Nonerosive Reflux Disease

Nonerosive reflux disease is a form of gastro oesophageal reflux disease in which typical symptoms (heartburn, regurgitation) occur with a normal endoscopy (no mucosal breaks or erosive oesophagitis of grade B or above). Reflux monitoring shows abnormal oesophageal acid exposure (acid exposure time above 6%), and most patients respond to acid suppression. It accounts for about 60 to 70% of patients with gastro oesophageal reflux disease.

• Mechanisms: transient lower oesophageal sphincter relaxations (the dominant mechanism), a weak or hypotensive lower oesophageal sphincter, a hiatus hernia (loss of the diaphragm pinchcock effect), impaired oesophageal clearance (poor peristalsis, reduced saliva).
• Delayed gastric emptying, increased intra abdominal pressure (obesity, pregnancy, tight clothing), and an acid pocket at the gastro oesophageal junction. Oesophageal hypersensitivity contributes to symptoms.
• Risk factors: obesity (especially central obesity, with body mass index above 30), smoking, alcohol, large or fatty meals, late meals, hiatus hernia, pregnancy, scleroderma, medicines (calcium channel blockers, nitrates, anticholinergics, theophylline, bisphosphonates, NSAIDs, benzodiazepines), a family history, and stress.
• Prevalence: heartburn at least weekly affects 10 to 20% of adults in Western countries, and is lower (about 5%) in Asia, but increasing.
• The course is chronic and relapsing. Progression to erosive disease occurs in only 10 to 20% of patients, and the risk of Barrett oesophagus and adenocarcinoma is low, but it is not zero.
• Complications: reduced quality of life, sleep disturbance, respiratory symptoms (chronic cough, asthma, laryngitis), dental erosion, and, rarely, the development of erosive oesophagitis.

• Heartburn (retrosternal burning that rises towards the throat) and acid regurgitation (a sour or bitter taste in the mouth), occurring after meals, when bending or lying flat, and at night, relieved by antacids. Other symptoms include epigastric pain, belching, bloating, nausea, water brash, and a sensation of a lump in the throat.
• Extra oesophageal symptoms: chronic cough, hoarseness, throat clearing, globus, wheeze, dental erosion, and sleep disturbance.
• Examination is usually normal, except for obesity. Look for signs of systemic sclerosis and anaemia.
• Differential diagnosis: erosive reflux disease, reflux hypersensitivity, functional heartburn, eosinophilic oesophagitis, peptic ulcer disease, functional dyspepsia, gastroparesis, biliary disease, pill oesophagitis, achalasia, angina, and Barrett oesophagus.
• Red flags: dysphagia, odynophagia, weight loss, persistent vomiting, gastrointestinal bleeding or melaena, iron deficiency anaemia, a palpable mass, age over 55 years with new symptoms, and a family history of upper gastrointestinal cancer. Chest pain with exertion needs cardiac assessment.

• A presumptive clinical diagnosis from typical symptoms is adequate for starting empirical treatment in patients without alarm features. An 8 week course of a proton pump inhibitor is a diagnostic and therapeutic test.
• Upper endoscopy is indicated for alarm features, age over 55 years with new symptoms, and failure to respond to treatment after 8 weeks. It is also indicated for persistent symptoms with long duration (above 5 years) in men over 50 years with other risk factors for Barrett oesophagus (white race, central obesity, smoking, family history), and before antireflux surgery.
• A normal examination (or isolated minimal changes) in a patient with typical symptoms defines nonerosive disease when acid exposure is abnormal.
• Ambulatory reflux monitoring (24 hour pH-impedance, or a 96 hour wireless pH capsule) off proton pump inhibitors for 7 days is used for those with a normal endoscopy and persistent symptoms, and before surgery. Acid exposure time above 6% confirms the diagnosis, and a value of 4 to 6% is borderline.
• Oesophageal high resolution manometry before surgery (to exclude achalasia and to assess peristalsis).
• Barium swallow for dysphagia (hiatus hernia, stricture), and gastric emptying study for nausea and early satiety.
• Helicobacter pylori testing is not needed for reflux disease alone, but is offered when dyspepsia coexists.

