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

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 RegiSCAR-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.