concanavalin-a and Stevens-Johnson-Syndrome

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.

Topics: Adult; Anticonvulsants; Concanavalin A; Drug Eruptions; Drug Therapy, Combination; Half-Life; Humans; Lamotrigine; Liver; Lymphocyte Activation; Lymphocytes; Male; Risk Factors; Stevens-Johnson Syndrome; Triazines; Valproic Acid

An exfoliating substance elaborated by certain phage Group 2 staphylococci causes toxic epidermal necrolysis. Both in man and in the newborn mouse, intraepidermal cleavage is the predominant histologic feature following exposure to this toxin. Electron microscopic study of sequential biopsy specimens obtained from neonatal mice and from organ cultures of human skin revealed intercellular cleavage and cell separation. The extracellular nature of the exfoliative process was confirmed in several ways: (1) perfused tracers did not penetrate cells during cell separation; (2) cultured cells exposed to high doses of exfoliating fractions demonstrated no signs of injury; and (3) cleaved surfaces examined by scanning electron microscopy and surface replication demonstrated intact plasma membranes. When fractions capable of inducing exfoliation were applied to cultured keratinocytes of fibroblasts, sperm, or lymphocyte suspensions, and to human or mouse skin in vivo, they did not alter the distribution or intensity of concanavalin A binding, ruthenium red staining, pemphigus antibody binding, or HL-A surface antigens. Therefore, while the pathogenesis of staphylococcal toxic epidermal necrolysis involves intercellular cleavage, the molecular cell surface target remains unknown.

Topics: Animals; Binding Sites, Antibody; Cell Membrane; Concanavalin A; Cytotoxicity Tests, Immunologic; HLA Antigens; Humans; Lymphocytes; Mice; Organ Culture Techniques; Pemphigus; Ruthenium Red; Skin; Staphylococcal Infections; Stevens-Johnson Syndrome; Toxins, Biological