Anaemia is a frequent consequence of many gastrointestinal (GI) diseases in children and it can even be the initial presenting symptom of underlying chronic GI disease. The definition of anaemia is age and gender-dependent and it can be classified based on pathophysiology, red cell morphology, and clinical presentation. Although nutritional deficiencies, including GI malabsorption of nutrients and GI bleeding, play a major role, other pathophysiologic mechanisms seen in chronic GI diseases, whether inflammatory (e.g., inflammatory bowel disease) or not (e.g., coeliac disease and dysmotility), are causing anaemia. Drugs, such as proton pump inhibitors, mesalamine, methotrexate and sulfasalazine, are also a potential cause of anaemia. Not uncommonly, due to a combination of factors, such as iron deficiency and a chronic inflammatory state, the underlying pathophysiology may be difficult to decipher and a broad diagnostic work-up is required. The goal of treatment is correction of anaemia by supplementation of iron and vitamins. The first therapeutic step is to treat the underlying cause of anaemia including bleeding control, restoration of intestinal integrity and reduction of inflammatory burden. The route of iron and vitamin supplementation is guided by the severity of anaemia.

Abstract Background Data on upadacitinib therapy in children with Crohn’s disease (CD) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric CD. Methods A multicenter retrospective study of children treated with upadacitinib for the induction of remission of active CD from 30 centers worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN between 2022 and 2024. Demographic, clinical, laboratory, and imaging data as well as adverse events (AEs) were recorded at week 8 post induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle. Results One-hundred children (median age 15.8 [interquartile range 14.3–17.2] years) were included. All children were previously treated with biologic therapies and 89 with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) were observed in 75%, 56% and 52% of the children, respectively. Normal C-reactive protein was achieved in 68% of the children and fecal calprotectin (FC) <150 mcg/g in 58%. Combined CFR and FC remission was observed in 13/31 (42%) children with available data at 8 weeks [13% of the ITT population]. AEs were recorded in 24 children, the most frequent was acne (n=12). Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy. Conclusion Upadacitinib is an effective induction therapy for refractory pediatric CD. Efficacy should be weighed against the potential risks of AEs.

Background and aims Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking. We assessed the therapeutic response to help close this gap. Methods This retrospective study involved 30 sites worldwide. Demographic, clinical, and laboratory data were collected from patients with VEO-IBD who commenced adalimumab therapy before the age of 6 years. Results Seventy-eight patients (37 Crohn's disease, 26 ulcerative colitis, and 15 with IBD-unclassified) were included. Median age of IBD onset was 2.6 (1.3-4.1) years, with 30 (38.5%) patients diagnosed at age <2 years. Median age at adalimumab initiation was 4.2 (2.8-5.1) years. Adalimumab was used as second-line biologic therapy in 45 (57.7%) patients after infliximab. The median time to last follow-up was 63 (22-124) weeks. Significant improvement in clinical scores, CRP, fecal calprotectin, and weight Z-score were observed by Week 52. Adalimumab durability rates were 61.9%, 48.1%, and 35.6% after 1, 2, and 3 years, respectively. Drug discontinuation rates were not dependent on IBD type, age, prior anti-TNF exposure, or concomitant immunomodulatory treatment. Four (5.1%) patients developed serious infections, including 1 patient with TTC7A deficiency who died following adenovirus sepsis. Conclusion Adalimumab therapy is a viable therapeutic option in patients with VEO-IBD with an acceptable safety profile.

