Controversies in drug allergy: Testing for delayed reactions

Abstract

Controversies exist with regards to in vivo approaches to delayed immunologically mediated adverse drug reactions (ADR) such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruption. In particular, widespread differences exist between regions and practice on the availability and use of intradermal testing (IDT) and patch testing, the standard drug concentrations used, the use of additional drugs in IDT and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T-cell mediated reactions that have shed light on immunopathogenesis and provided a mechanism of pre-prescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine SJS/TEN in Southeast Asians. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches such as skin testing and patch testing combined with ex vivo and in vitro laboratory approaches.

Recent developments and highlights in drug hypersensitivity

“…86 In the case of NIR, due to the potential risk of triggering a severe reaction, the diagnostic procedure starts with a patch test and if negative, IDTs, although recent studies suggest the performance of IDTs with no need of a previous patch testing. 87,88 Unfortunately, the real diagnostic value of STs for SCARs is unknown, as confirmatory DPTs cannot be performed for ethical reasons due to the risk of inducing a severe reaction when reintroducing the culprit drug. 55 The value for new drugs as biologicals has been analysed and positive delayed-reading IDTs confirmed NIR to bortezomib.…”

Cross‐reactivity in beta‐lactams after a non‐immediate cutaneous adverse reaction: experience of a reference centre for toxic bullous diseases and severe cutaneous adverse reactions

“…Moreover, PT is cheaper, faster and easier to perform in routine practice in comparison to IDRs. However, as recently published, a collaboration of large international networks is needed to develop and standardize in vivo diagnostic approaches …”

“…However, as recently published, a collaboration of large international networks is needed to develop and standardize in vivo diagnostic approaches. 12,25 A limitation of our study is its retrospective design, but clinical data at the acute phase were correctly collected because all patients received care on our department. Allergologic explorations were always performed with the same protocol by two practitioners who collected data in a standardized form.…”

“…Cross‐reactivity among BL is usually explored by skin tests, sometimes followed by rechallenges . However, lack of consensus and standardization remains on how to explore different types of non‐immediate CADRs . Patch tests (PTs) have been long recommended to explore non‐immediate CADRs .…”

“…24 However, lack of consensus and standardization remains on how to explore different types of non-immediate CADRs. 25 Patch tests (PTs) have been long recommended to explore non-immediate CADRs. 26 They are followed, since more recently, by delayed readings of prick and IDRs (P-IDRs) in case of negative results and only for nonsevere cases, but their added value in non-immediate CADRs induced by BL remains under-reported.…”