Nonsteroidal Anti-Inflammatory Drug Enteropathy

Nonsteroidal anti-inflammatory drug (NSAID) enteropathy is small bowel injury caused by NSAIDs, including low dose aspirin. It ranges from asymptomatic erosions to ulcers, bleeding, protein loss and diaphragm like strictures.

Capsule endoscopy shows mucosal breaks in 50% to 70% of people taking NSAIDs for over 2 weeks. Clinically important bleeding or anaemia is less frequent, and strictures are rare but typical.

Risk factors are age over 65 years, higher doses, long duration, combination with aspirin or anticoagulants, previous gastrointestinal bleeding and non-selective agents. Selective cyclo-oxygenase-2 inhibitors cause less small bowel injury.

Pathophysiology.

NSAIDs uncouple mitochondrial oxidative phosphorylation and increase mucosal permeability, which allows bile acids, bacteria and luminal toxins to cause inflammation. Cyclo-oxygenase-1 inhibition then reduces prostaglandin mediated mucosal protection and blood flow.

Proton pump inhibitors do not protect the small bowel and may worsen injury through changes in the microbiota.

Iron deficiency anaemia, occult or overt bleeding, melaena, hypoalbuminaemia with oedema, diarrhoea, abdominal pain, and subacute obstruction from strictures.

Red flags.

• Haemodynamic instability or haemoglobin fall over 20 g/L.
• Colicky pain with vomiting (stricture).
• Peritonitis (perforation).

Exclude upper and lower sources with gastroscopy and colonoscopy. Capsule endoscopy is the main test and shows erosions, ulcers and strictures; use a patency capsule or cross-sectional enterography first if a stricture is suspected. Faecal calprotectin is often raised. Test haemoglobin, ferritin and albumin. Balloon assisted enteroscopy allows biopsy and treatment.

Differential diagnosis.

• Crohn disease.
• Small bowel tumour or lymphoma.
• Angiodysplasia.
• Coeliac disease.
• Ischaemic or radiation enteropathy.
• Infection (tuberculosis, cytomegalovirus).

Stop the NSAID if possible and substitute paracetamol, topical agents or a selective cyclo-oxygenase-2 inhibitor at the lowest dose when an NSAID is essential. Healing and normal capsule findings follow in weeks to months.

• Paracetamol: 1 g orally every 6 hours as needed; maximum 4 g daily; monitor liver enzymes in long courses; reduce to 2 to 3 g daily if weight is under 50 kg, in malnutrition, chronic alcohol use or hepatic impairment.
• Misoprostol (selected patients, limited evidence): 200 microgram orally four times daily with meals; 8 to 12 weeks; maximum 800 microgram daily; monitor diarrhoea and abdominal pain; contraindicated in pregnancy; reduce to 100 microgram four times daily if not tolerated; avoid in inflammatory bowel disease.
• Ferrous sulphate: 200 mg (65 mg elemental iron) orally once daily or on alternate days; until ferritin is over 100 microgram/L plus 3 months; maximum 200 mg three times daily; monitor haemoglobin at 2 to 4 weeks and ferritin; reduce frequency for gastrointestinal intolerance.
• Ferric carboxymaltose (intolerance or poor response): 15 mg/kg IV, up to 1,000 mg in a single dose, repeated after 7 days if needed; maximum 1,000 mg in a single dose and 1,000 mg weekly; monitor phosphate and blood pressure; avoid in iron overload.

Transfuse at haemoglobin 70 g/L (80 g/L with cardiovascular disease). Strictures need balloon assisted enteroscopic dilation or surgical resection.

Monitoring. Haemoglobin and ferritin every 3 months until stable; repeat capsule endoscopy at 3 months when the drug must continue.

Referral and escalation. Gastroenterology for obscure bleeding or strictures; surgery for obstruction or perforation.