Primary herpetic gingivostomatitis is a highly contagious infection of the oral cavity which typically affects children but can also occur in adults. Symptoms may vary widely from mild discomfort to life-threatening encephalitis.

The objective of this review was to evaluate the effectiveness of systemic acyclovir for primary herpetic gingivostomatitis.

We searched the following databases: Cochrane Oral Health Group's Trials Register (to 22 May 2008); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 2); MEDLINE (1950 to 22 May 2008); and EMBASE (1980 to 22 May 2008). There were no language restrictions.

Randomised controlled trials comparing acyclovir to placebo in children and young adults < 25 years of age with a diagnosis of primary herpetic gingivostomatitis with or without herpes labialis were considered.

Two review authors independently and in duplicate screened and extracted information from, and assessed the risk of bias in the included clinical trials. The Cochrane Collaboration statistical guidelines were followed for data synthesis.

Only two clinical trials, one with 72 participants and the other with 20 participants were included in this review. The second study failed to report several methodological items and was inconsistent in its reporting of the outcomes measurement.The first trial, with a moderate risk of bias, showed better results in the acyclovir group compared to the placebo group in children < 6 years of age in reducing the number of individuals with oral lesions (risk ratio (RR) 0.10 (95% confidence interval (CI) 0.02 to 0.38)), new extraoral lesions (RR 0.04 (95% CI 0.00 to 0.65)), difficulty in eating (RR 0.14 (95% CI 0.03 to 0.58)), and drinking difficulties (RR 0.11 (95% CI 0.01 to 0.83)) after 8 days of treatment.Following the onset of treatment, three patients from the placebo group were admitted to hospital for rehydration (P = 0.11).Four children (two from the acyclovir, and two from the placebo group) showed mild gastrointestinal symptoms that resolved spontaneously after 24 to 48 hours without a change in the study treatment.

We found two relevant trials in this systematic review, only one of them could provide some weak evidence that acyclovir is an effective treatment in reducing the number of oral lesions, preventing the development of new extraoral lesions, decreasing the number of individuals with difficulties experienced in eating and drinking and reducing hospital admission for children under 6 years of age with primary herpetic gingivostomatitis.