IL-10-producing regulatory cells impact on celiac disease evolution.

Celiac Disease (CD) is a T-cell mediated disorder caused by immune response to gluten, although the mechanisms underlying CD progression are still elusive. We analyzed immune cell composition, plasma cytokines, and gliadin-specific T-cell responses in patients with positive serology and normal intestinal mucosa (potential-CD) or villous atrophy (acute-CD), and after gluten-free diet (GFD). We found: an inflammatory signature and the presence of circulating gliadin-specific IFN-γ+ T cells in CD patients regardless of mucosal damage; an increased frequency of IL-10-secreting dendritic cells (DC-10) in the gut and of circulating gliadin-specific IL-10-secreting T cells in potential-CD; IL-10 inhibition increased IFN-γ secretion by gliadin-specific intestinal T cells from acute- and potential-CD. On GFD, inflammatory cytokines normalized, while IL-10-producing T cells accumulated in the gut. We show that IL-10-producing cells are fundamental in controlling pathological T-cell responses to gluten: DC-10 protect the intestinal mucosa from damage and represent a marker of potential-CD.

Esophageal food bolus impaction in pediatric age.

OBJECTIVES: Esophageal food impaction (EFI) is the sudden onset of dysphagia that occurs when a food bolus becomes lodged in the esophagus, requiring endoscopic removal. Scientific data on the prevalence and causes of EFI in children is lacking. The aim of this study was to provide further insights into EFI episodes in children. METHODS: We have prospectively enrolled all children admitted for a first episode of EFI between March 2018 and March 2023. A fluoroscopic contrast study was performed in all patients to confirm the boluses and assess their position. Boluses were extracted by esophagogastroduodenoscopies, and esophageal biopsies were routinely obtained for histologic evaluation. RESULTS: Over the study period, 41 children were admitted for a first episode of food impaction. Drooling was the most commonly reported symptom. Half children experiencing a first episode of food bolus were diagnosed with EoE (20/41, 48.8%). Almost a fourth of the episodes subtended a different condition, such as esophageal anastomotic, peptic or congenital strictures, stricturing caustic esophagitis, esophageal duplication, and achalasia. In the last fourth of patients the cause of EFI was not identified and thus probably related to quick eating and inadequate chewing of food. DISCUSSION: Our study represents the largest known series of pediatric patients evaluated for food bolus impaction. Our main finding is the high frequency of EoE, which accounts for a half of EFI episodes in pediatric age, especially in older children. This finding highlights the importance of obtaining esophageal biopsies after the endoscopic bolus removal in children with EFI to provide a complete diagnostic evaluation.

Effectiveness and safety of polyethylene-glycol-4000 versus sodium picosulphate plus magnesium oxide and citric acid for bowel cleansing before colonoscopy in children: A systematic review with meta-analysis.

Colonoscopy is performed for diagnostic and therapeutic purposes. The quality of colonoscopy depends on adequate bowel cleansing. However, there is no standardized protocol for bowel preparation in children. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the effectiveness, safety, and tolerability profile of polyethylene glycol (PEG) compared with those of sodium picosulfate (SPMC) in children. The primary sources of the reviewed studies were Scopus, PubMed, and Cochrane Library. The databases were systematically searched for RCTs comparing PEG 4000 to SPMC as a bowel cleansing solution. Six studies were included. The analysis showed that both PEG and SPMC are effective for bowel cleansing, while a split-dose regimen may be preferable to a day-before one. There were no differences between the two groups regarding adverse events such as abdominal pain, nausea, vomiting, bloating, and anal discomfort. Additionally, preparation with SPMC was preferred in terms of acceptability and compliance. Still, the need to place a nasogastric tube was significantly lower in the SPMC group compared to the PEG group and in the split dose regimen compared to the day before. In conclusion, PEG and SPMC are equally effective in obtaining an adequate bowel cleansing with a comparable adverse event rate; moreover, split-dose administration may be preferable to day-before one in terms of effective bowel cleansing. However, SPMC preparation is more acceptable seems to result in higher compliance, and to reduce the use of a nasogastric tube, that we encounter daily in clinical practice, is perceived as a stressful experience for children and their families.

Ocular endothelial dysfunction in pediatric inflammatory bowel disease.

