Correspondence

Diarrhea Associated with Mesalamine in a Patient with Chronic Nongranulomatous Enterocolitis

N Engl J Med 1998; 338:923-925March 26, 1998

Article

To the Editor:

The use of mesalamine (5-aminosalicylic acid) for the treatment of inflammatory bowel disease seems paradoxical, since structurally similar acetylsalicylic acid and other nonsteroidal antiinflammatory drugs (NSAIDs) can cause or exacerbate intestinal inflammation and diarrhea through their effects on arachidonic acid metabolism.1 We describe a patient with inflammatory bowel disease of the small bowel and colon who had large-volume diarrhea while fasting during treatment with mesalamine, which was associated with changes in fecal eicosanoid content that mimicked effects expected with the use of NSAIDs that relieve pain.

A 57-year-old man with a 10-month history of weight loss, abdominal pain, and diarrhea was given a diagnosis of chronic nongranulomatous enterocolitis after an extensive evaluation that included biopsies of the small intestine and colon. This disease is histopathologically similar to Crohn's disease but manifests mainly with diarrhea and malabsorption.2 Initiation of complete bowel rest led to near resolution of the diarrhea; fecal weight fell from 2527 g per day while the patient was eating to 161 g per day while he was fasting. Medical treatment consisted of intravenous methylprednisolone and 4 g of oral mesalamine (Pentasa, Hoechst Marion Roussel) per day. After seven days, the patient was discharged in good condition while following this regimen, but he was readmitted one week later for severe diarrhea and volume depletion. Fecal sodium and potassium concentrations were 115 and 19 mmol per liter, respectively. Fecal weight during fasting (average, 880 g per day) decreased dramatically after the discontinuation of mesalamine, increased on rechallenge with the drug, and fell again after the drug was stopped. Radioimmunoassay was used to measure prostaglandin E₂ and leukotriene B₄ content in stools collected before, during, and after mesalamine therapy. During treatment, fecal output of prostaglandin E₂ was reduced by 45 percent, whereas output of leukotriene B₄ increased 500 percent over base-line values (Figure 1Figure 1Fecal Weight, Fecal Frequency, and Fecal Prostaglandin E₂ (PGE₂) and Leukotriene B₄ (LTB₄) Output during Fasting, and before, during, and after Mesalamine Treatment in a Patient with Chronic Nongranulomatous Enterocolitis.).

In trials of mesalamine for inflammatory bowel disease, about 5 percent of patients report diarrhea. This figure is lower than the 13 percent incidence of diarrhea associated with the use of olsalazine (a 5-aminosalicylic acid dimer linked chemically by an azo bond), which causes intestinal fluid and electrolyte secretion.3 Mesalamine may directly induce similar but less potent secretion; alternatively, the mechanism of secretory diarrhea may involve the effect of the drug on arachidonic acid metabolism. By inhibiting the enzyme cyclooxygenase and consequently decreasing prostaglandin synthesis, most NSAIDs are thought to shunt arachidonic acid into a lipoxygenase pathway producing leukotrienes and other hydroxyeicosatetraenoic acids. These substances can produce intestinal inflammation and diarrhea and are thought to mediate NSAID-induced flares of inflammatory bowel disease.1 Although mesalamine inhibits both lipoxygenase and cyclooxygenase in vitro (and should decrease the production of both leukotrienes and prostaglandins), clinical manifestations and results of fecal eicosanoid analysis in our patient suggest that this drug may stimulate leukotriene synthesis as do analgesic NSAIDs and, in turn, lead to diarrhea or intestinal inflammation (or both) in patients with inflammatory bowel disease.4,5

Kenneth D. Fine, M.D.
Harry E. Sarles, Jr., M.D.
Baylor University Medical Center, Dallas, TX 75246

Byron Cryer, M.D.
Dallas Veterans Affairs Medical Center, Dallas, TX 75216

5 References

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Citing Articles (3)

Citing Articles

1. 1

   2006. Aminosalicylates. , 138-148.
   CrossRef

2. 2

   Elizaveta Iofel, Anupama Chawla, Fredric Daum, James Markowitz. (2002) Mesalamine Intolerance Mimics Symptoms of Active Inflammatory Bowel Disease. Journal of Pediatric Gastroenterology and Nutrition 34:1, 73-76
   CrossRef

3. 3

   &NA;. (1998) Mesalazine. Reactions Weekly &NA;:695, 9
   CrossRef