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Background and Aims: A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients. Methods: A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature. Results: A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment ; macronutrients needs ; trace elements, minerals, and vitamins ; nutrition as a primary therapy of pediatric IBD ; probiotics and prebiotics ; specific dietary restrictions ; and dietary compounds and the risk of IBD. Conclusions: This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.

Objectives: The aims of our study were to evaluate health-related quality of life (HRQoL) in children affected by inflammatory bowel disease (IBD) during the first wave of Coronavirus disease 2019 (COVID-19) pandemic and after 12 months. Methods: This was a single-center, prospective, observational study conducted between April 2020 and April 2021. Children from 10 to 18 years with a confirmed diagnosis of IBD were enrolled during the first COVID-19-related national quarantine. The following information was collected at the baseline and after 12 months: IBD subtype, location and phenotype, disease activity, current and previous therapies. Patients were asked to complete the PROMIS Anxiety and IMPACT III questionnaires. Results: One hundred and eighteen patients were enrolled, of whom 54 (46%) were affected by Crohn disease (CD) and 64 (54%) with ulcerative colitis (UC; median age: 15.5 years, range 10.3-18; M/F: 68/50). Median HRQoL was significantly decreased after 12 months compared with the beginning of COVID-19-related quarantine (T1: 76.7 vs T2: 72.8; P < 0.001). At 12 months, a higher number of children were reported to be in active disease when compared with the enrollment [T2: 22/108 (20.4%) vs T1: 12/118 (10%); P = 0.02]. Multivariate analysis showed a significant influence on HRQoL of quarantine period (P < 0.001), female sex (P = 0.016), biologic therapy (P = 0.011), and active disease (P < 0.001). Conclusions: A deterioration of HRQoL after 12 months from COVID-19-related quarantine was observed. Additionally, the higher number of children with active disease at 12 months compared with enrollment may suggest detrimental consequences of the reduced disease control, contributing to decreased HRQoL.

Background Scarce data have investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and the possible peculiar phenotype and natural history of such an association. Methods Case-control study is based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a combined diagnosis of IBD and EoE were included. The overall prevalence and incidence in 2 periods, 2009 to 2015, and 2016 to 2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. Results Eleven patients (age 11.2 ± 2.8 years, Males 91%) with EoE-IBD out of 3090 patients with IBD were identified, resulting in an overall prevalence of 0.35% and an incidence of 0.18% for 2009 to 2015 and 0.45% for 2016 to 2021. Treatment escalation rates for IBD were significantly higher in patients with IBD compared with EoE-IBD at 12- and 24-month follow-up (0% vs 30%, P = .04; and 9% vs 45.5%, P = .03, respectively). Furthermore, patients with IBD were at a significantly higher risk of hospitalization than both EoE-IBD and EoE patients (log rank P Conclusions The incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in recent years. Having EoE appears to be associated with a milder IBD disease course, whereas having IBD does not seem to affect the natural history of EoE. More data are needed to better define the phenotype of such association.

Background The reduction of bone mineral density and osteoporosis have high impacts on the health of patients with inflammatory bowel diseases (IBD). We have previously shown that a dysregulated iron metabolism occurs in IBD and leads to a decrease in circulating iron concentration and excessive intracellular sequestration of iron. Studies suggest that iron overload significantly affects the bone, accelerating osteoclast (OC) differentiation and activation, promoting bone resorption. Moreover, we demonstrated that iron overload causes OC overactivity. The cannabinoid receptor type 2 (CB2) and the transient receptor potential vanilloid type-1 (TRPV1) are potential therapeutic targets for bone diseases. The aim of this study was to evaluate the roles of CB2 and TRPV1 receptors and of iron in the development of osteoporosis in pediatric IBD. Methods We differentiated OCs from peripheral blood mononuclear cells of patients with IBD and healthy donors and evaluated CB2 and TRPV1 receptor expression; OC activity, and iron metabolism by Western blot, TRAP assays, bone resorption assays, and iron assays. Moreover, we analyzed the effects of the pharmacological modulation of CB2 and TRPV1 receptors on OC activity and on the iron metabolism. Results We confirmed the well-known roles of CB2 and TRPV1 receptors in bone metabolism and suggested that their stimulation can reduce the OC overactivity induced by iron, providing new insights into the pathogenesis of pediatric IBD-related bone resorption. Conclusions Stimulation of CB2 and TRPV1 could reduce IBD-related osteoporosis due to their direct effects on OC activity and to modulating the iron metabolism.

