Lamotrigine-induced Stevens-Johnson syndrome: demonstration of specific lymphocyte reactivity in vitro.
The novel antiepileptic drug lamotrigine (LTG) is effective as an adjunctive medication in partial seizures. The main adverse effects of LTG are skin eruptions, occurring in 3-10% of the treated patients, but these are rarely severe. The risk of cutaneous side effects is increased in patients receiving sodium valproate comedication, probably by doubling the plasma half-life of LTG due to competition with hepatic glucuronidation. Conversely, the risk can be reduced by adding LTG in a lower dose. Here, we report a patient who developed Stevens-Johnson syndrome (SJS) 5 weeks after adding low-dose LTG comedication to sodium valproate. An LTG-induced pathogenesis of the SJS was considered likely by a positive lymphocyte transformation test to the drug. The patient showed maximal peripheral blood lymphocyte reactivity to 50 micrograms LTG/ml with a stimulation index of 4.7 but not to nontoxic concentrations of sodium valproate. Lymphocytes from untreated controls neither reacted to LTG nor to sodium valproate.
Sachs
B
B
Division of Immunology, Medical Institute of Environmental Hygiene, Düsseldorf, Germany.
Rönnau
A C
AC
von Schmiedeberg
S
S
Ruzicka
T
T
Gleichmann
E
E
Schuppe
H C
HC
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D003208:Concanavalin A / Q000494:pharmacology; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology; D004359:Drug Therapy, Combination; D006207:Half-Life; D006801:Humans; D000077213:Lamotrigine; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000139:chemically induced* / Q000473:pathology; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects
D000927:Anticonvulsants; D014227:Triazines; D003208:Concanavalin A; D014635:Valproic Acid; D000077213:Lamotrigine