Overview of the natural history and treatment of peptic ulcer disease
- Andrew H Soll, MD
Andrew H Soll, MD
- Emeritus Professor of Medicine
- University of California Los Angeles Center for Health Sciences
- Nimish B Vakil, MD, AGAF, FACP, FACG, FASGE
Nimish B Vakil, MD, AGAF, FACP, FACG, FASGE
- AGA Peer Reviewer
- Clinical Professor of Medicine
- University of Wisconsin School of Medicine and Public Health
Peptic ulcer disease (PUD) is a common problem. The natural history and an overview of the treatment of peptic ulcer disease will be reviewed here. Issues related to the treatment of Helicobacter pylori infection, treatment of complications of peptic ulcer disease, and the role of surgery are discussed separately. (See "Management of duodenal ulcers in patients infected with Helicobacter pylori" and "Treatment regimens for Helicobacter pylori" and "Overview of the complications of peptic ulcer disease" and "Surgical management of peptic ulcer disease".)
Data from the pre-H. pylori, pre-proton pump inhibitor (PPI) era provide important to insights into the natural history of PUD. Untreated, peptic ulcers have a widely variable natural history [1-7]. Some heal spontaneously, but recur within months or sometimes within a year or two. An illustrative report described patients who were followed for 12 months after documented healing of duodenal ulcers. Relapse occurred in 74 percent of cases; 33 percent had one recurrence, 24 percent two recurrences, and 17 percent experienced three or more recurrences . Other reports have confirmed a 50 to 80 percent recurrence rate during the 6 to 12 months following initial ulcer healing, although relapses are not always symptomatic [2,3].
Other ulcers cause complications or remain refractory despite antisecretory therapy. The patient's prior ulcer history tends to predict future behavior; those with a history of complications have an increased risk of future complications. Ulcers that take longer to heal initially are more likely to recur rapidly and ulcers that have recurred frequently are likely to continue to do so, unless the underlying cause (eg, H. pylori or nonsteroidal anti-inflammatory drugs [NSAIDs]) is removed. A long duration of symptoms prior to presentation is more likely to be associated with a poor response to medical therapy. (See "Refractory or recurrent peptic ulcer disease".)
Distal antral ulcers, especially prepyloric ulcers (within 2 to 3 cm of the pylorus), may have a different pattern of healing than ulcers at or proximal to the incisura because of different levels of acid secretion and the distribution of gastritis . Many studies did not analyze gastric ulcers by location, and available data are conflicting. Nevertheless, prepyloric ulcers appear to heal more slowly and may be more likely to recur [9,10].
Treatment of H. pylori in infected individuals dramatically alters the incidence of ulcer relapse [11,12]. In a meta-analysis that included 14 studies, duodenal ulcers recurred in fewer than 10 percent of patients successfully treated for H. pylori compared with 65 to 95 percent of those who remained infected . However, newer data from the United States suggest that recurrences after successful H. pylori antibiotic treatment may be more frequent . By contrast, relapse is the rule in the absence of successful anti-H. pylori therapy. (See "Management of duodenal ulcers in patients infected with Helicobacter pylori".)
- Bardhan KD, Cole DS, Hawkins BW, Franks CR. Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate? Br Med J (Clin Res Ed) 1982; 284:621.
- Gudmand-Høyer E, Jensen KB, Krag E, et al. Prophylactic effect of cimetidine in duodenal ulcer disease. Br Med J 1978; 1:1095.
- Current status of maintenance therapy in peptic ulcer disease. The ACG Committee on FDA-Related Matters. Am J Gastroenterol 1988; 83:607.
- Jorde R, Bostad L, Burhol PG. Asymptomatic gastric ulcer: a follow-up study in patients with previous gastric ulcer disease. Lancet 1986; 1:119.
- Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther 1990; 4:25.
- Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology 1990; 99:345.
- Kaneko E, Ooi S, Ito G, Honda N. Natural history of duodenal ulcer detected by the gastric mass surveys in men over 40 years of age. Scand J Gastroenterol 1989; 24:165.
