Despite the fact that treatment with twice daily proton pump inhibitors (PPIs) will result in healing of all benign ulcers, there are still a minority of patients who have ulcers refractory to treatment.
Before considering the presence of an underlying pathology other than benign peptic ulcer disease, patient compliance with therapy should be ensured, as non-compliance is the most common cause.
Next to treatment non-compliance, are the use of aspirin and Non-steroidal anti-inflammatory drugs (NSAIDs), and the presence of H Pylori infection.
Other causes that must be suspected based on the clinical data:
Cameron ulcers (linear ulcers in large hiatus hernias)
Treatment with bisphosphonate
Infections: Cytomegalovirus (CMV), and mucormycosis