In vitro diagnostic testing for drug allergy in children

Abstract

Diagnosing Drug Hypersensitivity Reactions (DHRs) could be a complicated process especially in children, since allergic-like manifestation at this age is more often the expression of concomitant infections rather than a actual DHRs. In vivo tests are usually suggested as a first step; however, prick and intradermal tests could be painful and have shown different sensitivity and specificity among published studies. In some cases, in vivo tests such as Drug Provocation test (DPT) could be even contraindicated. Therefore, the need for in vitro testing is compelling, to add useful information along the diagnostic pathway and to limit the need of DPT. In this review, we analyze the different types of in vitro tests, focusing on those used more widely such as specific IgE and on those that are still for research settings, such as basophil activation test and lymphocyte transformation test, but that have shown some useful diagnostic potential.

Drug-Induced Anaphylaxis in Children

“…The European Network for Drug Allergy/European Academy of Allergy and Clinical Immunology (ENDA/EAACI) guidelines advise conducting in vitro or in vivo tests 4 to 6 weeks after the reaction to await acute symptoms’ resolution and reduce false-negative results [ 29 ]. When parents do not consent to in vivo tests, including DPTs, in vitro tests represent a less risky method to assess drug allergies in children [ 30 ]. In vitro tests may be considered, particularly for those with a history of severe anaphylaxis, because of the risk of reproducing systemic reactions with in vivo tests [ 31 ].…”

Approach for delabeling beta-lactam allergy in children

“…However, the sensitivity values are limited (0%–50%), and evidences of not optimal specificity have been reported, related to false-positive to penicillin V and the influence of total IgE values ( 113 – 117 ). Moreover, its use is limited because it is only available for some BL structures (benzylpenicilloyl, amoxicilloyl, penicilloyl V, ampicilloyl, cefaclor) ( 118 ). Despite these limitations, their performance is recommended prior to in vivo tests in severe reactions, as reported by EAACI pediatric task force ( 106 ), or in complex cases with negative and/or confusing skin testing as proposed in a recent EAACI position paper ( 49 ), in order to reduce the need for DPT.…”

“…The sensitivity and specificity values range from 58% to 89% and from 85% to 100%, respectively ( 112 ). The differences in sensitivity values are related to clinical phenotypes, with higher values in mild and moderate reactions compared with that in severe reactions ( 112 , 118 ). Although most of the studies refer to adult population, a recent study including 25 children with positive clinical histories of delayed skin reactions to amoxicillin or the amoxicillin–clavulanic acid combination confirmed by DPT showed a lymphocyte transformation test sensitivity of 52% and specificity of 92%, with a positive predictive value of 86% and a negative predictive value of 65% ( 125 ).…”