Esophageal Disorders and Gastroesophageal Reflux Disease

Patients with esophageal disorders often present with difficulty swallowing, known as dysphagia, typically related to a structural or motility abnormality. Generally, patients present to the outpatient clinic with complaints of dysphagia, although some patients may be admitted as inpatients (e.g., food impaction).

• Oropharyngeal dysphagia (or transfer dysphagia) is characterized by difficulty in initiating a swallow and often presents with drooling, coughing related to aspiration, and sialorrhea.

• Esophageal dysphagia is experienced as the sensation of food going down slowly or getting stuck in the chest at least several seconds after initiating a swallow. The causes of esophageal dysphagia can be categorized as structural disorders or motility disorders.

  • Structural disorders include the following:

    • intrinsic esophageal obstruction

      • strictures related to esophagitis or malignancy

    • extrinsic esophageal stricture

      • vascular anomaly

      • malignancy/mass in chest or mediastinum

    • esophageal rings and webs

      • Plummer-Vinson syndrome (esophageal ring)

      • Schatzki ring

    • food impaction

  • Motility disorders can be categorized as primary and secondary esophageal motility disorders as defined in the following table:

(Source: Esophageal Motility Disorders and Gastroesophageal Reflux Disease. N Engl J Med 2020.)

Where the patient localizes the dysphagia is not always a good predictor of the location of the problem (for example, an obstruction at the lower esophageal sphincter may be experienced as dysphagia in the upper chest).

In this section, we review the following common esophageal disorders:

• Gastroesophageal Reflux Disease

• Eosinophilic Esophagitis

• Achalasia

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is the second most common gastrointestinal diagnosis in the ambulatory setting and affects 18%-28% of people living in North America. GERD is defined as symptoms, complications, or both related to refluxing of gastric contents into the esophagus, caused by transient relaxation of the lower esophageal sphincter (LES). More objectively, GERD is defined by the presence of characteristic mucosal injury on endoscopy or abnormal esophageal acid exposure on reflux monitoring studies.

Presentation

• heartburn and regurgitation (most common)

• globus sensation and noncardiac chest pain

• extraesophageal symptoms of cough, throat clearing, and hoarseness

Diagnosis

Most guidelines recommend an 8-week course of once-daily proton pump inhibitor (PPI) therapy as the means of clinical diagnosis in patients with typical symptoms. Upper endoscopy is the most common objective test to evaluate for GERD and is recommended in the following scenarios:

• patients who do not respond adequately to an 8-week trial of PPI

• patients whose symptoms return when PPI is discontinued

• as a first test in patients with alarm symptoms (e.g., dysphagia, weight loss, vomiting, iron-deficiency anemia, or bleeding)

• patients with multiple risk factors for Barrett esophagus

Management

• Proton pump inhibitor (PPI) or histamine-2 (H₂) blocker: Management of GERD includes inhibition of gastric acid secretion with a PPI or H₂ blocker. PPIs have been shown to be superior to H₂ blockers at providing heartburn and regurgitation relief, and for mucosal healing.

  • PPIs must be taken 30 to 60 minutes before a meal and are most effective when taken on an empty stomach.

  • First-line treatment is 8 weeks of PPI or H₂ blocker followed by a taper to the lowest dose of acid suppression needed for symptom control.

  • Further acid-inhibitor therapy (switching PPIs or increasing dose) and testing is indicated for patients with persistent symptoms following 6-8 weeks of therapy.

• Lifestyle measures: Recommended practices include the following:

  • avoiding trigger foods (e.g., chocolate, spicy meals, coffee, acidic drinks, large fatty meals)

  • avoiding food within 2-3 hours of bedtime

  • eating smaller meals

  • weight loss

  • smoking cessation

  • sleeping with the head of the bed raised

• Antireflux surgery (e.g., fundoplication or LINX procedure): Surgery is generally reserved for patients with objective evidence of GERD that is refractory to intensive medical therapy.

Barrett Esophagus

Barrett esophagus is the asymptomatic replacement of the normal squamous epithelium of the esophagus by metaplastic columnar epithelium caused by chronic esophageal inflammation secondary to acid reflux. Barrett esophagus is a rare but important precursor for esophageal adenocarcinoma.

Screening: Endoscopic evaluation should be considered in patients with chronic or frequent symptoms of gastroesophageal reflux and three or more risk factors (including age >50, male sex, white race, presence of obesity, smoking, or family history of Barrett esophagus or esophageal adenocarcinoma). Current guidelines recommend against repeat endoscopic screening in patients who have had a negative initial endoscopic screening examination.

