INTRODUCTION — A peptic ulcer is a defect in the gastric or duodenal wall that extends through the muscularis mucosa into the deeper layers of the wall. The management of patients with peptic ulcer disease is based on the etiology, ulcer characteristics, and anticipated natural history. This topic will review the initial management of peptic ulcer disease. The management of recurrent and refractory peptic ulcer disease, the complications of peptic ulcer disease, surgical management of peptic ulcer disease, and the clinical manifestations, diagnosis of peptic ulcer disease are discussed separately. (See "Approach to refractory or recurrent peptic ulcer disease" and "Overview of the complications of peptic ulcer disease" and "Surgical management of peptic ulcer disease" and "Peptic ulcer disease: Clinical manifestations and diagnosis".)

INITIAL MANAGEMENT

Eradication of Helicobacter pylori — All patients with peptic ulcers should be tested for infection with H. pylori and treated [1-4]. In patients treated for H. pylori, eradication of infection should be confirmed four or more weeks after the completion of therapy [4]. Diagnostic evaluation and treatment of H. pylori are discussed in detail, separately. (See "Indications and diagnostic tests for Helicobacter pylori infection" and "Treatment regimens for Helicobacter pylori".)

Eradication of H. pylori in patients with peptic ulcer disease is associated with higher healing rates in patients with duodenal and gastric ulcers. A meta-analysis of 24 randomized trials including 2102 patients with peptic ulcer disease revealed that the 12-month ulcer remission rates for gastric and duodenal ulcers were significantly higher in patients successfully eradicated of H. pylori infection as compared with those with a persistent infection (97 and 98 percent versus 61 and 65 percent, respectively) [5]. In addition, eradication of H. pylori infection is associated with lower ulcer recurrence rates in patients with gastric and duodenal ulcers who are not placed on maintenance antisecretory therapy [6].

Withdrawal of offending or contributing factors — Patients with peptic ulcers should be advised to avoid nonsteroidal anti-inflammatory drugs (NSAIDs). Contributing factors should be addressed and treated (eg, treating medical comorbidities, poor nutritional status, ischemia). While there are no convincing data that specific foods are associated with an increased risk of peptic ulcer disease, patients should avoid any foods that precipitate dyspeptic symptoms. Given the many benefits of smoking cessation, we advise patients to stop smoking and advise them to limit alcohol intake to one alcoholic beverage a day [7]. (See "Peptic ulcer disease: Genetic, environmental, and psychological risk factors and pathogenesis" and "Unusual causes of peptic ulcer disease".)

Antisecretory therapy — All patients with peptic ulcers should receive antisecretory therapy to facilitate ulcer healing (table 1).

Choice and duration of therapy — The choice and duration of antisecretory therapy varies based on the ulcer characteristics, risk factors for recurrent peptic ulcer disease (eg, continued NSAID use, failure to eradicate H. pylori), and the presence of ulcer complications (eg, bleeding, gastric outlet obstruction, ulcer penetration, perforation) [8].

●H. pylori-positive ulcer

•In patients with uncomplicated duodenal ulcers, the proton pump inhibitor (PPI), given for 14 days, along with the antibiotic regimen to treat H. pylori, is usually adequate to induce healing, and additional antisecretory therapy is not needed as long as they are asymptomatic following therapy [9,10]. Eradication of H. pylori even without concurrent acid suppression therapy heals >90 percent of duodenal ulcers [11,12].

•In patients with complicated duodenal ulcers, we suggest antisecretory treatment for four to eight weeks and in patients with gastric ulcers, we suggest antisecretory therapy for 8 to 12 weeks. In patients with gastric ulcers, we discontinue antisecretory therapy only after ulcer healing has been confirmed by upper endoscopy. However, the routine use of endoscopy to confirm healing may not be necessary and the decision must be individualized based on the size and location of the ulcer and risk of malignancy.

•Cure of H. pylori infection should be confirmed four or more weeks after completion of eradication therapy [13]. (See "Indications and diagnostic tests for Helicobacter pylori infection" and "Treatment regimens for Helicobacter pylori".)

●NSAID-induced ulcer – Patients with NSAID-associated ulcers should be treated with a PPI for a minimum of eight weeks (table 1). In patients with peptic ulcers who need to remain on NSAIDs or aspirin, maintenance antisecretory therapy with a PPI should be considered to reduce the risk of ulcer complications or recurrence [14]. (See "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity", section on 'Secondary prevention of gastroduodenal toxicity' and 'Maintenance therapy' below.)

●Non-H. pylori, non-NSAID ulcers – In patients with H. pylori-negative ulcers that are not associated with NSAID use, we suggest PPI therapy for four to eight weeks based on the ulcer location (gastric or duodenal) and the presence of complications. Although the natural history of these ulcers is unclear, it is important to review the patient's history for the adequacy of H. pylori testing and for a history of NSAID use. Limited data on the natural history of these ulcers suggest that they may be more difficult to heal and have a higher rate of recurrence. In the absence of H. pylori and NSAID use, we continue long-term acid inhibitory therapy with PPIs [15]. (See 'Maintenance therapy' below.)

