Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 15-23: Peptic Ulcer Disease + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ History of dyspepsia in 80–90% with variable relationship to meals Ulcer symptoms are characterized by rhythmicity and periodicity Ulcer complications without antecedent symptoms occur in 10–20% Most nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers are asymptomatic Upper endoscopy with gastric biopsy for Helicobacter pylori is diagnostic Gastric ulcer biopsy or documentation of complete healing is necessary to exclude gastric malignancy +++ General Considerations ++ Peptic ulcer is a break in the gastric or duodenal mucosa, extending through the muscularis mucosa, and usually > 5 mm in diameter In the stomach, benign ulcers are most common In the antrum (60%) At the junction of the antrum and body on the lesser curvature (25%) Major causes of peptic ulcer disease NSAIDs Chronic H pylori infection Less than 5–10% of ulcers are caused by other conditions, including Acid hypersecretory states such as Zollinger-Ellison syndrome or systemic mastocytosis Cytomegalovirus (especially in transplant recipients) Crohn disease Lymphoma Medications (eg, alendronate) Chronic medical illness (cirrhosis or chronic kidney disease) Up to 10% of ulcers are idiopathic In duodenal ulcer patients, prevalence of H pylori infection is ~70–90%; however, ulcers develop in only about 10% of infected persons In persons who take NSAIDs long-term, prevalence of gastric ulcers is 10–20% and duodenal ulcers is 2–5% H pylori infection increases risk of NSAID-induced ulcers and complications +++ Demographics ++ In the United States, ~500,000 new ulcer cases and 4 million ulcer recurrences per year Incidence of duodenal ulcer disease has been declining dramatically for the past 30 years (due to the eradication of H pylori) However, the incidence of gastric ulcers has not been declining (due to the widespread use of NSAIDs and low-dose aspirin) Lifetime prevalence of ulcers in adults is ~10% Duodenal ulcers are most common between the ages of 30 and 55 Gastric ulcers are most common between the ages of 55 and 70 + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Epigastric pain (dyspepsia) Present in 80–90% of persons, but such pain is not sensitive or specific enough to serve as a reliable diagnostic criterion Typically well localized to epigastrium and not severe Described as gnawing, dull, aching, or "hunger-like" Relieved by food or antacids in about 50% Ulcer complications, such as bleeding, occur in 20% with no antecedent symptoms ("silent ulcers") Nocturnal pain awakens two-thirds of patients with duodenal ulcers and one-third of patients with gastric ulcers Most patients have symptomatic periods lasting several weeks with intervals of months to years in which they are pain free (periodicity) Nausea and anorexia Significant vomiting and weight loss suggest gastric outlet obstruction or gastric malignancy Physical examination often normal Mild, localized epigastric tenderness to deep palpation +++ Differential Diagnosis ++ Functional dyspepsia Gastritis, eg, NSAIDs, alcohol, stress, H pylori Biliary disease or pancreatitis Gastroesophageal reflux disease "Indigestion" from overeating, high-fat foods, coffee Gastric or pancreatic cancer Angina pectoris Severe pain Esophageal rupture Gastric volvulus Gastric or intestinal ischemia Ruptured aortic aneurysm + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Anemia from acute blood loss with bleeding ulcer Leukocytosis suggests ulcer penetration or perforation Elevated serum amylase suggests ulcer penetration into the pancreas Fecal occult blood test (FOBT) and fecal immunochemical test (FIT) positive in one-third of patients Obtain fasting serum gastrin level to screen for Zollinger-Ellison syndrome, when suspected +++ NONINVASIVE TESTING FOR H PYLORI ++ H pylori fecal antigen or urea breath tests Proton pump inhibitors may cause false-negative urea breath tests and fecal antigen tests and should be withheld for at least 7 days before testing +++ ENDOSCOPIC TESTING FOR H PYLORI ++ In patients in whom an ulcer is diagnosed by endoscopy, gastric mucosal biopsies should be obtained both for a rapid urease test and for histologic examination Histology specimens are discarded if the urease test is positive +++ Imaging Studies ++ Obtain abdominal CT scan when complications of peptic ulcer disease (perforation, penetration, or obstruction) are suspected +++ Diagnostic Procedures ++ Upper endoscopy is procedure of choice Biopsy indicated to exclude H pylori infection or malignancy With benign-appearing gastric ulcers, cytologic brushings and biopsies of the ulcer margin reveal that 3–5% are malignant Nonhealing gastric ulcers may be malignant Duodenal ulcers are rarely malignant and do not require biopsy + Treatment Download Section PDF Listen +++ +++ Medications ++ See Table 15–10 ++Table Graphic Jump LocationTable 15–10.Treatment options for peptic ulcer disease.View Table||Download (.pdf) Table 15–10. Treatment options for