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Peptic ulcer is rare without H pylori or NSAID


Clinical bottom line

In the absence of Helicobacter pylori infection, or use of NSAID or aspirin, peptic ulcer is rare. In Spain only 49 cases in 50 are caused by H pylori or NSAID.


MT Arroyo et al. The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe. Helicobacter 2004 9: 249-254.


This multicentre study was conducted in Spain. Over six months 830 consecutive patients were recruited who had endoscopically-verified active peptic ulcer (stomach or duodenum) with a visual loss of mucosal integrity of 5 mm or more. Exclusion criteria were previous gastric surgery, malignancy, associated conditions, or prior H pylori eradication therapy. Use of antibiotics within 30 days and proton pump inhibitors was evaluated. NSAID or aspirin use was evaluated by using a structured questionnaire, and users were defined as having used them within 30 days.

All patients had four biopsy specimens taken from gastric antrum and corpus for staining for Helicobacter pylori, and for rapid urease test. Patients negative for these tests had a urea breath test performed at least two months after diagnosis of the ulcer. Proton pump inhibitor and antibiotic treatments were stopped 20 days before the breath test. If any test was positive patients were considered infected.


Out of 803 consecutively recruited patients, 754 were fully evaluable with all results reported. Seventy percent were men, and 40% had previous ulcer disease. Upper gastrointestinal bleeding occurred in 60%. Dyspepsia was common (33%)Reflux disease symptoms were rare, occurring in 2%, and anaemia was found in 2%. NSAID use occurred in 311 (41%), and of these 311, 93 (12% of the total) were using aspirin.

The results of association with H pylori infection and use of NSAIDs are shown in Table 1. Almost all patients were infected with H pylori, or, if not infected, used NSAIDs. Only 2% (1 in 50 of those with ulcers) had neither H pylori infection or were NSAID users.

Table 1: Results of 754 consecutive peptic ulcers

Number (%)
Ulcer location
HP +ve
HP-ve, NSAID +ve
HP-ve, NSAID -ve
452 (96)
12 (2.5)
8 (1.7)
168 (87)
17 (8.8)
8 (4.1)
89 (100)
709 (94)
29 (3.8)
16 (2.1)


This appears to be a clear-cut result, and is not dissimilar to other European reports of low rates of ulcer not associated with H pylori, or NSAID, or both. There are other reports, particularly from the USA, that suggest otherwise.

There are real methodological issues. These include:

This paper is useful because of the discussion of these and other issues, and because of the intelligent and perceptive discussion. The topic would repay a systematic review.