Caterina Strisciuglio

Objective: To provide an updated, evidence-based European Crohn’s and Colitis Organisation [ECCO]–European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN] guideline for the management, monitoring, and long-term care of pediatric Crohn’s disease [CD]. Methods: A multidisciplinary panel of 27 experts followed ECCO Standard Operating Procedures for guideline development. A systematic review of studies published between January 2018 and October 2024, with targeted updates through June 2025, was conducted across MEDLINE, EMBASE, and Cochrane Central. Evidence was graded using the Oxford Centre for Evidence-Based Medicine levels. Draft statements underwent two Delphi voting rounds involving the guideline panel, ECCO National Representatives, and an international sounding board; statements achieving ≥80% agreement were accepted. Results: This guideline provides updated recommendations across major domains of pediatric CD care, including risk stratification, treatment targets, induction and maintenance strategies, nutritional therapies, therapeutic drug monitoring, and the roles of imaging and endoscopy. High-risk patients should start anti-TNF therapy as first-line treatment, with proactive and reactive therapeutic drug monitoring to enhance efficacy. For low-risk luminal disease, exclusive enteral nutrition or the Crohn’s Disease Exclusion Diet with partial enteral nutrition are preferred induction options. Long-term management emphasizes achieving endoscopic remission, normal growth, improved quality of life, and reduction of bowel damage. This guideline also reviews emerging advanced therapies, including biologics and small molecules, which are increasingly used in practice but generally not yet approved for pediatric CD, to inform clinicians about their potential role. Conclusions: This updated ECCO–ESPGHAN guideline integrates new pediatric evidence with contemporary adult data and treat-to-target principles, providing practical recommendations to support personalized, multidisciplinary, and proactive management aimed at improving long-term outcomes in pediatric CD.

INTRODUCTION: Disorders of gut-brain interaction (DGBI) are frequently reported in patients with inflammatory bowel disease (IBD), but pediatric data are scarce. We aimed to determine the prevalence of DGBI-like symptoms in children with quiescent IBD compared with healthy controls (HC), and to evaluate their impact on health-related quality of life, anxiety and symptoms burden. METHODS: This multicenter, prospective, observational study enrolled children aged 10–18 years with biochemically quiescent IBD, with or without endoscopic confirmation of remission from 7 European Society of Pediatric Gastroenterology, Hepatology and Nutrition centers (January 2021–August 2023). Age and sex-matched HC were recruited through primary care pediatricians and screened for subclinical inflammation using fecal calprotectin. DGBI were assessed using Rome IV criteria. Health-related quality of life and psychological burden were evaluated using IMPACT III, PROMIS Anxiety, Visceral Sensitivity Index–Child, and Behavioral Response Questionnaire–Child. RESULTS: A total of 253 children were enrolled (IBD: n = 131; HC: n = 122). The prevalence of DGBI-like symptoms did not differ between IBD and HC (34.4% vs 41.8%, P = 0.30). Functional abdominal pain disorders were present in 24.4% of children with IBD. Children with IBD and DGBI-like symptoms showed significantly lower IMPACT III scores compared with those without DGBI [median 74 (interquartile range 62.5–81) vs 84 (70–90); P = 0.001], with the greatest impairment in IBD symptoms, energy, and social domains. PROMIS Anxiety scores were higher in the DGBI group [31 (20–44) vs 21.5 (16–28); P < 0.001], with a greater proportion exceeding the clinical threshold (>50) (17.8% vs 3.5%; P = 0.008). Female sex was the only independent predictor of DGBI (OR 5.2, 95% CI 1.6–16.1; P = 0.005). DISCUSSION: DGBI-like symptoms are common in children with quiescent IBD and are associated with a substantial psychological and quality-of-life burden.

