Faecal volatile organic compounds differ according to inflammatory bowel disease sub-type, severity, and response to treatment in paediatric patients.

BACKGROUND: Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. OBJECTIVE: To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. METHODS: Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography-mass spectrometry at presentation and 3 months later in children with IBD. RESULTS: In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3 years (10.2-14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p < 0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p < 0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p = 0.001) and UC (p = 0.012) compared with controls and decreased following treatment in UC (p = 0.01). In CD, propan-1-ol was significantly greater than controls (p < 0.001) and extensive colitis (p = 0.001) and fell with treatment (p = 0.05). Phenol was significantly greater in CD (p < 0.001) and fell with treatment in both CD (p = 0.02) and UC (p = 0.01). CONCLUSION: Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring.

Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS: A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS: A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION: Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

Swallowed topical steroid therapy for eosinophilic oesophagitis in children: practical, evidence-based guidance by the BSPGHAN Eosinophilic Oesophagitis Working Group.

OBJECTIVE: To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment. METHODS: A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical 'how to prepare and use' OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly. RESULTS: 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed. CONCLUSION: A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.

Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Variation in access and prescription of vedolizumab and ustekinumab in paediatric patients with inflammatory bowel disease: a UK-wide study.

BACKGROUND: Therapeutic options for paediatric inflammatory bowel disease (IBD) are limited, especially for younger children. Unlike in adults, vedolizumab and ustekinumab are not licensed for paediatric use in the UK. We aimed to understand the real-world access to, and use of, these therapies in the paediatric population. METHODS: We surveyed UK IBD centres to assess the incident use of vedolizumab and ustekinumab from 1 January 2021 to 31 December 2021. We collected information on funding, dose escalations and therapeutic drug monitoring. RESULTS: 18 of 21 centres responded, covering an estimated 5260 patients. One hundred and thirteen were started on vedolizumab, prescription incidence 2.2%, median prescriptions per centre was 4 (range 1-20). Considering ustekinumab, 73 patients were commenced, prescription incidence 1.4%. Median prescription per centre was 3.5 (range 1-13). Prescription rates at each centre were not predicted by patient number cared for at that centre (p=0.2). Dose escalation was common in vedolizumab (66.7% centres) and ustekinumab (55.5%).Funding strategies varied substantially, and multiple funding sources were used; 12 of 18 centres (66.7%) reported funding through routine National Health Service (NHS) England/Scottish arrangements. There was local NHS trust funding in 8 of 18 centres (44.4%). Individual funding requests (IFRs) were used in 5 of 18 (27.8%), although IFRs are reserved for patients with unique additional characteristics. Four centres were unable to achieve funding in pre-pubescent children. CONCLUSIONS: There is widespread use of vedolizumab and ustekinumab across the UK, although practice is highly variable. Access to therapy appeared to differ substantially. There is a growing disparity between international guidelines and real-world practice. Establishing early and effective therapy in all patients remains a priority.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Eosinophilic oesophagitis: improving diagnosis and therapy - reducing the burden of repeated endoscopy.

Eosinophilic oesophagitis is now being diagnosed more often, although there continues to be a significant delay in the recognition of the condition in primary care, and among patients presenting with food bolus obstruction to other specialities like Ears, Nose and Throat and Accident & Emergency. The diagnosis requires endoscopy and biopsy, with six biopsies taken from at least two different areas of the oesophagus. The diagnostic threshold is > 15 eosinophils/high power field or 0.3 mm2. Dietary management although effective is often difficult to carry out due to poor adherence by patients and the need for a specialist dietitian and repeated biopsies. Orodispersible budesonide is very effective for inducing remission and maintaining it long term, with fewer biopsies. Newer targeted biological agents are promising in the treatment of patients who have not responded to conventional treatments. Dilatation of strictures in this condition is safe.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Management of eosinophilic esophagitis associated food impaction in Europe and the United States.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge-The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings-Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

A Quantitative Assessment of Mucosal Eosinophils in the Gastrointestinal Tract of Children Without Detectable Organic Disease.

BACKGROUND: Accurate measurements of mucosal eosinophil concentrations in gastrointestinal tracts of healthy children are necessary to differentiate health and disease states in general, and better define eosinophilic gastrointestinal diseases. STUDY: We retrospectively reviewed gastrointestinal biopsies from children with macroscopically normal endoscopies, who, after a minimal follow-up of one year, were not diagnosed with any organic disease. Peak eosinophil concentrations and distributions were assessed from each segment of the gastrointestinal tract. RESULTS: Three centers (Italy, United Kingdom, and Israel) contributed 202 patients (median age 13 years IQR 9.5-15.5, range 1-18 years). Median (IQR, range) eosinophil concentrations (eos/mm2) were: esophagus 0 (0-0, 0-84), stomach 0 (0-4, 0-84), duodenal bulb 20 (13-30, 7-67), second part of duodenum 20 (13-29, 0-105), terminal ileum 29 (14-51, 0-247), cecum 53 (37-89, 10-232), ascending colon 55 (25-84, 0-236), transverse colon 38 (21-67, 4-181), descending colon 29 (17-59, 0-114), sigmoid colon 25 (13-40, 0-215) and rectum 13 (4-28, 0-152). Significant geographical variance was present, however, no differences in eosinophil concentrations were identified between children with resolving symptoms vs. those with functional diagnoses, nor across age groups. CONCLUSIONS: Standardized eosinophil concentrations from the gastrointestinal tracts of children without organic disease will serve to better define both health and disease states. No differences were found between resolved symptoms vs. functional diagnoses nor between age groups in this pediatric cohort.

Systemic steroids have a role in treating esophageal strictures in pediatric eosinophilic esophagitis.

BACKGROUND: The role of systemic steroids in the treatment of esophageal strictures in children with Eosinophilic Esophagitis (EoE) is poorly defined. AIMS: To describe a cohort of children with EoE-associated esophageal strictures responding to systemic steroids. METHODS: Retrospective review of medical records of children with EoE and moderate (<9 mm) to severe (<6 mm) strictures, who responded clinically and endoscopically to systemic steroids. RESULTS: Twenty children (median age 10.6 ±â€¯4.2 years; 17 males) from nine centers in six countries were included in the analysis; 16 had moderate and four, severe strictures; 18 had dysphagia or bolus impaction; median diagnostic delay was 8 months (IQR 3.5-35). Eighteen patients received oral systemic steroids (mean dose 1.4 mg/kg/day) for a median of 4 weeks, while two initially received IV steroids. All patients showed clinical improvement and 15/20 became asymptomatic. Stricture resolution at endoscopy was found in 19/20, while histological resolution of EoE (<15 eos/hpf) in 13/20. Only minor side effects were reported: hyperphagia (10/20); weight gain (5/20); hyperactivity (2/20) and acne (1/20). Esophageal dilation was required in 3/20 patients during a median follow-up of 48.5 months (IQR 26.7-73.2). CONCLUSION: Children with EoE and esophageal strictures, may benefit from the use of a short course of systemic steroids, avoiding mechanical dilation.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

Adaptations to the current ECCO/ESPGHAN guidelines on the management of paediatric acute severe colitis in the context of the COVID-19 pandemic: a RAND appropriateness panel.

OBJECTIVE: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison. DESIGN: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases. Panellists rated the appropriateness of interventions for ASC in the context of the COVID-19 pandemic. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended patients with ASC have a SARS-CoV-2 swab and expedited biological screening on admission and should be isolated. A positive swab should trigger discussion with a COVID-19 specialist. Sigmoidoscopy was recommended prior to escalation to second-line therapy or colectomy. Methylprednisolone was considered appropriate first-line management in all, including those with symptomatic COVID-19. Thromboprophylaxis was also recommended in all. In patients requiring second-line therapy, infliximab was considered appropriate irrespective of SARS-CoV-2 status. Delaying colectomy due to SARS-CoV-2 infection was considered inappropriate. Corticosteroid tapering over 8-10 weeks was deemed appropriate for all. After successful corticosteroid rescue, thiopurine maintenance was rated appropriate in patients with negative SARS-CoV-2 swab and asymptomatic patients with positive swab but uncertain in symptomatic COVID-19. CONCLUSION: Our COVID-19-specific adaptations to paediatric ASC guidelines using a RAND panel generally support existing recommendations, particularly the use of corticosteroids and escalation to infliximab, irrespective of SARS-CoV-2 status. Consideration of routine prophylactic anticoagulation was recommended.

Safety, Tolerability, and Pharmacokinetics of Oral Ferric Maltol in Children With Iron Deficiency: Phase 1 Study.

Iron deficiency is common in children and can have negative effects on behavior and function. Standard oral ferrous iron replacement is poorly absorbed and can cause treatment-limiting gastrointestinal adverse events (AEs). Ferric maltol is formulated to improve gastrointestinal absorption and tolerability versus oral ferrous compounds. In adult phase 3 trials, it increased hemoglobin and iron stores versus placebo, with a gastrointestinal AE profile similar to placebo. Here, we assess different doses of ferric maltol in children with iron deficiency. Methods: This phase 1 trial involved children of age 10 to 17 years with ferritin <30 µg/L (or <50 µg/L with transferrin saturation [TSAT] <20%). Children were randomized 1:1:1 to oral ferric maltol 7.8 mg, 16.6 mg, or 30 mg twice daily for 9 days and once on day 10. The primary outcomes were iron uptake measures (serum iron and TSAT) and population pharmacokinetic analyses. Results: The trial included 37 children (mean age 14.0 years; baseline mean ± standard deviation ferritin 16.3 ± 8.02 µg/L). Ferric maltol increased iron uptake nondose-proportionally: serum iron and TSAT plateaued between the 2 higher doses on day 1 and were comparable across all doses on day 10. Twenty children (54%) experienced AEs (all mild/moderate, gastrointestinal 32%), with similar frequencies in each group. Conclusions: All 3 ferric maltol doses increased iron uptake in children with iron deficiency, even over the short study duration, and were well tolerated. Nondose-dependent changes in serum iron and TSAT indicate physiologic regulation of iron uptake to meet the body's needs.