What are the differential diagnoses and recommended initial evaluation for epigastric pain?

Differential Diagnosis and Initial Evaluation of Epigastric Pain

Epigastric pain requires immediate exclusion of life-threatening cardiac and vascular causes before considering gastrointestinal pathology, as myocardial infarction presents atypically with isolated epigastric pain in 10–20% of patients and carries 10–20% mortality if missed. 1, 2, 3

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Life-Threatening Causes (Rule Out First)

Cardiovascular Emergencies

• Obtain a 12-lead ECG within 10 minutes of presentation for any patient with epigastric pain, especially women, diabetics, and elderly patients who frequently present without classic chest pain 1, 2, 3
• Measure serial cardiac troponins at 0 hours and 6 hours—a single troponin measurement is insufficient to exclude NSTEMI 1, 2, 3
• Acute aortic dissection causes sudden, severe epigastric pain radiating to the back or shoulders and requires emergent CT angiography for diagnosis 1, 2, 3
• Concurrent epigastric pain and dyspnea doubles mortality risk compared with typical angina and raises sudden cardiac death risk four-fold 1

Gastrointestinal Catastrophes

• Perforated peptic ulcer presents with sudden, severe epigastric pain that becomes generalized, accompanied by fever, abdominal rigidity, and absent bowel sounds; delayed treatment carries 30% mortality 1, 2, 3
• Contrast-enhanced CT demonstrates extraluminal gas in 97% of perforations, fluid/fat stranding in 89%, ascites in 89%, and focal wall defect in 84% 1, 2, 3
• Acute pancreatitis characteristically presents with epigastric pain radiating to the back; diagnose with serum amylase ≥4× normal or lipase ≥2× normal (80–90% sensitivity and specificity) 1, 2
• Mesenteric ischemia causes severe epigastric pain out of proportion to examination findings, particularly in elderly patients with vascular risk factors; requires CT angiography 1, 2

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Common Gastrointestinal Causes

Gastroesophageal Reflux Disease (GERD)

• GERD affects 42% of Americans monthly and 7% daily, presenting with heartburn, regurgitation, and epigastric pain 1, 2, 3
• Significant overlap exists: 63–66% of patients with heartburn also have coexisting epigastric pain 4
• More than 50% of GERD patients have normal endoscopy (non-erosive reflux disease), so absence of esophagitis does not exclude GERD 1
• Distal esophageal wall thickening ≥5 mm on CT has 56% sensitivity and 88% specificity for reflux esophagitis 2, 3

Peptic Ulcer Disease (PUD)

• PUD has an incidence of 0.1–0.3%, with complications (bleeding, obstruction, perforation) occurring in 2–10% of cases 1, 2, 3
• Bleeding is the most common complication, presenting as hematemesis 1, 2
• CT findings include gastric/duodenal wall thickening, mucosal hyperenhancement, fat stranding, and focal outpouching 2, 3
• H. pylori infection is the principal cause of peptic ulcers not related to NSAID use 1

Gastritis

• Gastritis appears on imaging as enlarged areae gastricae, disrupted polygonal pattern, thickened gastric folds, or erosions 1, 2
• May be H. pylori-related or NSAID-induced; both mechanisms require evaluation 1

Functional Dyspepsia

• Functional dyspepsia accounts for >50% of patients undergoing endoscopy for dyspepsia after organic causes are excluded 1
• Defined by chronic or recurrent upper abdominal pain/discomfort lasting ≥8 weeks with no structural disease on endoscopy 1
• Persistent vomiting is a red-flag that excludes functional dyspepsia and mandates investigation for structural disease 1, 2, 3

Gastric Cancer

• Gastric cancer may present with ulcer associated with nodularity of adjacent mucosa, mass effect, or irregular folds 1, 2
• Now the most common cause of gastric outlet obstruction in adults with 5-year survival of ~32% 1, 2

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Initial Diagnostic Evaluation

