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Journal of Pediatric Gastroenterology and Nutrition31:490–497 © November 2000 Lippincott Williams & Wilkins, Inc., Philade...
TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION                                                             491   The...
492                                                           GOLD ET AL.          TABLE 2. Tests for Helicobacter pylori ...
TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION                                                       493is difficult...
494                                                           GOLD ET AL.    Endoscopically Diagnosed or Radiographically ...
TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION                                                       495            ...
496                                                                    GOLD ET AL.TABLE 3. Recommended eradication therapi...
TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION                                                                  4972...
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Diagnosi e trattamento delle infezioni da H. Pylori in pediatria


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Diagnosi e trattamento delle infezioni da H. Pylori in pediatria

  1. 1. Journal of Pediatric Gastroenterology and Nutrition31:490–497 © November 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Medical Position Statement: The North American Society for Pediatric Gastroenterology and NutritionHelicobacter pylori Infection in Children: Recommendations for Diagnosis and Treatment *Benjamin D. Gold, †Richard B. Colletti, ‡Myles Abbott, §Steven J. Czinn, Yoram Elitsur, ¶Eric Hassall, #Colin Macarthur, **John Snyder, and ††Philip M. Sherman Division of *Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; †Pediatric Gastroenterology, University of Vermont, Fletcher Allen Health Center, Burlington, Vermont; ‡Berkeley California; §Pediatric Gastroenterology, Rainbow Babies and Children’s Hospital, Cleveland, Ohio; Division of Gastroenterology, Marshall University School of Medicine, Huntington, West Virginia; ¶Division of Gastroenterology, BC Children’s Hospital, Vancouver, British Columbia, Canada; Divisions of #General Pediatrics and ††Gastroenterology andNutrition, The Hospital for Sick Children, Toronto, Ontario, Canada; and **Pediatric Gastroenterology, University of California San Francisco, San Francisco, California, U.S.A. Helicobacter pylori infects at least 50% of the world’s been infected for many years before clinical symptomshuman population (1). However, most individuals in- appeared (6). The incidence of H. pylori infection infected with H. pylori do not experience symptoms or industrialized countries is estimated to be approximatelyhave signs of recognizable disease. In most children, the 0.5% of the susceptible population per year. In contrast,presence of H. pylori infection does not lead to clinically there is a significantly higher estimated incidence of H.apparent disease, even when the organism colonizing the pylori infection in developing countries of approximatelygastric mucosa causes chronic active gastritis (2). 3% to 10% per year (7). The limited data on the inci-Knowledge about H. pylori infection is evolving, par- dence of H. pylori infection in children consist largely ofticularly in the pediatric age group for which there are retrospective seroprevalence studies.still large gaps in knowledge. Humans appear to be the primary natural reservoir of Additional multicenter, randomized, placebo- H. pylori infection. Other reservoirs that have been pro-controlled treatment trials in children infected by H. py- posed include water, domestic cats, and houseflies (8–lori are critically needed to definitively characterize the 10). The risk factors described for acquiring infectioneffect of H. pylori eradication treatment during child- include residence in a developing country, poor socio-hood on symptoms and gastroduodenal mucosal disease. economic conditions, family overcrowding, and possibly There is compelling evidence that this organism is an ethnic or genetic predisposition. In North America,associated with a significant proportion of duodenal ul- the prevalence rates of H. pylori among Asian-Ameri-cers and, to a lesser extent, with gastric ulcers in children cans, African-Americans and Hispanics are similar to(3). There are epidemiologic data linking chronic H. py- those of residents of developing countries (11). The routelori infection, probably beginning in childhood, with the of transmission of H. pylori in humans is not known butdevelopment of gastric adenocarcinoma and gastric lym- is postulated to be fecal-oral, gastric-oral (in vomitus), orphoma (4). Findings in recently reported animal models oral-oral (12).support the role of H. pylori in the pathogenesis of gas- Although H. pylori infection may be acquired duringtric cancers (5). childhood, there are limited guidelines regarding its di- There are many studies describing the prevalence of agnosis and treatment in children and adolescents. SuchH. pylori infection. Most epidemiologic studies of H. evidence-based consensus guidelines are needed for bothpylori infection have been performed in adults who had primary care and specialty medical providers to ensure judicious use of diagnostic testing and appropriate thera- peutic regimens for the management of children with H. Received and accepted September 8, 2000. pylori infection. Therefore, the North American Society Address correspondence and reprint requests to Dr. Benjamin Gold, for Pediatric Gastroenterology and Nutrition (NASPGN)Emory University School of Medicine, 2040 Ridgewood Drive, NE,Atlanta, GA 30322, U.S.A.; or to Dr. Richard B. Colletti, University of appointed the Helicobacter pylori Infection GuidelineVermont, Department of Pediatrics, A-121 Given Medical Building, Committee to develop a clinical practice guideline forBurlington, VT 05405-5557, U.S.A. the child with H. pylori infection. 490
  2. 2. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 491 These clinical practice guidelines are designed to as- TABLE 1. Summary of recommendations and the quality ofsist primary care physicians, nurse practitioners, physi- the supporting evidencecian assistants, and pediatric gastroenterologists in the Quality ofevaluation and treatment of suspected or diagnosed H. Recommendations evidenceapylori–associated disease. The desired outcomes of these How reliable are tests for H. pylori infection?recommendations are the detection of children and ado- Currently, the diagnosis of H. pylori-mediated diseaselescents with H. pylori who need treatment. These rec- can be made reliably only through the use ofommendations are applicable to children in developed endoscopy with biopsy. II, IIIcountries where the prevalence of infection is low but Presently available commercial serologic tests are frequently unreliable for screening children for themay not be directly relevant to children living in com- presence of H. pylori infection. IImunities where there is a higher frequency of gastric Urea breath testing, although promising, has not beencolonization by H. pylori. These recommendations have studied sufficiently in children. IIbeen endorsed by the Executive Council of NASPGN When is testing indicated?and by the American Academy of Pediatrics. They are It is recommended that testing be performed in children with endoscopically diagnosed, orgeneral guidelines to assist medical care providers in the radiographically definitive, duodenal or gastric ulcers. Idiagnosis and treatment of H. pylori infection in chil- It is recommended that children with recurrentdren. They are not intended as a substitute for clinical abdominal pain, in the absence of documentedjudgment or as a protocol for the management of all ulcer disease, not be tested for H. pylori infection. II Testing for H. pylori infection is not recommended inpatients. asymptomatic children. II In its deliberations, the committee addressed four is- Routine screening of children with a family history ofsues about H. pylori infection in children: How reliable gastric cancer or recurrent peptic ulcer disease isare tests to detect H. pylori? When is testing for H. pylori not recommended. IIindicated? When is treatment of H. pylori infection in- Testing following treatment of documented H. pylori is recommended, especially with complicateddicated? What is the preferred treatment of H. pylori? A peptic ulcer disease (i.e., bleeding, perforation, orsummary of the recommendations of the H. pylori Infec- obstruction). For patients who remain symptomatiction Guideline Committee is presented in Table 1. after treatment, it is recommended that endoscopy and biopsy be performed to evaluate for the persistence of H. pylori-associated peptic ulcer METHODS disease. I, II If pathological evidence of MALT lymphoma is The H. pylori Infection Guideline Committee consisted of a documented, then testing for H. pylori isprimary care pediatrician, a clinical epidemiologist, and seven recommended. IIpediatric gastroenterologists. To develop evidence-based When is treatment of H. pylori infection indicated?guidelines, articles published in English from January 1966 Eradication treatment is recommended for children whothrough May 1999 on H. pylori in children were searched. have a duodenal ulcer or gastric ulcer identified at endoscopy and H. pylori detected on histology. IArticles on diagnosis and treatment were sought separately. A prior history of documented duodenal or gastricLetters, editorials, case reports, abstracts, and reviews were ulcer disease is an indication for treatment if activeexcluded. Evidence tables were prepared based on 16 articles H. pylori infection is documented. Ion clinical presentation, 9 articles on diagnostic studies, and 30 There is no compelling evidence for treatingarticles on therapy. Subsequently, additional articles were iden- children with H. pylori infection and non-ulcertified and reviewed. When the pediatric literature was insuffi- dyspepsia or functional recurrent abdominal pain. IIIcient, the adult literature was also considered. Articles were Treatment is not recommended for H. pylori-infectedevaluated using published criteria (13). The Committee based children residing in chronic care facilities; childrenits recommendations on an integration of a review of the medi- with unexplained short stature; or children at increased risk for acquisition of infection, includingcal literature and expert opinion. Consensus was achieved by asymptomatic children who have a family memberusing the nominal group technique, a structured quantitative with either peptic ulcer disease or gastric cancer. IIImethod, as described previously (14,15). By using the methods What is the preferred treatment of H. pylori infections in children?of the Canadian Preventive Services Task Force (16), the qual- It is recommended that treatment consist of three ority of evidence of each of the recommendations made by the four medications, given once or twice daily, forcommittee was determined and is summarized (Table 1). one to two weeks. I a Categories of the quallity of evidence: I Evidence obtained from at HOW RELIABLE ARE TESTS FOR least one properly designed randomized controlled study. II-1 Evidence obtained from well-designed cohort or case-controlled trials without H. PYLORI INFECTION? randomization. II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or Several invasive and noninvasive tests are available to research group. II-3 Evidence obtained from multiple time series withdetect H. pylori infection (Table 2). An ideal test for H. or without the intervention. Dramatic results in uncontrolled experi-pylori is noninvasive or minimally invasive, highly ac- ments (such as the results of the introduction of penicillin treatment incurate, inexpensive, and readily available and enables the 1940’s) could also be regarded as this type of evidence. III Opinions of respected authorities, based on clinical experience, descriptive stud-differentiation between active or past infection with the ies, or reports of expert committees. J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000
  3. 3. 492 GOLD ET AL. TABLE 2. Tests for Helicobacter pylori and study. The optimal staining of biopsy sections is best Helicobacter-related disorders determined by local expert pathologists. Endoscopic ex- Invasive tests requiring endoscopy amination of and specimens obtained in the esophagus, Biopsies and histology stomach, and duodenum also provide information about Rapid urease testing other upper gastrointestinal disorders that may be the Bacterial culture cause of clinical symptoms including, for example, Polymerase chain reaction of bacterial DNA esophagitis and peptic ulcer disease that is not due to H. Non-invasive tests Serum and whole blood antibody pylori. Saliva antibody There are drawbacks to diagnostic gastrointestinal en- Urine antibody doscopy. It is a relatively invasive procedure requiring Stool antigen sedation or anesthesia. Furthermore, the test remains Urea breath testing relatively expensive in many centers, and access to an endoscopist with specific pediatric expertise is limited in many geographic areas.organism. In addition, such a test enables discriminationbetween the presence of H. pylori infection and H. py-lori–associated disease. Because no such ideal test cur- Rapid Urease Testing of Biopsy Tissuesrently exists, the advantages and drawbacks of tests that Urease testing (CLO, TriMed, Kansas City, MO; Hp-are available require critical appraisal and must be as- Fast, GI Supply, Division of ChekMed Systems Inc.,sessed for their suitability for use in children. Camphill, PA; PyloriTek, Horizons International, Agua- Failure to reach an accurate diagnosis carries consid- dilla, Puerto Rico) provides indirect identification of H.erable financial and social costs including the expense of pylori infection within a few hours of endoscopy (20).more tests, repeated visits to health care providers, inap- However, these tests have a poor positive predictivepropriate treatment, and missed school or work. A de- value (as low as 50%) in children, even though the nega-finitive test, even if it is expensive, may result in overall tive predictive value is high (97–98%) (20,21). The ac-cost savings (17). curacy of the test is dependent on the number of tissue It is important to emphasize that the accuracy of a