Christine Spray

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

Aliment Pharmacol Ther 2011; 33: 946–953

Irritable bowel syndrome: the commonest cause of recurrent abdominal pain in children

Apley, working in Bristol, UK, defined recurrent abdominal pain (RAP) in 1958. After extensive investigations, he found that 8% of children presenting to his clinic with RAP had an organic pathology. The aims of this study were to identify (1) causes of RAP using modern methodology, (2) factors associated with organic RAP and (3) children with none-organic RAP who fulfill the diagnostic criteria for irritable bowel syndrome (IBS). Children, aged over 3 years, presenting with RAP were prospectively recruited to this study. They had a detailed questionnaire completed, a full examination with screening tests (blood for coeliac screen, Helicobacter pylori antibody titre, inflammatory markers, serum amylase, liver function tests, and full blood count, urine and stool analyses and abdominal ultrasonography). Endoscopy and oesophageal pH monitoring were performed if clinically indicated. IBS was diagnosed if the child had no organic pathology and fulfilled the Rome II criteria. Out of 103 children (median age of 10 years, mean 10.04, SD ±3.44,), 31 children (30%) had organic pathologies. Factors associated with organic pain were nocturnal symptoms (P<0. 01) and abdominal tenderness (P<0.005) and with non-organic pain were periumbilical locality (P<0.002), pain alleviation on defaecation (P<0.04) and low fibre diet (P<0.005). Of children with non-organic pain, 37/52 (51%) fulfilled the criteria for IBS (36% of the total). Conclusion:of children presenting with recurrent abdominal pain in a hospital setting, 30% have a diagnosable organic aetiology compared to 8% in Apley’s time. Irritable bowel syndrome, however, may be the commonest cause of recurrent abdominal pain and should be considered.

Feasibility of video capsule endoscopy in the management of children with Peutz-Jeghers syndrome: a blinded comparison with barium enterography for the detection of small bowel polyps.

Objectives: Peutz-Jeghers syndrome (PJS) in children may present with anaemia, intussusception, or obstruction from an early age and surgery is common. Prophylactic polypectomy may reduce subsequent complications. Traditional barium enterography (BE) has poor sensitivity and requires significant radiation. We compared the performance of capsule endoscopy (CE) with BE in children with PJS. Materials and Methods: Children with PJS (ages 6.0–16.5 years) were prospectively recruited and underwent BE followed by CE, each reported by expert reviewers blinded to the alternate modality. Number of “significant” (>10 mm) and total number of polyps were recorded. Child preference was assessed using a visual analogue questionnaire. Definitive findings were assessed at laparotomy or enteroscopy, when performed. Results: There was no significant difference for >10 mm polyp detection. Six polyps were found in 3 children by both modalities: 3 polyps in 2 children at CE, 3 polyps in 1 child at BE (P = 0.50). Re-review of 1 CE identified 3 polyps that were missed in 1 child at initial reading. Significantly more <10 mm polyps were identified by CE than BE: 61 vs 6 (P = 0.02). CE was significantly more comfortable than BE (median score CE 76 [interquartile range 69–87] vs BE 37 [interquartile range 31–68], P = 0.03) and was the preferred investigation in 90% (P = 0.02). Conclusions: CE is a feasible, safe, and sensitive test for small bowel polyp surveillance in children with PJS. It is significantly more comfortable than BE and is the preferred test of most children for future surveillance. There is a learning curve for reporting CE studies in PJS and appropriate training is essential.

Role of methotrexate in the management of Crohn disease.

Background: The majority of children with Crohn disease (CD) are likely to need some form of immunomodulatory therapy to maintain remission and to avoid long-term corticosteroid usage. Although thiopurine agents are commonly used, some children are unresponsive or intolerant to these drugs. Biological agents like infliximab are being increasingly used in these circumstances, but long-term safety has yet to be established. Methotrexate has been shown to induce and maintain remission in CD in many adult studies, but pediatric data are limited. The present report describes our experience of using methotrexate in CD in children. Patients and Methods: All children with CD treated with methotrexate were identified by the departmental database. Case records were reviewed for site of disease, Pediatric Crohn Disease Activity Index, medications, time to achieve remission, duration of remission, and complications. Results: A total of 10 children received methotrexate, 7 of whom were female and 3 of whom were male. All of the children had colonic involvement and had active disease despite previous standard medical treatments. Seven children exhibited remission with methotrexate treatment. Median time to achieve remission was 12 weeks and median duration of remission was 21 months to the point of assessment. One child had transient increase of alanine aminotransferase levels and another developed neutropenia, which remitted with dose reduction. None needed discontinuation of methotrexate treatment. Conclusions: Methotrexate is effective and well tolerated in children with CD. It should be considered in those patients who do not experience a remission with standard medications because it may avoid the use of biological agents and their potential uncertain long-term side effects.

