Simplifying the drug provocation test in non‐immediate hypersensitivity reactions to amoxicillin in children: The experience of a tertiary care allergy unit

Abstract

Background: Mild non-immediate reactions (NIR) to beta-lactams (βLs) are the most common manifestation of adverse drug reactions in children, and the drug provocation test (DPT) remains the gold standard for diagnosis. However, there are still controversies about the protocol that should be used, especially regarding the administration of doses and the DPT length.Objective: This study aimed to evaluate a pediatric population with a history of mild NIR to amoxicillin (AMX) or to amoxicillin-clavulanic acid (AMX/CL) who underwent a diagnostic workup including a DPT with the culprit drug, to understand if a graded DPT or, instead, a single full dose could be the most appropriate way of administration in clinical practice. Methods:The data of children were retrospectively analyzed for a 5-year period, with demographic and clinical characteristics collected. We reported the allergy workup and the results of the DPT performed with the administration of incremental doses and a prolonged DPT at home for a total of 5 days.Results: Three hundred fifty-four patients were included. Overall, 23/354 (6.5%) DPTs were positive: 11/23 patients showed a reaction after 2-8 h after the last dose on the 1st or 2nd day (1 reacted 30 min after the last dose), 1/23 reacted with urticaria 30 min after the first dose, 11/23 reacted at home on the 5th day of the DPT. Conclusion:This paper indirectly suggests that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild NIR to AMX/CL. Moreover, this could be less time-consuming as patients would spend less time in the hospital, also considering the public health restrictions imposed during the COVID-19 pandemic.

The importance of clinical history in the diagnosis of drug hypersensitivity in children

“…The definite diagnosis was “confirmed” or “excluded” according to the final results of the complete drug allergy work‐up, which were reported on the medical charts. Among patients with a confirmed diagnosis, some had undergone drug provocation tests (DPT) 17,18 in case of non‐severe reactions, while, in case of anaphylaxis or of SCARs, the diagnosis was confirmed by a history of severe drug HR and positive in vivo/in vitro tests. The standard procedures performed included in vivo tests (skin prick tests—SPT; intradermal tests—IDT; patch tests—PTs—and DPT) and in vitro tests (specific IgE for the culprit antibiotic, in some cases lymphocyte transformation test—LTT) following the European Network for Drug Allergy (ENDA) Guidelines 19 …”

New perspectives on drug allergy in children

“…The tendency beyond reducing unnecessary tests in this population, standing for direct DPT, is to prioritize less time-consuming protocols. In this sense, Giulia Liccioli et al 12 suggest that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild nonimmediate reactions to AX/CL. When patients are confirmed as allergic and the label is definitive, rapid drug desensitization (RDD) protocols have been developed to allow safe administration of the culprit drug if there is no alternative or the second-line treatment is less effective or more toxic.…”

“…The tendency beyond reducing unnecessary tests in this population, standing for direct DPT, is to prioritize less time‐consuming protocols. In this sense, Giulia Liccioli et al 12 suggest that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild nonimmediate reactions to AX/CL.…”

Drug provocation tests in children: All that glitters is not gold

“…The negative predictive value is comparable for single‐day and extended challenges (>90%); however, a single‐day DPT may have lower sensitivity (0%–7.2%) for reproducing the reaction (false‐negative results), whereas extending the challenge at home (from 1 to 10 days) may yield higher sensitivity (2%–17.2%) at the expense of an increased risk of incidental unrelated manifestations (false‐positive results) and a lower specificity and positive predictive value 21 . This question has been extensively analyzed by other authors and is not the focus of our study 22–29 . Rather, in this paper, we review the factors that may contribute to an incorrect interpretation of DPT results—especially focusing on the apparently positive ones—in the pediatric population, and which may have an impact on the positive predictive value of the test.…”

“…21 This question has been extensively analyzed by other authors and is not the focus of our study. [22][23][24][25][26][27][28][29] Rather, in this paper, we review the factors that may contribute to an incorrect interpretation of DPT resultsespecially focusing on the apparently positive ones-in the pediatric population, and which may have an impact on the positive predictive value of the test.…”