Peptic ulcer disease

Summary

Peptic ulcer disease (PUD) represents a spectrum of ulcerative lesions in the stomach or duodenum. Predominant causes include Helicobacter pylori infection, chronic NSAID usage, hypersecretory states, and stress-related factors. While epigastric pain is a common symptom, PUD can be asymptomatic in many cases. Management typically involves a test-and-treat approach for H. pylori in patients under 60, or empirical acid suppression therapy. In older patients or those with high-risk features, esophagogastroduodenoscopy (EGD) with biopsies is crucial for diagnosis and to exclude serious differentials like gastric cancer. Primary treatment focuses on symptom alleviation through acid-lowering medication, eradication of H. pylori, and discontinuation of causative agents. Proton-pump inhibitors are often prescribed for 4–8 weeks post-eradication and may extend as maintenance therapy in recurrent cases. Surgical options are reserved for exceptional circumstances. Endoscopic surveillance is advisable in persistent symptomatology or if malignancy is suspected.

Definitions

• Peptic Ulcer:
  • A lesion in the gastric or duodenal mucosa.
  • Diameter: At least 0.5 cm.
  • Depth: Penetrates through the muscularis mucosae.
• Gastric Ulcer:
  • A type of peptic ulcer located in the stomach's mucosa.
  • Typically found along the lesser curvature.
  • Located in the transitional area between the corpus and antrum of the stomach.
• Duodenal Ulcer:
  • A type of peptic ulcer occurring in the duodenal mucosa.
  • Commonly located on the anterior or posterior wall of the duodenal bulb.

Etiology

• Common Causes of PUD:
  • H. pylori Infection:
    • Accounts for 40–70% of duodenal ulcers and 25–50% of gastric ulcers.
    • The prevalence of H. pylori infection and related PUD is decreasing.
  • Chronic NSAID Use:
    • Increases PUD risk fourfold.
    • Heightens risk for PUD complications (refer to “Complications of peptic ulcer disease”).
    • Acid suppression medication recommended for ulcer prevention in chronic NSAID users.
• Associated Risk Factors:
  • H. pylori infection or NSAID use alone rarely causes ulcers; typically combined with other risk factors:
    • Shared risk factors with PUD, GERD, and gastritis (smoking, heavy alcohol use, glucocorticoids, caffeine).
    • Diet.
    • Psychological factors (anxiety, stress, PTSD).
    • Genetic predisposition.
• Rare Causes of PUD:
  • Acid Hypersecretory States:
    • Zollinger-Ellison syndrome (gastrinoma).
    • Systemic mastocytosis.
    • Hyperparathyroidism.
  • Non-NSAID Medications:
    • Acetaminophen, bisphosphonates, sirolimus, mycophenolate, SSRIs, chemotherapeutics (e.g., 5-FU).
  • Infections:
    • CMV, HSV-1, EBV, Helicobacter heilmannii.
  • Others:
    • Radiation, illicit drug use (e.g., cocaine, methamphetamine).
    • Systemic inflammatory diseases (e.g., Crohn's disease, sarcoidosis).
    • Mechanical causes (foreign body, GI tract obstruction, postsurgical anatomy).

Pathophysiology

• Overview of Peptic Ulcer Disease Pathophysiology:
  • Ulcers occur when protective mechanisms of the gastric mucosa are disrupted and/or excessive gastric acid or pepsin is secreted.
  • Normal physiology involves balance between gastric juice secretion and protective measures.
• Physiological Gastric Secretions:
  • Parietal Cells: Secrete hydrochloric acid (HCl) and intrinsic factor. Stimulated by acetylcholine, histamine, gastrin; inhibited by prostaglandins, somatostatin.
  • Mucosal Cells: Secrete protective mucus, stimulated by acetylcholine, prostaglandins (also inhibit HCl secretion), secretin.
  • Chief Cells: Secrete pepsinogen, stimulated by acetylcholine, gastrin, secretin, VIP.
• Mechanisms of Physiological Disruption:
  • H. pylori in Gastric Ulcers:
    • Secretes urease, converting urea to NH3 for survival in acidic environment.
    • Colonizes and attaches to epithelial cells, releases cytotoxins (e.g., cagA toxin), disrupting mucosal barrier.
  • H. pylori in Duodenal Ulcers:
    • Inhibits somatostatin secretion, increases gastrin and H+ secretion.
    • Spreads to duodenum, inhibits HCO3- secretion, leading to acidification.
  • NSAIDs:
    • Inhibit COX-1 and COX-2, reducing prostaglandin production, eroding gastric mucosa.
    • Decrease mucosal blood flow and inhibit mucosal cell proliferation.
  • Acid Hypersecretion (e.g., Zollinger-Ellison Syndrome):
    • Increased acid secretion and parietal cell mass, delivering excessive acid to the duodenum.