• Lifestyle and dietary measures for all patients:
  • Weight loss for those who are overweight or have gained weight recently (a loss of 5 to 10% of body weight reduces symptoms).
  • Raise the head of the bed by 10 to 15 cm, and sleep in the left lateral position for night symptoms.
  • Avoid meals within 3 hours of bedtime, large meals, and individual trigger foods or drinks (fatty and fried food, chocolate, mint, spicy food, citrus, tomato, coffee, alcohol, carbonated drinks).
  • Stop smoking, avoid tight clothing, and review medicines that worsen reflux (calcium channel blockers, nitrates, anticholinergics, theophylline, bisphosphonates, NSAIDs).
• Acid suppression (the main treatment):
  • Proton pump inhibitor once daily, taken 30 to 60 minutes before the first meal of the day, for 4 to 8 weeks. Doses: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, or rabeprazole 20 mg (child 1 to 12 years: omeprazole 10 to 20 mg daily by weight, 0.7 to 3.3 mg/kg).
  • Relief of heartburn occurs in 70 to 80% of patients with nonerosive disease, which is lower than in erosive disease.
  • If symptoms persist after 4 to 8 weeks, check adherence and timing, and consider doubling the dose (twice daily before breakfast and the evening meal) for 4 to 8 weeks, and review the diagnosis (investigate with endoscopy and reflux monitoring).
  • After symptom control, step down to the lowest effective dose. Use on demand therapy (a proton pump inhibitor taken only when symptoms occur, or for a few days), or an H2 receptor antagonist or antacid, for patients with mild and intermittent symptoms, because nonerosive disease does not need continuous long term treatment.
  • H2 receptor antagonist: famotidine 20 mg orally 12 hourly, or 40 mg at night, for mild or night symptoms (the effect is less than a proton pump inhibitor, and tolerance develops in 2 to 4 weeks). Ranitidine has been withdrawn in many countries.
  • Potassium competitive acid blocker: vonoprazan 10 to 20 mg orally once daily where available, for patients who do not respond adequately to proton pump inhibitors.
  • Antacid and alginate for rapid relief of breakthrough symptoms: calcium carbonate 500 to 1000 mg chewed as needed (maximum 7.5 g per day), or sodium alginate and potassium bicarbonate 10 to 20 mL after meals and at bedtime.
  • Prokinetic therapy for delayed gastric emptying: domperidone 10 mg orally 3 times daily before meals for the shortest time (check the QT interval and drug interactions), or metoclopramide 5 to 10 mg 3 times daily before meals for no more than 5 days.
  • Baclofen 5 to 10 mg orally 3 times daily before meals for regurgitation and belching that persist (specialist guided).
• Long term proton pump inhibitor use: review the need at least yearly, use the lowest effective dose, and monitor for adverse effects (hypomagnesaemia, vitamin B12 deficiency, fracture risk, Clostridioides difficile infection, community acquired pneumonia, and possible kidney disease).
• Calcium carbonate is better absorbed with food during proton pump inhibitor use, and calcium citrate is preferred.
• A proton pump inhibitor is not usually withdrawn abruptly (rebound acid hypersecretion lasts 2 to 4 weeks), so taper gradually and use an alginate or antacid as needed.
• Antireflux surgery (laparoscopic fundoplication) or endoscopic and magnetic sphincter augmentation procedures are options for patients with confirmed reflux (abnormal acid exposure on testing off treatment). Patients also need good symptom response to acid suppression, normal motility on manometry, and a preference to avoid lifelong medication, or for severe regurgitation.
• Results: 85% at 5 years in good response patients.
• Adverse effects include dysphagia, bloating and inability to belch.
• Surgery is not recommended in patients without objective evidence of reflux or with hypersensitivity or functional heartburn. Bariatric surgery (gastric bypass) is preferred for patients with severe obesity.
• Extra oesophageal symptoms: use the same proton pump inhibitor treatment, but with 8 to 12 weeks of twice daily dosing and objective confirmation of reflux, and consider other causes for cough and laryngeal symptoms.
• Special groups:
  • Pregnancy: lifestyle measures, antacids (calcium carbonate), alginate, and then famotidine 20 mg twice daily or omeprazole 20 mg daily when needed. Avoid sodium bicarbonate and antacids containing aluminium or magnesium trisilicate in large amounts.
  • Infants and children: reflux in infants is usually physiological and resolves by 12 to 18 months, so use thickened feeds, smaller feeds, and positioning, and avoid proton pump inhibitors unless there is proven oesophagitis or severe symptoms.
  • Children over 1 year with persistent symptoms: omeprazole 10 mg (weight 10 to 20 kg) or 20 mg (over 20 kg) once daily for 4 to 8 weeks.
  • Elderly: review polypharmacy (bisphosphonates, NSAIDs, calcium channel blockers), use the lowest effective dose of proton pump inhibitor, and monitor for adverse effects and drug interactions (for example, clopidogrel with omeprazole, so use pantoprazole).
  • Renal and hepatic impairment: no dose adjustment of proton pump inhibitors is usually needed, but reduce the dose in severe hepatic impairment (omeprazole 10 to 20 mg daily maximum), and avoid magnesium and aluminium antacids in renal impairment.
  • Obesity: weight loss, and bariatric surgery for severe obesity.
• Follow up: review at 4 to 8 weeks to assess response, then every 6 to 12 months. Refer to a gastroenterologist for alarm features, refractory symptoms, suspected Barrett oesophagus, or consideration of surgery. Offer endoscopic surveillance to patients with Barrett oesophagus under specialist care.