Donald J. S. Cameron

Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance

BACKGROUND Many infants with cows milk protein intolerance have adverse reactions to soy, casein and whey hydrolysate formula and to other foods. The recent development of Neocate, a hypoallergenic, nutritionally complete infant formula composed of individual amino acids and other nutrients, has enabled these infants to be stabilized. OBJECTIVE We observed the effect of food challenges in infants with reported hypersensitivity to hypoallergenic formulas. METHODS Eighteen infants (median age, 7 1/2 months) were given Neocate formula for 2 months and then underwent a 7-day double-blind placebo-controlled challenge with the formula previously best tolerated. RESULTS In 12 of the 18 infants irritability, vomiting, diarrhea, and/or eczema flares developed during the formula challenge. In two patients symptoms developed immediately, but in the remainder adverse reactions evolved within 7 days (range, 4 to 7 days). Adverse reactions were to soy formula (six patients), whey hydrolysate (two), and casein hydrolysate (four). When infants were 12 months of age, parents reported adverse reactions after the ingestion of other low allergen foods (median, six; from a panel of 10 such foods). CONCLUSION A group of infants with late-onset adverse reactions to soy, extensively hydrolyzed casein, and whey formulas and to other foods has been identified. Neocate formula proved to be an effective substitute formula for these patients.

Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Report on Celiac Disease

Mucosal Biology Research Center and Center for Celiac Research, University of Maryland School of Medicine, Baltimore, MD, {Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile, {Centre for Diarrheal Disease and Nutrition Research, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India, §Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital, Melbourne, Australia, jjDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Hopital Sainte-Justine, University of Montreal, Montreal, Canada, Departments of Pediatrics, Leiden University Medical Center and Free University Medical Center, Amsterdam, the Netherlands, {{Pediatric Gastroenterology and Nutrition Unit, Ntra Sra de Candelaria Universitary Hospital School of Medicine,

Increasing incidence of Crohn's disease in Victorian children

Background: The incidence of Crohns disease has been increasing in Western communities, but there are no published studies which have examined this change in children in Australia. The centralization of pediatric gastroenterology services in Victoria provides an opportunity to examine these changes within one state.

Mycobacterium avium subspecies paratuberculosis in children with early-onset Crohn's disease.

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is the most enduring infectious candidate that may be associated with inflammatory bowel disease (IBD). It is possible that the inconsistencies in the prevalence studies of MAP in adults reflect clinical differences in adult patients studied, including duration of disease and treatment regimens, and also in lack of specificity of some of the assays used. The aim was to determine the presence of MAP in children with symptoms of Crohns disease (CD) and ulcerative colitis (UC), using gut biopsy tissue and peripheral blood mononuclear cells (PBMC) collected at initial endoscopic examination prior to clinical treatment. Methods: Mucosal biopsies and/or PBMC specimens were collected from a total of 142 children, comprising 62 with CD, 26 with UC, and 54 with non‐IBD. MAP‐specific IS900 polymerase chain reaction (PCR) analysis was performed on all biopsies and PBMC specimens. Conventional MAP culture technique was performed on a subset of 10 CD, 2 UC, and 4 non‐IBD patients to isolate MAP. Results: MAP was identified by IS900 PCR significantly more often in mucosal biopsies from CD 39% (22/56) than from non‐IBD 15% (6/39) patients (P < 0.05), and in PBMC from CD 16% (8/50) than from non‐IBD 0% (0/31) patients (P < 0.05). Viable MAP were cultured from mucosal biopsies from 4/10 CD, 0/2 UC, and 0/4 non‐IBD patients, but were not cultured from PBMC specimens. Conclusions: This unique study on the occurrence of MAP in gut tissue and blood from pediatric IBD patients suggests the possible involvement of MAP in the early stages of development of CD in children. Inflamm Bowel Dis 2009

Upper and lower gastrointestinal endoscopy in children and adolescents with Crohn's disease: A prospective study

Fifty‐six children and adolescents with Crohns disease were prospectively investigated with gastroscopy and colonoscopy irrespective of localizing symptoms or signs. Routine biopsies were taken from endoscopically normal and abnormal areas.

Esophageal eosinophilia in children with dysphagia.

Objectives Children occasionally have dysphagia in the absence of an apparent primary cause. Esophageal eosinophilia is sometimes seen in these patients at the time of upper endoscopy but its significance is not clear. Although eosinophilia is regarded by some as a histologic hallmark of childhood reflux esophagitis, it may in fact signal a primary eosinophilic esophagitis in children with dysphagia. Our aim was to evaluate esophagitis, acid reflux determined by pH probe, and esophageal eosinophilia in children with the primary complaint of dysphagia. Methods A retrospective study was performed in 42 children, admitted for investigation of dysphagia, in whom no primary cause could be found. Twenty-one children (mean age ± SD, 10.1 ± 4.0 years) had esophageal eosinophilia and 21 children (8.3 ± 4.7 years) did not. Clinical, endoscopic, manometric and esophageal pH parameters in these two groups were compared. Results Patients with esophageal eosinophilia were more often male (p<0.01) with a history of allergy (p<0.001) and food bolus obstruction (p<0.05) requiring endoscopic removal. Their esophageal mucosa appeared wrinkled and thickened at endoscopy with basal cell proliferation, and large numbers of eosinophils in esophageal mucosal biopsies. Continuous esophageal pH records and motility studies, when obtained, were similar in both groups and were within normal values. Conclusion Children with dysphagia who have esophageal eosinophilia are unlikely to have pathologic gastroesophageal reflux.

Topical application of mitomycin-C in oesophageal strictures.

Background: Benign oesophageal strictures may occur as a complication of caustic ingestion or severe gastro-oesophageal reflux or as a sequela of oesophageal surgery and other fibrosing conditions. The traditional initial treatment of oesophageal strictures is intraluminal dilation; however, even if frequent, this occasionally may not provide adequate oesophageal lumen capacity or give significant symptom-free intervals, and restricturing after dilation is difficult and challenging. Topical postdilation application of an antifibrotic agent, mitomycin-C, in the treatment of an oesophageal stricture has been described. Patients and Methods: Eight centres participated, with a total of 16 patients (4 girls), median age 48 (range 0–276) months. The causes of stricture were as follows: caustic (10), post–trachea-oesophageal fistula repair (2), peptic (2), Crohn disease (1), and dystrophic epidermolysis bullosa (1). The median (range) length and diameter of the strictures were as follows: 22 mm (8–50 mm) and 1.5 mm (1–6 mm). Of the 16 patients, 15 had undergone repeated dilations varying from 3 to more than 1000 (daily self-bouginage) before mitomycin-C, and the median interval between dilations was 4 weeks. Mitomycin-C 0.1 mg/mL was applied after dilation for a median time of 3.5 minutes and a median of 3 (1–12) times. Results: Major success, both endoscopic and clinical improvement or cure, occurred in 10 of 16 patients. In 3 of 16 patients the interval period between dilations increased dramatically. Failure of therapy was considered in 3 of 16. All of the patients remained symptom free for a follow-up time of as long as 5 years. Conclusions: Postdilation application of topical mitomycin-C resulted in major success in 62.5% of patients and partial success in 19%, and it may be a useful strategy in oesophageal strictures of differing causes that are refractory to repeated perendoscopic dilation.

The natural history of intolerance to soy and extensively hydrolyzed formula in infants with multiple food protein intolerance.

Infants (n = 18) with intolerance to extensively hydrolyzed formulas and soy who responded to an L-amino acid-based elemental formula (AAF) were studied until 3 years of age. By 2 years of age most tolerated non-formula foods, and by 3 years only 3 required AAF. Growth normalized during AAF feeding in 4 infants with failure to thrive.

Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing.

Background: The role of bacteriophage in Crohn’s disease (CD) is unknown. This study investigated the abundance of phages in ileal and colonic samples from pediatric CD patients and controls. Methods: Ileal and colonic biopsies from 6 CD patients, gut wash samples from 3 CD patients, and ileal biopsies from 6 noninflammatory bowel disease patients (controls) were analyzed for the presence of bacteriophage using 454 high-throughput pyrosequencing. A sequence-independent single-primer amplification method was used to amplify viral sequences. Results: A total of 186,143 high quality reads were obtained from the 4 sample populations. Contigs and sequence clusters (generated from unassembled singletons) were aligned with sequences from the National Center for Biotechnology Information viral reference database and analyzed by MEGAN. The largest number of viral hits was obtained from the CD gut wash samples (n = 691), followed by CD ileal samples (n = 52), control ileum samples (n = 20), and CD colonic samples (n = 1). The most abundant virus sequences identified belonged to the Caudovirales phage. Conclusions: Our study characterized a diverse phage community in the gut of CD patients. In this study, we have identified differences in phage composition between CD patients and control individuals. The large abundance of phages in CD ileum tissue and CD gut wash sample suggests a role of phage in CD development. The role of phage dysbiosis in CD is currently unknown but opens up a new area of research.

Association between early-life factors and risk of child-onset Crohn's disease among Victorian children born 1983-1998: a birth cohort study.

Background: The incidence of Crohns disease (CD) with onset before age 16 has increased. Several perinatal characteristics have been associated with CD. Our objective was to examine the temporal change in CD incidence by period of birth and the extent that this could be attributed to perinatal characteristics associated with higher CD risk. Methods: A record linkage study was conducted utilizing the perinatal records of Victorian births 1983–1998 inclusive and a state‐based CD registry. Proportional hazards models were used to investigate the perinatal factors in relation to the onset of CD by age 16. Further, a nested case control study was conducted to examine the association between sibling exposure and CD risk. Results: The CD incidence rate for births 1983–1998 was 2.01 (95% confidence interval [CI] 1.79, 2.27) per 100,000 child‐years. A birth cohort effect was demonstrated, with higher CD risk for 1992–1998 versus 1983–1991 births (hazard ratio [HR] 1.56; 95% CI 1.18, 2.06). Perinatal characteristics associated with higher CD risk included urban location, higher socioeconomic status, married mother, a congenital abnormality and delivery by elective cesarean section. Sibling exposure during the first 6 years of life was not associated with CD risk. The increased CD incidence among more recent births was not accounted for by changes in these measured perinatal factors. Conclusions: The temporal increase in CD incidence documented for births up to 1990 has continued for children born after 1991 and was not accounted for by temporal changes in the measured perinatal factors.