Percutaneous endoscopic gastrostomy placement in paediatric Crohn's disease patients contributes to both improved nutrition and growth.

AIM: This paper describes the outcomes of gastrostomy feeding in patients with Crohn's disease (CD). METHODS: Patients with CD who attended the Royal Hospital for Children, Glasgow and received gastrostomy feeding for at least two years between 2003 and 2010 were identified from the clinical database. The data recorded included the anthropometric data, CD phenotype, the surgical technique that was used, complications, medication, feed type, median feed, calories, volume and clinical outcomes. RESULTS: The study identified 16 patients (14 male) who had a gastrostomy inserted using a pull technique at a median age of 12.6 years. Of these two required laparoscopic placement. Short-term complications lasting less than one month were experienced by nine (56%) patients and one (6%) experienced long-term complications. Anthropometry significantly improved at follow-up compared to baseline: at 12 months, the body mass index z-score was 1.11 (p = 0.005) and the weight z-score was 0.19 (p < 0.05). At 24 months, the height z-score was -1.03 (p = 0.04). The daily median volume and calories from feeds increased significantly from baseline to post-PEG insertion, from 400 to 738 mL and 705 to 860 kcal/day (p ≤ 0.01). CONCLUSION: Gastrostomy feeding for paediatric patients with CD was associated with improved nutrition, weight gain and growth outcomes.

The inflammatory milieu and the insulin like growth factor axis in children with inflammatory bowel disease following recombinant human growth hormone treatment.

It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.067 mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed as median (range). In the rhGH group, TNFα was 3.1pg/ml (2.9, 100.6) and 3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively (p=0.79). In the rhGH group, IL1ß was 18.0pg/ml (5.0,716.7) and 18.0pg/ml (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was 19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of the twenty-eight other cytokines analysed was different at T+6 in either group. Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3, was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04). Although changes in markers of the GH/IGF-1 axis do show an association with cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not associated with any significant changes in levels of a range of pro and anti-inflammatory cytokine. Careful evaluation of disease process is required in future trials of rhGH in paediatric IBD.

Anti-TNF therapy for paediatric IBD: the Scottish national experience.

BACKGROUND AND AIMS: Biological agents are being increasingly used in the UK for paediatric-onset inflammatory bowel disease (PIBD) despite limited evidence and safety concerns. We evaluated effectiveness and safety in the clinical setting, highlighting drug cost pressures, using our national Scottish PIBD biological registry. METHODS: Complete usage of the biological agents, infliximab (IFX) and adalimumab (ADA) for treatment of PIBD (in those aged <18 years) from 1 January 2000 to 30 September 2010 was collated from all treatments administered within the Scottish Paediatric Gastroenterology, Hepatology and Nutrition (PGHAN) national managed service network (all regional PGHAN centres and paediatric units within their associated district general hospitals). RESULTS: 132 children had biological therapy; 24 required both agents; 114 had Crohn's disease (CD), 16 had ulcerative colitis (UC) and 2 had IBD Unclassified (IBDU). 127 children received IFX to induce remission; 61 entered remission, 49 had partial response and 17 had no response. 72 were given maintenance IFX and 23 required dose escalation. 18 had infusion reactions and 27 had adverse events (infections/other adverse events). 29 had ADA to induce remission (28 CD and 1 UC), 24 after IFX; 10 entered remission, 12 had partial response and 7 had no response. All had maintenance; 19 required dose escalation. 12 children overall required hospitalisation due to drug toxicity. No deaths occurred with either IFX or ADA. CONCLUSIONS: Complete accrual of the Scottish nationwide 'real-life' experience demonstrates moderate effectiveness of anti tumour necrosis factor agents in severe PIBD but duration of effect is limited; significant financial issues (drug cost-need for dose escalation and/or multiple biological usage) and safety issues exist.

Detailed assessment of nutritional status and eating patterns in children with gastrointestinal diseases attending an outpatients clinic and contemporary healthy controls.

