My Patient With Collagenous Colitis Developed a Black Tongue With Bismuth. What Other Therapeutic Options Do I Have?
Collagenous colitis represents one of the two major forms of microscopic colitis. This is an idiopathic, chronic condition marked by nonbloody, watery diarrhea and characteristic histologic abnormalities on mucosal biopsy. Associated symptoms may include occasional fecal incontinence, abdominal cramping, nausea, weight loss, and abdominal distention. Endoscopy and radiographic studies are normal, and laboratory studies are generally unremarkable as well. The mucosal abnormalities of collagenous colitis include a thickened linear subepithelial collagen layer and frequently a mononuclear (lymphocytes, plasma cell, and/or macrophages) cellular infiltrate with epithelial cell damage. Collagenous colitis has an incidence of 4 to 6 per 100,000 people. It occurs more commonly in women and the elderly, with a median age at onset of 65 years, although it has been diagnosed in all ages, including children. There are no known long-term colonic complications of this condition. Although symptoms may wax and wane, the primary objective of treatment is the effective control of the diarrhea and any accompanying lower abdominal symptoms. A variety of treatments exist to include antidiarrheals, fiber supplementation, binding agents, 5-aminosalicylates, antibiotics, immunosuppressants, antisecretory agents, and surgery. There are limited controlled studies assessing these treatment strategies as their use is largely based on anecdotal evidence and that of small, poorly controlled trials. Thus, the choice of treatment is based on a careful balance of symptom severity with that of the risks of therapy.
Bismuth subsalicylate is frequently used as a first-line agent in the treatment of collagenous colitis given its low expense, ease of administration, and relatively low risk of side effects. Its effectiveness is largely based on a single small trial only published in abstract form.1 In this study, nine 262 mg tablets of bismuth subsalicylate taken daily in 3 divided doses for 8 weeks were compared to placebo in patients with collagenous colitis. Those receiving bismuth had clinical improvement, and 6 of 7 also had histologic improvement. However, bismuth subsalicylate is associated with a number of adverse effects that have limited its availability in a number of countries. The more common side effects include darkening of the stool, skin, and tongue. The grayish-black tongue discoloration with bismuth subsalicylate is due to formation of bismuth sulfide and is harmless, although unsightly. Tinnitus has been reported as a result of salicylate absorption. A rare but severe complication is that of bismuth-related encephalopathy, which has occurred more commonly with bismuth compounds other than bismuth subsalicylate. Other infrequent but observed side effects from bismuth include rash, constipation, diarrhea, nausea, and vomiting.
In the event of treatment failure with bismuth subsalicylate, other relatively safe and reasonably inexpensive treatment strategies include loperamide, cholestyramine, sulfasalazine, or 5-aminosalicylic acid.2 Although their effectiveness has only been reported in case reports and uncontrolled trials, they are frequently used in clinical practice. Boswellia serrata extract was studied in a single placebo-controlled trial involving 31 patients. A 6-week trial of therapy consisting of three 400-mg capsules daily only demonstrated a trend toward superiority over that of placebo in achieving clinical improvement. A number of probiotics have also been studied with some promising results, and antibiotics such as metronidazole and erythromycin have been reported to be effective in uncontrolled trials.
Budesonide, a glucocorticoid steroid with a high first-pass metabolism, is the best studied short-term treatment strategy for patients with collagenous colitis.3 Three randomized controlled trials involving a total of 93 patients demonstrated the superiority of budesonide over placebo in the treatment of diarrhea, improvement in quality of life, and resolution of mucosal abnormalities. In these studies, a daily dose of 9 mg of budesonide was used for a period of 6 to 8 weeks. A pooled analysis revealed a number needed to treat of 2 to achieve a clinical response to budesonide.2 However, the relapse rate upon discontinuation of budesonide was significant, occurring in 60% to 80% of patients within 2 weeks. An unproven strategy to prevent relapse may include the use of a low (3 mg to 6 mg) maintenance dose of budesonide. However, there is potential for the same adverse effects of long-term corticosteroid use (hyperglycemia, weight gain, osteoporosis, cataracts).
In the event of treatment failure with the previously described agents, more potent immunosuppressants such as prednisone, azathioprine, or methotrexate should be considered.3 Only prednisone (50 mg daily dose) has been studied in a small placebo-controlled trial involving 11 patients with collagenous colitis. This study was limited by a short treatment period (2 weeks) and a lack of clear superiority of prednisone over placebo. The use of azathioprine and methotrexate remain unproven. Given the significant risk of adverse effects with use of these agents, they should be reserved for severely symptomatic patients who have failed prednisone. Surgical procedures include colectomy, sigmoidostomy, and ileostomy and should be considered in the rare circumstance of disease that is refractory to all forms of medical therapy.
In summary, there are multiple treatment alternatives for collagenous colitis, although limited data exist on their effectiveness. Given the generally benign course of collagenous colitis, it is important to carefully weigh the benefits with the risks and costs of the therapy chosen.
1. Fine KD, Ogunji F, Lee E, Lafon G, Tanzi M. Randomized, double blind, placebo-controlled trial of bismuth subsalicylate for microscopic colitis [abstract]. Gastroenterology. 1999;116:A880.
2. Chande N, McDonald JW, MacDonald JK. Interventions for treating collagenous colitis. Cochrane Database Syst Rev. 2006;18(4):CD003575.
3. Nyhlin N, Bohr J, Eriksson S, Tysk C. Systematic review: microscopic colitis. Aliment Pharmacol Ther. 2006;23(11):1525-1534.