Clinical features

• Asymptomatic PUD:
  • Up to 70% of peptic ulcer patients may not experience symptoms.
  • NSAID users are more likely to have asymptomatic ulcers and present with complications.
• Symptomatic PUD:
  • Abdominal Pain:
    • The most common symptom.
    • Typically located in the epigastrium.
    • Often described as “gnawing” or “burning”.
    • Relationship to meal intake varies with ulcer location.
  • Other Associated Symptoms:
    • Belching.
    • Indigestion.
    • Gastrointestinal reflux.
    • Nausea and/or vomiting.
    • Bloating or abdominal fullness.
• Clinical Symptoms of Gastric and Duodenal Ulcers:
  • Common to Both:
    • Dyspepsia symptoms: postprandial heaviness, early satiety, epigastric pain.
    • Pain relief with antacids.
    • Potential signs of internal bleeding (anemia, hematemesis, melena).
    • Stool sample positive for occult blood.
  • Gastric Ulcer:
    • Pain increases shortly after eating, potentially leading to weight loss.
    • Less common nocturnal pain.
  • Duodenal Ulcer:
    • Pain relieved by food intake, potentially leading to weight gain.
    • Pain increases 2–5 hours after eating.
    • More common nocturnal pain.

Diagnostics

• Initial Evaluation:
  • All Patients:
    • Screen for common etiologies (e.g., NSAID use).
    • Consider CBC, BMP, fecal occult blood test for occult bleeding.
  • Patients ≤ 60 Years Without Red Flags:
    • Begin with noninvasive H. pylori testing (urea breath test, stool antigen test).
  • Patients > 60 Years or > 45 Years in High Gastric Cancer Prevalence Areas; Patients with Red Flags; Patients Unresponsive to Medical Therapy:
    • Direct referral for Esophagogastroduodenoscopy (EGD) or other diagnostics (e.g., liver chemistries, abdominal ultrasound).
• Further Evaluation:
  • For Uncertain Etiology:
    • Consider specialized tests (e.g., secretin stimulation test for gastrinoma).
  • Alarm Features Warranting EGD in Younger Patients:
    • Include progressive dysphagia, odynophagia, rapid weight loss, persistent vomiting, suspected GI bleeding, family history of upper GI malignancy.
• Esophagogastroduodenoscopy (EGD):
  • Most accurate test for confirming diagnosis.
  • Applications include malignancy screening, visualization, biopsy, invasive H. pylori testing, therapeutic measures.
• Endoscopic Findings:
  • Differentiating between benign and malignant ulcers based on base, edges, surrounding mucosa, and location.
  • Histopathology: Chronic inflammatory changes (benign) vs. dysplasia, deeper layer invasion (malignant).
• Indications for Biopsy:
  • Gastric Ulcers:
    • Recommended multiple biopsies from ulcer edge and base.
    • Biopsies from various stomach areas for H. pylori testing.
  • Duodenal Ulcers:
    • Biopsy ulcers with malignant features.
    • Usually benign, routine biopsy not required.
• Specialized Laboratory Studies:
  • Consider if unclear etiology or recurrent ulcers.
  • Tests: Fasting serum gastrin, secretin stimulation test (for Zollinger-Ellison syndrome), serum intact PTH level, testing for systemic inflammatory diseases.

Treatment

• General Measures:
  • Nonpharmacological: Avoid NSAIDs, restrict alcohol.
  • Follow-up: Confirm treatment success, consider endoscopic surveillance.
  • H. pylori test-and-treat strategy:
    • Positive: H. pylori eradication therapy (antibiotics + PPI), continue acid suppression for 4–8 weeks.
    • Negative: Trial of acid suppression (PPIs) for 4–8 weeks, followed by reevaluation.
  • Failure of medical treatment: Consider elective surgery.
• Medical Treatment of PUD:
  • Acid suppression therapy and H. pylori eradication if detected.
  • Complement with antacids for rapid symptom relief.
  • Cytoprotective agents for mucosal protection.
    • Sucralfate: Forms a protective barrier over mucosa, acts as acid buffer.
    • Misoprostol.
  • Antibiotics: Clarithromycin triple therapy (with amoxicillin and PPI).
• Nonpharmacological Measures:
  • Restrict alcohol, smoking, caffeine; avoid stress.
  • Discontinue or reduce medications worsening PUD (e.g., NSAIDs, corticosteroids).
  • Avoid eating before bedtime.
• Elective Surgical Treatment:
  • Indications: Refractory symptoms, NSAID continuation, intolerance to medical treatment.
  • Surgical Procedures:
    • Vagotomy: Division of vagal trunks, reduces acid production by ~70%. Possible complications include delayed gastric emptying, diarrhea, hypergastrinemia, dumping syndrome.
    • Combined with drainage procedures:
      • Pyloroplasty.
      • Antrectomy.
      • Subtotal or Partial gastrectomy (Billroth I or II).
      • Total gastrectomy and reconstruction (Roux-en-Y).