Diagnosis and Treatment of Peptic Ulcer Disease

Published:January 03, 2019DOI:


      Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspepsia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the management of complications related to peptic ulcer disease, including endoscopic intervention for peptic ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients at high risk, including those infected with H. pylori and users of NSAIDs.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Abbasi J
        Barry Marshall, MD: H pylori 35years later.
        JAMA. 2017; 317: 1400-1402
        • Warren JR
        • Marshall B
        Unidentified curved bacilli on gastric epithelium in active chronic gastritis.
        Lancet. 1983; 1: 1273-1275
        • Marshall BJ
        • Warren JR
        Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.
        Lancet. 1984; 1: 1311-1315
        • NIH Consensus Conference
        Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease.
        JAMA. 1994; 272: 65-69
        • Sonnenberg A
        Review article: historic changes of Helicobacter pylori-associated diseases.
        Aliment Pharmacol Ther. 2013; 38: 329-342
        • Garrow D
        • Delegge MH
        Risk factors for gastrointestinal ulcer disease in the US population.
        Dig Dis Sci. 2010; 55: 66-72
        • Lin KJ
        • García Rodríguez LA
        • Hernández-Díaz S
        Systematic review of peptic ulcer disease incidence rates: do studies without validation provide reliable estimates?.
        Pharmacoepidemiol Drug Saf. 2011; 20: 718-728
        • Kang JY
        • Tinto A
        • Higham J
        • Majeed A
        Peptic ulceration in general practice in England and Wales 1994-98: period prevalence and drug management.
        Aliment Pharmacol Ther. 2002; 16: 1067-1074
        • Sung JJ
        • Kuipers EJ
        • El-Serag HB
        Systematic review: the global incidence and prevalence of peptic ulcer disease.
        Aliment Pharmacol Ther. 2009; 29: 938-946
        • Post PN
        • Kuipers EJ
        • Meijer GA
        Declining incidence of peptic ulcer but not of its complications: a nation-wide study in The Netherlands.
        Aliment Pharmacol Ther. 2006; 23: 1587-1593
        • Sonnenberg A
        Time trends of ulcer mortality in Europe.
        Gastroenterology. 2007; 132: 2320-2327
        • Laine L
        • Yang H
        • Chang SC
        • Datto C
        Trends for incidence of hospitalization and death due to GI complications in the United States from 2001 to 2009.
        Am J Gastroenterol. 2012; 107 (quiz 1196): 1190-1195
        • Kurata JH
        • Nogawa AN
        Meta-analysis of risk factors for peptic ulcer. Nonsteroidal antiinflammatory drugs, Helicobacter pylori, and smoking.
        J Clin Gastroenterol. 1997; 24: 2-17
        • Lochhead P
        • El-Omar EM
        Helicobacter pylori infection and gastric cancer.
        Best Pract Res Clin Gastroenterol. 2007; 21: 281-297
        • Kusters JG
        • van Vliet AH
        • Kuipers EJ
        Pathogenesis of Helicobacter pylori infection.
        Clin Microbiol Rev. 2006; 19: 449-490
        • Garcia Rodriguez LA
        • Hernandez-Diaz S
        Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs.
        Am J Epidemiol. 2004; 159: 23-31
        • Tsamakidis K
        • Panotopoulou E
        • Dimitroulopoulos D
        • et al.
        Herpes simplex virus type 1 in peptic ulcer disease: an inverse association with Helicobacter pylori.
        World J Gastroenterol. 2005; 11: 6644-6649
        • McColl KE.
        How I manage H. pylori-negative, NSAID/aspirin-negative peptic ulcers.
        Am J Gastroenterol. 2009; 104: 190-193
        • Orton DI
        • Orteu CH
        • Rustin MH
        Cytomegalovirus-associated gastric ulcer in an immunosuppressed patient with pemphigus vulgaris.
        Clin Exp Dermatol. 2001; 26: 170-172
        • Lu CL
        • Chang SS
        • Wang SS
        • Chang FY
        • Lee SD
        Silent peptic ulcer disease: frequency, factors leading to “silence,” and implications regarding the pathogenesis of visceral symptoms.
        Gastrointest Endosc. 2004; 60: 34-38
        • Malfertheiner P
        • Chan FK
        • McColl KE
        Peptic ulcer disease.
        Lancet. 2009; 374: 1449-1461
        • Allen JI
        • Katzka D
        • Robert M
        • Leontiadis GI
        American Gastroenterological Association Institute technical review on the role of upper gastrointestinal biopsy to evaluate dyspepsia in the adult patient in the absence of visible mucosal lesions.
        Gastroenterology. 2015; 149: 1088-1118
        • Talley NJ
        • Vakil NB
        • Moayyedi P
        American Gastroenterological Association technical review on the evaluation of dyspepsia.
        Gastroenterology. 2005; 129: 1756-1780
        • Chey WD
        • Leontiadis GI
        • Howden CW
        • Moss SF
        ACG clinical guideline: treatment of Helicobacter pylori infection.
        Am J Gastroenterol. 2017; 112: 212-239
        • Dorward S
        • Sreedharan A
        • Leontiadis GI
        • Howden CW
        • Moayyedi P
        • Forman D
        Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.
        Cochrane Database Syst Rev. 2006; (CD005415)
        • Sreedharan A
        • Martin J
        • Leontiadis GI
        • et al.
        Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.
        Cochrane Database Syst Rev. 2010; (CD005415)
        • Gisbert JP
        • Khorrami S
        • Carballo F
        • Calvet X
        • Gene E
        • Dominguez-Munoz E
        Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer.
        Aliment Pharmacol Ther. 2004; 19: 617-629
        • Lai KC
        • Lam SK
        • Chu KM
        • et al.
        Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use.
        N Engl J Med. 2002; 346: 2033-2038
        • Scheiman JM
        • Yeomans ND
        • Talley NJ
        • et al.
        Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors.
        Am J Gastroenterol. 2006; 101: 701-710
        • Lanza FL
        • Chan FK
        • Quigley EM
        • Practice Parameters Committee of the American College of Gastroenterology
        Guidelines for prevention of NSAID-related ulcer complications.
        Am J Gastroenterol. 2009; 104: 728-738
        • Strand DS
        • Kim D
        • Peura DA
        25years of proton pump inhibitors: a comprehensive review.
        Gut Liver. 2017; 11: 27-37
        • Scarpignato C
        • Gatta L
        • Zullo A
        • et al.
        Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression.
        BMC Med. 2016; 14: 179
        • Sheen E
        • Triadafilopoulos G
        Adverse effects of long-term proton pump inhibitor therapy.
        Dig Dis Sci. 2011; 56: 931-950
        • Freedberg DE
        • Kim LS
        • Yang YX
        The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association.
        Gastroenterology. 2017; 152: 706-715
        • Lambert AA
        • Lam JO
        • Paik JJ
        • Ugarte-Gil C
        • Drummond MB
        • Crowell TA
        Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis.
        PLoS One. 2015; 10e0128004
        • Bavishi C
        • Dupont HL
        Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection.
        Aliment Pharmacol Ther. 2011; 34: 1269-1281
        • Lazarus B
        • Grams ME
        Proton pump inhibitors in kidney disease.
        Clin J Am Soc Nephrol. 2018; 13: 1458-1459
        • Walan A
        • Bader JP
        • Classen M
        • et al.
        Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.
        N Engl J Med. 1989; 320: 69-75
        • Hsu PI
        • Wu DC
        • Tsay FW
        • et al.
        Histamine-2 receptor antagonist cannot prevent recurrent peptic ulcers in patients with atherosclerotic diseases who receive platelet ADP receptor antagonist monotherapy: a randomized-controlled, double-blind, and double-dummy trial.
        Am J Gastroenterol. 2017; 112: 282-289
        • Malfertheiner P
        • Megraud F
        • O'Morain CA
        • et al.
        Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.
        Gut. 2017; 66: 6-30
        • Lau JY
        • Sung J
        • Hill C
        • Henderson C
        • Howden CW
        • Metz DC
        Systematic review of the epidemiology of complicated peptic ulcer disease: incidence, recurrence, risk factors and mortality.
        Digestion. 2011; 84: 102-113
        • Gurusamy KS
        • Pallari E
        Medical versus surgical treatment for refractory or recurrent peptic ulcer.