Abstract Background Pediatric Inflammatory bowel disease (IBD) is generally more aggressive and difficult to treat compared to adulthood IBD. The only biological agent approved for use in this population is Anti-TNF medications (Adalimumab and Infliximab). Other medications such as anti IL-23 and/or IL-12 antibodies are not officially approved, yet the adult literature showed efficacy even in refractory cases priorly exposed to biologics. Given the delay of new medications approval in children, we present the novel use and real world experience of risankizumab which is a p19 anti IL-23 antibody in children with refractory Crohn’s disease. Methods We present 5 cases of Crohn’s disease who have failed at least 1 biological agent, including Adalimumab, Infliximab, ustekinumab, Azathioprine and methotrexate. All of them developed pharmacodynamic loss of response to Anti-TNF and one patient developed neutralizing antibodies. MR enterography was showing active ileal disease prior to commencing risankizumab. One Patient had developed Pyoderma gangrenosum, and another patient underwent pan-endoscopy which showed inflamed mucosa. C-reactive protein and ESR did not correlate with disease activity or response to the medication. risankizumab was administered as per the protocol . After 1 year follow up, all patients were in clinical remission with normal calprotectin. Bedside intestinal Ultrasounds was done and showed normal bowel wall thickness. Pyoderma gangrenosum improved significantly as well. Only one patient had MR enterography after 1 year which was unremarkable. No side effects were observed within the follow up period. Results We demonstrate that risankizumab has been used for 5 patients who already lost response to one or two biological medications. This medication successfully induced clinical and radiological remission after 1 year. risankizumab could be used after Adalimumab, Infliximab or even ustekinumab. Despite lack of approval, cautious use of new biological agents might be the only choice to avoid surgical resection in refractory Crohn’s disease. No side effects were documented over short term follow up. Additionally, Pyoderma gangrenosum responded after treatment. Conclusion Risankizumab can be an effective choice in pediatric Crohn’s disease patients who have lost response to other biological treatment and who had surgical resection as well. Patients maintained remission over 1 year follow up, and did not exhibit any side effect. References Zare B, Gros B, Lal N, et alEffectiveness of risankizumab induction and maintenance therapy for refractory Crohn’s disease: a real-world experience from a preapproval access programme and early access to medicines schemeFrontline Gastroenterology 2024;15:499-506.

Background and aims: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. Methods: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction. Results: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with >= 2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses). Conclusion: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

Abstract Background Pediatric patients with IBD are at increased risk of Clostridium difficile infection, which can trigger disease flare-ups. Since treatment for flares and infections differs, identifying the infection and causative microorganism is crucial. There is limited data on the frequency of CDI in pediatric IBD patients in our region. This study aims to assess its incidence and identify possible risk factors. Methods We conducted a retrospective cross-sectional study from October 2017 to May 2024, which included 144 encounters of pediatric IBD patients who presented with exacerbation of GI symptoms suggestive of flare up and underwent stool testing (PCR, C.difficile toxin detection (ELISA), and culture). We analyzed the association between categorical variables using the Chi-square test to identify the predictors of CDI. All tests were considered significant with a P-value < 0.05. Results Stool PCR was positive in 45 encounters, with E.coli (11.8%) and C. difficile (10.4%)[a] being the most common pathogens. Other pathogens detected were Salmonella, Campylobacter, Norovirus, and Adenovirus. Patients with Crohn’s Disease had a higher rate of CDI than Ulcerative Colitis patients (17.2 vs 8.5%, P=0.151). Patients on biological therapies were significantly at a higher risk of developing CDI compared to patients who were not (17.9% vs 6.9%, P=0.042). We documented a higher rate of CDI in non-stricturing, non-fistulizing [b]CD patients. Additionally, we observed an increased rate of CDI in patients using azathioprine and corticosteroids, [c]though these findings were not statistically significant. Among patients hospitalized for flare-up symptoms, one-third were confirmed to have CDI. Conclusion CDI was common among pediatric IBD patients with flare-ups, particularly in those with Crohn's disease, non-stricturing, non-fistulizing[d] disease, on biologics, and those hospitalized for their symptoms. Early detection of CDI and other enteric pathogens is essential to guide appropriate management and prevent the harmful use of immunosuppressants during acute infections. References Kolho KL, Klemola P, Simonen-Tikka ML, Ollonen ML, Roivainen M. Enteric viral pathogens in children with inflammatory bowel disease. J Med Virol. 2012 Feb;84(2):345-7. doi: 10.1002/jmv.23193. PMID: 22170557. Axelrad JE, Joelson A, Green PHR, Lawlor G, Lichtiger S, Cadwell K, Lebwohl B. Enteric Infections Are Common in Patients with Flares of Inflammatory Bowel Disease. Am J Gastroenterol. 2018 Oct;113(10):1530-1539. doi: 10.1038/s41395-018-0211-8. Epub 2018 Aug 3. PMID: 30072777; PMCID: PMC7939066. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015 Jan 27;313(4):398-408. doi: 10.1001/jama.2014.17103. PMID: 25626036; PMCID: PMC6561347. Sehgal K, Yadav D, Khanna S. The interplay of Clostridioides difficile infection and inflammatory bowel disease. Therap Adv Gastroenterol. 2021 May 30;14:17562848211020285. doi: 10.1177/17562848211020285. PMID: 34104215; PMCID: PMC8170344.

