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We aimed to appraise the real‐life efficacy of Crohn's disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators. We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn's disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center. Sixty‐six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add‐on therapy. Forty‐six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn's Disease Activity Index < 12.5) at the end of phase 1, 44 (66.7%) normalized c‐reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 µg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p= 0.018). Among patients who received CDED + PEN as add‐on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p= 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p= 0.002). CDED with PEN confirmed its efficacy in a real‐life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of phase 1. Crohn's disease exclusion diet (CDED) plus partial enteral nutrition (PEN) has emerged as an alternative to exclusive enteral nutrition.CDED + PEN is effective in inducing remission in patients with mild‐to‐moderate Crohn's disease. Crohn's disease exclusion diet (CDED) plus partial enteral nutrition (PEN) has emerged as an alternative to exclusive enteral nutrition. CDED + PEN is effective in inducing remission in patients with mild‐to‐moderate Crohn's disease. In a real‐life setting, CDED + PEN has proven to be effective in inducing remission also in patients with clinically severe disease and in those with colonic phenotype.A higher inflammatory burden and the presence of extraintestinal manifestations are associated with lower remission rates at the end of phase I. In a real‐life setting, CDED + PEN has proven to be effective in inducing remission also in patients with clinically severe disease and in those with colonic phenotype. A higher inflammatory burden and the presence of extraintestinal manifestations are associated with lower remission rates at the end of phase I.

Inflammatory bowel diseases (IBD) encompass a group of chronic inflammatory disorders primarily affecting the gastrointestinal tract but capable of impacting various organs, including the eye, with uveitis being the most common ocular condition. We assessed uveitis prevalence and clinical features in a nationwide cohort of pediatric IBD. Among 4229 cases, six patients (four Crohn's disease, one ulcerative colitis, and one unclassified IBD) were identified, resulting in an overall prevalence rate of 141.8 per 100,000 patients. Uveitis onset varied: two before IBD, two after, and two concomitantly. Symptomatic uveitis occurred in 2/6 patients, with anterior involvement in all cases. Median follow‐up was 3 years (interquartile range 2–4.75 years). At the last follow‐up, 5/6 patients exhibited quiescent IBD, while 4/6 had inactive uveitis. One patient had ocular complications. Uveitis is a rare but potentially complicating manifestation of pediatric IBD. Inflammatory bowel diseases (IBD) are systemic disorders affecting primarily the gastrointestinal tract but encompassing a wide range of extraintestinal manifestations.Ocular involvement represents a common extraintestinal manifestation (EIM) in adult IBD, whereas lower prevalence has been reported in pediatric cohorts. Inflammatory bowel diseases (IBD) are systemic disorders affecting primarily the gastrointestinal tract but encompassing a wide range of extraintestinal manifestations. Ocular involvement represents a common extraintestinal manifestation (EIM) in adult IBD, whereas lower prevalence has been reported in pediatric cohorts. In a nationwide pediatric IBD cohort, uveitis prevalence was 141.8 per 100,000 patients (six cases out of 4229 patients).Uveitis onset varies as regards to IBD, with symptomatic ocular EIM occurring in only one out of three cases. At the last follow‐up, most of the patients had quiescent uveitis, albeit one of them had developed ocular complications. In a nationwide pediatric IBD cohort, uveitis prevalence was 141.8 per 100,000 patients (six cases out of 4229 patients). Uveitis onset varies as regards to IBD, with symptomatic ocular EIM occurring in only one out of three cases. At the last follow‐up, most of the patients had quiescent uveitis, albeit one of them had developed ocular complications.

There is a need for consensus on the recommendations for follow-up of children and adolescents with celiac disease. To gather the current evidence and to offer recommendations for follow-up and management. The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010–March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNFa) drug, stricture and surgery. Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P< 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3–82.4%), as was the response to oral steroids (70.4–76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti-TNFa earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC.

