Dyspepsia is a common condition, defined as predominantly epigastric pain lasting at least one month, and is often attributed to conditions affecting the stomach. Heartburn (or pyrosis) is used to describe predominantly esophageal symptoms. Although heartburn and dyspepsia have distinct definitions, the clinical features overlap and may be indistinguishable. Common causes of dyspepsia include Helicobacter pylori infection, gastritis, esophagitis, gastroesophageal reflux (GERD), and peptic ulcer disease (PUD). A thorough medical history, physical examination, screening for risk factors for common etiologies, and assessment of is imperative to guide initial management. Patients ≥ 60 years of age with/without red flag features should undergo an EGD to rule out neoplasia before initiating empirical pharmacotherapy. All patients with typical dyspepsia should be tested for H. pylori infection and, if detected, eradication therapy should be initiated. Patients < 60 years of age with typical heartburn and no major red flag features may be initiated on empirical therapy with , such as proton pump inhibitors (PPIs). Inadequate response to empirical therapy warrants further diagnostics and management. Patients with atypical features should be assessed for other possible etiologies of dyspepsia, such as symptomatic cholelithiasis, chronic pancreatitis, and stable angina. Patients in whom no organic cause can be identified likely have functional dyspepsia (accounts for ∼ 70% of all cases of dyspepsia), the likelihood of which should be assessed based on the .
- Dyspepsia: epigastric pain or burning that lasts for ≥ 1 month 
- Heartburn (pyrosis): burning retrosternal discomfort that often develops after eating and worsens when bending or lying down. Along with regurgitation, it is a classical symptom of gastroesophageal reflux disease (GERD). 
Dyspepsia can be associated with a variety of symptoms, e.g., heartburn, nausea, regurgitation, bloating, belching. Dyspepsia and heartburn may be clinically indistinguishable because of the significant overlap in symptoms.  
Red flag features of dyspepsia
- Family history of gastrointestinal cancer
- Dysphagia, odynophagia
- Early satiety
- Persistent vomiting
- Noncardiac chest pain (specific for patients presenting with heartburn)
- Suspicion of gastrointestinal bleeding (e.g., unexplained iron deficiency anemia, melena)
Patients ≥ 60 years of age 
The following is applicable to patients ≥ 60 years of age with or without red flag features for dyspepsia.
- Refer for EGD to exclude neoplasia.
- Test for the presence of H. pylori during the endoscopy using biopsies and/or a rapid urease test.
- If a clear etiology is identified using EGD (e.g., visualization of peptic ulcer, gastritis), manage accordingly.
- If the etiology remains unclear after EGD, consider further testing based on clinical suspicion.
Patients < 60 years of age 
- Red flags of dyspepsia present: Consider EGD on a case-by-case basis.
- Red flags of dyspepsia absent
Patients with typical features of GERD and no features of concomitant or past PUD do not require routine testing for H. pylori infection. If H. pylori infection is detected in a patient with GERD, H. pylori eradication therapy should be initiated. 
- Patients ≥ 60 years of age with dyspepsia with/without red flags for dyspepsia
- Select patients < 60 years of age with , assessed on a case-by-case basis 
- Inadequate response to empirical pharmacotherapy
- Findings: EGD (with or without biopsies) can help to identify the cause of dyspepsia; examples include
Helicobacter pylori diagnostics
- Absolute indications
- Relative indications
PPIs should be discontinued at least 2 weeks prior to most H. pylori testing modalities to minimize rates of false-negative results. However, some testing modalities, e.g., histology, are not affected by recent PPI treatment. 
Noninvasive methods 
Noninvasive methods to detect H. pylori infection are preferred for the initial diagnostics in patients < 60 years of age with typical dyspepsia symptoms who are low risk for malignancy as the underlying etiology. 
Urea breath test
- Detects a labeled carbon isotope in a breath sample
- Can be used for initial diagnosis or confirmation of eradication
- Sensitivity increases if PPIs have been discontinued for at least 2 weeks prior to testing.
- H. pylori stool antigen test: Can be used for initial diagnosis or confirmation of eradication
- Serum IgG antibodies against H. pylori
Invasive methods that require biopsies
- Rapid urease test
- Histology (gold standard)
- Culture and antibiogram
PCR of biopsy samples
- A highly sensitive and specific test that can provide rapid results and information regarding antibiotic resistance (e.g., identify specific mutations)
- Its use is limited because of accessibility and cost.
- Indications: inconclusive or negative EGD, negative H. pylori test, and/or inadequate response to empirical therapy
- Assess the pretest probability (PTP) of and workup accordingly.
- Examples include:
Differential diagnoses of dyspepsia 
|Characteristic clinical features||Possible etiology|
|Esophageal disorders|| |
|Gastric and duodenal disorders|
|Pancreatic disorders|| |
|Functional disorders|| |
The differential diagnoses listed here are not exhaustive.
- Typical heartburn (GERD) 
- Typical dyspepsia and negative test for H. pylori infection (PUD, gastritis) 
Positive test for H. pylori infection
- H. pylori eradication therapy
- Confirm eradication 4–6 weeks after completion of therapy.
- See relevant articles for details on the management of conditions diagnosed on EGD and further diagnostics.
- Consider antacids for rapid symptomatic relief as needed.
- Implement complementary nonpharmacological measures and lifestyle changes.
|Antacids and acid suppression medications |
|Drug class||Examples||Important considerations|
|Acid suppression medications||PPIs (most effective)|
|H2 antagonists (mostly for maintenance or in combination with PPIs, if needed)|
| Antacids |
(neutralize acid; mainly used alongside acid suppression for rapid symptom relief)
Nonpharmacological recommendations 
- Reduce portion size.
- Avoid eating at least 3 hours before laying down (e.g., before going to sleep). 
- Avoid foods and beverages that appear to trigger symptoms. 
- Patients with obesity should be encouraged to lose weight and should also receive advice on the best approach. 
- Elevate the head-end of the bed (10–20 cm) for patients who experience symptoms while sleeping. 
- Reduce or avoid triggers
Helicobacter pylori eradication therapy
First-line treatment options 
H. pylori eradication therapy typically comprises of PPIs twice daily PLUS two antibiotics with or without bismuth for 10–14 days. Local resistance patterns and adherence to treatment are the main determinants of the success of eradication therapy. 
|First-line options for H.pylori eradication therapy |
| Clarithromycin triple therapy |
Preferred in areas with low levels (< 15%) of clarithromycin resistance 
|Clarithromycin-based concomitant therapy |
| Bismuth quadruple therapy |
Preferred in areas with high levels (≥ 15%) of clarithromycin resistance. 
Bismuth binds to the affected mucosa, providing physical protection from acids, and stimulates gastric HCO3- secretion, which helps to restore the mucosal pH gradient and is hence used to treat peptic ulcers and H.pylori infection (as a part of Bismuth quadruple therapy). Bismuth subsalicylate is also an antidiarrheal agent and is used to treat traveler's diarrhea (caused by enterotoxigenic Escherichia coli).
Second-line treatment options
- Choose different antibiotics to those used as first-line therapy.
- Bismuth quadruple therapy: if first-line clarithromycin triple therapy was unsuccessful
- Levofloxacin-containing therapy: e.g., levofloxacin triple therapy
Follow-up: Confirm H.pylori eradication 
- Confirm that H. pylori has been eradicated 4–6 weeks after completion of the treatment regimen. 
- Preferred modalities: Urea breath test, stool antigen test, or biopsy
- Stop PPIs at least 2 weeks before the urea breath test is performed for accurate results.
- Serology is not recommended to confirm eradication, as H. pylori antibodies may still be present for weeks or months after eradication.
- Acid suppression medication can be discontinued once eradication is confirmed. 
Functional dyspepsia (nonulcer dyspepsia) is a common GI disorder characterized by upper GI symptoms (e.g., epigastric pain, bloating) without any identifiable cause. Symptoms may vary in intensity and can have a significant impact on patients' lives. Functional dyspepsia is heterogeneous and multifactorial, and its pathophysiology is not fully understood.
Rome IV criteria for functional dyspepsia 
- Any of the following symptoms experienced at least 3 days per week over the past 3 months
- Interference with daily activities
- Symptom duration ≥ 6 months
- First-line treatment: PPIs for 8 weeks at standard dose (see “Acid suppression medications”) 
- Second-line treatment (if no improvement after 8 weeks of PPIs): tricyclic antidepressants (e.g., amitriptyline )
- Third-line treatment: Consider if there is no response to PPIs or tricyclic antidepressants.