Arterial structure and function in children with inflammatory bowel disease.

Background and Aim: People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. Methods: We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. Results: We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. Conclusion: We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Inflammatory Bowel Disease in Children.

Inflammatory bowel disease is an important cause of chronic diarrhea in children, with a rising incidence, globally. The two main subtypes include Crohn's disease and ulcerative colitis. The clinical features are variable, and diagnosis requires initial first-line investigations followed by the involvement of specialist input for targeted imaging and endoscopy with biopsy, to confirm the diagnosis. Despite detailed investigation, inflammatory bowel disease may be clinically indistinguishable from chronic infections such as intestinal tuberculosis, and anti-tuberculosis treatment may be considered prior to further management considerations. The medical management of inflammatory bowel disease depends on subtype classification and severity, and may involve a step-wise approach to immunosuppressive therapies. In children, the consequences of poorly controlled disease are wide ranging, from psychosocial impacts and school non-attendance, to growth impairment and pubertal delay with subsequent impacts on bone health. In addition, an increased need for hospitalization and surgical intervention, and ultimately risk of cancer long-term. A multi-disciplinary team with expertise in inflammatory bowel disease is recommended to mitigate these risks and help to achieve the goal of sustained remission with endoscopic healing. This review focuses on updates on best clinical practice on the diagnosis and management of inflammatory bowel disease in children.

Long-term outcomes of liver transplantation for homozygous familial hypercholesterolaemia in Australia and New Zealand.

BACKGROUND AND AIMS: Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort. Newer drugs including lomitapide and evinacumab might reduce the need for apheresis and LT. We sought to determine the long-term outcomes following LT in Australia and New Zealand. METHODS: We analysed demographic, biochemical and clinical data from all patients in Australia and New Zealand who have received LT for homozygous FH, identified from the Australia and New Zealand Liver and Intestinal Transplant Registry. RESULTS: Nine patients (five female; one deceased; seven aged between 3 and 6 years at the time of LT and two aged 22 and 26 years) were identified. Mean follow-up was 14.1 years (range 4-27). Baseline LDL-cholesterol off all treatment was 23 ± 4.1 mmol/L. Mean LDL-cholesterol on medical therapy (including maximal statin therapy in all patients, ezetimibe in three and LA in five) was 11 ± 5.7 mmol/L (p < 0.001). After LT, mean LDL-cholesterol was 2.6 ± 0.9 mmol/L (p = 0.004) with three patients remaining on statin therapy and none on LA. One patient died from acute myocardial infarction (AMI) three years after LT. Two patients required aortic valve replacement, more than 10 years after LT. The remaining six patients were asymptomatic after eight to 21 years of follow-up. No significant adverse events associated with immunosuppression were reported. CONCLUSIONS: LT for homozygous FH was highly effective in achieving substantial long-term reduction in LDL-cholesterol concentrations in all nine patients. LT remains an option for severe cases of homozygous FH where drug therapy combined with apheresis is ineffective or unfeasible.

Management and monitoring of pediatric inflammatory bowel disease in the Asia-Pacific region: A position paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group: Surgical management, disease monitoring, and special considerations.

Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia-Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia-Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia-Pacific region.

Use of Dual-Energy X-ray Absorptiometry in Children with Inflammatory Bowel Disease: A Large Single Centre Study.

