Collin C. Barker

Can Tissue Transglutaminase Antibody Titers Replace Small-Bowel Biopsy to Diagnose Celiac Disease in Select Pediatric Populations?

Objectives. The use of screening tests for celiac disease has increased the number of patients referred for evaluation. We proposed that the subgroup of patients with very high tissue transglutaminase antibody (TTG) titers is positive for celiac disease and a small-bowel biopsy is not necessary to make the diagnosis. A gluten-free diet should be attempted and, if the patient’s symptoms do not improve, then a biopsy should be performed to confirm the diagnosis. Methods. A chart review of data for 103 patients who underwent both TTG testing and a small-bowel biopsy was performed. We examined the impact of using TTG values of >100 U and <20 U as cutoff values and suggested performing biopsies for patients with TTG values of 20 to 100 U, as is current practice. Results. Fifty-eight of 103 patients demonstrated positive biopsy results. Forty-nine of 103 patients had TTG levels of >100 U, with 48 of 49 exhibiting positive biopsy results. Only 7 of 16 patients with TTG values of 20 to 100 U exhibited positive biopsy results. Three patients with TTG levels of <20 U had positive biopsies; 2 were IgA negative and 1 had a duodenal ulcer. With the cutoff values of >100 U and <20 U with known IgA status, the sensitivity was 0.980 (48 of 49 cases) and the specificity was 0.972 (35 of 36 cases). An incremental cost analysis found that this proposal could potentially decrease the costs of investigation and diagnosis by almost 30%. Conclusions. When the cutoff values were changed to >100 and <20 U and IgA levels were verified, the sensitivity and specificity were very high. Patients with mid-range TTG values (20–100 U) or values of <20 U with negative IgA status should continue to undergo biopsies for diagnosis of celiac disease.

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.

Biliary Atresia in Canada: The Effect of Centre Caseload Experience on Outcome

Objectives: Biliary atresia (BA) is a leading cause of end-stage paediatric liver disease. Standard BA treatment is sequential surgery with an initial Kasai procedure (KP) followed by liver transplant (LT) for patients who progress to liver failure. A key determinant for the post-KP patient survival with their native liver is patient age at KP (older age, poorer outcome). Recently, European studies have reported that caseload experience influences prognosis with centres managing <5 cases per year (UK) or <2 cases per year (France) having worse survival. Our study investigates the effect of caseload experience on outcomes of Canadian patients with BA. Patients and Methods: A national database of cases with BA, born from 1992 to 2002, was examined. Patients were grouped according to treatment centre size (A: on average <1 case per year; B: 1 to 3 cases per year; and C: >3 cases per year). Overall patient, post-KP native liver, and LT survivals were compared between centres. Outcome parameters were reevaluated for patients grouped by the largest Canadian centre (>5 cases per year) and all other centres (<5 cases per year). Results: Two-hundred thirty patients were identified among 6 group A, 4 group B, and 2 group C centres. The overall median age at KP was 64 days. There were no significant differences in patient, post-KP native liver, or LT survivals between the sized centres and even the largest centre, with the overall 4-year post-KP native liver survival being 39%. Conclusions: Caseload experience does not importantly affect the outcomes for Canadian children with BA. Although outcomes in Canada are comparable to those elsewhere, national policies directed towards timely referral and earlier age at KP rather than centralisation of care are needed.

Does Adjuvant Steroid Therapy Post-Kasai Portoenterostomy Improve the Outcome of Biliary Atresia? A Systematic Review and Meta-Analysis

BACKGROUND The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear. OBJECTIVE To systematically review the literature and perform a meta-analysis to determine the efficacy of adjuvant steroid therapy post-Kasai portoenterostomy (KP) on BA outcome. METHODS A systematic review and meta-analysis of randomized trials and⁄or observational studies that examined the role of steroids on BA outcomes published between January 1969 and June 2010 was conducted. Studies were identified using the Medline, PubMed, EMBASE and Cochrane databases. RESULTS Sixteen observational studies and one randomized controlled trial (RCT) were found. Four of the 16 observational studies (160 participants) and the RCT (73 participants) met the entry criteria and were eligible to be included in the analysis. There was no statistically significant difference in the effect of steroids either on normalizing serum bilirubin levels at six months (pooled OR 1.48 [95% CI 0.67 to 3.28]) or in delaying the need for early liver transplantation (within the first year post-KP (pooled OR 0.59 [95% CI 0.21 to 1.72]). CONCLUSION The present meta-analysis did not find a significant effect of steroid over standard therapy, either in normalizing serum bilirubin levels at six months or at delaying the need for early liver transplantation post-KP. RCT studies of sufficient size and comprehensive design using high-dose steroids are needed to determine the effectiveness of steroids on the short and intermediate post-KP outcomes for BA patients.