BACKGROUND/OBJECTIVES: In the era of modern multidisciplinary clinical management, very little is known about the prevalence and presentation of malnutrition in children with gastrointestinal disorders (GastroD) particularly employing composite, global measures of nutritional status. SUBJECTS/METHODS: Anthropometry, body composition, dietary intake, eating habits and grip strength were assessed with bedside methods in 168 patients from outpatient gastroenterology clinics (n, median (IQR) years; Crohn's disease (CD): n=53, 14.2 (11.6:15.4); ulcerative colitis (UC): n=27, 12.2 (10.7:14.2); coeliac disease: n=31, 9.3 (7.5:13.6); other GastroD: n=57, 9.8 (7.2:13.8)) and compared with 62 contemporary healthy controls (n, median (IQR): 9.8 (6.9:13.8)) and the results of the recent UK, National Diet and Nutritional Survey (NDNS). RESULTS: Children with CD had lower BMI z-scores than controls (median (IQR): -0.3 (-0.9:0.4) vs 0.3 (-0.6:1.4); P=0.02) but only 2% were classified as thin (BMI z-score <-2 s.d.). The prevalence of obesity in children with UC was 19%, 6% in CD, 11% in children with other GastroD and 15% in controls. No difference was found in grip strength measurement between groups. Except for CD children, the proportion of patients with suboptimal micronutrient intake was similar to that of controls and the cohort of children from the latest NDNS. A higher proportion of children with CD had suboptimal intake for riboflavin, vitamin B6 and calcium and consumed significantly more meat products, juices (including carbonated drinks), spreads/jams and crisps and savoury snacks and significantly fewer portions of dairy, fish, fruits and vegetables compared with healthy controls. CONCLUSIONS: GastroD affect children's body composition, growth, strength, dietary intake and eating habits, particularly CD, but to a lesser extent than expected.

Pathophysiology and management of abnormal growth in children with chronic inflammatory bowel disease.

Many children with a variety of chronic diseases suffer from a variable component of chronic inflammation and often have co-existing growth retardation. The aetiology of this growth retardation may be multifactorial and in a condition such as inflammatory bowel disease it includes the effects of the disease on nutrition as well as the effect of drugs such as glucocorticoids. Growth is primarily regulated through the endocrine and paracrine component of the GH/IGF-1 axis which may be modulated by other factors such as sex steroids. There is increasing evidence that this axis may be affected in children with chronic inflammation. An improved understanding of the GH/IGF-1 axis and how it is affected in chronic inflammation will lead to an improved rationale for developing therapeutic regimens that can improve growth in those children whose growth does not improve despite optimal management of the disease. This review will illustrate these aspects by concentrating primarily on the pathophysiology of growth retardation in inflammatory bowel disease and possible interventions for improving growth.

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

BACKGROUND: Exclusive enteral nutrition (EEN) is an effective first line treatment for active paediatric Crohn's disease (CD). AIM: To examine the effect of EEN on short- and long-term clinical outcome together with anthropometric measurements. METHODS: Retrospective case-note review in newly diagnosed CD (<16 years) who completed 8 weeks of EEN. Demographics, anthropometry, disease characteristics and inflammatory markers were collected at EEN initiation and at 1, 2, 6, 12 & 24 months post treatment initiation. EEN response was determined by a patient global assessment. RESULTS: One hundred and nine patients were included (Males 68; Median age: 11.2 years). After 8 weeks EEN, 65 were in remission, 32 improved and 12 had no improvement. By 4 weeks, mean weight/BMI z-score (s.d.) increased (P < 0.02) and between 4 and 8 weeks (P < 0.05). Baseline inflammatory markers all improved significantly by week 4 (albumin, CRP and platelets; all P < 0.01) and ESR (P < 0.00001). 63/109(58%) relapsed during follow-up. 44/63(70%) patients completed a second course of EEN with similar response rate, but lower weight gain (3.3 vs. 5.1 kg, P < 0.05). Height z-score did not change significantly over the 24 months. Introduction of azathioprine within 6 months of diagnosis did not improve height outcomes at 24 months. CONCLUSIONS: Weight and BMI z-score improved with EEN and changes are sustained to 2 years, but height z-score did not. Seventy per cent of patients who relapsed during 2-year follow-up managed a 2nd course of EEN. The optimal therapeutic strategies for length of EEN course and to improve linear growth are awaited.

Impact of inflammatory bowel disease on pubertal growth.

