Sonny K. F. Chong

Evidence-based Guidelines From ESPGHAN and NASPGHAN for Helicobacter pylori Infection in Children

Objective: As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe. Methods: An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system. Results: A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection. Conclusions: These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.

Management guidelines of eosinophilic esophagitis in childhood

Objectives: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor–responsive esophageal eosinophilia. This position paper aims at providing practical guidelines for the management of children and adolescents with EoE. Methods: Relevant literature from searches of PubMed, CINAHL, and recent guidelines was reviewed. In the absence of an evidence base, recommendations reflect the expert opinion of the authors. Final consensus was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. Results: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid–based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved for severe symptoms requiring rapid relief or where other treatments have failed. Esophageal dilatation is an option in children with EoE who have esophageal stenosis unresponsive to drug therapy. Maintenance treatment may be required in case of frequent relapse, although an optimal regimen still needs to be determined. Conclusions: EoE is a chronic, relapsing inflammatory disease with largely unquantified long-term consequences. Investigations and treatment are tailored to the individual and must not create more morbidity for the patient and family than the disease itself. Better maintenance treatment as well as biomarkers for assessing treatment response and predicting long-term complications is urgently needed.

Recurrent Abdominal Pain in Children-A Retrospective Study of Outcome in a Group Referred to a Pediatric Gastroenterology Practice

Recurrent abdominal pain (RAP) affects a significant number of children each year. We reviewed our experience over a 2-year period to determine the outcome of patients who were referred for pediatric gastroenterology consultation. We identified 356 patients, 149 (42%) male and 207 (58%) female. All patients underwent a thorough interview and complete physical examination. Patients suspected of having irritable bowel syndrome (IBS) were treated as such without further initial evaluation. Others underwent an initial blood and urine evaluation. When these initial screening studies were negative, additional studies were performed including abdominal ultrasonography, radiography, and/or endoscopy of the upper gastrointestinal (GI) tract if the history suggested a possible diagnosis that could be excluded or confirmed by such tests. There was no identifiable diagnosis in 43.5% of the patients studied. IBS was diagnosed in 25.8% of all patients. Constipation was diagnosed in 3.7%. Miscellaneous causes, including GI mucosal lesions, and renal and pancreatic disorders were found in an additional 27% of patients. In a follow-up survey, more than 70% of the treated respondents were improved (i.e., their RAP had resolved or was markedly improved). We conclude that most children with RAP have a functional disorder. Patients with an organic cause for pain can be identified and treated in a cost-effective manner with carefully planned evaluation.

Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes.

BACKGROUND The relationship between symptoms, intestinal mucosal histology, and disaccharidase activities is not well defined. An analysis of disaccharidase activities was performed in children grouped by age, symptoms, and intestinal mucosal histology and normal values established. METHODS Disaccharidase activities and histology of 246 endoscopically obtained duodenal biopsies in 232 patients (121 girls; age range, 0.08-17 years; mean, 5.9 years) in a 3-year period were reviewed. Patients were divided into two groups based on absence (group 1; n = 142) or presence (group 2; n = 90) of diarrhea and were subdivided by age into, less than 24 months of age and 24 months of age or more. Histologic changes within groups were classified as (A) normal, (B) mild, or (C) moderate to severe based on villus height abnormalities. A questionnaire was sent to 34 patients with hypolactasia to assess the efficacy of lactose avoidance and/or lactase supplementation. RESULTS All group 1 patients had normal findings in analysis of mucosal specimens, and their disaccharidase activities showed normal values because they had no diarrhea. The geometric means (95% confidence interval) in children aged less than 24 months are (in micromoles of substrate hydrolyzed per minute at 37 degrees C per gram protein) (units [U]) lactase, 36.7 (13.4-100.4); maltase, 178.5 (88.9-356.3); palatinase, 12.7 (3.8-41.5); and sucrase 60.0 (24.0-148.1). In children 24 months of age or more, the values are 23.2 (3.9-108.1), 167.6 (78.8-355.9), 12.7 (4.9-32.9), and 51.0 (20.5-126.0), respectively. Only lactase activity decreased with age (p < 0.05). No differences in disaccharidase activities were noted in patients with and without diarrhea if the mucosal histology was normal (group 1A vs. 2A). In patients with diarrhea, values were commensurate with the degree of mucosal injury, especially in the older group. Twenty-two of 27 patients (81%) who responded to the questionnaire had benefited from lactase supplementation and/or lactose avoidance. CONCLUSIONS We have established normal values for disaccharidase activities in the pediatric population. Although the disaccharidase activities correlate more with degree of intestinal mucosal injury than with symptoms, their activities are difficult to predict accurately based on these criteria. If required, disaccharidase activities should be measured biochemically.

Experience with juvenile polyps in North American children: the need for pancolonoscopy

We report a recent experience with juvenile polyps (JP) in a large cohort of North American children to determine if a pancolonoscopy (PC) is needed in all children with suspected polyps. We reviewed hospital charts of all patients with JP seen over a 9-yr period (January, 1990–October, 1998). A total of 331 JP were encountered during 195 procedures in 184 patients (64% males, 88% white, mean age 5.93 yr [range 0.42–15.5 yr], median age 4.84 yr). Painless rectal bleeding was the commonest symptom. PC was performed in 42% (82/195) of procedures, and 177 JP were encountered: 54% (97/177) were in the rectosigmoid colon, 14% (24/177) were in the descending colon, and 32% (56/177) were proximal to the splenic flexure (i.e., proximal polyps). Overall, proximal polyps were seen in 37% (31/82) of PC. Only proximal polyps were noted in 12% (10/82) of PC. Five patients were re-endoscoped after an initial limited examination because of continuing symptoms from proximal polyps. All but one of the polyps had typical features of a JP on histological examination. Though most JP are located in the left colon, a PC should be the initial procedure because: 1) 37% of PC revealed proximal polyps, 2) 32% of polyps were located proximal to splenic flexure, 3) persistence of symptoms from missed proximal polyp(s) necessitates a repeat study with attendant risks, and 4) there is a possibility of malignant transformation in an unidentified JP.

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study

There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. Patients and methods Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. Results Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3±5.5 vs. 8.1±5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. Conclusion Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

BACKGROUND In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose. METHODS We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose. RESULTS In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores. CONCLUSIONS Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

Expression of inducible nitric oxide synthase (iNOS) mRNA in inflamed esophageal and colonic mucosa in a pediatric population.

Objective:Increasing evidence suggests that nitric oxide participates in the pathophysiology of intestinal barrier function/dysfunction and inflammation. Increases in inducible nitric oxide synthase (iNOS) mRNA and protein expression have been observed in colonic mucosal biopsies of adults with inflammatory bowel disease (IBD). It is unclear whether iNOS induction is specific for IBD or a reflection of nonspecific mucosal inflammation. Furthermore, the characteristics of iNOS mRNA expression in pediatric patients with gastrointestinal disorders remains ill-defined. Our objective was to examine the relationship between iNOS mRNA expression and gastrointestinal mucosal inflammation in a pediatric population.Methods:Esophageal and colonic mucosal biopsies were obtained during endoscopy. Total RNA was isolated from these biopsies and reverse transcription-polymerase chain reaction (RT-PCR) performed (35 PCR cycles) using two 20-bp primers that amplified a predicted 372-bp conserved iNOS mRNA fragment.Results:Biopsies were obtained from 29 children (22 boys; mean age 10.6 yr [range 1.7–16.5 yr]). Endoscopic and histological findings included normal esophageal mucosa (n = 3), esophagitis (n = 10), normal rectal mucosa (n = 2), ulcerative colitis (n = 10), and Crohn disease (n = 4). Evidence of iNOS mRNA was detected by PCR amplification in six of 10 patients with ulcerative colitis and in two of four patients with Crohn disease. However, iNOS mRNA was not amplified in any esophageal biopsy or in rectal mucosa biopsies with normal histology.Conclusions:These data indicate that upregulation of iNOS mRNA expression in colonic mucosa is a feature of IBD in children. iNOS mRNA expression is not upregulated in esophageal mucosa or in the absence of colonic inflammation. Further studies designed to determine the site- and cell-specificity of iNOS mRNA upregulation in mucosal biopsies from children with IBD may further illuminate the pathophysiology of these disorders.

Clinical applications of technetium Tc 99m hexamethyl propylene amine oxime leukocyte scan in children with inflammatory bowel disease

BACKGROUND Labeled leukocyte imaging is a helpful diagnostic tool in the detection of inflammation and sepsis. The technetium Tc 99m hexamethyl propylene amine oxime (99mTc HMPAO)-labeled leukocyte scan has been found to be more sensitive than the Indium-111 labeled leukocyte scan in detecting inflammatory bowel disease, with reported sensitivities of 95% to 100%. Experience with the 99mTc HMPAO-labeled leukocyte scan was examined and its clinical applications evaluated in the immediate treatment of patients with inflammatory bowel disease. METHODS A retrospective chart review was undertaken that included pediatric patients who underwent 99mTc HMPAO-labeled leukocyte scan at the James Whitcomb Riley Hospital for Children. The disease activity of patients with inflammatory bowel disease was assessed. The leukocyte scan was performed according to the manufacturers specifications, and images were obtained 30 minutes and 2 hours after administration of the radiopharmaceutical. RESULTS During the period of July 1996 through November 1997, 41 scans were performed in 35 patients. Twenty-nine patients had histologically proven inflammatory bowel disease: 24 with Crohns disease, 4 with ulcerative colitis, and 1 with indeterminate colitis. Active inflammatory bowel disease was suspected in 24 patients when the leukocyte scan was performed. Twenty of the 24 patients (83% sensitivity) had abnormal findings in leukocyte scans that prompted more aggressive management in 15 (75%). Six of the 15 who were receiving maximum medical therapy underwent surgical resection of severely affected bowel segments, and medical treatment was intensified in the other 9. The remaining 5 patients were receiving optimal medical therapy, instituted at their recent visit, and did not require further medication adjustments. Four of the 24 patients with active inflammatory bowel disease had normal leukocyte scans (17% false-negative rate), 3 of whom were receiving corticosteroid therapy at the time the scans were performed. All of the 11 patients in whom inflammatory bowel disease was in remission and 6 patients who did not have inflammatory bowel disease had normal findings in leukocyte scans (100% specificity). CONCLUSIONS Although a tissue diagnosis is still recommended, obtained during upper and lower gastrointestinal endoscopic examinations, and contrast radiography of the small bowel for the initial work-up of patients with suspected inflammatory bowel disease, the 99mTc HMPAO-labeled leukocyte scan is a safe and useful diagnostic adjunct for subsequent evaluation of patients known to have inflammatory bowel disease. The results of 99mTc HMPAO-labeled leukocyte scans directly influenced treatment of 75% of the study patients with active inflammatory bowel disease, which included the decision to refer patients for surgical intervention.

Hepatic granulomas in children : A clinicopathologic analysis of 23 cases including polymerase chain reaction for histoplasma

In a 15-year period at the Riley Hospital for Children, granulomas were found in 23 (4%) of a total of 521 liver biopsies. An etiology was identified in 87%: Histoplasma was diagnosed in 15 cases (65%) by polymerase chain reaction (PCR) on paraffin-embedded tissue, serology, and special stains; sarcoidosis was diagnosed in four cases; and schistosomiasis was diagnosed in one case. Serial liver biopsies were available from five patients; granulomas occurred in only one biopsy of the series from each patient. Extrahepatic tissue from six patients contained granulomas, and an etiology for the liver granulomas was identified in all six patients (four histoplasmosis, two sarcoidosis). The extrahepatic tissue from two patients with Histoplasma was diagnostic. We made the following conclusions: that PCR is applicable to archival material and greatly increases the yield of specific infectious diagnoses of liver granulomas compared with conventional diagnostic methods (65 versus 22%); that the infections causing liver granulomas are those that are endemic in a community (e.g., Histoplasma in Indiana); that Histoplasma can coexist with a wide variety of systemic and primary liver diseases; that the likelihood of identifying a cause of liver granulomas is increased if there are extrahepatic granulomas; and that hepatic granulomas may have a limited life span. Treatment of liver granulomas should be determined by the clinical setting and directed at the underlying cause.