Joint ESPGHAN/NASPGHAN guidelines for the management of helicobacter pylori in children and adolescents (Update 2016)

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

The use of an oral fluid immunoglobulin G ELISA for the detection of Helicobacter pylori infection in children.

BACKGROUND: Enzyme linked immunosorbent assay (ELISA) evaluation of oral fluid immunoglobulin G (IgG) antibodies to Helicobacter pylori is a unique approach for both epidemiological studies and the diagnosis of infection, especially in children. The use of oral fluid sampling to evaluate specific H. pylori IgG antibodies has advantages over serum, including reduced biohazard risk and noninvasive collection. Oral fluid sampling is fast and involves minimal patient discomfort. Since children facilitate transmission of H. pylori infection, a simple, accurate, noninvasive diagnostic test is necessary for large epidemiologic studies. The aim of our study was to evaluate a new oral fluid ELISA for detection of IgG antibodies to H. pylori in children. MATERIALS AND METHODS: We compared this new oral fluid ELISA with the HM-CAPTM serum ELISA and gastric biopsy histology using 779 oral fluid samples from children collected at 11 clinical sites across the United States. This cohort included 315 children symptomatic for abdominal pain and 464 asymptomatic. All samples were evaluated in a double blind manner. The oral fluid ELISA demonstrated a sensitivity of 76.2% and a specificity of 94.0% in children 2 months old to 201/2 years, as compared with the HM-CAPTM serologic assay. The assay's sensitivity improved to 81.3% in children aged 5 or greater and the specificity remained at 94.0%. When compared with gastric biopsy histology in the same age group, the oral fluid ELISA demonstrated a sensitivity of 71.7% and a specificity of 90.4%. RESULTS: This new oral fluid ELISA is moderately sensitive and offers a very specific method for detecting H. pylori infection in older children, but it is of little value in children under the age of 5 years. CONCLUSIONS: Overall, we conclude that this oral fluid ELISA does not appear to be a helpful clinical tool for the diagnosis of H. pylori infection in children.

T and B cell repertoire in gastric lymph follicles in children with Helicobacter pylori infection.

Helicobacter pylori infection has been implicated in the development of gastrointestinal malignancy in adults and children. The histopathological processes that lead to such development are unknown. We compared the immune cell repertoire of mucosal lymph follicles in children with H. pylori infection to B cell type mucosal associated lymphoid tissue (MALT)-lymphoma of adults. The B and T cell populations residing within the lymph follicles and/or within B cell type MALT lymphoma were characteriZed by an immunohistochemical technique, utilizing B and T cell markers including: CD3, CD4, CD8 (T cells); CD20, CD40, GD74, BLA36, CD80, CD86 (B cells). Stain intensity was compared between the samples. T cell repertoire was observed within the lymph follicles, but not in the B cell MALT-lymphoma specimens. No significant difference was observed between the staining of CD40, CD74, CD8, and BLA36. The B cell markers, CD80 and CD86, were found within the centrocytic zone of the lymph follicle. In the B cell repertoire, no significant difference was observed between the lymph follicles of children with H. pylori infection and the adult MALT-lymphoma specimens except in CD20. B and T cells were in close anatomical proximity, enabling them to interact and exchange immunological information.

Non-Helicobacter pylori related duodenal ulcer disease in children.

BACKGROUND: In spite of the worldwide distribution of Helicobacter pylori infection, recent data have reported an increased rate of non-H. pylori, non-NSAIDs-duodenal ulcer disease in adults. The estimated rate of these ulcers in children is unknown. We aimed to investigate the prevalence of non-H. pylori, non-NSAIDs-peptic ulcer disease in our pediatric patients who undergo upper endoscopic procedures. METHODS: A retrospective analysis of 622 upper endoscopic reports was performed. Reports that documented mucosal ulcerations were included in our study. The demographic, clinical, endoscopic, and histological data were retrieved. The H. pylori-negative, duodenal/gastric ulcer-positive patients were compared with H. pylori-positive, duodenal/gastric ulcer-positive patients. RESULTS: Out of the 622 upper endoscopy reports, a total of 11 (1.8%) children with mucosal ulceration were studied. Mucosal ulceration was distributed in the following locations: stomach-3 (27%), and duodenal bulb-10 (91%) (two children had ulcers in both the stomach and duodenal bulb). Helicobacter pylori infection was only detected in three (27%) children with duodenal ulcer. Gastritis was more severe in patients with H. pylori infection/duodenal ulcer compared with H. pylori-negative/duodenal ulcer group. No statistical difference in clinical symptoms or endoscopic appearance was observed between the H. pylori-negative and H. pylori-positive groups. CONCLUSION: 'Idiopathic' (H. pylori-negative, NSAIDs-negative) duodenal/gastric ulcers are present in symptomatic children. Clinical or endoscopic characteristics are insufficient markers to identify those 'idiopathic' ulcers. Investigating the 'risk factors' for those ulcers will be helpful in reducing the morbidity in these children.

