Herpes Infection References
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Amir J, Harel L, Smetana Z, Varsano I
Treatment of herpes simplex gingivostomatitis with aciclovir in children: a
randomised double blind placebo controlled study [see comments]
BMJ 1997; 314 1800-3]
OBJECTIVES: To examine the efficacy of aciclovir suspension for treating
herpetic gingivostomatitis in young children. DESIGN: Randomised double blind
placebo controlled study. SETTING: Day care unit of a tertiary paediatric
hospital. SUBJECTS: 72 children aged 1-6 years with clinical manifestations of
gingivostomatitis lasting less than 72 hours; 61 children with cultures
positive for herpes simplex virus finished the study. MAIN OUTCOME MEASURES:
Duration of oral lesions, fever, eating and drinking difficulties, and viral
shedding. INTERVENTION: Aciclovir suspension 15 mg/kg five times a day for
seven days, or placebo. RESULTS: Children receiving aciclovir had oral lesions
for a shorter period than children receiving placebo (median 4 v 10 days
(difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier
disappearance of the following signs and symptoms: fever (1 v 3 days (2 days,
0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral
cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days
(3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to
4.9)). Viral shedding was significantly shorter in the group treated with
aciclovir (1 v 5 days (4 days, 2.9 to 5.1)). CONCLUSIONS: Oral aciclovir
treatment for herpetic gingivostomatitis, started within the first three days
of onset, shortens the duration of all clinical manifestations and the
infectivity of affected children. Further studies are needed to evaluate the
ideal dose and length of treatment.

Comment: BMJ 1997;315:1162 (1 November) Letters
Aciclovir in herpes simplex gingivostomatitis
Children studied were not representative of those seen in casualty
departments.
Editor-Amir et al's paper on the treatment of primary herpes gingivostomatitis
covered a common clinical problem in young children1; few randomised placebo
controlled studies have been carried out of treatment for the condition. It is
disappointing that this paper has misleading key messages and is unhelpful for
those who have to decide how to treat this problem in casualty departments.

The study looked at a select population referred to a tertiary paediatric
hospital within 72 hours of the first appearance of lesions. Altogether 84% of
the children had <20 lesions. In my experience, few children present to
casualty departments in this manner. In a study of 31 children with
gingivostomatitis due to herpes simplex virus type 1 who presented to the
casualty department of a children's hospital in inner city London, 84% had had
lesions for over 72 hours (range 1-7 days (mean 5 days)).2 Sixty eight per
cent had multiple lesions and would have been classified by Amir et al as
having severe disease (>20 lesions), including three of the five children with
a history of illness of <72 hours.

Aciclovir inhibits viral replication, and thus it is not surprising that a
beneficial effect was found in children who presented early in their illness
with mild disease (<20 lesions). Aciclovir decreases antibody response to
herpes simplex virus proteins in primary genital herpes infections and has
been associated with earlier and more severe recurrences when treatment groups
were compared with placebo groups.3 4 It is a shame that Amir et al's study
did not address these two issues in detail.

Despite aciclovir being an expensive drug that is given five times a day at
recommended intervals of four hours, it is often readily prescribed for herpes
simplex gingivostomatitis by junior doctors in paediatrics. Until further
randomised placebo controlled clinical trials are performed, particularly
looking at children with multiple lesions or late presentation, it would seem
prudent to reserve aciclovir for patients who have altered immunity and
instead ensure that pain relief is given in all cases.

Helen M Goodyear, Consultant paediatrician
Birmingham Heartlands Hospital, Birmingham B9 5SS