OBJECTIVES: To assess ocular microvasculature changes using optical coherence tomography angiography (OCTA) in pediatric patients with inflammatory bowel disease (IBD). METHODS: Patients (aged 6-18 years) with IBD were recruited between September 2021 and May 2023. All eligible participants underwent comprehensive clinical assessment and laboratory investigation. Patients with functional gastrointestinal disorders served as the controls. This study assessed specific IBD phenotypes, disease duration, clinical and endoscopic activity indices, laboratory markers, and medication histories. OCTA was utilized to evaluate ocular microvasculature changes in both groups. RESULTS: A total of 63 children (mean age 12.9 ± 3.3 years) were enrolled, comprising 38 in the IBD group (16 ulcerative colitis, 22 Crohn's disease, and 25 in the control group). Most patients in the IBD group were in remission or had mild-to-moderate disease activity at enrollment. Analysis of the OCTA results revealed significant differences in the choroidal luminal area and total choroidal area between the IBD and control groups. CONCLUSIONS: The study identified distinct ocular microvasculature changes in pediatric IBD patients through OCTA, suggestive of potential systemic endothelial dysfunction. These findings underscore the utility of OCTA in evaluating microvascular alterations associated with pediatric IBD, offering insights into potential systemic complications linked to inflammation in IBD patients.

Helicobacter Pylori infection in children with inflammatory bowel disease: a prospective multicenter study.

BACKGROUND: The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET). METHODS: IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively. RESULTS: 76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached. CONCLUSION: The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.

Split-dose versus day-before regimen of sodium picosulfate plus magnesium citrate for bowel cleansing before colonoscopy in children: Randomized controlled trial.

OBJECTIVES: Polyethylene glycol (PEG) split-dose regimen is recommended as the option of choice for colon preparation before colonoscopy in children and adults. Sodium picosulfate plus magnesium citrate (SPMC) is equally effective but better tolerated than PEG for bowel preparation before colonoscopy in children. The aim of this study was to assess the superiority of SPMC split-dose regimen compared with SPMC day-before regimen for bowel cleansing before colonoscopy in children. METHODS: This was a multicenter, randomized, single-blind study. Pediatric inpatients undergoing colonoscopy received SPMC either in the day-before dosing or in split dosing. Overall bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS) and was rated as successful when BBPS was ≥6. Patient tolerability, acceptability, and compliance were recorded. RESULTS: The rate of successful cleansing level was significantly higher in the split-dose group than in the day-before group (P < 0.001). The BBPS scores were significantly higher in the split-dose group than in the day-before group for the whole colon (P < 0.001), the right colon (P < 0.001) and transverse colon (P < 0.001). Patient acceptability was better in the split-dose group (P = 0.0003; P = 0.005). The percentage of children needing nasogastric tube placement was better in the split-dose group (P = 0.007). CONCLUSIONS: The split-dose regimen of SPMC was superior to the day-before regimen in terms of successful colon cleansing and acceptability.

A possible unexpected link: Could wheat elimination trigger food protein-induced enterocolitis syndrome in a celiac disease patient?

Cases of association between celiac disease and wheat allergy have been described in the literature. However, to date, no reported cases have linked celiac disease with wheat food protein-induced enterocolitis syndrome (FPIES). We report a case of this association. A child diagnosed with celiac disease at the age of 2 years, following a gluten-free diet, experienced uncontrollable vomiting, and subsequent hypotension within 2 h of accidental ingestion of wheat flour. As a result, the child required hospitalization for fluid therapy. A similar episode occurred when the child turned 5 y, again resulting from accidental gluten ingestion. This time, the symptoms included vomiting, hypotension, and a loss of consciousness, leading to hospitalization for rehydration treatment. After this second episode, on suspicion of FPIES, the patient was referred to the pediatric allergists, who confirmed the diagnosis. To our knowledge, this is the first case of an association between celiac disease and FPIES. It has been hypothesized that exclusion diets in food-allergic children may lead to an increase in specific immunoglobulin E levels for those foods and, consequently, the risk of anaphylaxis. However, FPIES is not an immunoglobulin E-mediated condition. Hence, further investigations are warranted to elucidate the underlying mechanisms linking these 2 disorders.

Associations between immune biomarkers and symptoms of anxiety, depression, and insomnia in paediatric inflammatory bowel disease: A preliminary longitudinal analysis.

Innate immunity may influence the onset of affective symptoms and alter sleep patterns in chronic inflammatory conditions. Here, we tested the prospective associations between baseline serum C-reactive protein (CRP), albumin, and CRP/albumin ratio (CAR, i.e., an emerging biomarker of disease activity), and self-reported symptoms of anxiety, depression, and insomnia at 1-year follow up in paediatric inflammatory bowel disease (n = 17). After controlling for baseline values, CAR (ρ = 0.591, p = 0.026) predicted anxiety symptoms, while albumin predicted both anxiety (ρ = -0.687, p = 0.007) and insomnia symptoms (ρ = -0.648, p = 0.012). Current findings preliminarily suggest that inflammation may influence anxiety and sleep disturbance in paediatric IBD.