peptic ulcer disease. Active Helicobacter pylori–associated ulcer Treat with anti–H pylori regimen for 14 days. Treatment options: Standard Bismuth Quadruple Therapy Proton pump inhibitor orally twice daily1,2 Bismuth subsalicylate 262 mg two tablets orally four times daily or bismuth subcitrate 120–400 mg orally four times daily Tetracycline 500 mg orally four times daily Metronidazole 500 mg three times daily OR Proton pump inhibitor orally twice daily1 Bismuth subcitrate potassium 140 mg/metronidazole 125 mg/tetracycline 125 mg (Pylera) three capsules orally four times daily for 10 days3 Standard Nonbismuth Quadruple Therapy Proton pump inhibitor orally twice daily Amoxicillin 1000 mg orally twice daily Metronidazole 500 mg orally twice daily Clarithromycin 500 mg orally twice daily Standard Triple Therapy (No longer recommended except in locales where clarithromycin resistance is < 15%) Proton pump inhibitor orally twice daily Clarithromycin 500 mg orally twice daily Amoxicillin 1 g orally twice daily (or, if penicillin allergic, metronidazole 500 mg orally twice daily) Levofloxacin Triple Therapy (Recommended after failed previous treatment in a patient with clarithromycin and tetracycline allergy) Proton pump inhibitor orally twice daily Levofloxacin 500 mg orally twice daily Amoxicillin 1 g orally twice daily After completion of course of H pylori eradication therapy, continue treatment with proton pump inhibitor1 once daily for 4–6 weeks if ulcer is large (> 1 cm) or complicated. Confirm successful eradication of H pylori with urea breath test, fecal antigen test, or endoscopy with biopsy at least 4 weeks after completion of antibiotic treatment and 2 weeks after completion of proton pump inhibitor treatment. Active ulcer not attributable to H pylori Consider other causes: NSAIDs, Zollinger-Ellison syndrome, gastric malignancy. Treatment options: Proton pump inhibitors:1 Uncomplicated duodenal ulcer: treat for 4 weeks Uncomplicated gastric ulcer: treat for 8 weeks H2-receptor antagonists: Uncomplicated duodenal ulcer: cimetidine 800 mg, nizatidine 300 mg, famotidine 40 mg, orally once daily at bedtime for 6 weeks Uncomplicated gastric ulcer: cimetidine 400 mg, nizatidine 150 mg, famotidine 20 mg, orally twice daily for 8 weeks Complicated ulcers: proton pump inhibitors1 are the preferred drugs Prevention of ulcer relapse NSAID-induced ulcer: prophylactic therapy for high-risk patients (prior ulcer disease or ulcer complications, use of corticosteroids or anticoagulants, age > 60 years, serious comorbid illnesses). Treatment options: Proton pump inhibitor once daily Celecoxib (contraindicated in patients with increased risk of cardiovascular disease) Misoprostol 200 mcg orally 4 times daily Long-term “maintenance” therapy indicated in patients with recurrent ulcers who either are H pylori–negative or who have failed attempts at eradication therapy: once-daily oral proton pump inhibitor1 1Oral proton pump inhibitors: omeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, dexlansoprazole 30–60 mg, pantoprazole 40 mg, esomeprazole 40 mg. Proton pump inhibitors are administered 30 minutes before meals.2Preferred regimen in regions with high clarithromycin resistance or in patients who have previously received a macrolide antibiotic or are penicillin allergic. Effective against metronidazole-resistant organisms.3Pylera is an FDA-approved formulation containing bismuth subcitrate 140 mg/tetracycline 125 mg/metronidazole 125 mg per capsule.NSAIDs, nonsteroidal anti-inflammatory drugs. +++ PEPTIC ULCERS WITH ACTIVE H PYLORI INFECTION ++ Initial treatment for 10–14 days with one of the following Quadruple-therapy regimen (Table 15–10) Proton pump inhibitor before meals: omeprazole, 20-40 mg twice daily orally; rabeprazole, 20 mg twice daily orally; lansoprazole, 30 mg twice daily orally; dexlansoprazole, 30–60 mg once daily orally; pantoprazole, 40 mg twice daily orally; or esomeprazole 40 mg once daily; plus bismuth subsalicylate, 2 tablets four times daily orally; plus tetracycline, 500 mg four times daily orally; plus metronidazole, 250 mg four times daily orally, or 500 mg three times daily orally, or tinidazole, 500 mg four times daily orally Recommended for patients in whom an initial attempt at eradication with triple therapy fails Triple-therapy regimen (Table 15–10) No longer recommended except in locales where clarithromycin resistance is < 15% Proton pump inhibitor before meals: omeprazole, 20–40 mg twice daily orally; rabeprazole, 20 mg twice daily orally; lansoprazole, 30 mg twice daily orally; dexlansoprazole, 30–60 mg once daily orally; pantoprazole, 40 mg twice daily orally; or esomeprazole, 40 mg once daily orally; plus clarithromycin, 500 mg twice daily orally, and amoxicillin, 1 g twice daily orally (or metronidazole, 500 mg twice daily orally (in penicillin-allergic patients) Levofloxacin triple therapy (recommended after failed previous treatment patient with clarithromycin and tetracycline allergy) (Table 15–10) Proton pump inhibitor orally twice daily