Oren Ledder

Crohn's and colitis in children and adolescents

Crohns disease and ulcerative colitis can be grouped as the inflammatory bowel diseases (IBD). These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohns disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions: these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythema nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohns disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, thereby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult-onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohns disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.

Are thiopurines always contraindicated after thiopurine-induced pancreatitis in inflammatory bowel disease?

Background and Aims: Thiopurine use in inflammatory bowel disease (IBD) is well established for maintenance of disease remission. Approximately 3% of patients with IBD develop thiopurine-induced pancreatitis (TIP) as an idiosyncratic reaction. Patients diagnosed as having TIP are largely considered not to be candidates for future use of this drug. We hypothesize that previous TIP is not an absolute contraindication to retrialing a different thiopurine. Methods: This case series is a retrospective chart review of those patients with IBD in whom thiopurines were successfully reintroduced following suspected TIP. The patients were all cared for in 2 Australasian pediatric IBD services. Four cases are presented of TIP appropriately related temporally to azathioprine commencement, with no other apparent cause of pancreatitis identified. All of these patients were trialled on 6-mercaptopurine according to clinical need and this was well tolerated in all cases. Results and Conclusions: This report is the largest case series to date focusing on the reintroduction of a thiopurine following suspected thiopurine induced pancreatitis. All of the patients had a typical presentation of TIP. This case series should call into question the assumption that suspected TIP is an absolute contraindication for the future use of this class of drug. Cautious reintroduction of a thiopurine, in a controlled setting, should be considered in certain circumstances. The clinical relevance of this option is most marked in patients with complicated disease requiring long-term immunosuppression, in whom other therapies are poorly tolerated or contraindicated.

Early endoscopic, laboratory and clinical predictors of poor disease course in paediatric ulcerative colitis

Objective Data to support treatment algorithms in ambulatory paediatric UC are scarce. We aimed to explore the 1 year outcome in an inception cohort of paediatric UC patients and to identify early predictors of good outcome that might serve as short term treatment targets. Design A chart review of 115 children with new onset UC was performed (age 11±4.1 years; 58 (50%) males; 86 (75%) extensive colitis; 70 (61%) moderate–severe disease; 63 (55%) received steroids at baseline). We assessed the Paediatric Ulcerative Colitis Activity Index (PUCAI) and laboratory variables at the time of diagnosis and at 3 months, and endoscopy at diagnosis. Results The 3 month PUCAI was the strongest predictor of 1 year sustained steroid free remission (SSFR) (area under the receiver operating characteristic curve (AUROC)=0.7 (95% CI 0.6 to 0.8) and colectomy by 2 years (AUROC=0.75 (0.6 to 0.89)). SSFR was achieved in 9/54 (17%) children who had active disease (PUCAI ≥10) at 3 months (negative predictive value (NPV)=83%) and by 4/46 (8.6%) of those with a PUCAI score >10; (NPV=91%, positive predictive value=52%; p<0.001), implying that PUCAI >10 at 3 months has a probability of 9% for achieving SSFR versus 48% with a PUCAI value of ≤10. None of the variables at baseline was predictive of SSFR or colectomy (endoscopic severity, disease extent, age, PUCAI or C reactive protein/erythrocyte sedimentation rate/albumin/haemoglobin; all AUROC<0.6, p>0.05) but baseline PUCAI predicted subsequent acute severe colitis and the need for salvage medical therapy. Conclusions Completeness of the early response appears more important than baseline UC severity for predicting outcome in children, and supports using PUCAI<10 as a feasible treatment goal. Our data suggest that treatment escalation should be considered with a PUCAI value of ≥10 at 3 months.

Clinical Patterns and Outcome of Early-Onset Inflammatory Bowel Disease

ABSTRACT We sought to determine whether extremely-early-onset childhood inflammatory bowel disease (age <6 years; 20 ulcerative colitis [UC], 8 Crohn disease [CD], 2 indeterminate, sequentially diagnosed) was clinically more severe than in older children (6–17 years; 19 UC, 39 CD, 2 indeterminate). Early-onset UC was marked by less abdominal pain at presentation, but an aggressive course with a significant reduction in weight-for-age, increased use of immunosuppressants, and more surgery. Children with early-onset CD were more likely to have bloody stools at presentation and an isolated colitis. This study supports the suggestion that inflammatory bowel disease phenotype differs in early-onset disease.

Cystic fibrosis: an update for clinicians. Part 2: hepatobiliary and pancreatic manifestations.

This paper, the second in the series, will build on the first and explore the importance of liver and pancreatic manifestations of cystic fibrosis (CF) and the effect on morbidity and mortality of this multifaceted genetic condition. It will also further develop the critical role of the gastroenterologist as part of the multidisciplinary group of clinicians and allied health staff in the effective management of patients with CF.

Anti-TNF, infliximab, and adalimumab can be effective in eosinophilic bowel disease.

Background: Eosinophilic enterocolitis (EEC) is an emerging distinct inflammatory bowel disease of unknown etiology. There are no published data on the effect of infliximab (IFX) or adalimumab (ADA) for the treatment of refractory cases. Methods: A report of all pediatric cases with EEC treated with anti-tumor necrosis factor, identified after an open international call. Results: We describe here the first 8 children with refractory EEC who were treated with IFX (75% boys; mean age at diagnosis 8.6 ± 4.03 [range 1.6–14 years]; mean age at IFX treatment 11.7 ± 4.4 [range 4.2–16 years]). Allergic and infectious causes of EEC were excluded in all cases. Rapid and complete clinical remission was documented in 6 (75%) children following the induction infusions: 3 (38%) with endoscopic remission, 2 (25%) with endoscopic improvement, and 1 unknown. Four of the 6 responders had secondary loss of response and were switched to ADA, 3 of whom with sustained remission using high doses. Overall, the 6 responders were followed for a median of 7 years (range 4–12; interquartile range 6.4–8.8 years) without evidence of developing Crohn disease or ulcerative colitis. The only case with macroscopic findings on endoscopy was a primary nonresponder. Conclusions: IFX and ADA may be effective in cases of refractory idiopathic EEC; however, because this is an uncontrolled report, further prospective studies are warranted.

Clinical audit results in earlier nutritional intervention in malnourished children with cystic fibrosis with improved outcome.

The association between nutritional status, pulmonary function and survival in cystic fibrosis (CF) is well established. A previous case series from the Royal Childrens Hospital, Melbourne (RCH), demonstrated suboptimal referral practices and highlighted the importance of early nutritional interventions in children with CF. Various qualitative changes were made to our CF service, and this study assesses the effects of these practice changes timing of gastrostomy and clinical outcome in patients who underwent gastrostomy insertion.

Cystic fibrosis: An update for clinicians. Part 1: Nutrition and gastrointestinal complications

During three decades, the demographics of cystic fibrosis (CF) has undergone a significant change. Advances in nutritional and pulmonary management allow the vast majority of patients reaching adulthood today. With increasing survival, new and previously less common aspects of CF are encountered by the clinician expanding the concept of CF as a multisystem disease. The first part of this two‐part review will focus on the nutritional and gastrointestinal aspects of the CF phenotype and outline core principles of diagnosis and care.

Thiopurine-induced pancreatitis in inflammatory bowel diseases.

Crohn’s disease and ulcerative colitis are chronic inflammatory conditions affecting the gut and can present at any age with increased numbers of diagnoses seen in many countries in recent years. The thiopurine drugs, azathioprine and 6-mercaptopurine, are commonly used to maintain remission in Crohn’s disease and ulcerative colitis; however, the use of these drugs may be limited by the development of pancreatitis in some individuals. Recent data indicate a genetic risk factor and provides a potential immune-mediated mechanism for thiopurine-induced pancreatitis. Management of thiopurine-induced pancreatitis requires exclusion of the triggering drug, which leads to prompt resolution of symptoms. This thiopurine side-effect may limit therapeutic options for future management of patients.

Single High-Dose Oral Vitamin D3 Therapy (Stoss): A Solution to Vitamin D Deficiency in Children With Inflammatory Bowel Disease?

Objectives: Vitamin D deficiency is common in children with inflammatory bowel disease (IBD). The aim of this study was to determine the safety and efficacy of stoss therapy on vitamin D levels during a period of 6 months in children with IBD and vitamin D deficiency (<50 nmol/L). Methods: A retrospective chart review was undertaken, focusing upon children managed in the IBD clinic at Sydney Childrens Hospital between 2006 and 2010. Those with a 25-hydroxyvitamin D (25-OHD) level <50 nmol/L and those who received stoss therapy were included in this study. Results: A total of 76 children received stoss therapy. There was a significant and sustained increase in 25-OHD levels at all of the time points compared with baseline (40.8 ± 7.5 nmol/L), 1 month (145.6 ± 51.8 nmol/L), 3 months (87.1 ± 28.4 nmol/L), and 6 months 69.2 ± 31.3 nmol/L). There were no significant changes in serum calcium, phosphate, or parathyroid hormone at any time points. Conclusions: Stoss therapy safely and effectively achieved and maintained a level of 25-OHD >50 nmol/L during 6 months in these children with IBD. Further prospective studies are now required to confirm this finding and establish whether this intervention has other benefits.