Prolonged drug provocation with an initial full therapeutic dose to diagnose serum sickness-like reactions (SSLR) to β-lactams in childrenMarcel M Bergmanna,b,c, Eva Gomesd, Natalia Blanca-Lópeze, Jean-Christoph Caubeta, Philippe A Eigenmanna , Giulia Liccioli f, Francesca Morif, Marina Atanaskovic Markovicga Pediatric allergy unit, Department of women, children and adolescents, University Hospitals of Geneva, Geneva, Switzerlandb Centro Pediatrico del Mendrisiotto, Mendrisio, Switzerlandc Faculty of Biomedical Science, Università della Svizzera Italiana (USI), Lugano, Switzerlandd Serviço de Imunoalergologia, Centro Hospitalar Universitário do Porto, Porto, Portugale Servicio de Alergia, Laboratorio de Investigación, Hospital Universitario Infanta Leonor, Madrid, Spainf Allergy Unit, Meyer Children’s University Hospital, IRCCS, Florence, Italyg University of Belgrade Faculty of Medicine, University Children’s Hospital, Belgrade, Serbia

A proper allergy work-up, based on the gold standard drug provocation test (DPT), usually rules out suspected drug hypersensitivity in children. These tests are generally open, given their high efficiency compared to double-blind placebo-controlled DPTs. Although their negative predictive value is excellent, no studies have calculated their positive predictive value, highly dependent on the prevalence of the disease. Most studies have found a rate of less than 5% to 10% of true beta-lactam hypersensitivity in children. Given this low prevalence (pre-test probability), a few false positive results can significantly reduce the estimated positive predictive value. False positives may arise from the nocebo effect during the test, including nocebo by proxy, or from observer bias, which depends on professional expertise and organizational circumstances. Some studies have found a high rate of tolerance on a second DPT in children who failed the first, but these results may be affected by the interval between the two tests, of a year or more in most cases, reflecting a loss of hypersensitivity over time. Taking into account the low rate of positive DPTs, with commonly mild reactions, we suggest confirming non-severe positive DPTs with a second provocation performed soon after the first, especially in the case of beta-lactam antibiotics, in order to improve the diagnostic accuracy, de-label more patients, and achieve a better estimation of true drug hypersensitivity prevalence.

Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited and spontaneously resolve within days after drug discontinuation, sometime HRs reactions to AEDs can be severe and life threatening. Aim: This paper seeks to show examples on practical management of AEDs HRs in children starting from a review of what it is already known in literature. Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications and genetic factors. The diagnosis work-up consists of in vivo (Intradermal testing and Patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays and granulysin (Grl) in flow cytometry]. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. Conclusion: Dealing with AEDs HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternate anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

A document by Luca Pecoraro. Click on the document to view its contents.