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ABSTRACT & COMMENTARY
A randomized, double-blind, placebo-con- trolled study of herpes simplex virus gingivostomatitis was performed in 61 children 1-6 years old with culture-positive primary infection. Acyclovir 15 mg/kg/dose orally five times a day was started within 72 hours of onset of lesions and administered for seven days. Compared to placebo, treatment with acyclovir shortened the duration of oral lesions (from 10 days to 4 days), fever (3 days to 1 day), perioral lesions (5 days to none), eating and drinking difficulties (6-7 days to 3-4 days), as well as the duration of viral shedding from five days to one day. No complications were observed.
Primary herpes simplex virus infection in young children usually manifests as oral gingivostomatitis with symptoms of fever and discomfort in eating and drinking, with a typical course lasting approximately 7-10 days. Acyclovir therapy has been shown in other studies to be effective for other forms of primary (herpes genitalis, herpes neonatorum) as well as recurrent (herpes genitalis, herpes labialis) disease. The results of this study, the first to demonstrate the effectiveness of oral antiviral therapy for primary herpetic gingivostomatitis, are impressive. The study shows a significant decrease in duration of all clinical manifestations of disease, as well as decrease in duration of viral shedding. Although primary gingivostomatitis is not usually complicated in immunocompetent persons, the prolonged course and interference with oral ingestion are often problematic, especially in young children. Supportive measures, including topical anesthetics and mouthwashes and rinses, are generally distasteful and often logistically difficult to administer. The relief of symptoms provided by acyclovir treatment, if confirmed by larger studies, is sufficient to justify treatment of primary herpetic infection.
The additional costs associated with ill children not being able to attend day care and working parents or other adult patients not being able to return to work for several additional days provides further justification for treatment. The clinical presentation of primary herpetic gingivostomatitis is so characteristic that awaiting the results of viral cultures, which may require 3-4 days to confirm the diagnosis, would delay treatment and is not necessary. Therapy should be initiated within 72 hours of onset of symptoms as soon as a clinical diagnosis is made.
Recurrent disease is usually much less symptomatic and is not accompanied by fever, and, therefore, treatment is infrequently necessary. Acyclovir is available as an oral suspension containing 200 mg of acyclovir per 5 mL, and as tablets for older children and adolescents of 200 and 400 mg. (There is also an 800 mg tablet used for treatment of zoster in adults.) Topical acyclovir is not effective and is not recommended as an alternative to oral therapy.
As would be anticipated, there was no effect of treatment on the development of or the titer of antibodies. Treatment would not be expected to affect the possibility of recurrence during childhood or adulthood (at 16 months following the study, there was one episode of recurrence occurring in one child in the placebo group). Selection for or development of acyclovir-resistant virus strains is a potential risk that has been observed primarily in immunocompromised persons receiving prolonged courses of acyclovir. Treatment of an immunocompetent person with a single course for seven days is unlikely to lead to acyclovir resistance. (Dr. Jenson is Chief of Pediatric Infectious Diseases, University of Texas Health Science Center, San Antonio, TX.)