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Peptic ulcer disease

Last updated: July 17, 2021

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Peptic ulcer disease (PUD) is the presence of one or more ulcerative lesions in the stomach or duodenum. Etiologies include infection with Helicobacter pylori (most common), prolonged NSAID use (possibly in combination with glucocorticoids), conditions associated with an overproduction of stomach acid (hypersecretory states), and stress. Epigastric pain is a typical symptom of PUD; however, many patients remain asymptomatic. Usually, patients younger than 60 years of age can be managed with a test-and-treat strategy for H. pylori infection or with empirical acid suppression therapy. Older patients and those with high-risk clinical features benefit from an esophagogastroduodenoscopy (EGD) and biopsies to confirm the diagnosis or rule out differential diagnoses (especially gastric cancer). First-line treatment for most peptic ulcers involves symptom control (e.g., acid-lowering medication), H. pylori eradication therapy, and withdrawal of causative agents. Antisecretory drugs (e.g., proton-pump inhibitors), which reduce stomach acid production, are continued for 4–8 weeks after eradication therapy and may be considered for maintenance therapy if symptoms recur. Surgical intervention may be considered in rare cases. Some patients benefit from endoscopic surveillance, especially if symptoms persist or there is clinical suspicion for malignancy.

Erosions are more superficial than ulcers. Ulcers involve damage to the gastric mucosa extending beyond the muscularis mucosa layer into the submucosa.

Epidemiological data refers to the US, unless otherwise specified.

Common causes of PUD

The two major contributing factors to the development of PUD are gastrointestinal infection with H. pylori and nonsteroidal anti-inflammatory drug (NSAID) use. Both factors contribute to the development of PUD and interact with other risk factors to promote ulcer formation.

  • Helicobacter pylori infection
  • Chronic NSAID use
    • Associated with a fourfold risk of developing PUD [9]
    • Increases the risk for complications of PUD (see “Complications of peptic ulcer disease”)

Associated risk factors

H. pylori infection or NSAID use alone do not typically cause ulcer formation. There are often additional risk factors present, such as the following, that increase the probability of developing an ulcer:

Rare causes of PUD

Under typical physiological conditions, the cells of the gastric mucosa secrete a gastric juice (an acidic fluid composed of HCl, pepsinogen, intrinsic factor, and mucus), which may damage the native cells of the GI tract. Protective mechanisms (e.g., secretion of mucus and HCO3- to form a protective barrier) prevent the gastric juices from digesting and eroding the gastric epithelial cells. Ulcer formation occurs when either the protective mechanisms are disrupted and/or excessive acids or pepsin are secreted.

Physiological gastric secretions [12]

See “Secretory and regulatory products of the gastrointestinal tract” in “Gastrointestinal tract” for more details on typical physiological secretions.

Mechanisms of physiological disruption [12]

PUD may be asymptomatic or manifest with a variety of clinical features, e.g., general dyspepsia or complications such as perforation or bleeding.

Asymptomatic PUD

  • Up to 70% of patients with peptic ulcers do not experience symptoms. [13][14]
  • Patients who take NSAIDs are more likely to have asymptomatic ulcers and present with complications of PUD (see “Complications of peptic ulcer disease”).

Symptomatic PUD

  • Abdominal pain
  • Other associated symptoms
    • Belching
    • Indigestion
    • Gastrointestinal reflux
    • Nausea and/or vomiting
    • Bloating/abdominal fullness
Clinical symptoms of gastric and duodenal ulcers

Gastric ulcer

Duodenal ulcer

Findings common to both

Pain and eating
  • Pain increases shortly after eating → weight loss
  • Pain is relieved with food intake weight gain
  • Pain increases 2–5 hours after eating. [16]
Nocturnal pain
  • Less common [17]
  • More common [17]

Gastric ulcer is associated with pain after light (weight loss) Gorging. Duodenal ulcer is associated with relief after massive (weight gain) Desserts.

Stress ulcer

Imagine a hot curling iron to remember that Curling ulcers occur in patients with severe burns.

Imagine a brain resting on a cushion to remember that patients with brain injury can develop Cushing ulcers.

Approach [18][19][20][21]

Diagnostic approach for suspected PUD [22]
Patient group Testing strategy
Initial evaluation
  • All patients
  • Screen for common etiologies on history, e.g., NSAID use (see “Etiology”)
  • Consider the following if there is suspicion for occult bleeding:
Further evaluation
  • All patients with persistently uncertain etiology

Alarm features warranting an EGD in younger patients include progressive dysphagia, odynophagia, rapid weight loss, persistent vomiting, suspected GI bleeding, and a family history of upper GI malignancy.

