Nutritional perspectives of children with Crohn's disease: a single-centre cohort observation of disease activity, energy expenditure and dietary intake.

BACKGROUND/OBJECTIVES: Children with Crohn's disease often demonstrate nutritional recovery during primary therapy at diagnosis, but long-term nutritional support is sometimes necessary. Evidence to inform best nutritional practice including energy and micronutrient requirements is limited. The principal objective of this study was to determine how energy expenditure and physical activity vary with disease activity over the first year following diagnosis. SUBJECTS/METHODS: Twenty children were studied at diagnosis with Crohn's disease and were followed up over 1 year while receiving treatment according to national guidelines. The majority of children (13) were treated with exclusive enteral nutrition. At study visits, height, weight, bioelectrical impedance, resting energy expenditure by indirect calorimetry, tri-axial accelerometer and blood investigations were performed alongside clinical assessment. RESULTS: There was no significant effect of disease activity on resting energy expenditure (REE). Physical activity was greater after primary therapy (Z=3.31, P<0.01). Median wPCDAI fell from 58 at diagnosis to 7.5 after primary therapy and was 7.5 at 1 year. Weight s.d.s increased from -1.67 to -0.86 and lean index s.d.s increased from -2.93 to -1.64, although the increase was mostly in the first 2 months. Median height s.d.s was unchanged throughout this study. There was a significant association between dietary intake and weight gain (r=0.8 P<0.01) but not height gain. Persistent micronutrient deficits beyond diagnosis were seen for both iron and vitamin D. CONCLUSIONS: This study has demonstrated that REE does not change significantly through different phases of disease activity, but physical activity is low at diagnosis. Children with Crohn's disease should be screened for deficiencies of iron and vitamin D.

Presenting phenotype of paediatric inflammatory bowel disease in Wessex, Southern England 2010-2013.

AIM: There has been at least a twofold increase in the incidence of paediatric inflammatory bowel disease (PIBD) over the last 20 years; we report the presenting features from 2010 to 2013 and compare with previous data. METHODS: All patients diagnosed with PIBD at University Hospitals Southampton from 2010 to 2013 were identified from an in-house database. Data were obtained from paper and electronic notes. Height, weight and BMI SDS are presented as median values (95% CI). RESULTS: One hundred and seventy-two patients were included (median age at diagnosis 13.5, 115 male); Crohn's disease (CD) - 107, UC - 50, inflammatory bowel disease unclassified (IBDU) - 15. The most common presenting features of CD were abdominal pain (86%), diarrhoea (78.5%) and weight loss (56.1%); 42.1% of patients had all three. In UC blood in stool (92%), diarrhoea (92%) and abdominal pain (88%) were the most common; all three in 76% of patients. CD presented with ileocolonic disease in 52.5%. UC presented with pancolitis in 64%. There was growth delay in CD: height -0.37 (-0.60 to -0.14); weight -1.09 (-1.35 to -0.83). Growth was maintained in UC: height 0.53 (0.19 to 0.87); weight 0.14 (-0.20 to 0.48). CONCLUSION: Paediatric inflammatory bowel disease phenotype remains as extensive despite increasing incidence. Although the classical phenotype is common, a reasonable proportion present with atypical features, normal growth and normal blood markers.

Rising incidence of paediatric inflammatory bowel disease (PIBD) in Wessex, Southern England.

BACKGROUND: There has been a significant increase in the incidence of paediatric inflammatory bowel disease (PIBD) over the last 25 years although there is no recent data from England. We aimed to analyse changes in incidence within a defined English population over the last decade and compare this to recent and historical incidence data from comparable studies. METHODS: The new diagnosis incidence of PIBD (age less than or equal to 16 years) was recorded from a prospective database for a geographically defined area within Southern England (2002-2012). Data were analysed for two separate time periods (cohort 1:2002-2006 and cohort 2:2008-2012) and compared to data from the British Paediatric Surveillance Unit (BPSU) survey in 1998/1999. Data were analysed by age, sex and disease type. RESULTS: There has been an increase in incidence of PIBD from 6.39/100,000/year during cohort 1 to 9.37/100,000/year during cohort 2 (p=0.0002). This compares with the BPSU incidence data in England (1998-1999) of 5.2/100,000/year. There was no statistically significant difference in median age of diagnosis between cohorts (p=0.46). The incidence of Crohn's disease (CD) was 3.8/100,000/year in cohort 1 rising to 5.85/100,000/year in cohort 2 (p=0.001). The incidence of ulcerative colitis (UC) was 2.01/100,000/year in cohort 1 rising to 2.62/100,000/year in cohort 2 (p=0.1458). Overall PIBD incidence is higher in males in cohort 1 (male-to-female ratio 1.35:1) and cohort 2 (male-to-female ratio 1.5:1). CONCLUSIONS: The incidence of PIBD continues to increase with a rise of almost 50% in the last decade in Southern England. The reasons for this increase remain unclear.

