What are the differential diagnoses for a patient presenting with symptoms suggestive of H. Pylori (Helicobacter Pylori) infection?

Differential Diagnoses for H. Pylori-Like Symptoms

The most important differential diagnoses to consider are peptic ulcer disease (from NSAIDs or other causes), gastroesophageal reflux disease (GERD), functional dyspepsia, gastric cancer (especially in patients >45 years or with alarm symptoms), and irritable bowel syndrome. 1, 2

Key Clinical Distinctions

Age-Based Risk Stratification

Patients over 45 years with new or changed dyspeptic symptoms require endoscopy to exclude gastric cancer, regardless of suspected H. pylori status. 1, 2 The risk of missing gastric malignancy in this population is unacceptably high with non-invasive testing alone. 1

For patients under 45 years without alarm symptoms, the differential is broader and less immediately life-threatening. 1, 2

Alarm Symptoms Requiring Immediate Specialist Referral

The following symptoms mandate urgent endoscopy to exclude serious pathology: 1, 2

• Anemia (suggests chronic bleeding from ulcer or malignancy)
• Unintentional weight loss (concerning for malignancy)
• Progressive dysphagia (esophageal or gastric outlet obstruction)
• Palpable abdominal mass (advanced malignancy)
• Malabsorption symptoms (celiac disease, chronic pancreatitis)

Primary Differential Diagnoses

GERD/Reflux Disease: Presents with heartburn and regurgitation, typically responds to lifestyle modifications and acid suppression. 1 Unlike H. pylori gastritis, symptoms often worsen at night or after large meals. 1

NSAID-Induced Peptic Ulcer Disease: Critical to obtain detailed medication history including over-the-counter NSAIDs, aspirin, and anticoagulants. 1, 2 NSAID use is responsible for the majority of H. pylori-negative peptic ulcers. 3

Functional Dyspepsia/Irritable Bowel Syndrome: Patients with typical IBS symptoms (altered bowel habits, bloating, symptom relief with defecation) rather than true dyspepsia should not undergo endoscopy. 1 These patients have chronic functional disorders without structural pathology. 1

Gastric Cancer: The most critical diagnosis not to miss. Risk factors include: 1

• Age >45 years with new symptoms
• First-degree relatives with gastric cancer (2-3x increased risk)
• Corpus-predominant gastritis or multifocal atrophy
• Previous gastric surgery or neoplasia
• Heavy smoking or occupational dust exposure

Other Gastritis Causes: 1

• Crohn's disease (focal or granulomatous gastritis)
• Celiac disease (lymphocytic gastritis)
• Autoimmune gastritis/pernicious anemia (can cause false-positive urea breath tests due to urease-producing bacteria in achlorhydric stomach) 1

Diagnostic Approach Algorithm

Step 1: Assess for Alarm Symptoms

If present → immediate endoscopy with biopsy 1, 2

Step 2: Age Stratification

• Age ≥45 years with persistent symptoms → endoscopy 1, 2
• Age <45 years without alarm symptoms → non-invasive H. pylori testing 1, 2

Step 3: Medication History

Document all NSAID, aspirin, anticoagulant, and antibiotic use. 1, 3 Recent antibiotic, bismuth, or PPI use within 2 weeks can cause false-negative H. pylori tests. 1, 2

Step 4: Symptom Pattern Recognition

• Heartburn predominant → trial of PPI for GERD 1
• IBS pattern (bloating, altered bowel habits) → avoid endoscopy 1
• True dyspepsia (epigastric pain, early satiety) → H. pylori testing 2

Critical Pitfalls to Avoid

Do not rely on H. pylori testing alone in patients >45 years. Even if H. pylori positive, endoscopy is required to exclude concurrent gastric cancer. 1, 2

Do not test for H. pylori while patient is on PPIs, antibiotics, or bismuth. These medications reduce bacterial load and cause false-negative results. 1 Stop these medications for at least 2 weeks before testing. 1, 2

Do not assume negative H. pylori test excludes all pathology. NSAID ulcers, gastric cancer, and other conditions occur independently of H. pylori. 1, 3

Do not perform endoscopy for typical IBS symptoms. This represents inappropriate use of resources and exposes patients to unnecessary risk. 1

When Diagnosis Remains Unclear

If H. pylori testing is negative but symptoms persist despite empiric treatment, consider: 1

• Endoscopy with comprehensive biopsy to assess for atrophic gastritis, intestinal metaplasia, or other histologic patterns
• Culture for antibiotic resistance if previous H. pylori treatment failed 1
• Evaluation for non-GI causes (cardiac disease, biliary disease, medication side effects)