Key messages

• It is not clear if acyclovir reduces lesions or pruritus in patients with varicella because the certainty of the evidence is very low.
• Acyclovir might not reduce the complications associated with varicella, but the certainty of the evidence is low.

What is the evidence.
See evidence matrix  in Epistemonikos later

We found three systematic reviews [1],[2],[3] that included three primary studies [4],[5],[6], all corresponding to randomized trials.

What types of patients were included*

All trials considered only immunocompetent patients, with less than 24 hours from the beginning of symptoms. Two trials [4],[6] required laboratory confirmation, and one only a clinical diagnosis [5].
All trials included patients under 18 years of age. One trial included patients between 5 and 16 [4]; one trial between 2 and 12 [5] and one trial only included adolescents between 13 and 18 years [6].
Exclusion criteria were: participants over 18 years old, immunocompromised patients or who had received varicella vaccine [4],[5],[6].
All trials were performed on an outpatient basis [4],[5],[6].

What types of interventions were included*

All trials used acyclovir as an intervention and compared it against placebo.
One trial [4] adjusted the dose according to age: 20 mg/kg for those between 5 and 7, 15 mg/kg for patients between 7 and 12, and 10 mg/kg for adolescents between 12 and 16 years. One trial [5] administered 800 mg and one trial [6] adjusted the dose by body weight.
All trials used acyclovir for 5 days in 4 daily doses, initiated within the first 24 hours.

What types of outcomes
were measured

The trials measured multiple outcomes, which were pooled by the identified systematic reviews as follows:

• Days of appearance of new lesions.
• Total number of lesions.- Duration of fever (37.8 ° C).
• Duration of pruritus.
• Skin complications: Bacterial superinfection.
• Complications of the central nervous system: Ataxia, meningoencephalitis.
• Respiratory complications: Acute pneumonia, otitis media, pharyngitis and bronchitis.

The follow-up was 28 days in two trials [5],[6] and up to 1 year in one trial [4].

To whom this evidence does and does not apply

• The evidence presented in this summary applies to children and adolescents who have varicella in an outpatient setting, and who receive treatment with acyclovir in the first 24 hours from the onset of symptoms.
• It does not apply to patients with immunodeficiency, due to the direct exclusion of these in all the trials analysed.

• The outcomes reported are those considered critical for decision-making, according to the opinion of the authors of this summary, and are in agreement with the ones selected by the main systematic reviews.
• We considered the inclusion of the outcomes duration of lesions, hospitalizations and mortality; however, they were not reported. Considering the absence of effect in the other outcomes, there is no reason to expect an effect on the former.

• Although the intervention could reduce the duration of fever, this effect does not translate into a decrease in the complications associated with varicella. In summary, it could bring a marginal benefit in the acute course of the disease, decreasing the duration of fever.

• Considering that varicella is a self-limiting disease, that the trials used acyclovir in the first 24 hours of the rash, and that the economic cost of acyclovir is considerable, the clinical benefit of its use seems marginal in relation to its costs.

• Considering there was no effect on the complications of varicella or a clinically relevant benefit for patients, most patients and their doctors should lean against the use in a population similar to the one evaluated in the trials. However, it is particularly important to inform patients and their caregivers about the existing uncertainty.

Differences between this summary and other sources

• All the systematic reviews [1],[2],[3] excluded one trial [4] to estimate the benefits of acyclovir in terms of the total number of lesions and the days of appearance of new lesions, but this did not lead to different results to those obtained by this summary.
• The effect of acyclovir in varicella was similar in children (2-12 years) and adolescents (12-18 years), which contrasts with the common belief that treatment would have a larger effect on adolescent population.
• In the Varicella Zoster guideline of the Royal College of Physicians, symptomatic treatment is recommended acyclovir is not mentioned. This intervention is reserved for immunosuppressed or older adults [7].

• The probability of future evidence changing the conclusions of this summary is high, due to the existing uncertainty.
• We did not identify ongoing trials addressing this question in the International Clinical Trials Registry Platform of the World Health Organization or systematic reviews in progress in the PROSPERO International prospective register of systematic reviews.