Peptic Ulcer Disease (PUD): Diagnosis and Treatment
SUMMARY:
Dyspepsia (epigastric discomfort, abdominal pain or fullness, nausea, early satiety, and heartburn) can be due to peptic ulcer disease (PUD). Ulcers, or open sores, can develop if the inner lining of the gastrointestinal (GI) tract is damaged, exposing the muscularis propria layer of the gastric epithelium. Ulcers typically occur in the stomach or proximal duodenum, but they may extend to the lower esophagus, distal duodenum or even jejunum. Approximately 1 in 5 cases of PUD are due to Helicobacter pylori (H. Pylori). The second most common cause is nonsteroidal anti-inflammatory drug (NSAID) use. Proton pump inhibitors (PPIs) are first-line therapy for treatment of PUD.
Symptoms
- Episodic epigastric non-radiating pain, gnawing or burning
- Gastric ulcers, symptoms 15 to 30 minutes postprandially
- Duodenal ulcers, better with food, pain 2 to 3 hours postprandially
- Bloating
- Abdominal fullness
- Nausea and vomiting
- Hematemesis
- Melena
- Early satiety
Symptoms that require further workup and evaluation
- Unintentional weight loss
- Progressive dysphagia or odynophagia
- Overt GI bleeding
- Abdominal mass
- Iron deficiency anemia
- Recurrent emesis
- Jaundice
- Family history of upper GI malignancy
- Lymphadenopathy
Etiology and Risk Factors
Risk Factors
- Older age
- Previous ulcer
- Use of aspirin or other NSAIDs | anticoagulants | corticosteroids
Most Common Causes
- H. pylori infection: Gram-negative, spiral-shaped bacterium that has adapted to survive in the harsh acidic environment of the human stomach
- Prevalence varies by global region, with North American rates estimated at 30% to 40%, but as high as 60% to 70% in low-resource settings
- Can cause dyspepsia | gastritis | PUD | gastric cancer
- Mode of transmission is not clear
- Greatest benefit of H. Pylori eradication is gastric adenocarcinoma prevention | MALT lymphoma remission
- Alcohol and nicotine use can increase risk of ulcers in those with untreated H. Pylori
- NSAID use
Combination of H. Pylori and NSAID use increases risk of bleeding sixfold
Diagnosis and Workup of PUD
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 have further testing
- Patients younger than 60 without alarm symptoms should be tested for H. Pylori
- Physical exam may reveal epigastric tenderness and signs of anemia
Differential Diagnosis
- Gastritis: Inflammatory process affecting the gastric mucosa
- Gastroesophageal reflux disease (GERD): Reflux 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, allows for direct visualization of the upper GI tract. Indicated for:
- Patients >60 years of age and new onset of dyspepsia
- Any adult with alarm symptoms suggestive of malignancy or structural disease (above)
- Can include tissue biopsy, has high specificity for detecting H. Pylori
- H. Pylori testing should be obtained when PUD is suspected and eradication should be confirmed after treatment
- Urea breath test: Most sensitive test | | Cost and inconvenience are disadvantages | PPI treatment should be stopped 2 weeks prior to testing| Antibiotics should be stopped 4 weeks prior to testing | Can be used for test of cure
- Stool antigen test: Highly sensitive and same specificity as urea breath test | Cheaper and more convenient than urea breath test | PPI should be stopped 2 weeks prior to testing | Antibiotics should be stopped 4 weeks prior to testing| Can be used for test of cure |
- H. pylori serological antibody testing: Cannot distinguish between current and past infections | Low sensitivity and specificity | Does not require stopping PPI or antibiotic treatment | Not recommended for diagnosis
- Endoscopic biopsy: Invasive | highly specific but lower sensitivity than tests listed above | not useful to monitor treatment response | PPI should be stopped 2 weeks prior to testing | antibiotics should be stopped 4 weeks prior to testing
- Blood work should include CBC, liver function, amylase level and lipase
- 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
- First line PUD therapy is at least 8 weeks of PPI therapy.
- Omeprazole | lansoprazole | pantoprazole | rabeprazole | esomeprazole | dexlansoprazole
- Potential risks of long-term PPI use are minimal but there is some evidence of: interactions with antiplatelet medications | CKD | Clostridioides difficile infection in hospitalized patients | dementia | gastric cancer | micronutrient deficiencies (magnesium, calcium, B12)
- Canadian guidelines recommend deprescribing PPI by reducing dose or discontinuing after 4-week course due to possible risk
- H. pylori-induced PUD should be treated with quadruple therapy including bismuth, tetracycline and metronidazole (or tinidazole), and a PPI twice daily (first-line) for 14 days
- Alternative option is concomitant therapy (AKA nonbismith quadruple therapy): PPI + 3 antibiotics (clarithromycin, amoxicillin, and metronidazole or tinidazole) for 14 days
- Prior triple therapy no longer recommended due to increasing worldwide resistance to H. Pylori
- Many antibiotic regimens available for treatment in cases of antibiotic resistance or if initial therapy fails
- A test of cure is recommended by urea breath test or stool antigen test 4 weeks after therapy completion and at least 2 weeks after stopping PPI
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
Reducing Risk of PUD
- For long-term NSAID use
- Consider replacing NSAID with celecoxib, a COX-2 inhibitor, has less effect on gastric mucosa
- Add PPI, H2blocker, or misoprostol with NSAID prophylactically
- Patients at high risk of NSAID-induced PUD, who need to continue NSAID use, should be proactively testing for H. Pylori even in absence of dyspepsia
Primary Sources – Learn More:
AAFP: Peptic Ulcer Disease and H. pylori Infection (2023)
