Peptic Ulcer Disease

Aka: Peptic Ulcer Disease, PUD, Gastric Ulcer, Duodenal Ulcer, Peptic Ulcer

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II. Definitions

  1. Peptic Ulcer
    1. Esophageal, Stomach or duodenal erosion of the mucosa
    2. Mucosal erosions develop at sites of inflammation from Gastric Irritants (esp. NSAIDs) and infections (esp. Helicobacter Pylori)
    3. Presents with Dyspepsia, Epigastric Pain, Nausea, Vomiting and Upper Gastrointestinal Bleeding

III. Epidemiology

  1. Annual Incidence: 0.1 to 0.3% in western countries (1 case per 1000 person years)
  2. Worldwide lifetime Prevalence approaches 1 in 12 adults in the United States (5-10%)

IV. Pathophysiology

  1. Inflammation from Gastric Irritants (esp. NSAIDs) and infections (esp. Helicobacter Pylori)
  2. Further injury occurs with gastric acid and pepsin secretion
  3. Erosions and ulcerations form in the esophagus, Stomach and duodenum

V. Causes

  1. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
    1. Peptic Ulcers occur in 5-20% of longterm NSAID use (including Aspirin)
    2. Risk increases NSAIDS are used >1 year, multiple NSAIDs or Dual Antiplatelet Therapy
    3. Gonzalez-Perez (2014) PLoS One 9(7): e101768 [PubMed]
  2. Helicobacter Pylori
    1. Those taking NSAIDs who are infected with Helicobacter Pylori, have a marked PUD risk (RR 60), and GI Bleed risk (RR 6)
      1. Huang (2002) Lancet 359(9300):14-22 [PubMed]
    2. Prevalence is decreasing (from prior reported rates as high as 70-90%)
      1. Duodenal Ulcer: 25% Prevalence
      2. Gastric Ulcer: 17% Prevalence
      3. Sonnenberg (2020) Am J Gastroenterol 115(2): 244-50 [PubMed]
  3. Acid Induced Ulcers
    1. Idiopathic
    2. Zollinger-Ellison Syndrome
  4. Chronic Disease
    1. Stress Ulcers in chronic debilitated conditions
    2. Chronic Obstructive Pulmonary Disease
    3. Cystic Fibrosis
    4. Alpha-1-Antitrypsin Deficiency
    5. Systemic Mastocytosis
    6. Basophilic Leukemia
    7. Chronic Renal Failure
    8. Cirrhosis

VI. Risk Factors

  1. See Gastric Irritants
  2. See Helicobacter Pylori

VII. Symptoms

  1. Dyspepsia
  2. Duodenal Ulcer
    1. Mid-Epigastric Pain, deep recurring ache
    2. Relieved with food or Antacids
    3. Aggravated by general irritants (below)
    4. Nocturnal pain is present and is relieved with food
  3. Gastric Ulcer
    1. Mid-Epigastric Pain
    2. Relieved by Antacids
    3. Aggravated by food and general irritants (below)
    4. Constitutional symptoms
      1. Anorexia
      2. Weight loss
      3. Nausea or Vomiting

VIII. Red Flags

  1. See Dyspepsia Red Flags

IX. Presentations: Special cohorts

  1. Children (rare)
    1. May present with poorly localized Abdominal Pain, Iron Deficiency Anemia
  2. Elderly
    1. Presents asymptomatically or non-specifically (e.g. confusion, Abdominal Distention)
    2. High risk of perforation and mortality
    3. NSAID Gastrointestinal Adverse Effects are more common in older patients
      1. Compounded by comorbid condition management (e.g. Antiplatelet Therapy, chronic Anticoagulation)
  3. Stress Ulcers
    1. Presents in seriously ill hospitalized patients (Mechanical Ventilation, Burn Injury)
  4. Pregnancy
    1. See Dyspepsia in Pregnancy

X. Differential Diagnosis

  1. See Dyspepsia Causes
  2. See Medication Causes of Dyspepsia
  3. Most common misdiagnoses for Peptic Ulcer Disease
    1. Functional Dyspepsia
    2. Esophagitis
    3. Gastroesophageal Reflux
    4. Gastritis
    5. Gastroenteritis
  4. Less common misdiagnoses for Peptic Ulcer Disease
    1. Biliary tract disease (Cholecystitis, Cholelithiasis, Ascending Cholangitis)
    2. Celiac Sprue (Gluten Sensitive Enteropathy)
    3. Inflammatory Bowel Disease
    4. Irritable Bowel Syndrome
    5. Pancreatitis
    6. Appendicitis
  5. Uncommon misdiagnoses for Peptic Ulcer Disease
    1. Abdominal Aortic Aneurysm
    2. Acute Coronary Syndrome
    3. Barrett Esophagus
    4. Gastric Cancer
    5. Ischemic Bowel disease in the elderly
    6. Viral Hepatitis
    7. Zollinger-Ellison Syndrome

