OVERVIEW

What is non-erosive gastroesophageal reflux disease?

Non-erosive gastroesophageal reflux disease, also known as non-erosive reflux disease (NERD) or endoscopy-negative reflux disease, is characterized by troublesome GERD symptoms without visible esophageal mucosal damage.

The typical GERD symptoms include heartburn (a burning sensation behind the breastbone) and regurgitation. It is a common chronic condition that can significantly impact patients' quality of life.

Is non-erosive gastroesophageal reflux disease common?

A systematic review of 15 epidemiological studies found that the prevalence of GERD in Western countries ranges from 10% to 20%, while in Asia it is less than 5%. According to various international studies, NERD accounts for 50% to 81% of GERD cases.

What are the subtypes of non-erosive gastroesophageal reflux disease?

Research suggests that NERD consists of three subtypes:

• Pathological acid reflux type: Heartburn symptoms are associated with pathological acid reflux in the esophagus, accounting for about 50% of cases.

• Acid-sensitive esophagus type: Esophageal acid reflux is within the physiological range, but symptoms are related to acid reflux (positive SI), indicating esophageal hypersensitivity, accounting for about 18.5%.

• Functional heartburn type: Heartburn symptoms are unrelated to acid reflux. 24-hour esophageal pH monitoring shows physiological acid reflux, endoscopy is normal, and SI is negative, accounting for about 31.5%.

It is generally considered that NERD is a subset of GERD, meaning only the "pathological acid reflux type" qualifies as standard NERD. The latter two subtypes are independent conditions, classified under functional gastrointestinal disorders as reflux hypersensitivity and functional heartburn, or they may be considered part of a broader definition of NERD.

SYMPTOMS

What are the common manifestations of non-erosive gastroesophageal reflux disease?

Non-erosive gastroesophageal reflux disease shares the same clinical manifestations as typical GERD, except without evident endoscopic erosions. The main symptoms include:

• Common manifestations of GERD (often lasting no less than 3 months):

  • Heartburn: Typically described as a burning sensation behind the breastbone, most commonly occurring after meals. Symptoms are considered bothersome if mild heartburn occurs on 2 or more days per week, or moderate-to-severe heartburn occurs more than 1 day per week.

  • Regurgitation: The sensation of stomach contents flowing back into the mouth or lower throat. Patients often regurgitate acidic fluid containing small amounts of undigested food.

• Other symptoms of GERD: Dysphagia, chest pain, odynophagia, extra-esophageal symptoms (e.g., chronic cough, hoarseness, wheezing), and less commonly, nausea.

CAUSES

What causes non-erosive gastroesophageal reflux disease?

Currently, NERD is considered a heterogeneous group of diseases. The main pathogenesis of NERD includes gastric reflux, esophageal motility disorders, esophageal mucosal hypersensitivity, and psychological abnormalities.

• Gastric reflux: Acid reflux is the most common trigger;

• Esophageal motility disorders: Ineffective esophageal motility may occur;

• Esophageal mucosal hypersensitivity: Increased esophageal sensitivity to acid may be related to impaired esophageal mucosal barrier function, allowing substances like acid to act on nerve endings in the esophageal mucosa through widened intercellular spaces.

• Psychological abnormalities: NERD patients exhibit significant psychological issues, including anxiety, depression, somatic symptoms, and sleep disorders. Many studies have also confirmed that psychosocial stressors can worsen heartburn symptoms in NERD patients.

Why does non-erosive gastroesophageal reflux disease involve gastric reflux but no visible esophageal erosion?

In fact, most gastroesophageal reflux disease patients show no visible esophageal erosion upon macroscopic examination. However, the absence of visible erosion does not mean there is no tissue damage.

If samples from the lower esophagus of NERD patients are examined under a microscope, changes such as "infiltration of neutrophils and eosinophils in the squamous epithelium, dilation of blood vessels in the lamina propria papillae (vascular lakes), basal cell hyperplasia of the squamous epithelium, swollen squamous cells, and elongated epithelial papillae" can be observed.

In other words, the esophageal mucosa of these patients has already undergone some changes due to gastric reflux, but these changes are not yet visible to the naked eye.

DIAGNOSIS

How is Non-Erosive Gastroesophageal Reflux Disease Diagnosed?

Clinically, gastroesophageal reflux disease (GERD) can be initially diagnosed based on typical heartburn symptoms lasting for at least three months. If an endoscopic examination confirms normal esophageal mucosa, a diagnosis of NERD (Non-Erosive Reflux Disease) can be preliminarily established. Additional diagnostic methods may include 24-hour esophageal pH and bile reflux monitoring, as well as a PPI (Proton Pump Inhibitor) test.

• Endoscopy: Traditional endoscopy serves as an exclusionary test for NERD. It helps determine the absence of erosive lesions under endoscopy.

