Mark R. Oliver

Changing incidence of acute pancreatitis: 10-year experience at the Royal Children's Hospital, Melbourne

Background and Aim:  The aim of this study was to assess the incidence and etiology of acute pancreatitis at a major pediatric referral center in Australia.

Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease.

Aims: To study the effect of gluten-free diet on growth and diabetic control of children with type 1 diabetes mellitus and coeliac disease. Methods: Twenty one children (mean age 7.5 years, range 1.6–12.9) with type 1 diabetes, primarily initially identified on the basis of symptoms and consecutively diagnosed with coeliac disease by biopsy over a 10 year period, were matched by sex, age at onset, and duration of diabetes with two diabetic controls without coeliac disease. Weight, height, haemoglobin A1c, and insulin requirements were measured before and for 12 months after the diagnosis and treatment of coeliac disease. Dietary awareness and adherence were assessed by structured questionnaire. Results: A gluten-free diet resulted in a significant increase in weight-for-age z scores at 12 months after diagnosis (mean increase in z score 0.33) and in BMI (mean increase in z score 0.32). Increases in height did not achieve statistical significance. Controls showed no significant changes in weight, height, or BMI over the same period. Insulin dosage at diagnosis was less in coeliacs than in controls (mean difference 0.16 units/kg/day), but was similar to controls once a gluten-free diet had been established. Questionnaires were obtained in 20 patients. There appeared to be a relation between dietary awareness/adherence and growth parameters, but the small number of patients with “poor/fair” dietary adherence prevented meaningful analysis of this group. Conclusion: Identification and dietary treatment of coeliac disease in children with diabetes improved growth and influenced diabetic control. Evaluation of the outcome of treatment of coeliac disease in diabetics should include assessments of gluten intake.

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.

Slow-transit constipation in childhood.

BACKGROUND/PURPOSE Intestinal neuronal dysplasia (IND) as a cause for severe chronic constipation remains controversial. The authors have identified a deficiency of substance P (SP) immunoreactivity in the colonic nerve fibres of some children with severe constipation, and aim to correlate this with clinical features and transit studies. METHODS Over 100 children with intractable constipation with or without soiling have been assessed by clinical questionnaire, nuclear transit study, and laparoscopic seromuscular biopsy of the colon labelled with antibodies to SP and vasoactive intestinal peptide (VIP) using immunofluorescence. RESULTS More than 30% of children had delayed passage of meconium, and symptoms of constipation appeared by the age of 1 year in 63%. More than 80% had significant delay in colonic transit, and of these, about 80% had reduced SP immunoreactivity in the axons of the colonic circular muscle. A further 6% had heterotopic ganglion cells or hypoplastic ganglia on routine histology. CONCLUSIONS In children with intractable constipation, features of early onset and delayed colonic transit correlated with deficiency of SP in myenteric axons. The authors propose that deficient SP immunoreactivity may be used as a histological marker for severe constipation. Defective excitatory neuromuscular transmission may be the cause of slow colonic transit.

Sixty-year study of incidence of childhood ulcerative colitis finds eleven-fold increase beginning in 1990s.

Background:We sought to define the point at which a recently noted marked increase in the incidence of ulcerative colitis (UC) had occurred in children in Victoria, Australia. Methods:A 60-year retrospective review (1950-2009) of children age 16 years or less diagnosed with UC in the state’s major pediatric centers was performed. Results:In all, 342 children were diagnosed with UC (male to female ratio of 1.25:1.0, median age 10.9 years, interquartile range [IQR] 7.0, 13.2). The overall median annual incidence of UC was 0.36/105 children ⩽16 years of age (IQR 0.18, 0.66). The number of reported cases increased by 11-fold during the study period (P < 0.001). This marked increase appeared to occur from the early 1990s and has yet to plateau. Children diagnosed during the last two decades were older at diagnosis (median 10 years vs. 11.6, P < 0.0001), and had higher weight- and height-for-age z scores than those diagnosed during the first 40 years (mean weight-for-age [standard deviation] 1950−1989: −0.80 [1.56] vs. 1990–2009: −0.11 [1.17], P < 0.001; mean height-for-age 1950–1989: −0.50 [1.15] vs. 1990–2009: –0.13 [1.12], P < 0.05). More recently diagnosed children also had more extensive disease (1950–1989: 52% vs. 1990–2009: 71%, P < 0.01). Conclusions:The incidence of UC has increased markedly in Victorian children since 1990. Although some of this change may be attributable to earlier diagnosis, it is unlikely that this can provide a complete explanation for this still-increasing condition.

Herpes Simplex and Eosinophilic Oesophagitis: The Chicken or the Egg?

Eosinophilic oesophagitis is being recognised more frequently in developed countries (1). It is more commonly seen in male individuals (2) and presents with symptoms of gastroesophageal reflux, dysphagia, and episodes of food bolus obstruction. Many patients have a positive history of atopy (3). In some if not all patients, the isolated eosinophilic inflammation of the oesophagus is thought to be part of an allergic response to food antigens (4) or aeroallergens (eg, pollen), perhaps triggered by environmental factors that predispose the patient to the development of an eosinophilic response in the presence of such antigens or allergens. One such trigger could be a viral agent such as herpes simplex virus (HSV), a common infection in the community. The following case series describes 3 patients with HSV infection in whom the endoscopic features of eosinophilic oesophagitis developed. The implications of a possible link between the 2 conditions are discussed. Eosinophilic oesophagitis is variously defined in the literature. For the purposes of these case reports, it is defined as more than 20 eosinophils per high-power field (>20/HPF) associated with basal cell hyperplasia, reflecting the recently published Melbourne experience (3,5).

Can Celiac Serology Alone be Used as a Marker of Duodenal Mucosal Recovery in Children with Celiac Disease on a Gluten-Free Diet?

