Abstract

Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic “in clinic” approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT are, in general, performed no sooner than 4–6 weeks after resolution of the acute reaction at the maximum non-irritating concentrations. Functional in vitro and ex vivo assays have largely remained the province of research laboratories and include lymphocyte transformation test (LTT) and cytokine release enzyme linked ImmunoSpot (ELISpot) assay, an emerging diagnostic tool which uses cytokine release, typically IFN-γ, after the patient’s peripheral blood mononuclear cells are stimulated with the suspected drug(s). Genetic markers such as human leukocyte antigen have shown recent promise for both pre-prescription screening as well as pre-emptive and diagnostic testing strategies.

Highlights

  • In this review, we will address the immune mechanisms of delayed hypersensitivity and how they have formed the premise for diagnostic methods used in the clinic and research laboratory such as intradermal skin testing (IDT), patch testing (PT) and new and investigational laboratory-based methods such as the lymphocyte transformation test (LTT) and the enzyme linked ImmunoSpot (ELISpot) assay

  • maculopapular exanthema (MPE) or morbilliform drug eruption is the most common of the self-limiting reactions to drugs characterized by erythematous macules and papules that can become generalized and confluent and are associated with pruritis and/or mild eosinophilia (Peter et al, 2017)

  • The main clinical features of drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) are erythematous urticaria-like plaques or violaceous skin eruption that can progress to exfoliative dermatitis, facial and extremity edema, lymphadenopathy, fever, biological abnormalities and internal organ involvement

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Summary

INTRODUCTION

The role of genetic markers such as human leukocyte antigen (HLA) in screening, early diagnosis and diagnosis will be discussed

Diagnostic Methods in Delayed Drug Hypersensitivity
Findings
DIAGNOSTIC METHODS
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