Correspondence
Uveitis and Pseudojaundice During a Regimen of Clarithromycin, Rifabutin, and Ethambutol
N Engl J Med 1994; 330:438-439February 10, 1994
- Article
To the Editor:
We report the occurrence of uveitis and pseudojaundice in patients with AIDS who were receiving the combination of clarithromycin, rifabutin, and ethambutol for the treatment of Mycobacterium avium complex bacteremia.
We are conducting a prospective, randomized, multicenter study comparing two oral multidrug regimens for the treatment of M. avium complex bacteremia in adults with AIDS. As of November 5, 1993, 119 patients had entered this study, 59 of whom were assigned to receive a regimen consisting of 1000 mg of clarithromycin twice daily, 600 mg of rifabutin daily, and 15 mg of ethambutol per kilogram of body weight daily. To date, pseudojaundice, characterized by yellow pigmentation of the skin but not the sclera, has developed in 13 patients at eight centers. The serum bilirubin concentrations were normal in all but one patient, who had a slightly elevated level (46 μmol per liter). The yellow skin pigmentation has not been associated with pruritus or other symptoms. The pseudojaundice was noted during week 12 of the study in eight patients and between weeks 10 and 28 in the others.
In addition, acute uveitis has been diagnosed in 23 patients from 15 centers. The uveitis was bilateral in 16 patients and unilateral in 7 and developed after a mean of 65 days (range, 27 to 197). It was treated with topical corticosteroids and mydriatic agents, with a generally favorable response, although three patients required vitrectomy and one underwent a vitreous tap with intravitreal injection of antibiotics for an inflammation so severe it mimicked infectious endophthalmitis. Six of these patients had both uveitis and pseudojaundice. Because neither uveitis nor pseudojaundice has been observed in the other treatment arm of this study, consisting of rifampin, ethambutol, ciprofloxacin, and clofazimine, these two adverse effects are clearly related to the treatment regimen. We believe that the pseudojaundice is attributable to rifabutin, because this adverse effect has been reported in HIV-infected patients receiving high doses of rifabutin.1 The cause of the uveitis is less certain, but two cases have been reported in HIV-infected patients receiving high doses (1800 to 1950 mg per day) of rifabutin.1 We are unaware of reports of uveitis attributed to treatment with either clarithromycin or ethambutol, and the absence of such reports has been corroborated by the manufacturers of these two agents. We are continuing to study the association of uveitis and pseudojaundice with this particular treatment regimen and are performing more detailed pharmacologic analyses. In addition, the Safety and Efficacy Review Committee of the Canadian HIV Trials Network has recently recommended a reduction in the dose of rifabutin to 300 mg daily and the discontinuation of this drug in patients with uveitis.
1 ReferencesStephen D. Shafran, M.D.
University of Alberta, Edmonton, AB T6G 2B7, CanadaJean Deschenes, M.D.
Mark Miller, M.D.
McGill University, Montreal, QC H3G 1Y6, CanadaPeter Phillips, M.D.
University of British Columbia, Vancouver, BC V6L 1Z1, CanadaEmil Toma, M.D.
Universite de Montreal, Montreal, QC H3C 3T7, Canadafor the MAC Study Group of the Canadian HIV Trials Network
1
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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