What are the differential diagnoses for a patient with epigastric pain, dyspepsia, nausea, and possible gastrointestinal bleeding suggestive of a peptic ulcer?

Differential Diagnosis for Peptic Ulcer

When evaluating a patient with suspected peptic ulcer disease presenting with epigastric pain, dyspepsia, nausea, and possible GI bleeding, the differential diagnosis must prioritize life-threatening conditions first, followed by common gastrointestinal pathology, with systematic exclusion of cardiac, vascular, and other serious organic diseases.

Immediate Life-Threatening Conditions to Exclude First

Cardiac Causes

• Acute coronary syndrome must be ruled out immediately, as myocardial infarction can present atypically with isolated epigastric pain, especially in diabetics, elderly patients, and women, with mortality rates of 10-20% if missed 1, 2
• Obtain an ECG within 10 minutes of presentation and measure serial cardiac troponins at 0 and 6 hours—never rely on a single troponin measurement 1, 2
• Cardiac causes should never be dismissed regardless of how "typical" the GI presentation appears 2

Perforated Peptic Ulcer

• Presents with sudden, severe epigastric pain that becomes generalized, accompanied by fever, abdominal rigidity, and absent bowel sounds 2
• Mortality reaches 30% if treatment is delayed 3, 2
• CT abdomen/pelvis with IV contrast is the gold standard, showing extraluminal gas in 97% of cases, fluid or fat stranding in 89%, ascites in 89%, and focal wall defect in 84% 3, 2, 4
• If CT is unavailable, obtain chest/abdominal X-ray as initial assessment to detect free air 3

Acute Pancreatitis

• Characteristically presents with epigastric pain radiating to the back 2
• Diagnosed by serum amylase ≥4x normal or lipase ≥2x normal with 80-90% sensitivity and specificity 2
• Overall mortality is <10% but reaches 30-40% in necrotizing pancreatitis 2, 4

Vascular Emergencies

• Mesenteric ischemia presents with "pain out of proportion to examination," especially in elderly patients with vascular risk factors 1, 4
• Leaking abdominal aortic aneurysm causes constant epigastric pain radiating inferiorly and is immediately life-threatening 1, 4
• Both conditions require urgent vascular imaging in patients over 50 years with risk factors 1, 4

Common Gastrointestinal Differential Diagnoses

Functional Dyspepsia

• The most common diagnosis in patients undergoing endoscopy for dyspepsia, accounting for >50% of cases 4
• Characterized by bothersome postprandial fullness or early satiation at least 3 days per week for a minimum of 8 weeks 1, 4
• Critical caveat: Persistent vomiting excludes functional dyspepsia and mandates investigation for structural disease 4
• Physical examination tenderness suggests organic pathology rather than purely functional disease 1

Gastroesophageal Reflux Disease (GERD)

• Affects 42% of Americans monthly and 7% daily 2, 4
• Approximately 66% of patients with GERD and heartburn also experience epigastric pain 2
• More than 50% of GERD patients have normal endoscopy (non-erosive reflux disease), so absence of esophagitis does not exclude the diagnosis 4
• Esophagitis manifests as fine nodularity or granularity of mucosa, erosions or ulcers, thickened longitudinal folds, and scarring with strictures 2, 4

Gastritis

• Appears as enlarged areae gastricae, disruption of normal polygonal pattern by multiple uniform nodules, thickened gastric folds, or erosions 2, 4
• May be H. pylori-related or NSAID-induced 4
• Often associated with alcohol use 1

Gastroparesis

• Characterized by postprandial nausea, bloating, and epigastric pain 1
• Overlaps significantly with functional dyspepsia and cannot be fully distinguished based on symptoms alone 1

Gastric Malignancy

• May present with an ulcer associated with nodularity of adjacent mucosa, mass effect, or irregular radiating folds 2, 4
• Now the most common cause of gastric outlet obstruction in adults 2
• Absence of weight loss does not exclude malignancy 1

Irritable Bowel Syndrome (IBS)