Purpose: Low bone mineral density (BMD) is a complication in children with inflammatory bowel disease (IBD). There are limited data evaluating dual-energy x-ray absorptiometry (DXA) as a screening tool for low BMD in children with IBD. We performed a single site retrospective analysis of DXA use. Methods: Children aged 5-18 years with IBD diagnosed between 2013 to 2017 at the Royal Children's Hospital, Australia, were included. Patient demographics, measures of disease activity, DXA scores, and factors related to BMD were collected. Results: Over a median follow up of 5.1 (4-6.4) years, 72/239 (30.1%) children underwent DXA, and 28/239 (11.7%) children had a second DXA. Our DXA practice differed to consensus guidelines regarding initial screening based on height and/or body mass index (BMI) z-score (8/17 [47.1%]), and repeat surveillance (13/42 [31.0%]). Children had a median lumbar spine (LS) z-score -0.80 (-1.65-0.075). Children with LS z-score≤-2.0 (n=14) had lower weight (6.57 [1.78-23.7] vs. 51.1 [26.5-68.7], p=0.0002) and height centiles (3.62 [1.17-17.1] vs. 42 [16.9-67.1], p=0.0001), and higher faecal calprotectin (FCP) (3041 [1182-4192] vs. 585 [139-2419], p=0.009) compared to children with LS z-score>-2.0. No fractures were reported. Of 28 children who underwent a second DXA 1.6 (1.1-2.2) years following initial DXA, no significant change in z-scores occurred. Conclusion: Children with IBD had low BMD. In addition to height centile and weight centile, FCP was associated with lower BMD, and should be considered in DXA screening guidelines. Greater clinician awareness of DXA consensus guidelines is required. Future prospective studies are required.

Medical Management of Pediatric Inflammatory Bowel Disease (PIBD) in the Asia Pacific Region: A Position Paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group.

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialised and affluent areas in the Asia Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up-to-date, evidence-based approach to PIBD in the Asia Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine-S-methyltransferase (TPMT). The main considerations in the use of biologics in the Asia Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. Conclusion: This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia Pacific region.

Impact of ulcerative colitis on liver-related outcomes of children with primary sclerosing cholangitis.

AIM: Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disorder associated with ulcerative colitis (UC). Although the inflammatory bowel disease phenotype has been characterised in patients with PSC, the impact of UC on the course and progression of PSC-UC is less clear. We aimed to evaluate the effects of UC on liver-related outcomes in children with PSC. METHODS: Retrospective analysis of children aged ≤18 years diagnosed with PSC with/without UC at a single tertiary paediatric liver unit between January 1998 and May 2016. Patients were followed up until transition to an adult service. Outcomes studied included biliary complications, clinically significant portal hypertension, need for liver transplantation and post-transplantation recurrence. RESULTS: Fifty-one children (31 female) were diagnosed with PSC (median age - 11.3 years (interquartile range 7)), follow-up median duration 54 months (interquartile range 56). Thirty-seven (73%) patients had concurrent UC, of which 26 had their diagnosis confirmed prior to or within 6 months of PSC diagnosis (early-onset). PSC complications were more common in children with PSC-UC compared with PSC alone (24/37 (65%) vs. 2/14 (14%); P = 0.001). Furthermore, children with endoscopically mild or moderate UC at diagnosis showed a greater propensity for liver-related complications compared with children with severe UC (24/32 vs. 0/5; P = 0.003). Children with late-onset UC had higher rates of clinically significant portal hypertension (5/11 (45%) vs. 3/26 (12%); P = 0.007) and liver transplantation (5/11(45%) vs. 2/26 (8%); P = 0.02). Children with PSC-UC had significantly higher rates of pancolitis, rectal sparing and milder colitis than those with UC alone. CONCLUSION: The presence and a later-onset of UC are associated with more significant progression to end-stage liver disease. There is an inverse trend between UC severity and PSC severity in children with concurrent PSC-UC.

Immunisation status of children and adolescents with a new diagnosis of inflammatory bowel disease.

BACKGROUND: Patients with Inflammatory Bowel Disease (IBD) are at increased risk of serious infections, including vaccine preventable diseases. Current evidence suggests uptake of additional recommended special risk vaccinations is low. Identification of IBD patients prior to commencing immunosuppressive therapy allows for optimisation of vaccination, including timely administration of live-attenuated and additional recommended vaccines, such as influenza and pneumococcal vaccines. METHODS: Paediatric patients (0-18 years) seen at the tertiary Royal Children's Hospital, Melbourne, Australia, with a recent diagnosis of IBD were referred by the Gastroenterology Unit to our Specialist Immunisation Clinic (SIC) for assessment and provision of routine and special risk vaccines. Data was collected via a standardised REDCap questionnaire completed in or post attendance at the SIC and included serology results where available. RESULTS: Sixty-nine paediatric patients were recruited to the study between 2014 and 2017. Median age at IBD diagnosis was 11.25 years (IQR 4.64 years), with median time between diagnosis and SIC review of 0.88 years (IQR 2.84 years). At initial review 84.1% (58/69) of patients were up to date with vaccines on the Australian National Immunisation Program (NIP) schedule. Of those who were tested, serological evidence of immunity was demonstrated in 38.3% (23/60) of patients for Hepatitis B, 66.7% (36/54) for measles, 51.9% (28/54) for rubella and 41.9% (26/62) for Varicella Zoster Virus. Prior to SIC review 47.8% (33/69) had additional vaccinations and 92.8% (64/69) had vaccinations administered in the 12 months following SIC assessment. The Pneumococcal conjugate vaccine (76.8%, 53/69) was the most commonly administered vaccine after SIC review, followed by influenza vaccine (69.6%, 48/69). Within 12 months of SIC review 43.5% (30/69) of patients had completed the schedule and were up-to-date as recommended by the SIC. CONCLUSIONS: Children with IBD and other special risk groups can benefit from early referral to a SIC team to ensure optimal administration of routine and additionally recommended vaccines, especially live and additional special risk vaccines. The value of optimising immunisations could also be applied to other special risk groups, including adult IBD cohorts, particularly those commencing newer biologic immunosuppressive medications.

Assessment of Disease-related Knowledge Among Children With Inflammatory Bowel Disease and their Family Using IBD-KID2: Evaluating Tool Generalizability.

Children with inflammatory bowel disease (IBD) and their families benefit from improved knowledge of their disease and treatment. Knowledge levels of individual family members are infrequently studied but may identify where education is best directed. We aimed to assess disease-specific knowledge among children with IBD, parents, and siblings, using a validated assessment tool (IBD-KID2), and to establish generalizability of IBD-KID2. Methods: Children with IBD and family members were recruited from tertiary IBD clinics in New Zealand, Australia, and Canada. All participants completed IBD-KID2 online at baseline, and the children with IBD again after 2 weeks to assess reliability. Results: Participants included 130 children with IBD, 118 mothers, 55 fathers, and 37 siblings. Children with IBD had a mean score of 9.1 (SD 2.9) (maximum 15 points), significantly lower than parents (P < 0.005) and higher than siblings (P < 0.005). Scores of children with IBD were positively associated with current age (P < 0.005), age at diagnosis (P = 0.04) and fathers education level (P = 0.02). Significant score correlations were seen between children with IBD and their mother (P < 0.005) but not father. Sibling scores were not correlated with either parent. Test-retest reliability was high. The cohorts from each country were comparable, and no difference in group scores was seen between countries. Conclusion: IBD-KID2 is a generalizable and reliable tool for the assessment of disease and treatment knowledge for children with IBD and their families. Score correlations between parents and children with IBD suggest transfer of knowledge, but sibling knowledge is low and targeted education may be beneficial.

Medication Adherence Across the Life Span in Inflammatory Bowel Disease: Implications and Recommendations for Nurses and Other Health Providers.

This article reviews the differences and similarities in medication adherence between adolescent and adult cohorts with inflammatory bowel disease. The review covers the rates of medication adherence, as well as predictors, consequences, and related interventions. Rates of adherence were more favorable among adolescents (65%-90%) than among adults (55%-70%). Major risk factors for poor adherence in adolescents include low medication knowledge, not establishing good medication habits initially, and peer victimization with low social support. For adults, nonadherence is more frequently unintentional (e.g., forgetting) and occurs more often in the context of a poor-quality patient-physician relationship, low medication knowledge, infrequent/missed appointments, busy lifestyle, and concurrent mental health concerns. Nonadherence to medication is associated with worsening of symptoms and risk of relapse in adults and adolescents. Nurses can play a significant role in influencing adherence to medication in patients with inflammatory bowel disease. In particular, nurses can help to impart knowledge on the importance of medication and identify factors that may help or hinder an individual in terms of adherence. Based on the current review, implications for practice and recommendations for nurses to promote medication adherence across both adolescent and adult cohorts are provided. Limitations of the currently available evidence and suggestions for future research are discussed.