Diagnosis: The diagnosis is confirmed by targeted and random biopsies of salmon-colored mucosa extending 1 cm or more from the gastroesophageal junction to identify intestinal metaplasia with goblet cells. These changes are highlighted in the following diagram:

(Source: Barrett’s Esophagus. N Engl J Med 2014.)

Surveillance: Regular surveillance with endoscopy according to the following grades of dysplasia are important recommendations for assessing potential malignant transformation. The screening interval depends on the level of dysplasia. Patients with high-grade dysplasia are considered for surgery or endoscopic mucosal ablation or resection.

• No dysplasia: Assess with follow-up endoscopy in 3 years if the longest segment is >3 cm or 5 years if <3 cm.

• Low-grade dysplasia: Endoscopic eradication therapy (EET) can be considered to prevent progression to high-grade dysplasia or, alternatively, surveillance endoscopy can be performed at 6 months and 12 months from diagnosis, and then annually until dysplasia is absent on two consecutive examinations.

• High-grade dysplasia: EET of all visible lesions is recommended followed by endoscopic surveillance at 3, 6, and 12 months from complete eradication and annually thereafter. EET is recommended over surgical management, given the morbidity and mortality associated with esophagectomy.

Maintenance acid-inhibitor therapy: At least once-daily PPI is recommended for all patients with Barrett esophagus irrespective of reflux symptoms.

Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic, allergen-driven, immune-mediated disease that has increasingly been recognized as a cause for dysphagia, heartburn unresponsive to antireflux measures, and food-bolus impaction. EoE is often associated with atopy, asthma, and other allergic manifestations outside of the gastrointestinal tract. A clue to EoE is burning, itching, or tingling of the lips, mouth, and throat when the trigger food is ingested. The incidence and prevalence of EoE has increased significantly during the past few decades.

Diagnosis

Esophageal biopsy: Diagnosis of EoE requires an esophageal biopsy showing infiltration of eosinophils of at least 15 eosinophils per high-power microscopy field. Biopsies are taken from the mid and distal esophagus separately, preferably with the patient off PPI therapy because eosinophilia can be responsive to PPI.

• A characteristic finding of EoE on endoscopy is “trachealization” of the esophagus, or circular rings that contribute to dysphagia. Note that GERD can also cause similar findings and must be ruled out before a diagnosis of EoE is made.

• With GERD, eosinophilia is typically found on distal esophageal biopsies but not on mid-esophageal biopsies.

• In contrast, with EoE, eosinophilia is found in both locations if the patient is not on PPI at the time of the diagnosis.

(Source: “Trachealization” of the Esophagus. N Engl J Med 2019.)

Management

Treatment of EoE includes the following:

• PPIs

• trial of an elimination diet to remove potential allergens

• swallowed topical glucocorticoids

No one therapy is recommended over the other. The goal of treatment is histologic remission with <15 eosinophils/high power field, as well as improvement in symptoms and if applicable, endoscopic findings.

Dupilumab is an interleukin-4 (IL-4)-receptor agonist that has been recently approved for use in patients with EoE. Dupilumab is a once-weekly, 300-mg, subcutaneous injection. Experience with dupilumab is evolving; currently, it may be considered for patients with refractory EoE.

Mechanical dilation is recommended in patients with EoE and dysphagia from an associated stricture. However, dilation must be performed carefully because it has been associated with deep esophageal tears and esophageal perforation.

The following table summarizes medical treatment options for EoE:

(Source: Eosinophilic Esophagitis. N Engl J Med 2015.)

Achalasia

Achalasia is a rare motility disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and failure of the esophageal smooth muscle to produce adequate peristalsis. Clinically, patients report dysphagia of solids and liquids, regurgitation, nocturnal cough, chest pain, heartburn, and weight loss.

Diagnosis

• Manometry is the most sensitive test for the diagnosis of achalasia. The classic manometric findings are diminished or absent primary peristalsis, increased resting LES pressure, and impaired LES relaxation during a test swallow.

• CT can be used to rule out pseudoachalasia caused by gastric or intrathoracic malignancy but is nondiagnostic.

• Endoscopy is required to exclude malignancy and other causes of dysphagia but is not diagnostic on its own. Findings include dilated esophagus and retained saliva with a puckered gastroesophageal junction.

• Barium esophagram can assist in diagnosis. The classic appearance consists of a dilated esophageal body and a tapered bird’s-beak appearance, as shown in the following image:

(Source: Achalasia. N Engl J Med 2012.)

Treatment

Treatment of achalasia is aimed at reducing the high pressure in the LES, either via endoscopy or surgery, with the modalities outlined in the following table: