What is the best way to diagnose a stomach ulcer in a patient with a history of Helicobacter pylori infection, NSAID use, or a family history of stomach ulcers?

Diagnosing a Stomach Ulcer

The preferred diagnostic approach is noninvasive testing with a urea breath test (13C-UBT) or stool antigen test for H. pylori in patients under 60 years without alarm symptoms, while patients 60 years and older or those with alarm symptoms require upper endoscopy with gastric biopsies. 1

Initial Clinical Assessment

When evaluating for peptic ulcer disease, focus your history on:

• Duration and character of epigastric pain (typically burning, gnawing pain that may improve or worsen with eating) 1
• NSAID use history, including aspirin and over-the-counter medications 1, 2
• Alarm symptoms: unintentional weight loss, progressive dysphagia, recurrent vomiting, evidence of GI bleeding (melena, hematemesis), or family history of gastric cancer 1, 2

Physical examination should document vital signs and assess for epigastric tenderness, though approximately two-thirds of patients with peptic ulcer disease are asymptomatic 3.

Age-Stratified Diagnostic Algorithm

Patients Under 60 Years Without Alarm Symptoms

First-line: Noninvasive H. pylori testing 1, 4

1. Urea breath test (13C-UBT) is the preferred first-line diagnostic test 1
2. Stool antigen test is an acceptable alternative if breath testing is unavailable 1
3. Validated laboratory serology (>90% sensitivity and specificity) can be used only if the patient cannot stop PPIs, but this detects exposure rather than active infection 5, 1

Critical caveat: Patients must discontinue PPIs for at least 2 weeks and antibiotics/bismuth for at least 4 weeks before testing, as these medications reduce bacterial load and cause false-negative results 2. Office-based serologic tests are less accurate than laboratory-based tests and should be avoided 5.

Patients 60 Years and Older OR Any Age with Alarm Symptoms

Mandatory: Upper endoscopy with biopsies 2, 4

Even if H. pylori testing is positive, endoscopy is required to exclude concurrent gastric cancer in this population 2. The endoscopy should include:

• For suspected peptic ulcer: Biopsies from the base and edges of gastric ulcers (duodenal ulcers typically don't require routine biopsy) 5
• For H. pylori detection: At least 2 biopsies from the antrum and 2 from the gastric body, ideally in separately labeled jars 5
• Immunohistochemistry with H. pylori-specific antibodies is the most accurate histologic detection method 5

The proximal migration of H. pylori from antrum to body occurs in patients on potent acid suppression, making gastric body biopsies especially important 5.

Special Populations Requiring Testing

Beyond typical dyspepsia presentations, proactively test for H. pylori in:

• Individuals with current or past gastric/duodenal ulcers (100% agreement, high evidence) 5
• Family members in the same household of H. pylori-positive patients (91% agreement, moderate evidence) 5
• Individuals with family history of peptic ulcer disease (91% agreement, moderate evidence) 5
• Regular NSAID users, as H. pylori and NSAIDs synergistically increase bleeding ulcer risk more than sixfold 4, 6
• First-generation immigrants from high-prevalence countries (82% agreement, high evidence) 5

Confirming H. pylori-Negative, NSAID-Negative Ulcers

If a patient has documented peptic ulcer disease but tests negative for H. pylori, you must:

1. Reconfirm H. pylori negativity using a different testing method, as false negatives are common 7
2. Obtain detailed medication history for all NSAIDs, aspirin, anticoagulants, and recent antibiotics 2
3. Perform endoscopy with biopsies of the ulcer and surrounding mucosa to exclude malignancy, lymphoma, Crohn's disease, and unusual infectious agents 7
4. Consider gastrinoma (Zollinger-Ellison syndrome) with fasting gastrin levels if the etiology remains unexplained 7

Common Diagnostic Pitfalls

• Never rely on H. pylori testing alone in patients over 60 years—endoscopy is mandatory to exclude gastric cancer regardless of H. pylori status 2
• Avoid testing while patients are on PPIs, antibiotics, or bismuth, as these cause false-negative results 2
• Do not use antibody tests to confirm cure after treatment, as antibody levels remain elevated after eradication 5
• Serology only indicates exposure, not active infection, and its positive predictive value falls dramatically in populations where many patients have been previously treated 5

Test of Cure After Treatment

After completing H. pylori eradication therapy, perform a test of cure 6-8 weeks post-treatment using urea breath test or stool antigen test (not serology) 1. This confirms successful eradication and prevents ulcer recurrence, which occurs in approximately 1 in 6 infected individuals over their lifetime 5.