Esophagitis

Esophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Diagnosis is by endoscopy and biopsy. Laboratory tests and imaging are obtained, depending on the degree of damage and involvement of other organ systems. Treatment for esophagitis depends on the underlying etiology and includes dietary changes, avoidance of offending agents, antibiotic therapy, or proton pump inhibitor use. In severe cases such as in corrosive injury, surgery may need to be performed. If left untreated, esophagitis can lead to complications such as strictures, metaplasia of the esophagus, and development of malignancy.

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Overview

  • Esophagitis: inflammation of or injury to the esophageal mucosa
  • Major etiologies:
    • Medication-induced/pill-induced esophagitis
    • Infectious esophagitis
    • Eosinophilic esophagitis
    • Corrosive esophagitis
    • Reflux esophagitis
  • Diagnosis is done by upper endoscopy; findings vary per etiology.

Mnemonic

To remember the common causes of esophagitis: “PIECE”

  • Pill-induced esophagitis
  • Infectious esophagitis
  • Eosinophilic esophagitis
  • Corrosive esophagitis
  • Etc. (reflux esophagitis)

Medication-induced Esophagitis

Etiology

  • Antibiotics: tetracyclines, doxycycline, clindamycin
  • Anti-inflammatories: Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin
  • Bisphosphonates: alendronate, risedronate
  • Others: potassium chloride, quinidine, iron supplements, ascorbic acid

Pathophysiology

  • Prolonged, direct contact between the medication(s) and the mucosa causes irritation, erosions, and ulcerations
  • Frequently affects site(s) of anatomical narrowing (mid-esophagus, near level of the aortic arch)
  • Mechanisms:
    • Disruption of the normal protective mucosal barrier: aspirin, NSAIDs
    • Local caustic damage (e.g., doxycycline is acidic once dissolved)
    • Hyperosmotic solutions contribute to tissue and vascular injury (e.g., potassium chloride).

Risk factors

  • Occurs more often in elderly patients
  • Position of patient (supine > upright)
  • Size of medication (delayed transit with large tablets)
  • Amount of fluid ingested with medication (intake of at least > 100 mL advised)

Clinical presentation

  • Heartburn
  • Retrosternal pain
  • Odynophagia, dysphagia

Diagnosis

  • Clinical diagnosis based on history
  • Upper endoscopy: 
    • Perform if with severe or persistent symptoms (despite discontinuation of the offending medication) 
    • Findings: discrete ulcer, with normal bordering mucosa
Cloxacillin-induced esophagitis

Stellate erosions in the midesophagus (white arrows) in a patient with cloxacillin-induced esophagitis

Image: “Cloxacillin: A New Cause of Pill-Induced Esophagitis” by Zezos P, Harel Z, Saibil F. License: CC BY 4.0

Prevention and management

  • Avoid the medication. 
  • Resolution expected in < 2 weeks after discontinuation.
  • If medication is necessary, take the medication with enough water and maintain an upright position for at least 30 minutes. 

Infectious Esophagitis: Cytomegalovirus (CMV)

Etiology

  • Past CMV infection + CD4 cell count < 50 cells/microL → ↑ risk of reactivation → infection of organs such as the esophagus
  • Gastrointestinal (GI) disease from CMV is not frequent but is a serious complication of AIDS (acquired immunodeficiency syndrome).

Risk factors

  • Patients with AIDS (occurrence decreased since availability of antiretroviral therapy)
  • Solid-organ and bone marrow transplant recipients
  • Patients receiving immunosuppressive therapy and chemotherapy

Clinical presentation

  • Odynophagia with dysphagia
  • Nausea, fever, substernal burning pain
  • Can have concurrent infection in retina, lung, liver, colon

Diagnosis

Diagnosis is done by upper endoscopy.

  • Linear or longitudinal deep ulcerations, erosions
  • Biopsy: cytomegalic cells (with intracytoplasmic or intranuclear inclusions)
Cytomegalovirus esophagitis

Upper gastrointestinal endoscopic findings in a patient with cytomegalovirus esophagitis. An ulcer with a white base is seen in the esophagus.

Image: “Cytomegalovirus esophagitis developing during chemoradiotherapy for esophageal cancer” by Journal of Medical Case Reports. License: CC BY 4.0

Management

  • Ganciclovir or foscarnet
  • With AIDS: antiretroviral therapy

Infectious Esophagitis: Herpes Simplex Virus (HSV)

Etiology

  • Majority are HSV type 1.
  • Can be primary infection or reactivation of HSV

Risk factors

  • AIDS
  • Organ or bone marrow transplant recipients
  • Patients on immunosuppressive therapy

Clinical presentation

  • Odynophagia with dysphagia
  • Retrosternal chest pain, +/- fever, concurrent oropharyngeal ulcers

Diagnosis

Diagnosis is done by upper endoscopy.

  • Early lesion: vesicles (rarely seen)
  • Punched-out ulcers, +/- plaques
  • Biopsy: HSV-infected cells with Cowdry type A inclusion bodies
  • Viral culture if no treatment response
Herpetic esophagitis

Upper digestive endoscopy of a patient showing numerous injuries on the esophageal surface that are yellow-whitish in color, pleomorphic, and isolated small circular plaques with central erosions.

Image: “Herpetic esophagitis in immunocompetent medical student” by Marinho AV, Bonfim VM, de Alencar LR, Pinto SA, de Araújo Filho JA. License: CC BY 3.0

Management

  • Acyclovir
  • With HIV/AIDS: antiretroviral therapy

Infectious Esophagitis: Candidiasis

Etiology

  • Candida albicans: most frequently occurring
  • Candida glabrata, Candida krusei: less common

Risk factors

  • Human immunodeficiency virus (HIV) with CD4 cell count < 100 cells/μL
  • Hematologic malignancy
  • Hematopoietic cell transplant recipient
  • Patients under cytotoxic chemotherapy
  • Possible in patients on chronic inhaled corticosteroids

Clinical presentation

  • Odynophagia with dysphagia
  • May or may not have oral thrush

Diagnosis

Diagnosis is done by upper endoscopy.

  • White pseudomembrane or plaque lesions
  • Biopsy: yeasts and hyphae in mucosal cells
  • Culture shows Candida
Epigastric Distress Caused by Esophageal Candidiasis

Esophagogastroduodenoscopy illustrates diffuse white lesions in the esophagus characteristic of Candida esophagitis.

Image: “Epigastric Distress Caused by Esophageal Candidiasis” by Chen KH, Weng MT, Chou YH, Lu YF, Hsieh CH. License: CC BY 4.0

Management

  • Candida: oral fluconazole (nystatin for concurrent oral thrush)
  • With HIV/AIDS: antiretroviral therapy

Eosinophilic Esophagitis

Etiology

  • Allergic disorder associated with:
    • Antigen sensitization through foods or aeroallergens
    • Eosinophilia and esophageal dysfunction
  • Note: Eosinophils are not normally found in the esophagus.

Risk factors

  • Asthma
  • Atopy
  • Allergies

Epidemiology

  • Men > women
  • Common age of presentation: 20–30 years
  • Caucasians are more affected.

Pathophysiology

  • Eosinophils are recruited on exposure to inhaled or congested allergens.
  • Eosinophilic infiltration occurs → eosinophils release interleukins → inflammatory response

Clinical presentation

  • Dysphagia (to solid foods)
  • Food impaction
  • Odynophagia

Diagnosis

Diagnosis is done by upper endoscopy.

  • Mucosal rings in the esophagus
  • Biopsy showing eosinophils (> 15/HPF (high-power field)) 
  • Other features:
    • Esophageal eosinophilia persists even with proton pump inhibitor (PPI) intake.
    • Normal pH monitoring
Eosinophilic esophagitis

Images of eosinophilic esophagitis:
A. Esophagram in a patient with history of recurrent food impactions and dysphagia shows multiple esophageal rings (white arrow), giving the appearance of a corrugated or ringed esophagus, and mucosal irregularity (black arrow).
B. Endoscopy shows multiple transverse rings (arrows) and mucosal furrowing (arrowhead).

