Reflux esophagitis / gastroesophageal reflux disease

Topic Completed: 1 October 2012

Minor changes: 27 September 2021

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PubMed Search: Reflux esophagitis[TI] OR gastroesophageal reflux disease[TI] pathology free full text[sb]

Elliot Weisenberg, M.D.
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Cite this page: Weisenberg E. Reflux esophagitis / gastroesophageal reflux disease. website. Accessed October 15th, 2021.
Definition / general
  • Most common cause of esophagitis
  • Due to reflux of gastric or duodenal contents into lower esophagus
  • Esophageal squamous epithelium is prone to injury from acid
  • May be erosive or nonerosive (Clin Gastroenterol Hepatol 2007;5:690)
  • Long term consequences are bleeding (almost never massive), stricture, Barrett esophagus with possible Barrett ulcer
  • Reports of incidence vary from 3 - 40% in US; higher incidence in northern Iran and China, usually mild or moderate disease
  • Usually adults over age 40, occasionally children
  • Transient reflux is normal, especially postprandial but usually asymptomatic; when threshold exceeded, GERD occurs
  • Chronic exposure to gastric juices impairs reparative capacity of esophageal mucosa; gastric acid injury to mucosa is critical to pathophysiology (Med Clin North Am 2005;89:219); bile reflux may also contribute (J Pediatr Gastroenterol Nutr 2003;36:266)
  • Due to decreased efficiency of esophageal antireflux mechanisms, especially lower esophageal tone, the primary barrier to reflux
  • Increased risk with alcohol and other central nervous system depressants (clomipramine, Am J Gastroenterol 2007;102:1870)
  • Other risk factors are delayed gastric emptying, hypothyroidism, nasogastric tube, pregnancy, sliding hiatal hernia, systemic sclerosing disorders, tobacco
Clinical features
  • Symptoms: heartburn, dysphagia; severity of symptoms is NOT related to histology (Dig Dis Sci 2002;47:2565); pain may be mistaken for myocardial infarction
  • Endoscopy: linear ulcers at distal esophagus, often with exudate; also erythema or edema; normal in 50 - 60% of symptomatic patients - thus biopsy required if clinically suggestive of reflux esophagitis even if normal endoscopy
  • Clinical (heartburn, regurgitation), intraesophageal pH monitoring to detect acid, Bernstein acid infusion test to assess mucosal sensitivity to acid, endoscopic and histologic examination (multiple biopsies since changes are nonspecific, Arch Pathol Lab Med 2005;129:159); methods may not correlate and no "gold standard" exists for diagnosis
  • Motility promoting drugs, H2 receptor antagonists, proton pump inhibitors, surgery to reduce hiatal hernia
Gross description
  • Severe cases have hyperemic mucosa with focal hemorrhage
Microscopic (histologic) description
  • No consensus on mimimal criteria to diagnosis GERD
  • In very mild disease hyperemia may be only finding, up to 1/3 of patients with chronic GERD symptoms have normal endoscopic findings
  • Inflammatory cells in epithelial layer (eosinophils, neutrophils, excess T cells); basal cell hyperplasia exceeding 15 - 20% of epithelial thickness, elongation of lamina propria papillae into upper 1/3 of epithelium; ballooned squamous cells in 65% (resemble glycogenic acanthosis but PAS negative and positive for immunoglobulin or albumin, Mod Pathol 1988;1:175), vascular dilatation in 60% (usually at superficial papillae, also associated with varices), also multinucleated squamous epithelial giant cells simulating viral cytopathic effect (Am J Surg Pathol 1998;22:93)
  • No interstitial cells of Cajal at GE junction (Med Sci Monit 2005;11:BR452)
  • Eosinophils - seen early in 30% but:
    1. Uncommon in infants (J Pediatr Gastroenterol Nutr 2007;44:27)
    2. Present in 52% of adults (Am J Surg Pathol 1984;8:899) - correlates best with endoscopic findings
    3. Difficult to identify with Bouin or Hollande fixative
    4. Occasional eosinophils are also present in normal lamina propria and in non-GERD esophagitis
    5. Rarely large numbers mimic eosinophilic esophagitis (Am J Gastroenterol 2006;101:1666)
    6. Report of rare eosinophils in 1/3 of normal adults (Am J Clin Pathol 1987;87:43) so not a reliable diagnostic criterion but some believe rare eosinophils in normal subjects represent subclinical disease and will diagnose GERD with rare eosinophils in appropriate clinical context
    7. Universal agreement that eosinophils not normally present in children
  • Neutrophils: present in 15%; indicates more severe injury including ulceration and erosion; search for fungi if prominent neutrophils or purulent exudate
  • Lymphocytes: normal component of squamous mucosa (T cells), no diagnostic significance
  • Cardiac mucosa at GE junction: GERD causes H. pylori like changes with neutrophils, plasma cell or eosinophilic infiltrates
Microscopic (histologic) images

Images hosted on other servers:

Thin basal zone layer, papillae
< 50% epithelial thickness

Elongated papillae

Moderate basal cell hyperplasia

Differential diagnosis
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