Vikki Garrick

The use of exclusive enteral nutrition for induction of remission in children with Crohn’s disease demonstrates that disease phenotype does not influence clinical remission

Background  Exclusive enteral nutrition (EEN) achieves variable remission rates in patients with Crohn’s disease (CD).

Decline in Presumptively Protective Gut Bacterial Species and Metabolites Are Paradoxically Associated with Disease Improvement in Pediatric Crohn’s Disease During Enteral Nutrition

Background:The gut microbiota is implicated in the pathogenesis of Crohn’s disease (CD). Exclusive enteral nutrition (EEN) is a successful treatment, but its mode of action remains unknown. This study assessed serial changes in the fecal microbiota milieu during EEN. Methods:Five fecal samples were collected from CD children: 4 during EEN (start, 15, 30, end EEN approximately 60 days) and the fifth on habitual diet. Two samples were collected from healthy control subjects. Fecal pH, bacterial metabolites, global microbial diversity abundance, composition stability, and quantitative changes of total and 7 major bacterial groups previously implicated in CD were measured. Results:Overall, 68 samples were from 15 CD children and 40 from 21 control subjects. Fecal pH and total sulfide increased and butyric acid decreased during EEN (all P < 0.05). Global bacterial diversity abundance decreased (P < 0.05); a higher degree of microbiota composition stability was seen in control subjects than in CD children during EEN (at P ⩽ 0.008). Faecalibacterium prausnitzii spp concentration significantly decreased after 30 days on EEN (P < 0.05). In patients who responded to EEN, the magnitude of the observed changes was greater and the concentration of Bacteroides/Prevotella group decreased (P < 0.05). All these changes reverted to pretreatment levels on free diet, and EEN microbiota diversity increased when the children returned to their free diet. Conclusions:EEN impacts on gut microbiota composition and changes fecal metabolic activity. It is difficult to infer a causative association between such changes and disease improvement, but the results do challenge the current perception of a protective role for F. prausnitzii in CD.

Clinical progress in the two years following a course of exclusive enteral nutrition in 109 paediatric patients with Crohn's disease

Exclusive enteral nutrition (EEN) is an effective first line treatment for active paediatric Crohns disease (CD).

Cerebral thromboembolic events in pediatric patients with inflammatory bowel disease

Background: There is a recognized association between pediatric inflammatory bowel disease (IBD) and cerebral thromboembolic events (CTEs). Historical reporting had described the association as strongest between ulcerative colitis (UC), rather than Crohns disease (CD). We describe the incidence and outcome of CTE in pediatric IBD patients from a single center over 5 years and the relative proportion of stroke reported in the literature in patients with UC and CD before and after January 2000. Methods: Demographic data were extracted on all newly diagnosed cases of IBD in our center from January 2003 to January 2008 to ascertain patient characteristics, disease type, risk factors for CTE, modality of neuroimaging, and outcome. A literature search was performed to identify all articles describing stroke in pediatric IBD. All identified studies were stratified into those published before and after January 1 2000. Results: In all, 154 new patients diagnosed with IBD (male 56%) (UC 30%, CD 64%, IBD unclassified [IBDU] 6%) were reviewed. Four cases of CTE occurred in our population over 5 years (2.6%). All patients had a risk factor for CTE. Fifteen case series were identified with 32 patients. There was a significant increase in the proportion strokes affecting patients with CD reported after January 2000 (P = 0.02). Conclusions: CTE affects a proportion of pediatric IBD patients. Although resolution of physical impairment is the norm, significant morbidity exists. Our study suggests a secular trend toward CTE in CD. Primary prevention with the identification and amelioration of identifiable risk factors should be the clinical objective in future studies. (Inflamm Bowel Dis 2009)

A case of posterior reversible encephalopathy syndrome in a child with Crohn's disease treated with Infliximab

BACKGROUND AND AIMS Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity characterised by headache, seizures, visual disturbance, altered mental status and vasogenic oedema on neuro-imaging. We report a rare case of PRES in a 8-year-old female with Crohns disease (CD) following Infliximab administration and colectomy. METHOD Clinical case reported including a review of current literature regarding PRES and Infliximab. RESULTS This is one of several cases of PRES reported recently in proximity to Infliximab administration. CONCLUSIONS Awareness of this rare condition in patients receiving immunosuppressive treatment is important to prevent poor outcomes for patients. The increasing number of these cases recognised in patients receiving Infliximab should be kept under close clinical surveillance due to the possibility of a link between the two.

Management of Crohn's disease

Crohns disease (CD) is rapidly increasing in children so an up to date knowledge of diagnosis, investigation and management is essential. Exclusive enteral nutrition is the first line treatment for active disease. The vast majority of children will need immunosuppressant treatment and around 20% will need treatment with biologics. Recent guidelines have helped make best use of available therapies.

Successful implementation of a nurse-led teaching programme to independently administer subcutaneous methotrexate in the community setting to children with Crohn's disease.

Background  Methotrexate is increasingly used as a third line immunosuppression agent in children with Crohn’s disease (CD). Methotrexate is traditionally administered in the hospital setting.

Letter: Epstein-Barr virus status may be especially important in paediatric IBD populations.

Remission in proton pump inhibitor-responsive esophageal eosinophilia correlates with down regulation of eotaxin-3 and TH2 cytokines, similarly to eosinophilic esophagitis after steroids. Gastroenterology 2013; 144(Suppl. 1): S-484. 7. Dranove JE, Horn DS, Davis MA, et al. Predictors of response to proton pump inhibitor therapy among children with significant esophageal eosinophilia. J Pediatr 2009; 154: 96–100. 8. Sayej WN, Patel R, Baker RD, et al. Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2009; 49: 393–9. 9. Peterson KA, Thomas KL, Hilden K, et al. Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis. Dig Dis Sci 2010; 55: 1313–9. 10. Abe Y, Iijima K, Ohara S, et al. A Japanese case series of 12 patients with esophageal eosinophilia. J Gastroenterol 2011; 46: 25–30. 11. Francis DL, Foxx-Orenstein A, Arora AS, et al. Results of ambulatory pH monitoring do not reliably predict response to therapy in patients with eosinophilic oesophagitis. Aliment Pharmacol Ther 2012; 35: 300–7. 12. Schroeder S, Capocelli KE, Masterson JC, et al. Effect of proton pump inhibitor on esophageal eosinophilia. J Pediatr Gastroenterol Nutr 2013; 56: 166–72. 13. Fujiwara Y, Sugawa T, Tanaka F, et al. A multicenter study on the prevalence of eosinophilic esophagitis and PPI-responsive esophageal eosinophilic infiltration. Intern Med 2012; 51: 3235–9. 14. Moawad FJ, Schoepfer A, Ally MR, et al. Eosinophilic esophagitis and proton pump inhibitor responsive esophageal eosinophilia: are they one and the same? Gastroenterology 2013; 144(Suppl. 1): S489 (Su1845). 15. Mangla S, Singal G, Hornick JL, et al. Clinical predictors of response to proton pump inhibitors in patients with esophageal eosinophilia. Gastroenterology 2013; 144(Suppl. 1): S495–6 (Su1866). 16. Dellon ES, Speck O, Woodward K, et al. Clinical and endoscopic characteristics do not reliably differentiate PPIresponsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study. Am J Gastroenterol 2013; doi: 10.1038/ajg.2013.363 [Epub ahead of print].

Effect of exclusive enteral nutrition on colonic bacterial activity in paediatric Crohn's disease

Crohn’s disease (CD) is an uncommon chronic gastrointestinal disorder. The endogenous gut microbiota is believed to be important in its aetiology. Exclusive enteral nutrition (EEN) is the mainstream treatment for children with active CD with comparable efficacy to steroids. The mechanisms of action remain unknown. Modulation of the dominant gut microbiota metabolic activity has been suggested as a mechanism but has not been addressed by a study yet. The aim of the present study was to investigate the effect of EEN on faecal biomarkers of bacterial metabolic activity in children with active CD. Fresh stool samples were collected from sixteen children (nine boys) with active CD at four different time points over their 8 weeks of treatment with EEN (Modulen1; Nestle, Croydon, Surrey, UK). Faecal biomarkers were measured at different time points (Table) and the clinical disease activity was assessed at baseline and at the end of treatment with a validated paediatric CD activity index (PCDAI). Seven children achieved clinical remission (PCDAI £ 10) and nine had still-active disease (PCDAI >10). In those children that achieved clinical remission, significant changes in faecal biomarkers were observed (Table). Colonic pH increased to the alkaline range, whereas butyrate production and proportion decreased significantly from baseline. A fivefold increase in the production of total sulphide, but not free sulphide, was observed over the treatment period. D-Lactate but not its L-isomer decreased significantly from baseline. None of these changes were observed for the children with active disease activity (PCDAI >10) at the end their treatment.

Changes in dominant gut microbial species and metabolites in children with Crohn's disease during exclusive enteral nutrition

ro ce ed in gs o f th e N u tr it io n So ci et y Winter Meeting, 11–12 December 2013, Diet, gut microbiology and human health Changes in dominant gut microbial species and metabolites in children with Crohn’s disease during exclusive enteral nutrition K. Gerasimidis, M. Bertz, L. Hanske, J. Junick, O. Biskou, M. Aguilera, V. Garrick, R. K. Russell, M. Blaut, P. McGrogan and C. A. Edwards Human Nutrition, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, G3 8SJ, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Sick Children, Glasgow, G3 8SJ, Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany and Department of Microbiology, Faculty of Pharmacy, University of Granada, Granada, Spain The gut microbiota is implicated in the pathogenesis of Crohn’s Disease (CD). Exclusive enteral nutrition (EEN) is a successful treatment but its mode of action remains unknown. We assessed changes in the fecal microbiota milieu during EEN. Five faecal samples were collected from CD children; 4 during EEN (start, 15, 30, end EEN∼60 days) and a fifth on free habitual diet. Two samples were collected from healthy controls. Faecal pH, bacterial metabolites (Figure) and quantitative changes (q-PCR) of total and 7 major bacterial groups implicated in CD were measured. 68 samples were from 15 CD children and 40 from 21 controls. Faecal pH and total sulphide increased and butyric acid decreased during EEN (Figure). F. prausnitzii spp. concentration significantly decreased after 30 d on EEN (Figure). In patients who responded to EEN, the magnitude of the observed changes was greater and the concentration of Bacteroides/Prevotella group also decreased. All these changes reverted to pre-treatment levels when the children returned to their free habitual diet.