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
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.
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.
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.
Hernborg A. Stevens-Johnson syndrome after mass prophylaxis with
sulfadoxine for cholera in Mozambique (Letter). Lancet
1985;2:1072-3.
CDC. Update: acquired immunodeficiency syndrome--United States.
MMWR
1985; 34:245-8.
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.
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.
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.
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.
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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