• Affects 9-23% of the population and frequently overlaps with functional dyspepsia, with up to 40-50% of patients having both conditions 1, 4
• Characterized by postprandial fecal urgency, bloating, and constipation changes 1

Chronic Pancreatitis

• Suggested by epigastric pain radiating through the midline, aggravated by sitting, with nausea and bloating 1
• Postprandial symptoms occur due to pancreatic enzyme insufficiency 1
• Fecal elastase testing is warranted to evaluate for pancreatic insufficiency 1

Inflammatory Bowel Disease (Pediatric/Adolescent Consideration)

• Pediatric-onset IBD accounts for 10-15% of all IBD cases presenting before age 18 4
• In children with ulcerative colitis, extensive colitis occurs in 42-90% of cases 4
• Endoscopic evaluation with mucosal biopsies remains the gold standard for diagnosis 4

Other Important Differential Diagnoses

Colorectal Malignancy

• Consider in patients with new-onset constipation, right iliac fossa tenderness, and postprandial symptoms 1
• Absence of weight loss does not exclude malignancy 1

Pelvic Floor Dyssynergia

• Characterized by constipation with fecal urgency and suprapubic tenderness 1
• Digital rectal examination can identify increased sphincter tone or pelvic floor dyssynergia 1

Helicobacter pylori Gastritis

• H. pylori infection is the principal cause of peptic ulcers not related to NSAID use, affecting approximately 42% of patients with peptic ulcer disease 4, 5
• Testing and treating H. pylori eliminates peptic ulcer mortality risk and reduces symptoms 1
• Eradication decreases ulcer recurrence rates from 50-60% to 0-2% 5

Pregnancy-Specific Considerations (When Applicable)

• Preeclampsia can present with epigastric or right upper quadrant pain, headaches, visual changes, or swelling 4
• HELLP syndrome should be considered with epigastric pain, nausea, vomiting, and malaise 4
• Acute fatty liver of pregnancy may present with malaise, headache, nausea, vomiting, jaundice, and epigastric pain 4

Critical Diagnostic Algorithm

Initial Assessment

• Check vital signs for hypotension, tachycardia ≥110 bpm, or fever ≥38°C, which predict perforation or sepsis with high specificity 2
• Perform physical examination looking for peritoneal signs, cardiac findings, and reproducible pain with palpation 2
• Assess timing (sudden vs. gradual), severity (1-10 scale), and associated symptoms (hematemesis, heartburn, regurgitation) 2, 4

Laboratory Studies

• Order complete blood count (to detect anemia), C-reactive protein, serum lactate, liver and renal function tests 2, 4
• Measure serum amylase or lipase to exclude pancreatitis 2, 4
• Obtain serum electrolytes and glucose 2, 4
• Measure cardiac troponins at 0 and 6 hours 2

Imaging

• CT abdomen and pelvis with IV contrast is the gold standard when diagnosis is unclear, identifying pancreatitis, perforation, and vascular emergencies 1, 2
• Chest/abdominal X-ray if CT not promptly available 3, 4

Endoscopic Evaluation

• Upper endoscopy is indicated for adults with treatment-resistant dyspepsia, alarm features (persistent vomiting, weight loss, anemia, dysphagia, hematemesis), or age ≥55 years with new-onset symptoms 1, 4
• Endoscopy definitively diagnoses peptic ulcer disease and allows for H. pylori testing via rapid urease test with or without histology 6, 5
• If initial H. pylori test is negative, perform delayed 13C-urea breath test or serology 6

Common Pitfalls to Avoid

• Never dismiss cardiac causes in patients with "atypical" epigastric pain regardless of age or presentation 2
• Do not attribute persistent vomiting to functional dyspepsia—it is a red flag for structural disease 4
• Do not delay endoscopy in patients with alarm features (persistent vomiting, weight loss, anemia, dysphagia, age ≥55 years) 1, 4
• Do not assume functional dyspepsia without excluding IBD in adolescents, given the relatively high prevalence of organic disease 4
• Do not rely on absence of weight loss to exclude malignancy or serious pathology 1