Immediate hypersensitivity reactions to penicillins are often labeled on the basis of a similar set of symptoms, but a key feature of these reactions that can be reproduced in diagnostic testing may be the timing of a reaction in relation to the dose administration.

We evaluated 1,074 patients by performing skin tests (STs), serum specific IgE assays (ImmunoCAP), and challenges. Patients who were evaluated by us more than 6 months after their reactions and found negative were re-evaluated within 2-4 weeks.

Patients who had reacted ≤ 1 hour after the first dose, ≤ 1 hour after subsequent doses, > 1 hour - ≤ 6 hours after the first dose, or > 1 hour - ≤ 6 hours after subsequent doses were classified as group A (758 individuals), B (92), C (67), or D (157), respectively. Penicillin hypersensitivity was diagnosed in 707 patients (65.8%) by STs (407 patients, 57.6%), ImmunoCAP (47, 6.6%), both tests (232, 32.8%), or challenges (21, 3%). A conversion to allergy-test positivity occurred in 7 of 10 patients with anaphylactic reactions and in one of 28 patients with other reactions who were re-evaluated after negative challenges. The rate of penicillin-allergic patients in groups A, B, C, and D was 85%, 35.9%, 35.8%, and 3.8%, respectively. Only one of 107 patients reporting cutaneous reactions lasting more than one day was positive to allergy tests.

IgE-mediated hypersensitivity can be diagnosed by STs in about 70% of subjects who react within one hour (e.g., patients from groups A and B). This hypersensitivity can be lost over time, as demonstrated by the negativization of allergy tests in follow-up studies. In subjects with anaphylactic reactions, however, it is advisable to not consider this phenomenon definitive. In fact, a conversion to allergy test positivity can be observed in up to 20% of such subjects retested after negative challenges.