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Epidemiologic Notes and Reports -- Fansidar-Associated Fatal React ion in an HIV-Infected Man

In March 1987, a 48-year-old homosexual man with oral thrush and a single dermatome zoster infection was found to be human immunodeficiency virus (HIV)- seropositive by enzyme immunoassay and Western blot. He had a depressed T4 lymphocyte count of 359 cells/mm3 (normal: greater than or equal to800 T4 cells/mm3), and weekly pentamidine aerosol treatments were begun for prophylaxis against Pneumocystis carinii pneumonia (PCP). In late July 1987, the patient's T4 count had decreased to 311 cells/mm3, and weekly pyrimethamine 25 mg/sulfadoxine 500 mg (Fansidar*) was added to his prophylactic regimen.

In late August, while still on weekly pentamidine aerosols and oral Fansidar, he developed a maculopapular rash on his neck. During the next 10 days, the rash spread to his arms, legs, and trunk, and multiple bullae developed. He took one or two additional doses of Fansidar during this time. In early September, the patient was hospitalized with oropharyngeal blisters and extensive cutaneous lesions and was diagnosed initially as having disseminated zoster; treatment with intravenous acyclovir was begun. The next day, a skin biopsy showed toxic epidermal necrolysis. Despite aggressive intensive care, the patient rapidly developed fever, hypotension, and acute renal failure and died 48 hours after admission. Reported by: Malaria Br and Parasitic Diseases Br, Div of Parasitic Diseases; AIDS Program, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: This is the first report of a fatal cutaneous adverse reaction associated with Fansidar prophylaxis for PCP in an HIV-infected patient. Four nonfatal cases of Stevens-Johnson syndrome (severe erythema multiforme) in AIDS patients receiving Fansidar prophylaxis have been reported (1). Severe cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis) also have been reported among American travelers using Fansidar for malaria prophylaxis. These studies have estimated the incidence of these reactions to be one per 5,000-8,000 users, and fatalities, one per 11,000-25,000 users (2). A comparable incidence was noted when sulfadoxine alone was used for prophylaxis of meningococcal disease in Morocco (3) and for cholera in Mozambique (4).

PCP, the most frequent opportunistic infection in American patients with AIDS, occurs in 56% of patients as the initial manifestation of the syndrome (5). In addition, PCP frequently recurs after successful treatment. Trimethoprim/sulfamethoxazole is effective in treating PCP in AIDS patients but is associated with rash, fever, and neutropenia in up to 54% of cases, which may necessitate discontinuation or change of therapy (6). Parenteral pentamidine is an effective chemotherapeutic agent but also may be associated with a high frequency of unacceptable adverse reactions including neutropenia, azotemia, and severe rash (7).

While trimethoprim/sulfamethoxazole and pentamidine are considered, respectively, the first and second drugs of choice for the treatment of PCP in AIDS patients, data concerning comparative safety and efficacy of various chemoprophylactic regimens are limited. Because of the high morbidity and mortality associated with first and recurrent episodes of PCP, some investigators have proposed chemoprophylaxis for asymptomatic HIV-seropositive patients with low T4 lymphocyte counts as well as for AIDS patients with a history of PCP. Drugs used in this setting have included trimethoprim/sulfamethoxazole, intramuscular or aerosolized inhaled pentamidine, dapsone, and Fansidar (8,9). A multicenter, randomized double-blind, placebo-controlled study is scheduled to ascertain the comparative efficacy and safety of trimethoprim/sulfamethoxazole, Fansidar, and aerosolized pentamidine for prophylaxis of PCP in AIDS patients receiving azidothymidine. However, no experimental evidence is available to suggest that Fansidar is biologically more active than trimethoprim/sulfamethoxazole against P. carinii. In addition, longer-acting sulfonamides (such as sulfadoxine) have been implicated as the cause of severe mucocutaneous reactions 10-20 times more frequently than shorter-acting congeners (10). Consequently, the only advantage of selecting Fansidar as a first-line prophylactic drug in these patients would be potentially improved patient compliance due to weekly rather than daily dosing.

This report emphasizes the importance of closely monitoring AIDS patients for adverse reactions to prophylactic drugs. In any patient receiving Fansidar or other prophylactic medication, the appearance of new cutaneous lesions should prompt immediate discontinuation of the drug until the etiology of the lesions is determined.

References

  1. Navin TR, Miller KD, Satriale RF, Lobel HO. Adverse reactions associated with pyrimethamine-sulfadoxine prophylaxis for Pneumocystis carinii infections in AIDS (Letter). Lancet 1985;1:1332.

  2. Miller KD, Lobel HO, Satriale RF, Kuritsky JN, Stern R, Campbell CC. Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. Am J Trop Med Hyg 1986;35:451-8.

  3. Bergoend H, Loffler A, Amar R, Maleville J. Reactions cutanees survenues au cours de la prophylaxie de masse de la meningite cerebro-spinale par un sulfamide long-retard (a propos de 997 cas). Ann Derm Syph 1968;95:481-90.

  4. Hernborg A. Stevens-Johnson syndrome after mass prophylaxis with sulfadoxine for cholera in Mozambique (Letter). Lancet 1985;2:1072-3.

  5. CDC. Update: acquired immunodeficiency syndrome--United States. MMWR 1985; 34:245-8.

  6. Gordin FM, Simon GL, Wofsy CB, Mills J. Adverse reactions to trimethoprim- sulfamethoxazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1984;100:495-9.

  7. Wharton JM, Coleman DL, Wofsy CB, et al. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med 1986;105:37-44.

  8. Gottlieb MS, Knight S, Mitsuyasu R, Weisman J, Roth M, Young LS. Prophylaxis of Pneumocystis carinii infection in AIDS with pyrimethamine-sulfadoxine (Letter). Lancet 1984;2:398-9.

  9. Vieira J. Fansidar prophylaxis of Pneumocystis carinii pneumonia in asymptomatic HIV+ persons and persons with ARC (Abstract). III International Conference on AIDS, Washington, DC, June 1-5, 1987:99.

  10. Carroll OM, Bryan PA, Robinson RJ. Stevens-Johnson syndrome associated with long- acting sulphonamides. JAMA 1966;195:691-3. *Use of trade names is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.



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