Esophagitis

Esophagitis is the inflammation of the esophageal mucosa secondary to direct mucosal injury (e.g., gastroesophageal reflux or GERD, substance-induced esophagitis) or to an inflammatory process (e.g., eosinophilic esophagitis). It can also occur secondary to local infection (e.g., esophageal candidiasis, HSV esophagitis, CMV esophagitis), especially in immunosuppressed individuals. The typical manifestation of esophagitis is retrosternal pain (heartburn). Associated features such as regurgitation, odynophagia, or dysphagia may provide clues to the underlying etiology. Coronary artery disease (CAD) may mimic the retrosternal symptoms of esophagitis and should be ruled out if suspected (e.g., chest pain on exertion, presence of risk factors for CAD). Empiric pharmacotherapy with a trial of proton pump inhibitors (PPIs) is recommended in patients with typical features of GERD. Inadequate response to empiric therapy or atypical features at presentation (e.g., significant dysphagia, odynophagia, fever), risk factors for esophageal cancer, or red flags for dyspepsia should prompt an esophagogastroduodenoscopy (EGD) to directly visualize the esophageal mucosa and obtain biopsies from areas of mucosal abnormalities. Further diagnostics (e.g., esophageal pH monitoring, high-resolution esophageal manometry) should be considered if EGD is inconclusive. Specific management depends on the underlying cause and includes PPIs, dietary restriction and topical steroids for eosinophilic esophagitis, and systemic antifungal or antiviral therapy for infectious esophagitis. Complications of prolonged or severe esophagitis include Barrett esophagus, esophageal strictures, hematemesis, and aspiration.

• Esophagitis: inflammation of the esophageal mucosa that is secondary to direct mucosal injury or to inflammatory infiltrates due to a systemic inflammatory disorder ^[1]
• Eosinophilic esophagitis: chronic immune-mediated eosinophil-predominant inflammation of the esophageal mucosa ^[2]
• Infectious esophagitis: inflammation of the esophageal mucosa secondary to a local infection; most common in patients with immunosuppression.
• Substance-induced esophagitis: esophageal mucosal injury caused by direct contact with an irritant substance
• Medication-induced esophagitis: a type of substance-induced esophagitis caused by prolonged contact with certain types of oral medications (e.g., antibiotics, antiinflammatory medications, bisphosphonates).

The most common cause of esophagitis is GERD, in which gastric acid refluxes into the esophagus and results in direct mucosal injury and subsequent inflammation. ^[1]

• Retrosternal burning chest pain (heartburn)
• May be associated with dyspepsia, regurgitation, belching, and globus sensation
• Features of the underlying etiology, e.g.:
  • Heartburn that worsens on lying down or bending forward: GERD
  • Retrosternal chest pain, dysphagia, and reflux of undigested food particles: achalasia cardia
  • Dysphagia, weight loss, hematemesis: esophageal cancer
  • See also “Infectious esophagitis” and “Eosinophilic esophagitis.”

Approach ^[3][4][6]

• Assess the pretest probability of the underlying etiology based on a thorough medical history and physical examination.
  • Typical features and risk factors for GERD: trial of empiric pharmacotherapy with PPIs
  • Atypical features at presentation or inadequate response to PPI trial: EGD with biopsies of mucosal abnormalities
    • Atopy: increased likelihood of eosinophilic esophagitis
    • Immunosuppression: increased likelihood of infectious esophagitis
    • Recent ingestion of caustic/corrosive substances or medications: increased likelihood of substance-induced esophagitis
    • Red flags for dyspepsia and/or risk factors for esophageal cancer: increased likelihood of esophageal cancer
  • Consider cardiovascular causes of retrosternal pain in patients with red flags for chest pain and/or risk factors for CAD: See “Chest pain.”
• Diagnosis confirmed on EGD with biopsy: Administer specific treatment (see relevant sections in this article or “GERD” for details).
• Inconclusive EGD
  • Features not attributable to esophageal motility disorders: esophageal pH monitoring to evaluate for nonerosive reflux disease (NERD)
  • Features attributable to esophageal motility disorders: barium swallow and high-resolution esophageal manometry
• See also “Approach to dyspepsia.”

