Amoxicillin-Induced Hypersensitivity Versus Viral Exanthem in Epstein-Barr Virus Infection: A Paediatric Case Series

Epstein-Barr virus (EBV) infection is often associated with skin rashes following aminopenicillin treatment, such as amoxicillin, typically considered a benign and transient reaction. However, distinguishing between non-allergic exanthems and true hypersensitivity remains a clinical challenge, especially in children and adolescents. This case series reports three cases of adolescents who developed generalized exanthematous eruptions following the administration of amoxicillin during acute EBV infection, confirmed by serological testing. All patients underwent standardized allergy evaluation through drug provocation testing at least ten weeks after rash resolution, which confirmed true delayed hypersensitivity to amoxicillin. These three pediatric cases reinforce the need for heightened clinical vigilance when a skin rash occurs during EBV infection treated with amoxicillin. While such rashes are often attributed to transient viral-drug interactions, our findings highlight the importance of considering the possibility of true amoxicillin hypersensitivity. Careful evaluation, including comprehensive allergy work-up when appropriate, is essential to accurately identify a true aminopenicillin allergy and thereby reduce the risk of future severe hypersensitivity reactions.