Levofloxacin 500 mg orally twice daily Amoxicillin 1 g orally twice daily Quadruple therapy, although a more complicated regimen, achieves > 90% eradication—even in strains with metronidazole resistance A large multicenter European controlled trial conducted in regions of high clarithromycin resistance reported 92% eradication with a 14-day quadruple therapy consisting of a proton pump inhibitor, amoxicillin, clarithromycin, and nitroimidazole (the latter drug not available in the United States) Bismuth-based quadruple therapy is recommended as first-line therapy for patients in areas with high clarithromycin resistance (> 20%), in patients who have previously been treated with a macrolide antibiotic, or as second-line therapy for patients whose infection persists after an initial course of triple therapy Several studies report eradication rates of > 90% using a 10-day sequential regimen of four drugs: a proton pump inhibitor and amoxicillin for 5 days, followed by a proton pump inhibitor, clarithromycin, and tinidazole for 5 days; however, equivalent efficacy is achieved by giving all 4 drugs together for 10 days A 2013 meta-analysis did not detect superiority compared with 14-day triple therapy or bismuth-based therapy, except in patients with organisms exhibiting clarithromycin resistance Following initial therapy, continue treatment for 4–8 weeks with omeprazole, 20-40 mg once daily orally; rabeprazole, 20 mg once daily orally; lansoprazole, 30 mg once daily orally; dexlansoprazole, 30–60 mg once daily orally; pantoprazole, 40 mg once daily orally; or esomeprazole, 40 mg once daily orally +++ PEPTIC ULCERS WITH NO H PYLORI INFECTION ++ Proton pump inhibitors Omeprazole, 20-40 mg once daily orally; rabeprazole, 20 mg once daily orally; lansoprazole, 30 mg once daily orally; pantoprazole or esomeprazole, 40 mg once daily orally; or dexlansoprazole 30–60 mg given 30 min before breakfast heals > 90% of duodenal ulcers after 4 weeks and 90% of gastric ulcers after 8 weeks H2-receptor antagonists May be used as a less expensive alternative to proton pump inhibitors Nizatidine, 300 mg at bedtime orally; famotidine, 40 mg at bedtime orally; or cimetidine, 800 mg at bedtime orally heals 85–90% of duodenal and gastric ulcers within 6–8 weeks Maintenance therapy Indicated in patients with recurrent ulcers who are H pylori negative, who have failed attempts at eradication therapy, or who require long-term therapy with NSAID or low-dose aspirin Omeprazole, 20–40 mg once daily orally; rabeprazole, 20 mg once daily orally; lansoprazole, 30 mg once daily orally; dexlansoprazole, 30–60 mg once daily orally; esomeprazole, 40 mg once daily orally; pantoprazole, 40 mg once daily orally Cimetidine, 400–800 mg at bedtime orally; nizatidine, 150–300 mg at bedtime orally; famotidine, 20–40 mg at bedtime orally +++ Surgery ++ For complications of peptic ulcer disease—including perforation, penetration, gastric outlet obstruction, and bleeding—that cannot be controlled with endoscopic therapy +++ Therapeutic Procedures ++ Moderate alcohol intake Discontinue smoking Discontinue NSAIDs when possible + Outcome Download Section PDF Listen +++ +++ Follow-Up ++ For gastric ulcers repeat endoscopy after 2–3 months of therapy to verify complete healing; biopsy if gastric ulcer unhealed to exclude malignancy +++ Complications ++ See Peptic Ulcer Disease, Complications +++ Prognosis ++ If H pylori is not eradicated, 85% of patients will have ulcer recurrence within 1 year, half symptomatic; if successfully eradicated, recurrence rates are reduced dramatically to 5–20% at 1 year +++ Prevention ++ For patients requiring NSAID therapy, to prevent NSAID-induced gastric and duodenal ulcers, consider the following options: Oral proton pump inhibitor given once daily (rabeprazole 20 mg, omeprazole 20–40 mg, lansoprazole 30 mg, dexlansoprazole 30–60 mg, or pantoprazole or esomeprazole 40 mg) Misoprostol, 100–200 mcg four times daily orally; use is limited by side effect profile and frequency of dosing For patients at low risk for cardiovascular disease, consider using celecoxib or one of the "safer" nonselective NSAIDs (etodolac, meloxicam, naproxen, ibuprofen) +++ When to Refer ++ Patients with persistent dyspepsia after 1–2 weeks of medical treatment Complications of peptic ulcer disease +++ When to Admit ++ Complications of peptic ulcer disease + References Download Section PDF Listen +++ + +Crowe SE. Helicobacter pylori infection. N Engl J Med. 2019 Mar 21;380(12):1158–65. [PubMed: 30893536] + +Fallone CA et al. Reconciliation of recent Helicobacter pylori treatment guidelines in a time of increasing resistance to antibiotics. Gastroenterology. 2019 Jul;157(1):44–53. [PubMed: 30998990] + +Kavitt RT et al. Diagnosis and treatment of peptic ulcer disease. Am J Med. 2019 Apr;132(4):447–56. [PubMed: 30611829] + +Lanas A et al. Peptic ulcer disease. Lancet. 2017 Aug 5;390(10094):613–24. [PubMed: 28242110] + +Vaezi MF et al. Complications of proton pump inhibitor therapy. Gastroenterology. 2017 Jul;153(1):35–48. [PubMed: 28528705]