What are the differential diagnoses for a patient presenting with epigastric pain, hypogastric pain, nausea, vomiting, and anorexia?

Differential Diagnoses for Epigastric Pain with Hypogastric Pain, Nausea, Vomiting, and Anorexia

Immediate Life-Threatening Conditions to Exclude First

The combination of epigastric and hypogastric pain with vomiting mandates immediate exclusion of surgical emergencies and cardiac causes before considering functional or less urgent diagnoses. 1

Cardiovascular Emergencies

• Myocardial infarction must be ruled out immediately with ECG within 10 minutes and serial cardiac troponins at 0 and 6 hours, as epigastric pain can be the primary manifestation especially in women, diabetics, and elderly patients, with mortality rates of 10-20% if missed 1
• Acute aortic dissection and leaking abdominal aortic aneurysm require urgent consideration, particularly in patients over 50 years with vascular risk factors 1

Gastrointestinal Surgical Emergencies

• Perforated peptic ulcer presents with sudden severe epigastric pain that becomes generalized, accompanied by fever, abdominal rigidity, and absent bowel sounds, with mortality reaching 30% if treatment is delayed 1
• Acute pancreatitis characteristically presents with epigastric pain radiating to the back, diagnosed by serum amylase ≥4x normal or lipase ≥2x normal, with overall mortality <10% but reaching 30-40% in necrotizing pancreatitis 1
• Mesenteric ischemia must be excluded, particularly in elderly patients with vascular risk factors and pain out of proportion to examination 2
• Bowel obstruction can present with epigastric and hypogastric pain, vomiting, and anorexia, requiring urgent imaging 3

Common Gastrointestinal Causes

Peptic Ulcer Disease with Gastritis

• Peptic ulcer disease has an incidence of 0.1-0.3% and presents with epigastric pain not relieved by antacids, with complications occurring in 2-10% of cases 1
• The combination of recurrent epigastric pain, vomiting, and anorexia strongly suggests PUD with gastritis, particularly when occult blood is present 4
• Bleeding is the most common complication (73% of complicated cases) and can manifest as hematemesis or melena 4
• Marginal ulcer or gastritis is characterized by pain during meals, acid reflux, and nausea, confirmed via gastroscopy 5

Functional Dyspepsia

• Functional dyspepsia is diagnosed when one or more cardinal symptoms (postprandial fullness, early satiation, epigastric pain, epigastric burning) are present for more than 8 weeks without structural abnormality 5
• However, persistent vomiting is atypical for functional dyspepsia and suggests another disorder, requiring investigation for structural disease 2
• The Rome IV criteria state that vomiting should prompt consideration of another disorder and carries high risk of missing serious pathology 2

Gastroesophageal Reflux Disease

• GERD affects 42% of Americans monthly and 7% daily, presenting with epigastric pain often accompanied by heartburn and regurgitation 1
• Approximately 66% of patients with GERD and heartburn also experience epigastric pain 1
• Esophagitis manifests as fine nodularity or granularity of mucosa, erosions or ulcers, and thickened longitudinal folds 1

Post-Surgical Complications (if applicable)

• Internal herniation results in pain, sometimes colic pain, sensation of fullness quickly after meals, ileus and vomiting, confirmed via CT or diagnostic laparoscopy 5
• Stenosis or anastomoses present with symptoms similar to marginal ulcer accompanied by dysphagia, confirmed via gastroscopy or barium swallow 5
• Dumping syndrome should be considered in patients with history of upper GI or bariatric surgery, presenting with cramp-like contractions, bloating, and diarrhea 5

Hepatobiliary and Pancreatic Causes

Gallstone Disease

• Symptomatic gallstone disease is characterized by colicky pain attacks with urge to move, nausea, and often vomiting, with pain generally lasting at least 1 hour 5
• Diagnosis confirmed with ultrasound showing gallbladder stones and blood testing confirming liver function abnormalities 5

Exocrine Pancreatic Insufficiency

• EPI presents with diarrhea, abdominal distention, abdominal pain, increased flatulence, and unexplained weight loss 5
• Common overlapping conditions include celiac disease, small intestinal bacterial overgrowth, inflammatory bowel disease, and long-standing diabetes 5

Less Common but Important Differentials

Superior Mesenteric Artery Syndrome

• Wilkie's syndrome presents with epigastric pain, nausea, early satiety, and significant weight loss due to duodenal compression between the SMA and aorta 6
• This diagnosis should be suspected in patients with persistent nausea, abdominal pain, and significant weight loss 6

Inflammatory Bowel Disease

• IBD can cause abdominal pain and occult blood, but typically presents with diarrhea rather than primarily vomiting 4
• Focal chronic inflammation and architectural abnormalities in biopsies favor Crohn's disease 4

Gastric Cancer

• Gastric cancer may present with an ulcer associated with nodularity of adjacent mucosa, mass effect, or irregular radiating folds 1
• Weight loss is an alarm feature that mandates urgent endoscopy 2

Critical Diagnostic Approach

Immediate Assessment

• Check vital signs for hypotension, tachycardia ≥110 bpm, or fever ≥38°C, which predict anastomotic leak, perforation, or sepsis with high specificity 1
• Perform physical examination looking for peritoneal signs (rigidity, rebound tenderness, absent bowel sounds), epigastric tenderness, and hypogastric tenderness 1

Essential Laboratory Testing

• Order immediately: complete blood count, C-reactive protein, serum lactate, liver and renal function tests, serum amylase or lipase, serum electrolytes and glucose 2, 1
• Cardiac troponins at 0 and 6 hours (do not rely on single measurement) 1
• Pregnancy test in patients with female reproductive organs 7
• Fecal elastase if EPI is suspected, with levels <100 mg/g providing good evidence of EPI 5

Imaging Studies

• CT abdomen/pelvis with IV contrast is the gold standard when diagnosis is unclear, identifying pancreatitis, perforation, and vascular emergencies 1
• Ultrasonography is the study of choice for right upper quadrant pain and suspected gallstone disease 7
• Upper endoscopy is indicated for patients with alarm features (persistent vomiting, weight loss, anemia, dysphagia) and allows direct visualization of ulcers, histopathological confirmation, and H. pylori testing 4

Common Pitfalls to Avoid

• Never dismiss cardiac causes in patients with "atypical" epigastric pain regardless of age or presentation 1
• Delaying endoscopy in patients with alarm features such as persistent vomiting, weight loss, anemia, or dysphagia can lead to poor outcomes 2
• Missing perforation by not obtaining imaging when peritoneal signs are present, as mortality reaches 30% with delayed treatment 1
• Attributing persistent vomiting to functional dyspepsia carries high risk of missing serious pathology 2