Unusual treatments for herpesvirus infections. II. Herpes zoster

Abstract

As is the case with herpes simplex, the diverse array of remedies proposed for herpes zoster (HZ) raises doubts as to their overall efficacy. Three critical issues must be addressed in the therapy of patients with this disorder: (1) control of the pain of the acute eruption, (2) prevention of postherpetic neuralgia (PHN), i.e., pain persisting 2 months or longer after the attack of HZ, and (3) alleviation of the discomfort of PHN, should it occur. Unfortunately, many studies fail to distinguish between the clinical symptoms of acute HZ and those of the postherpetic syndrome. The usefulness of agents purported to control the pain of acute HZ must be assessed keeping in mind the natural tendency of the eruption to heal spontaneously. The site of the vesicles, concomitant infection, and the patient's immune status may all affect the clinical course. In addition, pain is a highly subjective sensation; uncontrolled studies are often unreliable, and the placebo effect may be marked. For a given drug to be clinically useful, it must be shown to be at least as safe and effective in controlling pain as the many analgesic agents now available. The beneficial effects of antiviral chemotherapy, if any, would be expected to be apparent only if used during the early stages of the illness. Idoxuridine ointment provides little relief. JuelJensen et al 1 found that continuous topical application of 40% idoxuridine in dimethyl sulfoxide (DMSO) reduced the duration of pain from the acute eruption. Wildenhoff et al z demonstrated that the acute inflammatory reaction was greatly suppressed by such treatment, although they observed a less dramatic amelioration of pain. Unfortunately, 40% idoxuridine is exceedingly expensive, and the use of DMSO is restricted in many countries. (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is a nucleoside analogue related to idoxuridine, and is highly active against the varicella zoster virus in vitro. 3 One practical advantage is that it can be taken by mouth. Treatment with orally administered BVDU caused prompt recovery of patients with severe HZ in a study reported by De Clercq et al. 4 Carefully controlled studies are needed to confirm the clinical value of BVDU as a systemic antiherpetic agent. Vidarabine, like idoxuridine, has been used to treat acute attacks of HZ. One studyp which appeared to demonstrate its efficacy in the therapy of t tZ in immunosuppressed patients, was not truly double blind and showed no significant effect on mortality or on the incidence of PHN. Other trials* have been more promising. An accurate assessment of the overall value of vidarabine in the treatment of HZ requires further investigation. Acyclovir is a nucleoside analogue which is unique in that it is preferentially absorbed and activated by infected cells. 6 This theoretically provides a much greater margin of safety over many older antiviral agents, like idoxuridine, which may have significant effects on cellular DNA synthesis. Selby et al 7 used parenteral acyclovir to treat