eMedicine Specialties > Gastroenterology > Stomach

Helicobacter Pylori Infection: Differential Diagnoses & Workup

Author: Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Coauthor(s): Giuseppe Miragliotta, MD, Chairman, Professor, Department of Microbiology, University of Bari, Italy; Manoop S Bhutani, MD, FACG, FACP, Professor, Department of Medicine, Division of Gastroenterology, Director, Center for Endoscopic Ultrasound, Co-Director, Center for Endoscopic Research, Training and Innovation, University of Texas Medical Branch at Galveston
Contributor Information and Disclosures

Updated: Aug 14, 2008

Differential Diagnoses

Duodenal Ulcers
Gastritis, Chronic
Gastric Cancer
Gastritis, Stress-Induced
Gastric Ulcers
Gastroesophageal Reflux Disease
Gastrinoma
Lymphoma, Non-Hodgkin
Gastritis, Acute
Gastritis, Atrophic

Workup

Laboratory Studies

  • H pylori fecal antigen test 
    • This novel rapid test is based on monoclonal antibody immunochromatography of stool samples. The test has been reported to be very specific (98%) and sensitive (94%).
    • The results are positive in the initial stages of infection and can be used to detect eradication after treatment.
    • Although the H pylori fecal antigen test is an interesting tool, information about the cost of the test is pending.
  • Carbon 13 urea breath test  
    • The carbon 13 urea breath test (UBT) is based on the detection of the products created when urea is split by the organism.
    • Patients are asked to drink urea (usually with a beverage) labeled with a carbon isotope (carbon 13 or carbon 14). After a certain duration, the concentration of the labeled carbon is measured in the breath. The concentration is high only when urease is present in the stomach. Because the human stomach does not produce urease, such a reaction is possible only with H pylori infection.
    • The breath test is expensive but is becoming increasingly more available.
    • Other problems include false-negative results due to infection with coccoid forms of H pylori that do not produce as much urease or intake of antibiotics, bismuth, histamine 2 (H2) blockers, or proton pump inhibitors.
  • H pylori serology  
    • The serology test has a high (>90%) specificity and sensitivity. It is currently based on the quantitation of immunoglobulin G antibodies against H pylori by the means of an enzyme-linked immunosorbent assay.
    • It is useful for detecting a newly infected patient, but it is not a good test for follow-up of treated patients because the results do not indicate present infection with H pylori. The antibody titer may remain elevated for a long time after H pylori eradication. The number of false-positive results is age related and increases with age.
  • Antibiogram  
    • In geographic areas with a high resistance rate against metronidazole and clarithromycin, culture for antibiotic susceptibility testing (antibiogram) seems to be useful.
    • Alternatively, metronidazole and clarithromycin should not be recommended as first-line drugs in such areas.

Imaging Studies

  • Imaging studies are not helpful in the diagnosis of H pylori infection. Otherwise, they may be useful in patients with complicated disease (eg, ulcer disease, gastric cancer, MALToma).

Other Tests

  • Esophagogastroduodenoscopy  
    • An esophagogastroduodenoscopy (EGD) is often necessary in patients with symptoms of peptic ulcer disease in order to view the condition of the mucosal lining of the stomach and duodenum and to obtain biopsy specimens from the gastric antrum.
    • An echography associated with an EGD is mandatory in patients with biopsy results that are positive for gastric MALTomas in order to allow a more precise staging of the disease.
  • Peptic ulcer disease and gastric cancer may manifest with the same symptoms, and the only way to differentiate them is to view the lesion and to perform a histologic examination on biopsy specimens.

Procedures

  • Patients with new peptic ulcer disease should have a UBT, they should be tested for antibody titers, or they may require an investigation for stool antigens.
  • In patients with prior peptic ulcer disease, an EGD with biopsy and histological studies may be performed. Also, a UBT is helpful in these patients.

Histologic Findings

H pylori is a gram-negative bacterium. It produces urease, has a spirallike conformation, and is microaerophilic and motile because of the flagella. Flagella and urease are very important for its colonization of the gastric mucosa. Urease neutralizes gastric acidity, converting the gastric urea to ammonium ions, and flagella help the bacterium pass from the acidic gastric lumen into the mucus of the stomach. Two of the most important genes of H pylori are VACA and CAGA. The VACA gene codes the Vac-A cytotoxin, a vacuolizating toxin, and the CAGA gene codes for Cag-A protein, which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric epithelium of the host.

