A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn’s disease (CD) should improve patient management and reduce complications. We aimed to identify ...evidence-based predictors of outcomes with the goal of optimizing individual patient management.
A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence.
Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density.
These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.
Inflammatory bowel disease (IBD) is the result of an altered immune homeostasis within the intestinal mucosa against the gut microbiota, leading to chronic inflammation in genetically predisposed ...individuals. Under normal conditions, the immune system defends against pathogens and prevents the passage of excessive intestinal bacteria; regulatory pathways must maintain a low-grade, controlled inflammation in a healthy gut, but also induce a protective response against pathogens. The innate immune system is the first-line defense from microbes; dendritic cells, macrophages, and epithelial cells produce an initial, immediate response. The immune system constantly controls commensal bacteria and utilizes constitutive antimicrobial mechanisms to sustain immune homeostasis. The discovery that several genes linked to IBD modulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), and genes that mediate autophagy (ie, ATG16L1, IRGM), has highlighted the critical role of host-microbe interactions in controlling intestinal immune homeostasis. Commensal microorganisms actively interact with the intestinal mucosa and influence the activity of the immune system as well as the amplitude of the immune response. In contrast, host factors can influence microbes, which in turn modulate disease susceptibility. In this paper, we focus on the mechanisms that mediate host-microbe interactions and how the disruption of this balance leads to chronic intestinal inflammation in IBD.
Abstract
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 < .001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared with EoE ones.
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.
Lay Summary
We investigated the association between pediatric inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). Our results showed that having an EoE might be associated with a milder IBD disease course, but larger cohort analyses are needed to confirm such result.
Objectives
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) often requiring endoscopic evaluations, which can be uncomfortable and costly, especially for children. This study ...aimed to evaluate the diagnostic accuracy of a noninvasive approach combining fecal calprotectin (FCP), colonic ultrasonography (US), and colon capsule endoscopy (CCE) compared with standard ileocolonoscopy in pediatric UC.
Methods
UC children were enrolled and underwent FCP and US on Day 0, followed by CCE on Day 1 and ileocolonoscopy on Day 2. All procedures were performed by operators who were blinded to the patient's clinical history and all test results. The accuracy for disease activity and extension of each technique and their combination was assessed and compared. Tolerability and safety were also evaluated.
Results
Thirty‐two patients were enrolled (15 males, mean age 13.2 ± 3.2 years). CCE showed a sensitivity of 95% and specificity of 100% in detecting colonic inflammation, with positive predictive value (PPV) and negative predictive value (NPV) of 100% and 92%, respectively. US demonstrated a sensitivity of 85% and specificity of 92%, with PPV and NPV of 94% and 79%. The combination of FCP, US, and CCE achieved 95% sensitivity and 100% specificity, with PPV of 100% and NPV of 92%. The noninvasive approach was better tolerated than colonoscopy (p < 0.05), and no serious adverse events were reported.
Conclusion
The noninvasive approach combining fecal calprotectin (FCP), ultrasonography, and colon capsule endoscopy demonstrated high diagnostic accuracy and better tolerability compared with standard ileocolonoscopy in pediatric ulcerative colitis follow‐up. Further multicenter studies are needed to confirm these findings and evaluate the reproducibility of this noninvasive approach.
What is Known
Pediatric patients with ulcerative colitis (UC) require regular and objective evaluation of disease extent, activity, and mucosal healing.
The gold standard for assessing the colonic mucosa is currently ileocolonoscopy.
Colonic ultrasonography (US) and colon capsule endoscopy (CCE) have demonstrated high accuracy in evaluating mucosal changes, disease extent, and activity, particularly in children with UC.
What is New
The implementation of a multimodal noninvasive approach, incorporating CCE, US and fecal calprotectin, has shown optimal diagnostic accuracy for pediatric patients with UC.
This novel noninvasive follow‐up method is better tolerated by patients compared with traditional ileocolonoscopy, leading to improved patient compliance and overall experience.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
ABSTRACT
Objectives:
We aimed to identify early noninvasive predictors of clinical and endoscopic remission in children with Crohn disease (CD) under infliximab (IFX).
Methods:
Prospective ...observational study conducted in children with moderate‐to‐severe CD starting IFX. All patients underwent weighted pediatric CD activity index (wPCDAI) assessment, C‐reactive protein and fecal calprotectin (FC) at week 0, 14, and 48. Endoscopy was performed at 0 and 48 weeks. The primary outcome was to determine the ability of 14‐week wPCDAI, C‐reactive protein, and FC to predict 1‐year steroid‐free clinical remission and mucosal healing. As a secondary outcome we evaluated their concordance with Simple Endoscopic Score for CD (SES‐CD) at week 48.
Results:
Forty‐one children were enrolled. At 1 year, 21 (51%) and 16 (39%) were in clinical and endoscopic remission. Only combined postinduction FC and wPCDAI were able to predict 1‐year clinical and endoscopic remission (hazard ratio 4.81 95% confidence interval 1.76–20.45, P = 0.05 and hazard ratio 5.51 95% confidence interval 1.83–26.9, P = 0.03). One‐year SES‐CD moderately correlated with FC (r = 0.52; P = 0.001). The FC cut‐off value for mucosal healing was 120.5 μg/g (area under the curve 0.863, 83% sensitivity, 75.5% specificity; P = 0.005). The concordance between wPCDAI and SES‐CD was excellent and good for severe disease and remission (k 0.87 and 0.76).
Conclusions:
Post induction FC combined with wPCDAI can predict 1‐year clinical and endoscopic response to IFX in pediatric CD. FC shows a moderate correlation with SES‐CD, whereas wPCDAI has a good concordance with endoscopic remission or severe disease, but not with mild and moderate disease.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Inflammatory bowel diseases are chronic disorders of the gastrointestinal tract that include Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBDU). The ...latter defines a subgroup of patients with clinical and endoscopic evidence of chronic colitis, without specific features of either CD or UC. These patients will possibly be re-classified as having UC or CD during the follow-up, although a significant percentage of them will keep the diagnosis of IBDU. IBDU is the rarest subtype of IBD, both in children and in adults, although it is twice as common among the pediatric population, especially in the younger ages. The diagnosis can only be made after a comprehensive diagnostic work-up, combining clinical history, physical and laboratory examination, upper and lower gastrointestinal endoscopy, with histology and imaging of the small bowel. The therapeutic strategy is borrowed from that of UC and CD, although recent data suggest that IBDU has a lower therapeutic burden with a generally mild disease course and a good response to mesalamine. Since there are only few published data on pediatric IBDU, and no guidelines on its management are available, this review aims at summarizing the most recent evidence for the diagnostic work-up with a specific focus on medical and surgical options in the treatment of IBDU.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic ...cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC).
Methods
Hospitalized children with ASC (pediatric ulcerative colitis activity index PUCAI ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin IVCS+AB), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome.
Results
Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 82% with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm.
Conclusion
Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408).
Acute severe colitis is one of the emergent situations in gastroenterology with steroid failure rate of ~30%. Antibiotics have been shown to exert remission in ulcerative colitis, but the diversity of the intervention limits applicability. The microbiome during episodes of acute severe colitis have not been studied to date. What is new here? Two thirds of children had a predominant bacterial species (>33% abundance) at admission. Adding antibiotic cocktail to intravenous corticosteroids improved disease activity at day 5; sample size was too small to evaluate second-line therapy rates. PUCAI score at day 3 and 5 predicted corticosteroids response. This pilot trial, the first in pediatric ASC, should now prompt larger studies.
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