OBJECTIVES:Assessment of treatment response in children with celiac disease (CD) after commencing a strict gluten-free diet (GFD) is generally based on the resolution of clinical features and normalization of serology. Recent adult studies have shown that serologic markers do not correlate with mucosal recovery. We aimed (i) to determine whether anti-tissue transglutaminase immunoglobulin (Ig)A (tTG) and anti-deamidated gliadin peptide IgG (DGP) antibodies are sensitive and specific markers of mucosal recovery in children with CD on a GFD for at least 12 months, and (ii) to determine whether a validated dietary questionnaire of compliance can identify patients with mucosal recovery.METHODS:A total of 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies at ≥12 months on GFD, paired with repeat tTG and DGP serology. The biopsies were reviewed in a blinded manner by two histopathologists and graded by Marsh criteria. A validated questionnaire of dietary compliance was also administered.RESULTS:Of 150 children recruited, 27 (18%) had positive serology, 97 (65%) had negative serology, and 26 (17%) had equivocal serology. Of the 97 children with negative serology, none had Marsh type 3 enteropathy. Of the 27 patients with positive serology, only 6 had Marsh type 3 changes. The sensitivity and specificity of serology as a marker of significant mucosal pathology was 75 and 85%, respectively, with a positive predictive value of 22% but a negative predictive value of 98%. Of the 129 (86%) questionnaires completed, 88% reported good or excellent compliance with a GFD (negative predictive value 97%).CONCLUSIONS:This study suggests that follow-up using two serological tests in children with CD on a GFD may obviate the need for repeat mucosal biopsy in the majority of patients. A standardized dietary questionnaire may be useful in identifying patients who require further evaluation.

Synopsis of recent guidelines on pancreatic exocrine insufficiency

Background In recent years, three national gastroenterology societies established guidelines for the diagnosis and therapy of pancreatic exocrine insufficiency (PEI). In addition, the Cochrane Collaboration issued a review. Objective The purpose of this paper is to present an overview of the recommendations and concordance between the four recent published guidelines and stimulate further discussion. Methods A review of the Australian, German and Italian guidelines and the Cochrane review was conducted, and a synthesis was made of common statements. Results There is a high degree of agreement on almost all items within these guidelines, both in the diagnosis of PEI and in terms of therapy and approach to management of PEI. In addition, novel emerging developments are highlighted, such as the fecal elastase-1 test, which is widely used but is not suitable for measuring mild-to-moderate PEI despite its ability to positively establish the diagnosis of severe PEI. One of the few novel tests proving to be useful is the 13C mixed-chain triglycerides (MCT) breath test. This test, albeit an excellent quantitative test, is not widely used and is rarely available. The use of this test is making it apparent that there is a difference between treating the symptoms of PEI and treating malnutrition, the broader underlying defect. This may have direct consequences for the dosing of pancreatic enzymes (pancreatin), in that the consensus starting dose of all guidelines may be too low for some patients. Although chronic pancreatitis in adults and cystic fibrosis in children account for the main evidence base used for PEI, other indications are also discussed. Conclusions There is good concordance between recommendations provided by international groups. More prospective studies are required in many areas, including the use of pancreatic enzymes in other gastrointestinal disorders, such as celiac disease and irritable bowel syndrome (IBS). We also need to assess the feasibility of the 13C MCT breath test. At the same time, it needs to be confirmed that higher doses of pancreatic enzymes are really necessary to not only relieve the symptoms of PEI but also treat malnutrition appropriately.

Severe colonic diverticulitis in an adolescent with Williams syndrome.

Abstract:  Williams Syndrome (WS) is a condition with multisystemic involvement caused by a genetic deletion in chromosome 7. Colonic diverticulosis has been described in adults with WS; however, it has not previously been reported in adolescents with WS. We report an adolescent boy with WS who developed complicated colonic diverticulitis and briefly review the possible aetiology of diverticular disease.

An australian audit of vaccination status in children and adolescents with inflammatory bowel disease

BackgroundChildren and adolescents with inflammatory bowel disease (IBD) are at increased risk of vaccine preventable diseases (VPD). This includes invasive pneumococcal disease and influenza. The primary aim of this study was to describe compliance with current Australian guidelines for vaccination of children and adolescents diagnosed with IBD. A secondary aim was to review the serological screening for VPD.MethodsA random sample of patients (0-18 years at diagnosis), were selected from the Victoria Australia state based Pediatric Inflammatory Bowel Disease Register. A multi-faceted retrospective review of immunization status was undertaken, with hospital records audited, a telephone interview survey conducted with consenting parents and the vaccination history was checked against the primary care physician and Australian Childhood Immunization Register (ACIR) records. The routine primary childhood vaccinations and administration of the recommended additional influenza and pneumococcal vaccines was clarified.ResultsThis 2007 audit reviewed the immunization status of 101individuals on the Victorian Pediatric IBD database. Median age at diagnosis was 12.1 years, 50% were on active immunosuppressive therapy. 90% (38/42) [95% confidence intervals (CI) 77%; 97%] with complete immunization information were up-to-date with routine primary immunizations. Only 5% (5/101) [95% CI 2%; 11%] received a recommended pneumococcal vaccine booster and 10% (10/101) [95% CI 5%; 17%] had evidence of having ever received a seasonal influenza vaccine. Those living in rural Victoria (p = 0.005) and younger at the age of diagnosis (p = 0.002) were more likely to have ever received an influenza vaccine Serological testing, reviewing historical protection from VPD, identified 18% (17/94) with evidence of at least one serology sample.ConclusionThis study highlights poor compliance in IBD patients for additional recommended vaccines. A multi-faceted approach is required to maximize protection from VPD in this vulnerable special risk population.