In an otherwise healthy adult with epigastric pain that occurs only on an empty stomach, what are the likely causes and the recommended evaluation and management?

Epigastric Pain on an Empty Stomach: Likely Causes and Management

In an otherwise healthy adult with epigastric pain occurring only when the stomach is empty, peptic ulcer disease—particularly duodenal ulcer—is the most likely diagnosis, and you should start high-dose PPI therapy immediately while testing for H. pylori and ruling out cardiac causes first. 1, 2, 3

Immediate Priority: Rule Out Life-Threatening Causes

Before assuming benign gastrointestinal pathology, you must exclude cardiac causes:

• Obtain an ECG and cardiac troponins immediately (at 0 and 6 hours—never rely on a single measurement), as myocardial infarction can present with isolated epigastric pain and carries 10-20% mortality if missed, especially in women, diabetics, and elderly patients 1, 2, 4
• This is non-negotiable regardless of age or "typical" presentation—cardiac causes must never be dismissed in patients with epigastric pain 1, 2

Most Likely Diagnosis: Peptic Ulcer Disease

The classic pattern of epigastric pain occurring when the stomach is empty strongly suggests duodenal ulcer:

• Peptic ulcer disease affects approximately 10% of patients presenting with upper abdominal pain in primary care, with duodenal ulcers characteristically causing pain in fasting conditions that is relieved by food 3, 5, 6
• The principal causes are H. pylori infection (42% of cases) and NSAID use (36% of cases) 3
• Approximately two-thirds of peptic ulcers are asymptomatic, but when symptomatic, epigastric pain, burning, or discomfort is the predominant complaint 4

Other Differential Diagnoses to Consider

• Functional dyspepsia is possible but less likely given the specific pattern of pain on an empty stomach; FD typically presents with persistent symptoms unrelated to fasting 5, 7
• GERD/esophagitis is less likely as the primary diagnosis without heartburn, though 66% of GERD patients do experience epigastric pain 5, 2
• Gastritis can present with similar symptoms and is often associated with NSAIDs, alcohol, or H. pylori 1, 2

Diagnostic Workup

Initial Laboratory Testing

• Complete blood count to assess for anemia from occult bleeding (the most common complication of peptic ulcer disease) 1, 2
• Stool for occult blood to detect gastrointestinal bleeding 1
• H. pylori testing using stool antigen test or urea breath test (not serology) 1

Physical Examination Focus

• Check for peritoneal signs (guarding, rebound tenderness, rigidity) which would indicate perforation requiring immediate imaging 1, 2
• Assess vital signs for tachycardia, fever, or hypotension suggesting complications like perforation or bleeding 1, 2
• Note that up to one-third of patients with perforated peptic ulcer may have minimal or absent peritoneal signs, so maintain high suspicion 4

When to Order Endoscopy

The British Society of Gastroenterology provides clear criteria 5:

• Urgent 2-week wait endoscopy if:

  • Age ≥55 years with new-onset dyspepsia
  • Any age with dyspepsia plus weight loss
  • Family history of gastro-oesophageal malignancy

• Non-urgent endoscopy if:

  • Treatment-resistant dyspepsia after 4-8 weeks of PPI therapy
  • Age ≥55 years with persistent symptoms 5, 1

Treatment Algorithm

Step 1: Immediate PPI Therapy

Start omeprazole 40 mg once daily, taken 30-60 minutes before breakfast 1, 2, 3:

• This achieves 80-90% healing rates for duodenal ulcers and 70-80% for gastric ulcers within 4-8 weeks 1, 3
• PPIs must be taken before meals (preferably breakfast) for optimal acid suppression 1
• Continue treatment for 4-8 weeks unless healing is demonstrated earlier by endoscopy 8, 3

Step 2: H. Pylori Management

• If H. pylori positive: Start triple therapy (bismuth, metronidazole, tetracycline plus omeprazole) to reduce ulcer recurrence from 50-60% to 0-2% 3
• If H. pylori negative: Continue omeprazole alone 1

Step 3: Critical Lifestyle Modifications

• Eliminate NSAIDs completely—they worsen peptic ulcer disease and increase bleeding risk; discontinuing NSAIDs heals 95% of ulcers and reduces recurrence from 40% to 9% 1, 3
• Avoid late meals and remain upright for 2-3 hours after eating to reduce nocturnal acid exposure 1, 2
• Counsel on smoking cessation and alcohol reduction—these have a synergistic dose-dependent effect on gastric ulcer risk 2

Critical Pitfalls to Avoid

• Never assume benign disease without excluding cardiac causes first—obtain ECG and troponins in all patients with epigastric pain 1, 2, 4
• Do not rely on antacid response to rule out serious pathology—peptic ulcer disease often fails to respond to antacids but responds well to PPIs 1
• Watch for alarm symptoms indicating complications:
  • Sudden severe pain with fever/rigidity suggests perforation (30% mortality if delayed) 1, 2, 4
  • Hematemesis, melena, or occult blood indicates bleeding 1, 2
  • Progressive symptoms despite PPI therapy warrant endoscopy 5, 1

Follow-Up Strategy

• Reassess at 4-8 weeks: If symptoms persist despite high-dose PPI therapy, refer for endoscopy 5, 1
• All gastric ulcers require biopsy to exclude malignancy, as ulceroproliferative features can represent adenocarcinoma 4
• Maintenance therapy: If ulcers recur, consider long-term PPI at lower doses (omeprazole 20 mg daily) or sucralfate 1 g twice daily 8