What are the differential diagnoses for a patient presenting with eructation, fullness, and nausea?

Differential Diagnosis for Burping, Fullness, and Nausea

The most likely diagnosis in a patient presenting with burping (eructation), postprandial fullness, and nausea is functional dyspepsia, which accounts for approximately 80% of patients with these upper gastrointestinal symptoms after investigation, though gastroesophageal reflux disease (GERD), peptic ulcer disease, and gastroparesis must be systematically excluded. 1

Primary Differential Diagnoses

Functional Dyspepsia (Most Common)

• Functional dyspepsia is the underlying cause in most patients with these symptoms, affecting up to 16% of the general population and representing approximately 80% of cases after endoscopic evaluation. 1, 2
• The Rome IV criteria define functional dyspepsia as one or more of: bothersome epigastric pain, epigastric burning, postprandial fullness, or early satiation, with no structural disease on endoscopy. 1
• Two subtypes exist: postprandial distress syndrome (PDS) characterized by meal-related fullness and early satiation, and epigastric pain syndrome (EPS) with epigastric pain or burning. 1
• Supportive symptoms include postprandial bloating, excessive belching, and nausea—all matching your patient's presentation. 1

Gastroesophageal Reflux Disease (GERD)

• GERD overlaps considerably with functional dyspepsia, with more than 50% of GERD patients having no esophagitis on endoscopy, making it clinically indistinguishable from functional dyspepsia initially. 1
• Patients with predominant heartburn or acid regurgitation occurring more than once weekly should be considered to have GERD until proven otherwise. 1
• There is significant symptom overlap between GERD and dyspepsia, and it is often difficult to distinguish between the two in uninvestigated patients. 1, 3

Peptic Ulcer Disease

• Peptic ulcer disease accounts for approximately 10% of upper gastrointestinal symptoms in patients presenting with dyspepsia. 1
• Risk factors include Helicobacter pylori infection (the main cause of non-NSAID peptic ulcers) and NSAID use. 1
• Upper endoscopy is required to definitively diagnose or exclude peptic ulcer disease. 1, 4

Gastroparesis

• Gastroparesis characteristically presents with nausea, vomiting, postprandial fullness, early satiation, bloating, and epigastric pain—symptoms that overlap significantly with functional dyspepsia. 5, 6
• Gastroparesis and functional dyspepsia are indistinguishable based on symptoms alone and may represent the same spectrum of gastric neuromuscular dysfunction. 6
• Delayed gastric emptying occurs in 25-40% of functional dyspepsia patients. 6
• Common etiologies include diabetes (25% of cases), post-surgical causes, medications (opioids, GLP-1 agonists), and idiopathic (largest category). 7

Other Organic Causes to Consider

• Gastric or esophageal malignancy (particularly in patients ≥55 years with alarm features). 1
• Pancreatic or biliary disorders. 4
• Medication-induced dyspepsia (NSAIDs, opioids, anticholinergics). 1, 6
• Metabolic causes including diabetic gastropathy and hyperglycemia. 6, 7

Critical Alarm Features Requiring Urgent Investigation

Age ≥55 years with any of the following mandates endoscopy: 1

• Dyspepsia with weight loss (urgent 2-week wait endoscopy)
• Treatment-resistant dyspepsia (non-urgent endoscopy)
• Dyspepsia with nausea/vomiting or raised platelet count (non-urgent endoscopy)
• Dysphagia at any age (urgent endoscopy)
• Haematemesis (non-urgent endoscopy)
• Upper abdominal mass (2-week outpatient referral)

Diagnostic Approach Algorithm

Step 1: Initial Clinical Assessment

• Obtain detailed symptom history focusing on timing relative to meals, character of symptoms, duration (symptoms >6 months favor functional dyspepsia), and presence of alarm features. 1
• Assess for risk factors: female sex, smoking, NSAID use, H. pylori infection, psychological comorbidity, recent gastroenteritis, diabetes, prior gastric surgery. 1, 2
• Evaluate medication history, particularly opioids, NSAIDs, and anticholinergics. 1, 6

Step 2: Age and Alarm Feature Stratification

• Patients <55 years without alarm features: Proceed with H. pylori test-and-treat strategy followed by empirical PPI therapy if symptoms persist. 1
• Patients ≥55 years OR any age with alarm features: Perform upper endoscopy to exclude structural disease before diagnosing functional dyspepsia. 1

Step 3: H. pylori Testing (in patients <55 without alarm features)

• Use 13C-urea breath test or stool antigen test (optimal methods). 1
• If positive, provide eradication therapy—this is the only treatment known to change the natural history of functional dyspepsia. 1, 8
• If negative or symptoms persist after eradication, prescribe empirical PPI trial for 4-8 weeks. 1

Step 4: Consider Gastroparesis Testing (if symptoms persist)

• Persistent vomiting warrants consideration of gastroparesis regardless of age, as Rome IV criteria state vomiting suggests another disorder beyond functional dyspepsia. 1, 6, 7
• Perform 4-hour gastric emptying scintigraphy using standardized low-fat radiolabeled solid meal (gold standard test). 5, 6
• Normal gastric retention at 4 hours is <10%; gastroparesis is confirmed when retention is >10%. 5, 6
• Medications affecting gastric emptying must be withdrawn 48-72 hours before testing, and blood glucose should be controlled during testing in diabetic patients. 5, 6

Step 5: Exclude Cardiac Causes in High-Risk Patients

• In patients with diabetes or vascular risk factors presenting with epigastric pain and nausea, obtain ECG within 10 minutes and serial cardiac troponins at 0 and 6 hours to exclude atypical myocardial infarction. 7

Common Diagnostic Pitfalls to Avoid

• Do not diagnose functional dyspepsia without endoscopy in patients ≥55 years or those with alarm features—structural disease must be excluded. 1
• Do not attribute persistent or severe vomiting to functional dyspepsia—Rome IV criteria state this warrants investigation for another disorder. 1, 7
• Do not rely on symptoms alone to distinguish between functional dyspepsia and gastroparesis—they are clinically indistinguishable and require gastric emptying testing for differentiation. 6
• Do not dismiss cardiac causes in patients with "atypical" epigastric presentations—always obtain ECG and troponins in high-risk patients. 7
• Do not perform gastric emptying studies shorter than 2 hours—they miss approximately 25% of gastroparesis cases; 4-hour testing is superior. 5, 6
• Do not overlook medication history—opioids, NSAIDs, and anticholinergics commonly cause or worsen these symptoms. 1, 6

Initial Management Pending Workup

• Start empirical high-dose PPI therapy (omeprazole 20-40 mg once daily before meals) immediately for suspected acid-related pathology while awaiting investigation. 7
• Provide dietary counseling: smaller, more frequent meals with lower fat and fiber content. 5
• Ensure adequate hydration (≥1.5 L fluids/day). 5, 6
• Address modifiable risk factors: smoking cessation, NSAID discontinuation if possible, stress reduction. 1, 2