Progressively Simplified Testing in the Evaluation of Nonimmediate Reactions to Penicillins.

Background: Morbilliform drug eruptions (MDEs) and delayed-appearing urticaria are the most frequently reported nonimmediate reactions to penicillins. Direct challenges have recently been suggested in adults reporting distant MDEs or isolated urticaria.

Objective: To assess the usefulness of patch tests (PTs), intradermal tests (IDTs), challenges, and relevant reagents in evaluating nonimmediate reactions to penicillins, and to determine the predictive value of their morphology and duration for a positive allergy test result.

Methods: All patients older than 15 years evaluated in 5 European centers between 2001 and 2022 with well-characterized nonimmediate reactions to penicillins were included. Patients were evaluated with skin tests (PTs and/or delayed-reading IDTs) and, when skin test results were negative, drug challenges.

Results: We evaluated 872 patients: 583 reported MDEs, 193 urticarial/angioedematous reactions, 73 erythemas, and 23 other reactions; 647 patients underwent PTs and/or IDTs with benzylpenicillin reagents, amoxicillin, and suspected penicillins, while 225 only with the suspected penicillin and amoxicillin. Results of PTs and/or delayed-reading IDTs were positive in 291 patients (33.4%) and challenges in 26 (3%). In 583 patients with MDEs, the rate of positive delayed-reading IDTs increased in accordance with the duration from 10.9% of 221 patients with eruptions lasting 2 to 4 days to 82.7% of 52 patients with MDEs lasting more than 28 days. No patient tested negative for suspected penicillins and positive for other reagents.

Conclusions: IDTs appear particularly useful in patients with well-characterized MDEs lasting more than 4 days. Direct challenges are advisable in patients reporting urticarial and/or angioedematous reactions lasting more than 1 day or other cutaneous reactions lasting 4 or fewer days, even well-characterized MDEs. In the latter patients, however, delayed-reading IDTs with only the suspected penicillins, and clavulanic acid if involved, could reduce the number of positive challenges.