Association of HLA-B∗35 and moderate or severe cutaneous reactions secondary to benznidazole treatment in chronic chagas disease. (June 2022)

• Record Type: Journal Article
• Authors: Bosch-Nicolau, Pau; Salvador, Fernando; Sánchez-Montalvá, Adrián; Franco-Jarava, Clara; Arrese-Muñoz, Iria; Sulleiro, Elena; Roure, Silvia; Valerio, Lluis; Oliveira-Souto, Inés; Serre-Delcor, Núria; Pou, Diana; Treviño, Begoña; Aznar, María L.; Espinosa-Pereiro, Juan; Molina, Israel
• Is Part Of: Clinical microbiology and infection. Volume 28:Number 6(2022)
• Page Start: 881.e1
• Page End: 881.e5
• Publication Date: 2022-06
• Subjects: Benznidazole -- Chagas disease -- Cutaneous hypersensitive reactions -- Human leucocyte antigen -- Pharmacogenetics; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2021.11.021
• Languages: English
• ISSNs: 1198-743X

Abstract

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.