Background Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available. We herein present for the first time longitudinal assessment of bowel morphology in a GSD Ib child suffering from Crohn disease-like enterocolitis treated with empagliflozin. Case presentation A 14-year-old boy with GSD Ib and severe IBD was (off-label) treated with empagliflozin (20 mg/day) after informed oral and written consent was obtained from the patient’s parents. No adverse events were noted. Clinical symptoms and stool frequency improved within the first week of treatment. Pediatric Crohn disease activity index (PCDAI) normalised within the first month of treatment. Abdomen magnetic resonance imaging (MRI) performed 3 months after treatment initiation showed dramatic decrease in disease activity and length. Similar findings were reported on histology at 5.5 months. At 7.5 months hemoglobin levels normalised and fecal calprotectin almost normalised. Improved neutrophil count, metabolic control and quality of life were also noted. G-CSF dose was decreased by 33% and the patient was partly weaned from tube feeding. Conclusions This is the first report presenting extensive gastrointestinal morphology follow-up in a GSD Ib patient receiving empagliflozin. The present case suggests that empagliflozin can be safe and effective in inducing IBD remission in GSD Ib patients and can even postpone surgery. Future studies are required to confirm its effect over time and assess its benefit in various disease stages. The development of an international collaborating networks for systematic data collection is worthy.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.

Background: The new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing. Aims: We aimed to evaluate endoscopic and histologic healing in children with Ulcerative Colitis (UC) and Crohn's disease (CD) in clinical remission after 52 weeks of Azathioprine. Methods: From December 2012 to July 2015 we prospectively enrolled IBD children starting Azathioprine. Enrolled patients in clinical remission underwent colonoscopy after 52 weeks. Macroscopic assessment was described with Mayo score and the simplified endoscopic score for UC and CD, respectively. For microscopic assessment, an average histology score was used. Data on inflammatory markers and fecal calprotectin were also collected. Results: Fourty-seven patients were included in the analysis. Endoscopic healing was detected in 20/26 (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and simplified endoscopic score were significantly decreased at week 52 (p < 0.001; p = 0.005). Median average histology score was not significantly different at week 52 in both diseases. Fecal calprotectin was directly correlated with simplified endoscopic score (T0: r = 0.4, p = 0.05; T52: r = 0.5, p = 0.01), but not with Mayo score. No correlation was found between endoscopic and histologic scores. Conclusions: IBD children under Azathioprine reach endoscopic healing, but not histological remission.

The primary role of environment on inflammatory bowel disease (IBD) onset has been recently stressed. We aimed to investigate the effect of environmental factors in an IBD pediatric cohort.A total of 467 subjects (264 IBD and 203 controls) were enrolled. All patients underwent a questionnaire including 5 different groups of environmental risk factors: family history of IBD and autoimmune diseases, perinatal period, home amenities and domestic hygiene, childhood diseases and vaccinations, and diet.In a multivariate model, mother's degree (odds ratio [OR]: 5.5; 2.5-11.6), duration of breast feeding3rd month (OR: 4.3; 1.6-10.5), father's employment (OR: 3.7; 1.2-8.7), gluten introduction6th month (OR: 2.8; 1.5-5), number of siblings2 (OR: 2.8; 1.5-5.3), and family history of autoimmune diseases (OR: 2.7; 1.4-5.3) were significant risk factors for Crohn disease. Low adherence to Mediterranean diet (OR: 2.3; 1.2-4.5), gluten introduction6th month (OR: 2.8; 1.6-4.9), and number of siblings2 (OR: 2; 1.1-3.6) were significant risk factors for ulcerative colitis. Owning pets (OR: 0.3; 0.1-0.7) and bed sharing (OR: 0.2; 0.1-0.6) were protective factors for Crohn disease, whereas owning pets (OR: 0.4; 0.2-0.8) and family parasitosis (OR: 0.07; 0.01-0.4) were protective factors for ulcerative colitis.Our study confirms that environmental factors are closely linked to IBD onset and may partly explain IBD rise in developed countries.

