Jonathan E. Teitelbaum

Association of Schatzki Ring With Eosinophilic Esophagitis in Children

Objective: To describe the clinicopathologic characteristics of children with Schatzki ring and to determine if Schatzki ring is associated with eosinophilic esophagitis. Methods: The authors report 18 adolescents with radiographically diagnosed Schatzki ring (SR). Their clinical and histologic characteristics were reviewed in a blinded fashion. Results: The mean age of the patients was 15.8 ± 0.8 years and mean duration of symptoms was 2.6 ± 0.4 years. By histologic criteria, two groups of patients were defined. Eight had clinical and histologic criteria of eosinophilic esophagitis (EE) and 10 of peptic esophagitis. There were no differences in the symptoms or radiographic findings in the two groups. The SR was not identified by endoscopy in any EE patient and was identified in 70% of peptic esophagitis patients. Grossly apparent mucosal features associated with EE were significantly more common in those with EE. Those with peptic esophagitis had a significantly higher acid exposure than did those with EE (12.6 ± 2.9 v 2.0 ± 1.1%; P < 0.01) by esophageal pH probe. Patients with peptic esophagitis responded to proton pump inhibitors and/or dilatation, whereas those with EE did not have good response and required specific therapy for EE. Conclusions: EE may play a role in the pathogenesis of some patients with SR.

Use of Enteral Nutrition for the Control of Intestinal Inflammation in Pediatric Crohn Disease

Exclusive enteral nutrition is an effective yet often underused therapy for the induction of remission in pediatric Crohn disease. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition formed the Enteral Nutrition Working Group to review the use of enteral nutrition therapy in pediatric Crohn disease. The group was composed of 5 pediatric gastroenterologists and 1 pediatric nutritionist, all with an interest and/or expertise in exclusive enteral nutrition. Specific attention was placed upon review of the evidence for efficacy of therapy, assessment of the variations in care, identification of barriers to its widespread use, and compilation of the necessary components for a successful program. The present guideline is intended to aid physicians in developing an enteral nutrition therapy program and potentially promote its use.

Mitochondrial Neurogastrointestinal Encephalomyopathy: Diagnosis by Rectal Biopsy

A 14-year-old girl with the mitochondrial neurogastrointestinal encephalopathy syndrome had an 8-year history of intestinal pseudoobstruction with abdominal pain, persistent vomiting, gastric and duodenal dilatation, and duodenal diverticulosis. The child appeared chronically malnourished and had severe growth failure. Multisystem involvement was evident with the presence of ptosis, external ophthalmoplegia, muscle wasting, peripheral neuropathy, and diffuse white matter disease seen on magnetic resonance imaging. Lactic acidosis and increased cerebrospinal fluid protein were observed. Mitochondrial enzyme analysis of fresh-frozen skeletal muscle revealed a respiratory chain defect. Molecular genetic studies showed multiple mitochondrial DNA deletions. Pathologic findings in the intestine included atrophy of the external layer of the muscularis propria and an increased number of abnormal-appearing mitochondria in ganglion and smooth-muscle cells. Microvesicular steatosis was observed in liver, skeletal, and gastrointestinal smooth muscle, and Schwann cells of peripheral nerve. Brightly eosinophilic inclusions in the cytoplasm of gastrointestinal ganglion cells were visible by light microscopy, which were confirmed to be megamitochondria by ultrastructural studies. This is the first report of abnormal mitochondria observed in intestinal ganglion and smooth-muscle cells in this syndrome.

Diagnosis and management of MNGIE syndrome in children: case report and review of the literature.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare disorder that presents in childhood; however, marked delay in diagnosis is common. We report a case and review the literature describing the typical features that should alert pediatricians to the diagnosis. We also describe a novel management strategy for providing symptomatic relief.

Elevated galactose in newborn screening due to congenital absence of the portal vein

J. Raymond á M. Bergeret Department of Microbiology, Hoà pital Saint Vincent de Paul, 82, Avenue Denfert Rochereau, 75674 Paris Cedex 14, France N. Kalach á P.H. Benhamou á L. Senouci á D. Gendrel á C. Dupont Division of Gastro-enterology, Department of Paediatrics, Hoà pital Saint Vincent de Paul, 82, Avenue Denfert Rochereau, 75674 Paris Cedex 14, France, Tel.: (33) 1-40 48 81 11, Fax: (33) 1-40 48 83 20 j

Long-term efficacy of low-dose tricyclic antidepressants for children with functional gastrointestinal disorders.

Objective: The aim of the study was to determine the long-term efficacy of the tricyclic antidepressant (TCA) drugs amitriptyline or imipramine in treating functional gastrointestinal disorders (FGIDs) in pediatric patients. Materials and Methods: A retrospective chart review of children with a diagnosis of irritable bowel syndrome, functional dyspepsia, and functional abdominal pain diagnosed on the basis of the Rome III criteria was performed. Charts were analyzed for response to the medication and the duration of the response. Results: A total of 98 patients took a TCA for an FGID. Of the 98 patients, 77 patients (78.6%) responded to the treatment for an average of 10.73 (range 1–45) months. Conclusions: TCAs are effective in treating FGIDs in pediatric patients for a long duration.

Correlation of health-related quality of life in children with inflammatory bowel disease, their parents, and physician as measured by a visual analog scale.

Background and Aims: Inflammatory bowel disease has been shown to affect childrens health-related quality of life (HRQOL) through the use of lengthy questionnaires. We examined whether a pediatric patients HRQOL, measured by a rapid visual analog scale (“feeling thermometer”), correlates with the perceptions of the HRQOL as determined by the patients pediatric gastroenterologist and parent(s). Additionally, we attempted to determine whether the HRQOL correlates with the patients disease activity as determined by validated activity indices. Methods: A cross-sectional study of pediatric patients (ages 7–21 years) who were diagnosed as having Crohn disease, ulcerative colitis, or indeterminate colitis was conducted from January 2011 to May 2011. Each participant (patient, parent(s), and treating pediatric gastroenterologist) completed feeling thermometers to determine the symptom burden as well as therapeutic burden of the patient. The parent(s) and doctor were blinded to the patients results. Pediatric Ulcerative Colitis Activity Index or a Short Pediatric Crohn Disease Activity Index (S-PCDAI) was calculated. Correlations between the participants perceived burdens as well as their calculated disease activity were determined. Results: Sixty-seven children and their families participated, resulting in 101 visits. Patients had a mean age of 15.0 years, and there were 38 boys. There was a strong significant correlation between the patients perceived symptom burden and that of the parents (&rgr; 0.59, P < 0.001) and physician (&rgr; 0.48, P < 0.001). Similarly, there was a strong significant correlation between patients perceived treatment burden and that of the parent treatment burden (&rgr; 0.49, P < 0.001) and, to a lesser degree, the physician (&rgr; 0.29, P < 0.003). The correlation coefficient was strongest between the physicians perception of the patients symptom burden against the standard disease activity indices Pediatric Ulcerative Colitis Activity Index (&rgr; 0.69, P < 0.001) and Short Pediatric Crohn Disease Activity Index (&rgr; 0.65, P < 0.001). Conclusions: The patients HRQOL was highly correlated to both the physicians and parents perceptions as well as their disease activity. The feeling thermometer is a quick, easy-to-use, visual analog scale that can be implemented in everyday practice to measure a pediatric patients HRQOL.

Uneven Distribution of Microgranules in Divided Lansoprazole Tablets.

Objectives: Lansoprazole is a proton pump inhibitor commonly used in children <12 months of age despite a lack of efficacy and safety data in this age group. To achieve lower doses in this population, many divide standard oral disintegrating tablets. This study seeks to determine if the medication is equally distributed within the tablet to allow for accurate dosing. Methods: Ten 15-mg Prevacid SoluTabs were divided. Each portion was dissolved separately (half A, B, and the residual “dust” C) and photographed. A magnified view of the image allowed for counting each microgranule. Results: The mean number and standard deviation of microgranules in half A, B, and part C were 2514.7 ± 130.5, 2342.9 ± 130.1, and 49.4 ± 38.8, respectively. The total number of microgranules per tablet was 4907 ± 140.5. There was a statistically significant difference in the mean number of microgranules in half A versus B (P = 0.0086). Conclusions: There are statistically significant differences in the amount of lansoprazole-containing microgranules within each half of a divided tablet. Clinicians must determine whether this difference is clinically relevant when prescribing “divided” medication to children.

Infantile allergic colitis after supplementation with long-chain polyunsaturated fats.

