Pediatric Crohn's Disease Research Articles

Paediatric obesity and Crohn's disease: a descriptive review of disease phenotype and clinical course.

In an era of increasing paediatric obesity and inflammatory bowel disease (IBD), this study evaluates the disease phenotype and clinical course of Crohn's disease (CD) in paediatric patients who are obese or overweight. This is a retrospective, single-center, descriptive observational study from January 2010 to May 2020. Participants were included if they were: aged 2 to 18 years at the time of diagnosis, had a confirmed diagnosis of CD, and met WHO criteria for overweight or obesity at the time of diagnosis or within one year before diagnosis. A total of 345 patient charts with CD were screened during the study period, with 16 patients meeting inclusion criteria. Median age of patients was 15.5 years (IQR = 13.6, 16.1). Of the 15 patients over 10 years of age, median anthropometrics at diagnosis included body mass index (BMI) of 27.2 (IQR = 24.9, 29.4) and BMI for age z-score of 1.82 (IQR = 1.58, 2.19). Presenting symptoms included abdominal pain (80.0%), diarrhea (66.7%), hematochezia (66.7%), and weight loss (26.7%). Five patients (33.3%) had obesity-related complications. Median time from symptom onset to diagnosis was 146 days (IQR = 31, 367), and median time from diagnosis to remission was 229 days (IQR = 101.8, 496.3). Patients with elevated BMI and CD present with typical symptoms of IBD, although weight loss was a less common presenting symptom. Time to disease remission is delayed, and obesity-related complications are common. Primary care providers must have a high degree of clinical suspicion in patients to prevent delays to gastroenterology referral and to improve time to disease remission.

Nationwide Real-World Exclusive Enteral Nutrition Practice Over Time: Persistence of Use as Induction for Pediatric Crohn's Disease and Emerging Combination Strategy With Biologics.

Exclusive enteral nutrition (EEN) is the recommended first-line induction treatment in pediatric patients with active luminal Crohn's disease (CD). We aimed to provide a nationwide overview of evolving EEN practices during an era of increasing biologic use. We analyzed a prospectively identified nationwide cohort of newly diagnosed pediatric patients with CD in Scotland between January 1, 2015, and June 30, 2022. Patients who received EEN for any indication were divided into 6-monthly epochs and examined over time. Differences during the COVID-19 pandemic (March 16, 2020, to July 19, 2021) were examined. Data were retrospectively collected from electronic medical records: demographics, anthropometrics, concomitant treatments, aspects of EEN administration, and remission/response rates. Descriptive statistics and linear regression were used for analyses. A total of 649 patients with CD were identified (63% male; median age 12.6 [interquartile range, 10.8-14.8] years); 497 (77%) of 649 received EEN as postdiagnosis induction therapy with a median course length of 7.7 (interquartile range, 5.9-8.0) weeks. Including repeat courses, 547 EEN courses were examined. An increasing incidence of CD was observed over time with no significant changes in EEN usage, remission or response rates, nasogastric tube usage, or course completion (all P > .05). Increasing use of EEN combined with biologics (combination induction) as first-line induction was observed over time (P < .001). Considering COVID-19, lower rates of EEN usage were observed (P = .008) with no differences in remission, oral administration, and course completion rates (all P > .05). Over the past 7.5 years, except during the COVID-19 pandemic, EEN usage rates have not changed despite an increase in biologic use, although combination induction is an emerging trend.

The Future of Advanced Therapies for Pediatric Crohn's Disease.

Pediatric Crohn's disease commonly presents with moderate-to-severe intestinal inflammation with a greater risk of complications if remission is not achieved. Anti-tumor necrosis factor therapies have offered the possibility of deep and durable remission; however, many children do not respond or no longer respond over time. Further, some children do not require broader systemic immunosuppression to achieve remission and are better served by an alternative treatment strategy. Proper utilization of advanced biologic and small-molecule therapies, which have become available for adult patients since anti-tumor necrosis factor medications, is paramount for tighter disease control for a large proportion of children. Newer advanced therapies such as anti-integrin and anti-interleukin biologics, and several small-molecule agents capitalize on various mechanisms through narrower immunologic targets and reduced immunogenicity. Given limited regulatory approvals of these agents for use in children with Crohn's disease, clinicians continue to rely on data extrapolated from clinical trials in adult patients, sparse pediatric studies, and a growing real-world experience for treatment selection and optimization. In this article, we discuss currently available treatment options, pipeline drugs, and relevant data as they pertain to some of the most pressing clinical challenges faced in treating pediatric Crohn's disease.

