What is the likely diagnosis for a patient experiencing nocturnal epigastric, lower chest, and left upper quadrant pain that occurs between 3 to 6 AM and resolves with eating?

Likely Diagnosis: Peptic Ulcer Disease (Duodenal Ulcer)

The clinical presentation of nocturnal epigastric pain between 3-6 AM that resolves with eating is classic for duodenal ulcer disease, which characteristically causes pain when the stomach is empty and improves with food intake. 1, 2

Pathognomonic Clinical Features

The timing and pattern of this pain are highly characteristic of peptic ulcer disease:

• Nocturnal pain that awakens the patient between 3-6 AM occurs specifically with duodenal ulcers because gastric acid secretion peaks during these hours when the stomach is empty, directly irritating the ulcer 1
• Pain relief with eating is pathognomonic for duodenal ulcer - food buffers gastric acid and temporarily neutralizes the acidic environment irritating the ulcer 1, 2
• Pain that occurs between meals (when acid levels are high and food buffering is absent) further supports this diagnosis 1

Epidemiology and Risk Factors to Assess

• Peptic ulcer disease affects 1% of the U.S. population, with approximately 10% of patients presenting with upper abdominal pain in primary care having a peptic ulcer 2
• The two principal causes require immediate investigation: Helicobacter pylori infection (42% of cases) and NSAID/aspirin use (36% of cases) 2
• Obtain a detailed medication history focusing on NSAIDs, aspirin, anticoagulants, and corticosteroids 2

Critical Warning Signs Requiring Urgent Evaluation

Before proceeding with routine workup, immediately assess for life-threatening complications:

• Sudden severe epigastric pain with fever and abdominal rigidity suggests perforation, which carries mortality rates up to 30% if treatment is delayed 3, 4
• Hematemesis, melena, or occult blood in stool indicates gastrointestinal bleeding (the most common complication, occurring in 73% of complicated cases, with 30-day mortality of 8.6%) 3, 2
• Persistent vomiting suggests gastric outlet obstruction (3% of complicated cases) 2

Diagnostic Algorithm

For patients without alarm features (no bleeding, perforation signs, or obstruction):

1. Test for H. pylori infection first - this is the cornerstone of diagnosis in younger patients without alarm symptoms 3, 2
2. Upper endoscopy with biopsy is the definitive diagnostic test when alarm features are present, allowing direct visualization, histopathological confirmation, and simultaneous H. pylori testing from tissue samples 3
3. At least two biopsy samples from both antrum and body should be obtained during endoscopy to improve H. pylori detection sensitivity 3

CT abdomen/pelvis with IV contrast is indicated when:

• Diagnosis remains unclear after initial evaluation 4
• Perforation is suspected (shows extraluminal gas in 97%, focal wall defect in 84%, and wall thickening in 72% of perforations) 5, 4

Differential Diagnoses to Exclude

While the nocturnal pattern strongly suggests duodenal ulcer, consider:

• Gastroesophageal reflux disease (GERD) affects 42% of Americans monthly, but typically causes heartburn and regurgitation rather than pain relieved by eating 5, 4
• Gastritis can cause similar epigastric pain but lacks the characteristic nocturnal timing and food relief pattern 5
• Myocardial infarction can present atypically with epigastric pain, especially in women, diabetics, and elderly patients - obtain ECG within 10 minutes if any cardiac risk factors are present 4

Treatment Approach

Initiate empiric therapy immediately while awaiting diagnostic results:

• Start high-dose proton pump inhibitor (omeprazole 20-40 mg once daily or equivalent) - this heals 80-100% of duodenal ulcers within 4 weeks and 70-80% of gastric ulcers 4, 6, 2
• Alternatively, ranitidine 150 mg twice daily (if available) heals 73% of duodenal ulcers by week 4 6
• If H. pylori is confirmed, eradication therapy (such as bismuth, metronidazole, and tetracycline combined with omeprazole) decreases ulcer recurrence from 50-60% to 0-2% 2
• Discontinue all NSAIDs immediately - this alone heals 95% of NSAID-induced ulcers and reduces recurrence from 40% to 9% 2

Critical Pitfalls to Avoid

• Never dismiss the possibility of myocardial infarction in patients with epigastric pain, regardless of age or typical presentation - cardiac causes can masquerade as GI symptoms with mortality rates of 10-20% if missed 4
• Do not delay imaging in patients with peritoneal signs, as perforated ulcer mortality increases significantly with delayed diagnosis 4
• Symptoms are nonspecific and overlap extensively between GERD, gastritis, and peptic ulcer disease - the nocturnal timing and food relief pattern are the key distinguishing features 5, 1