Pediatric Inflammatory Bowel Disease Research Articles

Advancements in the Management of Pediatric and Adult Inflammatory Bowel Disease: A Systematic Review of Treatment Strategies and Long-Term Outcomes.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), remains a clinically complex condition in children and adults. This study is a systematic analysis of key developments in the treatment of inflammatory bowel diseases, as well as their efficacy and safety over time. Early diagnosis of pediatric IBD is very important since it affects growth and development in children. New therapeutic approaches like biological agents, small molecules, and gene or targeted drugs have given the medical fraternity new treatment protocols. There is a trend towards more selective therapies for adult IBD, especially for anti-tumor necrosis factor (anti-TNF) biologics, integrin antagonists, and interleukin-12/23 (IL-12/23) inhibitors. This review emphasizes the need for patient management where early intervention leading to mucosal healing has been identified to predict durable outcomes. Systematic analysis of existing literature comparing childhood and adult populations shows that morbidity, pathophysiology, therapeutic outcome, as well as the potential for adverse outcomes are dissimilar, which supports the need for differentiated therapy. This work also looks at long-term consequences of the intervention course, the avoidance of surgery, and an improvement in the quality and stability of life as well as reduction in further development of malignant transformation. The new developing strategy of gut microbiome modification and nutrition support for maintaining remission is also argued. Despite these progresses, issues still persist concerning the effectiveness of treatments, side effects, and patients' compliance. These recommendations give this review a prospective outlook of treatment regimens likely to define the future of IBD management for all age groups.

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Association of paediatric autoimmune cytopenia and inflammatory bowel disease suggests a common genetic origin.

The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy.

The Interplay of Inflammatory Bowel Disease (IBD) and Diabetes in Pediatrics: A Systematic Review.

The main objective of this study is to provide insights into the clinical problems and considerations in managing pediatric patients with both diabetes and inflammatory bowel disease (IBD) by summarizing the available information.We conducted a comprehensive search across electronic resources, including ScienceDirect, PubMed, Cochrane Library, and Scopus. Two independent reviewers evaluated and retrieved information from qualifying papers. Our data consists of five studies with 79,878 patients, 38225 (47.9%) of whom were female. Three studies included 2432 children diagnosed with IBD, and 17 (0.7%) were found with type 1 diabetes (T1D). Two studies comprised 77,446 children diagnosed with T1D and 83 (0.1%) had IBD. Children with immune-mediated diseases are more likely to have IBD, especially Crohn's disease. The included studies found no connection between T1D and childhood IBD.The important but little-known connection between diabetes and IBD in pediatric populations is brought to light by this comprehensive study. We were unable to discover a connection between pediatric IBD and DM. The review does, however,point out significant gaps in the literature, highlighting the need for more studies to comprehend the intricate interactions between these disorders and to create practical management plans for impacted children.

Pediatric Inflammatory Bowel Disease Type Unclassified: A Nationwide Cohort Study in Scotland With up to 20 Years Follow-up Shows Reclassification in the Majority and Mild Course in Those Whose Diagnosis Is Unchanged.

Given the paucity of long-term longitudinal data for inflammatory bowel disease type unclassified (IBDU), we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years of follow-up. We analyzed a prospectively identified 11-year cohort of pediatric patients diagnosed with IBDU between January 1, 2003 and December 31, 2013 at all Scottish pediatric IBD centers and followed up into adult services until December 31, 2022. Data were obtained from electronic medical records at fixed timepoints (5 and 10 years post-diagnosis) and at the final follow-up. Overall, 102 patients were included in the analysis (57/102 [56%] male, median [interquartile range {IQR}] age at diagnosis: 11.5 [9.1-13.2] years) with a median (IQR) follow-up length of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61 of 102 patients (60%); of these, 30 patients (29%) were reclassified to Crohn's disease (CD) and 31 patients (30%) to ulcerative colitis (UC). Patients who remained with IBDU had higher 1- to 5-year remission rates (IBDU 30/39 [77%] vs reclassified 16/57 [28%], P < .05), with lower rates of moderate-to-severe disease (IBDU 3/39 [8%] vs reclassified 31/57 [54%], P < .05) and less need for biologics across all timepoints (IBDU vs reclassified: first timepoint 1/39 [3%] vs 17/57 [30%], second timepoint 1/33 [3%] vs 26/56 [46%], third timepoint 0/18 [0%] vs 16/33 [49%]; all P < .05). Higher rates of surgical resections were observed in reclassified patients (reclassified 11/61 [18%] vs IBDU 1/41 [2%], P = .02). In our nationwide pediatric IBDU cohort, 60% of patients were reclassified to either UC or CD over 10.5 years of median follow-up; those who remained with IBDU had a milder disease course.