Immediate Assessment

• Check vital signs for tachycardia ≥110 bpm, fever ≥38°C, or hypotension—these predict perforation, anastomotic leak, or sepsis with high specificity 1, 2
• Examine for peritoneal signs (rigidity, rebound tenderness, absent bowel sounds) indicating perforation 1, 2
• Epigastric tenderness on examination suggests organic pathology rather than functional disease and warrants further investigation 1, 3

Laboratory Testing

• Complete blood count to detect anemia—an alarm feature mandating urgent endoscopy 1, 3
• Serum amylase or lipase to exclude acute pancreatitis 1, 2
• Serial cardiac troponins at 0 and 6 hours (never rely on single measurement) 1, 2, 3
• C-reactive protein, serum lactate levels, liver and renal function tests 1, 2

Imaging Strategy

• Contrast-enhanced CT of abdomen and pelvis is the gold standard when diagnosis is unclear, identifying pancreatitis, perforation, and vascular emergencies 1, 2, 3
• 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, 3
• Bedside ultrasound is rapid, noninvasive, and can identify biliary, pancreatic, and hepatic pathology in the emergency setting 5

Endoscopic Evaluation

• Upper endoscopy provides definitive diagnosis for PUD, gastritis, and esophagitis when patient is stable 1, 2, 3
• Urgent endoscopy (2-week wait) is mandatory for alarm features: age ≥55 years with new-onset symptoms, unintentional weight loss, anemia, dysphagia, persistent vomiting, hematemesis, or palpable epigastric mass 1, 3

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Alarm Features Requiring Urgent Investigation

Alarm Feature	Action Required	Evidence
Age ≥55 years with new-onset dyspepsia	Urgent endoscopy (2-week wait)	[1,3]
Unintentional weight loss	Urgent endoscopy (2-week wait)	[1,3]
Anemia on CBC	Urgent endoscopy (2-week wait)	[1,3]
Dysphagia	Urgent endoscopy (2-week wait)	[1,3]
Persistent vomiting	Urgent endoscopy (2-week wait)	[1,3]
Hematemesis or melena	Urgent endoscopy (2-week wait)	[1,3]
Palpable epigastric mass	Urgent endoscopy (2-week wait)	[1,3]
Epigastric tenderness on exam	Non-urgent endoscopy within 4–8 weeks	[1,3]

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H. pylori Testing Strategy

• Perform non-invasive testing using ^13C-urea breath test or stool antigen assay for patients with predominant epigastric pain; serology is not recommended 1, 3
• In patients with alarm features, endoscopic biopsy is preferred because it simultaneously provides histopathology and H. pylori testing 3
• Test-and-treat approach is appropriate for uninvestigated dyspepsia in populations where H. pylori prevalence is ≥10–20% 1

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Empiric Management While Awaiting Diagnosis

• Start high-dose PPI therapy immediately (omeprazole 20–40 mg once daily before meals) while diagnostic workup is pending 1, 2, 3
• Full-dose PPI achieves 80–90% healing of duodenal ulcers and 70–80% healing of gastric ulcers within 4 weeks 1, 2, 3
• For nausea: ondansetron 8 mg sublingual 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 1
• Maintain NPO status until surgical emergency is excluded 1, 2
• Avoid NSAIDs as they worsen PUD and increase bleeding risk 1, 2

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Critical Pitfalls to Avoid

• Never dismiss cardiac causes based on age or "atypical" presentation—myocardial infarction may present only as epigastric pain 1, 2, 3
• Do not delay imaging in patients with peritoneal signs, as perforated ulcer mortality increases significantly with delayed diagnosis 1, 2, 3
• Never rely on single troponin measurement—serial measurements at least 6 hours apart are required to exclude NSTEMI 1, 2, 3
• Do not assume GERD without excluding life-threatening causes first, even in patients with known reflux disease 1, 2
• Delaying endoscopy in patients ≥55 years with new-onset symptoms is a frequent error—age alone is an alarm feature 1, 3
• Attributing persistent vomiting to functional dyspepsia ignores its status as a red-flag for organic disease 1, 2, 3
• Patients with heartburn and epigastric pain find it difficult to describe their predominant symptom—use word descriptions (burning feeling starting in epigastrium and rising toward neck) to help differentiate 4