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.

Collagenous gastritis: a case report and review

In this article, we report a case of collagenous gastritis in a child and review the paediatric cases reported to date. Collagenous gastritis is a rare entity, with only less than 30 cases reported so far, including 12 children, since the first description of this entity by Colletti and Trainer in 1989. This is a histological diagnosis characterised by a dramatically thickened subepithelial collagen band in the gastric mucosa associated with an inflammatory infiltrate. Children with this condition often present with epigastric pain and severe anaemia, with no evidence of extragastric involvement, in contrast to the adult patients, where chronic watery diarrhoea is the main presentation due to associated collagenous colitis. A macroscopic pattern of gastritis with nodularity of gastric mucosa, erythema and erosions are characteristic endoscopic findings in paediatric patients. Specific therapy has not been established and resolution of the abnormalities, either endoscopic or histological, has not been documented. In conclusion, collagenous gastritis is a rare entity of unknown aetiology, pathogenesis and prognosis. Gastroenterologists and pathologists need to be aware of this condition when evaluating a child with epigastric pain, anaemia and upper gastrointestinal bleeding, particularly when endoscopy reveals the nodularity of gastric mucosa. The identification, reporting and long-term follow-up of cases will shed more light on this puzzling condition.

Vitamin B12 deficiency presenting as oedema in infants of vegetarian mothers

We report two cases of nutritional vitamin B12 deficiency in infancy, highlighting the importance of B12 supplementation to vegetarian mothers during pregnancy and breast-feeding. The first patient, a 9-month-old Caucasian girl, presented with a 3-week history of generalised puffiness. She was born at term to a vegetarian mother. The infant was exclusively breast-fed as she was not interested in solids. Her height and weight were above the 75th percentile and head circumference just below the 75th percentile. She could sit without support and was pale with an expressionless face. Laboratory investigations demonstrated macrocytic anaemia (haemoglobin 8.3 g/dl, MCV 101.4 fl) and hypoalbuminaemia (23 mg/l). Serum vitamin B12 was low at 49 ng/l (reference range 150–900 ng/l). Ferritin and folate levels were normal. Maternal vitamin B12 level was 185 ng/l. Following intramuscular injections of vitamin B12, her oedema resolved and she became more responsive. Two months later, she had a normal clinical examination and blood parameters had returned to normal. The second patient was a 10-month-old female Caucasian infant, born at term, and admitted for investigation of failure to thrive. From 6 months of age, she had suffered repeated infections. She was exclusively breastfed, as weaning was unsuccessful. Her weight was below the 3rd percentile, height along the 25th percentile and head circumference between the 25th and 50th percentiles. She was unable to sit and was making no attempt to crawl or vocalise. Laboratory investigations showed a haemoglobin of 4.6 g/dl, a blood film confirmed megaloblastic anaemia and the serum albumin was low at 26 g/l. Her vitamin B12 level was 19 ng/l. Serum folate and iron levels were normal. Her mother’s vitamin B12 level was 159 ng/l. Vitamin B12 was given intramuscularly followed by oral vitamin B12 and folate. Within 48 hours, the infant became more alert and active. Two months later, her development was age appropriate. Her height, weight and head circumference were between the 25th and 50th percentiles. All blood parameters had returned to normal. The causes of infantile vitamin B12 deficiency are broadly divided into maternal pernicious anaemia [3] and maternal vegetarian diet [1]. Neonates of vitamin B12 deficient mothers have poor B12 stores [2]. The vitamin B12 content of the breast milk of deficient mothers is low [4]. Neurological findings in the form of apathy, hypotonia and developmental delay are usually noted in exclusively breast-fed infants of vitamin B12 deficient mothers between the 3rd and 6th months of life, along with anaemia and failure to thrive [4]. Presentation with oedema and hypoalbuminaemia has only been reported once in the literature [6]. There are reports of vitamin B12 deficient infants with cerebral atrophy on MRI brain scans [5]. The response of the neurological abnormalities due to vitamin B12 deficiency to treatment is usually quite dramatic [1]. Physicians should be aware of vitamin B12 deficiency in breast-fed infants presenting with anaemia, oedema, failure to thrive and neurological symptoms, when the mothers’ dietary history is suggestive.