To the Editor: Advances in the production of cow s milk based formulas have been remarkable over the past 100 years, as formula manufactures strive to make a formula that is similar to breast milk. The most recent change in formula production has been the addition of long chain polyunsaturated fats. Evidence suggests premature infants who are provided formula supplemented with arachidonic acid (AA) and docosahexaenoic acid may be afforded some benefit in visual acuity (1). However, the safety of such supplementation has not been established despite much scrutiny. Although no major adverse events have been proven to be related to AA and docosahexaenoic acid supplementation there have been questionable trends in greater numbers of deaths and necrotizing enterocolitis in the preterm population who received these supplemental fatty acids (2,3), thus prompting some concern about the effect of supplementation on immune function. Food allergy is relatively common and is noted to occur in up to 6% of children younger than 3 years of age (4). In young children such allergy commonly results in an allergic colitis with the development of hematochezia. The pathophysiology of these allergic reactions is incompletely understood, but a simplified model suggests that during the complex process of sensitization a protein is processed through M cells and is presented to the T cells in the lamina propria. Through the synthesis and release of pro-allergic cytokines such as interleukin-4, TH2 cells induce B cell production of antigen-specific immunoglobulins such as immunoglobulin E. Binding of immunoglobulin E to mast cells and basophils occurs and, on re-exposure to antigen, immunoglobulin E is cross-linked, inducing signal transduction pathways and the production of proinflammatory mediators (5). AA, one of the polyunsaturated fats being supplemented in infant formulas, is the principal precursor of various inflammatory cytokines termed eicosanoids. Eicosanoids include prostaglandins, thromboxanes and leukotrienes, lipoxins, hydroperoxyeicosatetraenoic acids and hydroxyeicosatetraenoic acids (6). Studies suggest that AA can stimulate superoxide production, induce degranulation, suppress cell chemotaxis and down-regulate expression of occluden, a transmembrane protein integral in the formation of tight junctions (6). This raises the concern that the addition of AA may accentuate allergic reactions by further fueling the inflammation with the production of potent cytokines. Indeed, experience with a recent patient highlights this concern. At 3 months of age a previously healthy girl changed formula to the same brand of cow s milk protein based formula but with additional AA and docosahexaenoic acid. Within 3 days the child s stools became more watery in consistency and somewhat more frequent at three to four times per day and then were found to have some associated bloody mucus. Stool cultures were performed for routine bacterial pathogens and were negative. After 1 week of bloody diarrhea the baby s formula was changed to a soy-based formula, but there was no resolution of the bloody diarrhea after a 1-week trial. Finally, a change to a protein hydrolysate formula without additional AA and docosahexaenoic acid resulted in resolution of the blood and mucus and a return to baseline in the stooling pattern and consistency within 3 days. One month later, with the introduction of cereal with trace quantities of soy protein the patient was once again noted to have blood in the stool. This resolved with elimination of soy protein from the cereal by changing cereal brand. The family history is notable for atopy in that the patient s father and sibling have eczema. This case thus illustrates the development of allergic colitis in an infant after supplementation with AA. Clearly, more studies are needed to determine if the addition of AA and docosahexaenoic acid carries risks that outweigh the benefits. This is particularly relevant for full-term infants, in which efficacy data is lacking. Special attention must also be paid to those allergic infants with pre-existing hematochezia or vomiting who will then be supplemented with AA. While manufacturers strive to make a formula that resembles breast milk, one should consider that breast milk is inherently hypoallergenic and therefore greater concentrations of AA may be better tolerated than in a formula with foreign/antigenic proteins.

3710 HIGH RESOLUTION PROBE ENDOSONOGRAPHY IN ALLERGIC ESOPHAGITIS.

Allergic esophagitis (AE) is an inflammatory disorder of the esophagus characterized by lack of response to medical and surgical anti-reflux therapies, normal esophageal pH recording, distinctive mucosal histopathology, and response to anti-allergic treatments (Am J Surg Pathol, 1999;23:390-6). Dysphagia and food impaction occur frequently, despite the absence of stricture, and resolve with medical therapy. The pathophysiology of this dysphagia is unknown but may relate to reversible changes in the esophageal wall. High-resolution probe endosonography (HRPE) provides detailed radial imaging and permits real-time measurement of individual layers of the esophageal wall.We have applied HRPE to investigate changes in children with AE and report our initial findings. Methods: Children with AE and control children without esophagitis were enrolled for study. The Olympus EU-M30 ultrasound processor and 20 MHz miniprobe were utilized. Probes were passed through the operating channel of a gastroscope at the time of diagnostic endoscopy. Small amounts of water were infused into the esophageal lumen for acoustic coupling. Duplicate real-time measurements (0.1mm resolution) of the esophagus were obtained with the probe tip positioned 3-5 cm above the lower esophageal sphincter and with the esophagus in a non-contracted state. Measurements were taken from areas of maximal thickness where all of the echo layers could be clearly distinguished and included thickness of the total wall (tw), combined mucosa and submucosa (m/sm), and muscularis propria (mp). Comparisons were made with control patients without esophagitis. The Mann-Whitney test was used for non-parametric statistical analysis of mean values. Results: Eight children with AE (mean age, 10.1 ± 5.2yr) were compared with four control children (mean age, 7.8 ± 6.3yr)(p=0.396). Seven echo layers were seen in all patients. Echo layers were significantly thicker in AE patients compared with control patients. Mean tw thickness was 2.2 ± 0.1mm (control) compared with 2.8 ± 0.7mm (AE)(p=0.035). Mean m/sm thickness was 1.1 ± 0.2mm (control) versus 1.6 ± 0.4mm (AE)(p=0.017). Mean mp thickness was 1.0 ± 0.1mm (control) compared with 1.3 ± 0.3mm (AE)(p=0.025). Conclusion: HRPE identifies significant thickening of the mucosa/submucosal and muscle layers of esophageal wall in children with allergic esophagitis compared to normal controls. This thickening may contribute to the observed dysmotility in these patients.