S2k Leitlinie akute infektiöse Gastroenteritis im Säuglings-, Kindes- und Jugendalter ­ Update 2024.

The aim of the interdisciplinary S2k guideline "Acute infectious gastroenteritis in infants, children and adolescents" is to summarise the current state of knowledge on the clinical presentation, diagnosis, treatment, prevention and hygiene of acute infectious gastroenteritis, including nosocomial gastrointestinal infections, in infants, children and adolescents on the basis of scientific evidence, to evaluate it by expert consensus and to derive practice-relevant recommendations from it. The guideline provides a corridor for action for frequent decisions. It also serves the purpose of evidence-based further education and training and is thus intended to improve the medical care of children with acute gastroenteritis. In particular, the guideline aims to avoid unnecessary hospitalisation of children with AGE and to take preventive measures to avoid and spread infection.

Uncovering the gap: Coeliac disease knowledge among healthcare professionals in the Danube region.

BACKGROUND: Several studies have shown that the knowledge about coeliac disease (CD) is not satisfactory among healthcare professionals (HCP). The aim of our study was to assess the knowledge of HCPs about CD in the Danube region. METHODS: HCPs from 8 countries in the Danube region were asked to complete the web-based questionnaire about CD. Scores of HCPs were compared according to their speciality, work experience and country of residence. The results were compared with the results of a similar study conducted in Central Europe within the Focus IN CD project in 2016. RESULTS: Questionnaire was completed by 799 HCPs from Austria, Croatia, Czech Republic, Hungary, Moldova, Romania, Serbia, and Slovenia. Mean score achieved by HCPs was 52.2%. Paediatric gastroenterologists scored the highest (75.3%). Comparing the data with the study conducted in Central Europe in 2016, we found a significant rise (p < 0.001) in the knowledge of paediatric gastroenterologists. Also, HCPs who previously took part in the Focus IN CD project, achieved higher score (61.1% vs. 50.8%; p < 0.001). CONCLUSION: The knowledge about CD among HCPs in Danube region is not satisfactory. There has been a significant increase in the knowledge of paediatric gastroenterologists, showing the benefit of various awareness raising activities that were carried out recently.

Anthropometric assessment: ESPGHAN quality of care survey from paediatric hospitals in 28 European countries.

OBJECTIVES: Assessment of anthropometric data is essential for paediatric healthcare. We surveyed the implementation of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) evidence-based guidelines and practical recommendations on nutritional care, particularly regarding anthropometric measurements. METHODS: Paediatric hospitals from 28 European countries provided pseudonymized data through online questionnaires on hospital characteristics and their standards of nutritional care. Practical tasks assessed an unbiased collection and reporting of anthropometric measurements in random patients' files and discharge letters. RESULTS: Of 114 hospitals (67% academic), 9% have no nutritionist/dietitian available, 18% do not provide standard policy to assess weight and height and 15% lack training for nursing staff for accurate performance. A wall-mounted stadiometer to measure standing height and equipment for sitting weight is unavailable in 9% and 32%, respectively. Infant length is measured by one instead of two healthcare professionals and with a tape instead of a rigid length measuring board in 58% and 15% of hospitals, respectively. The practical tasks reviewed 1414 random patients, thereof 446 younger than 2 years of age. Missing documentation occurred significantly more often for height versus weight and their percentiles in infants ≤2 years versus older children, and in general paediatric versus gastrointestinal patients, with no difference between academic and nonacademic hospitals. Review of documented anthropometric data in discharge letters disclosed that consultants significantly underestimated the deficits in their units compared to documented data. CONCLUSIONS: The survey revealed significant gaps in performance and documentation of anthropometry in the participating hospitals. A resurvey will assess changes in quality of care over time.

Gut Microbiota Dysbiosis in Suspected Food Protein Induced Proctocolitis-A Prospective Comparative Cohort Trial.

