Twenty patients who suffered from more than four attacks of
erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of
acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent
herpes simplex. In the
acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo-treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous
acyclovir did not have any attacks of EM while taking the
drug, and one showed almost complete disease suppression. Following treatment with
acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the
acyclovir-treated group nine of the 11 patients had
herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on
acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic
infection. In this study, we have shown that continuous
acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission.