Toba Weinstein

Failure to respond to hepatitis B vaccine in children with celiac disease

Objectives: To determine whether children with celiac disease (CD) fail to show a response to hepatitis B virus (HBV) vaccine more frequently than children without CD. Patients and Methods: This was a prospective study that compared the response to HBV, tetanus, rubella, and Haemophilus influenzae type b (Hib) vaccines between children with CD and age- and sex-matched control subjects. Results: The study population included 26 patients with CD and 18 age- and sex-matched controls. All had received the full complement of childhood vaccinations. A significantly higher proportion of subjects in the CD group (14 of 26) failed to respond to HBV vaccine compared with controls (2 of 18; 53.9% vs 11.1%; P < 0.05). Patients with CD were 8.33 times more likely to test negative for hepatitis B surface antigen than control subjects (95% CI, 1.5–46.5). By contrast, all of the subjects in both groups tested positive for rubella antibodies; only 1 subject in the CD group tested negative for tetanus antibody versus none in the control group (3.9% vs 0%; P = 1.0). The percentage of subjects who tested negative for Hib antibodies was similar in the 2 groups (CD, 33.3%; control, 44.4%; P = 0.53). Conclusions: More than 50% of children with CD do not show a response to standard vaccination regimens for HBV. Given the large number of children with CD throughout the world, this observation suggests that there is a large HBV-susceptible population despite widespread vaccination. Current immunization strategies may need to be reassessed to protect this population and achieve the goal of universal protection.

Pediatric inflammatory bowel disease and imaging-related radiation: are we increasing the likelihood of malignancy?

Background and Aims: Increasing use of diagnostic radiography has led to concern about the malignant potential of ionizing radiation. We aimed to quantify the cumulative effective dose (CED) from diagnostic medical imaging in children with inflammatory bowel disease (IBD) and to identify which children are at greatest risk for high amounts of image-related radiation exposure. Patients and Methods: A retrospective chart review of pediatric IBD patients seen between January 1 and May 30, 2008 was conducted. The effective dose of radiation received from all of the radiology tests performed during the course of each patients treatment was estimated using typical effective doses and our institutions computed tomography dose index. A CED ≥50 mSv was considered high. Results: Complete records were available for 257 of 372 screened subjects. One hundred seventy-one had Crohn disease (CD) and 86 had ulcerative colitis (UC). The mean CED was 17.56 ± 15.91 mSv and was greater for children with CD than for those with UC (20.5 ± 17.5 vs 11.7 ± 9.9 mSv, P < 0.0001). Fifteen children (5.8%) had a CED ≥50 mSv, including 14 of 171 (8.2%) with CD and 1 of 86 (1.2%) with UC (P = 0.02). In children with CD, factors associated with high CED per multivariate analysis were any IBD-related surgery (odds ratio 42, 95% confidence interval 8–223, P < 0.0001) and platelet count (odds ratio 16, 95% confidence interval 1.5–175, P = 0.02). Conclusions: Although all doses of ionizing radiation have some malignancy-inducing potential, a small but important percentage of children with IBD are exposed to particularly high doses of ionizing radiation from diagnostic tests and procedures. Physicians caring for such patients must seek to limit radiation exposure whenever possible to lessen the lifetime risk of malignancy.

Vitamin D in pediatric gastrointestinal disease

Purpose of review The purpose of this review is to examine the prevalence of vitamin D deficiency in pediatric gastrointestinal disease, specifically celiac disease and inflammatory bowel disease (IBD); to discuss the role of vitamin D and its deficiency in gastrointestinal disease pathophysiology; and to present current literature regarding diagnosis and treatment of vitamin D deficiency in these pediatric gastrointestinal diseases. Recent findings Vitamin D deficiency is common in children with gastrointestinal symptoms and disease processes. In celiac disease, vitamin D status should be routinely assessed at the time of diagnosis and during subsequent follow up if deficient. There is growing evidence to suggest an inverse association between vitamin D and IBD activity; however, the therapeutic role of vitamin D in IBD patients requires further investigation. Summary Suboptimal vitamin D status commonly occurs in children with gastrointestinal disease. It is advisable to check serum 25-hydroxy vitamin D levels in children with newly diagnosed celiac disease and IBD. In celiac disease, vitamin D status should be assessed during subsequent follow up if deficient. In IBD, 25-hydroxy vitamin D levels should be checked at least yearly. Therapy should be provided to maintain a level of greater than 30 ng/ml but less than 100 ng/ml; however, the ideal vitamin D dosing regimen to treat vitamin D deficiency and to maintain this optimum level remains unknown. The role of vitamin D as a therapeutic agent in IBD is still under investigation.