Background: Gastroesophageal reflux disease (GERD) is a common reason for referral to pediatric and gastroenterology clinics. Still, uncertainty and variability exist in the evaluation, diagnostic approaches and management among different age groups and clinicians. This study aimed to report the results of a Guidelines process and an Italian expert Consensus focusing on the diagnosis of GERD in children to improve the clinical approach to these patients. Methods: A multidisciplinary board of 16 participants identified eight PICO (Population/Patient/Problem, Intervention, Comparator and Outcome) questions, including definition, signs and symptoms, risk factors, diagnostic tests, treatment and prognosis of gastroesophageal reflux (GER) and GERD in children: four PICO questions were related to the diagnosis of GERD. Four databases (PubMed/Medline, Embase, Web of Science and Google Scholar) were searched from their inception to May 11, 2024, limited to children (0–18 years) and English language. For each PICO question a specific search string was developed. Guidelines, systematic reviews and clinical studies on diagnosis and management in children were considered to formulate evidence-based recommendations. Agreement was defined based on a 9-point Likert scale. A two-round Delphi method was conducted and consensus was defined as ≥ 80% agreement or disagreement. This paper focused on clinical symptoms and diagnosis of GER and GERD in pediatric ages. Results: 123 studies were included that satisfied systematic research criteria. The panel provided 14 recommendations on diagnosis of GER and GERD and practice points for specific questions to clarify some clinical issues. Conclusion: Symptoms of GER(D) are common in the pediatric population while regurgitation is frequently reported in the first months of life. In infancy symptoms mostly disappear spontaneously or after dietary modification. In infants and children with esophageal or extresophageal persistent symptoms, esophageal pH-MII monitoring and endoscopy are indicated to detect and characterize reflux episodes, phenotypes of GERD and esophagitis. In older children and adolescents reporting typical heartburn or in those with severe neurological impairment, a time-limited empirical trial of PPI can be considered as an initial diagnostic approach, with further testing reserved for non-responders.

Background: Suspected gastroesophageal reflux disease (GERD) is one of the most common reasons for referral to pediatric and gastroenterology clinics, and proton pump inhibitors (PPIs) are frequently prescribed. Currently, there is still wide heterogeneity in treatment, especially in neonates and extraesophageal presentations. This article aimed to provide guidelines and a consensus of Italian experts on the management of GERD in infants, children, and adolescents, in order to improve the care and treatment of these patients. Methods: A multidisciplinary pediatric panel identified four key clinical questions (PICOs) regarding pharmacological and non-pharmacological treatments, surgical intervention, and prognosis of pediatric GERD. Four databases (PubMed/Medline, Embase, Web of Science, and Google Scholar) were searched from inception to May 2024, using a specific search string for each PICO and limiting the search to children (0–18 years) and to English language. Previous pediatric guidelines, systematic reviews, and clinical trials focused on the treatment of GERD were considered to formulate evidence-based recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and AGREE II systems were used to assess study quality; a 9-point Likert scale was used to rate the recommendations. A two-round Delphi method was conducted to reach consensus, defined as ≥ 80% agreement or disagreement. Results: The systematic review identified three previous pediatric guidelines, eight systematic reviews, 83 RCTs, and three observational studies. The panel provided 26 recommendations regarding the management and treatment of GERD in pediatric patients. All reached consensus, with the majority expressing strong support for the intervention. The panel also provided practice insights for each PICO to improve the clinical application and clarity of these guidelines. Conclusion: Regurgitation is common in infants, but in most cases, no treatment is necessary. When regurgitation causes discomfort, a brief trial of alginate or thickened formulas or a cow’s milk elimination diet may be considered, particularly if other symptoms, including crying and dermatitis, are associated. For children who complain of heartburn or have severe neurologic deficits, a short course of empirical PPIs treatment may be considered, monitoring the clinical response and testing if no improvement is seen. PPIs are recommended in infants and children with reflux esophagitis, or acid reflux detected by esophageal pH monitoring. Children at high- risk for chronic GERD requiring prolonged treatment and multidisciplinary care have been identified. Surgery should be considered for severe or complicated GERD after a comprehensive diagnostic workup and optimal pharmacological management.

Crohn's disease (CD) is an inflammatory gastrointestinal disorder marked by impaired autophagy due to inefficient bacterial uptake. We studied the effects of autophagy modulation using Tat-beclin-1 and carbamazepine (CBZ) on dendritic cells (DCs) and Paneth cell functionality in pediatric CD patients. Twenty CD children genotyped for the ATG16L1 rs2241880 polymorphism and 10 healthy controls were enrolled. DCs were incubated with fluorochrome-conjugated particles of Escherichia coli or DQ-ovalbumin after pretreatment with CBZ or Tat-beclin-1 to evaluate antigen processing. Treated DCs were stained for P62, LAMP1, and LC3, and analyzed by confocal microscopy. Paneth cells from biopsies were pretreated with both drugs, stained for lysozyme, and analyzed by transmission electron microscopy. Antigen processing increased after Tat-beclin-1 and CBZ treatment in all groups. DCs expressed higher activation markers HLA-DR and CD86+, notably in high-risk patients, who also showed increased DQ-OVA processing. The number of lysozymes in Paneth cells from controls did not change after Tat-beclin-1 treatment, while in the CD group, it decreased significantly, suggesting increased exocytosis. CBZ treatment increased secretory granules only in CD inflamed tissue. Our results indicate that CBZ and Tat-beclin-1 enhance autophagic flux, representing a novel approach to treating pediatric CD patients.

