ObjectivesTo examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions.DesignSubjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home.ParticipantsChildren and adolescents aged 0–18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included.ResultsA total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1–8 hours after the first full dose. Additional 10 positive reactions were observed during the prolonged provocation. Seven subjects reacted after the second full dose and three reacted after 3–6 days. Only mild skin rashes were observed. Eighteen subjects had a specific IgE to a penicillin >0.1 kU/L. Only one of these had a positive DPT.ConclusionIn children, a DPT with penicillins should include at least two full doses. In children with mild hypersensitivity reactions it may be safe to perform DPTs despite a low specific IgE.Trial registration numberNCT04331522
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