Surgical Management of Crohn Disease in Children: Guidelines From the Paediatric IBD Porto Group of ESPGHAN

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

G81(P) Impact of socio-economic position on incidence of Inflammatory Bowel Disease

Background Inflammatory bowel disease (IBD) is understood to result from the interaction of genetic, immunological and environmental factors. There has been a marked increase in the incidence of IBD over the last 25 years, suggesting environmental factors are important. A previous study found a higher incidence of Coeliac disease in the least deprived socioeconomic groups.1 The objective of this study was to investigate the relationship between IBD and socioeconomic position. Methodology Bristol Children’s Hospital is the single regional centre where all children with suspected IBD from the South-west of England are referred. Data was collected prospectively on all children diagnosed between May 2004–March 2013. Socioeconomic status was determined by quintile rank of Index of multiple deprivation score (IMD-10 score) based on postcode at diagnosis. This has been shown to provide a nationally consistent measure of how deprived an area is. Population data was obtained from the 2011 Census. Data was analysed using Pearson Chi Squared test. Children with a postcode outside of the City of Bristol were excluded from the analysis. Results 384 children aged 0–17 years were diagnosed with IBD over the study period of which 50 had a postcode of residence within the City of Bristol. The incidence of IBS was higher in the three lower socio-economic classes compared to the two highest socio-economic classes (see Figure 1). However, the difference in incidence between the socio-economic classes was not statistically significant. Abstract G81(P) Figure 1 Conclusion Our data suggests a higher incidence of diagnosed IBD in children from lower socioeconomic classes which may favour an environmental aetiology. However this did not reach statistical significance, possibly due to small numbers. A larger study is warranted. Reference Whitburn and Sandhu. Coeliac disease and relationship to socio-economic status. Arch Dis Child 2013;98:A86

pANCA and ASCA in Children with IBD-Unclassified, Crohn's Colitis, and Ulcerative Colitis-A Longitudinal Report from the IBD Porto Group of ESPGHAN.

Introduction:No study to date has evaluated perinuclear antineutrophil cytoplasmic antibody (pANCA) and anti–Saccharomyces cerevisiae antibody (ASCA) in pediatric inflammatory bowel disease–unclassified (IBDU) as compared with Crohns colitis (CC) and ulcerative colitis (UC), which represent the diagnostic challenge. We aimed to explore the diagnostic utility of serology and to assess whether serology can predict disease severity in these subgroups. Methods:This was a multicenter retrospective longitudinal study including 406 children with inflammatory bowel diseases (IBD) from 23 centers affiliated with the Porto group of European Society of Pediatric Gastroenterology, Hepatology and Nutrition (mean age 10.5 ± 3.9, 54% males); 117 (29%) with CC, 143 (35%) with UC, and 146 (36%) with IBDU. Median follow-up period was 2.8 years (interquartile range, 1.6–4.2). Results:The most prevalent serologic profile in IBDU was pANCA−/ASCA− (41%), followed by pANCA+/ASCA− (34%) and pANCA−/ASCA+ (17%). pANCA−/ASCA+ differentiated well between CC versus IBDU (83% specificity, 96% positive predictive value [PPV]) and UC (97% specificity, 90% PPV) patients, albeit with a low negative predictive value (13% and 40%, respectively). pANCA+/ASCA− did not differentiate as well between IBD subgroups, but UC children with pANCA+/ASCA− had more often severe disease at diagnosis (36 [62%] versus 22 [38%], P = 0.033) and needed more often calcineurin inhibitors, biologics, or colectomy (25 [80%] versus 6 [20%], P = 0.026). In CC, double positivity for ASCA and not pANCA−/ASCA+ profile was associated with disease severity. Conclusions:Serology may have some role in predicting disease course and outcomes in colonic IBD, but its routine use needs to be supported by more studies. Serology cannot routinely be recommended for differentiating between IBDU versus CC or UC as a sole diagnostic criterion given its low diagnostic utility.