Challenges in Managing Paediatric Crohn's Disease With Crohn's Disease Exclusion Diet (CDED): The First Single-Center Study in the United Arab Emirates.

Inflammatory bowel disease has been increasing significantly. For that, many modalities of treatment have shown promising results including a special diet. In our study, we looked at Crohn's disease dietary management for induction and subsequently maintenance of treatment. The research question was how feasible was applying this approach and what difficulties the patients and their parents faced. We reviewed the electronic medical system. We had 32 paediatric patients who were diagnosed with Crohn's disease and used the special diet plan (Crohn's disease exclusion diet orexclusion enteral nutrition) to induce remission or maintenance. Then, we used a questionnaire to identify the difficulties they faced while using the special diet. We have found that the cohort had used the special diet for a variableduration. The majority of patients opted to start with Crohn's disease exclusion diet. The clinical response was inconsistent due to poor compliance. Only 57 % of the patients were able to bear with the dietary plan beyond 12 weeks. Patients reported the following factors which caused non-compliance: intolerance/difficulty to follow(40%), cost (19%), poor clinical response (19%), and others. In managing Crohn's disease, a multidisciplinary approach, including dietary interventions, is crucial. However, adherence to specialized diets poses several challenges identified in this study based on patient feedback. Addressing barriers and prioritizing dietitians' role is essential for improved patient outcomes in inflammatory bowel disease management.

Circ_0001666 upregulation promotes intestinal epithelial cell fibrosis in pediatric Crohn's disease via the SRSF1/BMP7 axis.

The epithelial-mesenchymal transition (EMT) is closely associated with Crohn's disease (CD) related intestinal fibrosis, a condition whose prevalence is increasing annually among children. Recently, the CD marker gene microarray screening revealed an upregulation of circ_0001666 in the colon tissues of CD patients, but its underlying mechanisms remain unclear. In this study, we explored the molecular mechanism of circ_0001666 in regulating EMT-mediated fibrosis in CD in vitro. The levels of circ_0001666 and EMT-associated proteins were assessed in CD clinical samples, and a CD cell model was established using TGF-β1 to induce human intestinal epithelial cells (HIECs). Additionally, the expression levels of genes and proteins related to EMT and fibrosis were analyzed by quantitative real-time PCR and western blot, cell migration, and invasion were assessed via wound healing assay and transwell, respectively, and RNA pull-down and RNA immunoprecipitation assays were performed to verify the relationship between SRSF1 and BMP7 or circ_0001666. Circ_0001666 was overexpressed in the intestinal mucosal tissues of CD patients and was positively correlated with EMT. Silencing circ_0001666 inhibited the migration, invasion, EMT, and fibrosis of HIECs induced by TGF-β1. Mechanistically, circ_0001666 regulated BMP7 expression by interacting with SRSF1. Furthermore, the effects of inhibiting circ_0001666 on HIECs could be partially reversed by overexpressing SRSF1 or silencing BMP7. Collectively, circ_0001666 regulates TGF-β1-induced HIEC migration, invasion, EMT, and fibrosis. Circ_0001666 also promoted EMT-mediated fibrosis by interacting with SRSF1 to accelerate BMP7 mRNA decay. These findings provide new insights into the pathogenesis of CD and suggest that circ_0001666 might be a potential therapeutic target for CD.

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

Identifying predictors of clinical outcomes using the projection-predictive feature selection-a proof of concept on the example of Crohn's disease.

