Reactive gastropathy

Reactive gastropathy refers to a group of endoscopic and histologic findings caused by chemical injury to the gastric mucosa ¹. The histologic picture is characterized by foveolar hyperplasia with edema, interfoveolar smooth muscle hyperplasia, erosions, and congestion of superficial capillaries in the lamina propria in the absence of significant inflammation ². These features were originally described in biopsy specimens obtained from patients who had undergone gastric surgery and were felt to be specific for bile reflux ³. It has since become apparent, however, that the constellation of histologic features seen in reactive gastropathy is a nonspecific response to chemical injury of the gastric mucosa ⁴. Their respective occurrence in a set of gastric biopsies can be placed on a spectrum of diagnostic certainty that is never absolute because each of such changes can and does occur in other conditions. Although a correlation between histological evidence of chemical gastropathy and clinical manifestations, particularly risk of bleeding, is yet to be documented, reporting the suspicion of drug-induced gastric damage may help clinicians to identify patients that might benefit from change, reduction, or discontinuation of certain medications ⁵.

Reactive gastropathy has also been referred to as chemical gastropathy, reflux gastritis, and type C gastritis ⁶. The term “chemical gastropathy” was recommended by the Updated Sydney System ⁷, because it indicates an underlying chemical injury that is not associated with infection ⁸.

At present, reactive gastropathy is usually encountered in the clinical setting of chronic nonsteroidal anti-inflammatory drug (NSAID) use. The reported prevalence of reactive gastropathy among patients taking daily NSAIDs for at least 1 month ranges from 30% to 40% ⁹.

Figure 1. Reactive gastropathy

Footnote: Antral mucosa exhibiting the features of reactive gastropathy, including ‘corkscrew‐like’ foveolar hyperplasia, a mucin depleted epithelium and bundles of hyperplastic smooth muscle arranged perpendicular to the surface.

[Source ¹⁰ ]

Reactive gastropathy causes

Reactive gastropathy most common causes:

• Ingested agents
  • Alcohol
  • Drugs
  • Aspirin / nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Iron and potassium
  • Corrosive agents
• Physical injury
  • Radiation
  • Instrumentation
  • Hepatic artery chemotherapy
• Gastrointestinal motility problems
  • Prolapse gastropathy
  • Post-gastrectomy bile reflux
  • Occasionally seen with intact stomach
• Ischemia
• Stress
• Idiopathic

The common underlying causes of reactive gastropathy include chronic bile reflux and long-term intake of nonsteroidal anti-inflammatory drugs (NSAIDs) ². Bile reflux usually occurs in patients who have undergone a Billroth 2 partial gastrectomy; it is also recognized to occur in intact stomachs in individuals with alcohol abuse, cigarette smoking, chronic respiratory disease, or duodenal ulcer, and even in healthy subjects ¹¹.

The duodenogastric reflux results in disruption of the protective mucus barrier and direct injury to the gastric mucosa, causing backflow of hydrogen ions and epithelial damage ¹². The various bile acid species differ in their capacity to cause injury to the gastric mucosa ³. The secondary (deoxycholic and lithocholic) and deconjugated bile acids are more injurious to the gastric mucosa than the primary (colic and chenodeoxycholic) and conjugated bile acids.

In situations of upper gastrointestinal (GI) stasis, as is seen after gastric surgery, bacterial overgrowth occurs within the proximal small intestine. This increase in intraluminal bacteria leads to subsequent generation of relatively increased concentrations of deconjugated and secondary bile acids within the refluxate. The increased concentration of the more toxic forms of bile acid, coupled with the decreased gastric emptying time of the refluxed bile, results in gastric mucosal injury and subsequent reactive gastropathy (chemical gastropathy).

The predominant mechanism of NSAID-induced gastric injury involves decreased synthesis of mucosal prostaglandins ¹³. Prostaglandins are derived from arachidonic acid via the cyclooxygenase (COX) pathway. Thus, inhibition of COX by NSAIDs reduces prostaglandin synthesis, thereby diminishing mucosal blood flow and decreasing mucus and bicarbonate secretion.

Furthermore, NSAIDs, being weak organic acids, can freely diffuse into the gastric epithelium. As a result of the neutral pH within the surface epithelial cells, the NSAID compound dissociates into its ionized form, contributing to direct cell injury ¹⁴.

Although it is known that NSAIDs that selectively inhibit COX-2 cause significantly fewer gastrointestinal complications than nonselective COX inhibitors do, it is still unclear whether administration of selective inhibitors results in less severe reactive gastropathy (chemical gastropathy) ¹⁵. However, most of these COX-2 inhibitors have been withdrawn from the market or have had their indications drastically limited in view of their potential serious cardiovascular side effects ¹⁶.

The epithelial injury results in excessive exfoliation of the surface epithelial cells, which gives rise to a reactive foveolar hyperplasia ¹⁷. The accompanying histamine-mediated vascular response leads to edema and hyperemia. Persistent epithelial damage may result in the release of platelet-derived growth factor (PDGF), which stimulates smooth muscle proliferation, followed by fibroblastic proliferation ¹².

The mucosal changes seen in reactive gastropathy are usually most prominent in the antrum and prepyloric region. When associated with bile reflux secondary to partial gastrectomy, the lesions develop near the surgical stoma ¹⁸, but the more proximal oxyntic mucosa may also be affected.

To date, no specific genetic predisposing factors for the development of reactive gastropathy have been identified.

Reactive gastropathy symptoms

The clinical features associated with reactive gastropathy are determined by its underlying cause.

Patients with reactive gastropathy secondary to bile reflux typically have an enterogastric anastomosis and most commonly present with continuous burning midepigastric pain that is often exacerbated by food and recumbency. Nausea, bilious vomiting, and other dyspeptic symptoms may also be present ¹⁹. Although the findings are not specific, several authors claim that weight loss and a hypochromic microcytic anemia are also associated features ³.

The most common complaint associated with NSAID-induced reactive gastropathy is mild dyspepsia. Chronic consumption of these drugs, however, can lead to the development of erosions and ulcers, increasing the risk for complications such as obstruction, perforation, and bleeding ¹⁴.

Reactive gastropathy diagnosis

The endoscopic findings of reactive gastropathy are mostly nonspecific. The mucosa may be normal or may exhibit erythema, congestion, edema, or erosions ⁸. The bile reflux may be visible ²⁰.

Reactive gastropathy diagnosis is by examination of tissue, e.g. a stomach biopsy.

Reactive gastropathy is characterized, histologically, by ²¹:

• foveolar hyperplasia with gland tortuosity and dilation,
• smooth muscle hyperplasia in the lamina propria, and
• scant or minimal inflammation, i.e. lack of large numbers of neutrophils and plasma cells.

Reactive gastropathy treatment

If long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) leads to reactive gastropathy, your doctor may recommend that you stop taking NSAIDs, take a lower dose, or take a different medicine for pain. Doctors may also recommend taking a proton pump inhibitor (PPI) and prostaglandin analogues along with NSAIDs to prevent or treat reactive gastropathy and its possible complications.

If bile reflux is causing reactive gastropathy, doctors may prescribe ursodiol, a medicine that contains bile acids and can help heal the stomach lining, or surgery to stop flow of bile into the stomach.

Reactive gastropathy prognosis

Stump carcinoma has been reported in postgastrectomy stomachs. Bile reflux is thought to play a key role in the development of dysplasia and carcinoma in the gastric remnant ²². In fact, some studies have reported improvement of preneoplastic changes after diversion of the enteric reflux ²³. Regular endoscopic surveillance starting 10 to 15 years after surgery is recommended.

With the advent of highly effective medical treatment for Helicobacter pylori infection, there has been a decline in such surgical procedures, paralleled by a reduction in the incidence of stump carcinoma ¹².

Despite the occasional development of stump carcinomas in postgastrectomy stomachs, reactive gastropathy is not a major risk factor for the development of gastric carcinoma.

References

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