Mucosal healing (MH) and histological healing (HH) have been recently proposed as a novel treatment target for inflammatory bowel disease (IBD). The aim of the present study was to evaluate real-life achievement of such outcomes in a cohort of pediatric patients with IBD treated with anti-TNF-alpha (ATA) agents. A retrospective analysis was performed on patients affected by IBD who received ATA and were followed up at two referral centers. Incidence and cumulative rates for MH and HH for each group were calculated. Of 170 (105 Crohn's disease [CD] and 65 ulcerative colitis [UC]) patients, 78 with CD and 56 with UC underwent endoscopic re-assessment during the study period. MH was achieved by 32 CD (41%) and 30 UC (53.6%) patients; 26 CD (33.3%) and 22 UC (39.3%) patients achieved HH. MH incidence rate was 19.1/1000 and 47/1000 person-months, whereas HH incidence rate was 15.5/1000 and 34.7/1000 person-months for CD and UC, respectively. Remission at the end of induction was associated with higher MH and HH rates (HR: 2.43, P= 0.049 and HR: 2.94, P= 0.046, respectively) in CD. In UC, adalimumab was associated with lower MH and HH rates (HR: 0.16, P= 0.004 and HR: 0.07, P= 0.003). We reported a real-life experience arising from a large cohort of pediatric IBD who received ATA scheduled treatment. Less than half of patients with CD and only a little >50% of UC patients achieved MH. Microscopical inflammation was observed in 18.8% CD and 26.7% UC patients who achieved MH. Overall, MH and HH rates appear lower compared to previously published data.

The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schönlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pyloriinfection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

Acute severe colitis (ASC) is a potentially life-threatening event. Optimal timing for second-line treatment in children is mainly based on the clinical score Pediatric Ulcerative Colitis Activity Index. The aim of our study was to evaluate the potential role of bowel ultrasound scan (BUS) in predicting the need of second-line therapy in ASC. Patients younger than 18 years admitted to a single tertiary referral center with ASC were included. We retrospectively reviewed medical records collecting clinical and BUS data. Colonic wall thickness (CWT), loss of colonic wall stratification (CWS), presence of hyperechoic lymph nodes, and colonic wall flow evaluated at power Doppler were assessed at BUS performed within the third day of hospitalization. Sixty-nine ASC episodes from 52 different patients were identified. CWT showed significantly higher values in patients who required second-line therapy (5.14 vs 3.69?mm; P?3.4?mm) and loss of CWS as independent predictors of steroid resistance. BUS is a noninvasive, easily accessible, and cost-effective resource that may identify at an early stage first-line therapy failure in pediatric ASC.

The aim of the study was to establish an apparent diffusion coefficient (ADC) cut-off value to classify active and non-active lesions in inflammatory bowel disease. We reviewed 167 paediatric magnetic resonance enterographies executed for suspected inflammatory bowel disease by using a 1.5- and 3-T scanner. We assessed the presence and activity of the disease by using morphologic and functional parameters such as the ADC. Each patient could have more than 1 examinations. Quantitative assessment of disease activity in the ADC map was measured placing 3 regions of interest in the areas of highest inflammation and the mean value was calculated, patients without sign of inflammation were assessed at 2 standardised site. Ileocolonoscopy, esophagogastroduodenoscopy, surgery, and video-capsule endoscopy were used as standards of reference. We enrolled 34 patients and 35 examinations: radiological findings of disease were identified in 29 examinations and 44 lesions were detected. Six patients had negative results and ADC assessment was taken at the terminal ileum and cecum. A total of 56 bowel segments were included in the study. Image analysis revealed 39 active lesions (69.6%) and their ADC values were lower compared to the ones of non-active segments. For each scanner a cut-off value was found (sensitivity: 0.91, specificity: 0.89 for 1.5 T and 0.81 for 3 T). Inter-rater agreement on disease activity between ADC values and magnetic resonance enterography results and between ADC values and the standard of reference were very good. ADC can provide a scanner-based quantitative measurement of disease activity.

