Nonimmediate reactions to penicillins: towards simplified testing

Published online May 28, 2025

Direct challenges have been suggested for adults reporting distant morbilliform drug eruptions (MDEs) lasting < 7 days or isolated urticaria. However, the combination of chronology (i.e. both the time interval between penicillin exposure and onset of symptoms and the duration of the index reaction) and morphology (i.e. the type of cutaneous eruption) are essential for an appropriate risk stratification.

In a recently published multicentric study in The Journal of Allergy and Clinical Immunology: In Practice, Romano and colleagues characterized 872 patients with nonimmediate reactions to penicillins through the combined use of chronological and morphological criteria. Patients were evaluated with patch tests (PTs) and/or delayed-reading intradermal tests (dIDTs) and, when negative, drug challenges. During the study, the allergy workup has been progressively simplified. 

The study shows that dIDTs are particularly useful in MDEs lasting > 4 days and direct challenges can be considered in urticarial reactions lasting > 1 day or other cutaneous reactions lasting ≤ 4 days. Moreover, it is possible to simplify the allergy workup carrying out PTs only in patients with SCARs or severe complicated MDEs and performing skin tests only with the suspected penicillins.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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