TY - JOUR
T1 - Evaluation of cytokine profile and HLA association in benznidazole related cutaneous reactions in patients with chagas disease
AU - Salvador, Fernando
AU - Sánchez-Montalvá, Adrián
AU - Martínez-Gallo, Mónica
AU - Sala-Cunill, Anna
AU - Viñas, Laura
AU - García-Prat, Marina
AU - Aparicio, Gloria
AU - Sao Avilés, Augusto
AU - Artaza, M. Ángeles
AU - Ferrer, Berta
AU - Molina, Israel
PY - 2015/12/1
Y1 - 2015/12/1
N2 - © 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Background. Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients. Methods. Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment. Results. Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B∗3505 allele (45.5% vs 15.4%, P =. 033). No differences in benznidazole serum concentration were found. Conclusions. Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B∗3505 allele could be associated with moderate-severe cutaneous reaction.
AB - © 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Background. Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients. Methods. Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment. Results. Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B∗3505 allele (45.5% vs 15.4%, P =. 033). No differences in benznidazole serum concentration were found. Conclusions. Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B∗3505 allele could be associated with moderate-severe cutaneous reaction.
KW - benznidazole
KW - Chagas disease
KW - cutaneous drug reaction.
KW - Trypanosoma cruzi
U2 - 10.1093/cid/civ690
DO - 10.1093/cid/civ690
M3 - Article
SN - 1058-4838
VL - 61
SP - 1688
EP - 1694
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -
