Medline ® Abstracts for References 14,21-23

OBJECTIVE: To determine the effect of acyclovir and prednisone treatment of herpes zoster on chronic pain and quality-of-life outcomes.

DESIGN: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design.

SETTING: 15 university hospitals or affilliated clinics.

PATIENTS: 208 immunocompetent patients older than 50 years of age who had localized herpes zoster that developed less than 72 hours before study enrollment.

INTERVENTION: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The fourtreatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone.

MEASUREMENTS: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinical visit. An intention-to-treat analysis was used.

RESULTS: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% Cl, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group.

CONCLUSIONS: In relatively healthy persons older than 50 years of age who have localized herpes zoster, combined acyclovir and prednisone therapy can improve quality of life.

BACKGROUND: Acyclovir given for 7 to 10 days is of proved benefit in acute herpes zoster, but studies of its effectiveness in preventing postherpetic neuralgia have had conflicting results. The role of corticosteroids in the treatment of herpes zoster is also controversial.

METHODS: We conducted a double-blind, controlled trial in patients with acute herpes zoster to determine whether either 21 days of acyclovir therapy or the addition of prednisolone offered any improvement over 7 days of acyclovir therapy. Patients with a rash of less than 72 hours' duration were assigned to receive acyclovir (800 mg orally, five times daily) for 7 days with either prednisolone or placebo, or acyclovir for 21 days with either prednisolone or placebo. Prednisolone therapy was initiated at a dose of 40 mg per day and tapered over a three-week period. Patients were assessed frequently through day 28 and then monthly through month 6 to assess postherpetic neuralgia.

RESULTS: Of 400 patients recruited, 349 completed the study. No significant differences were detected between the four groups in the progression of the rash (P>0.1). With steroid therapy, a significantly higher proportion of the rash area had healed on days 7 and 14 (P = 0.02). Pain reduction was greater during the acute phase of disease in patients treated with steroids or 21 days of acyclovir (P<0.01 and P = 0.02, respectively, on day 7; P<0.01 for steroid therapy on day 14). However, on follow-up there were no significant differences between any of the groups in the time to a first or a complete cessation of pain. The steroid recipients reported more adverse events.

CONCLUSIONS: In acute herpes zoster, treatment with acyclovir for 21 days or the addition of prednisolone to acyclovir therapy confers only slight benefits over standard 7-day treatment with acyclovir. Neither additional treatment reduces the frequency of postherpetic neuralgia.

In a randomised, double-blind, controlled study of the effect of prednisolone on the development of post-herpetic neuralgia 78 patients with herpes zoster whose pain and exanthema had been present for less than 96 h were given 800 mg acyclovir five times daily for 7 days and prednisolone in a total dose of 575 mg, starting with 40 mg daily in the first week and tapering off over the next 2 weeks. 18 (23%) of the patients had post-herpetic neuralgia at 6 months after the acute zoster, 9 (24.3%) having received prednisolone and 9 (22.5%) placebo. The 95% CI for the difference between the placebo and prednisolone groups in the proportion of patients having pain at 6 months was minus 17% to plus 20%. Prednisolone, however, relieved pain for the first 3 days. The 1-2 week interval between admission and reappearance of pain and development of triggered pain seems to be the time needed to establish neuralgia. Once established, the type and intensity of pain remained largely unaltered.

The effects of prednisone, oral acyclovir, and radiotherapy were compared with placebo in the prevention of post-herpetic neuralgia. No treatment used was able to prevent, with statistical significance, post-herpetic neuralgia, although prednisone and acyclovir showed some pain reduction in the acute phase. Radiotherapy was of no value in either the acute or post-herpetic phase.