Gastrointestinal bleeding in children: diagnostic approach.

Different conditions may underlie gastrointestinal bleeding (GIB) in children. The estimated prevalence of GIB in children is 6.4%, with spontaneous resolution in approximately 80% of cases. Nonetheless, the initial approach plays a pivotal role in determining the prognosis. The priority is the stabilization of hemodynamic status, followed by a systematic diagnostic approach. GIB can originate from either upper or lower gastrointestinal tract, leading to a broad differential diagnosis in infants and children. This includes benign and self-limiting disorders, alongside serious conditions necessitating immediate treatment. We performed a nonsystematic review of the literature, in order to describe the variety of conditions responsible for GIB in pediatric patients and to outline diagnostic pathways according to patients' age, suspected site of bleeding and type of bleeding which can help pediatricians in clinical practice. Diagnostic modalities may include esophagogastroduodenoscopy and colonoscopy, abdominal ultrasonography or computed tomography and, when necessary, magnetic resonance imaging. In this review, we critically assess these procedures, emphasizing their respective advantages and limitations concerning specific clinical scenarios.

Probiotics and other adjuvants in allergen-specific immunotherapy for food allergy: a comprehensive review.

This review delves into the potential of manipulating the microbiome to enhance oral tolerance in food allergy, focusing on food allergen-specific immunotherapy (FA-AIT) and the use of adjuvants, with a significant emphasis on probiotics. FA-AIT, including oral (OIT), sublingual (SLIT), and epicutaneous (EPIT) immunotherapy, has shown efficacy in desensitizing patients and achieving sustained unresponsiveness (SU). However, the long-term effectiveness and safety of FA-AIT are still under investigation. Probiotics, particularly strains of Lactobacillus, play a crucial role in enhancing immune tolerance by promoting regulatory T cells (Tregs) and modulating cytokine profiles. These probiotics can induce semi-mature dendritic cells, enhance CD40 expression, inhibit IL-4 and IL-5, and promote IL-10 and TGF-ß, thus contributing to mucosal defense and immunological tolerance. Clinical trials combining probiotics with FA-AIT have demonstrated improved desensitization rates and immune tolerance in food-allergic patients. For example, the combination of Lactobacillus rhamnosus with peanut OIT resulted in a significantly higher rate of SU compared to the placebo group, along with notable immune changes such as reduced peanut-specific IgE and increased IgG4 levels. The review also explores other adjuvants in FA-AIT, such as biologic drugs, which target specific immune pathways to improve treatment outcomes. Additionally, nanoparticles and herbal therapies like food allergy herbal formula 2 (FAHF-2) are discussed for their potential to enhance allergen delivery and immunogenicity, reduce adverse events, and improve desensitization. In conclusion, integrating probiotics and other adjuvants into FA-AIT protocols could significantly enhance the safety and efficacy of FA-AIT, leading to better patient outcomes and quality of life.

Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: A multicentric randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of co-micronized palmitoylethanolamide (PEA)/polydatin (PD) in the treatment of abdominal pain symptoms in pediatric patients with irritable bowel syndrome (IBS). METHODS: This was a multicenter trial conducted at three Italian pediatric gastroenterology centers, employing a double-blind, placebo-controlled, parallel-arm design. Participants were ages 10 to 17 y and met Rome IV criteria for pediatric IBS. They were randomly allocated to receive either co-micronized PEA/PD or placebo, administered three times daily in a 1:1 ratio, over a 12-wk period. The study assessed baseline severity using the IBS-Severity Scoring System (IBS-SSS) at enrollment and after 4, 8, and 12 wk of treatment. Abdominal pain frequency was assessed on a scale from 1 to 7 d/wk, while stool consistency was classified using the Bristol Stool Scale (BSS) to categorize various IBS subtypes. The primary outcome was the percentage of patients who achieved complete remission, defined as IBS-SSS score <75 points after 12 wk of therapy. RESULTS: The study involved 70 children with IBS. Of the participants, 34 received co-micronized PEA/PD, and 36 received a placebo. As compared with the placebo group, the co-micronized therapy group had significantly more patients achieving complete remission after 12 wk (P = 0.015), with particular benefit in the IBS-diarrhea subtype (P = 0.01). The treatment group also experienced a significant reduction in abdominal pain intensity and frequency compared with the placebo group. No adverse events were recorded during the study period. CONCLUSIONS: Co-micronized PEA/PD is a safe and effective treatment to treat abdominal pain symptoms in pediatric IBS.