Efficacy

●PPIs heal NSAID-related ulcers more effectively as compared with H2RAs and are therefore the antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are continued. In a prospective study that included 541 patients with NSAID-related ulcers, who were treated with omeprazole (40 or 20 mg) or ranitidine (150 mg twice daily), ulcer healing rates at eight weeks were significantly higher in patients treated with omeprazole as compared with an H2RA (79, 80, and 63 percent, respectively) [16].

●Combining PPIs and H2RAs adds to cost without enhancing healing. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pharmacology'.)

●Although antacids and sucralfate can heal duodenal ulcers, they are not routinely recommended to treat peptic ulcers as PPIs heal ulcers more rapidly and to a greater extent [17]. (See "Antiulcer medications: Mechanism of action, pharmacology, and side effects".)

ENDOSCOPY AFTER INITIAL THERAPY

Duodenal ulcers — Given the low risk of malignancy in patients with duodenal ulcers, a repeat upper endoscopy is not routinely recommended after initial treatment unless symptoms persist or recur. In such cases, the upper endoscopy serves to rule out refractory peptic ulcers and ulcers with nonpeptic etiologies. (See "Indications and diagnostic tests for Helicobacter pylori infection".)

Gastric ulcers — The decision to repeat endoscopy in patients with a gastric ulcer should be individualized. We suggest a surveillance endoscopy (with biopsies of the ulcer if still present) be performed after 12 weeks of antisecretory therapy in patients with gastric ulcers and any one of the following:

●Symptoms despite medical therapy.

●Unclear etiology.

●Giant ulcer (>2 cm).

●Biopsies not performed or inadequate sampling on the index upper endoscopy (total of <4 biopsies obtained from four quadrants of the ulcer and additional biopsies of the edges with jumbo forceps if there are endoscopic features of a malignant gastric ulcer).

●Ulcer appears suspicious for malignancy on index upper endoscopy (mass lesion, elevated irregular ulcer borders, or abnormal adjacent mucosal folds).

●Initial endoscopy was performed for bleeding.

●Risks factors for gastric cancer (eg, age >50 years, H. pylori, immigrants from a region with high prevalence of gastric cancer [eg, Japan, Korea, Taiwan, Costa Rica], family history of gastric cancer, the presence of gastric atrophy, adenoma, dysplasia, intestinal metaplasia).

Our approach is not to perform an upper endoscopy for surveillance in patients with small benign-appearing antral gastric ulcers due to NSAID use that have been adequately biopsied and have no evidence of dysplasia or malignancy if the patient has no risk factors for gastric cancer [18-20].

There are limited prospective outcome data to guide which patients with peptic ulcers should undergo surveillance endoscopy. Our recommendations are consistent with the 2010 guidelines by the American Society for Gastrointestinal Endoscopy [21]. The incidence of gastric cancer on follow-up endoscopy of an apparently benign gastric ulcer ranges from 0.8 to 4.3 percent. The rationale behind endoscopic follow-up of a patient with a gastric ulcer is that the absence of symptoms does not reliably exclude malignancy and surveillance endoscopy may identify patients with gastric cancer at an early stage [22,23]. However, it is unclear if endoscopic surveillance is cost-effective or improves survival [22,24].

REFRACTORY ULCERS — A refractory peptic ulcer is defined as an endoscopically proven ulcer greater than 5 mm in diameter that does not heal after 12 weeks of treatment with a proton pump inhibitor (PPI). Approximately 5 to 10 percent of ulcers are refractory to initial PPI therapy. The evaluation and management of refractory ulcers is discussed elsewhere. (See "Approach to refractory or recurrent peptic ulcer disease".)

MAINTENANCE THERAPY — We continue maintenance antisecretory therapy with a proton pump inhibitor in the following high-risk subgroups of patients with peptic ulcer disease (table 1) [25-30]:

●Giant (>2 cm) ulcer and age >50 years or multiple co-morbidities

●H. pylori-negative, nonsteroidal anti-inflammatory drug (NSAID)-negative ulcer disease

●Refractory peptic ulcer (see 'Refractory ulcers' above)

●Failure to eradicate H. pylori

●Frequently recurrent peptic ulcers (>2 documented recurrences a year)

●Continued NSAID use

MANAGEMENT OF COMPLICATIONS — Complications of peptic ulcer disease include gastrointestinal bleeding, gastric outlet obstruction, penetration, fistulization, and perforation. The management of these complications is discussed in detail, separately. (See "Overview of the complications of peptic ulcer disease" and "Overview of the treatment of bleeding peptic ulcers" and "Surgical management of peptic ulcer disease" and "Gastric outlet obstruction in adults".)