        Cochrane Database Syst Rev. 2016; 3CD011523
        • Gralnek IM
        • Dumonceau JM
        • Kuipers EJ
        • et al.
        Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
        Endoscopy. 2015; 47: a1-46
        • Laine L
        • Jensen DM
        Management of patients with ulcer bleeding.
        Am J Gastroenterol. 2012; 107 (quiz 361): 345-360
        • Lau JY
        • Barkun A
        • Fan DM
        • Kuipers EJ
        • Yang YS
        • Chan FK
        Challenges in the management of acute peptic ulcer bleeding.
        Lancet. 2013; 381: 2033-2043
        • Laine L
        • McQuaid KR
        Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials.
        Clin Gastroenterol Hepatol. 2009; 7 (quiz 31-32): 33-47
        • Millward SF
        ACR Appropriateness Criteria on treatment of acute nonvariceal gastrointestinal tract bleeding.
        J Am Coll Radiol. 2008; 5: 550-554
        • Søreide K
        • Thorsen K
        • Harrison EM
        • et al.
        Perforated peptic ulcer.
        Lancet. 2015; 386: 1288-1298
        • Chung KT
        • Shelat VG
        Perforated peptic ulcer - an update.
        World J Gastrointest Surg. 2017; 9: 1-12
        • Thorsen K
        • Soreide JA
        • Soreide K
        What is the best predictor of mortalityin perforated peptic ulcer disease? A population-based, multivariable regression analysis including three clinical scoring systems.
        J Gastrointest Surg. 2014; 18: 1261-1268
        • Lei JJ
        • Zhou L
        • Liu Q
        • Xu CF
        Acquired double pylorus: Clinical and endoscopic characteristics and four-year follow-up observations.
        World J Gastroenterol. 2016; 22: 2153-2158
        • Banerjee S
        • Cash BD
        • et al.
        • ASGE Standards of Practice Committee
        The role of endoscopy in the management of patients with peptic ulcer disease.
        Gastrointest Endosc. 2010; 71: 663-668
        • Appasani S
        • Kochhar S
        • Nagi B
        • Gupta V
        • Kochhar R
        Benign gastric outlet obstruction–spectrum and management.
        Trop Gastroenterol. 2011; 32: 259-266
        • Chan FK
        • Wong VW
        • Suen BY
        • et al.
        Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial.
        Lancet. 2007; 369: 1621-1626
        • Laine L
        • Takeuchi K
        • Tarnawski A
        Gastric mucosal defense and cytoprotection: bench to bedside.
        Gastroenterology. 2008; 135: 41-60
        • Sostres C
        • Carrera-Lasfuentes P
        • Benito R
        • et al.
        Peptic ulcer bleeding risk. The role of Helicobacter pylori infection in NSAID/low-dose aspirin users.
        Am J Gastroenterol. 2015; 110: 684-689
        • Lai KC
        • Lam SK
        • Chu KM
        • et al.
        Lansoprazole reduces ulcer relapse after eradication of Helicobacter pylori in nonsteroidal anti-inflammatory drug users–a randomized trial.
        Aliment Pharmacol Ther. 2003; 18: 829-836
        • García Rodríguez LA
        • Lin KJ
        • Hernández-Díaz S
        • Johansson S
        Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications.
        Circulation. 2011; 123: 1108-1115
        • Derogar M
        • Sandblom G
        • Lundell L
        • et al.
        Discontinuation of low-dose aspirin therapy after peptic ulcer bleeding increases risk of death and acute cardiovascular events.
        Clin Gastroenterol Hepatol. 2013; 11: 38-42
        • Sung JJ
        • Lau JY
        • Ching JY
        • et al.
        Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial.
        Ann Intern Med. 2010; 152: 1-9
        • Laine L
        Upper gastrointestinal bleeding due to a peptic ulcer.
        N Engl J Med. 2016; 375: 1198
        • Wong GL
        • Au KW
        • Lo AO
        • et al.
        Gastroprotective therapy does not improve outcomes of patients with Helicobacter pylori-negative idiopathic bleeding ulcers.
        Clin Gastroenterol Hepatol. 2012; 10: 1124-1129