BackgroundVaccine-preventable diseases and opportunistic infections in pediatric inflammatory bowel disease (IBD) are increasingly recognized issues. The aims of this study were to evaluate vaccinations, immunization status, and consequent therapeutic management in children with IBD and to analyze the differences among patients diagnosed before (Group 1) and after June 2012 (Group 2).MethodsThis was a multicenter, retrospective cohort investigation. Between July 2016 and July 2017, 430 children with IBD were enrolled in 13 centers. Diagnosis, therapeutic history, vaccinations, and immunization status screening at diagnosis and at immunosuppressant (IM)/biologic initiation and reasons for incomplete immunization were retrieved.ResultsVaccination rates at diagnosis were unsatisfactory for measles, mumps, and rubella (89.3%), Haemophilus influenzae (81.9%), meningococcus C (23.5%), chickenpox (18.4%), pneumococcus (18.6%), papillomavirus (5.9%), and rotavirus (1.9%). Complete immunization was recorded in 38/430 (8.8%) children, but specific vaccines were recommended in 79/430 patients (18.6%), without differences between the 2 groups. At IM start, 22% of children were tested for Epstein-Barr virus (EBV) status, with 96.2% of EBV-naïve patients starting azathioprine, without differences between Groups 1 and 2. Screening for latent tuberculosis (TB) before start of biologics was performed in 175/190 (92.1%), with up to 9 different screening strategies and numerous inconsistencies.ConclusionsWe demonstrated a poor immunization status at diagnosis in children with IBD, which was not followed by proper vaccination catch-up. EBV status before IM initiation and latent TB before biologics were not adequately assessed. Thus, the overall impact of the current guidelines seems unsatisfactory.

We sought to correlate hepcidin levels in inflammatory bowel disease [IBD] children with disease activity, inflammatory markers, and iron load test [ILT] and to compare IBD patients with coeliac and healthy patients.Between December 2012 and June 2013, 145 subjects [50 IBD patients, 45 coeliac patients and 50 healthy controls] were included in the study. All patients underwent the following examinations: blood count, iron status, erythropoiesis parameters, serum hepcidin, C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]. In order to evaluate the efficacy of iron absorption, ILT was performed in IBD patients. Disease activity indexes and IBD duration, localisation, and therapy were also evaluated, and a faecal sample for calprotectin collected.Serum hepcidin was significantly higher in IBD patients with active disease compared with both coeliac and healthy patients [p = 0.005, p = 0.003 respectively]. In a multivariate logistic regression model, having a Paediatric Crohn's Disease Activity Index [PCDAI] / Paediatric Ulcerative Colitis Activity Index [PUCAI] ≥ 30 resulted in the only variable independently associated with a positive serum hepcidin (odds ratio [OR] = 6.87; 95% confidence interval [CI] 1.4-33, p = 0.01]]. Patients with iron malabsorption [IM] showed higher values of ESR, CRP, and hepcidin [p = 0.02, p = 0.001, and p = 0.06, respectively]. Eight out of 12 [66.7%] children with IM showed an active disease compared with 6/31 [19.3%] children with normal ILT [p = 0.01]. Hepcidin levels correlated negatively with ILT [r = -0.451, p = 0.002], and positively with ferritin and CRP [r = 0.442, p = 0.0001; r = 0.243, p = 0.009, respectively]Our study demonstrates that serum hepcidin is increased in IBD children with active disease and it is responsible for IM.

OBJECTIVES Existing studies usually do not measure the free vitamin D in pediatric patients with inflammatory bowel disease (IBD) and not consider the effect of inflammation on vitamin D levels. The aim of our study was to evaluate the concentrations of vitamin D-binding protein (VDBP), total and free 25-hydroxyvitamin-D (25(OH)D), and to correlate these values with the disease activity markers. METHODS Newly diagnosed children with IBD and a group of healthy controls (HCs) were enrolled. VDBP and total and free 25(OH)D levels were measured by enzyme-linked immunosorbent assay and compared using the Student t test. In each patient with IBD, the activity scores of disease and the main inflammation markers were correlated to total and free 25(OH)D levels. C-reactive protein was also measured in the control group, and it was related to VDBP by a linear regression test for all the groups. RESULTS Fifty-one consecutive children were enrolled: IBD = 33, HC = 18. Levels of total 25(OH)D were higher in HC than in patients with IBD (P = 0.01). The free/total 25(OH)D ratio was, however, higher in patients with IBD compared to HC (P

