Abstract
Cutaneous adverse drug-induced reactions are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. Patients with cutaneous adverse drug-induced reactions are often exposed simultaneously to a few potentially culprit drugs. Diagnosis of cutaneous adverse drug-induced hypersensitivity relies on clinical history, skin tests, in vitro tests and provocation tests. In vitro methods are necessary to establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risk of drug provocation testing. In this review we focus on best investigated in vitro techniques for the diagnosis of T cellmediated delayed-type drug hypersensitivity reactions (DTHs) during the resolution phase. As drug hypersensitivity involves different pathomechanisms and a single diagnostic test usually does not cover all possible reactions, the combination of different tests is required to increase overall sensitivity. Standard proliferation-based assays have been supplemented by a panel of novel in vitro tests allowing analysis of the cytotoxic or secretory potential of effectors cells, and up-regulation of cell surface activation markers. We discuss the latest findings and readout systems to identify causative drugs by detecting functional and phenotypic markers of drug-reacting cells, and their ability to enable a more conclusive diagnosis of drug allergy.
Keywords: Acute generalized exanthematous pustulosis (AGEP), Delayed-type drug hypersensitivity type IV reactions (DTH), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), drug-specific cytotoxic T lymphocytes, drug-specific Lymphocyte transformation test/LTT, granulysin-ELISA test, granzyme B-ELIspot, IFNgamma-ELIspot, Stevens- Johnson/Lyell-toxic epidermal necrolysis (SJS/TEN)syndromes.
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