Treatment of erythema multiforme (EM) is not codified. We performed a systematic review of the effect of any topical or systemic treatment on time to healing and frequency of episodes with acute and chronic forms of EM in adults. Four databases (MEDLINE, CENTRAL, EMBASE and LILACS) and other sources were searched for articles published up to 20 March 2018. Randomized control trials (RCTs), observational studies and case series (n ≥ 10) were considered.
From 1558 references, we included one RCT and six case series. The RCT (n = 20) showed a significant difference in complete remission of EM with continuous acyclovir vs. placebo over 6 months. One case series found a mean reduction in flare duration with thalidomide for recurrent EM (5.1 vs. 16.2 days; n = 20).
Adverse events were poorly or not reported in included studies. Quality of life was never assessed. One limitation of our study is that we excluded the cases of isolated mucosal EM in order to prevent inclusion of Stevens‐Johnson syndrome cases. In conclusion, there is low‐level evidence for continuous acyclovir treatment for recurrent EM (one RCT). Evidence for other treatments is only based on retrospective case series. Results for thalidomide, in particular, encourage further research.