Surgery for children with Crohn's disease: indications, complications and outcome.

BACKGROUND: Outcome data for surgery in paediatric Crohn's disease are limited. We report 10 years' experience at a regional paediatric gastroenterology centre. METHODS: Children undergoing surgery for Crohn's disease (January 2002-December 2012) were identified from an onsite patient register. Patients were followed until transition to adult services. Data were obtained from medical records and are expressed as median (range). RESULTS: Sixty-nine children, aged 13.8 years (6.3-17.0) at diagnosis, were included. 42 were male (61%). Follow-up was 1.8 years (27 days-6 years). Surgery followed diagnosis by 9 months (0 days-7 years). 52 children (75%) received thiopurines and 5 (7%) anti-TNF (tumour necrosis factor) therapy preoperatively. 58 (84%) underwent intra-abdominal surgery (40 right hemicolectomy, 8 stoma formation, 2 subtotal colectomy, 2 small bowel resection, 6 other) and 10 (14%) underwent surgery for perianal disease. The commonest indications for intra-abdominal surgery were stricturing disease 35 (60%) and unresponsive luminal disease 13 (22%). There were 13 (22%) early, and 5 (8.6%) late, complications following intra-abdominal surgery. Nine children had disease relapse, five required further surgery. Height SD scores (SDS) did not increase between diagnosis; -0.5 (-3.4-2.1) and most recent follow up; -0.4 (-3.0-1.1). Body Mass Index (BMI) SDS increased from -1.0 (-6.3-1.5) to -0.3 (-3.3-2.0) (p<0.05). CONCLUSIONS: Surgery was associated with a 22% early complication rate and a 15% risk of relapse. 21% of patients required a second unplanned intra-abdominal procedure. Surgical intervention was associated with an increase in BMI SDS, but not in height SDS.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease.

BACKGROUND: Adalimumab is efficacious therapy for adults with Crohn's disease (CD). AIM: To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. METHODS: British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow-up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). RESULTS: Seventy-two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric-centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1-17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ(2) 8.8, P=0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). CONCLUSIONS: Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.

Recognition and treatment of genitourinary complications in paediatric Crohn's disease using Infliximab.

UNLABELLED: Although genitourinary complications of Crohn's are well recognized, available information regarding their clinical course and management is sparse especially in the paediatric population. We report a myriad of urological complications in five paediatric cases, our experience from a tertiary paediatric urological and gastroenterological centre. All children with urological complications had severe Crohn's disease which necessitated the use of immuno-suppressants including Infliximab. Three of four children healed and closed their fistulas after treatment, although failed to avoid future surgery, albeit for other reasons. CONCLUSION: We suggest Infliximab should be considered as a treatment option but in the absence of a common consensus, treatment be tailored to individual cases.

Outcome of childhood ulcerative colitis at 2 years.

AIM: Ulcerative Colitis (UC) has an incidence of 1.4 per 100,000 in childhood. There is a paucity of data regarding outcome particularly with the increased use of early immunosuppression. This study reviews outcome at 2 years in a cohort with UC referred to a single centre. METHOD: Patients were recruited on the basis of a diagnosis made between 2000 and 2003 as a consecutive cohort. All had UC according to standard clinicopathological criteria. Children with indeterminate colitis were excluded. Follow-up data was collected at 2 years by case notes review. RESULTS: Thirty-two children are reported. The median age at diagnosis was 11 years (range 2-16). All were treated with corticosteroids and 5-ASA derivatives at diagnosis. The majority of patients (94%, 30/32) received more than one course of steroids. By 2 years azathioprine use was high with 75% (24/32) of patients on treatment for steroid-dependent disease. There were 6 extra-intestinal manifestations and 8 disease related complications occurring in 12 patients (38%). The colectomy rate was 9% (3/32) for unresponsive disease. CONCLUSION: There is a high need for Azathioprine in childhood UC. Colectomy rate at 2 years was around 10%. Extra-intestinal manifestations and disease related complications are common.