specimens tested, the location of biopsy sites, bacterialdiagnostic test is greatly impacted by the prevalence of load, and previous usage of antibiotics and proton pumpH. pylori in the population tested. There is a need for inhibitors, as well as the prevalence of H. pylori in thestudies to assess the accuracy and potential utility of population tested.various noninvasive diagnostic tests in populations inNorth America that differ in demographic factors thatmay influence the prevalence and natural history of H. Bacterial Culturepylori infection (18). Culture of H. pylori from the gastric mucosa provides an opportunity to obtain a profile of antibiotic sensitivity Invasive Testing Through Endoscopy that could identify potential treatment failure due to an- tibiotic resistance (22). Culture also provides a bacterial Biopsies and Histopathology strain for use in epidemiologic studies to examine asso- ciations of virulence characteristics with disease out- The definitive diagnosis of H. pylori and the evidence come. However, bacterial culture for H. pylori is rela-of the consequences of infection can be made reliably tively expensive and success rates for recovery of theonly by endoscopy with multiple biopsy specimens ob- organism in many clinical laboratories are low (23). Cur-tained in one or more regions of the stomach including rently, standardization of culture procedures has not beenantrum, body, and transition zones (i.e., cardia and inci- established, and bacterial cultures are only obtained rou-sura). Histology provides information regarding the pres- tinely in research settings.ence of H. pylori and the severity and topographic dis-tribution of gastritis including the presence of atrophic Polymerase Chain Reactiongastritis, intestinal metaplasia, and mucosa-associatedlymphoid tissue (MALT) lymphoma (3). As in adults, Polymerase chain reaction (PCR) is a highly sensitivebiopsy specimens obtained in the prepyloric antrum have technique that can be used to detect the presence of H.the highest yield in H. pylori infection. Tissue specimens pylori in body fluids (e.g., gastric juice and stool), tissuesoften are also obtained from the body and the transition (e.g., gastric mucosa), and water (24). Testing of H. py-zones of the stomach, particularly if the patient has re- lori genomic DNA by PCR can be used to advancecently taken acid-suppressing medication (19). It is rec- knowledge at the molecular level—for example, by pro-ommended that multiple biopsies be performed in chil- viding information about point mutations conferringdren with endoscopically documented peptic ulcer dis- resistance to antibiotics and about putative bacterialease or peptic ulcer suspected as a result of radiographic virulence factors. However, PCR is expensive, the assayJ Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000
  4. 4. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 493is difficult to set up, specificity may be compromised by cation therapy. However, patients may be reluctant toinadvertent contamination, and it is not widely available collect stool specimens. In addition, refrigerated stoolsoutside the research laboratory. are more difficult to test. Additional pediatric studies evaluating the accuracy of stool antigen testing for both initial diagnosis and posttreatment follow-up are re- Noninvasive Testing quired before specific recommendations can be consid- Immunoassay Tests to Detect H. pylori Antibodies ered (32). Enzyme-linked immunosorbent assays (ELISAs) to Urea Breath Testingdetect H. pylori antibodies are relatively inexpensive andeasy to implement in the clinical setting. Many tests areavailable for use to test whole blood, plasma, or serum. Urea breath tests are noninvasive and have high sen-However, compared with histology, the sensitivity and sitivity and specificity (>95%) both in adults (33) andspecificity of serologic assays are poor in both adults and children (34,35). The test requires the ingestion of eitherchildren unless used in the populations in which they radiolabeled 14C-urea or urea tagged with the stable iso-were initially developed (25). In general, the accuracy of tope 13C. Test results may be influenced by concurrentserum-based immunoassays and whole-blood tests for use of antibiotics and acid-suppressing medications anduse in the physician’s office in symptomatic children in by the presence of other urease-producing organismsdeveloped countries is poor, with a range of sensitivity of present in the oral cavity. Test parameters are currentlyonly 60% to 70% (26–28). Furthermore, age-related cut- laboratory-specific (e.g., dosages for differing ages ofoff values for commercial immunologic tests have not children, cutoff values, duration of fasting, use of a testbeen established for children. One immunoassay devel- meal, times of sampling, and timing of posttherapy test-oped in a research center to detect H. pylori–specific ing) and have not been well standardized for childrenimmunoglobulin (Ig)G in children was 91% sensitive (36). In addition, urea breath testing is technically morecompared with sensitivity of less than 70% in three com- difficult to perform in small children and infants, withmercially available assays (28). In areas with low preva- failure rates in collection up to 10%, especially outsidelence of H. pylori infection, such as in developed coun- the clinical research setting (34).tries, testing of serum and whole blood is not sufficiently In summary, the diagnosis of H. pylori–associated dis-accurate to diagnose H. pylori infection in children. Ac- eases currently can be made reliably only by endoscopycordingly, treatment regimens based on the results of with biopsies. The most commonly used noninvasive testthese tests cannot be recommended. Serologic tests may to screen adults for H. pylori infection is serology. Un-not be used reliably to verify eradication of H. pylori, fortunately, currently available commercial serologicbecause antibody titers can remain positive for months, tests are frequently unreliable for screening children fordespite resolution of infection. the presence of H. pylori infection. Current whole-blood, saliva, and urinary immunoassays are insufficiently sen- sitive or specific to be effective as diagnostic tools. In- Saliva and Urine Tests for H. pylori Antibodies sufficient data are available in children to confirm the accuracy of the recently approved H. pylori stool antigen Similar to serologic tests, saliva-based tests also detect test. The urea breath test has the promise to providethe presence of H. pylori–specific IgG antibodies. The noninvasive and accurate diagnosis of H. pylori infec-tests are easy to perform, painless, and inexpensive. Sa- tion; but currently, there is insufficient evidence that itliva tests are less sensitive than assays of serum or whole can be used to reliably diagnose or exclude H. pylori–blood (29). The protein concentration of saliva appears to associated diseases.affect the accuracy of test results. Urine-based assays areeasy to perform, require minimal labor for collection,and are painless (30). However, these assays are highlyvariable and are not yet commercially available. There- WHEN IS TESTING INDICATED?fore, saliva and urine assays for the detection of H. pyloriantibodies cannot be recommended. The primary goal of testing is to diagnose the cause of clinical symptoms and not simply to detect the presence Stool Test for H. pylori Antigens of H. pylori infection. Testing is not helpful unless it will alter the management of the disease. Testing of H. pylori antigens in stools has shown A variety of invasive and noninvasive tests exist forpromising results in adults for the noninvasive diagnosis the detection of H. pylori infection, but their degree ofof gastric infection using a commercially available kit sensitivity and specificity vary, as do their suitability for(31). Testing for H. pylori antigens in feces also appears clinical use in children. Thus, there is potential for inap-to be accurate for use in monitoring the success of eradi- propriate testing or misuse of tests in children. J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000
  5. 5. 494 GOLD ET AL. Endoscopically Diagnosed or Radiographically dicates that there is a link between gastric cancers (both Definitive Peptic Ulcer adenocarcinoma and lymphoma) and H. pylori infection. However, no studies have shown that H. pylori eradica- The causal relationship between H. pylori infection tion during childhood prevents subsequent developmentand primary duodenal ulcers is compelling (37). There- of gastric malignancies. Until evidence is available tofore, it is recommended that testing for the presence of H. better define the role of H. pylori in a variety of gastricpylori infection be performed in children with endo- cancers and the role of H. pylori eradication in diseasescopically diagnosed or radiographically definitive duo- prevention, routine screening of children with a familydenal ulcer. Although the data in children are less com- history of gastric cancer or recurrent peptic ulcer diseaseplete, evidence from studies in adults (38) supports the is not recommended.recommendation that testing for H. pylori also be per-formed in subjects with a documented gastric ulcer. Histologic Evidence of Lymphoma Abdominal Pain Unrelated to Peptic Ulcers In the rare circumstance in which histopathologic evi- Several lines of evidence, including serologic surveys, dence of MALT lymphoma is documented in a child,endoscopic evaluations, and treatment trials indicate that testing for H. pylori is recommended.H. pylori is not a frequent cause of recurrent abdominalpain in children. There have been six studies performedin North America, Europe, and Australia, with 2715 chil- Follow-up of Therapy for H. pylori Infectiondren evaluated by esophagogastroduodenoscopy and bi-opsy, serology, or urea breath test (39–44). Although 5% Testing to confirm eradication of infection and theto 17% of children with abdominal pain had evidence of resolution of associated symptoms and disease sequelaeinfection with H. pylori, 5% to 29% of children without is advisable in selected children. Guidelines in adultsabdominal pain were also infected with H. pylori. There recommend testing after treatment of complicated pepticare no convincing data to support routine testing of chil- ulcer (52), but studies in children are limited. As such,dren with recurrent abdominal pain (39–45). Investiga- few data are available on the effectiveness of therapy intors have also looked for specific symptom patterns in H. children, testing after treatment is recommended in thosepylori–infected children, but none so far has been de- with complicated peptic ulcer disease (i.e., bleeding, per-tected (46–50). Future studies are needed to determine foration, or obstruction) or lymphoma. For patients whowhether subsets of children with abdominal pain can be remain symptomatic, it is recommended that endoscopyidentified in whom signs and symptoms are caused by H. and biopsy be performed to evaluate for the persistencepylori infection. It is recommended that children with of H. pylori-associated peptic ulcer disease. For patientsrecurrent abdominal pain, in the absence of documented with an uncomplicated ulcer who are asymptomatic afterulcer disease, not be tested for H. pylori infection. completion of eradication therapy, testing for persistence of infection is not necessary. However, some physicians Asymptomatic Children, Including Those at advocate the use of urea breath testing in this clinical Increased Risk of Acquiring H. pylori Infection setting. There are no compelling data to support routine testingin asymptomatic children. Testing for H. pylori infection WHEN IS TREATMENT OF H. PYLORIis not recommended in children without clinical symp- INFECTION INDICATED?toms, including those residing in long-term care facili-ties, children with short stature, and those at increased Eradication therapy is recommended for children whorisk of acquiring H. pylori infection. In addition, pur- have both known active H. pylori infection and symp-ported extraintestinal manifestations of H. pylori infec- tomatic gastrointestinal disease. Known active H. pylorition have not been demonstrated in a convincing fashion infection is defined as identification of the organisms by(51). Accordingly, a test-and-treat approach is not rec- histopathologic examination or as a positive culture fromommended in these circumstances. endoscopic gastric biopsy. Serology is not a reliable test for active disease, because it may indicate past but not Family History of Gastric Cancer or Recurrent current infection with H. pylori. Peptic Ulcer Disease There are no randomized controlled trials in children that determine the precise clinical settings in which No currently available data support routine testing in eradication therapy is indicated. Although additionalchildren with a positive family history of diseases related studies in children are needed (53), the available evi-to H. pylori infection (52). Epidemiologic evidence in- dence supports the following recommendations.J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000
  6. 6. TREATMENT RECOMMENDATIONS FOR HELICOBACTER INFECTION 495 Duodenal and Gastric Ulcers cost of care. Therefore, the H. pylori Infection Guideline Committee concludes that there is insufficient evidence Eradication treatment is recommended for children to support either initiating or withholding eradicationwho have a duodenal ulcer or gastric ulcer identified at treatment in this situation.endoscopy and H. pylori documented by histopathology.A prior history of duodenal or gastric ulcer disease is alsoan indication for treatment if active H. pylori infection is Recurrent Abdominal Pain anddocumented. If a definitive ulcer is present on contrast Asymptomatic Childrenradiography (e.g., an ulcer crater is present), eradicationtherapy is indicated if either a noninvasive or invasivetest result is positive for H. pylori. There is no compelling evidence, at the present time, for treating children with H. pylori infection and either Lymphoma nonulcer dyspepsia or functional recurrent abdominal pain. There is also no convincing evidence currently The rare child with pathologic evidence of MALT available that asymptomatic children who have a familylymphoma and H. pylori infection should be treated with member with H. pylori infection, peptic ulcer, or gastriceradication therapy. Further studies of pediatric