Background: The incidence of rash after aminopenicillin treatment in children with Epstein-Barr Virus (EBV) infection was reported to be 80–100%. A few recent studies suggested that the incidence may be much lower during EBV infection. There are no clear data on the incidence of true drug hypersensitivity among these patients. The aim of this study is to determine the incidence of rash and antibiotic allergy after antibiotic treatment in children with EBV infection. Methods: Drug hypersensitivity was investigated in antibiotic-treated patients with a positive EBV IgM who developed a rash between 2013 and 2016. Results: During the study period, 221 children were diagnosed with EBV infection, and 120 (54.3%) patients were treated with antibiotics during disease. Rash developed in 41 (41/221, 18.6%) patients, and 20 of them (total 120; 16.6%) were treated with antibiotics (most frequently aminopenicillins: 72.5%), and 21 of them (total 101, 20.8%) were not treated with antibiotics (p = 0.43). For 10 of the 20 antibiotic-treated patients with a rash, parents did not consent to an allergy workup. Three of the 10 patients who were tested for drug allergy were proven to have amoxicillin-clavulanate hypersensitivity (30%). Five of the patients without workup reacted after reuse of the suspected drug for infection treatment. Conclusion: In this study, the incidence of drug hyper-sensitivity was much lower than previously reported. Some of the reactions that occur during infectious mononucleosis are transient, and some are true drug hypersensitivity reactions. Thus, these patients should be evaluated with allergy tests before these drugs are used again after EBV infection.

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