Giuseppina Oderda

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.

Detection of Helicobacter pylori in stool specimens by non›invasive antigen enzyme immunoassay in children: multicentre Italian study

Helicobacter pylori infection is mainly acquired in childhood and may predispose to peptic ulcer or gastric cancer later in life.1 Non-invasive diagnostic tools are particularly useful in children as screening tests and for epidemiological studies, but their accuracy has to be tested against that of invasive tests in symptomatic patients before they are used in any particular population. Of the non-invasive tests now available, serological testing is not accurate in young patients and the 13C urea breath test is expensive. In 1998 an enzyme linked immunoassay (ELISA) (Premier-Platinum-HpSA, Meridian Diagnostics, Cincinnati, OH, USA) was approved by the Food and Drug Administration for both diagnosis in adult symptomatic patients, and monitoring the response to treatment. It is now commercially available, but its correlation with gastric infection has not been assessed in children. We evaluated its diagnostic accuracy against invasive tests in children undergoing endoscopy for clinical evaluation, and we determined the cut off values for the paediatric population. View this table: Test performance calculated according to different reading techniques (at 450 …

AMOXYCILLIN PLUS TINIDAZOLE FOR CAMPYLOBACTER PYLORI GASTRITIS IN CHILDREN: ASSESSMENT BY SERUM IgG ANTIBODY, PEPSINOGEN I, AND GASTRIN LEVELS

32 children (mean age 12 years, range 6-18) with non-specific abdominal pain and Campylobacter pylori positive gastritis received a six week course of daily oral amoxycillin (50 mg/kg) and tinidazole (20 mg/kg). Before treatment and one month after stopping treatment, endoscopic biopsy samples were taken from the antral mucosa and serum C pylori IgG antibody, pepsinogen I, and gastrin levels were measured in fasting blood samples. One month after treatment 30 children (94%) were cleared of C pylori and gastritis had resolved in 27 (84%) and was improved in the remaining 5. Serum IgG, pepsinogen I, and gastrin levels were significantly decreased after treatment. Of 12 children assessed at six months, 9 remained free of C pylori. Increases or decreases in IgG level indicated clearance or recurrence, respectively, of C pylori.

Validation of the 13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a multicenter study.

OBJECTIVE:The 13C-urea breath test (13C-UBT) is a safe, noninvasive, and accurate test for the detection of Helicobacter pylori (H. pylori) infection in adults. The aim of this study was to evaluate sensitivity and specificity of 13C-UBT in children using different types of test meal, doses of 13C-urea and breath sampling intervals. As yet, a validated, standardized 13C-UBT protocol for children has not been formulated.METHODS:13C-UBT was performed in 115 children and repeated within 3 days, modifying the test meal or the dose of 13C-urea. H. pylori status was assessed by histology and rapid urease test. 13C-UBT was performed using 100 mg or 50 mg of 13C-urea and a fatty test meal (100 FA; 50 FA), 50 mg of 13C-urea, and a carbohydrate test meal (50 CA). Breath samples were collected every 10 min for 60 min.RESULTS:The 13C-UBT in children was highly sensitive and specific with all three protocols used. The best combination of sensitivity (97.92%) and specificity (97.96%) was obtained with Protocol 50 FA at 30 min with a cut-off of 3.5 per mil.CONCLUSIONS:The 13C-UBT is an accurate test for the detection of H. pylori infection also in children. Administration of 50 mg of 13C-urea, a fatty test meal, and breath sampling at 30 min appears to be the most convenient protocol.

Helicobacter pylori in children with peptic ulcer and their families

Little is known about the source and spread ofHelicobacter pylori, but transmission from infected family contacts has been suggested. We have therefore investigated 15 children with peptic ulcer and their first-degree relatives forH. pylori. Serum anti-H. pylori IgG, pepsinogen I, and gastrin levels were measured. Endoscopy was carried out on the children and relatives, and biopsies were taken from the gastric antrum for histology, microbiology, and urease testing. Six of 11 children with duodenal ulcer (55%) and two of four children with gastric ulcer (50%) were positive forH. pylori. Fourteen of 16 parents (87%) and eight of 13 siblings (61%) ofH. pylori-positive children with peptic ulcer were also infected compared with eight of 14 parents (57%) and none of four siblings ofH. pylori-negative children with peptic ulcer (P< 0.10, >0.05, and NS, respectively). The children withH. pylori-negative peptic ulcer and negative siblings combined were younger than positive children with peptic ulcer and positive siblings (P<0.001). The reliability of serum anti-H. pylori IgG level as a screening test for infection was confirmed. These findings call into question a pathogenetic role forH. pylori in some childhood peptic ulceration, but do suggest that person-to-person spread of infection occurs.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohns disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

Background and Aim:  Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field.

