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Peptic ulcer disease

Last updated on May 12, 2023

Peptic ulcer diseaseDescription of Medical Condition

A chronic ulcer in the lining of the gastrointestinal tract.

Duodenal ulcer (DU): Most located in the duodenal bulb. Multiple ulcers, and if distal to the bulb raise the possibility of Zollinger-Ellison syndrome.

Gastric ulcer (GU): Much less common than DU (in NSAID absence). Commonly located along lesser curvature of the antrum near the incisura and in the pre-pyloric area.

Esophageal ulcers: A peptic ulcer in the distal esophagus may be part of Barrett’s epithelial change due to chronic reflux of gastroduodenal contents

Ectopic gastric mucosal ulceration: May develop in patients with Meckel diverticula or other sites of ectopic gastric mucosa

System(s) affected: Gastrointestinal

Genetics: Higher incidence with HLA-B12, B5, Bw35 phenotypes, identical twins

Incidence/Prevalence in USA:

  • DU: 4 times more common than GU. Lifetime prevalence = 10% for men; 5% for women (gender gap is closing). 200,000-400,000 new DU cases/annually.
  • GU: 87,500 new cases annually. Incidence of new GU in adults; 50/100,000

Predominant age:

  • DU 25-75 years (rare before age 15)
  • GU peak incidence age 55-65; rare < age 40

Predominant sex:

  • DU: Male > Female (slightly)
  • GU: Male = Female (female predominance among NSAID users)

Medical Symptoms and Signs of Disease

In adults (DU)

– Gnawing or burning epigastric pain 1 -3 hours after meals, relieved by food, antacids, or antisecretory agents

– Nocturnal pain causing early morning awakening

– Epigastric pain in 60-90% (often vague discomfort, cramping, hunger pangs). Non-specific dyspeptic complaints (belching, bloating, abdominal distention food intolerance) in 40-70%.

– Upto 1/3 of adults >60 years old do not report abdominal pain

– Symptomatic periods occur in clusters lasting a few weeks followed by symptom-free periods for weeks to months. Some seasonal occurrence (spring and fall).

– Early satiety, anorexia, weight loss, abnormal saline load test, succussion splash, gastric retention of barium, nausea, vomiting suggest pyloric obstruction

– Heartburn (suggesting reflux disease)

– Sudden, severe mid-epigastric pain radiating to right shoulder, peritoneal signs and free peritoneal air may indicate perforation

– Dizziness, syncope, hematemesis or melena suggest hemorrhage

In adults (GU)

– Symptom complex similar to DU

– NSAID-induced ulcers often silent; perforation or bleeding may be initial presentation

– Epigastric pain following a meal an uncommon finding; early satiety, nausea, vomiting suggest gastric outlet obstruction

– Weight loss can occur with either benign or malignant gastric ulcers

In children (DU)

– Positive family history in 50% of early onset DU patients (under age 20)

– May account for chronic abdominal pain syndrome in young children

– Gastric outlet obstruction from ulcer must be distinguished from congenital infantile hypertrophic pyloric stenosis (seen within the first month after birth along with visible peristalses and a palpable pyloric mass)

What Causes Disease?

Etiology of DU and GU is multifactorial. H. pylori gastritis is present in >80% of DU and >60% of GU.

  • Imbalance between aggressive factors (e.g., gastric acid, pepsin, bile salts, pancreatic enzymes) and defensive factors maintaining mucosal integrity (e.g., mucus, bicarbonate, blood flow, prostaglandins, growth factors, cell turnover) which may relate to H. pylori infection
  • Ulcerogenic drugs (e.g., NSAIDs)
  • Zollinger-Ellison syndrome
  • Other hypersecretory syndromes
  • Retained gastric antrum

Risk Factors

  • Strongly associated: Drugs (e.g., NSAID use), family history of ulcer, Zollinger-Ellison syndrome (gastrinoma), cigarettes (>1/2 pack/day)
  • Possibly associated: Corticosteroids (high dose and/or prolonged therapy); blood group O; HLA-B12, B5. Bw35 phenotypes; stress; lower socioeconomic status; manual labor
  • Poorly or not associated: Dietary spices, alcohol, caffeine, acetaminophen
  • Lifetime risk for PUD in H. pylori infected individuals is 15%
  • Annual risk of DU developing in H. pylori — positive individual <1%

Diagnosis of Disease

Differential Diagnosis

  • Non-ulcer dyspepsia
  • Gastric carcinoma
  • H. pylori-associated gastritis (without ulcer)
  • Gastroesophageal reflux (with or without esophagitis)
  • Crohn disease (gastroduodenal)
  • Pancreatitis
  • Variant angina pectoris
  • Cholelithiasis syndrome
  • Atrophic gastritis


