The diagnosis of peptic ulcer disease rests on two questions: does the patient have an ulcer, and is Helicobacter pylori present? The two are answered by different tests, and which test is used depends on whether the patient has already been sent for endoscopy.
Endoscopy
Upper gastrointestinal endoscopy, also called esophagogastroduodenoscopy (EGD), is the reference test. It shows the ulcer directly, tells a duodenal ulcer from a gastric one, and allows tissue to be sampled. The distinction matters because the two behave differently. A duodenal ulcer is almost never malignant, so it is not routinely biopsied. A gastric ulcer is different: a benign ulcer cannot be reliably separated from a malignant one at endoscopy, so several biopsies are taken from its base and edge, and in some settings a repeat endoscopy is arranged to confirm that it has healed.
Endoscopy is preferred over empirical treatment when the patient has alarm features or is older, because the chance of finding a cancer rises with age. The age threshold is usually taken as 50, with a range of about 45 to 55 years between regions.
Testing for H. pylori
Every patient with a confirmed ulcer should be tested for H. pylori, because eradicating the infection changes the course of the disease. The tests divide into those that need endoscopy and those that do not.
The invasive tests use a biopsy taken at endoscopy and examined by a rapid urease test, histology, culture or molecular testing. They are accurate, but they require the endoscopy itself.
The non-invasive tests avoid it. The urea breath test and the stool antigen test detect active infection and are the tests of choice for both diagnosis and for confirming that treatment has worked; the urea breath test is the most accurate non-invasive test, with a sensitivity of about 94%. Serology detects antibodies against H. pylori and is cheaper and simpler, but it cannot separate an active infection from a past one, because antibodies fall only slowly after the bacterium has gone. A positive serology may therefore reflect an infection that has already cleared, which is why serology is not used to confirm eradication. It remains useful where other tests are unreliable, for instance in bleeding ulcers or after recent antibiotics.
Two practical points affect the results. Proton pump inhibitors suppress the bacterium and can cause a false-negative test, so they are stopped for about two weeks before testing; antibiotics and bismuth are stopped for four weeks. And after treatment, a test for cure should wait at least four weeks, so that any surviving bacteria have time to regrow and be detected.
Test and treat, or scope first
For a younger patient with dyspepsia and no alarm features, a non-invasive test-and-treat strategy is recommended: test for H. pylori and treat the infection if it is found. Compared with simply suppressing acid, it gives the same short-term relief of symptoms, but only eradication can cure an ulcer and prevent its return. Endoscopy is chosen instead when the patient is older, has alarm features, or has a family history of gastric cancer, because these raise the chance of a lesion that only endoscopy can see.
When the ulcer does not behave, and other causes
A peptic ulcer that recurs or resists treatment, or that comes with diarrhoea, multiple ulcers, or an ulcer beyond the first part of the duodenum, raises the possibility of Zollinger-Ellison syndrome, a gastrin-producing tumour, and a fasting serum gastrin is measured. In most patients, however, no ulcer is found despite compatible symptoms; that picture is called functional dyspepsia, and it is diagnosed after the treatable causes — ulcer, H. pylori infection and malignancy — have been excluded.