Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption

TLDR

Lymphocyte transformation test (LTT) is a reproducible in‑vitro assay for drug‑specific T‑cell activation, yet its accuracy depends on timing and treatment. This study aimed to identify the optimal timing for LTT to pinpoint the causative drug in various drug‑reaction phenotypes. LTT was performed at multiple stages during the course of maculopapular eruptions, Stevens‑Johnson syndrome/toxic epidermal necrolysis, and drug‑induced hypersensitivity syndrome/drash and eosinophilia with systemic symptoms. The test yielded positive results at the acute phase for maculopapular eruptions and SJS/TEN, but only at the recovery phase for DIHS/DRESS, indicating that LTT should be conducted within one week of rash onset for the former and 5–8 weeks after onset for the latter.

Abstract

Background: Lymphocyte transformation test (LTT) is a safety and reproducible test to assess activation of drug‐specific T cells in vitro ; however, there are several practical concerns such as the time of testing and the influence of treatment. Our aim was to define the right timing to perform LTT for determining the causative agent in various types of drug reactions. Methods: Lymphocyte transformation test was performed at different time points during the evolution of three types of drug reactions, maculo‐papular type of drug eruptions (MP), Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and drug‐induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS). Results: Positive LTT reactions were obtained when the test was performed at the acute stage but not the recovery stage in MP and SJS/TEN, while positive LTT reactions were obtained at the recovery stage but not the acute stage in DIHS/DRESS, regardless of treatment with systemic prednisolone. Conclusions: Lymphocyte transformation test is a reliable method to define the causative agent, when LTT is performed at the right timing depending on the type of drug reactions. Lymphocyte transformation test should be performed within 1 week after the onset of skin rashes in patients with MP and SJS/TEN; and 5–8 weeks after in patients with DIHS/DRESS, respectively.