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Progressively Simplified Testing in the Evaluation of Nonimmediate Reactions to Penicillins
Antonino Romano1, Rocco Luigi Valluzzi2, Francesco Gaeta3
1Oasi Research Institute-IRCCS, Troina, Italy; BIOS S.p.A. Società Benefit, Rome, Italy.
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.
Insights
Delayed-reading intradermal tests (IDTs) are useful for diagnosing penicillin allergies, especially for morbilliform drug eruptions (MDEs) lasting over 4 days. Direct challenges are recommended for urticarial reactions and other cutaneous reactions, with IDTs potentially reducing positive challenge rates.
Area of Science:
- Allergy and Immunology
- Dermatology
- Pharmacology
Background:
- Morbilliform drug eruptions (MDEs) and delayed urticaria are common nonimmediate penicillin reactions.
- Direct challenges are increasingly suggested for diagnosing these reactions.
Purpose of the Study:
- To evaluate the utility of patch tests (PTs), intradermal tests (IDTs), and challenges for nonimmediate penicillin reactions.
- To determine the predictive value of reaction morphology and duration for positive allergy test results.
Main Methods:
- Retrospective analysis of 872 patients (age >15) across 5 European centers (2001-2022) with nonimmediate penicillin reactions.
- Patients underwent skin tests (PTs and/or delayed-reading IDTs) and, if negative, drug challenges.
- Evaluated reactions included MDEs, urticarial/angioedematous reactions, and erythemas.
Main Results:
- Positive skin tests (PTs/IDTs) occurred in 33.4% (291/872) and challenges in 3% (26/872).
- For MDEs, positive delayed-reading IDTs increased with duration: 10.9% (2-4 days) to 82.7% (>28 days).
- No patients tested negative for suspected penicillins but positive for others.
Conclusions:
- Delayed-reading IDTs are valuable for MDEs lasting over 4 days.
- Challenges are recommended for urticarial/angioedematous reactions (>1 day) or other cutaneous reactions (≤4 days).
- Using suspected penicillins and clavulanic acid in IDTs may decrease positive challenge rates.
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