patients cancer need treatment.with lymphoma should be performed to monitor the re-currence, progression, or remission of the tumor aftertherapy. WHAT IS THE PREFERRED TREATMENT OF H. PYLORI INFECTION IN CHILDREN? Atrophic Gastritis With Intestinal Metaplasia The optimum treatment regimen for eradicating H. py- Eradication treatment is recommended for the rare lori in children has not been determined (59). Effectivechild who has pathologically proven atrophic gastritis therapy in adults is defined as successful eradication ofwith intestinal metaplasia, according to the updated Syd- H. pylori infection in a minimum of 80% of treated sub-ney classification of gastritis (54), plus coexisting H. jects (60). Although it appears that treatment options thatpylori infection. Because of the preneoplastic nature of have been effective in adults will also be efficacious inthese pathologic changes, follow-up endoscopy is rec- children, controlled studies in pediatric populations areommended to confirm that the H. pylori infection has needed to confirm or refute this supposition. Unfortu-been eradicated and to ensure that there is no subsequent nately, the limited data currently available in children areprogression of gastric mucosal disease. open-label, case series and uncontrolled, anecdotal ob- servations that do not meet the minimum criteria for Gastritis Without Peptic Ulcer Disease determining efficacy. In vitro sensitivity of H. pylori to a specific drug does not guarantee that the bacterium will The finding of H. pylori–associated gastritis in the be effectively eradicated from the human stomach.absence of peptic ulcer disease during diagnostic endos- Therefore, current treatment strategies to eradicate H.copy poses a dilemma for the endoscopist. The decision pylori have been developed primarily by trial-and-errorto treat H. pylori–associated gastritis without duodenal or methodology (61).gastric ulcer in this situation is subject to the judgment of The single most important determinant of successfulthe clinician and deliberations with the patient and fam- eradication therapy is compliance with the prescribedily. Studies in adults on the effect of eradication treat- combination treatment regimen (62). There are well-ment on abdominal symptoms have produced conflicting described treatment failures due to suboptimal compli-results (55–58). There are no randomized controlled tri- ance. To enhance adherence to the treatment regimen,als in children. The long-term impact of the eradication the number of medications prescribed, the frequency ofof H. pylori and the healing of gastritis on the subsequent administration, and the duration of therapy are best keptdevelopment of peptic ulcer disease, adenocarcinoma, or to the minimum required for successful treatment.lymphoma is uncertain. Although there is a small life- It is recommended that initial treatment consist oftime risk of development of peptic ulcer disease associ- three medications, administered twice daily, for 1 to 2ated with H. pylori gastritis, there are no randomized weeks (63). Specifically, as shown in Table 3, three first-controlled trials demonstrating that eradication of H. py- line therapy options are recommended for use in childrenlori results in prevention of peptic ulcer disease. In ad- and adolescents. For patients in whom initial treatmentdition, there are no data showing that eradication therapy has failed, two other options are recommended, includ-influences the long-term risk for development of gastric ing one option with four medications. It is recommendedcancers. Antibiotic treatment can result in adverse drug that monotherapy and two-drug regimens be avoided,reactions, promote antibiotic resistance, and increase the because they are ineffective and increase the likelihood J Pediatr Gastroenterol Nutr, Vol. 31, No. 5, November 2000
  7. 7. 496 GOLD ET AL.TABLE 3. Recommended eradication therapies for H. pylori pump inhibitor also reduces the effectiveness of eradica- disease in children tion treatment protocols. Studies are needed to determineFirst-line the relative importance of these risk factors in pediatric options Medications Dosage populations. 1 amoxicillin 50 mg/kg/day up to 1 g bid REFERENCES clarithromycin 15 mg/kg/day up to 500 mg bid 1. Ernst PB, Gold BD. Helicobacter pylori in childhood: new insights proton pump inhibitor: 1 mg/kg/day up to 20 into the immunopathogenesis of gastric disease and implications omeprazole (or comparable mg bid for managing infection in children. J Pediatr Gastroenterol Nutr. acid inhibitory doses of 1999;28:462–73. another PPI) 2. Drumm B. Helicobacter pylori in the pediatric patient. Gastroen- 2 amoxicillin 50 mg/kg/day up to terol Clin North Am. 1993;22:169–82. 1 g bid 3. Dohil R, Hassall E, Jevon G, et al. 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