OBJECTIVES: In infants with suspected food protein induced proctocolitis (sFPIP) only a minority of patients are finally diagnosed with the disease following diagnostic dietary intervention (DDI). There is a need for a pathophysiological explanation for the cause of hematochezia in the majority of sFPIP infants. METHODS: We prospectively recruited infants with sFPIP and healthy controls. Fecal samples were collected at inclusion, week 4 (end of DDI in sFPIP), and week 8. For 16S rRNA sequencing (515F/806R) we used Illumina MiSeq sequencing system. Amplicon sequence variants were generated using Qiime2 and DADA2. Qiime diversity alpha and beta group comparisons and linear discriminant analysis effect size analysis was performed. For shotgun metagenomic analysis on species level we used KneadData and MetaPhlAn2. RESULTS: Fourteen sFPIP infants were compared to 55 healthy infants. At inclusion overall microbial composition of sFPIP infants differed significantly from controls (weighted UniFrac; Pairwise PERMANOVA, P = 0.002, pseudo- F = 5.008). On genus level healthy infant microbiota was significantly enriched with Bifidobacterium ( B ) compared to sFPIP patients (linear discriminant analysis [LDA] = 5.5, P < 0.001, 31.3% vs 12.1%). sFPIP stool was significantly enriched by Clostridium sensu stricto 1 over controls (LDA = 5.3, P = 0.003, 3.5% vs 18.3%). DDI caused a significant and sustained increase of Bifidobacterium (LDA = 5.4, P = 0.048, 27.9%) in sFPIP infants. Species level analysis revealed significant reduction of abundance of B longum in sFPIP patients, which after DDI was reversed by B. species other than B longum . CONCLUSIONS: We revealed a gut microbiota dysbiosis phenomenon in sFPIP infants. DDI induces a microbiota composition comparable to that of healthy infants. In most sFPIP infants hematochezia might be triggered by a gut microbiota dysbiosis phenomenon.

Pediatric endoscopy training across Europe: a survey of the ESPGHAN National Societies Network 2016-2019.

Background and study aims The ability to perform endoscopy procedures safely and effectively is a key aspect of quality clinical care in Pediatric Gastroenterology, Hepatology and Nutrition (PGHN). The aim of this survey, which was part of a global survey on PGHN training in Europe, was to assess endoscopy training opportunities provided across Europe. Methods Responses to standardized questions related to endoscopy training were collected from training centers across Europe through the presidents/representatives of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition National Societies from June 2016 to December 2019. Results A total of 100 training centers from 19 countries participated in the survey. In 57 centers, the endoscopy suit was attached to the PGHN center, while in 23, pediatric endoscopies were performed in adult endoscopy facilities. Ninety percent of centers reported the availability of specialized endoscopy nurses and 96 % of pediatric anesthetists. Pediatric endoscopies were performed by PGHN specialists in 55 centers, while 31 centers reported the involvement of an adult endoscopist and 14 of a pediatric surgeon. Dividing the number of procedures performed at the training center by the number of trainees, ≤ 20 upper, lower, or therapeutic endoscopies per trainee per year were reported by 0 %, 23 %, and 56 % of centers, respectively, whereas ≤ 5 wireless capsule endoscopies per trainee per year by 75 %. Only one country (United Kingdom) required separate certification of competency in endoscopy. Conclusions Differences and deficiencies in infrastructure, staffing, and procedural volume, as well as in endoscopy competency assessment and certification, were identified among European PGHN training centers limiting training opportunities in pediatric endoscopy.

Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry.

Objective: Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4-0.9% in hospitalised children with IBD. Methods: Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung - large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist. Results: Over 10 years, 4,153 paediatric patients with IBD (0-18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn's disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56-22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela. Conclusion: Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.

Training in pediatric neurogastroenterology and motility across Europe: a survey of the ESPGHAN National Societies Network 2016-2019.