  • Anemia uncommon in absence of hemorrhage. Fecal occult blood requires colonic evaluation before attributing positive test to ulcer alone (especially in patients > 40 years).
  • Elevated serum gastrin (to rule out Zollinger-Ellison syndrome)
  • Gastric analysis (to rule out achlorhydria, acid hyperse-cretion)
  • Secretin stimulation test (paradoxical rise seen in ZE)
  • Serum pepsinogen

Drugs that may alter lab results: Antisecretory medications may give falsely low gastric analysis or elevated gastrin

Disorders that may alter lab results: N/A

Pathological Findings

  • Helicobacter pylori gastritis, atrophic gastritis, mucosa-associated lymphoid tissue (MALT)
  • Ulcer crater usually > 5 mm diameter; extends through the mucosa (in contrast to stress-related ulceration)

Special Tests

Serology, stool antigen, rapid urease test or urea breath test for H. pylori


  • Endoscopy more accurate than radiography
  • Radiographic features of benign GU include ulcer projecting beyond the lumen, radiolucent band (Hampton line) paralleling ulcer base, radiating folds

Diagnostic Procedures

  • Endoscopy (accuracy > 95%)
  • Barium meal (accuracy 70-90%)
  • Mucosal biopsy, cytology (excludes malignancy in > 99%)
  • Exploratory laparotomy
  • Histology, blood antibody, stool antigen or urea breath test for H. pylori
  • Current recommendations for diagnosing H. pylori in PUD

Onew onset PUD by endoscopy or radiography: rapid urease test (RUT) or specimen obtained by biopsy of the antrum or serum antibody; if negative, perform histology, stool antigen or urea breath test (UBT)

– History of uncomplicated PUD or those receiving maintenance antisecretory therapy for suspected PUD: nonendoscopic detection method; if negative, maintenance therapy can be discontinued; confirm negative H. pylori status by UBT or stool antigen 2-4 weeks later

Onew onset ulcer-like dyspepsia under age 50 without alarm symptoms: blood antibody testing, UBT or stool antigen. Overage 50 or any patient with alarm symptoms should have endoscopy and RUT or histology.

Treatment (Medical Therapy)

Appropriate Health Care

  • H. pylori should be sought in all patients with new onset PUD, those with a history of PUD, those with MALT-lymphoma or in otherwise healthy patients with ulcer-like dyspepsia
  • Empiric treatment for young healthy patients with dyspepsia, otherwise endoscopy or barium meal for suspected complications, weight loss, persistent vomiting, etc., or symptom onset after age 50 years
  • A noninvasive “test and threat” strategy for H. pylori in patients with ulcer-like dyspepsia results in an equivalent outcome compared to prompt endoscopy
  • Patients with nonulcer dyspepsia are unlikely to benefit from H. pylori therapy
  • Emergency endoscopy and hospitalization for suspected ulcer bleeding
  • ICU care for severe hemorrhage

General Measures

  • Reduce use of NSAIDs and psychic stress
  • Avoid or eliminate cigarette smoking

Surgical Measures

For bleeding complication, obstruction or perforation


Fully active in uncomplicated


Regular meals; avoid dietary irritants

Medications (Drugs, Medicines)

Drug(s) of Choice

Acid suppression

– H2 blocker: ranitidine or nizatidine 150 bid or 300 mg hs; cimetidine 400 mg bid or 800 mg hs; famotidine (Pepcid) 20 mg bid or 40 mg hs for 8-12 weeks

– Proton pump inhibitor, e.g., omeprazole 20 mg, lansoprazole 15 mg qd, rabeprazole 20 mg, esomeprazole 40 mg, or pantoprazole 40 mg daily for 4 weeks

Eradication of Helicobacter pylori (HP), single antibiotic regimens discouraged. Currently optimal HP eradication regimens:

– Proton pump inhibitor bid plus 2 antibiotics (e.g., clarithromycin 500 mg bid and amoxicillin 1 gm bid for 14 days)

– Ranitidine-bismuth-citrate 400 mg bid plus clarithromycin 500 mg bid and amoxicillin 1 gm bid for 14 days

– Alternative antibiotics: tetracycline, metronidazole, rifampin

– 2nd line regimen for treatment failures using rabeprazole, levofloxacin and rifabutin with or without bismuth subcitrate for 7 days had an eradication rate of 91%


– Treatment of H. pylori-negative ulcers: Most are due to NSAIDs; treat acutely with proton pump inhibitor for 4-12 weeks. Optimally, the NSAID should be discontinued, or switch to selective COX-2 inhibitor

– Unhealed refractory ulcers: higher doses of H2 Mockers or proton pump inhibitors or surgery and exclude surreptitious NSAID or salicylate use

  • Reduced risk of recurrent ulcer bleeding after endoscopic therapy followed by 72 hour IV infusion of omeprazole
  • Successful management of ZES with IV pantoprazole when po not possible

Contraindications: Known hypersensitivity to the drug or another member of the class


