Daniel A. Lemberg

Inflammatory Bowel Disease in the South Asian Pediatric Population of British Columbia

BACKGROUND:Geographical differences, population migration, and changing demographics suggest an environmental role in prevalence, modulation, and phenotypic expression of inflammatory bowel disease (IBD).AIM:To determine the incidence of IBD and disease subtype in the pediatric South Asian population in British Columbia (BC) compared with non-South Asian IBD patients in the same geographic area.METHODS:Chart review with data collected for all patients ≤16 yr of age diagnosed with IBD at B.C. Childrens hospital, January 1985 to June 2005. Age, gender, family history, duration of symptoms, type, and extent of disease were extracted. Identified South Asian subjects were prospectively interviewed.RESULTS:Seventy-five South Asian patients were diagnosed with IBD, 48% Crohns disease (CD), 33.3% ulcerative colitis (UC), and 18.7% with indeterminate colitis (IC), in contrast to 71%, 18.8%, and 10.2%, respectively, in the non-South Asian population. The incidence rate for South Asian IBD patients, for the period 1996–2001 was 15.19/105 (6.41/105 for CD, 6.70/105 for UC, and 2.08/105 for IC) compared with 5.19/105 for the non-South Asian IBD group (3.69/105, 0.96/105, and 0.54/105, respectively). The South Asian male/female ratio was significantly different from that observed for the rest of the population.CONCLUSION:These data suggest a significantly higher incidence of IBD in the South Asian pediatric population compared with the rest of the BC pediatric population, with a different pattern of phenotypic expression, a male predominance, and more extensive colonic disease. These data suggest a potential effect of migration, and environmental and lifestyle change on the incidence of IBD and disease subtype.

Exclusive enteral feeding as primary therapy for Crohn’s disease in Australian children and adolescents: A feasible and effective approach

Background:  Exclusive enteral feeding has been shown to be as efficacious as corticosteroids in inducing remission in children with Crohn’s disease (CD), with additional nutritional benefits. The use of polymeric formulae provides superior palatability and acceptance over elemental feeds, but polymeric formulae have not been universally adopted. The present retrospective analysis of enteral feeding in children with Crohn’s disease aims to demonstrate the short‐term benefits of enteral feeding in children upon disease activity and nutrition parameters.

Systematic review: nutritional therapy in paediatric Crohn's disease.

Background At least 25% of individuals diagnosed with Crohn’s disease (CD) have onset of disease in childhood. Almost all children with CD have nutritional impairments, such as weight loss or stunting, at diagnosis or subsequently. Nutritional therapy (exclusive enteral nutrition) is established as a valid and effective treatment in paediatric CD. The advantages of this approach are induction of remission and control of inflammatory changes, mucosal healing, positive benefits to growth and overall nutritional status, and avoidance of other medical therapies.

Campylobacter concisus and other Campylobacter species in children with newly diagnosed Crohn's disease

Background: Campylobacter concisus and other members of the Campylobacter genus have recently been suggested as possible etiological agents of Crohns disease (CD). To further investigate this issue we determined the prevalence of these organisms in pediatric patients newly diagnosed with CD. Methods: DNA was extracted from fecal specimens collected from 54 children with CD, 27 noninflammatory bowel disease (non‐IBD), and 33 healthy controls and subjected to polymerase chain reaction (PCR) sequencing. Results: Detection of C. concisus DNA using a newly developed PCR assay targeting the 16S rRNA gene of C. concisus showed that 65% (35/54) of fecal samples from CD children were positive, a prevalence significantly higher than that in the healthy (33%, 11/33, P = 0.008) and non‐IBD controls (37%, 10/27, P = 0.03). The prevalence of all Campylobacter DNA using genus‐specific primers in children with CD was 72% (39/54), which was significantly higher than the 30% (10/33, P = 0.0002) and 30% (8/27, P = 0.0003) observed in healthy and non‐IBD controls, respectively. Conclusions: Given the strengthening evidence for a significantly higher prevalence of C. concisus and other non‐jejuni Campylobacter species in pediatric CD, investigation into the role of these non‐jejuni Campylobacter species in the initiation of human IBD is clearly a priority. (Inflamm Bowel Dis 2009;)

Defensins and inflammation: The role of defensins in inflammatory bowel disease

Defensins are antimicrobial peptides produced at a variety of epithelial surfaces. In the intestinal tract, they contribute to host immunity and assist in maintaining the balance between protection from pathogens and tolerance to normal flora. However, attenuated expression of defensins compromises host immunity and hence may alter the balance toward inflammation. Altered defensin production is suggested to be an integral element in the pathogenesis of inflammatory bowel disease (IBD). Evidence for this is shown in Crohns disease where reduced α‐defensin levels are seen in patients with ileal disease and reduced β‐defensin levels in those with colonic involvement. Further evidence is provided by research linking nucleotide oligomerization domain 2 (NOD2) mutations and deficient defensin expression. However, alternate studies suggest that NOD2 status and defensin expression are independent, and that defensin deficiency is due to mucosal surface destruction as a result of inflammatory changes, indicating that reduced defensin expression is a symptom of the disease and not the cause. Although it is clear that defensin expression is altered in IBD, it is less clear whether defensin deficiency is implicated in the pathogenesis of IBD or is a consequence of the disease process. The aim of this article is to review the current knowledge of defensins in IBD and discuss their potential role in IBD pathogenesis.

Detection and isolation of Campylobacter species other than C. jejuni from children with Crohn's disease.

ABSTRACT The presence of Campylobacter species other than Campylobacter jejuni and antibodies to Campylobacter concisus in children were investigated. A significantly greater presence of C. concisus and higher levels of antibodies to C. concisus were detected in children with Crohns disease (CD) than in controls. Campylobacter species other than C. jejuni were isolated from intestinal biopsy specimens of children with CD.

Positron emission tomography in the investigation of pediatric inflammatory bowel disease

Background: Endoscopic and radiologic studies are frequently required in inflammatory bowel disease (IBD) to determine disease activity, extent of disease, and delineating disease type. Positron emission tomography (PET) using fluorine‐18‐fluoro‐deoxyglucose to identify metabolically active tissues may offer a simple noninvasive alternative to conventional studies in identification and localization of active intestinal inflammation in children with IBD. The aim of this study was to assess the value of PET in identifying active intestinal inflammation compared with conventional endoscopic and radiologic studies, including small bowel follow‐through and colonoscopy. Methods: Sixty‐five children were enrolled in the study. This included 55 children (mean age, 13.3 yr; range, 7‐18 yr; 20 girls) with newly diagnosed IBD (37) or symptoms suggestive of recurrent disease (18) and 10 children with recurrent abdominal pain (mean age, 12.7 yr; range, 8‐15 yr; 7 girls) who were studied with PET, and the results were compared with small bowel follow‐through with pneumocolon and/or colonoscopy. Thirty‐eight patients had Crohns disease (17 ileal, 12 ileocolic, 5 pancolonic, 3 left‐sided disease, 1 right‐sided disease), and 17 had ulcerative colitis (15 pan‐colitis, 2 left‐sided colitis). Mean time interval between PET and other studies was 30 ± 17.6 days. Results: PET correctly identified active inflammatory disease in 80% of children with IBD (81.5% with Crohns disease; 76.4% with ulcerative colitis) and correctly showed no evidence of inflammation in children with recurrent abdominal pain. Gluorine‐18‐fluoro‐deoxyglucose accumulated at sites that corresponded with active disease at colonoscopy in 83.8% of patients and with small bowel follow‐through with pneumocolon 75.0% of the time. Conclusion: This study suggests that PET offers a noninvasive tool for identifying and localizing active intestinal inflammation in children with IBD. PET may not be able to replace conventional studies; however, it may be useful when conventional studies cannot be performed or fail to be completed.

Microbial Dysbiosis in Pediatric Patients with Crohn's Disease

ABSTRACT Microbial dysbiosis has been suggested to be involved in the pathogenesis of Crohns disease (CD); however, many studies of gut microbial communities have been confounded by environmental and patient-related factors. In this study, the microbial flora of fecal samples from 19 children newly diagnosed with CD and 21 age-matched controls were analyzed using high-throughput sequencing to determine differences in the microbial composition between CD patients and controls. Analysis of the microbial composition of specific bacterial groups revealed that Firmicutes percentages were significantly lower in CD patients than in controls and that this was due largely to changes in the class Clostridia. Bacteroidetes and Proteobacteria percentages were higher and significantly higher in CD patients than in controls, respectively. Both the detection frequencies of Bacteroidetes and Firmicutes correlated (positively and negatively, respectively) with the calculated pediatric Crohns disease activity index scores of patients. Upon further analysis, differences in the microbial compositions of patients with mild disease and moderate to severe disease were identified. Our findings indicate that a combination of different bacterial species or a dynamic interplay between individual species is important for disease and is consistent with the dysbiosis hypothesis of CD.

Update of fecal markers of inflammation in inflammatory bowel disease.

The diagnosis, prognosis, and assessment of disease activity of inflammatory bowel disease (IBD) require investigating clinical, radiological, and histological criteria, as well as serum inflammatory markers. However, a range of fecal inflammatory markers now appears to have the potential to greatly assist in these processes. Calprotectin, a prominent neutrophil protein, was identified two decades ago as a potentially revolutionary marker for IBD. Following this discovery, numerous additional markers, including S100A12, lactoferrin, and M2‐pyruvate kinase, have also been suggested as novel markers of IBD. In the present study, we provide an up‐to‐date review of fecal markers of IBD, and further, provide a novel analysis of each of these fecal markers in severe ulcerative colitis and compare their expression pattern in contrast to calprotectin.

Eosinophilic esophagitis in children with celiac disease

Background and Aims:  Eosinophilic esophagitis and celiac disease are distinct gastrointestinal disorders. The present study in children highlights the possible coexistence of these two conditions. This study also analyzes the epidemiological and clinical profiles of these patients.