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Three Part Question

[In a child] with [herpes simplex gingivostomatitis], will [antiviral treatment aid their recovery]?

Clinical Scenario

A child presents to the ED with ulcers in their mouth causing significant pain and difficulties with eating and drinking. You wonder if they may have Herpes gingivostomatitis and whether antiviral therapy may speed their recovery.

Search Strategy

Medline and Embase 1996 to date via Dialog Datastar and Cochrane library The Cochrane Database of Systematic Reviews (Cochrane Reviews), The Cochrane Central Register of Controlled Trials (Clinical Trials)
Medline; Search Hepes simplex virus AND children AND oral-ulcer#. DE. OR stomatitis. W..DE, OR Gingivostomatitis thesaurus mapped to STOMATITIS-HERPETIC.DE. OR STOMATITIS.W..DE. OR GINGIVITIS.W..DE. OR HERPES-SIMPLEX.DE. OR ORAL-ULCER.DE. OR GINGIVAL-DISEASES.DE. AND aciclovr OR acyclovir. Limited to clinical trials and human.
Embase ;
Herpes simplex virus AND (gingivostomatitis thesaurus mapped to stomatitis or gingivitis or herpes virus infection or herpes or herpes simplex virus or gingivadisease) AND (acyclovir OR acyclovir). AND children limited to clinical trials and human. 42 results, titles and abstracts screened,
Cochrane;
Herpes simplex virus AND gingivostomatitis AND (acyclovir OR aciclovir) AND children

Search Outcome

Altogether 11 papers were found via medline,. 42 papers were found via Embase and two via Cochrane. Screening of abstracts identified five papers of relevance and one proposal for a Cochrane Review yet to be completed. Two papers were excluded as written in French and Hebrew. The remaining three papers were reviewed and two excluded as these were reviews. Scanning the references of these papers did not identify any further papers of relevance or sufficient quality to be included. One RCT cited in a reference was unavailable as it has not been published. The relevant paper is summarised in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Jacob Amir 21 June 1997	Children 1-6 yrs of age with a clinical manifestation of ginigivostomatitis lasting <72hrs presenting to 2 different medical centres	RCT 1B	Duration of oral lesions	Median duration reduction of 5 days for aciclovir vs. placebo 95% CI 2.4 -7.6	Exclusion criteria not stated in methodology. Blinding process not described for the assessor. The author performed the follow up assessments with no second checker. No comparison of demographic variables for patients used for intention to treat analysis.
			Duration of eating difficulties	Median duration reduction of 3 days for aciclovir vs. placebo 95% CI 1.2-4.8
			Duration of drinking difficulties	Median duration reduction of 2 days for aciclovir vs. placebo 95% CI 0.3-3.7
			Viral shedding	Median duration reduction of 4 days for aciclovir vs. placebo 95% CI 2.7-5.3

Comment(s)

Herpes gingivostomatitis is a common problem affecting children with significant morbidity. This small RCT is the only trial to help identify an evidence based answer to the question. There are methodological floors to this trial which may bias the results. The results may be statistically and clinically significant to support the use of aciclovir to speed the recovery of children and also to decrease the duration of infectivity via viral shedding. Aciclovir is a relatively cheap, widely available medication with limited side effect profile supporting its use in a primary care/ED setting.

Clinical Bottom Line

I would support the use of aciclovir, 15mg/kg, 5 times per day for 5 days for the treatment of likely herpes gingivostomatitis in children presenting with symptoms for less than 72 hours.

References

1. Jacob Amir Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study BMJ 1997;314:1800