Evaluation of the duration of supervised ambulatory drug provocation tests in children with mild non-immediate reactions to beta-lactams

Guidelines recommend to explore mild delayed hypersensitivity reactions to beta-lactams (BL) in children with direct drug provocation tests (DPTs). The optimal duration of these DPTs remains unknown and DPTs lasting 1 to 10 days are proposed. No study has directly compared the frequency of positivity of directs DPTs according to their duration. To compare the frequency of positivity of DPTs of different duration performed to explore mild delayed hypersensitivity reactions to beta-lactams (BL) in children in different centers. Data from children explored between January 2019 and December 2021 for delayed mild reactions (isolated urticaria, maculopapular exanthema or non-specific skin rashes) to oral BL in six different pediatric centers performing DPTs of varying duration (1 day or 3 days or 2 days more than the index reaction) were analysed. In total, 673 children were included. The duration of the DPTs were 1 day in 60 cases (8.9%), 3 days in 69 cases (10.3%), and 2 days more than the index reaction in 544 cases (80.8%). The median age at the index reaction was 1.7 years [0.8–3.7] in the “group 1 day”, 1.9 [1–3.6] years in the group “3 days” and 1.5 [1–3.3] in the group “2 days more”. Amoxicillin was the main BL involved (72.8%). The median age at workup was 4.6 years [2.7–8.7] in the “group 1 day”, 3.8 years [1.8–8.3] in the “group 3 days” and 3 years [1.7–7] in the group “2 days more”. General characteristics of patients in the 3 groups were similar. Fifty-eight DPTs were positive (8.6%); reactions occurring during DPTs were all mild and delayed isolated skin rashes resolving spontaneously or with H1-antihistamines. One DPT was positive in the “group 1 day” (1.5%), 4 (5.8%) in the “group 3 days”, and 53 (9,7%) in the “group 2 days more than the index reaction” (P = 0.08). The frequency of positive DPTs was higher for long DPT (“2 days more”) than short DPT (1 or 3 days) (3.9% vs. 9.7%, P < 0.05). Our results support that increasing the duration of DPTs to explore mild delayed reactions to BL in children may improve their diagnosis performance.