BACKGROUND: Puberty is thought to be commonly affected in adolescents with inflammatory bowel disease (IBD). AIMS: To determine the impact of Crohn's disease (CD) and ulcerative colitis (UC) on the pubertal growth spurt. METHODS: Retrospective study of 30 boys with CD (CD-M), 11 girls with CD (CD-F), 14 boys with UC (UC-M) and 12 girls with UC (UC-F). Pubertal growth was assessed by calculating peak height velocity SDS (PHV SDS), height SDS at diagnosis (Ht(Diag)) and height SDS at PHV (Ht(PHV)) and age at PHV (Age(PHV)). Systemic markers of disease activity were also collected. RESULTS: Altered parameters of pubertal growth were observed in the CD groups compared to the normal population: in the CD-M group, median Ht(Diag) was -0.56 (p = 0.001) and median Age(PHV) was 14.45 years (p = 0.004), and in the CD-F group, median Ht(Diag) was -1.14 (p = 0.007) and Ht(PHV) was -0.79 (p = 0.039). Individually, 8/30 CD-M cases had one or more parameter affected: 2 boys had Ht(Diag )<-2, 3 boys had Ht(PHV) <-2, 2 boys had an Age(PHV) >2 years above population mean, and 2 boys had a PHV SDS <-2. In the whole group, Age(PHV) showed an association with erythrocyte sedimentation rate (r = 0.4; p = 0.005) and an inverse association with BMI (r = 0.4; p = 0.001). CONCLUSION: Disorders of pubertal growth are more likely to occur in CD and, particularly, in boys.

Evaluating the use of metabolite measurement in children receiving treatment with a thiopurine.

BACKGROUND: Clinical response to thiopurine medication is related to the concentration of its metabolites. Proxy measures are traditionally used to assess dose adequacy. We present our experience of using tioguanine (previously known/formerly referred to as thioguanine) metabolite measurements in paediatric patients and evaluate their effect on clinical practice. AIMS: To report our experience of using tioguanine metabolite measurements in paediatric patients and to evaluate their effects on clinical practice. METHODS: The 6-tioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) were measured in children prescribed thiopurine medication for at least 3 months. Data were collected on thiopurine methyl transferase (TPMT) genotype, drug dose, laboratory indices and management changes. Therapeutic 6-TGN levels were defined as 235-400 pmol/8 × 10(8) RBCs. Seventy individuals (30 males) with a median age of 15 years. Underlying diagnoses were 'IBD' (68/70) and two cases of eosinophilic colitis. Sixty-three were treated with azathioprine and seven with mercaptopurine. A total of 103 separate measurements were made. RESULTS: On initial measurement, 68% of patients had 6-TGN levels outside therapeutic levels despite standard thiopurine dosing. Initial 6-TGN levels were significantly higher in patients with TPMT mutations. Toxicity occurred in seven cases. The 6-TGN levels were significantly higher in those with signs of marrow toxicity. The 6-TGN level correlated with WBC, leukocyte count, mean corpuscular volume (MCV) and ΔMCV; however, the ability of each of these to predict therapeutic 6-TGN levels was poor. After initial measurement, management was changed in 25/70 cases (36%). CONCLUSIONS: 6-TGN levels were therapeutic in a minority of those patients who were tested. Proxy measures perform poorly in predicting therapeutic 6-TGN levels. Measuring thiopurine metabolites is useful for dosage adjustment in children, and for the detection of potential toxicity.

Cycled enteral antibiotics reduce sepsis rates in paediatric patients on long-term parenteral nutrition for intestinal failure.

BACKGROUND: Long-term parenteral nutrition has transformed the prognosis for children suffering from intestinal failure. However, parenteral nutrition itself is associated with considerable morbidity and mortality including that caused by sepsis. AIM: To examine a strategy of cycled enteral antibiotics in reducing the incidence of sepsis in paediatric intestinal failure patients. METHODS: Retrospective analysis of the incidence of sepsis rates of patients on long-term parenteral nutrition, at a tertiary paediatric hospital. Patients were separated into those who received cycled enteral antibiotics and a control group. Sepsis rates before and during cycled enteral antibiotics were compared with comparable timeframes between the cycled enteral antibiotics and control groups. Central venous catheter removal rates were also compared. RESULTS: Fifteen patients (eight cycled enteral antibiotics, & seven controls) received 9512 parenteral nutrition days, with a total of 132 sepsis episodes. All eight patients of the treatment group demonstrated a decrease in the frequency of episodes of sepsis following the introduction of cycled enteral antibiotics. The cycled enteral antibiotics group had a significant reduction in infection rate during the treatment period (from 2.14 to 1.06 per 100 parenteral nutrition days, P = 0.014: median effect size -1.04 CI 95%-1.93, -0.22), whereas the controls had no significant change (1.91 - 2.36 per 100 parenteral nutrition days P = 0.402: median effect size 0.92 CI 95%-1.96, 4.17). The central venous catheter survival rates increased in the cycled enteral antibiotics group from 0.44 central venous catheter removals per 100 parenteral nutrition days to 0.27 central venous catheter removals per 100 parenteral nutrition days, although this was not statistically significant. CONCLUSIONS: Cycled enteral antibiotics significantly reduced the rate of sepsis in a small group of paediatric intestinal failure patients. Larger well-designed prospective studies are warranted to further explore this finding.

