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.