Several clinical disease activity indices (DAIs) have been developed to noninvasively assess mucosal healing in pediatric Crohn's disease (CD). However, their clinical application can be complex. Therefore, we present a new way to identify the most informative biomarkers for mucosal inflammation from current markers in use and, based on this, how to obtain an easy-to-use DAI for clinical practice. A further aim of our proof-of-concept study is to demonstrate how the performance of such a new DAI can be compared to that of existing DAIs. The data of two independent study cohorts, with 167 visits from 109 children and adolescents with CD, were evaluated retrospectively. A variable selection based on a Bayesian ordinal regression model was applied to select clinical or standard laboratory parameters as predictors, using an endoscopic outcome. The predictive performance of the resulting model was compared to that of existing pediatric DAIs. With our proof-of-concept dataset, the resulting model included C-reactive protein (CRP) and fecal calprotectin (FC) as predictors. In general, our model performed better than the existing DAIs. To show how our Bayesian approach can be applied in practice, we developed a web application for predicting disease activity for a new CD patient or visit. Our work serves as a proof-of-concept, showing that the statistical methods used here can identify biomarkers relevant for the prediction of a clinical outcome. In our case, a small number of biomarkers is sufficient, which, together with the web interface, facilitates the clinical application. However, the retrospective nature of our study, the rather small amount of data, and the lack of an external validation cohort do not allow us to consider our results as the establishment of a novel DAI for pediatric CD. This needs to be done with the help of a prospective study with more data and an external validation cohort in the future.

Relationship between disease activity index and sleep disorders in children with inflammatory bowel diseases.

The aim of the study was to assess the prevalence of sleep disturbance in pediatric IBD patients and evaluate the relationship between clinical features of IBD, disease activity, inflammatory markers and quality of sleep. A total of 99 patients who were followed-up with the diagnosis of IBD (44 Crohn's disease (CD), 55 Ulcerative colitis (UC)) between 2015-2020 and 80 healthy controls were enrolled in the study. The clinical and demographic characteristics, laboratory parameters and disease activities were obtained from medical reports retrospectively. Pittsburgh sleep quality index (PSQI) was administered to all participants. PSQI score was significantly higher in patient group than the control group (P < 0.001). The sleep time of patient group, especially patients with UC was later than the control group (P = 0.008). Sleep duration was longer in control group than the patient group (P < 0.001). A positive strong correlation was obtained in disease activity index (r = 0.886; P < 0.001) and abdominal pain (r = 0.781; P < 0.001) with PSQI scores of CD patients. Disease activity index, rectal bleeding, diarrhea and number of stool had statistically significant positive strong correlation with PSQI scores of UC patients (P < 0.001). Pediatric Crohn's disease activity index and Pediatric ulcerative colitis activity index were the only independent risk factors affecting sleep disturbances (80% sensitivity and 91.67% specificity, 93.1% sensitivity and %96.15 specificity, respectively). Conclusion: Increased disease activity has adverse effects on sleep quality. PSQI and PCDAI were strong tests for predicting sleep disorders in pediatric patients with IBD. What is Known: •Sleep disturbances are common complaint in inflammatory bowel disease (IBD), even in clinical remission. •Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality of patients. What is New: •PSQI and Pediatric Crohn Disease Activity index (PCDAI) were strong tests for predicting sleep disorders in pediatric patients with IBD. •PSQI and PCDAI scores correlated significantly with the severity of the sleep disturbances.

Clinical course of new-onset Crohn's disease in children and adolescents in dependency of age, initial location, initial severity level and therapy over the period 2000-2014 based on the Saxon Pediatric IBD-Registry in Germany.

