What are the differential diagnoses of peptic ulcer disease?

Differential Diagnosis of Peptic Ulcer Disease

When a patient presents with epigastric pain suggestive of peptic ulcer disease, the differential diagnosis must systematically exclude life-threatening conditions first, then distinguish between upper gastrointestinal pathologies that share overlapping symptoms. 1

Immediate Life-Threatening Conditions to Exclude First

• Myocardial infarction can present with epigastric pain as the primary manifestation and must be ruled out with ECG and troponins before attributing symptoms to gastrointestinal causes 2
• Acute aortic syndromes require immediate consideration when epigastric pain is accompanied by pain radiating to the back 1
• Acute pancreatitis presents with severe epigastric pain radiating to the back and requires urgent evaluation 1

Upper Gastrointestinal Differential Diagnoses

Gastroesophageal Reflux Disease (GERD)

• Significant symptom overlap exists, with 63-66% of patients experiencing both epigastric pain and heartburn simultaneously, making differentiation challenging 2
• GERD typically presents with heartburn, regurgitation, and retrosternal discomfort, though patients often struggle to identify their predominant symptom 3, 2
• Distal esophageal wall thickening ≥5 mm on CT has moderate association with reflux esophagitis (sensitivity 56%, specificity 88%) 1

Gastritis

• Gastritis frequently coexists with peptic ulcer disease and shares the primary symptom of epigastric discomfort 4
• CT findings include gastric wall thickening due to submucosal edema, mucosal hyperenhancement, and fat stranding from inflammation 1
• Both conditions are commonly caused by Helicobacter pylori infection (affecting approximately 42% of peptic ulcer patients) and NSAID use (36% of cases) 1, 5

Esophagitis

• Retrosternal pain can occur with esophagitis, which frequently coexists with peptic ulcer disease 4
• Symptoms overlap substantially with GERD and gastritis, requiring endoscopic evaluation for definitive diagnosis 1

Gastric Malignancy

• All gastric ulcers require biopsy and histological examination to exclude adenocarcinoma, as symptomatic response to proton pump inhibitors does not preclude malignancy 2, 6
• Patients older than 55-60 years with new-onset dyspepsia should undergo upper endoscopy to rule out malignancy 7, 8
• Never assume benign disease without tissue diagnosis 2

Inflammatory Bowel Disease (IBD)

• IBD can cause abdominal pain and occult gastrointestinal bleeding, but the predominant epigastric location and retrosternal pain are more consistent with upper GI pathology rather than the colonic/terminal ileal involvement typical of IBD 4
• IBD typically presents with diarrhea rather than primarily vomiting, and in children, granulomas are more frequently identified (67% at initial colonoscopy) 1, 4
• Focal chronic inflammation and architectural abnormalities in biopsies favor Crohn's disease over peptic ulcer disease 1

Functional Disorders

Irritable Bowel Syndrome (IBS)

• IBS does not cause occult blood in stool, fever, or systemic signs, which indicate organic disease requiring investigation 4
• The presence of alarm symptoms (bleeding, weight loss, fever) effectively excludes IBS from consideration 4

Abdominal Migraine

• Does not explain occult blood in stool or fever 4
• Typically presents with periumbilical rather than epigastric pain 4

Critical Complications Requiring Immediate Recognition

Peptic Ulcer Perforation

• Sudden severe epigastric pain with fever and abdominal rigidity suggests perforation, which carries mortality rates up to 30% if treatment is delayed 1, 4, 2
• CT findings include extraintestinal gas, focal wall defect, free fluid, and fat stranding along the gastroduodenal region 3
• Perforation is a surgical emergency requiring immediate surgical consultation 4

Peptic Ulcer Bleeding

• Hemorrhage is the most common complication (73% of complicated cases), with annual incidence of 0.02-0.06% and 30-day mortality of 8.6% 1, 5
• Presents as hematemesis, melena, or occult blood in stool 3, 4
• Occult blood with fever and tachycardia raises concern for active bleeding with potential perforation 4, 2

Gastric Outlet Obstruction

• Rare complication (3% of complicated cases) presenting with persistent vomiting and early satiety 5
• Chronic fibrotic disease causing obstruction has become uncommon with improved medical management 1

Key Diagnostic Pitfalls to Avoid

• Never dismiss cardiac causes in patients presenting with epigastric pain—obtain ECG and troponins first 2
• Symptoms are nonspecific and overlap extensively between GERD, gastritis, esophagitis, and peptic ulcer disease, requiring careful history and often endoscopic evaluation 1
• Two-thirds of peptic ulcer cases are asymptomatic, so absence of classic symptoms does not exclude the diagnosis 9, 5
• The combination of H. pylori infection and NSAID use synergistically increases bleeding risk more than sixfold 8
• If peritoneal signs develop (rigidity, rebound tenderness), immediate surgical consultation is mandatory 4