What is the differential diagnosis and treatment approach for functional dyspepsia?

Differential Diagnosis for Functional Dyspepsia

Before diagnosing functional dyspepsia, you must systematically exclude organic causes through targeted investigation based on age, alarm features, and symptom pattern—most patients will ultimately have functional dyspepsia, but missing gastric cancer or peptic ulcer disease has catastrophic consequences for mortality.

Key Organic Causes to Exclude

Malignancy (Highest Mortality Risk)

• Gastric or esophageal cancer: Urgent endoscopy is mandatory for patients ≥55 years with dyspepsia and weight loss, or those >40 years from high gastric cancer risk areas or with family history of gastro-esophageal cancer 1, 2
• Pancreatic cancer: Urgent abdominal CT scanning should be considered in patients ≥60 years with abdominal pain and weight loss 1
• Alarm features mandating urgent endoscopy include dysphagia, weight loss in patients over 55 years, hematemesis, or persistent vomiting 2

Peptic Ulcer Disease and H. pylori-Related Pathology

• Peptic ulcer disease: All patients without alarm features should undergo non-invasive H. pylori testing ("test and treat" strategy), as this will cure most underlying peptic ulcer disease and prevent future gastroduodenal disease 1, 3
• H. pylori infection itself is a pathogenic factor that can cause organic inflammation and ulceration 3, 4

Gastroesophageal Reflux Disease (GORD)

• GORD with or without esophagitis: This represents the most common overlap condition with dyspepsia, as patients with predominant heartburn may present with upper abdominal symptoms 1, 3
• Suspected atypical GORD can be tested with 24-hour esophageal pH monitoring or a high-dose diagnostic course of PPI therapy 1
• However, routine 24-hour pH monitoring should not be undertaken in patients with typical FD symptoms 1

Medication-Induced Dyspepsia

• NSAID-induced gastropathy: Patients taking standard non-steroidal anti-inflammatory drugs regularly should be referred for early upper endoscopy 1
• Drug intolerance to various medications can cause dyspeptic symptoms 3

Biliary and Pancreatic Disorders

• Biliary disorders (cholecystitis, cholelithiasis) and pancreatic disorders should be considered, particularly when pain radiates to the back or right upper quadrant 3
• Abdominal ultrasonography can evaluate these structural causes 3

Metabolic and Systemic Diseases

• Celiac disease: Full blood count should be performed in patients aged ≥55 years with dyspepsia, and coeliac serology in all patients with FD and overlapping IBS-type symptoms 1
• Other systemic diseases and metabolic disorders can present with dyspeptic symptoms 3, 5

Post-Infectious Causes

• Post-infectious dyspepsia: Acute gastroenteritis increases the odds of developing functional dyspepsia almost threefold at 6 months or more after infection 6
• Other infectious organisms beyond H. pylori can trigger dyspeptic symptoms 3

Diagnostic Algorithm Based on Risk Stratification

High-Risk Patients (Urgent Endoscopy Required)

• Age ≥55 years with dyspepsia and weight loss 1, 2
• Age >40 years from high gastric cancer risk area or with family history of gastro-esophageal cancer 1
• Any patient with alarm symptoms (dysphagia, hematemesis, persistent vomiting) regardless of age 2
• Regular NSAID users 1

Intermediate-Risk Patients (Non-Urgent Endoscopy Considered)

• Age ≥55 years with treatment-resistant dyspepsia 1
• Age ≥55 years with raised platelet count or nausea/vomiting 1

Low-Risk Patients (Non-Invasive Testing First)

• Age <55 years without alarm features: Proceed with non-invasive H. pylori testing 1, 2
• If H. pylori positive: Eradication therapy 1
• If H. pylori negative or symptoms persist after eradication: Empirical acid suppression therapy with PPIs 1, 2

Common Pitfalls to Avoid

Do not perform routine gastric emptying testing or 24-hour pH monitoring in patients with typical FD symptoms—these have low diagnostic yield and delay appropriate treatment 1.

Do not assume all dyspepsia is functional in patients ≥55 years—approximately 80% will have functional dyspepsia after investigation, but the 20% with organic disease includes life-threatening conditions like gastric cancer 1, 2, 4.

Do not overlook celiac disease in patients with overlapping IBS symptoms—this represents a treatable organic cause that significantly impacts quality of life 1.

Do not repeat endoscopy unnecessarily in confirmed functional dyspepsia—once organic pathology is excluded and H. pylori status documented, focus shifts to symptom management rather than repeated investigation 1.

After Exclusion of Organic Causes

Once organic causes are excluded through appropriate investigation, functional dyspepsia becomes a positive diagnosis characterized by bothersome epigastric pain or burning, early satiation, and/or postprandial fullness of greater than 8 weeks duration in the absence of structural disease 1. Approximately 80% of patients with dyspepsia will ultimately receive this diagnosis after investigation 1, 2.