Infliximab delays but does not avoid the need for surgery in treatment-resistant pediatric Crohn' disease.

The aim of this study was to review the impact of infliximab therapy on children with treatment-resistant Crohn's disease. Treatment resistance was defined as clinically active disease despite >4 months of immunosuppressive therapy. The outcome variables were time to first remission, duration of remission and the need for surgery. 24 children received 90 infusions of infliximab (16 boys; median 10.3y, range 1.0-14.4y); all had three infusions as an induction course. 17 (70.8%) achieved clinical remission, with 14/17 (82.3%) relapsing within 4 months of the third infusion. 6/7 in the non-responding group and 8/17 of the responders required surgery with an insignificant difference in the median time to surgery (p=0.49). Four remain dependent on regular infliximab. Infliximab is well-tolerated and highly effective in achieving clinical remission in children with refractory Crohn's disease but may only delay and not avoid the need for surgery. Failure to achieve clinical remission by the 3rd infusion significantly increases the risk of surgery.

Inflammatory bowel disease.

Twenty five per cent of inflammatory bowel disease presents in childhood. Growth and nutrition are key issues in the management with the aim of treatment being to induce and then maintain disease remission with minimal side effects. Only 25% of Crohn's disease presents with the classic triad of abdominal pain, weight loss, and diarrhoea. Most children with ulcerative colitis have blood in the stool at presentation. Inflammatory markers are usually although not invariably raised at presentation (particularly in Crohn's disease). Full investigation includes upper gastrointestinal endoscopy and ileocolonoscopy. Treatment requires multidisciplinary input as part of a clinical network led by a paediatrician with special expertise in the management of the condition.

Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory bowel disease.

BACKGROUND: Discrimination between ulcerative colitis (UC) and Crohn disease (CD) may be difficult on ileo-colonoscopy alone because of a lack of definitive lesions. Retrospective studies show upper gastrointestinal endoscopy may be helpful in confirming diagnosis in such cases. AIMS: To prospectively determine importance of upper gastrointestinal endoscopy in diagnosis of inflammatory bowel disease (IBD) and assess factors predictive of upper gastrointestinal involvement in IBD. METHODS: All pediatric patients were enrolled prospectively and consecutively over a 2-year period and investigated with an ileo-colonoscopy and barium meal follow-through. Children with procto-sigmoiditis, later confirmed histologically to be typical of UC, were excluded from the study. The remainder underwent upper gastrointestinal endoscopy. The protocol and methodology were determined a priori. RESULTS: 65 children suspected of IBD underwent colonoscopy. Of the total, 11 had recto-sigmoiditis with typical macroscopic appearances of UC; once this was confirmed on histology these patients were excluded from the study. Of the 54 children (males, 31; median age, 11.1 years) remaining, 23 were initially diagnosed with CD on ileo-colonoscopy and 18 (33%) were diagnosed with UC. The diagnosis remained ambiguous in 13 (six colonic, four ileo-colonic, three normal colon) on clinical, radiologic and histologic grounds. Upper GI endoscopy helped to confirm CD in a further 11 (20.4%). Two patients were diagnosed with indeterminate colitis. Upper gastrointestinal inflammation was seen in 29 of 54 (22 CD; 7 UC ). Epigastric and abdominal pain, nausea and vomiting, weight loss and pan-ileocolitis were predictive of upper gastrointestinal involvement (P < 0.05). However, 9 children with upper gastrointestinal involvement were asymptomatic at presentation (31%). Overall upper gastrointestinal tract inflammation was most common in the stomach (67%), followed by the esophagus (54%) and duodenum (22%). CONCLUSIONS: Upper gastrointestinal tract endoscopy should be part of the first-line investigation in all new cases suspected of IBD. Absence of specific upper gastrointestinal symptoms do not preclude presence of upper gastrointestinal inflammation.

Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition.

BACKGROUND: Crohn's disease is a chronic debilitating disorder affecting a child's physical and emotional well-being. Recent emphasis on 'quality of life' (QOL) has led to re-evaluation of available medical treatments. AIM: To assess prospectively change in QOL, clinical disease activity and intestinal mucosal inflammation in active paediatric Crohn's disease after treatment with exclusive enteral nutrition. In addition, we evaluated whether change in QOL could predict changes in paediatric Crohn's disease activity index (PCDAI) and mucosal inflammation (endoscopic and histologic). METHODS: The IMPACT II questionnaire was used prospectively and longitudinally in 26 consecutively recruited children [16 males (67%), median 14 years, s.d. = 1.7 years] with active Crohn's disease (PCDAI > 20). They were treated with a new polymeric enteral feed (ACD004, Nestle) for a period of 8 weeks. All had PCDAI, QOL and endoscopic assessment at the time of diagnosis and after 8 weeks of treatment. RESULTS: Twenty-three of 26 children achieved a clinical remission at 8 weeks, with improvement in the QOL scores (P < 0.05). The change in QOL score after treatment was predictive of achieving a clinical remission, but not of histological improvement. CONCLUSIONS: Although children may find dietary restrictions difficult, this study confirms a clear improvement in QOL after treatment with exclusive enteral nutrition. However, improvement in QOL scores is not reflected by improvement in mucosal inflammation. Whilst improving QOL remains a core principal in patient management, the long-term consequences of ongoing mucosal inflammation must be better understood before relying only on short-term QOL measures to dictate treatment choices.

Use of unlicensed and off-label medications in paediatric gastroenterology with a review of the commonly used formularies in the UK.

BACKGROUND: Use of unlicensed and off-label medications is common in hospital based paediatric practice. Whilst inpatient prescription can be closely monitored within the hospital setting, it is subspecialties like paediatric gastroenterology, caring for chronically ill children on an outpatient basis that require administration of regular medications in the community. Local practitioners rely on available paediatric formularies or information provided by the tertiary unit for monitoring and dispensing further prescriptions. AIM: To assess the proportion of unlicensed and off-label medications prescribed in a paediatric gastroenterology unit to children discharged to the community and assess adequacy of information about these medications in commonly used British formularies. METHODS: All prescriptions prescribed over a six-month period (Jan-Jul 2002) either in the paediatric gastroenterology outpatient department or for children discharged home after an inpatient stay, were retrieved from the pharmacy database. The main outcome measures were to assess the proportion of medications prescribed for unlicensed or off-label use. RESULTS: 308 patients received 777 prescriptions of which 384 (49%) were for unlicensed or off-label use. Of these 291 (76%) were off-label; 208 in relation to indication and 83 to child's age. 93 of the prescribed medications were unlicensed; 37 were due to manipulation of formulation. Of the commonly used formularies in the UK, only 'Medication for Children(R)' contained dosage information on more than half (9/13) of the most often prescribed off-label/unlicensed medications in paediatric gastroenterology. CONCLUSIONS: Use of unlicensed and off-label medications remains a problem in paediatric practice. Until licensing laws change and more drugs are licensed in children, paediatric gastroenterologists remain responsible for provision of information to families, local practitioners, nurses and pharmacists. Of the commonly used formularies, 'Medicines for Children' is the most detailed and comprehensive, and should be available to all general practitioners and pharmacists in the UK. Clear communication between specialist units and local practitioners is imperative to ensure safe and effective prescribing to children.

Refeeding syndrome with enteral nutrition in children: a case report, literature review and clinical guidelines.

Refeeding syndrome is a potentially fatal complication of the nutritional management of severely malnourished patients. The syndrome almost always develops during the early stages of refeeding. It can be associated with a severe derangement in electrolyte and fluid balance, and result in significant morbidity and mortality. It is most often reported in adults receiving total parenteral nutrition (TPN), although refeeding with enteral feeds can also precipitate this syndrome. We report what we believe to be the first case of refeeding syndrome in an adolescent with newly diagnosed Crohn's disease. This developed within a few days of starting exclusive polymeric enteral nutrition. A systematic literature review revealed 27 children who developed refeeding syndrome after oral/enteral feeding. Of these, nine died as a direct result of complications of this syndrome. We discuss the implications of this syndrome on clinical practice and propose evidence-based guidelines for its management.

Portal vein thrombosis and pancreatic failure.

We report a case of a child with portal vein thrombosis presenting with protein losing enteropathy. He later developed exocrine and endocrine pancreatic failure. This association has not been reported before.