TREATMENT DURING PREGNANCY AND LACTATION — When peptic ulcer disease is diagnosed in a woman who is pregnant, the focus of treatment is typically acid suppression with a proton pump inhibitor (PPI) [31]. If H. pylori is present, antimicrobial treatment is typically deferred until after delivery. However, there is some evidence that H. pylori can cause severe nausea/vomiting in pregnancy, including hyperemesis gravidarum [32,33]. Thus, if indicated, H. pylori treatment can be considered in pregnancy. A meta-analysis of safety studies showed no significant adverse outcomes with PPI use in pregnant women [34]. The available evidence based on clinical studies in pregnancy supports the safety of older proton pump inhibitors such as omeprazole and pantoprazole with little data available on the newer proton pump inhibitors. Similarly, limited data with omeprazole and pantoprazole suggest that excretion in milk does occur but the levels are low [35-37]. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Pregnancy and lactation' and "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Antibiotics'.)

DISEASE COURSE — Approximately 60 percent of peptic ulcers heal spontaneously but with eradication of H. pylori infection, ulcer healing rates are >90 percent [5,38-41]. Even with continued proton pump inhibitor (PPI) use, approximately 5 to 30 percent of peptic ulcers recur within the first year based on whether H. pylori has been successfully eradicated [42,43]. Approximately 5 to 10 percent of ulcers are refractory to antisecretory therapy with a PPI. The risk of complications in patients with chronic peptic ulcer disease is 2 to 3 percent per year. (See "Approach to refractory or recurrent peptic ulcer disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Peptic ulcers (The Basics)" and "Patient education: H. pylori infection (The Basics)" and "Patient education: Gastritis (The Basics)")

●Beyond the Basics topics (see "Patient education: Peptic ulcer disease (Beyond the Basics)" and "Patient education: Helicobacter pylori infection and treatment (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Patients with peptic ulcer disease should be tested for H. pylori. Patients with H. pylori should be treated with a goal of eradication of H. pylori infection. In patients treated for H. pylori, eradication of infection should be confirmed four or more weeks after the completion of eradication therapy. (See "Indications and diagnostic tests for Helicobacter pylori infection".)

●Patients with peptic ulcers should be advised to avoid nonsteroidal anti-inflammatory drugs (NSAIDs). Contributing factors should be addressed and treated (eg, treating medical comorbidities, poor nutritional status, ischemia). (See "Peptic ulcer disease: Genetic, environmental, and psychological risk factors and pathogenesis" and "Unusual causes of peptic ulcer disease".)

●All patients with peptic ulcer disease should receive antisecretory therapy to facilitate ulcer healing. The choice and duration of therapy varies based on the etiology, ulcer location (eg, gastric or duodenal), and the presence of ulcer complications (eg, bleeding, gastric outlet obstruction, ulcer penetration, perforation). (See 'Antisecretory therapy' above.)

●Patients with duodenal ulcers who have been treated do not need further endoscopy unless symptoms persist or recur. (See 'Duodenal ulcers' above.)

●The decision to perform surveillance endoscopy in patients with a gastric ulcer should be individualized. We suggest surveillance endoscopy (with biopsies of the ulcer if still present) be performed after 12 weeks of antisecretory therapy in patients with gastric ulcers and any one of the following (see 'Endoscopy after initial therapy' above):

•Symptoms despite medical therapy.

•Unclear etiology.

•Giant gastric ulcer (>2 cm).

•Biopsies not performed or inadequate sampling on the index upper endoscopy.

•Ulcer appears suspicious for malignancy on index upper endoscopy (mass lesion, elevated irregular ulcer borders, or abnormal adjacent mucosal folds).

•Initial endoscopy was performed for bleeding.

•Risks factors for gastric cancer.

●Maintenance antisecretory therapy should be limited to high-risk subgroups of patients with peptic ulcer disease. These include individuals with any one of the following. (See 'Maintenance therapy' above.):

•Refractory peptic ulcer

•H. pylori-negative, NSAID-negative ulcer disease

•Giant (>2 cm) ulcer and age >50 years or multiple comorbidities

•Failure of H. pylori eradication

•Frequently recurrent peptic ulcers (>2 documented recurrences a year)

•Continued NSAID use

●Approximately 60 percent of peptic ulcers heal spontaneously but with eradication of H. pylori infection, ulcer healing rates are >90 percent. Even with continued proton pump inhibitor (PPI) use, approximately 5 to 30 percent of peptic ulcers recur within the first year based on whether H. pylori has been successfully eradicated. Approximately 5 to 10 percent of ulcers are refractory to antisecretory therapy with a PPI. The risk of complications in patients with chronic peptic ulcer disease is 2 to 3 percent per year. (See 'Disease course' above and "Approach to refractory or recurrent peptic ulcer disease" and "Overview of the complications of peptic ulcer disease".)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Andrew H. Soll, MD, who contributed to an earlier version of this topic review.