- Savarino V, Zentilin P, Celle G, Mela GS. Ulcer heterogeneity: further arguments for a range of antisecretory treatment. Dig Dis Sci 1990; 35:921.
- Lauritsen K, Bytzer P, Hansen J, et al. Comparison of ranitidine and high-dose antacid in the treatment of prepyloric or duodenal ulcer. A double-blind controlled trial. Scand J Gastroenterol 1985; 20:123.
- Ström M, Bodemar G, Gotthard R, Walan A. Duodenal, prepyloric, and combined duodenal/prepyloric ulcer disease: three distinct entities of juxtapyloric ulcer disease? Scand J Gastroenterol 1986; 21:1105.
- Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology 1996; 110:1244.
- Marshall BJ, Goodwin CS, Warren JR, et al. Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 1988; 2:1437.
- Laine L, Hopkins RJ, Girardi LS. Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials. Am J Gastroenterol 1998; 93:1409.
- Wong GL, Wong VW, Chan Y, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology 2009; 137:525.
- Wilhelmsen I, Haug TT, Berstad A, Ursin H. Increased relapse of duodenal ulcers in patients treated with cognitive psychotherapy. Lancet 1990; 336:307.
- NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA 1994; 272:65.
- Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56:772.
- Chiorean MV, Locke GR 3rd, Zinsmeister AR, et al. Changing rates of Helicobacter pylori testing and treatment in patients with peptic ulcer disease. Am J Gastroenterol 2002; 97:3015.
- Borody TJ, George LL, Brandl S, et al. Helicobacter pylori-negative duodenal ulcer. Am J Gastroenterol 1991; 86:1154.
- Arroyo MT, Forne M, de Argila CM, et al. The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe. Helicobacter 2004; 9:249.
- Greenberg PD, Koch J, Cello JP. Clinical utility and cost effectiveness of Helicobacter pylori testing for patients with duodenal and gastric ulcers. Am J Gastroenterol 1996; 91:228.
- Lee J, O'Morain C. Who should be treated for Helicobacter pylori infection? A review of consensus conferences and guidelines. Gastroenterology 1997; 113:S99.
- Gisbert JP, Calvet X, Feu F, et al. Eradication of Helicobacter pylori for the prevention of peptic ulcer rebleeding. Helicobacter 2007; 12:279.
- Reinbach DH, Cruickshank G, McColl KE. Acute perforated duodenal ulcer is not associated with Helicobacter pylori infection. Gut 1993; 34:1344.
- Laine LA. Helicobacter pylori and complicated ulcer disease. Am J Med 1996; 100:52S.
- Leung WK, Sung JJ, Siu KL, et al. False-negative biopsy urease test in bleeding ulcers caused by the buffering effects of blood. Am J Gastroenterol 1998; 93:1914.
- Lee JM, Breslin NP, Fallon C, O'Morain CA. Rapid urease tests lack sensitivity in Helicobacter pylori diagnosis when peptic ulcer disease presents with bleeding. Am J Gastroenterol 2000; 95:1166.
- Chan FK, To KF, Wu JC, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial. Lancet 2002; 359:9.
- Venerito M, Malfertheiner P. Interaction of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in gastric and duodenal ulcers. Helicobacter 2010; 15:239.
- Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet 2002; 359:14.
- Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001; 344:967.
- 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.
- Lam SK, Ching CK, Lai KC, et al. Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer? A randomised double blind placebo controlled study. Gut 1997; 41:43.
- Sung JJ, Chung SC, Ling TK, et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med 1995; 332:139.
- Gisbert JP, Khorrami S, Carballo F, et al. 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.
- Buckley M, Culhane A, Drumm B, et al. Guidelines for the management of Helicobacter pylori-related upper gastrointestinal diseases. Irish Helicobacter Pylori Study Group. Ir J Med Sci 1996; 165 Suppl 5:1.
- Professional Advisory Panel (CRAG) and Scottish Intercollegiate Guidelines Network (SIGN). Helicobacter pylori eradication therapy in dyspeptic disease: A clinical guideline. 1996.