BACKGROUND:There are scarce data available on upadacitinib in children with Crohn's disease (CD). AIM:To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD. METHODS:This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle. RESULTS:We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy. CONCLUSION:Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.

Background: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. Methods: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (>= 20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. Results: We included 101 children with a mean age at diagnosis of 12.8 +/- 2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. Conclusions: In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5–16.5] years) were included. All had failed biologic therapies, and 38 (66

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.

BACKGROUND:Whether primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed before 6 years (ie, VEO-IBD) has a distinct phenotype and disease course is uninvestigated. We aimed to analyze the characteristics and natural history of VEO-PSC-IBD, compared with early and adolescent-onset PSC-IBD. METHODS:This is a multicenter, retrospective, case-control study from 15 centers affiliated with the Porto and Interest IBD group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every 6 months. Inflammatory bowel disease-related (clinical remission, need for systemic steroids and biologics, and surgery) and PSC-related (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, or death) outcomes were compared between the 2 groups. RESULTS:Sixty-nine children were included, with a median follow-up of 3.63 years (interquartile range, 1-11): 28 with VEO-PSC-IBD (23 UC [82%], 2 IBD-U [7%] and 3 [11%] CD), and 41 with PSC-IBD (37 UC [90%], 3 IBDU [7.5%] and 1 [2.5%] CD). Most patients with UC presented with pancolitis (92% in VEO-PSC-UC vs 85% in PSC-UC, P = .2). A higher number of patients with VEO-PSC-IBD were diagnosed with PSC/autoimmune hepatitis overlap syndrome than older children (24 [92%] vs 27 [67.5%] PSC-IBD, P = .03), whereas no other differences were found for PSC-related variables. Time to biliary strictures and infective cholangitis was lower in the VEO-PSC-IBD group (P = .01 and P = .04, respectively), while no difference was found for other outcomes. No cases of cholangiocarcinoma were reported. CONCLUSIONS:Primary sclerosing cholangitis related to inflammatory bowel disease has similar baseline characteristics whether diagnosed as VEO-IBD or thereafter. A milder disease course in terms of biliary complications characterizes VEO-PSC-IBD.

What is Known Botulinum toxin (BoNT) causes muscle relaxation by inhibiting acetylcholine release from presynaptic motor neurons at the neuromuscular junction.What is New In children with achalasia, BoNT can be considered only in patients in whom rapid weight gain is important to improve surgical outcomes. BoNT has been suggested for treating cricopharyngeal achalasia and delayed gastric emptying. Anal achalasia and constipation after Hirschsprung disease corrective surgery are very promising indications for BoNT use. In selected children with resistant type of functional constipation and chronic anal fissure, BoNT is a viable option for treating.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory esophageal disease presenting as dysphagia to solid food and non-obstructive food impaction. Knowledge gaps exist in its diagnosis and management. These expert recommendations focused on the diagnosis of EoE in the United Arab Emirates. An electronic search of PubMed and Embase databases was used to gather evidence from systematic reviews, randomized controlled trials, consensus papers, and expert opinions from the last five years on the diagnosis of EoE. The evidence was graded using the Oxford system. Literature search findings were shared with the expert panel. A 5-point scale (strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree) was used, and a concordance rate of >75% among experts indicated agreement. Using a modified Delphi technique, 18 qualified experts provided 17 recommendations. Eleven statements achieved high agreement, four got moderate agreement, and two got low agreement. Challenges exist in diagnosing EoE, particularly in children. Esophageal biopsies were crucial in diagnosis, irrespective of visible mucosal changes. Further research on diagnostic tools like endoscopic mucosal impedance and biomarkers is needed. Diagnosis relies on esophageal biopsies and symptom-histology correlation; however, tools like EoE assessment questionnaires and endoscopic mucosal impedance could enhance the accuracy and efficiency of EoE diagnosis. The diagnosis of EoE is challenging since the symptoms seldom correlate with the histological findings. Currently, diagnosis is based on patient symptoms and endoscopic and histological findings. Further research into mucosal impedance tests and the role of biomarkers is needed to facilitate diagnosis.