The aetiology and impact of malnutrition in paediatric inflammatory bowel disease.

Disease-associated undernutrition of all types is very common in paediatric inflammatory bowel disease (IBD). Recent weight loss remains one of the triad of clinical manifestations and a cornerstone for the diagnosis of Crohn's disease (CD), although significantly fewer patients now present as being underweight. Recent evidence suggests that the introduction of medical treatment will quickly restore body weight, although this does not reflect concomitant changes in body composition. CD children present with features of nutritional cachexia with normal fat stores but depleted lean mass. Poor bone health, delayed puberty and growth failure are additional features that further complicate clinical management. Suboptimal nutritional intake is a main determinant of undernutrition, although activation of the immune system and secretion of pro-inflammatory cytokines exert additional independent effects. Biochemically low concentrations of plasma micronutrients are commonly reported in IBD patients, although their interpretation is difficult in the presence of an acute phase response and other indices of body stores adequacy are needed. Anaemia is a common extraintestinal manifestation of the IBD child. Iron-deficient anaemia is the predominant type, with anaemia of chronic disease second. Decreased dietary intake, as a result of decreased appetite and food aversion, is the major cause of undernutrition in paediatric IBD. Altered energy and nutrient requirements, malabsorption and increased gastrointestinal losses are additional factors, although their contribution to undernutrition in paediatric CD needs to be studied further.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

BACKGROUND: It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS: To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING: Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION: Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE: Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS: Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS: Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

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.

Improvement in growth of children with Crohn disease following anti-TNF-α therapy can be independent of pubertal progress and glucocorticoid reduction.

BACKGROUND AND AIM: Treatment with antitumour necrosis factor-α therapy such as infliximab may improve growth in children with Crohn disease (CD), but the extent of improvement in growth and its relation to pubertal progress and glucocorticoid (GC) therapy are unclear. This is a retrospective study of growth, puberty, and disease activity during the 6 months before starting infliximab (T - 6), at baseline (T0), and for the following 6 months (T + 6) and 12 months (T + 12) in children with CD. PATIENTS AND METHODS: The growth and treatment details of 28 children (male, 17) who were given infliximab at a median (10th, 90th) age of 13.1 years (10.0, 15.7) were reviewed. Data on disease markers (C-reactive protein, erythrocyte sedimentation rate, and albumin), total alkaline phosphatase, and a physician's global assessment were also collected. Results are expressed as median (10th, 90th). RESULTS: Of the 28 cases, 21 (75%) demonstrated a clinical response to infliximab treatment. Overall, height velocity (HV) increased from 3.6 cm/y (0.4-7.8) at T0 to 5.5 cm/y (2.1-9.2) at T + 6 (P = 0.003). In infliximab responders, HV increased from 2 cm/y (0.3-7.1) to 6.4 cm/y (2.3-9.1) (P = 0.004) and in the nonresponders, HV remained static at 4.3 cm/y (2.5-8.6) at T0 and 3.0 cm/y (2.0-11.3) (P = 0.701) at T + 6. HV also increased in the subgroup of 13 children who had remained prepubertal from 4.5 cm/y (0.4-8) to 5.5 cm/y (3.3-8.4) (P = 0.050). In the subgroup of 11 children who had a reduction (n = 2) or cessation in GC (n = 9), HV increased from 1.8 cm/y (0.3-8.3) at T0 to 5.6 cm/y (2.2-9.2) at T + 6 (P = 0.14), whereas those children who did not receive GC during the 12 months had an increase from 3.7 cm/y (0.6-6.5) to 6.4 cm/y (2.9-9.0) (P < 0.05). HV at T0 and T + 6 showed a significant association with the average alkaline phosphatase during the prior 6 months (r = 0.39, P < 0.05). HV did not show any association with individual markers of disease activity. CONCLUSIONS: Clinical response to infliximab therapy is associated with an improvement in linear growth in the short term in children with CD. This increase in height may not be simply due to progress in pubertal status or reduction in GC dose.

