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Three Part Question

In [immunocompetent adults with acute shingles] is [early acyclovir better than late acyclovir] at [promoting rash healing and minimising the painful period]?

Clinical Scenario

A 56 year old immunocompetent man presents to the emergency department at 10pm on a Saturday night with acute shingles. You know acyclovir is effective but wonder how quickly it needs to be started.

Search Strategy

Medline 1966-05/00 using the OVID interface.
({exp herpes zoster OR herpes zoster.mp OR shingles} AND {exp acyclovir OR acyclovir.mp OR exp antiviral agents OR antiviral agent$.mp OR anti viral.mp OR anti-viral.mp}) AND maximally sensitive RCT filter LIMIT to human AND english.

Search Outcome

23 papers found of which 20 were irrelevant or of insufficient quality for inclusion, or subject to metaanalysis. The remaining 3 papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Jackson JL et al, 1997, USA	5 placebo controlled randomised clinical trials. All trials used acyclovir 800mg 5 times daily within 72 h of onset	Metaanalysis	Pain at 6 months	Summary odds ratio 0.54 (0.36-0.81) in patients treated with acyclovir
Whitley RJ et al, 1998 USA	6 randomised controlled double blind studies. Trials 1 to 3 compared oral acyclovir with placebo	Metaanalysis	Factors influencing duration of pain	Age, prodromal pain, acute pain intensity	No separate data for trials 1-3.
			Factors not influencing duration of pain	Sex, time from rash onset to initiation of treatment
Wood MJ et al, 1998, UK	3 placebo-controlled studies or oral acyclovir. All trials used acyclovir 800mg 5 times daily.. Early (< 48 h) vs late (48 - 72h) treatment	Metaanalysis	Resolution of zoster-related pain in:
			All patients	Hazard ratio 1.79 (1.43-2.39)
			Patients over 50 y	Hazard ratio 2.13 (1.42-3.19)

Comment(s)

All 3 metaanalyses used 3 core papers - but there was enormous variation in the other papers otherwise. Thus selection bias may have occurred.

Clinical Bottom Line

Early oral acyclovir (less than 48 hours after onset of rash) will significantly shorten the duration of herpes related pain in shingles.

References

1. Jackson JL, Gibbons R, Meyer G et al. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia Arch Intern Med 1997;157:909-12.
2. Whitley RJ, Shukla S, Crooks RJ. The identification of risk factors associated with persistent pain following herpes zoster J Infect Dis 1998;178 (Suppl 1):S71-S75.
3. Wood MJ, Shukla S, Fiddian AP et al. treatment of acute herpes zoster: Effect of early (< 48 h) versus late (48-72 h) therapy with acyclovir and valaciclovir on prolonged pain J Infect Dis 1998;178 (Suppl 1):S81-S84.