Biopsy specimens from EGD, stained with Giemsa stain, usually demonstrate a variable number of H pylori organisms adhering to the gastric epithelium, both coating the gastric wall and lining the gastric glands. The mucous film appears decreased. A large inflammatory infiltrate is present, with lymphocytes, neutrophils, and a variable number of mast cells that seem to play an important role in the pathogenesis of the gastric injury of persons infected with H pylori. Other stains are Genta, Warthin-Starry silver, and the classic hematoxylin and eosin. A rapid urease test may demonstrate the presence of the H pylori in the gastric mucosa via histochemistry results. Bacterial culture is very difficult. It is not used for diagnosis; it is used for experimental purposes only.

Staging

Although a staging system for the H pylori infection does not exist, some steps of the disease are well described. The first step is chronic gastritis, followed after a time by the second step, atrophic gastritis. The third step is intestinal metaplasia, which may evolve into dysplasia. The last step in this process is gastric adenocarcinoma. This process is very slow and may stop at any step because gastric cancers undoubtedly require several other factors to develop, not only an H pylori infection. As reported above, ultrasound and EGD should be considered in patients with gastric MALTomas in order to allow a more precise staging of the disease.

More on Helicobacter Pylori Infection

Overview: Helicobacter Pylori Infection
Differential Diagnoses & Workup: Helicobacter Pylori Infection
Treatment & Medication: Helicobacter Pylori Infection
Follow-up: Helicobacter Pylori Infection
Multimedia: Helicobacter Pylori Infection
References
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References

  1. Tomb JF, White O, Kerlavage AR, et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. Aug 7 1997;388(6642):539-47. [Medline].

  2. Giannakis M, Chen SL, Karam SM, et al. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc Natl Acad Sci U S A. Mar 2008;105(11):4358-63. [Medline].

  3. Lee SB, Yang JW, Kim CS. The association between conjunctival MALT lymphoma and Helicobacter pylori. Br J Ophthalmol. Apr 2008;92(4):534-6. [Medline].

  4. Aanpreung P. Suggestive parameters for eradication therapy in children with Helicobacter pylori gastritis. J Med Assoc Thai. Nov 2005;88 Suppl 8:S21-6. [Medline].

  5. Adachi K, Hashimoto T, Komazawa Y, et al. Helicobacter pylori infection influences symptomatic response to anti-secretory therapy in patients with GORD--crossover comparative study with famotidine and low-dose lansoprazole. Dig Liver Dis. Jul 2005;37(7):485-90. [Medline].

  6. Alexander GA, Brawley OW. Association of Helicobacter pylori infection with gastric cancer. Mil Med. Jan 2000;165(1):21-7. [Medline].

  7. Ceponis PJ, Jones NL. Modulation of host cell signal transduction pathways by Helicobacter pylori infection. Can J Gastroenterol. Jul 2005;19(7):415-20. [Medline].

  8. Chelimsky G, Czinn SJ. Helicobacter pylori infection in children: update. Curr Opin Pediatr. Oct 2000;12(5):460-2. [Medline].

  9. Cheng TY, Lin JT, Chen LT, et al. Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma. J Clin Oncol. Jul 20 2006;24(21):3483-9. [Medline].

  10. Chitsazi MT, Fattahi E, Farahani RM, e al. Helicobacter pylori in the dental plaque: is it of diagnostic value for gastric infection?. Med Oral Patol Oral Cir Bucal. Jul 1 2006;11(4):E325-8. [Medline].

  11. Craanen ME, Blok P, Dekker W, et al. Helicobacter pylori and early gastric cancer. Gut. Oct 1994;35(10):1372-4. [Medline].

  12. Davydov L, Cheng JW. The association of infection and coronary artery disease: an update. Expert Opin Investig Drugs. Nov 2000;9(11):2505-17. [Medline].

  13. Demirel A, Oncel S, Caydere M, et al. Helicobacter pylori infection in gastrectomy specimens. The Internet Journal of Gastroenterology 2000; 1 (1). [Full Text].

  14. Dunn BE, Cohen H, Blaser MJ. Helicobacter pylori. Clin Microbiol Rev. Oct 1997;10(4):720-41. [Medline].

  15. Eaton KA, Benson LH, Haeger J, et al. Role of transcription factor T-bet expression by CD4+ cells in gastritis due to Helicobacter pylori in mice. Infect Immun. Aug 2006;74(8):4673-84. [Medline].

  16. El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. Mar 23 2000;404(6776):398-402. [Medline].

  17. Ercan I, Cakir BO, Uzel TS, et al. The role of gastric Helicobacter pylori infection in laryngopharyngeal reflux disease. Otolaryngol Head Neck Surg. Jul 2006;135(1):52-5. [Medline].

  18. Fallone CA. Epidemiology of the antibiotic resistance of Helicobacter pylori in Canada. Can J Gastroenterol. Nov 2000;14(10):879-82. [Medline].

  19. Fallone CA, Barkun AN, Friedman G, et al. Is Helicobacter pylori eradication associated with gastroesophageal reflux disease?. Am J Gastroenterol. Apr 2000;95(4):914-20. [Medline].

  20. Farag TH, Stoltzfus RJ, Khalfan SS, et al. Helicobacter pylori infection is associated with severe anemia of pregnancy on Pemba Island, Zanzibar. Am J Trop Med Hyg. Mar 2007;76(3):541-8. [Medline].

  21. Fischbach W. Primary gastric lymphoma of MALT: considerations of pathogenesis, diagnosis and therapy. Can J Gastroenterol. Nov 2000;14 Suppl D:44D-50D. [Medline].

  22. Freston JW. Management of peptic ulcers: emerging issues. World J Surg. Mar 2000;24(3):250-5. [Medline].

  23. Garcia-Altes A, Rota R, Barenys M, et al. Cost-effectiveness of a 'score and scope' strategy for the management of dyspepsia. Eur J Gastroenterol Hepatol. Jul 2005;17(7):709-19. [Medline].

  24. Gatopoulou A, Mimidis K, Giatromanolaki A, et al. Impact of Helicobacter pylori infection on histological changes in non-erosive reflux disease. World J Gastroenterol. Apr 15 2004;10(8):1180-2. [Medline].

  25. Graham DY. Therapy of Helicobacter pylori: current status and issues. Gastroenterology. Feb 2000;118(2 Suppl 1):S2-8. [Medline].

  26. Graham DY, Lew GM, Lechago J. Antral G-cell and D-cell numbers in Helicobacter pylori infection: effect of H. pylori eradication. Gastroenterology. Jun 1993;104(6):1655-60. [Medline].

  27. Graham DY, Lew GM, Malaty HM, et al. Factors influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology. Feb 1992;102(2):493-6. [Medline].

  28. Graham DY, Malaty HM, Evans DG, et al. Epidemiology of Helicobacter pylori in an asymptomatic population in the United States. Effect of age, race, and socioeconomic status. Gastroenterology. Jun 1991;100(6):1495-501. [Medline].

  29. Guslandi M. Stool immunoassay for Helicobacter pylori is not specific enough. BMJ. Jun 3 2000;320(7248):1541. [Medline].

  30. Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. Am J Gastroenterol. Dec 1998;93(12):2330-8. [Medline].

  31. Jamieson GG. Current status of indications for surgery in peptic ulcer disease. World J Surg. Mar 2000;24(3):256-8. [Medline].

  32. Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. Jul 2006;19(3):449-90. [Medline].

  33. Leinonen M, Saikku P. Infections and atherosclerosis. Scand Cardiovasc J. 2000;34(1):12-20. [Medline].

  34. Lewis JD. Population screening and treatment of Helicobacter pylori. Gastroenterology. Dec 2000;119(6):1795-7. [Medline].

  35. Logan R. Epidemiology could yield new ways to manage H. pylori infection. Lancet. Sep 18 1999;354(9183):1006. [Medline].

  36. Lopes AI, Victorino RM, Palha AM, et al. Mucosal lymphocyte subsets and HLA-DR antigen expression in paediatric Helicobacter pylori-associated gastritis. Clin Exp Immunol. Jul 2006;145(1):13-20. [Medline].

  37. Mesquita MA, Lorena SL, Almeida JR, et al. One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the treatment of Helicobacter pylori infection in Brazilian patients with peptic ulcer. World J Gastroenterol. Jun 21 2005;11(23):3566-9. [Medline].

  38. Miragliotta G, Del Prete R, Mosca A. Helicobacter pylori infection and coronary heart disease. Lancet. Sep 10 1994;344(8924):751. [Medline].

  39. Nakajima S, Krishnan B, Ota H, et al. Mast cell involvement in gastritis with or without Helicobacter pylori infection. Gastroenterology. Sep 1997;113(3):746-54. [Medline].

  40. O'Morain C, Montague S. Challenges to therapy in the future. Helicobacter. 2000;5 Suppl 1:S23-6; discussion S27-31. [Medline].

  41. Padol S, Yuan Y, Thabane M, et al. The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis. Am J Gastroenterol. Jul 2006;101(7):1467-75. [Medline].

