom resolution as compared to adults. Unresponsive children with short stature must be assessed for comorbidities.