Budesonide is a glucocorticoid with strong topical anti‐inflammatory properties and minimal systemic effects due to extensive first‐pass hepatic metabolism. It is designed for targeted delivery within the gastrointestinal (GI) tract and is available in oral and rectal formulations. Budesonide is indicated for various GI disorders, including Crohn's disease (CD, ulcerative colitis (UC) and eosinophilic oesophagitis (EoE), with specific formulations approved for different disease locations and severities. This narrative review evaluates the pharmacological profile, clinical applications and guideline recommendations surrounding the use of budesonide in both paediatric and adult GI disorders. Evidence from randomised controlled trials and real‐world studies supports the efficacy of budesonide in inducing remission in mild to moderate ileocaecal CD. It is recommended by ESPGHAN/ECCO [European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Crohn's and Colitis Organisation] guidelines as a therapeutic alternative in selected paediatric patients when exclusive enteral nutrition is not feasible. In UC, budesonide‐multimatrix tablets and rectal foam formulations may be effective for distal and left‐sided disease, though they are generally less effective than systemic corticosteroids or 5‐aminosalicylic acid and are reserved for patients with contraindications to standard therapies. In EoE, topical swallowed budesonide has shown promising results in inducing clinical and histological remission, with increasing data supporting its use in children. Although budesonide is associated with fewer systemic adverse effects, long‐term use may still pose risks such as growth suppression and hypothalamic‐pituitary adrenal axis suppression, necessitating careful monitoring. Budesonide offers a valuable treatment option when used in alignment with disease phenotype, formulation properties and patient‐specific considerations.

Aim: Determination of faecal gluten immunogenic peptides (f‐GIP) has recently been proposed as new noninvasive method to detect gluten intake in celiac disease (CD). Our aim was to evaluate the use of f‐GIP for the adherence to gluten‐free diet (GFD) and to compare this new marker with traditional methods. Methods: We enrolled both newly diagnosed cases and children in follow‐up with CD. Adherence to the GFD was assessed using the Biagi score, IgA anti‐transglutaminase (tTG IgA) and f‐GIP. Results: Seventy‐one CD children, 40.8% new diagnosis and 59.2% in follow‐up, were enrolled. Significant differences were found in the levels of faecal GIP between new diagnosis and follow up (median 185.7 ng/mL, IQR 67.8–318.8 ng/mL and 16.6 ng/mL, IQR 6.9–61 ng/mL respectively, p < 0.001). A significant direct correlation was found between faecal GIP and tTG IgA in the total cohort of enrolled patients ( r = 0.5, p < 0.001). In the follow up group, 21.4% tested positive for GIP and, of these GIP + patients, 78% had a high Biagi score. Conclusion: Our data shows that faecal GIP offers a precise assessment of even occasional exposure to gluten and suggests it might represent a less invasive instrument to check dietary adherence compared to traditional methods.

Macrophages play a crucial role in maintaining intestinal homeostasis and can exhibit either pro-inflammatory M1 or anti-inflammatory M2 phenotypes. The cannabinoid receptor type 2 (CB2) is involved in immune regulation and may represent a therapeutic target in inflammatory bowel disease (IBD). Our study investigates the phenotype of circulating macrophages and CB2 expression in children with IBD, assessing the role of CB2 stimulation in macrophage polarization, iron metabolism, and intestinal barrier function. Macrophages were isolated from 17 children with ulcerative colitis (UC), 21 with Crohn’s disease (CD), and 12 healthy controls (CTR). Cells were treated with a CB2 agonist (JWH-133) and an inverse agonist (AM630). CB2 expression and macrophage polarization were assessed by Western blot. Iron metabolism was evaluated through IL-6, hepcidin levels, FPN-1 expression, and iron concentration. Inflammation was assessed by cytokine release. An in vitro “immunocompetent gut” model was used to study the effects of CB2 stimulation on macrophage polarization and intestinal barrier function. CB2 expression was reduced in IBD macrophages. Compared to controls, IBD patients showed increased M1 markers and pro-inflammatory cytokines, with a reduction in M2 markers and IL-13. Altered iron metabolism was observed, with increased [Fe³⁺], hepcidin release, and DMT1 expression, and reduced FPN-1. CB2 stimulation restored iron metabolism, induced M2 polarization, and improved intestinal barrier function. CB2 could represent a novel therapeutic target for IBD by modulating macrophage function, iron metabolism, and mucosal barrier restoration.