Most peptic ulcers respond to treatment with antimicrobial therapy for Helicobacter pylori, withdrawal of NSAIDs, or to treatment with potent antisecretory drugs. However, in some individuals, the ulcer is either refractory to conventional therapy, or recurs following successful initial treatment. (See "Overview of the natural history and treatment of peptic ulcer disease".)
The same overlapping set of factors underlies ulcers that fail to heal or that recur (table 1). The most important aspect of the assessment of such ulcers is to discriminate several elements that may influence natural history:
- The presence of factors that perpetuate the ulcer itself, such as gastric hypersecretion due to gastrinoma, failed H. pylori detection or eradication, undiscovered or undisclosed occult continued use of NSAIDs, severe local scarring that retards healing, and comorbid disease.
- Pathology that mimics ulcer disease, such as carcinoma.
- Refractory symptoms in the absence of refractory ulceration, which are often part of a functional GI or somatoform disorder.
- Poor patient compliance or true resistance to secretory inhibition.
In the H2 receptor antagonist (H2RA) era, ulcers were considered refractory if healing was not evident after eight weeks of therapy, with the time frame adjusted somewhat for ulcer size . Ulcer management has undergone revolutionary change, and ulcers refractory to H2RA are substantially different from ulcers refractory to current management. However, eight weeks remains a reasonable period to define refractory ulceration.
Much more rapid ulcer healing can be anticipated with proton pump inhibitors (PPI), with successful cure of H. pylori, or removal of NSAIDs, as appropriate. Slower healing should be anticipated for a variety of reasons, such as large ulcer size, a history of complications (such ulcers are often deep), or ulcers associated with scarring or deformity, persisting NSAID or aspirin use and/or H. pylori infection, or ongoing inflammation from another cause.