Management of inflammatory bowel disease in children: It is time for an individualised approach.

Paediatric-onset inflammatory bowel disease (PO-IBD) is associated with greater morbidity compared to adult-onset IBD. However, as not all children with PO-IBD will have poor outcome and the best management decisions involve weighing risks versus benefit and wishes of patient's and family, we review risk factors of IBD progression in children and summarise rapidly expanding treatment choices, potential drug-related adverse events and risk minimisation strategies, ending with new treatment paradigms focusing on long-term goal of intestinal healing. For the purpose of this article, we have outlined the conventional approach, including medications currently licenced and available for use in Australia for paediatric IBD through the Pharmaceutical Benefit Scheme and briefly discuss other promising therapies that are shown to be effective in adults but are undergoing paediatric clinical trials.

Variation of Gut Mucosal Microbiome With Anti-Saccharomyces cerevisiae Antibody Status in Pediatric Crohn Disease.

OBJECTIVES: Crohn disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. Approximately 30% to 60% of patients with CD have anti-Saccharomyces cerevisiae antibody (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype. METHODS: Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity, and clinical characteristics. RESULTS: ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease, and long-term risk of surgery. Microbial alpha and beta diversity were similar in patients with CD with or without ASCA, but significantly less when compared to noninflammatory bowel disease controls. Microbial richness was similar across all 3 groups. Fourteen bacterial species were associated with ASCA-positive patients with CD and 14 species with ASCA-negative patients (P < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterocolitica 61 remained significantly associated with CD ASCA positivity (P = 0.0178), whereas Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (P = 0.0178 and 0.0342). CONCLUSION: ASCA-positive and ASCA-negative patients with CD have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.

Impact of Changing Treatment Strategies on Outcomes in Pediatric Ulcerative Colitis.

BACKGROUND: In recent years, treatment strategies for ulcerative colitis have evolved with an early step-up approach, the availability of biologicals, and therapeutic drug monitoring.We carried out this study to evaluate the effect of these changes on disease outcomes. METHODS: In this retrospective review, 2 time periods were defined: Group 1 (2005-2010) and Group 2 (2011-2016). Baseline demographic, endoscopic parameters, and medication use were compared. Overall colectomy rate, number of disease flares per year, and number of hospital admissions per year were compared between the 2 groups. RESULTS: Group 1 had 71 children, and in children in Group 2. The use of 5-ASA increased in Group 2 (Group 2, 99.2% vs. Group 1, 84.5%, P = 0.0007). In addition, infliximab and thiopurines were introduced earlier in the disease course.The 2-year cumulative probability of colectomy decreased from 14% to 3% (P = 0.02) between the 2 periods. No change in median number of flares per year [Group 1, 0.41 (IQR 0.6) vs. Group 2, 0.62 (IQR 0.91), P = 0.28] or median number of hospital admissions per year [Group 1, 0.30 (IQR 0.77) vs. Group 2, 0.21 (IQR 0.75), P = 0.52] was seen.Thereafter, we proceeded to identify the changes in treatment strategies that were responsible for the reduction in colectomy and we found that the use of infliximab OR 3.7 (95% CI 1.1-11.7), P = 0.02, was independently associated with it. CONCLUSIONS: A reduction in 2-year colectomy rates has been observed in patients with pediatric ulcerative colitis since biologics have become available for its treatment. The numbers of disease-flares rates and hospital admissions remain unchanged.

The Microbiome in Paediatric Crohn's Disease-A Longitudinal, Prospective, Single-Centre Study.