Background: Pediatric gastrointestinal motility disorders present significant challenges for diagnosis and management, emphasizing the need for appropriate training in Pediatric Neurogastroenterology and Motility (PNGM). The aim of this survey, part of a comprehensive survey on training in pediatric gastroenterology, hepatology and nutrition, was to evaluate training related to PNGM across European training centers. Method: Standardized questionnaires were collected from training centers through the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), from June 2016 to December 2019. Results: In total, 100 training centers from 19 countries participated in the survey. Dedicated PNGM clinics were available in 22 centers; pH-monitoring in 60; pH/impedance in 66; standard manometry in 37; and high-resolution manometry in 33. If all motility studies were performed partially or fully by the trainees, the median (range) annual numbers/per trainee were as follows: pH-monitoring 30 (1-500); pH/impedance 17 (1-131); standard manometries 10 (1-150); and high-resolution manometries 8 (1-75). The motility assessment was performed by pediatric gastroenterologists (43 centers); adult gastroenterologists (10 centers); pediatric surgeons (5 centers); and both pediatric gastroenterologists and pediatric surgeons (9 centers). Annual numbers ≤10 for pH-monitoring, pH/impedance, standard manometries and high-resolution manometries were reported by 7 (12%), 15 (23%), 11 (30%) and 14 (42%) centers, respectively. Conclusions: Significant differences exist in PNGM-related infrastructure, staff and procedural volumes at training centers across Europe. ESPGHAN and the National Societies should take initiatives to ensure the acquisition of competence in PNGM-related knowledge and skills, and develop strategies for assessment and accreditation.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-AG6486.pdf.

Association of training standards in pediatric gastroenterology, hepatology and nutrition in European training centers with formal national recognition of the subspecialty: a survey of the ESPGHAN National Societies Network 2016-2019.

Background: This survey evaluated the effects of the recognition of pediatric gastroenterology, hepatology and nutrition (PGHN) on European PGHN training centers. Method: Standardized questionnaires were collected from training centers via the presidents/representatives of the National Societies Network of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, from June 2016 to December 2019. Results: A total of 100 training centers from 19 countries participated in the survey: 55 from 12 countries where PGHN is formally recognized (Group 1) and 45 from 7 countries where it is not (Group 2). Training centers in Group 2 were less likely to have an integrated endoscopy suite, a written training curriculum and a training lead (P=0.059, P<0.001 and P=0.012, respectively). Trainees in Group 2 were less likely to be exposed to an adequate number of diagnostic endoscopies, while no differences were found in relation to liver biopsies. Half of the training centers in both Groups do not have dedicated beds for PGHN patients, while in 64% and 58%, respectively, trainees do not participate in on-call programs for PGHN emergencies. Research training is mandatory in 26% of the centers. The duration of training, as well as the assessment and accreditation policies, vary between countries. Conclusions: This study has revealed significant discrepancies and gaps in infrastructure and training programs, training leadership, and assessment of training and certification across European training centers in PGHN. Strategies to support the recognition of PGHN and to standardize and improve training conditions should be developed and implemented.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic_AG-6496.pdf.

Training in pediatric hepatology across Europe: a survey of the National Societies Network (2016-2019) of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition.

Background: The widely recognized burden of liver diseases makes training in pediatric hepatology (PH) imperative. The aim of this survey, which was part of a global survey on training in pediatric gastroenterology, hepatology and nutrition (PGHN) across Europe, was to assess the PH and liver transplantation (LT) infrastructure, staff and training programs in PGHN training centers. Method: Standardized questionnaires were collected from training centers via the presidents/representatives of the National Societies Network of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) from June 2016 to December 2019. Results: A total of 100 PGHN training centers participated in the survey (14/100 were national referral centers in PH and/or LT). Dedicated PH clinics were available in 75%, but LT clinics in only 11%. Dedicated beds for PGHN inpatients were available in 47/95 (49%) centers. Full-time or part-time specialists for PH care were available in 31/45 (69%) and 11/36 (31%) centers, respectively. Liver biopsies (LB) were performed in 93% of centers by: a PGHN specialist (35%); an interventional radiologist (26%); a pediatric surgeon (4%); or a combination of them (35%). Dividing the annual number of LBs in the centers performing LBs by the number of trainees gave a median (range) of 10 (1-125) per trainee. Transient elastography was available in 60/92 (65%) of centers. Conclusions: The survey highlighted the differences and shortcomings in PH training across Europe. ESPGHAN should take initiatives together with National Societies to ensure the acquisition of PH knowledge and skills according to the ESPGHAN curriculum.An infographic is available for this article at: http://www.annalsgastro.gr/files/journals/1/earlyview/2022/Infographic-Hepatology-training-paper.pdf.

