What is reactive gastropathy?

Reactive Gastropathy

Reactive gastropathy is a histopathological pattern of chemical injury to the gastric mucosa characterized by specific epithelial and vascular changes in the absence of significant inflammation, most commonly caused by NSAIDs, aspirin, bile reflux, or alcohol. 1

Histopathological Features

The diagnosis relies on identifying a constellation of nonspecific elementary lesions that occur in varying degrees and proportions: 1

• Foveolar hyperplasia - elongation and tortuosity of gastric pits creating a characteristic serrated profile 1
• Interfoveolar smooth muscle fiber proliferation - smooth muscle extends upward between the gastric pits 1
• Epithelial damage - ranging from surface erosions to frank ulceration 1, 2
• Vascular changes - edema, capillary congestion, hemorrhage, and vascular proliferation 2
• Minimal or absent inflammatory infiltrate - this is the key distinguishing feature that differentiates it from other forms of gastritis 1, 2

The absence of significant inflammation has led some pathologists to prefer the term "gastropathy" over "gastritis," as the "-itis" suffix implies inflammation that is characteristically lacking in this condition. 2

Common Etiologies

NSAIDs and aspirin are the most frequent causes, producing gastropathy through cyclooxygenase blockade that reduces cytoprotective gastric prostaglandins. 3 This mechanism differs fundamentally from acid-mediated peptic ulcer disease. 3

Bile reflux from duodenogastric reflux represents another major cause, with bile acids and pancreatic secretions producing similar histological patterns. 1, 2

Other causes include alcohol, chemotherapeutic agents, and various exogenous noxious substances. 2

Clinical Significance and Epidemiology

Reactive gastropathy is the second most common diagnosis made on gastric biopsies, affecting 15.6% of patients in large database studies. 4, 5

The condition shows a striking age-dependent increase, rising from 2.0% in the first decade of life to over 20% in octogenarians. 5

Important clinical pitfall: Symptoms do not correlate reliably with the presence or severity of lesions - silent gastropathy is common, and patients may present with bleeding or other complications without preceding dyspeptic symptoms. 3 This asynchrony between symptoms and lesional disease makes endoscopic surveillance important in high-risk populations rather than relying on symptom reporting alone. 3

Associated Conditions

Reactive gastropathy shows significant associations with inflammatory conditions throughout the gastrointestinal tract: 5

• Barrett's esophagus (OR 1.21) 5
• Duodenitis (OR 1.36) 5
• Duodenal intraepithelial lymphocytosis (OR 1.25) 5
• Active ileitis (OR 1.88) 5
• Focal active colitis (OR 1.57) 5
• Collagenous colitis (OR 1.50) 5

These associations support the hypothesis that reactive gastropathy shares common etiological factors (particularly NSAID use) with other inflammatory conditions of the digestive tract. 5

Molecular Alterations

Mucin expression is frequently modified in reactive gastropathy, with patterns distinct from H. pylori gastritis: 4

• Loss of MUC1 (membrane mucin involved in cell adhesion and polarity) occurs in 67% of cases, which may contribute to the development of the serrated foveolar profile 4
• Aberrant MUC5AC expression in pyloric glands occurs in 81% of cases 4
• Aberrant MUC6 expression in upper foveolar epithelium occurs in 14% of cases, with more extensive changes correlating with severe gastropathy 4

These mucin alterations differ from H. pylori gastritis (which shows increased MUC6 and reduced MUC5AC), highlighting mechanistic differences between chemical injury and infectious gastritis. 4

Diagnostic Spectrum and Limitations

The diagnosis exists on a spectrum of certainty that is never absolute, as each histological feature can occur in other conditions. 1 The diagnosis requires integrating multiple features rather than relying on any single finding. 1

Mixed patterns commonly occur, with reactive gastropathy coexisting with H. pylori infection or other forms of gastritis, requiring careful evaluation to identify all contributing factors. 2

Clinical Management Implications

While correlation between histological findings and clinical manifestations (particularly bleeding risk) remains incompletely documented, reporting suspected chemical gastropathy helps clinicians identify patients who may benefit from medication changes, dose reduction, or discontinuation of offending agents. 1

For NSAID-related gastropathy, long-term studies demonstrate that normal gastric adaptation mechanisms eventually fatigue with sustained anti-inflammatory therapy, leading to persistent gastropathy with increased bleeding risk and mortality. 3 This contrasts with short-term studies in healthy volunteers showing mucosal resilience and healing. 3