NSAID-Induced Gastritis

Gastric mucosal injury (erythema, erosions, petechiae, ulcers) caused by non-steroidal anti-inflammatory drugs, including aspirin, mainly through inhibition of cyclooxygenase 1 and prostaglandin synthesis, with additional direct topical injury.

• Endoscopic erosions occur in 30 to 50% of long-term users, ulcers in about 15 to 25%, and serious bleeding or perforation in about 1 to 2% per year; NSAIDs account for about 25 to 40% of peptic ulcer bleeding.
• Risk factors: age 65 years or more, previous ulcer or bleeding, concurrent anticoagulant, antiplatelet (including dual antiplatelet therapy), corticosteroid or selective serotonin reuptake inhibitor use, high dose or multiple NSAIDs, H. pylori infection, heavy alcohol use, smoking, and serious illness.
• Mechanism: loss of prostaglandin-driven mucus, bicarbonate and mucosal blood flow, with epithelial damage by weak acid NSAIDs, neutrophil adhesion and microvascular injury.
• Symptoms correlate poorly with injury; many serious complications occur without warning.

Dyspepsia, epigastric pain, nausea, bloating, reflux; about half of those with erosions and ulcers are asymptomatic.

• Haematemesis, melaena, iron deficiency anaemia, collapse from bleeding; sudden severe abdominal pain from perforation.
• Examination: epigastric tenderness, pallor, tachycardia; peritonism in perforation.
• Differential diagnosis: H. pylori gastritis, peptic ulcer, functional dyspepsia, reflux, pancreatitis, biliary disease, gastric cancer, small bowel injury from NSAIDs.
• Complications: bleeding, perforation, gastric outlet obstruction, iron deficiency anaemia, NSAID related small bowel and colonic injury, and renal injury and cardiovascular events that accompany NSAID use.

Drug history including over-the-counter, herbal and traditional medicines (many contain NSAIDs or corticosteroids), and low-dose aspirin.

• Endoscopy for dyspepsia with alarm features, bleeding, age 55 years or more with new symptoms, or anaemia; biopsies for H. pylori and exclusion of malignancy (for gastric ulcers).
• Helicobacter pylori test (urea breath test or stool antigen after 2 weeks off proton pump inhibitors, or histology) in all NSAID users with dyspepsia or ulcer, and before starting long-term NSAIDs in high-risk patients.
• Full blood count, ferritin, urea, creatinine, liver tests, and clotting profile.

Stop the NSAID (or reduce to the lowest dose for the shortest time) and replace with paracetamol 1 g four times daily, topical NSAID (diclofenac gel 1% 2 to 4 g four times daily), physiotherapy, or tramadol 50 mg every 6 hours for short periods if needed.

• Treat the injury: omeprazole 20 to 40 mg daily for 4 to 8 weeks (40 mg daily for ulcer), taken 30 minutes before breakfast.
• Bleeding: omeprazole 80 mg IV bolus then 8 mg/hour for 72 hours, resuscitation, endoscopic therapy within 24 hours, transfuse at 70 g/L (80 g/L in cardiovascular disease).
• Helicobacter pylori eradication when positive for 14 days: omeprazole 20 mg twice daily, amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily; or omeprazole 20 mg twice daily, bismuth subsalicylate 524 mg four times daily, tetracycline 500 mg four times daily and metronidazole 500 mg three to four times daily.
• When an NSAID must continue (for example inflammatory arthritis), use gastroprotection:
  • Omeprazole 20 mg daily (or esomeprazole 20 mg, pantoprazole 40 mg, lansoprazole 15 to 30 mg daily): the first choice.
  • Misoprostol 200 micrograms two to four times daily with food (avoid in pregnancy and women who may conceive; diarrhoea and abdominal pain limit use).
  • Famotidine 40 mg twice daily reduces duodenal ulcers but is less effective for gastric ulcers.
  • High-risk patients: a selective cyclooxygenase 2 inhibitor (celecoxib 100 to 200 mg twice daily) plus omeprazole 20 mg daily.
• Low-dose aspirin 75 to 100 mg daily: continue for secondary prevention, with omeprazole 20 mg daily; after aspirin-related bleeding, restart aspirin within 1 to 7 days once haemostasis is secure; with clopidogrel use pantoprazole 40 mg daily (avoid omeprazole and esomeprazole).
• Anticoagulant plus NSAID: avoid NSAIDs when possible; if essential, add a proton pump inhibitor.
• Monitor and manage anaemia: ferrous sulfate 200 mg once daily or on alternate days, or ferric carboxymaltose 1000 mg IV once if intolerant.
• Special groups: children (ibuprofen 5 to 10 mg/kg every 6 to 8 hours with food, avoid aspirin in viral illness; omeprazole 1 mg/kg daily if gastritis); pregnancy (avoid NSAIDs, especially from 20 weeks; use paracetamol; alginates or famotidine for symptoms); elderly (avoid NSAIDs, use paracetamol or topical agents, add a proton pump inhibitor); renal impairment (avoid NSAIDs; reduce famotidine dose); heart failure and cardiovascular disease (avoid NSAIDs, celecoxib has less gastric but not less cardiovascular risk); arthritis (paracetamol, biologics or disease-modifying agents rather than long-term NSAIDs).
• Red flags: haematemesis or melaena, collapse, severe abdominal pain with rigidity, vomiting from outlet obstruction, weight loss, anaemia, anticoagulant use.
• Follow-up: review at 4 to 8 weeks with repeat endoscopy for gastric ulcer, test of cure for H. pylori at 4 to 8 weeks, haemoglobin and ferritin at 3 months, and an annual review of long-term NSAID or aspirin users to confirm gastroprotection.