Effect of testosterone therapy for delayed growth and puberty in boys with inflammatory bowel disease.

BACKGROUND: pubertal delay and growth retardation are common in children with inflammatory bowel disease (IBD). AIMS: To assess pubertal status and growth in a group of boys with IBD undergoing testosterone therapy for pubertal induction. METHODS: retrospective study of height, weight and pubertal status in 8 boys with IBD before and after testosterone therapy. Height velocity (HV) over the 6 months before each assessment was converted to standard deviation score. Markers of disease activity and concomitant medication were recorded. Response was based on an advance in pubertal status and a greater than 50% increase in HV. RESULTS: eight boys with IBD, median age 14.8 years, had pubertal induction using either monthly injections of 50 mg Sustanon or daily 2.5/5 mg Andropatch. Seven boys showed an advance of pubertal status. Six boys had a greater than 50% increase in HV; median HV at T0 was 1.6 cm/year (0, 5) compared with 6.9 cm/year (1, 11.7) at T6 (p = 0.005). C-reactive protein during testosterone therapy had a significant association with HV at T6 (r = -0.786; p = 0.021). CONCLUSION: in most cases, testosterone therapy in boys with IBD and delayed growth and puberty is associated with an advance in pubertal status and an improvement in growth.

The growth hormone insulin-like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation.

CONTEXT: There is scarce knowledge about the growth hormone (GH) insulin-like growth factor-1 (IGF1) axis in children & adolescents with inflammatory bowel disease (IBD) and growth retardation. OBJECTIVE: To describe the pattern of GH and IGF1 secretion in children & adolescents with IBD. DESIGN: A retrospective review of 28 patients (23 M) of IBD (25 Crohn's Disease and three Ulcerative Colitis) and growth retardation who had investigation of the GH/IGF-1 axis. Height velocity (HV) and serum IGF1 were converted to standard deviation score (SDS); to account for delayed puberty in girls over 11 years and boys over 12 years, HV and serum IGF1 SDS were adjusted for bone age. RESULTS: Median (range) age and Ht SDS at the time of endocrine evaluation was 14.3 years (7.7,17.0) and -2.0(-3.6,-0.9), respectively. Median HVSDS over the prior 12 months was -2.2(-7.7,2.8). Median peak serum GH on insulin tolerance test (ITT) was 5.8 mcg/l (1.3, 24.0), and median serum IGF1 SDS was -0.9(-3.1, 0.1). Five of 28 (18%) had a peak serum GH of >12 mcg/l. Overall, four had biochemical evidence of functional GH deficiency (peak GH < 3 mcg/l and IGF1 SDS < 0) and 11 children had biochemical evidence suggesting GH resistance (peak GH > 6 mcg/l and IGF1 SDS < 0). However, only one child had a peak serum GH > 6 mcg/l and a very low IGF1 SDS of <-2.0. There was a negative association between peak serum GH and Ht SDS (r = -0.49, P = 0.008), but there was no association with HV and there was no association between IGF1 SDS and Ht or HV SDS. IGF1 SDS showed a negative association with erythrocyte sedimentation rate (r = -0.41, P = 0.04). CONCLUSION: Growth retardation in children and adolescents with IBD is commonly associated with a range of biochemical abnormalities ranging from functional GH deficiency to GH resistance. In these children, poor relationship between systemic markers of growth and height velocity point to an important role of growth factors at the target organ level in modulating growth in children with IBD. The value of assessing the GH/IGF-1 axis and whether it predicts subsequent response to growth-promoting therapy requires further exploration.

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 Crohn's 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.

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). AIM: To describe our experience of treating CD with an 8-week course of primary EEN and to study factors affecting treatment outcome. METHODS: All CD patients treated with EEN in our centre between 2004 and 2007 were included in the study. Remission was determined by a combination of clinical parameters. Disease phenotype was assigned using published classifications. Inflammatory markers and anthropometry (Z-scores) were calculated before and after treatment. RESULTS: A total of 114 children were treated (four were excluded). Median age at diagnosis was 11.6 years. Fifty-seven (51.8%) were fed orally whilst 53 (48.2%) were fed by tube. Eighty-eight (80%) achieved remission with consequent reductions in erythrocyte sedimentation rate and C-reactive protein (P < 0.001). Patients in remission had comparative improvements in weight (-1.04 cf. -0.40) and BMI Z-scores (-0.98 cf. -0.03) by the end of treatment (P < 0.001). Individuals with isolated terminal ileal disease (n = 4) had lower remission rates than other locations (P = 0.02). No other significant differences in remission rates for any other disease locations were found. CONCLUSIONS: Exclusive enteral nutrition induces clinical remission, normalization of inflammatory markers and improves weight/BMI Z-scores in most patients. This study demonstrates that disease phenotype should not influence clinicians when commencing patients on EEN.

Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) has a high prevalence of coexistent atopy. Filaggrin (FLG) loss-of-function variants (null-alleles) are associated with eczema and asthma in association with eczema. The aim was to assess the contribution of FLG null-alleles to pediatric IBD susceptibility and to coexistent atopy (eczema, asthma, allergic rhinitis, or food allergy). METHODS: FLG variants (R501X and 2282del4) were genotyped in 403 children with IBD, 683 parents, and 996 population controls. RESULTS: In all, 11% of IBD patients carried at least 1 FLG null-allele compared to 11% of population controls (P > 0.4). Carriage of 1 or more null-alleles in patients with atopy (present in 52% of IBD patients) differed from IBD patients without atopy (14% versus 6%, P = 0.01; odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1). The effect of FLG null-alleles was strongest for eczema (19% versus 7%, P = 0.0003; OR 3.3, 95% CI 1.7-6.6) and food allergy (28% versus 8%, P = 0.0001; OR 4.5, 95% CI 2.0-10.0). The presence of more than 1 atopic disease tended to increase the associated OR: eczema + asthma (23% versus 7%, P = 0.001; OR 3.9, 95% CI 1.6-9.1), eczema + asthma + allergic rhinitis (29% versus 7%, P = 0.0006; OR 5.4, 95% CI 1.9-15.4) and eczema + asthma + allergic rhinitis + food allergy (45% versus 6%, P < 10(-4); OR 12.2, 95% CI 3.2-46.3). Logistic regression analysis of IBD cases confirmed the association of carriage of an FLG null-allele with atopy (P = 0.01; OR 2.4, 95% CI 1.2-5.1) and co-occurrence of different forms of atopy (P = 0.003; OR 3.5, 95% CI 1.5-8.1). CONCLUSIONS: Filaggrin null-alleles have no effect on IBD susceptibility but contribute to coexistent eczema and food allergy.

Anti-Saccharomyces cerevisiae antibodies status is associated with oral involvement and disease severity in Crohn disease.

OBJECTIVES: To determine anti-Saccharomyces cerevisiae antibodies (ASCA) status and its relation to disease phenotype in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: A total of 301 Scottish patients with early-onset IBD-197 Crohn disease (CD), 76 ulcerative colitis (UC), 28 indeterminate colitis (IC)-and 78 healthy control individuals were studied. ASCA status (IgA, IgG) was determined by enzyme-linked immunosorbent assay. ASCA status was then analyzed in relation to CD phenotype. RESULTS: Patients with CD had a higher prevalence of ASCA than patients with UC and healthy controls: 82/197 versus 12/76, odds ratio (OR) 3.80 (1.93-7.50) and 82/197 versus 6/78, OR 8.56 (3.55-20.62), respectively. Univariate analysis showed that positive ASCA status was associated with oral CD (17/25 vs 59/153, OR 3.39 [1.38-8.34]), perianal CD (39/77 vs 38/108, OR 1.89 [1.04-3.44]) and the presence of granulomata (63/132 vs 15/52, OR 2.25 [1.13-4.48]) and also with markers of disease severity: raised C-reactive protein (44/90 vs 12/49, OR 2.95[1.36-6.37]), hypoalbuminemia (44/85 vs 20/74, OR 2.28[1.19-4.37]), and surgery (27/49 vs 54/147, OR 2.11 [1.10-4.06]). From multivariate analysis, the presence of oral disease (adjusted P = 0.001, OR 22.22 [3.41-142.86]) and hypoalbuminemia (adjusted P = 0.01, OR 4.78 [1.40-16.39]) was found to be independently associated with ASCA status. No association was demonstrated between ASCA and IBD candidate genes. CONCLUSIONS: Patients with CD had a higher prevalence of ASCA than did other patients with IBD. ASCA status described patients with CD who had a specific phenotype, showing an association with markers of disease severity and oral CD involvement.