Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis

  • Kenneth D. Fine*,‡
    Division of *Gastrointestinal Research, Baylor University Medical Center, Dallas; and Departments of Internal Medicine and §Pathology, Dallas Veterans Affairs Medical Center and University of Texas-Southwestern Medical Center, Dallas, Texas
    Search for articles by this author
  • Edward L. Lee§
    Division of *Gastrointestinal Research, Baylor University Medical Center, Dallas; and Departments of Internal Medicine and §Pathology, Dallas Veterans Affairs Medical Center and University of Texas-Southwestern Medical Center, Dallas, Texas
    Search for articles by this author


      Background & Aims: The pathogenesis of the microscopic colitis syndrome is unknown but may involve bacteria, an intestinal luminal antigen, and/or autoimmunity. It was hypothesized that bismuth subsalicylate would resolve both diarrhea and colonic inflammation in microscopic colitis because it possesses antidiarrheal, antibacterial, and anti-inflammatory properties. Methods: Thirteen patients with microscopic colitis (7 with subepithelial collagen deposition and 6 without) were treated with eight chewable 262-mg bismuth subsalicylate tablets per day for 8 weeks. Patients recorded the frequency of bowel movements daily. Forty-eight–hour stool collections and flexible sigmoidoscopy with 24 biopsies were performed before and after treatment in each patient. Results: Twelve patients completed the trial. Eleven patients had a resolution of diarrhea and a reduction in fecal weight. The average time to respond was 2 weeks. In 9 patients, colitis resolved. When present before treatment, subepithelial collagen thickening disappeared. Those completing the trial experienced no side effects. Posttreatment follow-up for 7-28 months shows that 9 patients remain well having undergone no further treatment, 2 are well but required retreatment, and 1 has continued diarrhea. Conclusions: Bismuth subsalicylate treatment for 8 weeks is safe and well tolerated. This regimen appears to be efficacious for the treatment of microscopic colitis and is worthy of further study in a controlled trial.
      GASTROENTEROLOGY 1998;114:29-36