In Saxony, the incidence of Crohn's disease (CD) in children and adolescents increased significantly from 3.3 per 100,000 person-years in 2000 to 5.1 in 2014. The aim of this study was to describe the initial characteristics and the clinical course of CD in children and adolescents and to identify drug treatment options associated with an advantage for a mild course or remission. Clinical data were collected from patients who suffered from inflammatory bowel disease (IBD) and were recruited in the Saxon Pediatric IBD-Registry. All children newly diagnosed with CD in this registry in Saxony between 2000 and 2014 were included in this registry study. Characteristics such as age, disease location and extra-intestinal manifestations at diagnosis were accessed. The severity level of the disease at diagnosis as well as at follow-up were analysed by PCDAI index. Patients were divided into 3 groups according to length of follow-up: 1-3 years, 4-6 years and 7-9 years after diagnosis. A logistic regression model was conducted to examine which baseline parameters are associated with disease progression. There were 338 children and adolescents with CD included in this registry study. At diagnosis, the median age of patients was 12.0 (0.7-14.9), 61.5% (n = 208) of the patients were male. The most common disease location observed in pediatric CD patients was the L3 (55%, n = 176). Patients aged 10-14 years were significantly more likely to present an L2 than patients aged 0-4 years (80.3%, n = 53 vs. 19.7%, n = 13, p = 0.01). During the follow-up, data from 71.3% (n = 241) othe patients were available. Disease activity measured by PCDAI decreased in 47.7% (n = 115) of the patients, 40.7% (n = 98) of the patients were stable and increased in 11.6% (n = 28) of the patients. Patients with intermediate/severe disease at onset were more likely to have an active disease at the end of follow up, too (p = 0.00). Logistic regression analysis of the initial characteristics showed that the age at diagnosis, gender, initial location and initial extra-intestinal manifestation are not associated with the progression of the disease (p>0.05). Furthermore, drug treatment options could be identified from our data, which are associated with benefits for a milder course or remission. From 2000 to 2014, the health status of most pediatric patients with CD had improved or remained stable. Initial characteristics including age at diagnosis, initial localization and initial extra-intestinal manifestation are not associated with the progression of the disease, only the initial activity by PCDAI.

Can We Rely on Resting Metabolic Rate Equations? Large Variance in Crohn Disease Pediatric Patients.

Inadequate caloric intake is common in Crohn disease (CD) and nutrition support plays an important role in remission induction and in meeting nutritional needs. For nutritional planning, determining resting metabolic rate (RMR) is essential in pediatric patients with CD. To measure RMR in CD pediatric patients using indirect calorimetry, and compare it with estimated RMR (eRMR) calculated by Schofield equation. Children with CD treated in a tertiary pediatric inflammatory bowel disease center in Israel participated in the cross-sectional study. At study visits, weight, height, clinical and laboratory assessments, bioelectrical impedance, and RMR measured by indirect calorimetry were done. Additionally, disease severity was determined by the Pediatric Crohn Disease Activity Index and eRMR was calculated using the Schofield equation. The ratio of the measured RMR to eRMR was performed in addition to the Spearman correlation test. The study group included 73 children (49 boys) with mean age of 13.9 ± 2.3 years. Children with moderate or severe disease had lower weight for age z score, lower BMI- z , and lower RMR compared to children with mild disease. However, when RMR was adjusted for fat free mass (n = 50), the association between RMR and disease severity disappeared. Variance in RMR was high between subjects. Our data suggest that the Schofield equation is inadequate for determining RMR in pediatric CD and that RMR should be measured to guarantee the most appropriate nutritional intervention.

Pediatric Crohn's Disease Presenting with Gastrocnemius Myositis.

Pediatric Crohn's Disease Presenting with Gastrocnemius Myositis.

Comparison of Clinical Outcomes in Pediatric Patients with Ileocolonic Crohn Disease Treated with Infliximab Versus Adalimumab.

Infliximab is considered superior to adalimumab in patients with ulcerative colitis, especially in severe cases. Whether this is true for Crohn disease (CD) patients with colonic involvement is unclear. Our aim was to compare the clinical effectiveness of infliximab versus adalimumab in pediatric ileocolonic (L3) CD. This retrospective study included patients <18 years with ileocolonic CD treated with infliximab or adalimumab between 2014 and 2021. Primary outcome was steroid-free clinical remission by week 52. Secondary outcomes were treatment modifications, drug discontinuation, inflammatory bowel disease (IBD)-associated hospitalizations, and surgery during the first year of treatment. We identified 74 patients treated with adalimumab and 41 with infliximab, with comparable demographic features. Concomitant immunomodulator therapy at biologic initiation was significantly lower in the adalimumab group (28% vs 85%, P < 0.001). Rates of drug intensification were higher in the infliximab group at end of induction (EOI) and at 52 weeks (55% vs 32% and 88% vs 46%, P < 0.001). Given significant differences between initial median Pediatric Crohn Disease Activity Index scores (20.0 [interquartile range, IQR 15.0-27.5] vs 11.0 [IQR 7.5-20.0] for infliximab and adalimumab groups, respectively, P < 0.001), propensity score matching was performed. Following matching, the rate of patients in steroid-free clinical remission by EOI was significantly higher in the adalimumab group (93.8% vs 46.9%, P < 0.001), but comparable by 1 year. Moreover, inflammatory markers and fecal calprotectin values were also similar at these time points. Rates of drug discontinuation, IBD-associated admissions, and surgery were similar between groups. In a retrospective study of patients with ileocolonic CD, adalimumab and infliximab had comparable outcomes by 52 weeks.

