Elsevier

Mayo Clinic Proceedings

Volume 70, Issue 1, February 1995, Pages 55-61
Mayo Clinic Proceedings

Case Report
Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy: Case Discussion and Review of the Literature

https://doi.org/10.4065/70.1.55Get rights and content

The adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the upper gastrointestinal tract are well described. Evidence also shows that NSAIDs can be harmful to the small intestine. The use of NSAIDs has been associated with small intestinal strictures, ulcerations, perforations, diarrhea, and villous atrophy. Herein we present a case of NSAID-induced enteropathy with multiple diaphragmlike strictures that involved the distal 3S em of ileum and review the literature of other cases of NSAID-induced enteropathy in which biopsy specimens were obtained for histologic analysis to rule out other causes. The prevalence of NSAID-induced enteropathy is unknown. Diagnosis can be made by endoscopy or at abdominal exploration. The role of radionuclide scans for diagnosis remains unclear. The pathogenesis is likely multifactorial. Mucosal diaphragms may be specific for NSAID-related disease. Treatment options for NSAID-induced enteropathy are discussed.

Section snippets

REPORT OF CASE

A 37-year-old woman was hospitalized because of nausea, vomiting, large-volume diarrhea, and hypokalemia. Three years before the current admission, she underwent antrectomy, vagotomy, and gastroduodenostomy with a Billroth I anastomosis because of a nonhealing gastric ulcer. Two years previously, malaise, diarrhea, and persistent iron deficiency anemia developed; at that time, the hemoglobin concentration was 6.0 g/dL, and the ferritin level was 3 μglL. She had been taking 800 mg of ibuprofen

LITERATURE REVIEW OF NSAID-INDUCED ENTEROPATHY

Twenty-five patients with NSAID-induced enteropathy have been described in the literature9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 (Table 1). These patients, whose ages ranged from 40 to 78 years (mean, 66), were taking many types of NSAIDs for inflammatory conditions such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis. The clinical manifestations were GI bleeding, obstruction, or diarrhea. Of the 21 patients in whom gender was reported, 14 were

PREVALENCE

NSAIDs are among the most widely prescribed medications in the industrialized world; more than 100 million NSAID prescriptions are written annually by US physicians.32 Long-term NSAID therapy is common for patients with either rheumatoid arthritis or osteoarthritis.

Bjarnason and associates8 examined 97 patients with rheumatoid arthritis and osteoarthritis who had been taking NSAIDs for more than 2 months and determined that two-thirds of these patients had intestinal inflammation, as

DIAGNOSIS

In up to 50% of patients who take NSAIDs and have iron deficiency anemia, no identifiable source of blood loss can be detected by gastroscopy and colonoscopy.34 A small intestinal barium study may show strictures and areas of dilatation, factors that suggest focal obstruction even when a precise site is not evident. Small bowel strictures or diaphragms may be overlooked radiographically; thus, radiologists should be alerted to the possibility of these lesions before the study is performed.17

MECHANISM OF NSAID-INDUCED INJURY TO SMALL INTESTINE

Potential mechanisms of NSAID-induced injury to the small intestine are as follows.

  • 1.

    NSAIDs (like aspirin) inhibit cyclooxygenase and thereby inhibit formation of prostaglandins and divert arachidonic acid metabolism to the lipoxygenase pathway.41 Prostaglandin inhibition by NSAIDs may predispose a patient to gastric ulcers and erosions.42 Whether prostaglandins are necessary to protect the small intestinal mucosa is unknown. Subcutaneous administration of indomethacin caused intestinal

TREATMENT

Data on the natural history of NSAID-induced enteropathy are scant; however, this situation may change with increasing awareness by clinicians. Recognizing the cause of the enteropathy and discontinuing use of the offending agent are the mainstay of treatment. These two factors have been reported to be successful in patients diagnosed with villous atrophy due to mefenamic acid and sulindac.16, 25 Nonetheless, no data are available on the natural course of small intestinal ulcerations and

CONCLUSION

Virtually all classes of NSAIDs have been implicated in the development of enteropathy with erosions, ulcerations, blood loss, villous atrophy, and strictures. The pathogenesis is unclear but likely multifactorial. In patients taking NSAIDs who have iron deficiency and normal findings on assessment of the upper and lower GI tract, discontinuation of the NSAID therapy must be considered. Because of their lack of availability and expense, radionuclide laboratory tests have limited use. Inasmuch

ACKNOWLEDGMENTS

We gratefully acknowledge Dr. Piet C. de Groen for providing the endoscopic photograph of the NSAID-related diaphragm.

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