Abstract Background Patients with very early onset inflammatory bowel disease (VEOIBD) often present with severe disease course and require escalation to biologics. Exclusion of pediatric patients from clinical trials lead to scarcity of efficacy and safety data on TNFa antagonists therapy in VEOIBD. We aimed to assess safety and efficacy of adalimumab (ADM) induction and maintenance therapy in patients with VEOIBD. Methods This was a retrospective study involving 31 sites affiliated with the IBD Porto Group and IBD Interest Group of ESPGHAN, as well as centers in North America. Demographic, clinical and laboratory data were collected from patients diagnosed with VEOIBD who commenced ADM therapy before 6 years of age between 2014 to 2023. Results We identified 77 VEOIBD patients with a median age at diagnosis of 2.6 years (interquartile range [IQR] 1.3–4.1), of whom 29 (38%) were diagnosed at age <2 years (infantile-onset IBD). Thirty-seven (48%) patients were diagnosed with Crohn’s disease, 25 (32%) with ulcerative colitis and 15 (20%) with IBD-unclassified. Five (9%) from those genetically tested were diagnosed with monogenic disease. Median age at initiation of ADM was 4.2 (IQR 2.8-5.1) years. Forty-four patients (57%) were Infliximab experienced, discontinued mainly due to pharmacokinetic (20 [45%]) and pharmacodynamic (13 [30%]) failures. At initiation of ADM, concomitant corticosteroids and immunomodulators were given in 37 (48%) and 29 (37%) patients, respectively. The median wPCDAI and PUCAI scores at baseline were 45 [37.5-60] and 45 [27.5-57.5], respectively. Median follow-up time was 85.4 (IQR 40.4-139.2) weeks. While patients with CD showed significant clinical improvement after 26 and 52 weeks (PCDAI decreased to 10 [0-33.4], p<0.001, and 10 [0-25], p<0.05, respectively), No significant improvement in PUCAI score was observed among patients with UC (Figure 1). Inflammatory markers and calprotectin showed a gradual decrease over time (Figure 1). Weight and Height Z scores did not differ significantly throughout the follow-up period. ADM discontinuation rates after 1 and 3 years were 40% and 65%, respectively, mainly due to primary non-response (14, 29.8%) and loss of response (19, 40.4%). Drug discontinuation rates were not dependent on concomitant immunomodulator treatment or ADM initiation or on age (less or above 3 years). Four patients (5.2%) developed severe infections, including a patient with TTC7A mutation who died following septic shock. Conclusion Adalimumab therapy was relatively safe and seemed more effective in young patients with Crohn’s disease, but not in those with ulcerative colitis. Durability was relatively low due to high rates of primary non-response and secondary loss of response.

Ustekinumab is an effective therapy for adult Crohn’s disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn’s Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7–17.2) with a median follow-up of 7.4 months (IQR 5.6–11.8). Ninety-nine percent had received prior anti-TNF, 63

OBJECTIVES: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). METHODS: Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. RESULTS: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). CONCLUSIONS: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

Achalasia is uncommon in pediatrics and typically presents after five years of age. It is often managed medically, endoscopically, or surgically such as myectomy. This case highlights an exceptionally rare occurrence of achalasia at the age of eight weeks, successfully treated with endoscopic CRE (R) balloon dilatation, providing prompt relief of symptoms. From birth, this full-term infant experienced persistent vomiting and choking, coupled with suboptimal weight gain and unresponsiveness to anti-reflux measures. Diagnostic assessments revealed notable findings a barium meal demonstrated contrast pooling in the esophagus with distal rat tail narrowing, and esophageal manometry identified elevated pressure at the lower esophageal sphincter (LES) and inadequate esophageal contractions consistent with the diagnosis of achalasia. The infant underwent two sessions of esophageal CRE (R) balloon dilatation under fluoroscopy 10 days apart. Possible associated syndromes were ruled out. No further interventions were needed for a followup duration of one year. The literature review reveals several modalities for treating achalasia in adults and older children, but there is a scarcity of data on younger children and infants. In this article, we reviewed current available evidence regarding treatment modalities and the success rate. There is an obvious lack of recommendations for children, particularly at younger ages, and the outcome is various given the rarity of this condition and the limited experience.