A prospective study of inflammatory bowel disease phenotypes in extremes of age and comparison with adults.

Pediatric and elderly inflammatory bowel disease (IBD) are less explored, often in retrospective studies. The pediatric group has a more extensive and aggressive disease phenotype requiring aggressive treatments, whereas the elderly group may have less aggressive diseases. We prospectively compared disease characteristics of a single center cohort of IBD patients (pediatric age ≤ 16years; adults 17 to 59years; and elderly ≥ 60years) seen between September 2018 and November 2019 with at least sixmonths of follow-up. Total 266IBD patients (137 males) included 47 pediatric, 175 adults and 44 elderly patients. Among ulcerative colitis (UC) patients, pancolitis was more common in the pediatric group (p = 0.018), while the elderly group had more indolent behaviors and infrequent extraintestinal manifestations (p = 0.005). Among patients with Crohn's disease (CD), the pediatric group had more often colonic diseases (p = 0.02) and the elderly, ileal diseases (p = 0.04). The disease behavior was similar in the three age groups. Perianal disease was least common in elderly CD patients (p = 0.03). There was no treatment difference among different age groups in UC. In CD, pediatric patients needed biologics more frequently (p = 0.005), while elderly CD patients less frequently required steroids, biologics, immunosuppressants and surgery (p < 0.05). We noted differences compared to western literature such as colonic location in pediatric CD and ileal location in elderly CD. Perianal disease was less frequent in the elderlyCD group. There was no difference in treatment in the three age groups in UC, while there were no inter-age-group disease behavioral differences for UC and CD.

Clinical guidelines for endoscopic diagnosis and monitoring of Crohn’s disease in children (Draft)

The article summarizes guidelines for endoscopic examinations in children with Crohn’s disease (CD). The article may be useful for endoscopists, pediatric gastroenterologists, pediatricians, pathologists, pediatric surgeons. Issues of endoscopic examinations and monitoring of pediatric CD (esophagogastroduodenoscopy, ileocolonoscopy, video capsule endoscopy, panintestinal capsule) are considered.

Infliximab vs adalimumab: Points to consider when selecting anti-tumor necrosis factor agents in pediatric patients with Crohn's disease.

Biologic agents with various mechanisms against Crohn's disease (CD) have been released and are widely used in clinical practice. However, two anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADL), are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently. Therefore, in pediatric CD, the choice of biologic agents should be made more carefully to achieve the therapeutic goal. There are currently no head-to-head trials of biologic agents in pediatric or adult CD. There is a lack of accumulated data for pediatric CD, which requires the extrapolation of adult data for the positioning of biologics in pediatric CD. From a pharmacokinetic point of view, IFX is more advantageous than ADL when the inflammatory burden is high, and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase. Additionally, we reviewed the safety profile, immunogenicity, preference, and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD. Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents. In addition, factors such as the efficacy of induction and maintenance of remission, safety profile, immunogenicity, patient preference, and compliance play an important role in evaluating and selecting treatment options.

Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.

Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.

Lymphocytic Esophagitis: A Case Series of Esophageal Disease with Increasing Frequency.

Lymphocytic esophagitis (LE) is a poorly understood clinical finding that has been increasingly identified in the last decade. Previous studies proposed increased frequency of LE in elderly females, as well as associations with smoking and pediatric Crohn's disease. We aimed to determine the patient characteristics and clinical features of our adult LE patients. As inflammation in the esophagus has been linked to cancer, this review also describes this association. However, there are no reported cases of malignant transformation in those with underlying lymphocytic esophagitis. We retrospectively reviewed records for patients at the University of Missouri Hospital- Columbia (located in the USA) who had a histopathological diagnosis of LE. Cases of LE were identified using the pathology reporting system at the University of Missouri Hospital for esophageal biopsy specimens for the above-mentioned period. The data of a total of 20 adult cases with esophageal biopsy specimens consistent with LE were included. LE seems to be a benign but disturbing clinical problem and should be remembered in elderly females complaining of dysphagia or refractory reflux symptoms. It has similar endoscopic findings of eosinophilic esophagitis with rings and esophagitis. Smoking and hiatal hernia are common risk factors. The majority of LE patients can respond to proton pump inhibitor (PPI) therapy. Endoscopic dilations and steroid therapy should be considered for PPI nonresponder LE patients.