• 24-Hour Esophageal pH and Bile Reflux Monitoring: This helps confirm the presence of acid reflux.

• PPI Test: Currently the most practical clinical method for diagnosing NERD. If typical reflux symptoms like heartburn disappear or significantly improve after PPI treatment (various acid-suppressing proton pump inhibitors, such as "azole" drugs), and no esophageal mucosal damage is found during endoscopy, NERD can be clinically diagnosed.

Which Diseases Should Non-Erosive Gastroesophageal Reflux Disease Be Differentiated From?

• Other esophageal disorders: Such as fungal esophagitis, drug-induced esophagitis, achalasia, and esophageal cancer.

• Other digestive system diseases: Such as peptic ulcers and biliary or pancreatic disorders.

• For patients presenting primarily with chest pain, differentiation should be made between cardiac chest pain and other non-cardiac causes of chest pain.

• Functional gastrointestinal disorders: Such as functional heartburn, functional chest pain, and functional dyspepsia.

TREATMENT

Which department should I visit for non-erosive gastroesophageal reflux disease?

Generally, you should visit the gastroenterology department of a hospital. However, for gastroesophageal reflux caused by certain surgical conditions, you may consult the thoracic surgery department.

How should non-erosive gastroesophageal reflux disease be treated?

The treatment principle for NERD is to relieve symptoms and improve the patient's quality of life.

• General treatment:

  • Adjust diet and lifestyle habits, such as actively losing weight if overweight;

  • Avoid lying down after meals and refrain from eating 2–3 hours before bedtime;

  • If nocturnal reflux occurs, elevate the head of the bed by 15–20 cm;

  • Eliminate dietary triggers, including greasy foods, caffeine, chocolate, spicy foods, high-fat foods, carbonated beverages, and mint.

• Drug treatment:

  • For patients with mild intermittent symptoms (heartburn occurring ≤ 2 times per week), low-dose H2 receptor antagonists (e.g., ranitidine, 150 mg per dose) are recommended as needed.

  • If symptoms persist, switch from as-needed H2 receptor antagonist use to a standard dose (e.g., ranitidine at 150 mg per dose, twice daily) for at least 2 weeks.

  • If heartburn symptoms continue or if the initial frequency exceeds twice per week, initiate once-daily standard-dose PPI (see "Appendix" for details). If necessary, increase to twice-daily standard-dose PPI to control symptoms. Adjust the treatment intensity gradually at 2–4 week intervals. Once symptoms are controlled, continue maintenance therapy for at least 8 weeks.

  • For treating GERD during pregnancy, first adjust diet and lifestyle, then consider sucralfate for medication. Antacids containing sodium bicarbonate or magnesium trisilicate should be avoided during pregnancy. If sucralfate is insufficient, PPI therapy may also be considered.

Appendix: Standard-dose PPI dosages: Lansoprazole 30 mg, Esomeprazole 20 mg, Omeprazole 20 mg, Rabeprazole 20 mg, Pantoprazole 40 mg.

DIET & LIFESTYLE

What should patients with non-erosive gastroesophageal reflux disease pay attention to in daily life?

• Overweight patients (BMI > 25 kg/m²) or those with significant recent weight gain should lose weight through increased exercise and dietary adjustments;

• Quit smoking and drinking, maintain regular meals, and eat smaller, more frequent portions;

• Avoid foods that may trigger reflux, such as chocolate, coffee, spicy or acidic foods, acidic fruits and vegetables (e.g., tomatoes, citrus fruits), and high-fat foods;

• Try to avoid medications that reduce lower esophageal sphincter tension, such as anticholinergics, sedatives, theophylline, progesterone or progesterone-containing contraceptives, nitrates, and calcium channel blockers;

• Avoid lying flat or in a head-down position immediately after meals;

• Avoid situations that increase abdominal pressure (e.g., wearing tight belts);

• Patients with predominant nighttime symptoms should especially avoid eating within 2–3 hours before bedtime and elevate the head of the bed by 20–30 cm.

PREVENTION

How to prevent non-erosive gastroesophageal reflux disease?

Paying attention to the following three aspects can help prevent non-erosive gastroesophageal reflux disease to some extent:

• Maintain a normal weight: Obesity may increase abdominal pressure, leading to gastroesophageal reflux. Studies have found that obesity and weight gain significantly raise the risk of gastroesophageal reflux disease, and maintaining a normal weight can reduce this risk.

• Avoid smoking and limit alcohol consumption: Smoking can affect the barrier function of the esophageal mucosa and impair the function of the lower esophageal sphincter. High-concentration alcohol can directly damage the esophageal mucosa, and alcohol also stimulates stomach contractions. Excessive alcohol consumption can induce vomiting, which may lead to reflux esophagitis.

• Maintain healthy lifestyle habits: Eat regularly, avoid overeating, minimize staying up late, and keep a positive mood.