Biologic therapies have changed the outcome of both adult and pediatric patients with Inflammatory Bowel Disease (IBD). In September 2013, the first biosimilar of infliximab was introduced into the pharmaceutical market. In 2015, a first position paper on the use of biosimilars in pediatric IBD was published by the ESPGHAN IBD Porto group. Since then, more data have accumulated for both adults and children demonstrating biosimilars are an effective and safe alternative to the originator. In this updated position statement, we summarize current evidence and provide joint consensus statements regarding the recommended practice of biosimilar use in children with IBD.

The only available treatment for celiac disease (CD) is the gluten-free diet. It is unclear whether the presence of gluten in oral hygiene products and cosmetics that are applied on the mouth is a reason of concern for CD patients. The aim of this study was to test the level of gluten contamination in oral hygiene and cosmetic products available in the Italian market. A total of 66 products (toothpastes = 37; dental tablets = 2; mouthwashes = 5; lip-balms = 10; lipsticks = 12) labelled gluten-free or with unknown gluten content were randomly collected from different supermarkets and pharmacies. The gluten quantification was determined by the R5 ELISA method approved by EU regulations. Out of 66 oral hygiene and cosmetics, 62 products (94%) were found to be gluten-free (gluten level <20 ppm), while 4 (6%) (toothpastes = 3; lipsticks = 1) showed a gluten level >20 ppm (toothpastes: 20.7, 31.4, and 35 ppm; lipstick: 27.4 ppm). None of the selected products had ingredient derived from wheat, barley, or rye. Gluten contamination is currently not an issue in a wide array of cosmetic and oral hygiene products that are commonly in the market.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Because the patents for biopharmaceutical monoclonal antibodies have or soon will expire, biosimilars are coming to the market. This will most likely lead to decreased drug costs and so easier access to these expensive agents. Extrapolation, however, of the limited available clinical data from adults with rheumatologic diseases to children with inflammatory bowel disease (IBD) should be done with caution and needs some considerations. Postmarketing surveillance programs for efficacy, safety, and immunogenicity should become mandatory in children with IBD using biosimilars, as for all biological drugs.

The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. We aimed to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy. These revised Porto criteria for the diagnosis of PIBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.

Multichannel intraluminal impedance (MII) is a pH‐independent method of assessing gastroesophageal reflux. To evaluate the diagnostic accuracy of MII‐pH as compared with conventional pH monitoring in detecting reflux events (REs) and symptom association in different age groups. A prospective direct comparison of 2 diagnostic techniques on 291 consecutive patients referred for suspected gastroesophageal reflux disease. Sensitivity and diagnostic accuracy of MII‐pH versus pH monitoring and symptom association were measured. MII‐pH detected 13631 REs, 6260 (46%) of which were nonacid. The prevalence of weakly acid refluxes in the 24 hours and postprandial period as well as the proximal extension of refluxate were significantly greater in infants as compared with children (P< 0.001, P< 0.001, and P< 0.01, respectively). The diagnostic accuracy of combined MII‐pH in revealing all RE and acid RE were significantly higher in infants as compared with children (92% vs 82%, P< 0.01 and 83% vs 76%, P< 0.04, respectively). The addition of MII to conventional pH monitoring significantly increases the diagnostic yield of symptom association analysis in revealing an association between atypical symptoms and refluxes irrespective of age, whereas in studying typical symptoms it was true only for infants. Addition of MII to conventional pH monitoring significantly increases the diagnostic yield in detecting REs, prevalently in infants, and in revealing an association between refluxes and symptoms, prevalently respiratory ones and in infants group.

The relation between Crohn disease (CD) and mycobacterial infection is complex and intriguing. The 2 conditions share common immunopathogenic features, and the hypothesis that Mycobacterium aviumsubspecies paratuberculosismay cause CD is still under debate. Moreover, differential diagnosis between CD and intestinal tuberculosis (TB) may be challenging, especially in the growing proportion of children immigrating from countries with a high prevalence of TB. Thus, in Western countries, paediatricians who are involved in the diagnosis and management of children with CD are expected to face intestinal TB more frequently than in the past and should always consider the differential diagnosis between these 2 conditions. In addition, the use of biological agents in the treatment of CD, which may reactivate latent TB, requires the development of targeted diagnostic algorithms. Children with CD who are candidates for treatment with antitumour necrosis factor-a agents should be screened for latent or active TB and closely followed over time, also considering possible failure of antitubercular prophylaxis and the frequent uncharacteristic presentation of TB in children receiving antitumour necrosis factor-a agents. In the present review, the most recent literature findings on these topics are reported, focusing particularly on the paediatric age group.

