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Should we use aciclovir for children with primary herpetic stomatitis?

Three Part Question

In [children with primary herpetic stomatitis] is [the use of aciclovir better than conservative treament] at [reducing the duration of fever, oral lesions, extraoral lesions, eating difficulties and drinking difficulties]?

Clinical Scenario

A 5 year old girl presents to your ED complaining of a 2 day history of painful lesions in her mouth, fever and difficulty in eating. You diagnose primary herpetic stomatitis and wonder if aciclovir will reduce the duration of her symptoms.

Search Strategy

Medline1950-10/07 using the Ovid interface and The Cochrane Library 21-11-2007.
Medline: [exp Acyclovir/ OR ac$] OR [(exp Antiviral Agents/ OR antiviral OR anti-viral OR 'anti viral').mp] AND [exp Stomatitis, Herpetic/ OR herpes] LIMIT to (humans AND english language AND yr="1984 - 2007")
Cochrane Library: herpes stomatits OR herpetic gingivostomatitis AND aciclovir

Search Outcome

Altogether 119 papers were found in Medline of which 118 were irrelevant or of insufficient quality. 30 Clinical trials were found in Cochrane of which 28 were irrelevant or of insufficient quality and 1 was in French. 8 Cochrane Reviews were found of which 7 were irrelevant and 1 which was relevant was only in the protocol stage.
The relevant paper in both searches is the same and is summarised in the table below.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Amir J et al
72 children aged 1-6years with clinical manifestations of gingivostomatitis lasting less than 72 hours. They were given aciclovir suspension 15mg/kg five times a day for seven days, or placebo. 61 children with cultures +ve for HSV finished the study.Randomised double blind placebo controlledDuration of oral lesions (days)Median of 4 for aciclovir vs 10 for placebo (Mann-Whitney)Statistical reporting of p values was poor. Medication administered 5 times daily may affect the compliance. Small numbers in a single centre.
Duration of fever (days)Median of 1 for aciclovir vs 3 for placebo (Mann-Whitney)
Duration of drooling (days)Median of 2 for aciclovir vs 5.5 for placebo (Mann-Whitney)
Duration of eating difficulties(days)Median of 4 for aciclovir vs 7 for placebo (Mann-Whitney)
Duration of drinking difficulties (days)Median of 3 for aciclovir vs 6 for placebo (Mann-Whitney)
Number of days to last +ve viral culture results (days)Median of 1 for aciclovir vs 5 for placebo (t test)
Rate of hospital admissions0 for aciclovir vs 3 for placebo (p=0.11)


Good results were obtained in this study for commencing treatment in a time frame generally achievable in practice. It is a most unpleasant illness for both children and carers hence hastening resolution of the symptoms would be highly desirable. However, there is a lack of clear evidence on the impact on clinically significant events ie. reduction in hospital admission. The study shows the potential of aciclovir but many feel that a multicentre trial would be beneficial. Currently there is a protocol in the Cochrane Library for a systematic review into the use of aciclovir in the treatment of primary herpetic gingivostomatitis.

Clinical Bottom Line

At present time follow local guidelines.


  1. Amir J et al Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study BMJ 21 June 1997, pp 1800-1803