Madhur Ravikumara

The changing clinical presentation of coeliac disease

Background: There has been a growing recognition that coeliac disease is much more common than previously recognised, and this has coincided with the increasingly widespread use of serological testing. Aim: To determine whether the age at presentation and the clinical presentation of coeliac disease have changed with the advent of serological testing. Methods: A 21-year review of prospectively recorded data on the mode of presentation of biopsy confirmed coeliac disease in a single regional centre. Presenting features over the past 5 years were compared with those of the previous 16 years. Between 1983 and 1989 (inclusive), no serological testing was undertaken; between 1990 and 1998, antigliadin antibody was used with occasional use of antiendomysial antibody and antireticulin antibody. From 1999 onwards, anti-tissue transglutaminase was used. Results: 86 patients were diagnosed over the 21-year period: 50 children between 1999 and 2004 compared with 25 children between 1990 and 1998 and 11 children between 1983 and 1989. The median age at presentation has risen over the years. Gastrointestinal manifestations as presenting features have decreased dramatically. In the past 5 years, almost one in four children with coeliac disease was diagnosed by targeted screening. Conclusion: This study reports considerable changes in the presentation of coeliac disease—namely, a decreased proportion presenting with gastrointestinal manifestations and a rise in the number of patients without symptoms picked up by targeted screening. Almost one in four children with coeliac disease is now diagnosed by targeted screening. Most children with coeliac disease remain undiagnosed. Paediatricians and primary care physicians should keep the possibility of coeliac disease in mind and have a low threshold for testing, so that the potential long-term problems associated with untreated coeliac disease can be prevented.

Ninety percent of celiac disease is being missed.

Serological screening of 5470 children age 7.5 years from a cohort of 13,971 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) suggested the prevalence of celiac disease (CD) to be at least 1%. ALSPAC is an anonymous study, and hence seropositive children could not be individually identified or undergo biopsy. Inasmuch as all children within ALSPAC suspected of having CD are referred to just 1 center, we aimed to identify children with biopsy-confirmed CD who were likely to be in this cohort and to estimate the magnitude of discrepancy between serology-positive cases and biopsy-confirmed cases. The results suggest that more than 90% of CD in children goes undiagnosed.

Celiac disease and eosinophilic esophagitis: a true association

Background and Aim: Celiac disease (CD) and eosinophilic esophagitis (EE) are distinct disorders with specific clinico-pathological characteristics. Recent reports suggest an association between the 2. The aim of this study was to estimate the prevalence of EE among children diagnosed with CD in our institution in the last 8 years. Materials and Methods: Princess Margaret Hospital in Western Australia is the states only pediatric referral center and the Department of Anatomic Pathology handles almost all of the pediatric gastrointestinal biopsy specimens. All of the children who had histological confirmation of CD between January 2000 and November 2007 were identified. Among this cohort, those who had concurrent esophageal biopsies performed were obtained and those with histology consistent with EE identified. The slides of all of these cases were reviewed. Case notes of children with CD and EE were reviewed for demographic details, symptoms, endoscopic findings, and follow-up data. Results: Among the total of 250 children diagnosed with CD during the study period, 121 had concurrent esophageal biopsies. Ten children had histological findings consistent with EE, although only 7 had endoscopic findings suggestive of EE. Median eosinophil count in these esophageal biopsies was 52 per high power field (range 23–80). Four children had follow-up endoscopies and all 4 demonstrated recovery of duodenal mucosa but persistent esophageal eosinophilia on gluten-free diet. In 3 children resolution of EE occurred after specific treatment of EE. Conclusions: The prevalence of EE in this cohort of children with CD is at least 4%. This is likely to be an underestimation because only 121 of 250 children had concurrent esophageal biopsies. Coexistent EE should be kept in mind in children undergoing endoscopy for suspected CD, and esophageal biopsies should be obtained, irrespective of whether esophageal mucosa appears normal or abnormal at endoscopy.

Assessment and management of nutrition and growth in Rett syndrome.

Objectives: We developed recommendations for the clinical management of poor growth and weight gain in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. Methods: Initial draft recommendations were created based upon literature review and 34 open-ended questions in which the literature was lacking. Statements and questions were made available to an international, multidisciplinary panel of clinicians in an online format and a Microsoft Word–formatted version of the draft via e-mail. Input was sought using a 2-stage modified Delphi process to reach consensus. Items included clinical assessment of growth, anthropometry, feeding difficulties and management to increase energy intake, decrease feeding difficulties, and consideration of gastrostomy. Results: Agreement was achieved on 101 of 112 statements. A comprehensive approach to the management of poor growth in Rett syndrome is recommended that takes into account factors such as feeding difficulties and nutritional needs. A body mass index of approximately the 25th centile can be considered as a reasonable target in clinical practice. Gastrostomy is indicated for extremely poor growth, if there is risk of aspiration and if feeding times are prolonged. Conclusions: These evidence- and consensus-based recommendations have the potential to improve care of nutrition and growth in a rare condition and stimulate research to improve the present limited evidence base.

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.

Gastrointestinal dysmotility in Rett syndrome.