Reuse of negative CLOtest kits in children.

BACKGROUND: The rapid urease test, CLOtest, is used frequently in endoscopy suites. In the developed world, a negative CLOtest result is extremely common. The question of whether reuse of previously negative CLOtest kits is appropriate in children and the cost saving of such a practice were investigated. METHODS: Children who underwent diagnostic endoscopic procedures were prospectively recruited to the study. In each procedure gastric biopsy specimens were obtained for 2 rapid urease tests, one a new kit and the other a used negative kit obtained from previous procedures. In addition gastric specimens were also obtained for routine histologic examination. RESULTS: In 121 (99.2%) patients a complete concordance between new and used CLOtests was observed. Chi-square analyses showed a significant association between CLOtest results and each of the following factors: gastritis, the presence of Helicobacter pylori organisms, and H pylori-associated gastritis. Assuming an average rate of 15% positive CLOtest results in our pediatric population, the annual savings at the rural hospital was $265 and at the urban children's hospital, $1958. CONCLUSION: Reuse of a negative CLOtest is reliable and may reduce costs, especially in facilities with a high volume of endoscopic procedures.

Diagnosis and treatment of Helicobacter pylori infection in children: a survey of WV primary care physicians.

Helicobacter pylori infection has been implicated in the development of peptic ulcer disease in children. Although clinical protocols for the diagnosis and treatment of this infection in children are available, the implementation of those guidelines by primary physicians are insufficient. In this study, we surveyed the clinical practices of 409 primary physicians who practice in West Virginia and treat children with H. pylori infection. Results showed in contradiction with the recommendation, primary physicians are still using serology as the preferred diagnostic method for this disease. Most of the physicians treat this disease with a combination of two antibiotics and anti-acid medication (H2 blockers or PPI) for at least one week. We conclude that an increase in knowledge of those guidelines among primary physicians may improve physicians' compliance with H. pylori guidelines.

Propofol sedation for endoscopic procedures in children.

BACKGROUND AND STUDY AIMS: Propofol sedation has been used successfully in various outpatient minor procedures in children. Limited data are available on the usefulness of propofol sedation during gastrointestinal endoscopic procedures in children. The aim of this study was to evaluate our experience of propofol sedation in pediatric gastrointestinal endoscopic procedures. MATERIALS AND METHODS: The charts of all children who had undergone diagnostic endoscopic procedures, and were sedated by propofol, were retrospectively reviewed. Demographic data, cardiovascular monitoring, and drug dosages were recorded. Patients evaluated their sedation efficacy by answering a questionnaire before discharge. RESULTS: A total of 104 children underwent 107 procedures. Propofol alone was given in 19 procedures and in combination with midazolam and/or fentanyl in 88 procedures. All procedures were completed and significant complication occurred in only one patient. No significant difference was observed in the amount of sedative drugs or recovery time between upper and lower endoscopic procedures. A lower propofol dosage was needed when a combination of drugs was given compared to propofol drug alone. Patients' assessment of their sedation showed that the vast majority had experienced postendoscopic amnesia. CONCLUSION: Propofol sedation for endoscopic procedures is safe and acceptable for children. Propofol sedation should be offered to young children, especially those who express significant anxiety.

Helicobacter pylori serology and the diagnosis of H. pylori infection in children.

Serological screening accuracy rate may be dependent on clinical and pathological determinants. The aim of this study was to evaluate the accuracy of Hp serology test (Roche Biomedical Lab., Labcorp), in the diagnosis of Hp infection in 121 children who were seen in the Pediatric Gastoenterology Clinic at the Marshall University Joan C. Edwards School of Medicine in Huntington. Positive serology detected children with Hp-associated gastritis with a sensitivity of 51.6%. Positive serology significantly correlated with the degree of gastric inflammation and density of Hp organisms in the gastric mucosa (ANOVA p < 0.001). The Labcorp. Hp-ELISA test had a poor accuracy rate for the detection of Hp-gastritis in children. Gastric biopsies should always be performed to establish the diagnosis of Hp infection in children.