Image: “Eosinophilic esophagitis” by Al-Hussaini A, AboZeid A, Hai A. License: CC BY 4.0

Management

  • Referral to an allergist for guidance (dietary therapy)
  • Avoid known food allergens.
  • Medication therapy:
    • Topical glucocorticoids (e.g., swallowed fluticasone)
    • Systemic glucocorticoids if with significant dysphagia, weight loss, dehydration
    • PPI for reflux symptoms

Corrosive Esophagitis

Etiology

  • Alkali: 
    • Drain cleaners, household cleaning products, batteries, bleaches
    • Viscous, tasteless, colorless
  • Acids: 
    • Battery fluid, toilet bowl cleaners, metal-cleaning liquids, anti-rust solutions
    • Unpleasant taste, malodorous

Risk factors

  • Intentional (suicidality, underlying psychiatric illness)
  • Accidental (usually in children)

Pathophysiology

  • Alkali-induced injury:
    • Rapid damage, affecting esophagus more than the stomach
    • Large amounts, however, result in gastric injury.
    • Process: liquefactive necrosis in the esophagus
  • Acid-induced injury:
    • Pain on contact with the oropharynx limits the amount ingested.
    • More oropharyngeal and airway damage than with alkali solutions
    • Acid passes down faster, causing more stomach damage.
    • Process: superficial coagulation necrosis in the esophagus

Complications of severe damage

  • Perforation
  • Bleeding
  • Mediastinitis
  • Obstruction
  • Strictures
  • Fistulas
  • Laryngeal and tracheobronchial damage from aspiration
  • Increased risk for squamous cell cancer (SCC) of the esophagus

Clinical presentation

  • Oropharyngeal, retrosternal, or epigastric pain
  • Odynophagia and/or dysphagia
  • Hypersalivation
  • Stridor or wheezing from burning of the larynx
  • Dyspnea
  • Nausea/vomiting
  • Severe retrosternal pain (perforation and mediastinitis)
  • Abdominal tenderness and rigidity (perforation and peritonitis)

Diagnosis

  • History: Note type and amount of ingested agent.
  • X-rays:
    • Chest: check for pneumomediastinum, aspiration pneumonia, foreign body (e.g., battery)
    • Abdominal: check for pneumoperitoneum, foreign body 
  • Computed tomography (CT) scan: checks depth of necrosis and helps assess need for emergency surgery
  • Upper endoscopy:
    • Within 24 hours if without contraindications 
    • Contraindicated in hemodynamic instability, gastrointestinal perforation
Pyloric stenosis Esophagitis

Upper endoscopy finding in a child with alkali ingestion: Pyloric stenosis developed 2 months after injury.

Image: “Pyloric stenosis after 2 months” by Dehghani SM, Aldaghi M, Javaherizadeh H. License: CC BY 3.0

Classification of injury

  • 1st-degree injury: superficial mucosa affected; erythema, edema, hemorrhage, with healing expected
  • 2nd-degree injury: ulcers, exudates affect up to submucosal layer; scarring and strictures possible
  • 3rd-degree injury: transmural in-depth, with deep ulcers and perforation of the wall

Management

  • Airway protection; assess need for intubation
  • Fluid resuscitation
  • NPO (nothing by mouth)
  • No nasogastric insertion, no emetics
  • PPIs
  • Antibiotics for suspected perforation
  • Evaluate for surgical indications
  • Surveillance: upper endoscopy 15–20 years later to screen for SCC

Reflux Esophagitis

Reflux esophagitis is also known as gastroesophageal reflux disease (GERD).

Etiology and pathophysiology

  • Retrograde flow of stomach acid into the esophagus due to transient relaxation of the lower esophageal sphincter (LES) 
  • Most episodes of relaxation are triggered by gastric distention.
  • Some have incompetent LES.
  • Toxic substances (gastric acid, pepsin, bile salts) cause damage to the distal esophageal mucosa.

