Approach to refractory or recurrent peptic ulcer disease
- Nimish B Vakil, MD, AGAF, FACP, FACG, FASGE
Nimish B Vakil, MD, AGAF, FACP, FACG, FASGE
- Clinical Professor of Medicine
- University of Wisconsin School of Medicine and Public Health
Most peptic ulcers respond to treatment with antimicrobial therapy for Helicobacter pylori, withdrawal of nonsteroidal anti-inflammatory drugs, or treatment with potent antisecretory drugs. However, in some individuals, the ulcer is either refractory to conventional therapy or recurs following successful initial treatment. This topic will review the factors associated with refractory and recurrent peptic ulcer disease, and the evaluation and management of patients with refractory or recurrent peptic ulcer disease. The clinical manifestations, diagnosis, and initial management of peptic ulcer disease are discussed in detail, separately. (See "Peptic ulcer disease: Clinical manifestations and diagnosis" and "Peptic ulcer disease: Management".)
●A peptic ulcer is an excavated defect in the gastric or duodenal mucosa that extends through the muscularis mucosa into the deeper layers of the wall.
●A refractory peptic ulcer is defined as an endoscopically proven ulcer greater than 5 mm in diameter that does not heal after 8 to 12 weeks of treatment with a proton pump inhibitor.
●A recurrent peptic ulcer is defined as an endoscopically proven ulcer greater than 5 mm in diameter that develops following complete ulcer healing.
EPIDEMIOLOGY AND RISK FACTORS
In the absence of continued nonsteroidal anti-inflammatory drug (NSAID) use, acid suppression heals >90 percent of peptic ulcers. However, approximately 5 to 10 percent of ulcers are refractory to 12 weeks of antisecretory therapy with a proton pump inhibitor (PPI). Even with continued PPI use, approximately 5 to 30 percent of peptic ulcers recur within the first year based on whether H. pylori has been successfully eradicated [1,2]. Risk factors for refractory and recurrent peptic ulceration include the following (table 1 and table 2) [3-6].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology 1996; 110:1244.
- 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.
- Yuan Y, Padol IT, Hunt RH. Peptic ulcer disease today. Nat Clin Pract Gastroenterol Hepatol 2006; 3:80.
- Bardhan KD, Nayyar AK, Royston C. History in our lifetime: the changing nature of refractory duodenal ulcer in the era of histamine H2 receptor antagonists. Dig Liver Dis 2003; 35:529.
- Goodman AJ, Kerrigan DD, Johnson AG. Effect of the pre-operative response to H2 receptor antagonists on the outcome of highly selective vagotomy for duodenal ulcer. Br J Surg 1987; 74:897.
- Kim HU. Diagnostic and Treatment Approaches for Refractory Peptic Ulcers. Clin Endosc 2015; 48:285.
- Lanas A, Remacha B, Sáinz R, Hirschowitz BI. Study of outcome after targeted intervention for peptic ulcer resistant to acid suppression therapy. Am J Gastroenterol 2000; 95:513.
- Hirschowitz BI, Lanas A. Intractable upper gastrointestinal ulceration due to aspirin in patients who have undergone surgery for peptic ulcer. Gastroenterology 1998; 114:883.
- Hirschowitz BI, Lanas A. Atypical and aggressive upper gastrointestinal ulceration associated with aspirin abuse. J Clin Gastroenterol 2002; 34:523.
- Lanas AI, Remacha B, Esteva F, Sáinz R. Risk factors associated with refractory peptic ulcers. Gastroenterology 1995; 109:1124.
- STEIGMANN F, SHULMAN B. The time of healing of gastric ulcers: implications as to therapy. Gastroenterology 1952; 20:20.
- Reynolds JC, Schoen RE, Maislin G, Zangari GG. Risk factors for delayed healing of duodenal ulcers treated with famotidine and ranitidine. Am J Gastroenterol 1994; 89:571.
- Shih SC, Tseng KW, Lin SC, et al. Expression patterns of transforming growth factor-beta and its receptors in gastric mucosa of patients with refractory gastric ulcer. World J Gastroenterol 2005; 11:136.
- Annibale B, De Magistris L, Corleto V, et al. Zollinger-Ellison syndrome and antral G-cell hyperfunction in patients with resistant duodenal ulcer disease. Aliment Pharmacol Ther 1994; 8:87.
- Gasparoni P, Caroli A, Sardeo G, et al. [Primary hyperparathyroidism and peptic ulcer]. Minerva Med 1989; 80:1327.
- Lewis JH. Idiopathic gastric acid hypersecretion: treatment implications for refractory acid/peptic disorders. Aliment Pharmacol Ther 1991; 5 Suppl 1:15.
- Collen MJ, Stanczak VJ, Ciarleglio CA. Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication). Dig Dis Sci 1989; 34:233.
- 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.
- Tseng GY, Lin HJ, Fang CT, et al. Recurrence of peptic ulcer in uraemic and non-uraemic patients after Helicobacter pylori eradication: a 2-year study. Aliment Pharmacol Ther 2007; 26:925.
- Fujita T, Ando T, Sakakibara M, et al. Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: a case report. World J Gastroenterol 2010; 16:2183.
- Park TY, Choi CH, Yang SY, et al. A case of hypereosinophilic syndrome presenting with intractable gastric ulcers. World J Gastroenterol 2009; 15:6129.
- Tee HP, Swartz D, Tydd T, Leong RW. Gastrointestinal: Eosinophilic enteritis manifesting as brown-pigmented duodenal ulcers. J Gastroenterol Hepatol 2009; 24:1892.
- Siaw EK, Sayed K, Jackson RJ. Eosinophilic gastroenteritis presenting as acute gastric perforation. J Pediatr Gastroenterol Nutr 2006; 43:691.
- Boyd HK, Zaterka S, Eisig JN, et al. Helicobacter pylori and refractory duodenal ulcers: cross-over comparison of continued cimetidine with cimetidine plus antimicrobials. Am J Gastroenterol 1994; 89:1505.
- Mantzaris GJ, Hatzis A, Tamvakologos G, et al. Prospective, randomized, investigator-blind trial of Helicobacter pylori infection treatment in patients with refractory duodenal ulcers. Healing and long-term relapse rates. Dig Dis Sci 1993; 38:1132.
- Arkkila PE, Kokkola A, Seppälä K, Sipponen P. Size of the peptic ulcer in Helicobacter pylori-positive patients: association with the clinical and histological characteristics. Scand J Gastroenterol 2007; 42:695.
- Avsar E, Kalayci C, Tözün N, et al. Refractory duodenal ulcer healing and relapse: comparison of omeprazole with Helicobacter pylori eradication. Eur J Gastroenterol Hepatol 1996; 8:449.
- Walt RP, Daneshmend TK. Resistant duodenal ulcer: when, why and what to do? Postgrad Med J 1988; 64:369.
- Vakil N, Lanza F, Schwartz H, Barth J. Seven-day therapy for Helicobacter pylori in the United States. Aliment Pharmacol Ther 2004; 20:99.
- Chan FK, Sung JJ, Lee YT, et al. Does smoking predispose to peptic ulcer relapse after eradication of Helicobacter pylori? Am J Gastroenterol 1997; 92:442.
- Bardhan KD, Graham DY, Hunt RH, O'Morain CA. Effects of smoking on cure of Helicobacter pylori infection and duodenal ulcer recurrence in patients treated with clarithromycin and omeprazole. Helicobacter 1997; 2:27.
- Li LF, Chan RL, Lu L, et al. Cigarette smoking and gastrointestinal diseases: the causal relationship and underlying molecular mechanisms (review). Int J Mol Med 2014; 34:372.
- 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.
- Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Aliment Pharmacol Ther 1990; 4:25.
- Bardhan KD. Is there any acid peptic disease that is refractory to proton pump inhibitors? Aliment Pharmacol Ther 1993; 7 Suppl 1:13.
- Lagoo J, Pappas TN, Perez A. A relic or still relevant: the narrowing role for vagotomy in the treatment of peptic ulcer disease. Am J Surg 2014; 207:120.
- EPIDEMIOLOGY AND RISK FACTORS
- H. pylori infection
- Ulcer characteristics
- Inadequate inhibition of acid secretion
- Acid hypersecretory states
- Comorbid conditions
- Unusual causes of refractory ulceration
- INITIAL MANAGEMENT
- Eradicate H. pylori
- Avoid NSAIDs and tobacco
- Antisecretory therapy
- Endoscopic surveillance
- SUBSEQUENT MANAGEMENT
- Maintenance antisecretory therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS