When a two-tier algorithm of the C6 ELISA with the IgG or IgM WB was used, the positivity rate in convalescent EM dropped from 93.8% for the C6 as a single assay to 56.3% for the C6–IgM combination and to 34.4% for the C6–IgG combination. This evidence concerns the gene CD40LG and erythema multiforme.