- Gillen D, Wirz AA, Ardill JE, McColl KE. Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology 1999; 116:239.
- Sandvik AK, Brenna E, Waldum HL. Review article: the pharmacological inhibition of gastric acid secretion--tolerance and rebound. Aliment Pharmacol Ther 1997; 11:1013.
- Spencer CM, Faulds D. Lansoprazole. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy in acid-related disorders. Drugs 1994; 48:404.
- Maton PN. Omeprazole. N Engl J Med 1991; 324:965.
- Poynard T, Lemaire M, Agostini H. Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. Eur J Gastroenterol Hepatol 1995; 7:661.
- Dekkers CP, Beker JA, Thjodleifsson B, et al. Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study. Aliment Pharmacol Ther 1999; 13:179.
- Weberg R, Berstad A, Lange O, et al. Duodenal ulcer healing with four antacid tablets daily. Scand J Gastroenterol 1985; 20:1041.
- Poynard T, Pignon JP. Acute Treatment of Duodenal Ulcer. In: Analysis of 293 Randomized Clinical Trials, Poynard T, Pignon JP (Eds), John Libbey Eurotext, Paris 1989. p.7.
- Hawkey CJ, Walt RP. Prostaglandins for peptic ulcer: a promise unfulfilled. Lancet 1986; 2:1084.
- Bianchi Porro G, Lazzaroni M, Petrillo M. Giant duodenal ulcers. Dig Dis Sci 1984; 29:781.
- Jaszewski R, Crane SA, Cid AA. Giant duodenal ulcers. Successful healing with medical therapy. Dig Dis Sci 1983; 28:486.
- Barragry TP, Blatchford JW 3rd, Allen MO. Giant gastric ulcers. A review of 49 cases. Ann Surg 1986; 203:255.
- Farinati F, Cardin F, Di Mario F, et al. Early and advanced gastric cancer during follow-up of apparently benign gastric ulcer: significance of the presence of epithelial dysplasia. J Surg Oncol 1987; 36:263.
- Podolsky I, Storms PR, Richardson CT, et al. Gastric adenocarcinoma masquerading endoscopically as benign gastric ulcer. A five-year experience. Dig Dis Sci 1988; 33:1057.
- Dammann HG, Walter TA. Efficacy of continuous therapy for peptic ulcer in controlled clinical trials. Aliment Pharmacol Ther 1993; 7 Suppl 2:17.
- Lauritsen K, Andersen BN, Laursen LS, et al. Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial. Gastroenterology 1991; 100:663.
- Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006; 296:2947.
- Penston JG, Wormsley KG. Review article: maintenance treatment with H2-receptor antagonists for peptic ulcer disease. Aliment Pharmacol Ther 1992; 6:3.
- Bianchi Porro G, Parente F. Long term treatment of duodenal ulcer. A review of management options. Drugs 1991; 41:38.
- Penston JG. A decade of experience with long-term continuous treatment of peptic ulcers with H2-receptor antagonists. Aliment Pharmacol Ther 1993; 7 Suppl 2:27.
- Mahadevan U, Kane S. American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy. Gastroenterology 2006; 131:283.
- Dehlink E, Yen E, Leichtner AM, et al. First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population-based register study. Clin Exp Allergy 2009; 39:246.
- Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol 2007; 110:695.
- Mansour GM, Nashaat EH. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum. Arch Gynecol Obstet 2011; 284:843.
- NATURAL HISTORY
- General approach
- Eradication of H. pylori
- - Treatment of H. pylori in patients on NSAIDs
- - Antisecretory therapy after H. pylori eradication
- Initial approach to ulcers not due to H. pylori
- - Confirm H. pylori negativity
- - Antisecretory therapy
- - Giant ulcers
- FOLLOW-UP AFTER INITIAL THERAPY FOR PEPTIC ULCER
- Duodenal ulcers
- Gastric ulcers
- MAINTENANCE THERAPY
- Duodenal ulcers
- Gastric ulcers
- DISCONTINUING PPIs
- TREATMENT DURING PREGNANCY AND LACTATION
- REFRACTORY ULCERS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS