1. Typical symptoms: The typical symptoms of reflux esophagitis may include heartburn and acid regurgitation. Heartburn is a burning sensation felt behind the sternum within 60 minutes of eating, precipitated by exercising, and while lying recumbent. The pain usually starts in the epigastrium and radiates towards the neck. However, some patients with severe esophagitis or Barrett's esophagus may be symptom-free and have no heartburn.

Acid regurgitation where the patient may notice a sour or burning fluid in the throat or mouth may be present. Maneuvers increasing intra-abdominal pressure and bending forward could provoke regurgitation of gastric acid.[24]

Some dysphagia may be reported in 30% of patients with reflux esophagitis (usually present in the presence of peptic strictures, Schatzki rings, weak peristalsis, or mucosal inflammation).

Other symptoms include (i) Globus sensation (a sense of a lump in the throat) and (ii) Water brash (increased salivary secretions in response to the acidity of the esophagus).

2. Atypical symptoms: These include the following[25]:

(i) Chest pain: The esophageal reflux pain may mimic cardiac pain, and patients should be evaluated to exclude cardiac causes. Other causes of esophageal causes of chest pain, including esophageal motility disorders, diffuse esophageal spasms, or hypertensive peristalsis (nutcracker esophagus), may be considered in the evaluation. However, reflux esophagitis is more common than these esophageal disorders.(ii) Chronic cough: Reflux esophagitis is one of the causes of chronic cough. Other causes of chronic cough include post-nasal discharge, asthma, some medications such as angiotensin-converting enzyme inhibitors. The underlying pathogenesis cough in reflux esophagitis can be explained on the basis of acid stimulation of nerve endings in the lower esophagus causing activation of the cough center and cough response.(iii) Asthma: There is an association between asthma and reflux esophagitis. However, it is not clear if this relationship is an association or a cause-effect change. However, the underlying relationship could be explained on the basis of autonomic dysregulation that usually occurs in patients with asthma, resulting in an increased vagal tone. This change, together with the increased negative intrathoracic pressure during asthma, could enhance the tendency for reflux. Another contributing factor is related to medications used in managing asthma such as theophylline, alpha-2 adrenergic receptor agonists may promote reflux by lowering the pressure across the lower esophageal sphincter.   (iv) Dental erosions, dysphonia (voice disorder), sore throat, and laryngospasm may be present.

The diagnosis of esophageal reflux is usually made based on a combination of presenting symptoms, objective testing with endoscopy, ambulatory reflux monitoring, and response to a PPI therapy. A good percentage of patients present with typical symptoms of heartburn and gastric regurgitation and do not need investigations to make the diagnosis. Patients presenting with chest pain should be investigated to exclude cardiac causes of chest pain before the commencement of gastrointestinal evaluation.

Patients with atypical symptoms should undergo a diagnostic evaluation with endoscopy and pH monitoring before a PPI trial. Patients presenting with dysphagia should undergo an endoscopic examination to rule out reflux complications (esophageal strictures, peptic ulcerations, malignancy).

Performing endoscopy may be indicated in high-risk groups, particularly overweight, over the age of 50, with chronic esophageal reflux for more than five years. Also, it is indicated in patients at high risk of complications, including Barrett esophagus, dysphagia, anemia, bleeding, and weight loss. Esophageal biopsies should be taken as an adjunct to endoscopic examination, particularly in patients with non-erosive changes and those suspected to have eosinophilic esophagitis.

Esophageal manometry is of limited value in the primary diagnosis of reflux esophagitis disease.

Neither a decrease in lower esophageal sphincter pressure nor the presence of a motility abnormality is specific for the diagnosis of reflux esophagitis disease. However, manometry is recommended before the consideration of anti-reflux surgery (to rule out achalasia or severe hypomotility as in scleroderma-like esophagus where Nissen fundoplication is contraindicated).

Ambulatory reflux monitoring is the only test that allows the determination of abnormal esophageal acid reflux and reflux frequency. In patients with PPI-resistant symptoms, ambulatory 24-h pH-impedance monitoring can be used to assess whether there is a relationship between symptoms and reflux episodes. This test can help to exclude reflux esophagitis, but the test should be carried out after the cessation of PPI therapy.[26]

Patients with atypical symptoms should undergo a diagnostic evaluation with endoscopy and pH monitoring before a PPI trial. Barium studies to diagnose reflux esophagitis are of limited value. The presence or absence of reflux during barium esophagography does not correlate with the incidence or extent of reflux observed during 24-hour pH impedance monitoring and of no value in the diagnosis of reflux esophagitis.[27]

Los Angeles classification of severity of reflux esophagitis- four grades[28]:

• Grade A: One or more esophageal mucosal breaks less than 5 mm in length.
• Grade B: One or more mucosal breaks greater than 5 mm but with continuity across mucosal folds.
• Grade C: Continuous mucosal breaks between the tops of two or more mucosal folds, but involving less than 75% of the esophageal circumference.
• Grade D: Mucosal breaks involving more than 75% of the esophageal sphincter.