PET/MRI in paediatric inflammatory bowel disease – a prospective accuracy study

AbstractCross‐sectional imaging supplements endoscopy in detecting disease manifestations in inflammatory bowel diseases (IBD). This study aimed to evaluate the accuracy of PET/MRI in a paediatric population suspected of IBD. This prospective study consecutively included patients aged 8–17 years under diagnostic evaluation for IBD. Forty‐three patients underwent a PET/MRI scan and subsequent ileocolonoscopy, of whom 26 patients diagnosed with IBD participated in a follow‐up scan, hereof 19 with Crohn's disease (CD), five with Ulcerative colitis and two with unclassified IBD. The results of PET alone, MRI alone, and PET/MRI combined were compared to a reference standard of endoscopy and histopathology. Of the 208 intestinal segments analysed, 109 showed inflammation, and 99 had no inflammation. In the per‐segment analysis PET had a sensitivity of 0.83 (95% CI 0.73–0.93), specificity of 0.59 (95% CI 0.47–0.71), and area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI 0.67–0.80). MRI had a sensitivity of 0.52 (95% CI 0.41–0.64), specificity 0.89 (95% CI 0.82–0.96), and AUROC of 0.72 (95% CI 0.66–0.77). PET/MRI had a sensitivity of 0.83 (95% CI 0.74–0.94), specificity of 0.57 (95% CI 0.44–0.69), and AUROC of 0.77 (95% CI 0.71–0.84). At follow‐up, PET and MRI scores decreased, and the change in MRI was able to identify patients with a clinical response. The accuracy of the PET/MRI scan in detecting inflammation in the terminal ileum and colon was moderate and not superior to either modality alone. With technological advances and combined reading, PET/MRI may still be valuable in selected cases.

Differences in disease characteristics and treatment exposures between paediatric and adult-onset inflammatory bowel disease using a registry-based cohort.

Previous studies highlighted a more extensive phenotype for paediatric-onset than adult-onset inflammatory bowel disease (IBD). However, most lacked long-term follow-up, and some were conducted before the era of biologics. The aim of this study is to compare disease characteristics and treatment exposures between paediatric-onset and adult-onset IBD. From a registry that periodically and uniformly retrieves demographics, disease characteristics/phenotype, and treatments, we compared the characteristics of paediatric-onset (diagnosed at ≥6 and <18 years) and adult-onset IBD, diagnosed during 2000-2022 and with ≥12 months follow-up. Of the 2837 patients with Crohn's disease and 1332 with ulcerative colitis, 3316 had adult-onset and 853 paediatric-onset IBD. The median follow-up was 6 years. Patients with paediatric-onset presented with more extensive disease and received more intensified therapies, including biologics and JAK inhibitors than those with adult-onset IBD. Paediatric-onset ulcerative colitis showed a higher prevalence of E3 extensive colitis including pancolitis and a greater requirement for systemic steroids, immunomodulators, and biologics than adult-onset ulcerative colitis. Paediatric-onset versus adult-onset Crohn's disease exhibited greater L3 ileocolonic involvement and perianal disease phenotype, and higher exposure to immunomodulators and biologics. Kaplan-Meier curve and Cox proportional hazards analyses showed significantly lower 15-year biologic-free survival from diagnosis among those with paediatric-onset IBD than with adult-onset IBD (p = <0.001), indicating greater and earlier use of biologics in the former. Paediatric-onset presents with more extensive disease with higher exposures to immunomodulators and biologic therapies than adult-onset IBD.

Predicting complications in paediatric ulcerative colitis: A longitudinal multicentre cohort study.

To prevent complications of paediatric ulcerative colitis (UC), it is critical to understand their predictors. The Paediatric Inflammatory Bowel Disease Ahead (PIBD Ahead) program identified the relevant outcomes and their potential predictors. However, external validation of these results in larger cohorts is required. The aim of this study is to investigate these outcomes and their predictors. We included 743 patients aged under 18 years with UC from the multicentre German-Austrian CEDATA-GPGE registry. We performed Cox regressions, Kaplan-Meier estimator, and receiver operating characteristics curve analyses to analyse predictors of poor outcomes. Older age at diagnosis was associated with relapse, hospitalisation, the use of immunomodulators, use of biologics, and therapy escalation. Higher disease activity, as in acute severe colitis in the first 3 months, was significantly associated with further acute severe colitis and the need for biologics. Upper gastrointestinal tract involvement was a risk factor for the need of intravenous corticosteroids and biologics. A faecal calprotectin of >685 μg/g was associated with a higher risk of subsequent acute severe colitis with a sensitivity of 79.0% and a specificity of 59.1%. A lower haematocrit at diagnosis was predictive of the use of biologics. Colectomy was rare. This study validates predictors of poor outcomes in paediatric patients with UC. Our results might help physicians to anticipate poor outcomes and initiate appropriate treatment strategies at an early stage.

Transabdominal intestinal ultrasound and its parameters used in the assessment of pediatric inflammatory bowel disease.

This article extends on the use of transabdominal intestinal ultrasound in diagnosing pediatric inflammatory bowel disease. Some of the more essential features used in assessing bowel inflammation, such as hyperemia and wall thickness on ultrasound, are expanded upon from the publication on imaging and endoscopic tools in pediatric inflammatory bowel disease.

The association between erythema nodosum and pyoderma gangrenosum and pediatric inflammatory bowel disease.

The objectives of this study is to estimate rates and identify factors associated with erythema nodosum (EN) and pyoderma gangrenosum (PG) in pediatric patients with inflammatory bowel disease (IBD). This cohort study examined longitudinal visits of patients aged ≤ 21 years from the ImproveCareNow (ICN) registry. We evaluated the association of factors at the patient-level (demographics and IBD diagnosis age) and visit-level (IBD severity scores, markers and phenotypes, comorbidities, and treatment) with the presence of EN and PG, using longitudinal logistic regression models adjusted for time and within-patient clustering. A total of 285,913 visits from 32,497 patients aged ≤ 21 years from the ICN registry were analyzed. The occurrence of EN was 1.57% (95% confidence interval [95% CI]: 1.43%-1.71%) and the occurrence of PG was 0.90% (95% CI: 0.80%-1.00%). Co-occurrence of EN and PG was reported in 0.30% (95% CI: 0.25%-0.37%) patients. Both EN and PG were associated (p < 0.0001) with worse intestinal disease, lower remission, higher inflammatory markers, and extraintestinal manifestations (EIMs) arthritis and uveitis. EN and PG were associated with increased disease severity and other noncutaneous EIMs (arthritis and uveitis). A small subset of patients had developed both EN and PG.

Infliximab in paediatric inflammatory bowel disease: External evaluation of population pharmacokinetic models.

Use of infliximab (IFX) has improved outcomes in children with inflammatory bowel disease (IBD). However, a proportion of patients does not respond to IFX or loses response over time. Population pharmacokinetic (PopPK) modelling is a promising approach for IFX dose optimization, but with the increasing number of PopPK models in literature, model evaluation is essential. The aims of this study are: (i) to validate the predictive performance of existing IFX PopPK models using a cohort of children with IBD; and (ii) to perform a Bayesian estimation of the most suitable model to predict the next IFX concentrations. PubMed was searched for IFX PopPK models in children. Selected models were rebuilt and analysed using R. Model performance was assessed through goodness-of-fit-plots, residuals against time, prediction error and prediction-corrected visual predictive checks. The validation cohort consisted of 73 children with IBD who were treated with IFX in our centre between 2017 and 2023 (340 IFX measurements). We identified 9 PopPK models. Model bias for individual predicted values ranged from -9.29% to 8.01% compared to bias for population predicted values. The model by Vande Casteele et al. demonstrated superior performance (individual predicted bias 2.13, population predicted bias -6.11); upon Bayesian estimation, it predicted induction trough levels with median error of 12.95% but had a median error of -69% predicting maintenance concentrations. The model by Vande Casteele et al. displayed superior performance in initial evaluations but had a high error in estimating next IFX levels and can only be used in practice to predict induction levels.

