Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

Prediction of thiopurine failure in pediatric Crohn's disease: pediatric IBD Porto group of ESPGHAN.

BACKGROUND: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy. METHODS: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse. RESULTS: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031). CONCLUSIONS: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision. IMPACT: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

B cell-activating factor (BAFF) in children with inflammatory bowel disease.

BACKGROUND: Assessing the inflammation is important in the follow-up of paediatric patients with inflammatory bowel disease (IBD). We aim to evaluate the value of B cell-activating factor (BAFF) in paediatric IBD as a potential biomarker for follow-up. METHOD: We determined BAFF in serum and faeces and faecal calprotectin (CP) in 32 IBD children-16 Crohn's disease (CD) and 16 ulcerative colitis (UC). Twenty-six healthy children and 10 children with irritable bowel syndrome (IBS) were included as controls. RESULTS: No differences were found in serum BAFF between IBD, IBS, and healthy group: 1037.35, 990.9 and 979.8 pg/ml, respectively, all p > 0.05, but faecal BAFF was higher in the IBD group: 15.1, 8.5 and 8.2 pg/ml, respectively, p < 0.05, and higher in the UC group (55.975 pg/ml) compared to the CD group (10.95 pg/ml), p = 0.015. Splitting the IBD group in relation to the CP level, the serum BAFF had no significantly different values between the subgroups, but the faecal BAFF was significantly higher in the >250 µg/g subgroup. Cut-off values of BAFF were calculated. CONCLUSION: Faecal BAFF is a promising marker for monitoring the children with IBD, higher levels of BAFF being correlated with high CP. IMPACT: Faecal BAFF is a promising marker in monitoring the children with IBD, higher levels of BAFF being correlated with high faecal calprotectin. To our knowledge, this is the first paediatric study concerning BAFF evaluation in IBD. Faecal BAFF levels could be considered a potential non-invasive marker in monitoring IBD activity in paediatric population with clinically mild or inactive disease.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

BACKGROUND: The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. METHODS: A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. RESULTS: We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. CONCLUSIONS: Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines.

BACKGROUND AND AIMS: Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). METHODS: A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. RESULTS: A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. CONCLUSIONS: These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.