Splenic pseudoaneurysm in a child with hereditary pancreatitis.

686 doaneurysm (SAP) fo of pancreatitis. It is b S plenic artery pseu rmation is an uncommon complication elieved to be the result of vascular erosion by pancreatic enzymes, a process that compromises the integrity of the splenic artery wall. The final result is a weak, expanded vessel wall that may hemorrhage into the peritoneal cavity or retroperitoneal space (1). There are no known reports of SAP in the pediatric population or in patients with hereditary pancreatitis. We report a case of SAP formation in a 5-year-old child with hereditary pancreatitis that was successfully managed via transcatheter coil embolization of the splenic artery.

Polymorphisms in the tumor necrosis factor/lipopolysaccharides pathway in Crohn disease in the Jewish Ashkenazi population.

Objective: Tumor necrosis factor (TNF)-α plays a role in the inflammatory process in Crohn disease, a disease with an apparent polygenic basis. We investigated whether polymorphisms in multiple genes involved in the lipopolysaccharide–TNF inflammatory pathway are independently associated with Crohn disease in the Jewish Ashkenazi population. Polymorphisms in CD14, Toll-like receptor 4 (TLR4), and TNF-α were studied. In addition, we investigated polymorphisms in the TNF-α converting enzyme (TACE) gene, which to date has not been studied for an association with Crohn disease. Patients and Methods: To examine whether TLR4 Asp299Gly, CD14-260C/T, TNF-1031T/C, TNF-863C/A, TNF-857C/T, TACE-172C/T, and TACE-154C/A polymorphisms are associated with Crohn disease in the Ashkenazi Jewish population, we analyzed families with at least 1 child with Crohn disease for association with these mutations using a family-based association test (transmission disequilibrium test) for analysis. Results: The allelic frequency in the patient population of TLR4 G allele was 8.0%, CD14 T allele was 51.3%, TNF-1031C was 18.8%, TNF-863A was 14.2%, TNF-857T was 25.2%, TACE172T was 20.7%, and TACE154A was 24.5%. The transmission disequilibrium test transmitted:untransmitted (T:U) result for TLR4G was T:U = 32:20, for CD14T was T:U = 103:88, for TNF-1031C was T:U = 48:56, for TNF-863A was T:U = 39:42, for TNF-857T was T:U = 63:62, for TACE-172C/T was T:U = 48:59, and for TACE-154C/A was T:U = 52:55. No statistically significant associations were observed. Conclusions: The transmission disequilibrium test did not demonstrate preferential transmission of these variants in Jewish Ashkenazi patients with Crohn disease. These results suggest that these polymorphisms in the TNF/lipopolysaccharide pathway play little or no role in susceptibility to Crohn disease in the Jewish Ashkenazi population.

Combination of CFTR gene mutation and autoimmune pancreatitis presenting as necrotizing pancreatitis.

