Introduction
Beta-lactams (BLs) are the first-line antibiotic to control many bacterial infections1. Traditionally, the most frequently prescribed antibiotic in children has been amoxicillin (AX), which has been increasingly combined with clavulanic acid (CLAV); in recent years, this formulation has become the most dominant1-2. BLs are also the most common inducers of drug hypersensitivity reactions (DHR) in children. Since systematic reporting of side-chain-specific reactions to AX were first published in the late 1980s, diagnosis has required more determinants for evaluating DHRs3. In many countries, penicillin G (PG)(benzylpenicillin) is no longer the major determinant, and classical penicillin determinants yield low sensitivity, making drug provocation tests (DPTs) necessary for diagnosis4.
The prevalence of DHR in children ranges from 2.5% to 10.2%5. More than 10% of children develop skin rashes over the course of an antibiotic treatment for a viral infection. Allergological evaluation confirms that only a few cases are confirmed allergic5,6, while most skin exanthemas are due to underlying viral infections or to interactions between drugs and infectious agents5,7,8.
An accurate diagnosis is essential for avoiding the prescription of alternative antibiotics which may be less effective, more toxic, and larger contributors to bacterial resistance. Significant differences exist between European centers in terms of diagnosing BL hypersensitivity, particularly in children7,9. Although consensus protocols have helped to ensure patient safety and accurate diagnosis, these must be adapted to between-country variations in both patients’ response to BLs and health system capacities for diagnosis.
BLs DHRs are classified as immediate (IR) and nonimmediate reactions (NIR)10. IRs usually appear within 1 h after drug administration and include urticaria, angioedema, rhinitis, bronchospasm, and anaphylaxis11. NIRs, although assumed to occur 24-48 h after drug intake5, can actually occur anytime from 1 h after taking the medication12. Clinical presentation ranges from mild reactions, such as nonimmediate urticaria (NIU) and maculopapular exanthema (MPE), to more severe reactions like acute generalized exanthematous pustulosis, drug-induced hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis (13).
The diagnostic approach varies depending on whether the reaction is immediate (IgE mediated) or nonimmediate (T cell effector response), as well as the severity, symptoms elicited, and patient risk factors. Although they have low sensitivity, skin and SIgE testing may have a role in IR12,14. Several studies support direct DPT without skin testing (ST), especially in children with mild NIR7,15-17. However, if the results are positive, avoidance of the BL involved or all the drug group is controversial because reactions can be side-chain-specific to AX, cephalosporins, or another BLs, meaning that a different class of BL could still be administered3,18.
The aim of our study was to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to BLs.