Diagnosis and Differentiation of Upper Gastrointestinal Disorders

Core Diagnostic Framework

The diagnosis begins by asking the patient to identify their single most predominant symptom, which determines the primary diagnostic pathway: if heartburn or acid regurgitation occurs more than once weekly, treat as GERD; if epigastric pain, burning, or discomfort predominates, treat as dyspepsia. 1, 2

Definitions and Diagnostic Criteria

GERD (Gastroesophageal Reflux Disease)

Defined as heartburn (burning sensation starting in epigastrium radiating to chest) or acid regurgitation occurring more than once weekly 1, 2
Diagnosis is primarily clinical in adolescents and adults with typical symptoms 3
More than 50% of GERD patients have normal endoscopy (non-erosive reflux disease), so absence of esophagitis does not exclude GERD 1, 4
Endoscopy is NOT required for diagnosis in uncomplicated cases 3

Dyspepsia (General Term)

Chronic or recurrent pain or discomfort centered in the upper abdomen lasting at least 8 weeks 3, 2
Cardinal symptoms include: epigastric pain, epigastric burning, postprandial fullness, or early satiation 3, 5
Heartburn alone is NOT dyspepsia, though it can coexist 3
Persistent vomiting is atypical and should prompt investigation for other disorders 3, 6

Functional Dyspepsia (Previously "Non-Ulcer Dyspepsia" or NPUD)

Diagnosed when one or more cardinal dyspeptic symptoms are bothersome for >8 weeks AND endoscopy shows no structural disease 3, 5
Accounts for 80% of patients with dyspepsia after endoscopic investigation 3, 1
Two subtypes exist:
- Epigastric Pain Syndrome (EPS): Bothersome epigastric pain/burning ≥1 day per week 5
- Postprandial Distress Syndrome (PDS): Bothersome postprandial fullness/early satiation ≥3 days per week 5
Up to 50% overlap with IBS, but pain in functional dyspepsia is unrelated to defecation 3, 5

Peptic Ulcer Disease (PUD)

Accounts for approximately 10% of upper gastrointestinal symptoms in dyspeptic populations 1, 6
Diagnosed definitively by endoscopy showing ulcer crater in stomach or duodenum 3
H. pylori infection is the principal cause of non-NSAID-related peptic ulcers 6
Symptoms alone cannot reliably distinguish PUD from functional dyspepsia 3

"Hyperacidity"

Not a recognized diagnostic entity in modern gastroenterology guidelines 3
This term is outdated; patients describing "hyperacidity" typically have either GERD, functional dyspepsia, or PUD 7, 8
Gastric acid secretion is NOT elevated in most functional dyspepsia patients 8, 9

Clinical Overlap and Differentiation

Key Distinguishing Features

Feature	GERD	Functional Dyspepsia	PUD
Predominant symptom	Heartburn/regurgitation >1×/week [1,2]	Epigastric pain/discomfort [3,5]	Epigastric pain (indistinguishable clinically) [3]
Symptom location	Burning starts epigastrium, radiates to chest [3]	Upper central abdomen [3,5]	Epigastrium [6]
Relation to meals	May worsen after meals/lying down [3]	May be meal-related or fasting [3]	Variable [6]
Endoscopy findings	Esophagitis in <50% [1,4]	Normal [3,5]	Ulcer crater visible [3]
Response to PPI	80-90% improvement [6]	Variable, modest [5]	80-90% ulcer healing [6]

Critical Clinical Reality

63-66% of patients with heartburn also have coexisting epigastric pain, and approximately one-third of functional dyspepsia patients have coexisting GERD symptoms 1, 5. This massive overlap means:

You cannot rely on symptoms alone to differentiate 3
Ask which symptom is most bothersome and predominant 1, 2
Treat the predominant symptom first 1, 4

Diagnostic Algorithm

Step 1: Screen for Alarm Features (Require Urgent Endoscopy)

Perform urgent 2-week wait endoscopy if: 3, 6

Age ≥55-60 years with new-onset dyspepsia or heartburn 3, 6
Dysphagia (food sticking sensation) 3, 6
Unintentional weight loss 3, 6
Persistent vomiting 3, 6
Evidence of GI bleeding (hematemesis, melena, anemia on CBC) 3, 6
Epigastric mass on examination 3
Family history of gastroesophageal malignancy in patient from high-risk area 3

Common pitfall: Delaying endoscopy in patients ≥55 years with new symptoms—age alone is an alarm feature regardless of other symptoms 3, 6

Step 2: For Patients WITHOUT Alarm Features

If Heartburn/Regurgitation Predominates (>1×/week):

Diagnose as GERD clinically 1, 2
Start empiric PPI therapy (omeprazole 20-40 mg once daily before meals) for 4-8 weeks 6, 2
Endoscopy NOT required for diagnosis 3
If symptoms persist after 8 weeks of twice-daily PPI, then perform endoscopy 3

If Epigastric Pain/Discomfort Predominates:

Test for H. pylori using validated non-invasive test (^13C-urea breath test or stool antigen; NOT serology) 3, 6, 2
If H. pylori positive: Eradicate with standard triple or quadruple therapy 6, 2
If H. pylori negative OR symptoms persist after eradication: Start PPI trial (omeprazole 20-40 mg daily) for 4-8 weeks 6, 2
If symptoms persist beyond 8 weeks despite treatment: Consider endoscopy 3, 2

Note: Test-and-treat for H. pylori is preferred when local prevalence ≥10%; empiric PPI is acceptable in low-prevalence areas 2

Step 3: Endoscopic Findings Determine Final Diagnosis

If endoscopy shows:

Esophagitis: Confirms GERD with erosive disease 3
Ulcer crater: Confirms PUD; biopsy for H. pylori 3, 6
Normal mucosa with dyspeptic symptoms: Diagnose functional dyspepsia 3, 5
Normal mucosa with heartburn: Diagnose non-erosive reflux disease (NERD) 1, 4

Diagnostic Testing: When and What to Order

History and Physical Examination

Essential elements to document: 3

Which symptom is most bothersome and predominant 1
Frequency: How many days per week? 3
Duration: Present for >8 weeks? 3, 5
Timing: Fasting vs. postprandial vs. nocturnal 3
Relationship to defecation (if yes, consider IBS instead) 3, 5
NSAID or aspirin use 3, 6
Previous acute gastroenteritis (10% develop post-infectious functional dyspepsia) 3, 5
Alarm features (see above) 3, 6

Laboratory Tests

Order in patients ≥55 years or with alarm features: 3, 6

Complete blood count (to detect anemia) 3, 6
Consider coeliac serology if IBS-type symptoms overlap 3

H. pylori Testing

Use validated non-invasive tests: 3, 6, 2

^13C-urea breath test (preferred) 6
Stool antigen test 6, 2
Do NOT use serology (cannot distinguish active from past infection) 6

Upper Endoscopy with Biopsy

Indications: 3

Any alarm feature present 3, 6
Age ≥55-60 years with new-onset symptoms 3, 6
Symptoms persisting after 8 weeks of twice-daily PPI therapy 3
Treatment-resistant dyspepsia in patients ≥55 years 3
Obtain ≥5 esophageal biopsies if dysphagia present to exclude eosinophilic esophagitis 3

Common pitfall: Assuming normal endoscopy rules out GERD—it does not, as >50% of GERD is non-erosive 1, 4

Upper GI Series (Barium Study)

NOT recommended for routine diagnosis of GERD or dyspepsia 3

Too brief to rule out pathologic reflux 3
High false-positive rate for reflux 3
Only useful to delineate anatomy (stricture, hiatal hernia, malrotation) 3

Esophageal pH Monitoring or Impedance-pH

Reserved for: 3

Patients with typical GERD symptoms who failed twice-daily PPI AND have normal endoscopy 3
Performed OFF PPI for 7 days 3
Helps distinguish true refractory GERD from functional heartburn 3
Not needed for routine diagnosis 3

Esophageal Manometry