Oral acyclovir within 24 hours of onset of varicella rash reduced maximum number of lesions and time to full crusting in immunocompetent adults
ACP J Club. 1993 Jan-Feb;118:13. doi:10.7326/ACPJC-1993-118-1-013
Wallace MR, Bowler WA, Murray NB, Brodine SK, Oldfield EC III. Treatment of adult varicella with oral acyclovir. A randomized, placebo-controlled trial. Ann Intern Med. 1992 Sep 1;117:358-63.
To assess the effectiveness of oral acyclovir in the treatment of varicella in immunocompetent naval personnel.
Randomized, double-blind, placebo-controlled trial of 7 days duration, with patients stratified by time from onset to admission.
Isolation area in a naval hospital.
Adults aged ≥ 17 years who were admitted to the hospital < 72 hours after the onset of a varicella rash were eligible. Exclusion criteria were pregnancy, antiviral therapy or treatment with immunoglobulin products during the previous week, vaccination for varicella, human immunodeficiency virus positivity, acyclovir intolerance, or renal disease. Of 206 patients screened, 148 (mean age 20 y, 98% men) met the eligibility criteria and were divided into an early treatment group (rash for < 24 h, n = 76) and a late treatment group (rash for 25 to 72 h, n = 72).
74 patients were assigned to acyclovir, 800 mg orally 5 times per day for 7 days, and 74 to placebo. Acetaminophen was given for fever and diphenhydramine for pruritus.
Main outcome measures
Daily evaluations were made of the number and condition of lesions within a 25 × 25 cm area on the chest and back and of fever and complaints of pruritus, anorexia, and lethargy. Complications were recorded.
Early treatment with acyclovir shortened the time to maximum number of lesions from 2.1 to 1.5 days (P = 0.002); decreased time to healing from 3.3 to 2.6 days (P < 0.001); produced full crusting in 5.6 compared with 7.4 days (P = 0.001); and reduced the number of lesions by 46% (P = 0.04). Fewer patients in the early treatment group compared with those in the early placebo group took > 7 days for full crusting (P = 0.02) (Table). Early acyclovir treatment reduced the duration of fever from 2.7 to 2.2 days (P = 0.02), and other symptoms tended to be fewer. No differences were found between late treatment with acyclovir and with placebo. No severe cases of pneumonia or skin infections developed, and no deaths or cases of encephalitis occurred.
Treatment with acyclovir begun within 24 hours of onset of varicella rash reduced the time to full crusting and maximum number of lesions in immunocompetent young adults.
Source of funding: Burroughs-Wellcome Company (drug and placebo).
For article reprint: Dr. M.R. Wallace, Clinical Investigation Department, San Diego Naval Hospital, San Diego, CA 92134-5000, USA. FAX 619-532-8137.
Table. Acyclovir vs placebo within 24 hours of varicella rash onset in immunocompetent naval personnel*
|Outcome||Acyclovir||Placebo||RRR (95% CI)||NNT (CI)|
|> 7 days to achieve 100% crusting||32%||58%||45% (8 to 69)||4 (3 to 26)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
Wallace and colleagues' randomized, placebo-controlled study of the efficacy of oral acyclovir in adult varicella was well designed. A modest but clear benefit was shown for high-dose acyclovir if begun within 24 hours of the onset of the rash. The absence of benefits after 24 hours should, however, clearly tell clinicians not to treat normal persons who present with a rash of more than a day's duration.
In addition to military personnel, this study may be applicable to other groups such as health care workers, who may have both an increased risk for exposure in the workplace and an increased opportunity to transmit the infection. They may notice the initial lesions of varicella early, providing the opportunity for treatment. Even with treatment, it is important to quarantine infected persons from the workplace to limit transmission, to identify their contacts in the 1 to 2 days before and at the onset of the rash, and, if still hospitalized 10 days later, to isolate the contacts until at least day 21 after the contact (1). The study by Wallace and colleagues suggests that prompt treatment of persons with lesions could hasten recovery and return to work. The cost of acyclovir would then be favorably balanced against lost work time. Prompt recognition of infection and exclusion from work are, however, the established policies for controlling infection, and there is no evidence yet to suggest that acyclovir will limit transmission of varicella.
Presumably valacyclovir and famciclovir, currently licensed for the treatment of herpes zoster infections, would also be effective for adult varicella, but these regimens have not been studied in varicella.
Other questions still to be answered include whether severe complications of adult varicella are less frequent in patients treated with acyclovir and whether oral acyclovir should be used for prophylaxis of persons exposed to varicella, of particular concern for exposed pregnant women. Varicella immune globulin is recommended for immunosuppressed patients who have been exposed to varicella. But now, use of the varicella vaccine (where licensed) in susceptible adults to prevent injection should be the approach (2).
Martha Harwit, MD
Stanford UniversityStanford, California, USA