XI. Diagnostics

  1. See Dyspepsia for evaluation protocol
  2. No additional investigation necessary if
    1. Symptoms consistent with Duodenal Ulcer and
    2. Medication leads to healing within 6 weeks
    3. Test and treat Helicobacter Pylori if indicated (see below)
  3. Upper Endoscopy Indications
    1. Assess and reassess Gastric Ulcers
    2. Age over 60 years with new Dyspepsia
    3. Evaluate for Gastric Carcinoma or structural disorders in high risk groups
      1. See Dyspepsia Red Flags
  4. Upper GI with Follow Through
    1. May be sufficient for Duodenal Ulcers
  5. Helicobacter Pylori testing if ulcer not NSAID related
    1. See Helicobacter pylori Noninvasive Testing

XII. Management: General Measures

  1. Avoid Gastric Irritants
    1. Avoid Alcohol
    2. Avoid Tobacco
    3. Avoid Caffeine
  2. Avoid bland diets (not effective)
    1. May stimulate greater acid production
  3. Avoid Glycopyrolate Dartisla ODT
    1. Glycopyrolate was originally used in the 1960s for Peptic Ulcers to reduce gastric secretions
    2. However, since that time, much more effective medications are available (e.g. H2 Blockers, Proton Pump Inhibitors)
    3. Yet, in 2022 Dartisla ODT was released in 2022, at $500/90 tablets, a 10 fold markup over generic glycopyrolate
    4. Avoid glycopyrolate (including Dartisla ODT) in Peptic Ulcer Disease (we have much better. less expensive treatments)
    5. (2022) Presc Lett 29(4): 24

XIII. Management: Cause Specific

  1. Non-NSAID Associated Peptic Ulcer disease
    1. See Helicobacter Pylori
    2. Helicobacter Pylori test and treatment
    3. Proton Pump Inhibitor and antibiotic regimen
  2. NSAID associated Peptic Ulcer
    1. Stop all NSAIDs (and other Gastric Irritants)!
    2. Proton Pump Inhibitor (PPI)
      1. Continue for at least 8 weeks
      2. Uncomplicated empiric management without endoscopy is recommended (unless other endoscopy indications)
    3. Other gastric protection
      1. H2 Antagonists (healing rates are 50% that of PPI)
      2. Consider Misoprostol

XIV. Management: Refractory Peptic Ulcer

  1. Causes
    1. Persistent NSAID use
    2. Resistant Helicobacter Pylori infection
    3. Gastric Cancer
    4. Zollinger-Ellison Syndrome
  2. Measures
    1. Continue Proton Pump Inhibitors
    2. Consider surgical intervention in severe cases or those at high risk of complications
      1. Duodenal Ulcer: Vagotomy or Partial Gastrectomy
      2. Gastric Ulcer: Partial Gastrectomy

XV. Prevention

  1. Avoid NSAIDs
    1. See NSAID Gastrointestinal Adverse Effects for risks (and prophylaxis options if NSAIDS are needed)
    2. For those who cannot stop NSAIDs, consider COX-2 Inhibitor and continue Proton Pump Inhibitor

XVI. Prognosis

  1. Proton Pump Inhibitors have higher efficacy than H2 Antagonists
  2. On Proton Pump Inhibitor
    1. Duodenal Ulcers heal in 95% of cases within 4 week
    2. Gastric Ulcers heal in 80-90% of cases within 8 weeks
  3. Recurrence risk (Duodenal Ulcers)
    1. Non-smoker recurrence in 1 year: 60%
    2. Smoker recurrence in 1 year: >75%

XVII. Complications

  1. Complications occur in 25% of cases (especially in Elderly taking NSAIDs)
  2. Gastrointestinal Hemorrhage (15-20% of cases)
    1. See Upper Gastrointestinal Bleeding
  3. Gastrointestinal Perforation
    1. Incidence: 1 per 10,000 per year for non-NSAID related Peptic Ulcer perforation
    2. Presents with severe Abdominal Pain, Acute Abdomen, with regional inflammation (Pancreatitis, hepatitis)
    3. Lowest mortality (6-14%) is associated with the earliest management in younger patients without comorbidity
  4. Gastric Outlet Obstruction (rare)
    1. Duodenum narrows with recurrent or persistent ulceration and secondary inflammation and scarring
    2. Presents with Retching and hematemsis
    3. Evaluate differential diagnosis including cancer
  5. Effects of therapy
    1. Longterm Proton Pump Inhibitors risk C. difficile, Vitamin B12 Deficiency, decreased Bone Mineral Density

XVIII. References

  1. Soll in Goldman (2000) Cecil Medicine, p. 671-84
  2. Behrman (2005) Arch Surg 140:201-8 [PubMed]
  3. Kamada (2021) J Gastroenterol 56(4): 303-22 [PubMed]
  4. Fashner (2015) Am Fam Physician 91(4): 236-42 [PubMed]
  5. McConaghy (2023) Am Fam Physician 107(2): 165-72 [PubMed]
  6. Ramakrishnan (2007) Am Fam Physician 76(7):1005-12 [PubMed]
  7. Smoot (2001) Prim Care 28(3):487-503 [PubMed]

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