SUMMARY:

Peptic Ulcer Disease (PUD) is a common cause of epigastric pain.  Pathophysiology is due to discontinuation of the inner lining of the gastrointestinal (GI) tract due to gastric acid secretion or pepsin causing an ulcer.  The ulcer extends into the muscularis propria layer of the gastric epithelium and usually occurs in the stomach or duodenum.  Ulcers may extend to the lower esophagus, distal duodenum or jejunum.  Helicobacter pylori testing is recommended for all patients and, if positive, treatment with a proton pump inhibitor (PPI) based triple therapy usually manages most symptoms

Typical Symptoms

• Symptoms of PUD typically manifest as epigastric pain, and can vary based on ulcer location.
• Gastric ulcers typically present 15 to 30 minutes after a meal and delayed presentation of 2 to 3 hours after a meal with a duodenal ulcer
• General symptoms include
  • Epigastric pain or burning sensation
  • Bloating
  • Abdominal fullness
  • Nausea and vomiting
  • Hematemesis
  • Melena
  • Early satiety

Symptoms that require further workup and evaluation

• Unintentional weight loss
• Progressive dysphagia
• Overt GI bleeding
• Abdominal mass
• Iron deficiency anemia
• Recurrent emesis
• Jaundice
• Family history of upper GI malignancy

Etiology and Risk Factors 

 Common Causes of PUD include

• H. pylori infection-a gram-negative, helical, rod-shaped bacteria that colonizes the gastric mucosa in half the world’s population
  • Found in 70 to 95% of patients with PUD
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Other medications (corticosteroids, bisphosphonates, potassium chloride, selective serotonin reuptake inhibitors and others)

Less common causes of PUD

• Hypersecretory environments
  • Zollinger-Ellison syndrome | Systemic mastocytosis | Cystic fibrosis | Hyperparathyroidism | Antral G cell hyperplasia
• Malignancy
  • Gastric cancer | Lung cancer | Lymphoma
• Physical stress
  • Acute illnesses | Burns | Injuries
• Viral infections
• Vascular insufficiency
• Radiation therapy
• Crohn’s disease
• Chemotherapy

Unclear Etiologies

• Tobacco use-associated, but correlation is not linear
• Alcohol-irritates gastric mucosa and induces acidity

Diagnosis and Workup of PUD

History and Physical Exam

• Patients reporting the common symptoms, such as epigastric pain, abdominal fullness, and bloating, should raise suspicion for PUD
• Timing of pain related to meals can pinpoint location
  • Gastric ulcers associated with pain increasing with meals leading to weight loss
  • Duodenal ulcers present with decreased pain in relation to meals and may cause weight gain
• Any patient presenting with alarm symptoms listed above should be investigated further
• Physical exam may reveal epigastric tenderness and signs of anemia

Differential Diagnosis

• Gastritis: Inflammatory process affecting the gastric mucosa
• Gastroesophageal reflux disease (GERD): Reflex flow of gastric acid into the esophagus
• Gastric cancer-associated with alarm symptoms
• Pancreatitis: Elevated serum lipase and amylase are helpful for diagnosis
• Biliary colic: Usually precipitated by fatty meals
• Cholecystitis: Usually exacerbated by fatty meals and associated with
  •  Nausea | Vomiting | Fever | Leukocytosis | Abnormal liver function
• Celiac disease: Autoimmune disease triggered by gluten causing symptoms such as
  •  Bloating | Diarrhea | Constipation
• Myocardial infarction: Associated with dizziness, shortness of breath and abnormal vital signs
• Mesenteric ischemia: More common in patients of older age with risk factors for atherosclerosis
• Mesenteric vasculitis: Usually have symptoms of systemic vasculitis

Diagnostic Tests

• Esophagogastroduodenoscopy (EGD) is the gold standard for diagnosis | The American Society of Gastrointestinal Endoscopy guidelines recommend an EGD for
  • Patients >60 years of age and new onset of dyspeptic symptoms
  • Patients that present with  symptoms that require further workup (see above)
• Barium swallow may be indicated when EGD is contraindicated, such as severe COPD or patients at high risk for anesthesia complications
• Helicobacter pylori testing should be obtained when PUD is suspected and eradication should be confirmed after treatment
  • Urea breath test: Most sensitive and specific choice | May be used to confirm treatment 4 to 6 weeks after treatment completion | Cost and inconvenience are disadvantages | PPI treatment should be stopped 2 weeks prior to testing.
  • Stool antigen test: Also very sensitive and specific and can be used for test of cure, cheaper and more convenient than the urea breath test | PPI should be stopped 2 weeks prior to testing
  • Antibodies to H. pylori: Cannot distinguish between current and past infections, does not require stopping of PPI treatment | Not recommended for diagnosis  
  • Endoscopic biopsy
• Blood work should include CBC, liver function, amylase level and lipase
  • A serum gastric level should be included if Zollinger-Ellison syndrome is suspected
• Abdominal CT with contrast may be used to investigate for complications such as perforation or gastric outlet obstruction

Treatment Principles

Treatment includes removing any offending agent, such NSAIDs and anti-secretory drugs, and treating H. pylori infection

• Antisecretory drugs:  PPI have replaced H2 receptor blockers due to their efficacy
  • Consider calcium supplements to reduce risk of osteoporosis and bone fractures associated with long-term PPI use
• Prostaglandin analogs (misoprostol 200 mcg every 6 hours) may be used as prophylaxis for NSAID-induced peptic ulcers when NSAIDs are taken long-term
• H. pylori-induced PUD should be treated with a triple regimen consisting of 2 antibiotics and a PPI
  • Many antibiotic regimens available for treatment
  • Therapy must be chosen empirically based on regional bacterial resistance patterns, local recommendations, and drug availability
  • One common treatment regimen is pantoprazole 40 mg, clarithromycin 500 mg bid and metronidazole 500 bid or amoxicillin 1 gm bid for 7 to 14 days
  • If triple therapy fails, quadruple therapy with bismuth and different antibiotics is indicated

Failed Medical Management and Surgical Treatment

• Surgical treatment, including vagotomy or partial gastrectomy, should only be considered for patients who are
  • Unresponsive to treatment
  • Non-adherent to therapy
  • At high risk of complications
• Refractory ulcer >5 mm in diameter that does not heal with 8 to 12 weeks of PPI use may be caused by
  • Persistent H. pylori infection
  • Continued NSAID use
  • Significant comorbidities that impair healing such as gastric cancer or gastrinoma (Zollinger-Ellison syndrome which can be detected measuring serum gastrin level)

 Complications of PUD

• Bleeding
• Perforation
• Gastric outlet obstruction
• Cancer

Primary Sources – Learn More:

Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection

ACG Clinical Guideline: Treatment of Helicobacter pylori Infection

ACG and CAG Clinical Guideline: Management of Dyspepsia

Management of Patients With Ulcer Bleeding