Empiric pharmacotherapy

• Indication: underlying etiology is most likely GERD, i.e., a patient with all of the following features
  • Age < 60 years
  • Typical features of GERD (e.g., heartburn, regurgitation)
  • No major red flags for dyspepsia ^[4][7]
  • No major risk factors for Barrett esophagus
• Management
  • Initiate empiric therapy with a trial of PPIs at standard dosage for 8 weeks.
  • See “Antacids and acid suppression medications” for agents, detailed dosages, and pharmacological considerations.
  • See “Management of GERD” for details and subsequent management based on response to empiric pharmacotherapy.

Initial diagnostics

EGD

• Indications (any of the following)
  • Age ≥ 60 years with or without red flags for dyspepsia
  • Multiple or severe red flags for dyspepsia regardless of age
  • Multiple or major risk factors for Barrett esophagus (e.g., duration of symptoms > 5 years)
  • Atypical features, such as:
    • Systemic signs of infection or immunosuppression (suggestive of infectious esophagitis)
    • Features of atopy (suggestive of eosinophilic esophagitis)
  • Suspected GERD with inadequate response to empiric pharmacotherapy
• Findings
  • Nonspecific findings : mucosal erythema, edema, friability, and erosions
  • Specific findings
    • Infectious esophagitis: pseudomembranes (esophageal candidiasis), punched-out ulcers (herpes esophagitis), or linear ulcers (CMV esophagitis)
    • Eosinophilic esophagitis: circumferential mucosal lesions (e.g., rings, corrugations), with possible trachealization
    • Medication-induced esophagitis: punched-out ulcers, mild inflammatory changes of the surrounding mucosa
    • Barrett esophagus: tongue-shaped projections of salmon pink mucosa in the lower third of the esophagus
    • Esophageal cancer: intraluminal ulceroproliferative friable mass

Pathology

• Biopsies should be obtained from any area of mucosal irregularity seen on EGD.
• Histopathologic findings can often determine the etiology, e.g.:
  • Superficial coagulative necrosis of the squamous epithelium: reflux esophagitis
  • Pseudohyphae: esophageal candidiasis
  • Eosinophilic infiltrates: eosinophilic esophagitis
  • Metaplasia of squamous into columnar epithelium: Barrett esophagus

Obtaining biopsies from esophageal mucosa that appears normal on EGD is not routinely recommended. ^[8]

Additional diagnostics (not routinely required)

• Indications
  • Inconclusive EGD
  • Atypical symptoms (e.g., significant dysphagia)
• Modalities
  • Esophageal pH monitoring to evaluate for NERD
  • Barium swallow and high-resolution esophageal manometry for suspected motility disorders
  • Inflammatory markers and antibody panels (e.g., ANA, ANCA) for suspected immune-mediated disorder (see “Etiology” section)

Clinical features ^[3]

• Odynophagia, dysphagia (characteristic)
• Heartburn, regurgitation
• Lesions in the oral mucosa (e.g., ulcers, thrush) ^[3]
• Retrosternal chest pain
• Systemic signs of infection (e.g., fever)

Etiology

• Fungal: Candida spp. (most common)
• Viral: CMV, HSV (HSV-1)
• Uncommon: bacterial esophagitis , parasitic esophagitis

Infectious esophagitis is most commonly seen in patients with immunosuppression (resulting from, e.g., HIV, malignancies, transplantation, dialysis). A diagnosis of infectious esophagitis in patients with no known comorbidities should prompt studies for immunosuppression.

Diagnostics and treatment

In patients with AIDS with CD4 counts below 200/mcL, coexisting fungal and viral infections are possible. Consider extended testing and double therapy for refractory cases.