To the Editor: Pancreatitis associated with decreased cystic fibrosis transmembrane conductance regulator (CFTR) function and autoimmune pancreatitis (AIP) are two separate and rare conditions that cause acute and chronic pancreatitis in the pediatric population.1,2 Autoimmune pancreatitis is an uncommon cause of chronic pancreatitis in children, typically presenting with relatively mild symptoms with an autoimmune association. There are multiple genetic etiologies associated with pancreatitis, including CFTR gene mutations. The CFTR gene mutations have never been confirmed to be related to the degree or intensity of the symptoms of pancreatitis, although some have been linked with the disease. Identifying gene mutations may help recognize those patients who are at risk of developing recurrent and severe pancreatitis. We report the first case of a child who presented with necrotizing pancreatitis found to have a CFTR gene mutation and features of AIP. A 13-year-old boy presented with acute epigastric pain, fever, and vomiting. On physical examination, the patient was febrile with a distended abdomen and marked epigastric tenderness. He had an elevated white blood cell count (neutrophil predominant). Serum amylase and lipase were 858 U/L (25Y123 U/L) and 2528 U/L (7Y60 U/L), respectively. The patient had a pleural effusion on chest radiography. The abdominal ultrasound showed moderate ascites with a well-distended gallbladder, no gallstones, and no gallbladder wall thickening. The pancreas appeared enlarged and heterogeneous, with septations and debris, suggestive of pancreatitis with an infectious component. There was no family history of pancreatic disease or cystic fibrosis (CF). Computed tomographic (CT) scan and magnetic resonance imaging findings showed an abnormal pancreas with severe phlegmon and suggestion of necrotic tissue. The patient was diagnosed as having necrotizing pancreatitis, and by the eighth hospital day, the patient had clinically improved. Dietary restrictions were modified, and he was advanced to a low-fat diet and discharged home. Genetic testing revealed a heterozygous presence of R75Q variant CFTR gene. Despite compliance with a low-fat diet and use of pancreatic enzyme replacement, the patient had eight hospitalizations for pancreatitis during the next 3 years, which prompted further investigation. Endoscopic retrograde cholangiopancreatography showed a small and fibrotic major papilla, a stricture in the supra-ampullary portion of the pancreatic duct, but no pancreatic divisum. The patient had a positive antinuclear antibody and an IgG4 level of 332 mg/dL (normal range, 0.3Y 111.0 mg/dL). The diagnosis of AIP was made based on these findings. The patient and his family refused a pancreatic biopsy. Steroid therapywasdiscussed,however,not instituted because the patient was responsive to conservative medical management. The AIP is correlated with specific clinical, laboratory, radiographic, and histopathologic findings. Clinical findings consist of obstructive jaundice, weight loss, abdominal pain, nausea, and vomiting. Radiographic findings supporting the diagnosis of AIP include magnetic resonance imaging or CT scans showing a diffuse sausage-shaped enlargement of the pancreas.6 An irregular narrow pancreatic duct and/or multiple strictures without upstream ductal dilatation on pancreatic imaging are suggestive of AIP. In our patient, the initial CT scan revealed phlegmon and necrotic changes but did not visualize the pancreatic duct, leading to the diagnosis of necrotizing pancreatitis. The subsequent endoscopic retrograde cholangiopancreatography found the pancreatic duct to be difficult to cannulate with a stricture in the supra-ampullary portion without ductal dilation. Based on these findings, serological testing for AIP was obtained. Elevated levels of IgG4 are felt to be the best markers of AIP, with a sensitivity of 73.3% and a specificity of 95.1%. Despite lack of histology and the decision to hold on systemic steroid therapy, given the clinical, radiographic, and laboratory findings, our patient met the criteria for AIP based on the criteria stated by the Japanese Pancreas Society. In children, CF associated with CFTR gene mutations is the most common cause of chronic and recurrent pancreatitis. A recent study of pancreatic-sufficient CF patients determined that patients with genotypes associated with mild phenotypic effects (at least one CFTR mutation) had a greater risk of developing pancreatitis than patients with more severe phenotypes. The CFTR gene, R75Q, found in our patient was tested as a part of a multicenter study. Patients with a combined mutation in both SPINK-1 and CFTR R75Q were found to have a higher risk of pancreatitis. The conclusions drawn from this study were that the combination of a CFTR gene R75Q and SPINK-1 mutation increases the risk of chronic pancreatitis in a multiplicative manner.13 One could speculate from this study that the presence of the CFTR R75Q gene may carry a more significant and severe risk of pancreatitis in the setting of other risk factors or underlying etiologies, such as hereditary pancreatitis, pancreatic duct divisum, or AIP. In our patient with AIP, the presence of the CFTR gene mutation leads us to believe the severity of our patient’s attacks, specifically, the development of necrotizing pancreatitis, is a result of this combination.