BACKGROUND: Early-onset inflammatory bowel disease (IBD) is generally aggressive, with a high probability of complications and need of surgery. Despite the introduction of highly effective biological drugs, treatment with azathioprine continues to be important even for early-onset IBD; however, in these patients azathioprine response seems to be reduced. This study evaluated azathioprine doses, metabolite concentrations, and their associations with patients' age in children with IBD treated at 6 tertiary pediatric referral centers. METHODS: Azathioprine doses, metabolites, and clinical effects were assessed after at least 3 months of therapy in 17 early-onset (age < 6 yr, cases) and 51 nonearly-onset (aged > 12 and

Background: Few case reports describe the clinical features of pancreatic involvement in inflammatory bowel disease. Aim: To investigate prevalence and disease course of inflammatory bowel disease children with pancreatitis and with exclusive hyperamylasemia and hyperlipasemia. Methods: We used a web-registry to retrospectively identify paediatric inflammatory bowel disease patients with hyperamylasemia and hyperlipasemia. Participants were re-evaluated at 6 months and 1 year. Results: From a total of 649 paediatric patients, we found 27 with hyperamylasemia and hyperlipasemia (4.1%). Eleven patients (1.6%) fulfilled diagnostic criteria for acute pancreatitis. Female gender was significantly associated with acute pancreatitis (p = 0.04). Twenty-five children (92.5%) had colonic disease. At 6 months 1/11 children with acute pancreatitis (9%) showed acute recurrent pancreatitis, while 1 patient (9%) had persistent hyperamylasemia and hyperlipasemia. At 12 months, 1 patient showed chronic pancreatitis (9.1%). Of the 16 children with exclusive hyperamylasemia and hyperlipasemia, 4 developed acute pancreatitis (25%), while 1 patient (6.2%) still presented exclusive hyperamylasemia and hyperlipasemia at 6 months. At 12 months, 11/16 patients (68.7%) reached a remission of pancreatic involvement, whereas 5 remaining patients (32.3%) had persistent hyperamylasemia and hyperlipasemia. Conclusions: In inflammatory bowel disease children, acute pancreatitis is more common in colonic disease and in female gender. Pancreatic function should be monitored, considering that pancreatic damage may evolve. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background: Clostridium difficile infection is associated with pediatric inflammatory bowel disease (IBD) in several ways. We sought to investigate C. difficile infection in pediatric patients with IBD in comparison with a group of children with celiac disease and to evaluate IBD disease course of C. difficile infected patients. Methods: In this prospective, comparative, multicenter study, 211 pediatric patients with IBD were enrolled from October 2010 to October 2011 and tested for the presence of C. difficile toxins A and B in their stools at 0, 6, and 12 months. During the same study period, stool specimens for C. difficile toxins analysis were collected from 112 children with celiac disease as controls. Results: Clostridium difficile occurrence was significantly higher in patients with IBD compared with patients with celiac disease (7.5% versus 0.8%; P = 0.008). Clostridium difficile was associated with active disease in 71.4% of patients with IBD (P = 0.01). Colonic involvement was found in 85.7% of patients with C. difficile. Antibiotics, proton pump inhibitors, hospitalization, and IBD therapies were not associated with increased C. difficile detection. At 12 months, a higher number of C. difficile-positive patients at the enrollment started immunosuppressant/biological therapy compared with patients without C. difficile (P = 0.01). At 6 and 12 months, patients with C. difficile were more frequently in active disease than patients without C. difficile (P = 0.04; P = 0.08, respectively). Hospitalizations were higher at 6 months in C. difficile group (P = 0.05). Conclusions: In conclusion, this study demonstrates that pediatric IBD is associated with increased C. difficile detection. Patients with C. difficile tend to have active colonic disease and a more severe disease course. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