Risk factors

  • Smoking
  • Alcohol consumption
  • Obesity
  • Hiatal hernia
  • Stress
  • Scleroderma
  • Zollinger-Ellison syndrome causing increased acid secretion

Clinical presentation

  • Retrosternal “heartburn” or pyrosis
    • Worsens when postprandial or lying down
    • May cause awakening from sleep
    • May be exacerbated by emotional stress
  • Regurgitation
  • Hoarseness
  • “Brackish” taste in the mouth
  • Globus sensation
  • Chronic, non-productive cough

Complications

  • Erosive esophagitis
  • Barrett’s esophagus (at risk for adenocarcinoma)
  • Esophageal stricture

Diagnosis

  • Clinical (classic signs of heartburn and regurgitation)
  • Confirmed with esophageal pH monitoring if:
    • With unsatisfactory treatment
    • With atypical symptoms
    • Antireflux surgery being considered
  • Upper endoscopy is performed if with:
    • Dysphagia
    • Unexplained weight loss
    • Anemia or evidence of gastrointestinal bleeding
    • Refractory symptoms
    • New-onset GERD > 60 years
    • Odynophagia
    • High risk for Barrett’s esophagus
    • 1st-degree relative with gastrointestinal cancer
Reflux esophagitis

Reflux esophagitis in upper endoscopy:
A: high-definition image of esophageal changes in GERD
B: tone-enhancement image of GERD

Image: “Reflux esophagitis” by Netinatsunton N, Sottisuporn J, Attasaranya S, Witeerungrot T, Chamroonkul N, Jongboonyanuparp T, Geater A, Ovartlarnporn B. License: CC BY 4.0

Management

  • Lifestyle modification:
    • Weight loss 
    • Elevation of the head of the bed
    • Elimination of dietary triggers
    • Smoking/alcohol cessation
  • Medication therapy: PPIs
  • Surgical options include fundoplication, which is indicated for refractory symptoms.

References

  1. Azer, S., Reddivari, A. (2020). Reflux esophagitis. Retrieved Nov 9, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK554462
  2. Bonnis, P., Kotton, C., Hirsch, M., Mitty, J. (2020). Herpes simplex virus infection of the esophagus. UpToDate. Retrieved Nov 8, 2020, from https://www.uptodate.com/contents/herpes-simplex-virus-infection-of-the-esophagus
  3. Castell, D., Lamont, J., Grover, S. (2020). Medication-induced esophagitis. UpToDate. Retrieved 8 Nov 2020, from https://www.uptodate.com/contents/medication-induced-esophagitis
  4. De Lusong, M., Timbol, A., Tuazon, D. (2017). Management of esophageal caustic injury. World Journal of Gastrointestinal Pharmacology and Therapeutics 6; 8(2): 90–98.
  5. Greenberger, N.J. (2016). Eosinophilic esophagitis. Greenberger N.J., Blumberg R.S., Burakoff, R. (Eds.) Current Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 3rd ed. McGraw-Hill.
  6. Jacobson, M., Bartlett, J., Mitty, J. (2019). AIDS-related cytomegalovirus gastrointestinal disease. UpToDate. Retrieved Nov 8, 2020 from https://www.uptodate.com/contents/aids-related-cytomegalovirus-gastrointestinal-disease
  7. Kardon, E., Vearrier, D. (2018). Caustic ingestions. Medscape. Retrieved 8 Nov 2020, from https://emedicine.medscape.com/article/813772-overview
  8. McQuaid K.R. (2021). Caustic esophageal injury. Papadakis M.A., McPhee S.J., Rabow M.W. (Eds.) Current Medical Diagnosis & Treatment 2021. McGraw-Hill.
  9. McQuaid K.R. (2021). Gastroesophageal reflux disease. Papadakis, M.A., McPhee S.J., Rabow M.W. (Eds.) Current Medical Diagnosis & Treatment 2021. McGraw-Hill.
  10. Triadafilopoulos, G., Saltzman, J., Grover, S., Chen, W. (2019). Caustic esophageal injury in adults. UpToDate. Retrieved Nov 8, 2020 from https://www.uptodate.com/contents/caustic-esophageal-injury-in-adults

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