What is the differential diagnosis for epigastric pain?

Differential Diagnosis of Epigastric Pain

Life-Threatening Causes (Exclude First)

Myocardial infarction must be ruled out immediately in every patient with epigastric pain, as it presents atypically in 10-20% of cases—particularly in women, diabetics, and elderly patients—with mortality rates of 10-20% if missed. 1, 2, 3

Cardiac Causes

• Obtain a 12-lead ECG within 10 minutes of presentation and measure serial cardiac troponins at 0 and 6 hours; never rely on a single troponin measurement to exclude NSTEMI 1, 2, 3
• Atypical presentations include epigastric pain mimicking indigestion, isolated dyspnea, or pain without classic chest pressure 2, 3
• Signs suggesting acute coronary syndrome: diaphoresis, tachypnea, tachycardia, hypotension, pulmonary crackles, S3 gallop, or new mitral regurgitation murmur 2
• Acute aortic dissection causes sudden severe epigastric pain radiating to the back or shoulders; requires emergent CT angiography 1, 2
• Pulse differential in extremities (present in ~30% of dissections) plus widened mediastinum on chest X-ray predicts >80% probability of dissection 2

Gastrointestinal Emergencies

• Perforated peptic ulcer presents with sudden severe epigastric pain becoming generalized, accompanied by fever, abdominal rigidity, and absent bowel sounds; mortality reaches 30% if treatment is delayed 1, 2, 3
• CT with IV contrast shows extraluminal gas in 97% of cases, fluid or fat stranding in 89%, ascites in 89%, and focal wall defect in 84% 1, 2, 3
• Requires emergent surgical consultation for laparoscopic or open repair 2
• Acute pancreatitis characteristically presents with epigastric pain radiating to the back; diagnosed by serum lipase ≥2× normal or amylase ≥4× normal with 80-90% sensitivity 2, 4
• Can progress to necrotizing pancreatitis with multiorgan failure and 30-40% mortality 4

Vascular Emergencies

• Mesenteric ischemia causes severe epigastric pain with pain out of proportion to examination findings; requires CT angiography for diagnosis 2
• Elevated serum lactate indicates poor tissue perfusion and correlates with bowel ischemia 2
• Esophageal rupture presents with chest pain and painful, tympanic abdomen; constitutes a life-threatening emergency 2

Common Gastrointestinal Causes

Peptic Ulcer Disease (Non-Perforated)

• Population incidence of 0.1-0.3%, with complications (bleeding, obstruction, perforation) occurring in 2-10% of cases 1, 2
• CT features include gastric or duodenal wall thickening, mucosal hyperenhancement, adjacent fat stranding, focal outpouching, or interruption of mucosal enhancement 1, 2
• Active bleeding appears as hyperdense intraluminal blood products or active contrast extravasation on CT 2
• Bleeding is the most common complication, presenting as hematemesis 1

Gastroesophageal Reflux Disease (GERD)

• Affects 42% of Americans monthly and 7% daily, presenting with heartburn, regurgitation, and epigastric pain 1, 2, 3
• Distal esophageal wall thickening ≥5 mm on CT has 56% sensitivity and 88% specificity for reflux esophagitis 1, 2
• Esophagitis manifests as fine nodularity or granularity of mucosa, erosions, ulcers, thickened longitudinal folds, and strictures 1, 2, 3
• Biphasic esophagram has 88% sensitivity for detecting esophagitis when using combined technique 1, 2, 3

Gastritis

• Appears as enlarged areae gastricae, disrupted polygonal pattern by multiple uniform nodules, thickened gastric folds, or erosions 1, 2, 3
• Often associated with NSAID use, alcohol, or H. pylori infection 3
• Medication history is crucial: NSAIDs, bisphosphonates, potassium supplements, or iron can cause medication-induced gastritis 3

Gastric Cancer

• May present with ulcer associated with nodularity of adjacent mucosa, mass effect, or irregular radiating folds 1, 2, 3
• Now the most common cause of gastric outlet obstruction in adults with 5-year survival rate of 32% 2, 3
• Alarm features requiring urgent evaluation: weight loss, dysphagia, hematemesis, persistent vomiting, anemia 1, 2, 3

Noncardiac Causes (After Cardiac Exclusion)

Respiratory Causes

• Pulmonary embolism, pneumonia, and pneumothorax can present with epigastric pain; many patients have dyspnea in addition to pain 1

Musculoskeletal Causes

• Most common noncardiac cause includes costochondritis, muscle strain, and rib fracture 1
• Chest wall tenderness on palpation or pain worsening with inspiration markedly lowers probability of acute coronary syndrome 2
• Epigastric tenderness points toward esophagitis, peptic ulcer disease, or gallbladder pathology; tenderness over costochondral joints suggests musculoskeletal origin 2

Psychological Causes

• Usually diagnoses of exclusion but merit consideration in appropriate context 1
• For recurrent presentations with negative cardiac and GI workup, referral to cognitive-behavioral therapy is reasonable 1, 3

Diagnostic Algorithm

Initial Assessment (First 10 Minutes)

1. Check vital signs for tachycardia ≥110 bpm, fever ≥38°C, or hypotension, which predict perforation, anastomotic leak, or sepsis 2, 3
2. Obtain ECG within 10 minutes to exclude myocardial ischemia 1, 2, 3
3. Examine for peritoneal signs (rigidity, rebound tenderness, absent bowel sounds) indicating perforation 2, 3
4. Focused cardiovascular examination to identify aortic dissection, pulmonary embolism, or esophageal rupture 2

Laboratory Testing

• Cardiac troponins at 0 and 6 hours (never rely on single measurement) 1, 2, 3
• Complete blood count, C-reactive protein, serum lactate levels 2, 3
• Serum amylase or lipase to exclude acute pancreatitis 2, 3, 4
• Liver and renal function tests 2, 3
• Electrolyte and glucose levels 3

Imaging Strategy

• CT abdomen and pelvis with IV contrast is the gold standard when diagnosis is unclear, identifying pancreatitis, perforation, and vascular emergencies 1, 2, 3, 4
• Use neutral oral contrast (water or dilute barium) when gastric disease is suspected to delineate intraluminal space 1, 2
• CT angiography if mesenteric ischemia or aortic dissection suspected 1, 2
• Upper endoscopy is definitive for peptic ulcer disease, gastritis, and esophagitis when patient is hemodynamically stable 1, 2
• Fluoroscopic upper GI series evaluates structural and functional abnormalities of esophagus, stomach, and duodenum 1, 2

Empiric Management While Awaiting Diagnosis

• Maintain NPO status until surgical emergency is excluded 2, 3
• Establish IV access and provide fluid resuscitation if hemodynamically unstable 2, 3
• Start high-dose PPI therapy (omeprazole 20-40 mg once daily) for suspected acid-related pathology, with healing rates of 80-90% for duodenal ulcers and 70-80% for gastric ulcers 2, 3
• Avoid NSAIDs as they worsen peptic ulcer disease and bleeding risk 2, 3
• Symptomatic treatment for nausea: ondansetron 8 mg sublingually every 4-6 hours (obtain baseline ECG due to QTc prolongation risk), promethazine 12.5-25 mg orally/rectally every 4-6 hours, or prochlorperazine 5-10 mg every 6-8 hours 3

Critical Pitfalls to Avoid

• Never dismiss cardiac causes based on age alone or "atypical" presentation patterns; myocardial infarction can present as isolated epigastric pain 1, 2, 3
• Do not delay imaging in patients with peritoneal signs, as perforated ulcer mortality increases significantly with delayed diagnosis 2, 3
• Never rely on single troponin measurement; serial measurements at least 6 hours apart are required to exclude NSTEMI 2, 3
• Do not assume GERD without excluding life-threatening causes first, even in patients with known reflux disease 2, 3
• Persistent vomiting with epigastric pain excludes functional dyspepsia and mandates investigation for structural disease such as peptic ulcer or acute coronary syndrome 2, 3
• Do not delay endoscopy in patients with alarm features (persistent vomiting, weight loss, anemia, dysphagia), as this leads to poor outcomes 1, 2, 3
• If symptoms persist despite 8 weeks of optimized PPI therapy, refer for upper endoscopy; if endoscopy is normal and symptoms persist, consider esophageal function testing and pH monitoring to exclude esophageal motility disorders 3