Single-step Direct Drug Provocation Testing is Safe for Delabelling Selected Non−low-risk Penicillin Allergy Labels

Abstract

To describe the outcome of an oral amoxicillin challenge in patients labeled allergic to penicillin.One hundred forty nine patients from 1 to 98 years of age labeled allergic to penicillin were included in the study.Patients were categorized as low risk (side effects, family history of penicillin allergy, remote [>5 years] history of penicillin allergy without IgE-mediated features, or unknown reaction not requiring hospitalization, n = 64) or nonlow risk (anaphylaxis, urticaria within 2 hours of penicillin administration, or angioedema with or without urticaria, n = 85). The low risk patients underwent challenge with a single dose of oral amoxicillin (125 mg for patients 1 to 11 months of age, 250 mg for 1 to 11 years, and 500 mg for all patients more than 12 years) followed by 2 hours of observation to evaluate for Gell and Coombs type 1/IgE-mediated/immediate-type hypersensitivity reactions. The nonlow risk patients underwent penicillin skin testing and if negative, oral amoxicillin challenge. Excluded patients were those with history of: (1) Gell and Coombs type 2 reactions, for example, hemolytic anemia or thrombocytopenia; (2) type 3 reactions, for example, serum sickness or vasculitis; or (3) severe type 4 or severe cutaneous adverse reactions, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms.All (64 of 64, 100%) of the low risk patients tolerated the amoxicillin challenge without reaction during the observation period, although 3 developed a maculopapular rash subsequently. All (85 of 85, 100%) of the nonlow risk patients had negative penicillin skin testing, and 84 of 85 (99%) tolerated the amoxicillin challenge without reaction during the observation period, whereas 1 patient developed pruritus and rash that resolved with antihistamine treatment, and 2 subsequently developed a maculopapular rash.The authors conclude that a single step oral amoxicillin challenge is safe.Six percent of children are reported to be allergic to penicillin, although only about 5% of that 6% (0.3%) have positive penicillin skin tests. The remainder either never had IgE-mediated allergy or the allergy was lost over time. Being mislabeled as allergic to penicillin is not benign, but rather leads to suboptimal treatment, more side effects (eg, Clostridium difficile), higher costs, and more antibiotic resistance. Thus, there is currently a strong push to “delabel” the vast majority of children who are labeled as allergic to penicillin but are not. Children are typically referred to allergists to undergo oral amoxicillin challenges under observation with or without prior penicillin skin testing, depending on the history. However, this paper suggests that, given the safety of these challenges, consideration can be given to performing them in pediatricians’ offices. If a careful history excludes patients with histories of “nonlow risk” immediate allergic reactions and those with serious nonimmediate reactions, the remainder with low risk histories can undergo a single dose oral amoxicillin challenge, which the vast majority will tolerate and can be successfully “delabeled.”URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1016/j.anai. 2021.04.008