The Association of Leptin Gene Polymorphisms with Crohn's Disease in a Chinese Pediatric Population

Background: Leptin is thought to play an important role in Crohn's disease (CD) pathogenesis and progression. Independent studies have revealed a strong upregulation of leptin expression in the mesenteric fat of CD patients. Objectives: This study assessed the relationship between leptin gene polymorphisms and CD susceptibility in a Chinese pediatric population. Methods: A total of 86 patients with CD and 142 healthy controls were recruited for this case-control study. The genotypes of 4 single-nucleotide polymorphisms (SNPs; rs2071045, rs41457646, rs11761556, and rs2167270) in the leptin gene were determined by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing. Results: We found that leptin rs2167270 had a significantly different distribution of alleles and genotypes between CD patients and healthy controls (G is a risk allele: 83.7% of cases vs 72.5% of controls; odds ratio [OR] 1.947; 95% CI, 1.203-3.151; P = 0.006; GG is a risk genotype: 72.1% of cases vs 53.5% of controls; P = 0.021). Patients with the CC genotype (rs2071045) had a significantly increased risk of early onset of CD (58.3% in A1a vs 31.1% in A1b; P = 0.003). Similarly, patients carrying the G allele (100% in A1a vs 84.1% in A1b; P = 0.015) and GG genotype (100% in A1a vs 71.0% in A1b; P = 0.048) of rs41457646, A allele (93.3% in A1a vs 71.8% in A1b; P = 0.013) and AA genotype (93.3% in A1a vs 47.9% in A1b; P = 0.003) in rs11761556 had a higher risk of early onset of CD. However, there was no significant difference in any of these 4 SNPs between patients with and without perianal lesions, as well as in low and normal body mass index (BMI) patients. Conclusions: The leptin rs2167270 polymorphism is associated with the susceptibility to CD in a Chinese pediatric population. Leptin rs2071045, rs41457646, and rs11761556 might lead to the early onset of pediatric CD.

Combination therapy with methotrexate in paediatric Crohn's disease.

Combination therapy with methotrexate in paediatric Crohn's disease.

The Pediatric Crohn Disease Morbidity Index (PCD-MI): Development of a Tool to Assess Long-Term Disease Burden Using a Data-Driven Approach.

Heterogeneity and chronicity of Crohn disease (CD) make prediction of outcomes difficult. To date, no longitudinal measure can quantify burden over a patient's disease course, preventing assessment and integration into predictive modeling. Here, we aimed to demonstrate the feasibility of constructing a data driven, longitudinal disease burden score. Literature was reviewed for tools used in assessment of CD activity. Themes were identified to construct a pediatric CD morbidity index (PCD-MI). Scores were assigned to variables. Data were extracted automatically from the electronic patient records at Southampton Children's Hospital, diagnosed from 2012 to 2019 (inclusive). PCD-MI scores were calculated, adjusted for duration of follow up and assessed for variation (ANOVA) and distribution (Kolmogorov-Smirnov). Nineteen clinical/biological features across five themes were included in the PCD-MI including blood/fecal/radiological/endoscopic results, medication usage, surgery, growth parameters, and extraintestinal manifestations. Maximal score was 100 after accounting for follow-up duration. PCD-MI was assessed in 66 patients, mean age 12.5 years. Following quality filtering, 9528 blood/fecal test results and 1309 growth measures were included. Mean PCD-MI score was 14.95 (range 2.2-32.5); data were normally distributed ( P = 0.2) with 25% of patients having a PCD-MI < 10. There was no difference in the mean PCD-MI when split by year of diagnosis, F -statistic 1.625, P = 0.147. PCD-MI is a calculatable measure for a cohort of patients diagnosed over an 8-year period, integrating a wide-range of data with potential to determine high or low disease burden. Future iterations of the PCD-MI require refinement of included features, optimized scores, and validation on external cohorts.