To establish the prevalence of headache in children with celiac disease (CD), the response to a gluten-free diet, and the prevalence of CD in children affected by headache.

To establish the rate of Helicobacter pylorireinfection in children from an H. pylorihigh prevalence area, possible clinical features predictive of reinfection and the usefulness of re‐treatment. 65 consecutive children attending the authors' department between 1998 and 2000 who had proven successful H. pylorieradication were enrolled; 52 took part. Patients and family members were invited to undergo 13C‐urea breath testing and to complete a simple questionnaire regarding symptoms and socioeconomic status. Patients with H. pylorireinfection were offered treatment; eradication was assessed by 13C‐urea breath test 8 weeks after completion of treatment. Of 52 children, 15 (28.8%) were H. pyloripositive. Variables predictive of reinfection were age at primary infection and presence of an infected sibling. Although reinfected children were more frequently symptomatic than non‐reinfected patients, no specific symptom was associated with reinfection. Of the nine re‐treated patients who returned 8 weeks after completing therapy, the bacterium was eradicated in five (56%). The 12.8% per year reinfection rate in childhood at 2 years that we observed should prompt a re‐evaluation of H. pyloristatus even after a successful eradication. Living in an H. pylorihigh prevalence area increases the annual risk of reinfection by approximately fourfold over the annual risk in H. pylorilow prevalence areas.

Conflicting results have been reported in adults with human immunodeficiency virus (HIV-1) who were investigated for Helicobacter pyloriinfection. Most studies indicate a lower prevalence than is found in the general population. The purposes of this study were to evaluate H. pyloriprevalence by noninvasive methods in a population of children perinatally infected with HIV-1 and to correlate H. pyloriprevalence with HIV-1-related clinical and immunologic status.

Growth‐inhibitory autocrine polypeptides such as transforming growth factor (TGF)‐β may play a role in the control of normal epithelial cell proliferation and differentiation. In addition, TGF‐β has a central role in extracellular matrix homeostasis and regulates the immune response at the local level. In this study immunohistochemistry was used to examine the pattern of TGF‐β protein distribution and quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) to determine levels of TGF‐β messenger RNA expression in normal intestinal mucosa and in the flat mucosa of children with celiac disease. Small intestinal biopsies were performed in children with active celiac disease and in histologically normal control subjects. Frozen sections were single stained using an anti‐TGF‐β monoclonal antibody and were double stained for TGF‐β and T cell, macrophages, and the activation marker CD25. Total RNA was extracted from frozen specimens and competitive quantitative RT‐PCR performed for TGF‐β mRNA using internal synthetic standard RNA. In normal intestinal mucosa, by immunohistochemistry, TGF‐β expression was most prominent in the villous tip epithelium, whereas in the lamina propria, weak immunoreactivity was present. The celiac mucosa showed weak and patchy epithelial TGF‐β immunoreactivity. In contrast, an intense staining positivity was present in the lamina propria localized mostly in the subepithelial region where T cells, macrophages, and CD25+cells were detected by double staining. By quantitative RT‐PCR, levels of TGF‐β mRNA transcripts appeared to be increased in celiac intestinal mucosa compared with that in control subjects, although the difference did not reach statistical significance. These observations suggest that TGF‐β expression is associated with differentiated enterocyte function. In celiac disease the lower TGF‐β epithelial cell expression could be a consequence of the preponderance of a less differentiated epithelial cell phenotype also present in the surface epithelium. In contrast, the prominent TGF‐β positivity of the subepithelial lamina propria suggests an association with the local immune and inflammatory response, as well as a potential role of these peptides in mesenchymal‐epithelial cell interaction.