Cutaneous Disease and Drug Reactions in HIV Infection

Coopman, Serge A.; Johnson, Richard A.; Platt, Richard; Stern, Robert S.

doi:10.1056/nejm199306103282304

Cited by 443 publications

(257 citation statements)

References 22 publications

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“…Nausea, skin rash, headache, fever, and anemia were the most frequent reasons for discontinuation of the treatment. Hypersensitivity reactions are a well-recognized problem in the HIV-infected population, and on the basis of the toxicity profiles of dapsone and pyrimethamine, the reactions occurring in our study were most likely attributable to dapsone [50,51]. Hypersensitivity developed more frequently in participants with few CD4 lymphocytes, a circumstance that echoes the experience with amoxycillin-clavulanate [52] but is in contrast to a report associating hypersensitivity to trimethoprim-sulfamethoxazole with high CD4 counts [53].…”

Section: Discussionsupporting

confidence: 43%

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Opravil

Hirschel

Lazzarin

et al. 1995

Clinical Infectious Diseases

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To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/ or CD4 lymphocyte counts of <200/AL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/AL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/ pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.Prophylaxis for opportunistic infections has had a strong impact on the management of immunosuppressed human immunodeficiency virus (HIV)-infected patients in recent years, and epidemiological data indicate that Pneumocystis carinii pneumonia (PCP) has become less frequent as a consequence of prevention [1]. Aerosolized pentamidine became available in Switzerland in 1987 and was subsequently proven effective for both primary and secondary prophylaxis for PCP in controlled trials [2,3]. Among systemic prophylactic agents, trimethoprim-sulfamethoxazole became widely used [4] and was later shown to be more effective but also more toxic than aerosolized pentamidine [5,6] nations, such as dapsone and trimethoprim [7] or pyrimethamine and sulfadiazine [8], have been used for treatment of PCP before, but sparse data exist concerning their prophylactic efficacy [9]. Only recently, the prophylactic efficacy of the combination of dapsone and pyrimethamine against PCP and toxoplasmosis was demonstrated [ 10].Since in >95% of all AIDS patients with toxoplasmic encephalitis there is serological evidence of previous infection with Toxoplasma gondii [10][11][12][13], reactivation of a latent infection is the principal pathogenetic step in the development of toxoplasmic encephalitis during immunodeficiency. Considering the increasing frequency of toxoplasmic encephalitis among AIDS-defining opportunistic infections [ 1] and the 50% seroprevalence of toxoplasma antibodies in Switzerland [14], primary prophylaxis for toxoplasmic encephalitis seems desirable and clinically important, at least for seropositive patients.The sequential inhibition of dihydrofolate reductase by pyrimethamine and of dihydropteroate sy...

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Section: Discussionsupporting

confidence: 43%

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Opravil

Hirschel

Lazzarin

et al. 1995

Clinical Infectious Diseases

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“…Features of IgE-mediated hypersensitivity have not been observed. Hypersensitivity is significantly more common in patients with HIV infection than in those with other immunodeficiency disorders or in the general population [3][4][5][6][7]. Thc causes and mechanisms of this hypersensitivity are not known, but are likely to include a high dose or prolonged duration of therapy, the degree of immunodeficiency, a slow acetylation phenotype, glutathione deficiency, and perhaps coexisting viral infection or immune complex deposition [8][9][10], Hypersensitivity to trimethoprim-sulphamethoxazole Correspondence: Dr Andrew Carr, Centre for Immunology, Si.…”

Section: Introdi;ctionmentioning

confidence: 99%

Immunohistological assessment of cutaneous drug hypersensitivity in patients with HIV infection

Carr

Vasak

Munro

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe pathogenesis of drug hypersensitivity in patients with HIV infection is unknown. To study further the nature of hypersensitivity. the hi.slopathological features of morbilliform drug hypersensitivity reactions were examined in a group of HIV-infected patients. Skin sections from 23 HIV-infected subjects with morbilliform drug hypersensitivity reactions were examined by light microscopy, direct immunofluorescence and immunohistochemistry, to determine the nature of the infiammatory infiltrate and the role of immunoglobuhn. complement and cytokines.

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“…Sulfonamides are the first line drugs for the treatment of common OIs, in AIDS patients, but the frequent occurrence of allergic reactions in these patients can limit their use [4][5][6]. Oral desensitization to this class of drugs has been effective in most cases (50% to 80%), but the best regimen to accomplish this remains to be determined [7][8][9][10][11][12].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, these drugs are used for primary and secondary prophylaxis of these infections [3]. However, the use of sulfonamides is often associated with the development of diverse allergic reactions ranging from mild to severe, leading to the interruption of treatment or prophylaxis, and requiring the use of alternative drugs, usually less effective than the first-line approach [4][5][6].…”

mentioning

confidence: 99%

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

Straatmann¹,

Bahia²,

Pedral-Sampaio³

et al. 2002

Braz J Infect Dis

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Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient. Objective. Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides. Material and Methods. AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD 4 /CD 8 counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months. Results. Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD 4 counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD 8 counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed. Conclusion. Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.

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Cutaneous Disease and Drug Reactions in HIV Infection

Abstract: Cutaneous diseases, including drug reactions, are extremely common in patients with HIV infection, and their incidence increases as immune function deteriorates.

Cited by 443 publications

References 22 publications

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Immunohistological assessment of cutaneous drug hypersensitivity in patients with HIV infection

A randomized, pilot trial comparing full versus escalating dose regimens for the desensitization of AIDS patients allergic to sulfonamides

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