Response to therapy with PPI (twice daily) in patients suspected of reflux esophagitis confirms the diagnosis. However, the PPI test is a sensitive but less specific test.[29]

Recommendations for the management of reflux esophagitis include the following [30]:

• Weight loss, particularly in overweight patients and patients with obesity, will help in reducing the severity and frequency of symptoms.
• Elevation of the head of the bed during sleep and avoidance of meals 2 to 3 hours before sleep will reduce reflux at night.
• Avoidance of certain foods such as chocolate, caffeine, alcohol, and spicy food may help.
• Treatment of patients with a proton pump inhibitor for eight weeks is recommended. Usually, initiated as once daily before the first meal of the day. If there is a partial response, the dose should be increased to twice daily. PPIs are safe in pregnant women if clinically indicated.
• Maintain PPI therapy for patients who continue to have symptoms and in patients with erosive esophagitis and Barrett esophagus.
• Patients who need PPI therapy for longer durations or life because of recurrence of symptoms should be placed on the lowest dose required for maintenance. Chronic use of PPI is associated with complications, including increased risk of bone fractures, electrolyte deficiencies, and renal insufficiency. 
• Patients not responding to PPIs treatment should be evaluated by the treating physician. Other disorders should be considered, including eosinophilic esophagitis, delayed gastric emptying, irritable bowel syndrome, achalasia, and psychological disorders. 
• Surgical therapy is as effective as medical therapy in patients with chronic reflux esophagitis. It offers long-term treatment. Patients should be investigated (preoperative manometry) for surgery to rule out achalasia and scleroderma-like esophagus.
• Vonoprazan fumarate tablets (a new synthesized potassium-competitive acid blocker), used on-demand, is an effective alternative maintenance therapy for mild reflux esophagitis.[31]
• In patients with obesity, bariatric surgery- gastric bypass is usually recommended.
• Management of reflux complications such as Schatzki rings by esophageal dilatation followed with PPI treatment; esophageal adenocarcinoma; laryngitis, and idiopathic pulmonary fibrosis.

 The differential diagnosis of reflux esophagitis may include[32]:

• Coronary artery disease.
• Infectious esophagitis
• Eosinophilic esophagitis
• Peptic ulcer disease
• Biliary colic
• Esophageal motor disorders
• Esophageal stricture
• Esophageal cancer
• Dyspepsia
• Dysphagia
• Rumination syndrome
• Radiation and chemotherapy-induced esophagitis

Complications associated with reflux esophagitis include:

• Esophagitis varying in severity. Patients with Grade C and D in LA classification are characterized by severe reflux. These patients have the lowest healing rate with PPIs. Patients with severe reflux esophagitis usually relapse after treatment and are more likely to develop Barrett's esophagus. These patients should undergo endoscopy 8 to 10 weeks after PPI therapy to check on healing and assess for complications.[33][34]
• Lower esophageal rings (Schatzki)- This complication correlates with reflux esophagitis. Dilatation is the mainstay of management, followed by PPI treatment.
• Barrett esophagus: This complication presents in 5% to 15% of patients with reflux esophagitis. It is more likely to occur in white male patients with severe reflux esophagitis, who have the symptoms for a longer duration, and are over the age of 50.
• Peptic stricture tends to occur in older patients who have the reflux for a longer duration, together with abnormal esophageal motility and not receiving treatment for the reflux symptoms.
• Esophageal adenocarcinoma (8 to 1 male to female)
• Peptic ulceration, cancer of the gastric cardia, dysphagia and upper gastrointestinal bleeding.
• Other complications include anemia (due to chronic blood loss), laryngitis, cough, sinusitis, bronchial asthma, idiopathic pulmonary fibrosis, and dental erosions.

The diagnosis of esophageal reflux is usually made based on a combination of symptoms, objective testing with endoscopy, ambulatory reflux monitoring, and response to a PPI therapy. However, upper endoscopy is not required in patients presenting with typical esophagitis symptoms. Patients presenting with chest pain require investigation to exclude cardiac causes of chest pain.

The majority of patients with reflux esophagitis may present to the general practitioner. The public and patients require education about common presenting symptoms of reflux esophagitis and preventive measures. Because patients may present with atypical symptoms or with complications, healthcare workers, including doctors, gastroenterologists, pulmonary physicians, otolaryngologists, nurses, and pharmacists, all operating as an interprofessional team, need to be aware of the diagnosis, sequelae, and complications. Dentists should be aware of dental changes associated with reflux esophagitis. Patients presenting with atypical symptoms such as chronic cough, asthma, laryngitis, or dysphonia may seek medical advice from pulmonary physicians and otolaryngologists, not aware that esophageal reflux is the primary disease. Performing endoscopy may be indicated in high-risk groups, particularly overweight, over the age of 50, with chronic esophageal reflux. Also, it is indicated in patients at high risk of complications, including Barrett esophagus, dysphagia, and weight loss. Using new classifications to stage reflux esophagitis patients should aim at improving patient management.[35][36]

While the clinicians listed above will drive therapeutic interventions, they should enlist the assistance of the pharmacist. Pharmacists can help determine which agents would best suit the patient presentation, and counsel the patient regarding appropriate administration and dosing, as well as what adverse effects might occur. Nursing can answer patient questions, assess compliance, evaluate treatment progress, and inform the clinician staff of any concerns they encounter. This type of interprofessional teamwork will improve patient outcomes with reflux esophagitis. [Level 5]