Is gastric nodularity a sign for gastric inflammation associated with Helicobacter pylori infection in children?

The aim of this study was to investigate the accuracy of using gastric nodularity (GN) as a marker for gastric inflammation associated with Helicobacter pylori infection in children. A retrospective analysis of 395 upper endoscopies done in children between 1990-1996 was performed. Demographics, clinical symptoms, endoscopic features, rapid urease test (RUT), and histological results were collected from each report. GN was found in 13 (3.5%) children. GN showed a significant correlation with age but not with gender. Multiple regression analysis showed a significant correlation between GN and gastritis with RUT but not with other histological determinants alone (gastritis, RUT, or H. pylori organisms). Nevertheless, GN had a poor accuracy rate to determine H. pylori-associated gastritis (sensitivity, 61%; positive predictive value, 12%). GN is a poor predictor for gastric inflammation associated with H. pylori infection in children. During endoscopy, gastric biopsies should always be obtained in children to establish the presence of mucosal inflammation.

Is sudden infant death syndrome associated with Helicobacter pylori infection in children?

Helicobacter pylori infection has recently been implicated in the pathogenesis of sudden infant death syndrome (SIDS). We investigated this association. Twenty-five pairs of gastric and tracheal tissue specimens obtained from autopsies of 25 children with previous diagnoses of SIDS were available for this study. The presence of H. pylori organisms was evaluated by three different methods: histology (hematoxylin-eosin or Giemsa staining), immunohistochemistry, and nested polymerase chain reaction technique. We were unable to confirm the presence of H. pylori organisms by the first two methods. H. pylori DNA was identified by nested polymerase chain reaction in six different tissue specimens (stomach, 4; trachea, 2). In no case was H. pylori DNA detected in both tissues. We concluded that H. pylori infection is most likely not associated with SIDS.

Cow's milk allergy in infants.

Cow's milk allergy (CMA) is one of the most common food allergies in young infants affecting up to 7% of children less than six months of age. The clinical presentation of these infants may be very traumatic to their parents, as significant rectal bleeding is the most common symptom in this disease. This article describes our experience treating 44 infants who were diagnosed with CMA in the Pediatric Gastroenterology Clinic at Marshall University. The clinical symptoms, treatment and outcome are presented. To reduce apprehension from the parents, primary physicians should be familiarized with this disease.

Tryosine kinase and ornithine decarboxylase activation in children with Helicobactor pylori gastritis.

H. pylori infection has been considered a risk factor for the development of gastric malignancy. Ornithine decarboxylase and tyrosine kinases activities are increased in patients with colon or esophageal cancer. In this study we compared the ODC and tyrosine kinases activities in the gastric mucosa of children with H. pylori infection and normal mucosa. Gastric biopsies were prospectively collected from children during routine upper endoscopic procedure. H. pylori infection was determined histologically. Biopsies were analyzed for ODC activity, total tyrosine kinases activities, and for the activity of protooncogene tyrosine kinase pp60(c-src). The mean ODC activity (pmol 14CO2/mg. protein/hr) and total tyrosine kinases activity (pmol 32P/mg. protein) were 186 and 5877 for H. pylori infected mucosa; and 229 and 4300, for normal mucosa, respectively (p> 0.05). Tyrosine kinase pp60(c-src) protein levels were similar between H. pylori infected mucosa and normal mucosa (3.12 and 2.15 pmol 32P/mg. protein, respectively; p>0.05). There was no correlation between gastric inflammation and the level of ODC or tyrosine kinase activities. ODC and tyrosine kinase activities in the gastric mucosa are similar in children with H. pylori infection compared to normal mucosa. The data suggest that these enzymes cannot be used as markers for future cancer development in children.

Helicobacter pylori antibody profile in household members of children with H. pylori infection.

Intrafamilial spread is implicated as a major route for acquisition of Helicoobacter pylori infection. Investigating H. pylori cytotoxin-associated protein (CagA) and vacuolating toxin (VacA) antibodies within family members enabled the authors to evaluate this possibility further. Serum samples were collected prospectively from household members after their index children were diagnosed with active H. pylori infection. Serum samples were evaluated for anti-H. pylori immunoglobulin G antibody using the enzyme immunoassay (IEA) method and for H. pylori CagA and VacA antibodies with the commercially available immunoprobing Western blot kit. Ten different families participated in the study, including 10 pediatric patients and 31 household members. All patients and 28 household members (90%) were seropositive for H. pylori antibody by IEA and Western blot tests. Overall, 17 subjects (41.4%) were CagA positive, 14 (34.1%) were VacA positive, 11 (26.8%) were positive for both antibodies, and 22 (53.6%) were negative for both antibodies. A significant association in bacterial antibody profile was found between the patient index members and all household members (Cohen's kappa and Mentel-Haenszel methods). In four families, more than 66% of the household members harbored the same antibody profile, and in two families a completely different profile was observed. Moreover, a similar H. pylori antibody profile between the index patient and the mother was found in six families, and between the index patient and the father in two families. The data strongly suggest an intrafamiliar transmission for H. pylori infection.

Detection of Helicobacter pylori organisms by Hp-fast in children.

Hp-fast is a new rapid urease test (RUT) that has not been evaluated in children. The aim of the study was to prospectively compare the Hp-fast test to the CLOtest in children. Children with gastrointestinal symptoms who undergo diagnostic upper endoscopy were prospectively enrolled to the study. Antral gastric biopsies were evaluated for histology and for CLO-test and Hp-fast. Results were then compared to histology. Of the 94 children who participated, gastritis was found in 38 (40%), of whom 16 (42%) had associated H. pylori organisms. In two children, H. pylori organisms were identified without gastritis. The concordance between both RUT tests was 98%. A significant correlation was found between RUT results and histological factors or serology. The accuracy rate of both RUT increased significantly when different gold standards were utilized to detect Hp infection in children. The best correlation was found when histology and serology were considered as the gold standard for the diagnosis of H. pylori infection in children (sensitivity: 100% compared to 43-80% with other standards, respectively). In conclusion, the Hp-fast test result is comparable to CLOtest, but neither alone is sufficient to establish the diagnosis of Hp infection in children.

Prevalence of CagA, VacA antibodies in symptomatic and asymptomatic children with Helicobacter pylori infection.

BACKGROUND: Limited data are available on the prevalence of CagA and VacA Helicobacter pylori antibodies in children. The aim of this study was to investigate the antibody prevalence to the H. pylori virulence factors CagA and VacA in symptomatic and asymptomatic children with H. pylori infection and to correlate these antibodies with the severity of gastric inflammation or density of H. pylori organisms in the gastric mucosa. MATERIALS AND METHODS: Twenty-three symptomatic children and 132 asymptomatic children with positive H. pylori serology participated in this study. Anti-H. pylori IgG antibody and CagA or VacA H. pylori antibodies were measured by enzyme immunoassay (HM-CAP; sensitivity and specificity > 90%) and Western immunoblot (Helicoblot 2.0) methods, respectively. Gastric inflammation and H. pylori density were graded histologically using the revised Sydney criteria. RESULTS: The prevalence of CagA and VacA antibodies were 69% and 35% in symptomatic children and 54% and 52% in asymptomatic children, respectively. Multiple regression analysis showed a correlation between CagA antibody and the severity of gastritis but no correlation with other histological features, including the number of neutrophils or lymphoid follicles. Neither antibody correlated with the degree of bacterial density in the gastric mucosa. CONCLUSION: CagA and VacA H. pylori antibodies are common in the pediatric population. The combined CagA/VacA antibodies correlated weakly with the degree of mucosal inflammation.

Pancreas divisum--the role of ERCP in children.

Pancreas Divisum (PD) is the most common congenital anomaly of the pancreas leading to chronic pancreatitis in children. The best diagnostic procedure to establish this diagnosis is Endoscopic Retrograde Cholangiopancreatography (ERCP). Utilizing ERCP as a therapeutic modality (sphincterotomy, stone removal), enables the clinician to improve symptoms and reduce morbidity. In this report, we describe the clinical presentation and outcome of three children with chronic pancreatitis who were subsequently diagnosed with PD by ERCP. We recommend that ERCP should be considered in children with chronic pancreatitis of unknown etiology.