Association of HLA-B∗35 and moderate or severe cutaneous reactions secondary to benznidazole treatment in chronic chagas disease

Abstract

Objectives: Benznidazole is the first-line treatment for Chagas disease. Adverse events appear in more than 50% of patients, leading to discontinuation in approximately 15%. Cutaneous reactions are one of the most frequent adverse events. Human leucocyte antigen (HLA) genotyping studies identified an association between cutaneous reactions to benznidazole and carrying the specific allele HLA-B∗35:05. We designed the present study to prospectively confirm this association.

Methods: This is a prospective observational study including Chagas disease patients aged 18 years or more who accepted to receive benznidazole treatment following current guidelines. Allele genotyping of HLA-B was determined in all patients. Clinical and analytical follow up was performed at days 0, 7, 14, 30 and 60 of treatment.

Results: Two-hundred and seven individuals were included. Seventy per cent were female with a mean age of 45.1 (SD ± 9.86) years mainly from Bolivia (92.8%). In 102 (49.3%) cases a cutaneous reaction was diagnosed. Forty-eight (46.6%) were classified as mild, 37 (35.9%) as moderate and 18 (17.5%) as severe. Thirty-two (15.4%) patients had to definitively interrupt the treatment because of a cutaneous reaction. Female sex (OR 4.49; 95% CI 1.62-12.47), new-onset eosinophilia before cutaneous symptoms (OR 2.55; 95% CI 1.2-5.43) and carrying the HLA-B∗35 allelic group (OR 2.58; 95% CI 1.2-5.51) were all predictors of moderate to severe cutaneous reactions. No statistical significance was found when the specific allele HLA-B∗35:05 was analysed.

Conclusions: Patients carrying the HLA-B∗35 allelic group are at higher risk of moderate to severe reactions when taking benznidazole treatment.

Keywords: Benznidazole; Chagas disease; Cutaneous hypersensitive reactions; Human leucocyte antigen; Pharmacogenetics.