Objectives: Through evidence review and the consensus of an expert panel, we developed recommendations for the clinical management of gastroesophageal reflux disease, constipation, and abdominal bloating in Rett syndrome. Methods: Based on review of the literature and family concerns expressed on RettNet, initial draft recommendations were created. Wherein the literature was lacking, 25 open-ended questions were included. Input from an international, multidisciplinary panel of clinicians was sought using a 2-stage modified Delphi process to reach consensus agreement. Items related to the clinical assessment and management of gastroesophageal reflux disease, constipation, and abdominal bloating. Results: Consensus was achieved on 78 of 85 statements. A comprehensive approach to the assessment of gastroesophageal reflux and reflux disease, constipation, and abdominal bloating was recommended, taking into account impairment of communication skills in Rett syndrome. A stepwise approach to the management was identified with initial use of conservative strategies, escalating to pharmacological measures and surgery, if necessary. Conclusions: Gastrointestinal dysmotility occurs commonly in Rett syndrome. These evidence- and consensus-based recommendations have the potential to improve care of dysmotility issues in a rare condition and stimulate research to improve the present limited evidence base.

Experience of gastrostomy using a quality care framework: The example of rett syndrome

AbstractRett syndrome is one of many severe neurodevelopmental disorders with feeding difficulties. In this study, associations between feeding difficulties, age, MECP2 genotype, and utilization of gastrostomy were investigated. Weight change and family satisfaction following gastrostomy were explored.Data from the longitudinal Australian Rett Syndrome Database whose parents provided data in the 2011 family questionnaire (n = 229) were interrogated. We used logistic regression to model relationships between feeding difficulties, age group, and genotype. Content analysis was used to analyze data on satisfaction following gastrostomy.In those who had never had gastrostomy and who fed orally (n = 166/229), parents of girls <7 years were more concerned about food intake compared with their adult peers (odds ratio [OR] 4.26; 95% confidence interval [CI] 1.29, 14.10). Those with a p.Arg168* mutation were often perceived as eating poorly with nearly a 6-fold increased odds of choking compared to the p.Arg133Cys mutation (OR 5.88; 95% CI 1.27, 27.24). Coughing, choking, or gagging during meals was associated with increased likelihood of later gastrostomy. Sixty-six females (28.8%) had a gastrostomy, and in those, large MECP2 deletions and p.Arg168* mutations were common. Weight-for-age z-scores increased by 0.86 (95% CI 0.41, 1.31) approximately 2 years after surgery. Families were satisfied with gastrostomy and felt less anxious about the care of their child.Mutation type provided some explanation for feeding difficulties. Gastrostomy assisted the management of feeding difficulties and poor weight gain, and was acceptable to families. Our findings are likely applicable to the broader community of children with severe disability.

Epidemiology of Inflammatory Bowel Diseases in Childhood

Inflammatory Bowel Disease (IBD) is common in most industrialised countries and childhood IBD accounts for nearly 30% of total cases. Various studies, mostly from Europe and USA have reported epidemiological characteristics of childhood IBD. The incidence figures vary greatly from region to region and within a region over time. Almost all reported studies have documented an increase in the incidence, mainly of Crohn’s disease over the last few decades. The reasons for the increase are not clear but epidemiological observations have led to many postulates. Incidence in developing countries is perceived to be low, but limited data suggest that it may not be as uncommon as previously thought. IBD can occur at any age but is rare in infancy. Among childhood IBD, early onset IBD appears to be different epidemiologically and is characterised by predominance of colonic involvement and high positive family history. It has become apparent that only about 25% of childhood Crohns disease presents with classical triad of abdominal pain, diarrhoea and weight loss. Pediatricians should be aware of atypical manifestations and should maintain high index of suspicion.Though epidemiological studies of childhood IBD done so far have contributed towards understanding of IBD, they have differed in study design, population, time period, age group and case definitions. Unfortunately there are no uniform, clear diagnostic criteria which are evidence based. To address this problem, recently the IBD working group of European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has published “The Porto Criteria” which details a consensus based diagnostic criteria for the diagnosis of childhood IBD. This should bring uniformity in ascertainment of newly diagnosed IBD cases. An European multicentre prospective database has also been established to facilitate future epidemiological studies.

The long term physical consequences of gastroschisis.

PURPOSE To determine the progress, physical and metabolic outcomes of gastroschisis survivors. METHODS Fifty children born with gastroschisis were assessed with a health questionnaire, physical assessment, bone density and nutritional blood parameters at a median age of 9years (range 5-17). RESULTS After initial abdominal closure, 27/50 (54%) required additional surgical interventions. Ten (20%) children had complex gastroschisis (CG). Abdominal pain was common: weekly in 41%; and requiring hospitalization in 30%. The weight, length and head circumference z-scores improved by a median 0.88 (p=0.001), 0.56 (p=0.006) and 0.74 (p=0.018) of a standard deviation (SD) respectively from birth; 24% were overweight or obese at follow up. However, those with CG had significantly lower median weight z-scores (-0.43 v 0.49, p=0.0004) and body mass index (BMI) (-0.48 v 0.42, p=0.001) at follow up compared to children with simple gastroschisis. Cholesterol levels were elevated in 24% of children. Bone mineral density was reassuring. There were 15 instances of low blood vitamin and mineral levels. CONCLUSIONS Although gastroschisis survival levels are high, many children have significant ongoing morbidity. Children with simple gastroschisis showed significant catch up growth and a quarter had become overweight.

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.