Esophagogastroduodenoscopy (EGD) [22]

The most accurate test to confirm the diagnosis. Other clinical applications include:

Endoscopic findings [23]

Classic endoscopic appearance of peptic ulcers
Benign Malignant
  • Smooth
  • Ulcerated mass protruding into the lumen
  • Rounded, regular
  • Irregular, overhanging
Surrounding mucosa
  • Regular
  • Nodular, irregular
  • Atypical
  • Chronic inflammatory changes and active granulation

An atypical location is suspicious for carcinoma!

Indications for biopsy

To rule out gastric cancer, patients with suspicious gastric ulcers should undergo follow-up EGD and histology until the ulcer has healed completely!

Specialized laboratory studies [1]

Consider testing for rare causes if the etiology remains unclear or the patient presents with recurrent ulcers.

Differential diagnosis of gastric and duodenal ulcers

Gastric ulcers

Duodenal ulcers


H. pylori infection

  • 25–50%
  • 40–70%
Other causes
Pathophysiology H. pylori infection
  • H. pylori secretes urease alkalinization of acidic environment → survival of bacteria in gastric lumen
  • Release of cytotoxins (e.g., cagA toxin) → disruption of the mucosal barrier and damage to underlying cells
Other causes
  • Acid hypersecretion
  • Mucosal protection

Clinical features
Pain and eating
  • Pain increases shortly after eating weight loss
  • Pain is relieved with food intake weight gain
  • Pain increases 2–5 hours after eating. [16]
Nocturnal pain [17]
  • Less common
  • More common
Diagnostics General
  • Multiple biopsies are recommended in most cases and should be taken:
    • From the edge and base of the ulcer
    • From different areas of the stomach lining, including those not surrounding the ulcer (to test for H. pylori)
Carcinoma risk
  • Increased

The differential diagnoses listed here are not exhaustive.


Therapeutic approach to PUD [22]
Clinical scenario Management
All patients
  • Nonpharmacological measures: E.g., avoid NSAIDs, restrict alcohol.
  • Follow-up to confirm treatment success and possibly endoscopic surveillance (see “Follow-up” for more details)

H. pylori test-and-treat strategy


Medically refractory symptoms

  • Consider elective surgery.
Inability to tolerate or adhere to medical treatment
Confirmed upper GI malignancy

Medical treatment of PUD

Pharmacologic therapies for uncomplicated PUD include a trial of acid suppression therapy and, if H. pylori is detected, eradication therapy. These may be complemented with antacids for rapid symptom relief, and in some cases with cytoprotective agents for mucosal protection. All patients should also be counseled on lifestyle and risk factor modification.

Elective surgical treatment [24]

Surgical management of uncomplicated peptic ulcers is rarely necessary because they usually respond well to medical treatment. When malignancy is confirmed or complications such as massive bleeding or gastrointestinal perforation occur, surgery specific to these complications must be performed.

  • Indications (consider after thorough evaluation)
    • Refractory symptoms or recurrence of disease despite appropriate medical treatment
    • Diseases that require the continuation of NSAIDs
    • Inability to tolerate medical treatment
  • Surgical procedures
    • Vagotomy: surgical division of the anterior and posterior vagal trunk of the vagus nerve (truncal vagotomy), both located along the lower esophagus. Denervation through truncal vagotomy results in ∼ 70% reduction of acid production.
      • Complications include delayed gastric emptying, postvagotomy diarrhea , postvagotomy hypergastrinemia, and dumping syndrome.
      • To improve results, truncal vagotomy is combined with one of the following drainage procedures:
        • Pyloroplasty
        • Antrectomy
        • Subtotal gastrectomy
    • Partial gastrectomy (Billroth) and reconstruction
      • Billroth I: distal gastrectomy with end-to-end or side-to-end gastroduodenostomy
      • Billroth II: resection of the distal two-thirds of the stomach with a blind-ending duodenal stump and end-to-side gastrojejunostomy
    • Total gastrectomy and reconstruction: Roux-en-Y

The anterior and posterior branches of the vagus nerve (CN X) are also known as nerves of Latarjet, which divide into terminal branches that innervate the stomach and the pylorus. The terminal branches on the antropyloric area are sometimes referred to as “crow's foot.”

Bleeding (see “Gastrointestinal bleeding”)

Peptic ulcer perforation (see also “Secondary peritonitis” and “Gastrointestinal perforation”)

Posterior ulcers are more likely to bleed and anterior ulcers are more likely to perforate: Postal workers wear Blue collars and should not have an Antisocial Personality.

Ulcer penetration and fistula formation

Gastric outlet obstruction (GOO)

Malignant transformation

We list the most important complications. The selection is not exhaustive.

