Dyspepsia

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 red flag features for dyspepsia 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 acid suppression medications, 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 Rome IV criteria for functional dyspepsia.

• Dyspepsia: epigastric pain or burning that lasts for ≥ 1 month ^[1][2]
• 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). ^[3]

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. ^{[1][3] [1][3]}

Obtain a thorough medical history and physical examination, screen for risk factors for common etiologies (e.g., shared risk factors for PUD, GERD, and gastritis), and evaluate for red flag features in all patients.

Red flag features of dyspepsia

• Family history of gastrointestinal cancer
• Immunosuppression
• Clinically significant unintentional weight loss
• Anorexia
• 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 ^[1]

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 ^[1]

• Red flags of dyspepsia present: Consider EGD on a case-by-case basis.
• Red flags of dyspepsia absent
  • Typical dyspepsia; : Perform noninvasive tests for H. pylori infection, e.g., urea breath test
    • Positive: H. pylori eradication therapy
    • Negative: trial of acid suppression with proton pump inhibitors (PPIs)
  • Typical heartburn : trial of acid suppression with PPIs (empirical therapy) ^[3][4]

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. ^[4]

EGD ^[1][3]

• Indications
  • Patients ≥ 60 years of age with dyspepsia with/without red flags for dyspepsia
  • Select patients < 60 years of age with red flags for dyspepsia, assessed on a case-by-case basis ^[1][3]
  • Inadequate response to empirical pharmacotherapy
• Findings: EGD (with or without biopsies) can help to identify the cause of dyspepsia; examples include
  • Gastritis
  • PUD
  • Gastric cancer
  • GERD
  • Esophagitis

Obtain gastric biopsies to evaluate for H. pylori infection from all patients who undergo EGD for dyspepsia. ^[4]

Further workup

• Indications: inconclusive or negative EGD, negative H. pylori test, and/or inadequate response to empirical therapy
• Assess the pretest probability (PTP) of differential diagnoses of dyspepsia and workup accordingly.
• Examples include:
  • RUQ ultrasound for suspected symptomatic cholelithiasis
  • CT abdomen for suspected chronic pancreatitis
  • Assess the PTP of CAD; consider cardiac stress testing for stable angina.
  • Esophageal pH monitoring for persistent GERD symptoms despite adequate pharmacotherapy
  • Esophageal manometry or barium swallow for suspected esophageal motility disorders
  • Assess the Rome IV criteria for functional dyspepsia.

The differential diagnoses listed here are not exhaustive.

Approach ^[1][4]

• Typical heartburn (GERD) ^[3][9]
  • Trial of acid suppression therapy with PPIs for 8 weeks ^[3][4]
  • See “Management of GERD” for details on further management based on response to empirical therapy.
• Typical dyspepsia and negative test for H. pylori infection (PUD, gastritis) ^[10]
  • Trial of acid suppression therapy with PPIs for 8 weeks
  • See “Therapeutic approach to PUD” and “Gastritis subtypes” for further management.
• Positive test for H. pylori infection
  • H. pylori eradication therapy
  • H. pylori eradication confirmation 4–6 weeks after completion of therapy.
• Other etiologies
  • See relevant articles for details on the management of conditions diagnosed on EGD and further diagnostics.
• All patients
  • Consider antacids for rapid symptomatic relief as needed.
  • Implement complementary nonpharmacological measures and lifestyle changes.

Pharmacological therapy

“Eat with aluminum CHOPSticKs”: The most important side effects of aluminum hydroxide are Constipation, Hypophosphatemia, Osteodystrophy, Proximal muscle weakness, Seizures, and hypoKalemia.

Nonpharmacological recommendations ^[15][16][17]

• Dietary recommendations
  • Reduce portion size.
  • Avoid eating at least 3 hours before lying down (e.g., before going to sleep). ^[3]
  • Avoid foods and beverages that appear to trigger symptoms. ^[18]
• Physical recommendations
  • Patients with obesity should be encouraged to lose weight and should also receive advice on the best approach. ^[3]
  • Elevate the head-end of the bed (10–20 cm) for patients who experience symptoms while sleeping. ^[3]
• Reduce or avoid triggers
  • Reduce or avoid stress.
  • Avoid nicotine, alcohol, and caffeine (especially if they appear to trigger symptoms).
  • If possible, avoid medications that may worsen symptoms (e.g., NSAIDs, aspirin, corticoids, calcium channel blockers, diazepam) ^[3][19]

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 ^[2][16][20]

Functional dyspepsia is a diagnosis of exclusion that can be made if an organic cause cannot be identified after completing a diagnostic workup of dyspepsia and its differential diagnoses.

• Any of the following symptoms experienced at least 3 days per week over the past 3 months
  • Epigastric burning
  • Epigastric pain
  • Early satiety
  • Postprandial fullness
• Interference with daily activities
• Symptom duration ≥ 6 months

Treatment ^[1][16][20]

• First-line treatment: PPIs for 8 weeks at standard dose (see “Acid suppression medications”) ^[1]
• 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.
  • Prokinetic therapy (e.g., metoclopramide )
  • Psychological therapy (e.g., cognitive behavioral therapy)