Correspondence

Rifabutin Prophylaxis and Uveitis

N Engl J Med 1994; 330:1315-1316May 5, 1994

Article

To the Editor:

Nightingale et al. (Sept. 16 issue)1 reported no cases of uveitis among 292 patients taking 300 mg of rifabutin per day as prophylaxis against Mycobacterium avium complex infection, and there was no mention of uveitis in the guidelines on treatment and prophylaxis for M. avium complex disease (Sept. 16 issue)2. However, Shafran and colleagues (Feb. 10 issue)3 reported the development of uveitis in 39 percent of 59 patients treated for M. avium complex bacteremia with 600 mg of rifabutin daily (along with clarithromycin and ethambutol). We report a case of bilateral uveitis in a patient who was taking the currently recommended daily dose of 300 mg of rifabutin for M. avium complex prophylaxis.

A 62-year-old heterosexual man with human immunodeficiency virus infection, alcoholic cirrhosis, esophageal candidiasis, a CD4+ count of 15 cells per cubic millimeter, and an asthenic habitus (body-surface area, 1.68 m²) began taking 300 mg of rifabutin daily. Other medications included didanosine, trimethoprim-sulfamethoxazole, ranitidine, acyclovir, and fluconazole (100 mg daily). After only 10 days, rifabutin was discontinued for 3 weeks because of suspected pancreatitis.

Five weeks after rifabutin therapy was resumed, the patient experienced sudden pain in his left eye that was associated with severe itching, a foreign-body sensation, tearing, decreased vision, and photophobia. An examination revealed acute anterior uveitis, visual acuity of 20/25, a moderate number of white cells (3+), flare (2+), moderate vitritis, and fibrin exudate floating in the anterior chamber.

The patient was treated with a cycloplegic agent and topical steroids. On day 26, while symptoms were gradually improving, a foreign-body sensation, pain, and tearing developed in the right eye. On day 29 (while the patient was still taking rifabutin), an examination showed panuveitis in the right eye and persistent uveitis and vitritis in the left. On day 32, rifabutin was discontinued because of early reports of rifabutin-associated uveitis. The patient's symptoms disappeared, and his eyes returned to normal after six weeks.

Although our patient was taking a lower dose of rifabutin than those reported in previous cases of rifabutin-associated uveitis,3,4 he was also taking fluconazole, and fluconazole may substantially increase serum levels of rifabutin5. Our patient's lean body mass, the concomitant use of fluconazole, or decreased drug metabolism due to cirrhosis may have increased the rifabutin levels and the risk of uveitis.

Uveitis may be accompanied by severe pain and transient loss of vision and may require invasive diagnostic testing or empirical treatment3. Until the risk of rifabutin-associated uveitis is further defined, we urge clinicians to monitor eye symptoms carefully in patients taking rifabutin, especially those with hepatic dysfunction or lean body mass, and those also taking fluconazole.

Jon D. Fuller, M.D.
Lorraine E.D. Stanfield, M.D.
Donald E. Craven, M.D.
Boston University School of Medicine, Boston, MA 02118

5 References

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   Nightingale SD, Cameron DW, Gordin FM, et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993;329:828-833
   Full Text | Web of Science | Medline

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   Masur H, Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium Complex. Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. N Engl J Med 1993;329:898-904
   Full Text | Web of Science | Medline

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   Shafran SD, Deschenes J, Miller M, Phillips P, Toma E. Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. N Engl J Med 1994;330:438-439
   Full Text | Web of Science | Medline

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   Siegal FP, Eilbott D, Burger H, et al. Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis. AIDS 1990;4:433-441
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   Trapnell DB, Narang PK, Li R, et al. Fluconazole increases rifabutin (RIF) absorption in HIV(+) patients on stable zidovudine therapy. In: Proceedings of the Ninth International Conference on AIDS, Berlin, Germany, June 6-11, 1993. London: Wellcome Foundation, 1993:504. abstract.
   

Citing Articles (16)

Citing Articles

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   Yong Chul Park, Ji Woong Lee, Jae Pil Shin, Si Yeol Kim. (2009) Rifabutin Related Uveitis in AIDS: A Case Report. Journal of the Korean Ophthalmological Society 50:6, 951
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   Bennie H. Jeng, Gary N. Holland, Careen Y. Lowder, William F. Deegan, Michael B. Raizman, David M. Meisler. (2007) Anterior Segment and External Ocular Disorders Associated with Human Immunodeficiency Virus Disease. Survey of Ophthalmology 52:4, 329-368
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   2006. Macrolide antibiotics. , 2183-2195.
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   2006. Clarithromycin. , 799-805.
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   Anamaria Baptista Coutinho, Devinder Cheema, Patricia R. Pereira, João P. Souza Filho, Miguel N. Burnier. (2005) Corneal Endothelial Deposits Associated with Rifabutin Use. Journal of Ocular Pharmacology and Therapeutics 21:2, 166-169
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   Jeffrey J. Kuper, Michelle D??Aprile. (2000) Drug-Drug Interactions of Clinical Significance in the Treatment of Patients with Mycobacterium avium Complex Disease. Clinical Pharmacokinetics 39:3, 203-214
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   Karthik Venkatakrishnan, Lisa L. von Moltke, David J. Greenblatt. (2000) Effects of the Antifungal Agents on Oxidative Drug Metabolism. Clinical Pharmacokinetics 38:2, 111-180
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    K. Becker, H. Jablonowski, D. Häussinger, M. Schimkat. (1996) Anterior uveitis associated with rifabutin medication in AIDS patients. Infection 24:1, 34-36
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    Elizabeth Eccles, Judy Ptak. (1995) Mycobacterium avium complex infection in AIDS: Clinical features, treatment, and prevention. Journal of the Association of Nurses in AIDS care 6:5, 37-47
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    Leland S. Rickman, William R. Freeman. (1995) Medical and Virological Aspects of Ocular Human Immunodeficiency Virus Infection for the Ophthalmologist. Seminars in Ophthalmology 10:2, 91-110
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    &NA;. (1994) Rifabutin. Reactions Weekly &NA;:501, 12
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