Correspondence
Acyclovir for Herpes Zoster
N Engl J Med 1994; 331:481August 18, 1994
- Article
To the Editor:
In their report on the treatment of acute herpes zoster (March 31 issue),1 Wood et al. state that “intravenous and oral acyclovir in immunocompetent patients are associated with significant improvements in the rate of healing and the severity of the acute pain of herpes zoster,” and that “because the benefits of acyclovir therapy during the acute phase are established, it was considered unethical to include a placebo group.” Although the authors report a well-executed study, we would like to put these two statements into perspective.
It is true that in each of the published controlled studies, including our own,2 the rate of healing was faster in the acyclovir group. However, the period of healing in the studies ranged from 12 hours to two days, depending on the criterion for healing. Clinically, such differences are irrelevant. The reduction of pain during acyclovir therapy, especially with intravenous administration, is more impressive but temporary, and thus severe pain that does not respond to simple analgesic drugs can be considered an indication for acyclovir treatment. Another possible indication is zoster of the first trigeminal branch in immunocompetent adults. We and others2,3 have observed that in such patients ocular involvement may be prevented with acyclovir therapy.
Acyclovir is indicated only for a minority of immunocompetent patients with herpes zoster. For most, the side effects can be avoided, and considerable costs saved.
3 ReferencesPieter J. van den Broek, M.D.
University Hospital Leiden, 2333 AA Leiden, the NetherlandsPaul M.J. Stuyt, M.D.
Jos W.M. van der Meer, M.D.
University Hospital Nijmegen, 6500 HB Nijmegen, the Netherlands1
Wood MJ ,Johnson RW ,McKendrick MW ,Taylor J ,Mandal BK ,Crooks J . A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N Engl J Med 1994;330:896-900
Full Text | Web of Science | Medline2
van den Broek PJ ,van der Meer JWM ,Mulder JD ,Versteeg J ,Mattie H . Limited value of acyclovir in the treatment of uncomplicated herpes zoster: a placebo-controlled study. Infection 1984;12:338-341
CrossRef | Web of Science | Medline3
Juel-Jensen BE ,Khan JA ,Posvoe G . High-dose intravenous acyclovir in the treatment of zoster: a double-blind, placebo-controlled trial. J Infect Dis 1983;1:31-36
To the Editor:
Wood and colleagues present the results of an interesting trial showing that prolonged oral acyclovir therapy, with or without prednisolone, has little effect on postherpetic neuralgia. We take issue with their statement, “Because the benefits of acyclovir therapy during the acute phase are established, it was considered unethical to include a placebo group.” Previous trials of acyclovir in patients with acute zoster1,2 showed only a minimal benefit in terms of the duration of acute pain and healing, both being improved by only 24 to 36 hours, and no effect on postherpetic neuralgia. The cost of a seven-day course of acyclovir is considerable ($152 at our pharmacy).
It is not unethical to withhold such therapy, given the substantial cost and marginal benefit. In our opinion, it does seem unethical to include such a statement in a trial supported by the Wellcome Foundation.
2 ReferencesJohn C. Tangeman, M.D.
Antoinette M. Kuzminski, M.D.
David S. Svahn, M.D.
Bassett Healthcare, Cooperstown, NY 133261
Huff JC ,Bean B ,Balfour HH Jr , et al. Therapy of herpes zoster with oral acyclovir. Am J Med 1988;85:Suppl 2A:84-89
CrossRef | Web of Science | Medline2
Wood MJ ,Ogan PH ,McKendrick MW ,Care CD ,McGill JI ,Webb EM . Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med 1988;85:Suppl 2A:79-83
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Both van den Broek and Tangeman and their colleagues question our statement that it would have been unethical to include a placebo-treated group in our study. At the initiation of the trial, placebo-controlled clinical studies had unequivocally shown statistically significant benefits of high-dose acyclovir, in regard to both the rash and the pain, during the acute phase of herpes zoster1-3. In the United Kingdom, the drug was licensed and widely used by general practitioners for this indication.
Furthermore, we enrolled only patients with moderate or severe pain at the onset of the acute illness, and those with ophthalmic zoster (about 15 percent) were not excluded. As van den Broek and his colleagues point out, there is a consensus that such patients should be treated with acyclovir; hence, they could not have been in a placebo-controlled study.
Finally, the use of steroids carried the possibility of compromised host immunity and a theoretical but unquantified risk of viral dissemination. We and the relevant ethics committees believed that the optimal treatment that could be offered should be provided to all patients, even though it was recognized that there was no clear evidence that acyclovir offered any benefit in terms of long-term pain.
The judgment about whether acyclovir is appropriate treatment for herpes zoster in a particular clinical setting is a separate issue and requires consideration of a variety of other factors, including costs. The view expressed by Tangeman and his colleagues that “it is not unethical to withhold such therapy, given the substantial cost and marginal benefit” is held by many physicians, and the selection of patients for acyclovir therapy in no way conflicts with our views. Our study was not designed nor was the wording intended to suggest that all patients should receive acyclovir for herpes zoster. As clinicians working in the National Health Service, we reject the view that any statement in the paper was unethical.
3 ReferencesMartin J. Wood, F.R.C.P.
Birmingham Heartlands Hospital, Birmingham, B9 5ST, United KingdomMichael W. McKendrick, F.R.C.P.
Royal Hallamshire Hospital, Sheffield S10 2JF, United KingdomRobert W. Johnson, F.R.C.A.
Bristol Royal Infirmary, Bristol, BR2 8HW, United Kingdom1
Huff JC ,Bean B ,Balfour HH Jr , et al. Therapy of herpes zoster with oral acyclovir. Am J Med 1988;85:Suppl 2A:84-89
CrossRef | Web of Science | Medline2
Wood MJ ,Ogan PH ,McKendrick MW ,Care CD ,McGill JI ,Webb EM . Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med 1988;85:Suppl 2A:79-83
Web of Science | Medline3
Morton P ,Thomson AN . Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J 1989;102:93-95
Medline