Objectives Diagnostic and therapeutic benefits of double-balloon enteroscopy (DBE) have been documented in adults, with few data available on pediatric patients. We evaluated the diagnostic and therapeutic utility of DBE in children. Methods A prospective assessment of 113 DBE procedures in 58 consecutive children younger than 18 years (36 boys, 22 girls; median age 12.7 years, range 1-18 years) was performed for a variety of suspected small bowel (SB) disorders from January 2008 to August 2012 in a tertiary referral center for pediatric patients. All of the children had undergone upper gastrointestinal endoscopy and ileocolonoscopy. A total of 19 patients had undergone radiological investigations for SB (n = 11 magnetic resonance imaging; n = 5 barium enterography; n = 3 computed tomography) and 54 patients had undergone wireless capsule endoscopy (WCE). Results The overall median (range) examination time was 92.5 (45-275) minutes. The median (range) estimated insertion length of SB distal to pylorus was 230 (80-450) cm and proximal to ileocecal valve was 80 (5-275) cm. The common indications for DBE were polyposis syndromes (n = 21) and obscure gastrointestinal bleeding (n = 16). The findings included polyps (n = 19), mucosal ulcers and erosions (n = 8), submucosal elevations with white nodules (n = 4), and angioma/angiodysplasia (n = 2). The overall diagnostic yield for SB lesions using DBE was 70.7% (41/58) and for WCE was 77.7% (42/54). Endotherapeutic intervention was successfully used in 46.5% (n = 27/58). The endoscopic, medical, and surgical contributions to change in management by DBE were 72.4% (n = 42/58). Three complications (5.2%) were noted with uneventful recovery. Conclusions The diagnostic yield of DBE was comparable to WCE, but with the addition of therapeutic possibility and histological yield. We believe this technique could be a valuable addition to existing endoscopic techniques, complementary to WCE, and may be considered as an alternative diagnostic and therapeutic option in the SB in children.

AIM: To investigated the molecular cause of very early-onset ulcerative colitis (UC) in an 18-mo-old affected child. METHODS: We analysed the interleukin-10 (IL10) receptor genes at the DNA and RNA level in the proband and his relatives. Beta catenin and tumor necrosis factor-?? (TNF??) receptors were analysed in the proteins extracted from peripheral blood cells of the proband, his relatives and familial adenomatous polyposis (FAP) and PTEN hamartoma tumor syndrome (PHTS) patients. Samples were also collected from the proband's inflamed colorectal mucosa and compared to healthy and tumour mucosa collected from a FAP patient and patients affected by sporadic colorectal cancer (CRC). Finally, we examined mesalazine and azathioprine effects on primary fibroblasts stabilised from UC and FAP patients. RESULTS: Our patient was a compound heterozygote for the IL10RB E47K polymorphism, inherited from his father, and for a novel point mutation within the IL10RA promoter (the -413G->T), inherited from his mother. Beta catenin and tumour necrosis factor ?? receptors-I (TNFRI) protein were both over-expressed in peripheral blood cells of the proband's relatives more than the proband. However, TNFRII was over-expressed only in the proband. Finally, both TNF??-receptors were shown to be under-expressed in the inflamed colon mucosa and colorectal cancer tissue compared to healthy colon mucosa. Consistent with this observation, mesalazine and azathioprine induced, in primary fibroblasts, IL10RB and TNFRII over-expression and TNFRI and TNF?? under-expression. We suggest that ??-catenin and TNFRI protein expression in peripheral blood cells could represent molecular markers of sub-clinical disease in apparently healthy relatives of patients with early-onset UC. CONCLUSION: A synergistic effect of several variant alleles of the IL10 receptor genes, inherited in a Mendelian manner, is involved in UC onset in this young child.

Aim Aims of this study were to evaluate the efficacy of a cow's milk protein (CMP) elimination diet on induction and maintenance of remission and to define association with atopy in children with ulcerative colitis (UC). Methods Twenty-nine consecutive patients (mean age: 11.2 years; range: 4.6–17 years; F/M: 15/14) with newly diagnosed UC were randomized either to receive a CMP elimination diet (n = 14) or to continue a free diet (n = 15) associated with concomitant steroid induction and mesalazine maintenance treatment. Children were prospectively evaluated at four time points: within 1 month, 6 months and 1 year after diagnosis or at the time of relapse. Results Twenty-five of the 29 enrolled patients responded to the UC induction therapy with a complete remission (86.2%), 13 belonging to CMP elimination diet group and 12 to free diet group (p = 0.59). Overall, our data showed that 7 of 13 (53.8%) patients treated with CMP elimination diet and 8 of 15 (53.3%) patients on free diet and UC therapy relapsed within 1 year of follow-up (p = 1). Conclusions In conclusion, data of this paediatric, randomized trial suggest that CMP elimination has no role in the management of UC in non-sensitized children.