What are the differential diagnoses for a patient presenting with dyspepsia and heartburn?

Differential Diagnosis of Dyspepsia and Heartburn

When a patient presents with both dyspepsia and heartburn, gastroesophageal reflux disease (GERD) should be your primary diagnosis until proven otherwise, as heartburn occurring more than once weekly defines GERD by American Gastroenterological Association criteria. 1

Primary Diagnostic Framework

The key to approaching this presentation is determining the predominant symptom, as this guides both diagnosis and treatment:

If Heartburn is Predominant (>1x/week)

• GERD is the diagnosis until proven otherwise 1, 2
• Affects approximately 7% of Americans daily and 42% at least once monthly 3
• More than 50% of GERD patients will have normal endoscopy (non-erosive reflux disease), so absence of esophagitis does not exclude GERD 1

If Epigastric Pain/Discomfort is Predominant

• Consider dyspepsia as the primary diagnosis 2
• Dyspepsia is defined as chronic or recurrent pain or discomfort centered in the upper abdomen 1

Complete Differential Diagnosis

Gastrointestinal Causes (Most Common)

Functional Dyspepsia

• Accounts for the majority (>50%) of patients undergoing endoscopy for dyspepsia 1
• Diagnosed after excluding structural disease on endoscopy 4
• Most common diagnosis in primary care (80% of investigated dyspepsia) 2

Peptic Ulcer Disease

• Responsible for approximately 10% of upper gastrointestinal symptoms 1, 3
• H. pylori is the main cause of ulcers not associated with NSAIDs 1
• Can present with epigastric pain not relieved by antacids 3

Gastroesophageal Reflux Disease (GERD)

• Presents with heartburn and regurgitation as cardinal symptoms 3
• Esophagitis may show erosions, ulcers, thickened folds, or strictures 3
• 63-66% of patients with heartburn also have coexisting epigastric pain 2

Gastritis

• Appears as enlarged areae gastricae, nodular pattern, thickened folds, or erosions 3
• Can be H. pylori-related or NSAID-induced 1

Hiatal Hernia

• Detectable on imaging studies 3
• May contribute to reflux symptoms 3

Gastric Cancer (Rare but Critical)

• May present with ulcer associated with nodular mucosa 3
• More common in patients ≥55 years or with family history 5

Life-Threatening Causes (Must Exclude Urgently)

Acute Coronary Syndrome

• Myocardial infarction can present with isolated epigastric pain 3, 5
• Especially atypical in women, diabetics, and elderly patients 3
• Mortality rate of 10-20% if missed 3, 5
• Obtain ECG within 10 minutes and serial troponins at 0 and 6 hours 5

Acute Pancreatitis

• Check serum amylase (≥4x normal) or lipase (≥2x normal) 3
• Sensitivity and specificity of 80-90% 3
• Overall mortality <10% but reaches 30-40% in necrotizing pancreatitis 3

Perforated Viscus

• Presents with sudden, severe epigastric pain 3
• CT shows extraluminal gas (97%), fluid/fat stranding (89%), ascites (89%) 3
• Mortality rate up to 30% 3

Mesenteric Ischemia

• Consider in elderly patients with vascular risk factors 3
• Pain out of proportion to examination 3

Acute Aortic Syndrome

• Sudden, severe epigastric pain 3
• Consider in patients >50 years with vascular risk factors 3

Other Important Causes

Medication-Related

• NSAID-induced gastropathy or ulceration 1
• Consider medication history in all patients 4

Biliary/Pancreatic Disorders

• Check liver function tests and consider ultrasound 3, 5
• Serum amylase/lipase to exclude pancreatitis 3

Critical Clinical Pitfalls to Avoid

Symptom Overlap is the Rule, Not the Exception

• 63-66% of patients with heartburn also have epigastric pain 2
• 19% of patients cannot identify their predominant symptom 2
• Always ask patients to identify their single most bothersome symptom 2

Don't Assume Heartburn Always Means GERD

• Heartburn can coexist with dyspepsia 2
• More than 50% of GERD patients have normal endoscopy 1, 2

Never Miss Cardiac Causes

• Always obtain ECG to exclude myocardial ischemia, especially in high-risk patients 3, 5
• Atypical presentations are common in women, diabetics, and elderly 3

Recognize Alarm Features Requiring Urgent Endoscopy

• Age ≥55 years with new-onset symptoms 1, 5, 6
• Unexplained weight loss 3, 5
• Anemia on complete blood count 3, 5
• Dysphagia or food sticking 3, 5
• Persistent vomiting 3
• Hematemesis 3, 5
• Epigastric tenderness on examination 3

Check Vital Signs Immediately

• Tachycardia ≥110 bpm, fever ≥38°C, or hypotension predict perforation or sepsis with high specificity 3, 5