Epidemiology ^[2]

• Overall increasing incidence and prevalence
• Most commonly affects young individuals

Clinical features ^[2][12]

• Dysphagia, food bolus impaction
• Symptoms can be worsened by ingestion of food containing allergens.
• Associated features: atopy (e.g., asthma, rhinitis, atopic dermatitis, alimentary allergies)

Diagnostics ^[2][12][13]

• Diagnostic criteria (all are required) ^[13]
  • Features of esophageal dysfunction (see “Clinical features”)
  • Esophageal inflammation on biopsy with; ≥ 15 eosinophils per high-power field
  • Exclusion of differential diagnoses of esophageal eosinophilia
• Endoscopic findings
  • Circumferential mucosal lesions (e.g., rings, corrugations), with possible esophageal trachealization (presence of multiple rings in the esophagus, which results in a furrowed or corrugated appearance similar to the trachea)
  • Longitudinal furrows
  • Diffuse narrowing or isolated strictures
• Histopathologic findings ^[2]
  • Intraepithelial accumulation of eosinophils
  • Basal cell hyperplasia
  • Possibly eosinophilic microabscesses

Differential diagnoses of esophageal eosinophilia ^[13][14]

• GERD
• Drug hypersensitivity reaction
• Hypereosinophilic syndrome
• Pill esophagitis
• Achalasia
• Autoimmune conditions (e.g., Crohn disease)
• Infection (e.g., Candida esophagitis, HSV esophagitis)
• Connective tissue disease (e.g., Marfan syndrome)

Treatment ^[13][15]

General principles ^[13]

• Choose between empiric dietary elimination or pharmacotherapy through shared decision-making.
• Esophageal dilation is indicated for severe strictures.
• Evaluate response to therapy based on symptoms and endoscopic and biopsy findings during follow-up testing.

Pharmacotherapy ^[13][16][17]

• High dose PPIs (see “Acid suppression medications” for details on agents and dosages)
• Topical steroids (swallowed aerosolized steroids)
  • Steroid choice is based on availability and preference.
    • Fluticasone (off-label)
    • Budesonide (off-label)
  • Use after meals or at bedtime; avoid food or drinks for 30–60 minutes after use.
• Biological agents (e.g., dupilumab): considered in severe and/or refractory disease

Nonpharmacological therapy

• Dietary elimination (to identify and avoid allergens)
  • Empiric food elimination diets: recommended to reduce the inflammatory response in the GI tract
    • Exclude certain food groups (e.g., milk, wheat, soy, egg, nuts, fish, and
      shellfish) from the diet.
    • Begin with a less restrictive elimination diet (e.g., remove one or two specific food groups at a time). ^[13]
  • Allergy testing is not recommended.
• Esophageal dilation
  • Consider for patients with an esophageal stricture and dysphagia.
  • Use in combination with anti-inflammatory therapy (not recommended as monotherapy).

Approx. 50% of patients with eosinophilic esophagitis do not respond to acid suppression therapy.

Long-term maintenance therapy (dietary elimination and/or pharmacological therapy) is often required to maintain remission. ^[15][18]

Medication-induced esophagitis ^[19]

• Etiology: direct mucosal injury caused by prolonged contact with a certain drug
  • Antibiotics (e.g., tetracycline, doxycycline, and clindamycin)
  • Antiinflammatory drugs, NSAIDs, aspirin
  • Bisphosphonates (e.g., alendronate)
  • Others (e.g., potassium chloride, iron compounds, quinidine)
• Diagnostics
  • Endoscopy: punched-out ulcers, mild inflammatory changes of the surrounding mucosa
  • Histopathology: ulcerations, inflammatory and necrotic changes of the epithelium, giant cells with multiple nuclei
• Treatment: Most cases are self-limiting.
  • Discontinue the medication or substance causing esophagitis.
  • Ensure nutrition and hydration.
  • Consider antacids, sucralfate, or PPIs to ameliorate symptoms.
  • Some patients may develop strictures that require esophageal dilations.

Other substance-induced esophagitis

• Caustic ingestion: causes corrosive esophagitis (ulceration and fibrosis of the esophagus)
• Alcohol and tobacco ^[20]
  • Are risk factors for GERD and Barrett esophagus
  • May exacerbate other forms of esophagitis

• Chronic esophagitis (e.g., due to GERD): Barrett esophagus ^[6]
• Hematemesis (severe erosive esophagitis) ^[21]
• Esophageal stricture
• Aspiration

We list the most important complications. The selection is not exhaustive.