Training in Paediatric Clinical Nutrition Across Europe: A Survey of the National Societies Network (2016-2019) of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition.

OBJECTIVES/BACKGROUND: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. METHODS: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. RESULTS: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) andhome parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of <5 annually are reported by 13% and 43% of centres, respectively. CONCLUSIONS: The survey shows clear differences and deficits in Clinical Nutrition training infrastructure, including staff and patient volumes, in European PGHN training centres, leading to large differences and limitations in training opportunities in Clinical Nutrition.

Toxin-Producing Klebsiella oxytoca in Healthy Infants: Commensal or Pathobiont?

OBJECTIVES: Klebsiella oxytoca is a gastrointestinal pathobiont with the potential to produce the toxins tilivalline and tilimycin, which cause antibiotic-associated hemorrhagic colitis. Overgrowth of toxigenic K oxytoca has recently been implicated in necrotizing enterocolitis. K oxytoca colonizes 2-9% of healthy adults, however, there is no systematic data on colonization in healthy children. We investigated K oxytoca colonization and its toxigenic properties in healthy infants. METHODS: We sampled stool of healthy infants and determined K oxytoca colonization using stool culture and PCR (pehX). Toxin in stool was measured with HPLC/high-resolution mass spectrometry. K oxytoca isolates were typed using multi-locus sequence typing (MLST) and K oxytoca toxin PCR (npsA/B). Cytotoxin production of isolates was analyzed by MTT assay. RESULTS: K oxytoca was detected in 30 of 61 infants (49%) using stool culture and in 45 of 61 (73%) using PCR (pehX). Toxin marker PCR (npsA/B) was positive in 66% of stool samples positive for K oxytoca PCR. Stool toxin levels were too low for quantitation but traces of tilivalline were detected. Contrarily, 49% of K oxytoca isolates demonstrated toxicity in the MTT assay. MLST revealed 36 distinct sequence types affiliated with all known K oxytoca sequence type clusters (A, B1 and B2). CONCLUSIONS: More than 70% of healthy infants were colonized with K oxytoca. Toxin quantities in stool of colonized healthy infants were below detection level, yet half of the isolates produced toxin in vitro demonstrating their pathobiont potential. The high occurrence of toxigenic K oxytoca in healthy infants has to be considered for future disease association studies.

Running Behind "POPO"-Impact of Predictors of Poor Outcome for Treatment Stratification in Pediatric Crohn's Disease.

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease. Methods: CD patients (1-18 years) registered in CEDATA-GPGE® (2004-2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties. Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission >1 year (Odd Ratio (OR) 1.49 [1.07-2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89-131.62], p < 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39-33.58], p < 0.001; OR 2.56 [1.58-4.15], p < 0.001, respectively). Positive Predictive Value for lack of sustained remission was >60% for patients with initial growth failure, persistent or stricturing/penetrating disease. Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.

Diagnostic and Therapeutic Approach in Paediatric Inflammatory Bowel Diseases: Results from a Clinical Practice Survey.

OBJECTIVES: Despite existence of international guidelines for diagnosis and management of inflammatory bowel diseases (IBD) in children, there might be differences in the clinical approach. METHODS: A survey on clinical practice in paediatric IBD was performed among members of the ESPGHAN Porto IBD working group and interest group, PIBD-NET, and IBD networks in Canada and German-speaking countries (CIDsCANN, GPGE), using a web-based questionnaire. Responses to 63 questions from 106 paediatric IBD centres were collected. RESULTS: Eighty-four percentage of centres reported to fulfil the revised Porto criteria in the majority of patients. In luminal Crohn disease (CD), exclusive enteral nutrition is used as a first-line induction therapy and immunomodulators (IMM) are used since diagnosis in the majority of patients. Infliximab (IFX) is mostly considered as first-line biological. Sixty percentage of centres have experience with vedolizumab and/or ustekinumab and 40% use biosimilars. In the majority of ulcerative colitis (UC) patients 5-aminosalicylates are continued as concomitant therapy to IMM (usually azathioprine [AZA]/6-MP). After ileocaecal resection (ICR) in CD patients without postoperative residual disease, AZA monotherapy is the preferred treatment. CONCLUSIONS: A majority of centres follows both the Porto diagnostic criteria as well as paediatric (ESPGHAN/ECCO) guidelines on medical and surgical IBD management. This reflects the value of international societal guidelines. However, potentially desirable answers might have been given instead of what is true daily practice, and the most highly motivated people might have answered, leading to some bias.

Use of Biosimilars in Pediatric Inflammatory Bowel Disease: An Updated Position Statement of the Pediatric IBD Porto Group of ESPGHAN.

Biologic therapies have changed the outcome of both adult and pediatric patients with Inflammatory Bowel Disease (IBD). In September 2013, the first biosimilar of infliximab was introduced into the pharmaceutical market. In 2015, a first position paper on the use of biosimilars in pediatric IBD was published by the ESPGHAN IBD Porto group. Since then, more data have accumulated for both adults and children demonstrating biosimilars are an effective and safe alternative to the originator. In this updated position statement, we summarize current evidence and provide joint consensus statements regarding the recommended practice of biosimilar use in children with IBD.

Antibody Concentrations Decrease 14-Fold in Children With Celiac Disease on a Gluten-Free Diet but Remain High at 3 Months.

BACKGROUND & AIMS: Celiac disease can be identified by a serologic test for IgA against tissue transglutaminase (IgA-TTG) in a large proportion of children. However, the increased concentrations of antibody rarely normalize within the months after children are placed on a gluten-free diet (GFD). Early serologic predictors of sufficient adherence to GFD are required for optimal treatment. METHODS: In a prospective study, we observed the response to a GFD in 345 pediatric patients (67% girls; mean age, 8.4 y) who underwent duodenal biopsy to confirm or refute celiac disease from October 2012 through December 2015. Baseline serum samples were tested centrally for IgA-TTG and IgG against deamidated gliadin. Follow-up serologic analyses of children on a GFD were performed about 3 months later. RESULTS: The geometric mean concentration of IgA-TTG decreased from 72.4-fold to 5.2-fold the upper limit of normal (ULN), or by a factor of 14.0 (95% CI, 12.0-16.4). A substantial response (defined as a larger change than the typical variation in patients not on a GFD) was observed in 80.6% of the children. Only 28.1% of patients had a substantial response in the concentration of IgG against deamidated gliadin. Concentration of IgA-TTG remained above 1-fold the ULN in 83.8% of patients, and above 10-fold the ULN in 26.6% of patients with a substantial response. CONCLUSIONS: Serum concentration of IgA-TTG decreases substantially in most children with celiac disease within 3 months after they are placed on a GFD, but does not normalize in most. This information on changes in antibody concentrations can be used to assess patient response to the diet at short-term follow-up evaluations. Patients with a substantial response to a GFD often still have high antibody levels after 3 months. German Clinical Trials Registry no. DRKS00003854.

Causes of hematochezia and hemorrhagic antibiotic-associated colitis in children and adolescents.

Diseases causing hematochezia range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We studied the underlying causes and long-term outcome of hematochezia in children. We further investigated the relevance of antibiotic-associated hemorrhagic colitis in children, especially if caused by Klebsiella oxytoca.Infants, children, and adolescents with hematochezia were recruited prospectively. Patients were grouped according to age (<1 year, 1-5 years, 6-13 years, >14 years). In addition to routine diagnostics, K oxytoca stool culture and toxin analysis was performed. We collected data on history, laboratory findings, microbiological diagnostic, imaging, final diagnosis, and long-term outcome.We included 221 patients (female 46%; age 0-19 years). In 98 (44%), hematochezia was caused by infectious diseases. Endoscopy was performed in 30 patients (13.6%). No patient died due to the underlying cause of hematochezia. The most common diagnoses according to age were food protein-induced proctocolitis in infants, bacterial colitis in young children, and inflammatory bowel disease in children and adolescents. Seventeen (7.7%) had a positive stool culture for K oxytoca. Antibiotic-associated colitis was diagnosed in 12 (5%) patients: 2 caused by K oxytoca and 2 by Clostridium difficile; in the remaining 8 patients, no known pathobiont was identified.Infections were the most common cause of hematochezia in this study. In most patients, invasive diagnostic procedures were not necessary. Antibiotic-associated hemorrhagic colitis caused by K oxytoca was an uncommon diagnosis in our cohort. Antibiotic-associated colitis with hematochezia might be caused by pathobionts other than C difficile or K oxytoca.

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.

Validation of Antibody-Based Strategies for Diagnosis of Pediatric Celiac Disease Without Biopsy.

BACKGROUND & AIMS: A diagnosis of celiac disease is made based on clinical, genetic, serologic, and duodenal morphology features. Recent pediatric guidelines, based largely on retrospective data, propose omitting biopsy analysis for patients with concentrations of IgA against tissue transglutaminase (IgA-TTG) >10-fold the upper limit of normal (ULN) and if further criteria are met. A retrospective study concluded that measurements of IgA-TTG and total IgA, or IgA-TTG and IgG against deamidated gliadin (IgG-DGL) could identify patients with and without celiac disease. Patients were assigned to categories of no celiac disease, celiac disease, or biopsy required, based entirely on antibody assays. We aimed to validate the positive and negative predictive values (PPV and NPV) of these diagnostic procedures. METHODS: We performed a prospective study of 898 children undergoing duodenal biopsy analysis to confirm or rule out celiac disease at 13 centers in Europe. We compared findings from serologic analysis with findings from biopsy analyses, follow-up data, and diagnoses made by the pediatric gastroenterologists (celiac disease, no celiac disease, or no final diagnosis). Assays to measure IgA-TTG, IgG-DGL, and endomysium antibodies were performed by blinded researchers, and tissue sections were analyzed by local and blinded reference pathologists. We validated 2 procedures for diagnosis: total-IgA and IgA-TTG (the TTG-IgA procedure), as well as IgG-DGL with IgA-TTG (TTG-DGL procedure). Patients were assigned to categories of no celiac disease if all assays found antibody concentrations <1-fold the ULN, or celiac disease if at least 1 assay measured antibody concentrations >10-fold the ULN. All other cases were considered to require biopsy analysis. ULN values were calculated using the cutoff levels suggested by the test kit manufacturers. HLA typing was performed for 449 participants. We used models that considered how specificity values change with prevalence to extrapolate the PPV and NPV to populations with lower prevalence of celiac disease. RESULTS: Of the participants, 592 were found to have celiac disease, 345 were found not to have celiac disease, and 24 had no final diagnosis. The TTG-IgA procedure identified patients with celiac disease with a PPV of 0.988 and an NPV of 0.934; the TTG-DGL procedure identified patients with celiac disease with a PPV of 0.988 and an NPV of 0.958. Based on our extrapolation model, we estimated that the PPV and NPV would remain >0.95 even at a disease prevalence as low as 4%. Tests for endomysium antibodies and HLA type did not increase the PPV of samples with levels of IgA-TTG ≥10-fold the ULN. Notably, 4.2% of pathologists disagreed in their analyses of duodenal morphology-a rate comparable to the error rate for serologic assays. CONCLUSIONS: In a prospective study, we validated the TTG-IgA procedure and the TTG-DGL procedure in identification of pediatric patients with or without celiac disease, without biopsy. German Clinical Trials Registry no.: DRKS00003854.