  42. Peach HG, Barnett NE. Determinants of basal plasma gastrin levels in the general population. J Gastroenterol Hepatol. Nov 2000;15(11):1267-71. [Medline].

  43. Pratt JS, Sachen KL, Wood HD, et al. Modulation of host immune responses by the cytolethal distending toxin of Helicobacter hepaticus. Infect Immun. Aug 2006;74(8):4496-504. [Medline].

  44. Reyrat JM, Rappuoli R, Telford JL. A structural overview of the Helicobacter cytotoxin. Int J Med Microbiol. Oct 2000;290(4-5):375-9. [Medline].

  45. Rodrigues MN, Queiroz DM, Bezerra Filho JG, et al. Prevalence of Helicobacter pylori infection in children from an urban community in north-east Brazil and risk factors for infection. Eur J Gastroenterol Hepatol. Feb 2004;16(2):201-5. [Medline].

  46. Santacroce L, Bufo P, Latorre V, et al. [Role of mast cells in the physiopathology of gastric lesions caused by Helicobacter pylori]. Chir Ital. Sep-Oct 2000;52(5):527-31. [Medline].

  47. Smoot DT, Mobley HL, Chippendale GR, et al. Helicobacter pylori urease activity is toxic to human gastric epithelial cells. Infect Immun. Jun 1990;58(6):1992-4. [Medline].

  48. Stähler FN, Odenbreit S, Haas R, et al. The novel Helicobacter pylori CznABC metal efflux pump is required for cadmium, zinc, and nickel resistance, urease modulation, and gastric colonization. Infect Immun. Jul 2006;74(7):3845-52. [Medline].

  49. Tsai CJ, Perry S, Sanchez L, et al. Helicobacter pylori infection in different generations of Hispanics in the San Francisco Bay Area. Am J Epidemiol. Aug 15 2005;162(4):351-7. [Medline].

  50. Tytgat GN. Review article: Helicobacter pylori: where are we and where are we going?. Aliment Pharmacol Ther. Oct 2000;14 Suppl 3:55-8. [Medline].

  51. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. Jun 4 1983;1(8336):1273-5. [Medline].

  52. Vaira D, Gatta L, Ricci C, et al. Peptic ulcer and Helicobacter pylori: update on testing and treatment. Postgrad Med. Jun 2005;117(6):17-22, 46. [Medline].

  53. Wang X, Wattiez R, Paggliacia C, et al. Membrane topology of VacA cytotoxin from H. pylori. FEBS Lett. Sep 15 2000;481(2):96-100. [Medline].

  54. Watts TL. Smoking, Helicobacter pylori, and periodontitis. BMJ. Jun 24 2006;332(7556):1513. [Medline].

  55. Wotherspoon AC. A critical review of the effect of Helicobacter pylori eradication on gastric MALT lymphoma. Curr Gastroenterol Rep. Dec 2000;2(6):494-8. [Medline].

  56. Yagi K, Honda H, Yang JM, et al. Magnifying endoscopy in gastritis of the corpus. Endoscopy. Jul 2005;37(7):660-6. [Medline].

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Further Reading

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Keywords

Helicobacter pylori infection, H pylori infection , Helicobacter pylori, H pylori, peptic ulcer disease, gastric cancer, gastric lymphoma, gastritis, gastric ulcers, PUD, Campylobacter pylori, C pylori, extragastric disease, mucosa-associated lymphoid tissue lymphomas, MALTomas, coronaritis, gastroesophageal reflux disease, GERD, iron deficiency anemia, iron-deficiency anemia, gastrointestinal disease, GI disease, heartburn, acid reflux, sour stomach, acid stomach, coronaritis, gastric mucosal cell proliferation, mucous cell proliferation, adenocarcinoma, ulcer, chronic active gastritis, Hp, Hp infection, HP infection

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Contributor Information and Disclosures

Author

Luigi Santacroce, MD, Assistant Professor, Medical School, State University at Bari, Italy
Disclosure: Nothing to disclose.

Coauthor(s)

Giuseppe Miragliotta, MD, Chairman, Professor, Department of Microbiology, University of Bari, Italy
Disclosure: Nothing to disclose.

Manoop S Bhutani, MD, FACG, FACP, Professor, Department of Medicine, Division of Gastroenterology, Director, Center for Endoscopic Ultrasound, Co-Director, Center for Endoscopic Research, Training and Innovation, University of Texas Medical Branch at Galveston
Manoop S Bhutani, MD, FACG, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Institute of Ultrasound in Medicine, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Medical Editor

David Greenwald, MD, Fellowship Program Director, Associate Professor, Department of Medicine, Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine
David Greenwald, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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