Combined plasma protein and memory T cell profiling discern IBD-patient-immunotypes related to intestinal disease and treatment outcomes

Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn’s disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10–12 weeks’ induction therapy. At diagnosis, plasma protein profiles unveiled two UC and three CD clusters with distinct disease courses. UC patients displayed unchanged circulating Tmem, while CD exhibited increased frequencies of gut-homing ex-Th17, known for high IFN-γ production. UC#2 had elevated Th17/neutrophil-pathway-related proteins and severe disease, with higher endoscopic and histological damage and Th17/neutrophil infiltration. Although both UC#1 and UC#2 responded to therapy, UC#2 required earlier immunomodulation. CD#3 had lower plasma protein concentrations, especially IFN-γ pathway proteins, fewer gut-homing ex-Th17 and clinically milder disease, confirmed by intestinal gene expression. CD#1 and CD#2 had comparably high Th1-related immune profiles, but CD#1 exhibited higher concentrations of proteins previously associated with poorer prognosis. Both CD clusters responded to induction therapy, with similar one-year outcomes. This study highlights feasibility of discriminating patient-specific immunotypes in IBD, advancing our understanding of immune pathogenesis, needed for tailored treatment strategies.

Inflammatory Bowel Disease in Children

Background: Pediatric inflammatory bowel disease (IBD) is an idiopathic inflammatory disease in the digestive system with chronic onset, which often presents with unique and atypical phenotypes. This study aimed to dissect the important features of inflammatory bowel disease in children Discussion: The two types of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn’s disease (CD). In children, IBD may exhibit classic symptoms such as weight loss, abdominal pain, and bloody diarrhea. However, many patient present with atypical symptoms such as isolated poor growth, anemia, or other extraintestinal manifestations. Early diagnosis of IBD in children is crucial as delayed diagnosis may lead to serious complications like bowel narrowing or abnormal connections, and stunted growth. The recommended initial evaluations in a pediatric patient with suspected IBD are complete blood test, stool examination, endoscopy and imaging. Furthermore, the aims of IBD treatment in children are to improve quality of life, relieve symptoms, promote normal growth, and prevent complications, all while minimizing medication side effects. Conclusion: Early diagnosis and treatment are essential in managing pediatric IBD. Additionally, addressing the disease's impact on bone health, growth, development, and psychosocial well-being is also crucial to achieve comprehensive management.

Saudi consensus guidance for the diagnosis and management of inflammatory bowel disease in children and adolescents.

The management of inflammatory bowel disease (IBD) in children and adolescents is challenging. Clear evidence-based guidelines are required for this population. This article provides recommendations for managing IBD in Saudi children and adolescents aged 6-19 years, developed by the Saudi Ministry of Health in collaboration with the Saudi Society of Clinical Pharmacy and the Saudi Gastroenterology Association. All 57 guideline statements are based on the most up-to-date information for the diagnosis and management of pediatric IBD.

The Role of Vitamin D Levels in Optimizing Treatment for Pediatric Inflammatory Bowel Disease (IBD) Patients and an Examination Into Different Factors That Influence IBD Treatment Outcomes.

Background Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn's Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children's Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions.

Self-Compassion in Adolescents and Young Adults With Inflammatory Bowel Disease: Relationship of Self-Compassion to Psychosocial and Physical Outcomes.

Adolescents and young adults (AYAs) diagnosed with inflammatory bowel disease (IBD) are at an increased risk for poor physical and mental health due to the complexity of pediatric onset IBD and the unique developmental challenges of this period of life. Self-compassion is increasingly recognized as having an important role in explaining health outcomes and well-being across a range of populations. This study examines the relationship between self-compassion and psychosocial and physical health outcomes in AYAs with IBD. In this cross-sectional study, AYAs with IBD aged 15 to 25 years completed an online survey between February 2020 and October 2021. Questionnaires included the Self-Compassion Scale-Short Form, Patient-Reported Outcomes Measurement Information System (PROMIS) measures for psychosocial, physical and global health outcomes, and IBD disease activity indices. AYAs with higher levels of self-compassion were found to have better psychosocial (ie, anxiety, depressive symptoms, psychological stress, physical stress, peer relationships), physical (ie, fatigue), and global health outcomes. Self-compassion was a significant independent predictor of anxiety (β = -5.80, P = < .001), depressive symptoms (β = -7.09, P = < .001), psychological stress (β = -4.66, P = < .001), physical stress (β = -3.19, P = < .001), peer relationships (β = 3.39, P = .003), fatigue (β = -2.05, P = .019), and improved global health (β = 5.15, P = < .001). This study offers preliminary support for the importance of self-compassion in AYAs with IBD and demonstrates the need for further research in this area.

TNF inhibitors as a treatment of pediatric IBD

TNF inhibitors as a treatment of pediatric IBD

Multidisciplinary Perspectives on Medical Decision-Making for Ostomy Surgery in Pediatric IBD: Themes from Focus Groups.

Pediatric Inflammatory Bowel Disease (IBD) is a chronic illness where patients may undergo ostomy surgery. Medical decision-making (MDM) for ostomy surgery is complex for patients/families and multidisciplinary healthcare professionals (HCPs) alike, with current uncertainty about how multidisciplinary HCPs think about ostomy care to inform future interventions to facilitate equitable multidisciplinary care for patients. This study sought to understand pediatric IBD multidisciplinary HCPs' perceptions regarding ostomy-related MDM and education. Multidisciplinary HCPs (e.g., gastroenterology medical providers, social workers, surgeons, and ostomy nurses) participated in semi-structured focus groups. Focus group data underwent qualitative analysis to identify themes. Three multidisciplinary focus groups were conducted, with n = 12 participants across all groups. Qualitative analysis identified three main themes, including (1) HCP perceptions of ostomies, (2) Patient/family-related factors, and (3) Professional roles and collaboration challenges. Ostomy surgery in pediatric IBD requires complex multidisciplinary MDM and education. Perspectives of multidisciplinary HCPs identified patient, HCP, and systems factors that may impact MDM for ostomy surgery. This work highlights nuances in MDM and education in IBD, and the critical role of ongoing research and improved standardized processes to coordinate multidisciplinary ostomy-related MDM and education in this population.

Yoga in Pediatric Gastroenterology.

Pediatric use of yoga as an integrative medicine modality has increased in prevalence over the last several decades. In this article, we review the available evidence for yoga in pediatric gastrointestinal disorders. Evidence supports that in many pediatric disorders of gut brain interaction (DGBI), including irritable bowel syndrome, functional abdominal pain and functional dyspepsia, yoga decreases pain intensity and frequency and increases school attendance. Yoga has been shown to improve health-related quality of life and improve stress management as an effective adjunct to standard medical therapy in pediatric inflammatory bowel disease (IBD). Further studies are needed regarding optimal frequency, duration of practice and evaluation of the impact on IBD disease activity measures. Yoga may benefit pediatric gastroenterology patients with DGBIs and IBD through improving quality of life and reducing pain. Future yoga studies could investigate biomarkers and continued research will help integrate this modality into routine pediatric gastroenterology care.

Dietary habits in Italian children with inflammatory bowel disease: A case-control multicenter study.

Patients with inflammatory bowel disease (IBD) tend to self-modify their dietary habits according to disease activity and symptoms. This study aimed to assess the adequacy of the usual diet in Italian children with IBD in comparison to a control group and to the recommended dietary allowances (RDA). Dietary habits of IBD children and age- and gender-matched healthy controls were investigated using a validated Food Frequency Questionnaire in five Italian pediatric IBD centers. Adherence to the Mediterranean diet (MD) was assessed using the KID-MED test. Energy (EI), macro, and micronutrients intakes were compared between the two groups, to the RDA and the predicted total energy expenditure (EI/total energy expenditure [TEE]%). IBD subjects (n = 110) reported a lower EI, EI/RDA%, and EI/TEE% compared to controls (n = 110) (p = 0.012, p < 0.0002, and p = 0.014), lower total protein and fat intakes (p = 0.017, p < 0.0001) and lower minerals/RDA, vitamins/RDA and micronutrients/RDA ratio (%). Poor adherence to the MD was more frequent in IBD children compared to controls (p = 0.013). The total EI and carbohydrate intake were inversely correlated with higher disease activity. Italian children with IBD report an inadequate diet in terms of energy, macro, and micronutrients and have a low adherence to a high-quality MD pattern.