NSAID Associated Gastritis

3 Interesting Facts of NSAID Associated Gastritis

Histologically, gastritis refers to inflammation in the stomach. Endoscopically, gastritis refers to a number of abnormal features such as erythema, erosions, and subepithelial hemorrhages. Gastritis can also be subdivided into erosive, nonerosive, and specific types of gastritis with distinctive features both endoscopically and histologically.
•Most nonsteroidal antiinflammatory drugs (NSAIDs) currently available can be broadly classified as salicylates (e.g., aspirin), acetic acid derivatives (e.g., indomethacin), propionic acid derivatives (e.g., ibuprofen), and COX-2 inhibitors.
•The utility of all NSAIDs is limited by concerns of adverse events, including effects on the gastric mucosa (hemorrhagic gastric erosions in the corpus and antrum of the stomach), renal function, platelet reactivity, bone and tissue healing, cardiovascular risk, and interactions with other patient medications.

How common is NSAID Associated Gastritis – Epidemiology & Demographics

•The mortality rate attributed to NSAID-related GI toxic effects is 0.22% per year, with an annual relative risk of 4.21.
•NSAIDs are used on a regular basis by approximately 11% of the U.S. population. Regular use of NSAIDs increases the odds of GI bleeding up to five- to six-fold.
•Erosive and hemorrhagic gastritis is most commonly seen in patients taking NSAIDs, in alcoholics, and in critically ill patients (usually on ventilator support).

What causes NSAID Associated Gastritis?

Etiology & Risk Factors

Risk factors identified for the development of NSAID-induced ulcers include advanced age; history of ulcer; concomitant use of corticosteroids; higher doses of NSAIDs, including the use of more than one NSAID; concomitant administration of anticoagulants; serious systemic disorder; cigarette smoking; consumption of alcohol; and concomitant infection with Helicobacter pylori.

Pathophysiology

•NSAIDs cause ulceration in the stomach by their topical irritant effect on the epithelium and their ability to suppress PG synthesis.
•COX isoforms COX-1 and COX-2 are responsible for the synthesis of prostaglandins. COX-1 is expressed in the stomach and helps maintain the integrity of gastric epithelium and the mucous barrier. COX-2 is not expressed in the healthy stomach but is rapidly expressed in response to the cytokines generated by inflammatory processes. Conventional NSAIDs such as ibuprofen inhibit the COX-1 and the COX-2 isoenzymes more or less equally. COX-1 inhibition reduces prostaglandin synthesis, which leads to a reduction in mucosal defense.
•The ability of NSAIDs to cause gastric damage correlates with the time and dose dependency for PG suppression in the stomach. Inhibition of PG synthesis leads to a reduction in the ability of the gastric mucosa to defend itself against luminal irritants; bicarbonate secretions, blood flow, and epithelial cell turnover are influenced by PGs.
•Another feature of NSAIDs that probably contributes to gastric bleeding from preexisting ulcers is their effect on platelet aggregation through the suppression of thromboxane synthesis. Mediators in the pathway whereby decreased PG levels cause gastric irritation and damage have been extensively studied. These mediators include leukotrienes, tumor necrosis factor-α (TNF-α), and neutrophil adherence substances.
•Neutrophil adherence to the gastric microcirculation plays a critical role in initiating NSAID injury. Neutrophil adherence liberates oxygen free radicals, releases proteases, and obstructs capillary blood flow. Inhibition of neutrophil adherence has been shown to reduce NSAID-induced damage.

Clinical Manifestations

Presenting Signs & Symptoms of NSAID Associated Gastritis

•Patients with NSAID-induce gastritis may include epigastric pain, abdominal tenderness, nausea [with or without vomiting]).
•Hematemesis (“coffee grounds” emesis) can also occur.
•Absence of epigastric discomfort does not rule out gastritis.

How is NSAID Associated Gastritis diagnosed?

•Rule out other causes of gastritis (e.g., H. Pylori, alcohol, corticosteroids) with history and laboratory evaluation.
•Upper endoscopy.

Diagnostic Criteria

•The endoscopic appearance of the gastric mucosa of patients who exhibit reactive gastropathy demonstrates a spectrum of reddish streaks, subepithelial hemorrhages, erosions, and even acute ulcers. Acute erosions and ulcers are frequently multiple, and the base of these lesions often stains dark brown owing to exposure of hemoglobin to gastric acid. Grossly, most gastric erosions and acute gastric ulcers appear as well-defined hemorrhagic lesions 1 to 2 mm in diameter.

History & Physical Examination

•Most patients are asymptomatic.
•In symptomatic patients, epigastric pain/discomfort is common and is typically improved with food or antacids and worsened by fasting.
•Physical examination is often unremarkable.
•Patient may have epigastric tenderness, tachycardia, pallor, hypotension (from acute or chronic blood loss), nausea and vomiting, and hematemesis or melena (with significant bleeding).

Diagnostic Tests

•H. pylori testing by urea breath test, stool antigen test (H. pylori stool antigen), endoscopic biopsy, or specific antibody test to rule out H. pylori–induced gastritis
•CBC, ALT, AST, electrolytes, BUN, creatinine, lipase

Diagnostic Procedures

•Endoscopy with biopsy

Differential Diagnosis

•Gastritis from other causes (alcohol, stress [critically ill patients usually on mechanical respiration], hepatic or renal failure, multiorgan failure, H. pylori infection, bile reflux, pancreatic enzyme reflux)
•Peptic ulcer disease
•Gastroesophageal reflux disease
•Gastric lymphoma or carcinoma
•Pancreatitis
•Gastroparesis

How is NSAID Associated Gastritis treated?

Diagnostic workup includes a comprehensive history, physical examination, and endoscopy with biopsy.

First-Line Treatment

•Discontinue NSAIDs.
•For all patients, nonpharmacologic pain management methods (e.g., lifestyle changes) should be initiated in place of NSAIDs. Topical agents should be considered. Acetaminophen can be used safely for many conditions.

Pharmacologic Therapy

Proton pump inhibitors (PPIs) or H₂ receptor blockers (H2RB)

Nonpharmacologic & Supportive Care

•Avoidance of other mucosal irritants such as alcohol
•Lifestyle modifications with avoidance of tobacco and foods that trigger symptoms

Follow-Up

Complications

GI bleeding, perforation

Referral

To gastroenterologist for endoscopy

Admission Criteria

GI bleeding with hypotension

Prevention

In patients who are at risk for NSAID-induced GI complications and require an NSAID, an initial approach would be to prescribe a COX-2 inhibitor or a traditional NSAID and proton pump inhibitor.

References

1. Birmingham B, Asokumar Buvanendran A: Nonsteroidal anti-inflammatory drugs, acetaminophen, and COX-2 inhibitors. Practical management of pain, Philadelphia, 2014, Elsevier, pp 553-568.e5. Chapter 40
2. Garcia Rodriguez L.A., Hernandez-Diaz S.: Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 2001; 12: pp. 570-576.
3. Wallace J.L., McCafferty D.M., Carter L., et al.: Tissue-selective inhibition of prostaglandin synthesis in rat by tepoxalin: anti-inflammatory without gastropathy. Gastroenterology 1993; 105: pp. 1630-1636.
4. Wallace J.L., Keenan C.M., Granger D.N.: Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Am J Physiol 1990; 259: pp. 462-467.
5. Lanza F.L.: A review of gastric ulcer and gastroduodenal injury in normal volunteers receiving aspirin and other nonsteroidal anti-inflammatory drugs. Scand J Gastroenterol 1989; 24: pp. 24-31.
6. Hawkey C.J., Hawthrone A.B., Hudson N., et al.: Separation of the impairment of hemostasis by aspirin from mucosal injury in the human stomach. Clin Sci 1991; 81: pp. 565-573.
7. Vaananen P.M., Keenan C.M., Grisham M.B., et al.: A pharmacological investigation of the role of leukotrienes in the pathogenesis of experimental NSAID gastropathy. Inflammation 1992; 16: pp. 227-240.
8. Wallace J.L., Granger D.N.: The pathogenesis of NSAID-gastropathy—are neutrophils the culprits? Trends Pharmacol Sci 1992; 13: pp. 129-131.
9. Chen T.S., Li A.F.Y., Chang F.Y.: Gastric reddish streaks in the intact stomach: endoscopic feature of reactive gastropathy. Pathol Int 2010; 60: pp. 298-304.