"Delabeling" by direct provocation testing in children and adolescents with a suspected history of a delayed reaction to β-lactam antibiotics: Consensus paper of Gesellschaft für pädiatrische Allergologie und Umweltmedizin (GPAU), Deutsche Gesellschaft für Allergologie und klinische Immunologie (DGAKI), and Ärzteverband deutscher Allergologen (ÄDA).

Background: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to β-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection.
Materials and Methods: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies.
Results: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE.
Conclusion: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
Competing Interests: The author declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article. Table 1.Warning signs of β-lactam allergy, modified according to [1, 12]. Immediate reactionDelayed reactionConjunctival erythemaPronounced facial edemaShock symptoms (arterial hypotension/dizziness)Atypical target lesions, bullous lesionsCoughing, sneezing, wheezing ErythrodermaDyspneaHemorrhagic and necrotic lesionsHoarsenessPainful skin, mucous membrane involvementDysphagiaGeneralized lymphadenopathyPathological laboratory findings (e.g., liver enzyme elevation, impaired renal function) Table 2.Provocation regime [6, 8, 15]. Day 1 (practice/clinic)Day 2 (at home)Day 3 (at home)1 single doseDaily dose distributed in 2 – 3 doses (depending on the antibiotic)Daily dose distributed in 2 – 3 doses (depending on the antibiotic)Monitoring for 1 hourStart ~ 24 hours after the first dose day 1**Wash-out period should be ~ 24 hours so that delayed reactions can be recorded after the 1st dose during the time interval between reaching the therapeutic dose and the subsequent dose. Figure 1Estimates on the likelihood of allergic cross-reactions between the various β-lactam antibiotics ([14]).
(© Dustri-Verlag Dr. K. Feistle.)