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Benznidazole-related cutaneous reaction rate high in patients with Chagas’ disease
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Benznidazole yielded a high cutaneous reaction rate in patients with Chagas’ disease, according to Spanish researchers.
“This cutaneous reaction is produced by a delayed hypersensitivity reaction with a Th2 response, therefore treatment with corticosteroids seems to be the best option to prevent or manage this situation,” Fernando Salvador, MD, of Vall d’Hebron University Hospital in Barcelona, Spain, and colleagues wrote in Clinical Infectious Diseases. “Carrying HLA-B*3505 allele could be associated with moderate-severe cutaneous reaction, but larger studies are required to confirm this association.”
Although it is the treatment of choice for Chagas’ disease, benznidazole is associated with a high rate of adverse events, including cutaneous reactions. These events lead to treatment withdrawal in 15% to 30% of patients, according to the researchers.
Fifty-two adult patients with Chagas’ disease participated in this prospective observational study, conducted from March 2013 to July 2013 at Vall d’Hebron University Hospital. All patients were treated with 100 mg benznidazole every 8 hours for 60 days.
The researchers measured patients’ serum cytokine levels at days 0, 15 and 60 of treatment. Skin biopsies were performed after detecting cutaneous reactions, which were classified as mild, moderate or severe. Salvador and colleagues also examined the potential association between HLA alleles and benznidazole concentrations.
Twenty patients (38.5%) developed cutaneous reactions with a median time to appearance of 9 days. There were nine mild, eight moderate and three severe reactions. All patients developed exanthematous drug eruption, and one patient met drug reaction with eosinophilia and systemic symptom (DRESS) syndrome criteria.
The researchers restarted benznidazole treatment in progressively increasing doses with antihistamine drugs in all patients with moderate reactions; however, six of these patients were forced to stop treatment when the reaction reappeared.
Results also showed that patients with cutaneous reactions had higher eosinophilia rates during treatment as well as higher IL-5 and IL-10 serum concentrations at day 15. In addition, patients with the HLA-B*3505 allele were more likely to stop treatment (45.5% vs. 15.4%; P = .033).
“Considering the clinical presentation, the histopathological findings and the serum cytokine profile, the cutaneous reaction associated with benznidazole is an adverse drug reaction consistent with a non-IgE-mediated (delayed) hypersensitivity reaction,” the researchers wrote. – by Colleen Owens
Disclosure: The researchers report no relevant financial disclosures.
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