FOLLOW UP EXPERIENCE IN PEDIATRIC LIVER TRANSPLANTATION IN AN ACADEMIC, NON-TRANSPLANT BASED GASTROENTEROLOGY GROUP: 143

As pediatric liver transplantation has become relatively common since the early 1980s, most long-term follow-up care has shifted from transplant centers to the pediatric gastroenterologists at referring institutions. We reviewed our experience with 16 patients who have undergone liver transplantation at eight institutions from 1987 to 1996. Our initial follow-up visit took place at an average 4.1 months after the transplant. The mean duration of follow-up was 41 months. During this period 11 hospitalizations at the transplant center occured, including five that were to rule out lymphoma or post-transplant lymphoproliferative disease. At the Schneider Childrens Hospital, NY, USA, 158 outpatient visits were recorded. Forty-two hospitalizations occurred. Twenty of the hospital admissions were accounted for by two patients. Forty-nine outpatient/inpatient surgical or diagnostic procedures were performed, including 15 percutaneous liver biopsies. In only one biopsy was there a disagreement in the histologic diagnosis between our pathologist and the pathologist at the transplant center. In conclusion, comprehensive follow-up care can be provided by an academic hospital-based gastroenterology group in conjunction with a transplant center.

Screening for Iron Deficiency.

The diagnosis and prevention of iron deficiency and iron deficiency anemia are extremely important to children’s health, as outlined in the 2010 statement by the American Academy of Pediatrics (AAP) Committee on Nutrition.1 Given that Pediatrics is the official journal of the AAP and contains the policy statements of this organization and its committees, it is … E-mail: mpettei{at}nshs.edu

Baby Bottle Nipple Causing Small Bowel Obstruction

p JP A 13-year-old boy with neurodevelopmental delay and seizure disorder presented with 1 day of nonbilious, nonbloody emesis. Emesis progressed and became bilious and bloody. Abdominal examination was significant for diffuse tenderness. Abdominal radiograph revealed a distended air-fluid–filled stomach. Upper gastrointestinal series revealed a silicone nipple in the third portion of the duodenum (Fig. 1). Emergent esophogastroduodendoscopy was preformed and foreign body (FB) removal was attempted, but was unsuccessful. The wide end of the nipple produced a suction effect, causing an obstruction (Fig. 2). A repeat esophogastroduodendoscopy with FB removal was performed with surgery prepared for possible laparotomy. The nipple was dislodged and removed using rat-tooth forceps and persistent slow, gentle traction. Mucosal ulcerations, erosions, and erythema were noted at the impaction site. There was no evidence of perforation. A proton-pump inhibitor therapy was initiated and feedings resumed.

T1134 Management of Splenic Pseudoaneurysm Formation in a Child with Hereditary Pancreatitis

Splenic artery pseudoaneurysm (SAP) formation is an uncommon complication of pancreatitis. There are no known reports of SAP in the pediatric population or in patients with hereditary pancreatitis. We report a case in a child with hereditary pancreatitis that was successfully managed via transcatheter coil embolization of the splenic artery. A 5 year old male was referred with an elevated amylase and lipase, 200 and 188 u/L respectively, abdominal pain, and poor weight gain (BMI < 5%). Serology and pancreatic ultrasound confirmed the diagnosis of pancreatitis. The child had persistently elevated pancreatic enzymes and abdominal discomfort despite supportive therapy. Genetic testing revealed 2 mutations consistent with the diagnosis of hereditary pancreatitis: an R122H mutation in the PRSS1 gene and a SPINK1 gene mutation. Three months after presentation a CT scan was obtained secondary to severe abdominal pain, guarding, and fever. The study revealed an ill defined pancreas with heterogeneous enhancement. A CT angiogram confirmed the presence of a small splenic pseudoaneurysm. The area was selectively catheterized and embolized via the deployment of three coils in the distal splenic artery (Fig). Discussion: SAP is felt to be the result of weakening of the blood vessel wall by pancreatic enzymes. The lesion is typically first seen on CT. Direct catheter angiography serves to confirm the diagnosis and provide a means of therapy since embolization of the pseudoaneurysm can be accomplished during this procedure. Selective embolizaton with coils just distal and proximal to the lesion effectively excludes the aneurysm from circulation and enables thrombosis. Although SAP formation is seen in adults with chronic pancreatitis, there are no reports in patients with hereditary pancreatitis. This is the first report describing the use of transcatheter coil embolization in the management of a child with SAP.