      ANA (antinuclear antibody)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lindström CG
        “Collagenous colitis” with watery diarrhea: a new entity?.
        Pathol Eur. 1976; 11: 87-89
        • Read NW
        • Krejs GJ
        • Read MG
        • Santa Ana CA
        • Morawski SG
        • Fordtran JS
        Chronic diarrhea of unknown origin.
        Gastroenterology. 1980; 78: 264-271
        • Lazenby AJ
        • Yardley JH
        • Giardiello FM
        • Jessurun J
        • Bayless TM
        Lymphocytic (“microscopic”) colitis: a comparative histopathologic study with particular reference to collagenous colitis.
        Hum Pathol. 1989; 20: 18-28
        • Roubenoff R
        • Ratain J
        • Giardiello F
        • Hochberg M
        • Bias W
        • Lazenby A
        • Yardley J
        Collagenous colitis, enteropathic arthritis, and autoimmune disease: results of a patient survey.
        J Rheumatol. 1989; 16: 1229-1232
        • Zins BJ
        • Sandborn WJ
        • Tremaine WJ
        Collagenous and lymphocytic colitis: subject review and therapeutic alternatives.
        Am J Gastroenterol. 1995; 90: 1394-1400
        • Bohr J
        • Tysk C
        • Eriksson S
        • Abrahamsson H
        • Järnerot G
        Collagenous colitis—a retrospective study of the clinical presentation and treatment in 163 patients.
        Gut. 1996; 39: 846-851
        • Fasoli R
        • Jewell DP
        Response to treatment of microscopic colitis.
        Ital J Gastroenterol. 1994; 26: 229-232
        • Austin CA
        • Cann PA
        • Jones TH
        • Holdsworth CD
        Exacerbation of diarrhoea and pain in patients treated with 5-aminosalicylic acid for ulcerative colitis.
        Lancet. 1984; 1: 917-918
        • Sloth H
        • Bisgaard C
        • Grove A
        Collagenous colitis: a prospective trial of prednisolone in six patients.
        J Intern Med. 1991; 229: 443-446
        • Gorbach SL
        Bismuth therapy in gastrointestinal diseases.
        Gastroenterology. 1990; 99: 863-875
        • DuPont HL
        • Sullivan P
        • Evans DG
        • Pickering LK
        • Evans DJ
        • Vollet JJ
        • Ericsson CD
        • Ackerman PB
        • Tjoa WS
        Prevention of traveler's diarrhea (emporiatric enteritis). Prophylactic administration of subsalicylate bismuth.
        JAMA. 1980; 243: 237-241
        • Ericsson CD
        • Tannenbaum C
        • Charles TT
        Antisecretory and antiinflammatory properties of bismuth subsalicylate.
        Rev Infect Dis. 1990; 12: S16-S20
        • DuPont HL
        • Sullivan P
        • Pickering LK
        • Haynes G
        • Ackerman PB
        Symptomatic treatment of diarrhea with bismuth subsalicylate among students attending a Mexican university.
        Gastroenterology. 1977; 73: 715-718
        • Bierer DW
        Bismuth subsalicylate: history, chemistry, and safety.
        Rev Infect Dis. 1990; 12: S3-S8
        • Gryboski JD
        • Kocoshis S
        Effect of bismuth subsalicylate on chronic diarrhea in childhood: a preliminary report.
        Rev Infect Dis. 1990; 12: S36-S40
        • Figueroa-Quintanilla D
        • Salazar-Lindo E
        • Sack RB
        • León-Barúa R
        • Sarabia-Arce S
        • Campos-Sánchez M
        • Eyzaguirre-Maccan E
        A controlled trial of bismuth subsalicylate in infants with acute watery diarrheal disease.
        N Engl J Med. 1993; 328: 1653-1658
        • Farris RK
        • Tapper EJ
        • Powell DW
        • Morris SM
        Effect of aspirin on normal and cholera toxin–stimulated intestinal electrolyte transport.
        J Clin Invest. 1976; 57: 916-924
        • Graham DY
        • Estes MK
        • Gentry LO
        Double-blind comparison of bismuth subsalicylate and placebo in the prevention and treatment of enterotoxigenic Escherichia coli–induced diarrhea in volunteers.
        Gastroenterology. 1983; 85: 1017-1022
        • Manhart MD
        In vitro antimicrobial activity of bismuth subsalicylate and other bismuth salts.
        Rev Infect Dis. 1990; 12: S11-S15
        • Eherer AJ
        • Santa Ana CA
        • Porter JL
        • Fordtran JS
        Effect of psyllium, calcium polycarbophil, and wheat bran on secretory diarrhea induced by phenolphthalein.
        Gastroenterology. 1993; 104: 1007-1012
        • Tillman LA
        • Drake FM
        • Dixon JS
        • Wood JR
        Review article: safety of bismuth in the treatment of gastrointestinal diseases.
        Aliment Pharmacol Ther. 1996; 10: 459-467
        • Bohr J
        • Tysk C
        • Yang P
        • Danielsson D
        • Järnerot G
        Autoantibodies and immunoglobulins in collagenous colitis.
        Gut. 1996; 39: 73-76
        • Govers MJ
        • Termont DS
        • Van der Meer R
        Mechanism of the antiproliferative effect of milk mineral and other calcium supplements on colonic epithelium.
        Cancer Res. 1994; 54: 95-100
        • Govers MJ
        • Termont DS
        • Lapre JA
        • Kleibeuker JH
        • Vonk RJ
        • Van der Meer R
        Calcium in milk products precipitates intestinal fatty acids and secondary bile acids and thus inhibits colonic cytotoxicity in humans.
        Cancer Res. 1996; 56: 3270-3275
        • Hasking GJ
        • Duggan JM
        Encephalopathy from bismuth subsalicylate (letter).
        Med J Aust. 1982; 2: 167
        • Mendelowitz PC
        • Hoffman RS
        • Weber S
        Bismuth absorption and myoclonic encephalopathy during bismuth subsalicylate therapy.
        Ann Intern Med. 1990; 112: 140-141
        • Ryder SD
        • Walker RJ
        • Jones H
        • Rhodes JM
        Rectal bismuth subsalicylate as therapy for ulcerative colitis.
        Aliment Pharmacol Ther. 1990; 4: 333-338
        • Pullan RD
        • Ganesh S
        • Mani V
        • Morris J
        • Evans BK
        • Williams GT
        • Rhodes J
        Comparison of bismuth citrate and 5-aminosalicylic acid enemas in distal ulcerative colitis: a controlled trial.
        Gut. 1993; 34: 676-679
        • Ginochetti P
        • Campieri M
        • Ferretti M
        • Rizzello F
        • Venturi A
        • Belluzzi A
        • Brignola C
        • Miglioli M
        Bismuth carbomer enemas in treatment of chronic unremitting pouchitis (abstr).
        Gut. 1995; 37: A49
        • Tremaine WJ
        • Sandborn WJ
        • Wolff BG
        • Carpenter HA
        • Zinsmeister AR
        • Metzger PP
        Bismuth carbomer foam enemas for treatment resistant, active chronic pouchitis: a randomized, double-blind, placebo-controlled trial (abstr).
        Gastroenterology. 1997; 112: A1105
        • Fine KD
        • Meyer RL
        • Lee EL
        The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet.
        Gastroenterology. 1997; 112: 1830-1838