Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced Stevens- Johnson syndrome or toxic epidermal necrolysis.

Summary Background Prior use of 'lymphocyte transformation test' ( LTT) in Stevens- Johnson syndrome ( SJS) and toxic epidermal necrolysis ( TEN) provided conflicting results, possibly dependent on sampling dates (acute vs. late). Objective Evaluation of LTT in patients with SJS or TEN who reacted to lamotrigine ( LTG). In a small subgroup we explored the possible role of regulatory T cells (T-reg). Methods Acute phase samples (9) and post-recovery samples (14) from cases of SJS or TEN to LTG were provided by the Regi SCAR-study group. Controls were persons never exposed to LTG (12), patients exposed without reaction (6), and patients who developed a mild eruption to LTG (6). LTT was performed by measuring ³H-thymidine incorporation after 3 days of incubation with phytohemmaglutinin, LTG (10 μg/mL) or medium. Stimulation index ≥ 2 was considered positive. In 16 cases LTT was redone after depletion of T-reg by fluorescence activated cell sorting. Results Positive LTT was observed in 3/6 cases of mild eruptions, 1/9 SJS/ TEN-cases tested during the acute phase and 3/14 SJS/ TEN-cases tested after recovery. We noted a very mild and nonsignificant trend for an increased response after depletion of T-reg in late samples from SJS or TEN patients. Conclusions and Clinical Relevance With the largest number of LTT performed in patients with SJS or TEN to a single drug, we confirmed that reactive cells are rarely detected in these reactions. Poor reactivity did not seem related to T-reg. Other in vitro assays than those testing proliferation should be evaluated, before raising the hypothesis that specific cells disappeared by undergoing apoptosis during the reaction. [ABSTRACT FROM AUTHOR]