Biliary atresia with associated structural malformations in Canadian infants

Background: Biliary atresia (BA) is associated with extrahepatic congenital malformations in a minority of affected infants. The term commonly applied to this subgroup is ‘BASM’ for biliary atresia splenic malformation syndrome, as spleen abnormalities are prominent.

25-Hydroxyvitamin D Concentrations in Children with Crohn's Disease Supplemented with Either 2000 or 400 IU Daily for 6 Months: A Randomized Controlled Study

OBJECTIVES To assess vitamin D status of pediatric patients with Crohns disease (CD) and to compare their serum 25-hydroxyvitamin D (s-25OHD) with established cutoffs and assess whether 6 months of supplementation with 2000 IU/d, vs 400 IU/d, would reduce the group prevalence of vitamin D below these cutoffs. STUDY DESIGN Subjects 8-18 years (n = 83) with quiescent CD were randomized to either 400 or 2000 IU vitamin D3/d for 6 months. RESULTS Baseline mean ± SD s-25OHD was 24 ± 8 ng/mL; 13 subjects (16%) had an s-25OHD <16 ng/mL, 27 (33%) < 20 ng/mL, and 65 (79%) < 30 ng/mL. There was no significant difference between groups in achieving the cutoffs of 16 ng/mL or 20 ng/mL at 6 months; however, only 35% of the 400 IU group achieved the greater cutoff of 30 ng/mL compared with 74% in the 2000 IU group (P < .001). Baseline adjusted mean s-25OHD concentrations at 6 months were 9.6 ng/mL (95% CI 6.0-13.2, P < .001) greater in the 2000 IU than the 400 IU group. Disease activity was not affected by supplement dose. Few subjects exceeded safety marker cutoffs, and this did not differ by dose. CONCLUSIONS At baseline, a high proportion of patients had a mean s-25OHD >20 ng/mL. 2000 IU vitamin D3/d is more effective in raising s-25OHD concentrations to > 30 ng/mL in children with CD than 400 IU/d, but both treatments were equally effective at achieving 16 or 20 ng/mL.

Crohn-like enteritis presenting as hypoglycemia in a patient with glycogen storage disease type 1b, treated with granulocyte colony-stimulating factor and splenectomy.

Glycogen storage disease type 1b (GSD 1b) results from a defect in the microsomal membrane translocase system for glucose-6-phosphate. Glycogen storage disease type 1a (GSD 1a) differs from GSD 1b in that it results from a defect in the enzyme glucose-6phosphatase (1,2). This defect associated with GSD 1b inhibits the hydrolysis of glucose-6-phosphate by the microsome for transport into the lumen of the endoplasmic reticulum of hepatocytes (1). Features associated with GSD 1b, as in GSD 1a, include hypoglycemia, hepatomegaly, growth failure, lactic acidosis, hyperuricemia, and hyperlipidemia. Recurrent infection secondary to neutropenia and neutrophil dysfunction is a distinctive feature of GSD type 1b (3). Impaired neutrophil chemotaxis, mobilization, decreased superoxide production, and maturational arrest at various stages of myeloid development all contribute to the abnormal neutrophil function observed in this condition (3–5). Other associations include Crohn-like enteritis (6,7), oral and anal ulcerations (4), esophagitis (7), and iron deficiency anemia (5). Neutropenia and neutrophil dysfunction are probable causes of Crohn-like enteritis in GSD 1b. Crohn-like enteritis also has been reported in patients with neutropenia and other diseases characterized by neutrophil dysfunction, such as chronic granulomatous disease (8,9). Treatment with granulocyte colony-stimulating factor (G-CSF) improves neutropenia, neutrophil function, and Crohn-like enteritis in patients with GSD 1b (5,10,11). The purpose of this report is to increase awareness that hypoglycemia may be a sign of Crohn-like enteritis in patients with GSD 1b who have responded previously to G-CSF. Furthermore, as a consequence of G-CSF therapy, splenomegaly developed in the patient described in this case report. Splenectomy was performed to treat this side effect. CASE REPORT