BACKGROUND AND AIMS: The gut mucosa is the principal site where Crohn's disease [CD] inflammation occurs. Limited information is available about the gut mucosal microbiome during CD relapse and remission. The aim of our study was to characterize specific changes in the gut microbiome during relapse and remission in a large single-centre paediatric CD cohort. METHODS: We analysed the microbiome of 345 biopsies from 204 patients, including 88 CD first diagnosis [CDFD] patients, 38 relapse [CDRL] patients, 12 remission [CDRM] patients, and 66 controls. Species identification was conducted using oligotyping in combination with ARB/SILVA taxonomic annotation. RESULTS: We observed 45 bacteria to differ between CDFD samples and controls with statistical significance, with Fusobacterium being the most implicated species in CDFD patients. We also identified gender-specific differences in CD. Five species showed a strong association with CDRL patients and 10 species with CDRM patients. Three taxa showed a positive co-occurrence across the two groups. Hespellia porcina [closest taxonomic neighbour to Clostridium oroticum] was the most strongly associated with CDRL samples. Interestingly, Fusobacterium was not part of the CDRL-associated taxa group. Faecalibacterium prausnitzii was equally present in CDFD and control samples. CONCLUSION: This is the first study that has investigated the gut mucosal microbiome in a paediatric CD cohort with longitudinal sampling. Importantly, the microbiome of patients in CDRM did not return to a healthy control state. Neither did the microbiome of patients with CDRL return to the profile seen at CDFD.

Crohn's & Colitis Australia inflammatory bowel disease audit: measuring the quality of care in Australia.

BACKGROUND: Australia has among the highest prevalence of Crohn disease and ulcerative colitis in the world. Management of the chronic gastrointestinal disorders results in significant societal costs and the standard of care is inconsistent across Australia. AIM: To audit the quality of care received by patients admitted for inflammatory bowel disease (IBD) across Australia against national IBD standards. METHODS: A retrospective cross-sectional survey and clinical audit was undertaken assessing organisational resources, clinical processes and outcome measures. This study was conducted in Australian hospitals that care for inpatients with Crohn disease or ulcerative colitis. The main outcome measures were adherence to national IBD standards and comparison of quality of care between hospitals with and without multidisciplinary IBD services. RESULTS: A total of 71 hospitals completed the organisational survey. Only one hospital had a complete multidisciplinary IBD service and 17 had a partial IBD service (IBD nurse, helpline and clinical lead). A total of 1440 inpatient records was reviewed from 52 hospitals (mean age 37 years; 51% female, 53% Crohn disease), approximately 26% of IBD inpatient episodes over a 12-month period in Australia. These patients were chronically unwell with high rates of anaemia (30%) and frequent readmissions (40% within 2 years). In general, care was inconsistent, and documentation was poor. Hospitals with a partial IBD service performed better in many processes and outcome measures: for example, 22% reduction in admissions through emergency departments and greater adherence to standards for safety monitoring of biological (89% vs 59%) and immunosuppressive drugs (79% vs 55%) in those hospitals than those without. CONCLUSION: Patients admitted to hospital suffering from IBD are young, chronically unwell and are subject to substantial variations in clinical documentation and quality of care. Only one hospital met accepted standards for multidisciplinary care; hospitals with even a minimal IBD service provided improved care.

The burden of surgery and postoperative complications in children with inflammatory bowel disease.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) may be associated with a higher burden of surgery and postoperative complications. This study aimed to measure the burden in pediatric IBD over a 20-year period in a large tertiary referral center. METHODS: A retrospective review was conducted of children diagnosed with IBD between 1996 and 2015, with a focus upon operative intervention (excluding endoscopy) and postoperative outcomes. RESULTS: Of 786 IBD patients, 121/581 (20.8%) with Crohn's disease (CD) and 22/205 (10.7%) with ulcerative colitis (UC) underwent surgery during the study period. When comparing 10-year epochs for CD, median time from diagnosis to intervention decreased from 34 months to 3 months (P < 0.0001). Postoperative complications occurred in 16/121 (13%) CD patients (bowel obstruction: 10, anastomotic stricture: 4, stomal issues: 4, anastomotic leak: 1). Within the UC cohort, the median time from diagnosis to intervention decreased from 62 months to 6 months (P = 0.0019). Postoperative complications occurred in 9/22 (41%) UC patients (bowel obstruction: 7, stomal issues: 3, anastomotic stricture: 1). Compared with CD, complications were more frequent in UC patients (P = 0.004). CONCLUSION: Surgery and postoperative complications are common in pediatric IBD. The timing of intervention has trended towards earlier operations in both CD and UC. LEVEL OF EVIDENCE: Treatment study-level III (retrospective comparative study).