Endoscopic follow-up [19]

  • Indications
    • Gastric ulcer in patients with ≥ 1 of the following :
      • Refractory symptoms
      • Ulcer of unknown etiology
      • Ulcer that appears malignant in initial EGD (even if biopsies are negative)
      • No biopsies taken in initial EGD (e.g., due to active bleeding)
      • Ulcer diagnosed via radiological imaging
    • Duodenal ulcer: if symptoms persist after an appropriate course of antisecretory treatment
    • Bleeding peptic ulcer requiring initial emergency endoscopy: endoscopic control on the following day
    • Dysplasia: endoscopy every 6–12 months depending on the degree of dysplasia
    • Refractory ulcer: Consider repeated EGD until the ulcer heals or etiology is identified.
    • New onset of symptoms after successful H. pylori eradication
  • Surveillance method: Repeat endoscopy and obtain new biopsies.

H. pylori eradication confirmation [18]

Prophylaxis for stress ulcer disease should be considered in any critically ill patient with a risk of GI bleeding. Prophylaxis was formerly recommended for all ICU patients, but evidence suggests that risks (e.g., for pneumonia) outweigh the benefits in patients with low bleeding risk. [27][28][29][30]

Indications for stress ulcer prophylaxis in critically ill patients [30]
GI bleeding risk Indications
  • Prophylactic agents [30]
  • Duration: Continue prophylaxis for as long as significant risk factors are present or until critical illness resolves. [31]

Both PPIs and H2 receptor antagonists may increase the risk of pneumonia in critically ill patients. [30]

Stress ulcer prophylaxis likely has little effect on mortality, length of admission, length of stay in critical care units, and duration of mechanical ventilation. [30]

  1. Goldman L, Schafer AI. Goldman-Cecil Medicine, 2-Volume Set. Elsevier ; 2019
  2. Buendgens L. Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis. World J Crit Care Med. 2016; 5 (1): p.57-64. doi: 10.5492/wjccm.v5.i1.57 . | Open in Read by QxMD
  3. Parrillo JE, Dellinger RP. Critical Care Medicine E-Book. Elsevier Health Sciences ; 2018
  4. Stress ulcer prophylaxis. Updated: January 1, 2008. Accessed: March 23, 2020.
  5. Ye Z, Reintam Blaser A, Lytvyn L, et al. Gastrointestinal bleeding prophylaxis for critically ill patients: a clinical practice guideline. BMJ. 2020 : p.l6722. doi: 10.1136/bmj.l6722 . | Open in Read by QxMD
  6. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med.. 2017; 43 (3): p.304-377. doi: 10.1007/s00134-017-4683-6 . | Open in Read by QxMD
  7. Ciociola AA, McSorley DJ, Turner K, Sykes D, Palmer JBD. Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated. Am J Gastroenterol. 1999; 94 (7): p.1834-1840. doi: 10.1111/j.1572-0241.1999.01214.x . | Open in Read by QxMD
  8. Sonnenberg A, Turner KO, Genta RM. Low Prevalence of Helicobacter pylori-Positive Peptic Ulcers in Private Outpatient Endoscopy Centers in the United States. Am J Gastroenterol. 2020; 115 (2): p.244-250. doi: 10.14309/ajg.0000000000000517 . | Open in Read by QxMD
  9. Hooi JKY, Lai WY, Ng WK, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017; 153 (2): p.420-429. doi: 10.1053/j.gastro.2017.04.022 . | Open in Read by QxMD
  10. Huang J-Q, 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 (9300): p.14-22. doi: 10.1016/s0140-6736(02)07273-2 . | Open in Read by QxMD
  11. Aldoori WH, Giovannucci EL, Stampfer MJ, Rimm EB, Wing AL, Willett WC. Prospective study of diet and the risk of duodenal ulcer in men.. Am J Epidemiol. 1997; 145 (1): p.42-50. doi: 10.1093/oxfordjournals.aje.a009030 . | Open in Read by QxMD
  12. Miftahussurur M, Yamaoka Y. Helicobacter pylori virulence genes and host genetic polymorphisms as risk factors for peptic ulcer disease.. Expert Rev Gastroenterol Hepatol. 2015; 9 (12): p.1535-47. doi: 10.1586/17474124.2015.1095089 . | Open in Read by QxMD
  13. Costanzo LS. Physiology 5th Edition. Saunders Elsevier ; 2014 : p. 349-356
  14. Lu C-L, Chang S-S, Wang S-S, Chang F-Y, Lee S-D. Silent peptic ulcer disease: frequency, factors leading to “silence,” and implications regarding the pathogenesis of visceral symptoms. Gastrointest Endosc. 2004; 60 (1): p.34-38. doi: 10.1016/s0016-5107(04)01311-2 . | Open in Read by QxMD
  15. Hilton D, Iman N, Burke GJ, et al. Absence of abdominal pain in older persons with endoscopic ulcers: a prospective study. Am J Gastroenterol. 2001; 96 (2): p.380-384. doi: 10.1111/j.1572-0241.2001.03455.x . | Open in Read by QxMD
  16. Barkun A, Leontiadis G. Systematic Review of the Symptom Burden, Quality of Life Impairment and Costs Associated with Peptic Ulcer Disease. Am J Med. 2010; 123 (4): p.358-366.e2. doi: 10.1016/j.amjmed.2009.09.031 . | Open in Read by QxMD
  17. Kang JY, Yap I, Guan R, Tay HH. Acid perfusion of duodenal ulcer craters and ulcer pain: a controlled double blind study.. Gut. 1986; 27 (8): p.942-945. doi: 10.1136/gut.27.8.942 . | Open in Read by QxMD
  18. Malik TF, Gnanapandithan K, Singh K. Peptic Ulcer Disease. StatPearls. 2020 .
  19. Chey WD, Wong BC, Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007; 102 (8): p.1808-1825. doi: 10.1111/j.1572-0241.2007.01393.x . | Open in Read by QxMD
  20. Banerjee S, Cash BD, Dominitz JA, et al. Guideline: The role of endoscopy in the management of patients with peptic ulcer disease. Gastrointest Endosc. 2010; 71 (4): p.663-668. doi: 10.1016/j.gie.2009.11.026 . | Open in Read by QxMD
  21. Fashner J, Gitu AC. Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection. Am Fam Physician.. 2015; 91 (4): p.236-242.
  22. Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007; 76 (7): p.1005-12.
  23. Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol. 2017; 112 (7): p.988-1013. doi: 10.1038/ajg.2017.154 . | Open in Read by QxMD
  24. Chen C-Y, Kuo Y-T, Lee C-H, et al. Differentiation between Malignant and Benign Gastric Ulcers: CT Virtual Gastroscopy versus Optical Gastroendoscopy. Radiology. 2009; 252 (2): p.410-417. doi: 10.1148/radiol.2522081249 . | Open in Read by QxMD
  25. Wang A, Yerxa J, Agarwal S, et al. Surgical Management of Peptic Ulcer Disease. Curr Probl Surg. 2020 : p.100728. doi: 10.1016/j.cpsurg.2019.100728 . | Open in Read by QxMD
  26. Tarasconi A, Coccolini F, Biffl WL, et al. Perforated and bleeding peptic ulcer: WSES guidelines. World J Emerg Surg. 2020; 15 (1). doi: 10.1186/s13017-019-0283-9 . | Open in Read by QxMD
  27. Søreide K, Thorsen K, Harrison EM, et al. Perforated peptic ulcer. Lancet.. 2015; 386 (10000): p.1288-1298. doi: 10.1016/s0140-6736(15)00276-7 . | Open in Read by QxMD
  28. 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 (7): p.718-728. doi: 10.1002/pds.2153 . | Open in Read by QxMD
  29. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States.. Gastroenterology. 2002; 122 (5): p.1500-11. doi: 10.1053/gast.2002.32978 . | Open in Read by QxMD
  30. Sonnenberg A. Review article: historic changes ofHelicobacter pylori-associated diseases. Aliment Pharmacol Ther. 2013; 38 (4): p.329-342. doi: 10.1111/apt.12380 . | Open in Read by QxMD
  31. Sonnenberg A. Temporal trends and geographical variations of peptic ulcer disease.. Aliment Pharmacol Ther. 1995; 9 Suppl 2 : p.3-12.
  32. Waller DG, Sampson AP. Dyspepsia and peptic ulcer disease. Elsevier ; 2018 : p. 401-410
  33. Andersen BN, Johansen PB, Abrahamsen B. Proton pump inhibitors and osteoporosis. Curr Opin Rheumatol. 2016; 28 (4): p.420-425. doi: 10.1097/bor.0000000000000291 . | Open in Read by QxMD
  34. Brisebois S, Merati A, Giliberto JP. Proton pump inhibitors: Review of reported risks and controversies. Laryngoscope Investigative Otolaryngology. 2018; 3 (6): p.457-462. doi: 10.1002/lio2.187 . | Open in Read by QxMD
  35. John Cameron, Andrew Cameron. Current Surgical Therapy 13th Edition. Elsevier ; 2019
  36. JOHNSON HD. Gastric Ulcer. Ann Surg. 1965; 162 (6): p.996-1004. doi: 10.1097/00000658-196512000-00005 . | Open in Read by QxMD