BACKGROUND:Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD). METHODS:A retrospective study from 14 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded. RESULTS:Sixty-two children (35 Crohn's disease, 27 ulcerative colitis; median age 15.5 [interquartile range, 13.1-16.8] years) were included. They had all failed previous biologic therapies, and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to <250 µg/g were achieved in 75% and 64%, respectively, at 12 months of follow-up. Twenty-nine (47%) children sustained adverse events, 8 of which were regarded as serious and led to discontinuation of therapy in 6. CONCLUSIONS:Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.

Abstract Background Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis, accounting for <10% of cases. Here we aimed to characterize the clinical features and natural history of paediatric patients with UP, and to identify predictors of poor outcomes. Methods A retrospective cohort study involving 37 sites affiliated with the IBD Interest group of ESPGHAN. Data were collected at different timepoints from patients diagnosed with UP aged <18 years between 01/01/2016-31/12/2020. Outcomes included time to initiation of systemic steroids, thiopurines or biologics, time to acute severe colitis (ASC), IBD-related admission and colectomy. Univariate cox regression was used to study the association between potential predictors and study outcomes. Results Two hundred and fifty patients with UP were included, with a median age at diagnosis of 14.5 (IQR 12.3-15.9) years, and a median follow-up of 2.7 (IQR 1.7-3.9) years. The most common presenting symptoms were bloody stools (94%), abdominal pain (59%) and diarrhea (53%). At diagnosis, the median pediatric ulcerative colitis activity index (PUCAI) score was 25 (IQR 20-35), and only 3 patients (1.3%) presented with ASC. Most children had normal inflammatory markers and albumin levels. the median fecal calprotectin level was 720 mcg/g (IQR 310-1800), while 16 patients (9.9%) had a calprotectin level <100mcg/g at diagnosis. Administration of oral or topical 5-ASA resulted in clinical remission rates of 52% and 48%, respectively, by the end of induction, while the combination of both led to remission in 73% of patients. The rates of treatment escalation to thiopurines and biologics at 1, 3 and 5 years were 11%, 27% and 45%, and 11%, 23% and 45%, respectively (Figure 1). Within 5 years from diagnosis, 20% of patients had presented with ASC. The PUCAI score at diagnosis of UP was highly associated with initiation of systemic steroids, thiopurines or biologics, as well as later ASC event and IBD admission, while a Mayo endoscopic score of 3 was associated with the initiation of biologics and subsequent ASC event and IBD admission (Table 1). Seven patients (4%) underwent colectomy by the end of follow-up. Among the 151/250 patients who had a repeat endoscopy, only 16% achieved mucosal healing and in 48% inflammation extended proximally. Cecal patch (P=0.009) and higher PUCAI score (P=0.009) at diagnosis, as well as higher PUCAI score (P=0.009) and lack of steroid-free clinical remission (P=0.005) by the end of induction were associated with proximal disease extension. Conclusion Disease burden is significant in paediatric patients that present with UP, with high rates of proximal disease extension and requirement for treatment escalation.

Background and study aims Esophageal mucosal bridge (EMB) may be diagnosed at the anastomotic site in children operated on for esophageal atresia (EA) but so far only a few cases ( n = 4) have been reported. This study aimed to characterize EMB in children with EA, risk factors, and treatment. Patients and methods This retrospective multicenter study recorded patient’s characteristics, EMB diagnosis circumstances, endoscopic management, follow-up, and EMB recurrence in children with EA aged less than 18 years, compared with paired EA patients without EMB. Results Thirty patients were included (60% male, 90% EA/tracheoesophageal fistula, 43% associated malformations). Compared to 44 paired controls, EMB was associated with a history of nasogastric tube feeding (31% vs. 9.1%, p = 0.02) and severe gastroesophageal reflux disease (history of fundoplication: 41.4% vs. 13.6%, p < 0.01). 77% had symptoms (food impaction and/or dysphagia). Endoscopic management was performed in 53% of patients (83% electrocoagulation) with no technical difficulties or complications. 80% of the symptomatic patients with EMB improved after endoscopic treatment, independently of anastomotic stricture dilatation or not. Conclusion EMB endoscopic management by electrocoagulation is safe and often leads to symptom improvement.