Renal insufficiency (GFR < 30 mL/min): reduce H2 blocker dose by 50%. Avoid magnesium-containing antacids

Give sucralfate distant from meals

Bacterial resistance: clarithromycin 10%, amoxicillin 1-2%, metronidazole 3%

Antibiotic-related side effects:

– Diarrhea (10%): change amoxicillin to tetracycline

– Nausea/vomiting (20%)

– Unpleasant taste with clarithromycin

– Rash (5%): stop antimicrobial

– Pseudomembranous colitis (< 1%): treat with vancomycin

– Anaphylaxis, Stevens-Johnson syndrome (rare)

Significant possible interactions:

Cimetidine interacts with many drugs (e.g., theophylline, warfarin, phenytoin, lidocaine) via inhibition of cytochrome P-450 isozymes, leading to reduced drug clearance; avoid cimetidine with interacting drugs.

Ranitidine and famotidine rarely associated with increased theophylline levels; nizatidine not associated with drug interactions

Omeprazole may prolong the elimination of diazepam, warfarin and phenytoin

Sucralfate reduces absorption of tetracycline, norfloxacin, ciprofloxacin, and theophylline leading to subtherapeutic levels

Alternative Drugs

Alternative ulcer healing drugs

– Sucralfate 1 gm qid or 2 gm bid for 4-8 wks

– Antacids, e.g., magnesium hydroxide, aluminum hydroxide 1 and 3 hours after meals (4-7 doses daily)

Patient Monitoring

Eradication of H. pylori: Expected in >90% (with 2 antibiotic regimen)

– Confirm eradication by CLOtest biopsy, histology, urea breath test, or stool antigen (has high predictive value on day 7 after treatment) in patients who remain symptomatic or relapse

– Blood antibody less useful in the immediate post-treatment period

– Treatment failure: use different antimicrobial regimen or test for sensitivity

Acute DU: monitor clinical response. No need to repeat endoscopy or x-ray exam to document healing unless recurrence or complication suspected.

Acute GU: confirm healing (endoscopy after 6-12 weeks for cytology and biopsy of poorly or unhealed ulcer to rule out malignancy)

Symptomatic response to therapy does not preclude malignancy

Prevention / Avoidance

  • Eradication of HP: recurrence < 10% in the first year off of all therapies
  • Maintenance therapy (using proton pump inhibitor or H2 blocker) suppresses ulcer relapse indefinitely while treatment is continued — however, relapses occur in most patients who remain HP positive off therapy
  • Bleeding ulcers require continued maintenance therapy (e.g., H2 blocker or PPI if H. pylori not eradicated)
  • NSAID-related ulcers: avoid salicylates and NSAIDs. If NSAIDs needed, add misoprostol (Cytotec) or proton pump inhibitor.
  • To reduce ulcer risk, eradicate H. pylori prior to start of NSAIDs
  • Selective COX-2 NSAIDs (e.g., celecoxib) produce significantly fewer Gl ulcers; consider for use in patients at risk for ulceration
  • Eradication of H. pylori proven to reduce risk of gastric cancer

Possible Complications

  • Hemorrhage in up to 25% of cases (initial presentation in 10%)
  • Perforation occurs in < 5%, usually related to NSAID use
  • Gastric outlet obstruction occurs in up to 5% of patients with duodenal or pyloric channel ulcers. Men predominate.
  • Risk of gastric adenocarcinoma increased up to 9 fold in H. pylori infected patients

Expected Course / Prognosis

  • Ulcer relapse rates after H. pylori eradication low; suspect surreptitious NSAID use
  • Reinfection rates < 1% per year
  • Risk of rebleeding after successful H. pylori therapy is extremely low
  • NSAID-related ulcers occur less commonly after H. pylori eradication
  • Intractability now rare
  • Regression or resolution of atrophic gastritis or low-grade MALT-lymphoma with successful H. pylori eradication


Associated Conditions

  • Zollinger-Ellison syndrome (gastrinoma)
  • Systemic mastocytosis
  • MEN Type 1
  • COPD, chronic renal failure, cirrhosis, hyperparathy-roidism, cardnoid syndrome, polycythemia rubra vera. basophilic leukemia, porphyria cutanea tarda

Age-Related Factors

Pediatric: Uncommon before puberty; hemorrhage and perforation more common

Geriatric: N/A


PUD unusual in gestation; safety of H2 blockers and PPIs not established; studies with cimetidine, ranitidine and omeprazole suggest safe use if needed. Sucralfate and antacids appear safe.


  • Duodenal ulcer
  • Gastric ulcer
  • Helicobacter pylori gastritis

International Classification of Diseases

532.90 Duodenal ulcer, unspecified as acute or chronic, without mention of hemorrhage, perforation, or obstruction

531.90 Gastric ulcer, unspecified as acute or chronic, without mention of hemorrhage, perforation, or obstruction

See Also

Zollinger-Ellison syndrome Pyloric stenosis

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