Serum pepsinogen I and gastrin concentrations in children positive for Helicobacter pylori.

Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information.

Clinical pattern of celiac disease is still changing.

The clinical presentation of celiac disease in children changed in the last decades of the 20th century. To ascertain whether changes are still in progress, we analyzed symptoms at presentation and age at diagnosis in 307 children receiving diagnoses of celiac disease for the past 20 years. The prevalence of typical forms of celiac disease decreased in the past decade, particularly in the past 5 years (from 76% in 1987–1990 to 44%, P < 0.0001). Age at diagnosis (5.9 y, P = 0.01) and silent forms (10.6%, P = 0.003) have significantly increased in the past 5 years. Histological examination showed decreased subtotal and increased partial villous atrophy prevalence (P = 0.02).

Helicobacter pylori infection in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Helicobacter pylori–induced gastritis causing mucosal ulceration either in the stomach or the proximal duodenum is a relatively uncommon event in children compared with adults. When H. pylori–associated ulcers occur in children, duodenal ulceration is much more frequently identified than gastric ulcers. In children younger than 6 to 10 years of age, peptic ulcers are usually due to noxious agents (such as corticosteroids and nonsteroidal antiinflammatory agents) or after major stresses (for example, burns, head injury, systemic illness). In these settings, upper gastrointestinal tract hemorrhage, vomiting, or perforation are frequent presenting features. The ulcers tend not to recur after healing if either the offending agent or underlying disease predisposing to mucosal ulceration can be removed. In older children and adolescents, the clinical presentation and natural history of peptic ulcers are more comparable to those observed in adults. The ulcers present as epigastric and nocturnal abdominal pain in teenagers with a positive family history of peptic ulceration. In this setting, despite healing of the acute ulceration, the natural history is for the ulcer to recur. It is now clear that such ulcers are not related to a genetic predisposition to hyperpepsinogenemia but to infection of the stomach with the pathogen H. pylori. Recurrences of H. pylori–associated peptic ulceration are markedly reduced by treatment directed at eradicating the gastric infection. For example, duodenal ulcer recurrence rates in H. pylori–infected children have been reported to be reduced from 65% recurrence at 1 year of follow-up if ulcers are healed with acid suppressive agents alone compared with 1-year ulcer recurrence rates below 5% if the gastric pathogen is eradicated. This intervention therefore results in reduced global health care costs. Historical Perspective Peptic ulcer disease has been considered to arise as a result of an imbalance between mucosal defenses and aggressive factors, including acid and pepsin. Mucosal defenses against acid and pepsin include mucus and bicarbonate, mucosal blood flow, prostaglandins, trefoil peptides, and epidermal growth factor. Primary peptic ulcers are usually duodenal, chronic, and related to H. pylori, whereas secondary ulcers are gastric, acute, and unrelated to infection status. It is clear that marked overproduction of gastric acid, such as occurs in the Zollinger-Ellison syndrome and, more commonly in children, antral G cell hyperplasia (also referred to as pseudo-Zollinger Ellison syndrome) can cause duodenal ulceration. However, excess acid production does not account for the overwhelming majority of peptic ulcers in children. It has been known for many years that recurrent peptic ulcer disease in humans is accompanied by a chronicactive gastritis. In 1983, Drs. Barry Marshall and Robin Warren in Perth, Australia provided the explanation for the cause of the gastritis and accompanying peptic ulcer disease when they successfully cultured H. pylori from the gastric antrum of humans. Subsequent studies in children confirmed the findings first reported in adults. There is specificity to the infection, the infection is associated with previously unexplained recurrent peptic ulcers, and both gastritis and ulcers resolve when the infection is successfully eradicated (1). Although there is general consensus worldwide to treat H. pylori infection when there is endoscopic evidence of peptic ulceration, whether to intervene in other more frequently encountered clinical settings remains uncertain. Increasing knowledge of the natural history of the infection, routes of transmission in human populations, and potential environmental reservoirs will help to clearly define why, when, and in whom to treat H. pylori. Journal of Pediatric Gastroenterology and Nutrition 35:S128–S133