A Simple Endoscopic Score Modified for the Upper Gastrointestinal Tract in Crohn's Disease [UGI-SES-CD]: A Report From the ImageKids Study.

OBJECTIVE: There is no standardized endoscopic description of upper gastrointestinal [UGI] disease in Crohn's disease [CD]. We prospectively applied the Simple Endoscopic Score for CD [SES-CD] to the UGI tract as a planned sub-study of the multicentre prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in paediatric CD. DESIGN: Patients underwent an oesophagogastroduodenoscopy [EGD], ileocolonoscopy, and magnetic resonance enterography [MRE] with explicit clinical data recorded. SES-CD was scored at each region [oesophagus, stomach body, antrum, and duodenum]. Half of the patients were followed for 18 months, when a repeat MRE was performed. RESULTS: A total of 202 children were included 56% males, mean age 11.5 ± 3.2 years, median weighted Paediatric Crohn's Disease Activity Index [wPCDAI 25]). UGI-SES-CD score ranged 0-17, with 95 [47%] having a UGI-SES-CD ≥1; no narrowing was detected. UGI-SES-CD ≥1 was associated with higher: wPCDAI [32.5 vs 20; p = 0.03]; Physician's Global Assessment [PGA] of inflammation (45 mm visual analogue score [VAS] vs 30 mm VAS; p = 0.04); ileocolonoscopic SES-CD [10 vs 7; p = 0.004], faecal calprotectin [717 µg/g vs 654 µ/g; p= 0.046]; and radiological global assessment of damage by MRE [7 mm VAS vs 0; p = 0.04]. In all, 81 patients were followed for 18 months and no association was identified between initial UGI SES-CD and markers of disease course such as surgery, MRE assessment, or treatment escalation. CONCLUSION: UGI-SES-CD is an easily reported objective scoring system and is associated with a more severe disease phenotype but not with disease course.

Pediatric Collagenous Gastritis and Colitis: A Case Series and Review of the Literature.

INTRODUCTION: Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been described: a pediatric-onset and an adult-onset type. The adult-onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date. OBJECTIVE: We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition. METHODS: A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital, Melbourne, was performed. A literature review was also conducted. RESULTS: A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine. CONCLUSIONS: Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the "'adult" phenotype at a very young age. Patients with collagenous gastritis require long-term follow-up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.

Secondary Loss of Response to Infliximab in Pediatric Crohn Disease: Does It Matter How and When We Start?

OBJECTIVES: A significant proportion of children with Crohn disease develop a secondary loss of response (LOR) to infliximab. Our aim was to study the impact of initial treatment strategies on secondary LOR. METHODS: We reviewed the medical records of children with Crohn disease who received scheduled maintenance infliximab therapy for at least 12 months. We compared children who developed LOR with those who did not; with regards to their clinical and laboratory parameters, disease phenotype, and treatment strategy before developing LOR. RESULTS: A total of 73 children (median age at diagnosis 11 (2-16) years, 41 boys) who had received a median duration of 33 (13-110) months of infliximab therapy were included in the final analysis. LOR was seen in 25(34.2%). Demographic variables, disease phenotype (age, disease location, and behavior), inflammatory parameters, and pediatric Crohn disease activity index at induction with infliximab were similar between both groups. Children with LOR had a significantly greater number of flares of the disease when compared to those who did not have LOR (4 [1-8] vs 2 [1-5] P = 0.03). The choice of the concomitant immunomodulator-methotrexate (11/29 [37.9%]) versus azathioprine (11/36 [30.5%]) (P = 0.6) did not affect LOR rates. The median time-lag between diagnosis and induction with infliximab was significantly longer in children with LOR as compared to those who did not have an LOR (28 [4-90] months vs 12.5 [1-121] months, P = 0.004). CONCLUSION: Early use of infliximab in pediatric Crohn disease is associated with a decrease in secondary LOR. The type of concomitant immunomodulator used does not make a difference to LOR rates.