Establishing a Differential Diagnosis 1

The differential diagnosis for H. pylori-associated dyspepsia includes primarily:

  • Peptic ulcer disease (PUD)
  • Gastroesophageal reflux disease (GERD)
  • Nonulcer dyspepsia
  • Biliary tract disease
  • Pancreatitis
  • Cancer

No laboratory test can reliably distinguish between PUD and other causes of dyspepsia, and some patients have more than one disease concurrently (ie, PUD and GERD). Unless the patient has classic heartburn (suggesting GERD), there are no findings on history-taking or physical examination that reliably distinguish PUD from GERD.

Non-invasive testing should be limited to H. pylori tests that detect active infection only.
H. pylori antigen testing of human stool by enzyme immunoassay or immunochromatography is one of the simplest and least expensive methods available.

When to Test for H. pylori 1

Consider and test for H. pylori status if:

Patient is at a low risk for bilary tract disease, pancreatitis, or cancer:

  • <55 years of age and otherwise healthy
  • No warning signs or symptoms that suggest need for endoscopy

Use of NSAIDs has been stopped or ruled out.

Medical history suggests ulcer disease.

If the test result is positive, an anti-H. pylori treatment regimen should be initiated; if the test result is negative and symptoms persist, further evaluation may be required.

Alarm symptoms and signs of upper GI carcinoma

Signs and symptoms that raise the suspicion of upper GI carcinoma and indicate the need for upper GI endoscopy include:

  • Dysphagia
  • GI bleeding
  • New-onset symptoms after the age of 55 years
  • Unexplained anemia or weight loss
  • Severe vomiting

An H. pylori Diagnosis Can Have Larger Implications

Since 1994, H. pylori has been classified by WHO as a Group 1 Carcinogen for its causal relationship with gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma.2 A 2005 study presented at Digestive Disease Week showed that patients with peptic ulcers who underwent H. pylori  eradication had a reduced incidence of intestinal-type gastric cancer.3

Other implications associated with a diagnosis

  • PUD is a common and costly public health problem worldwide. Inexpensive, reliable diagnostic tests for H. pylori infection have been developed, and can be performed by primary care physicians. The infection can be cured by a combination regimen including selected antibiotics and proton pump inhibitor (PPI); an uncomplicated case of PUD does not usually require referral to a gastroenterologist
  • Patients suspected of having H. pylori infection should be tested prior to being prescribed a proton pump inhibitor (PPI). One out of every 4 patients on PPI therapy is H. pylori positive and can potentially be removed from PPI.4 Beyond the economic burden associated with the use of PPIs, there are medical risks associated with their use, including:


31% increase in risk of hip fractures and
54% increase in risk of vertebral fractures5

Clostridium difficile (C.difficile) associated disease

74% higher risk of nosocomial C.difficile in patients using PPI daily6

46% higher risk of recurrent C.difficile in patients on PPI therapy7

Decreased Vitamin B-12 levels

PPI therapy is associated with lower Vitamin B-12 levels in older patients which persist despite oral Vitamin B-12 supplementation.8

PPI dependency

Studies have shown that up to 33% of patients who initiate PPI treatment continue to refill their prescriptions without an obvious indication for maintenance therapy.9

*Risk is related to PPI treatment for over 1 year and with higher doses of PPI.

References:  1. Talley NJ; American Gastroenterological Association medical position statement: evaluation of dyspepsia: Gastroenterology. 2005; 129(5):1753-1780.  2. IARC Helicobacter pylori Working Group. Helicobacter pylori eradication as a strategy for preventing gastric cancer. Lyon, France: International Agency for Research on Cancer; 2014. Accessed January 12, 2016.  3. Takenaka R et al; Helicobacter pylori eradication prevents intestinal-type gastric cancer development in patients with H. pylori–related peptic ulcers, but not diffused-type cancer. Abstract presented at: Digestive Disease Week; May 14-19, 2005, Chicago IL.  4. Talley NJ, Vakil NB, Moayyedi P. American Gastroenterological Association medical position statement: evaluation of dyspepsia: Gastroenterology. 2005;129:1756-1780.  5. Eom CS, Park SM, Myung SK, Yun MJ, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med. 2011;9(3):257-267.  6. Howell MD, Novack V, Grgurich P, et. al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170(9):784-790.  7. Linsky A, Gupta K, Lawler EV, Fonda JR, Hermos JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med. 2010;170(9):772-778.  8. Lam JR, et al. Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency. JAMA. 2013;310(22):2435-2442.  9. Acid-reducing medicines may lead to dependency; EurekAlert! The Global Source for Science News, AGA 2009. Available at: Accessed February 12, 2016