Editorial Advisor
Gary Sibbald, MD FRGPC
Associate Professor of Medicine
University of Toronto
Toronto, Ontario
Herpes zoster is a common illness in general and family practice with an estimated lifetime prevalence of 20%. The incidence increases with age. About 50% of those who live until the age of 85 will experience at least one zoster episode during their lifetime.z
The most common complication of zoster infection is postherpetic neuralgia (PHN).' PHN may be defined as persistent pain immediately or 1 month after rash healing.Q The risk increases with age. PHN is present in an estimated 47% of untreated adults over age 60, and 73% of adults over age 70."
Acute zoster pain is typically described as a throbbing, stabbing, sharp or burning sensation that is superficial or deep and which may be intermittent or continuous. Pain with accompanying skin sensations (altered sensitivity hyperesthesia) may manifest a few days prior to the emergence of rash and may persist for several days thereafter. In contrast, PHN pain is described as chronic, unrelenting pain persisting for several months after rash healing and which is often associated with depressed mood and somatic signs, such as sleep disturbance, decreased appetite, lassitude, constipation and diminished libido.5
Pathogenesis of PHN
Following a primary varicella (chickenpox) infection, the varicella-zoster virus remains dormant in the dorsal root ganglia until it is reactivated." The clinical expression of
acute zoster is presumed to be due to waning cellular immunity to the virus as a result of advancing age or an immunocompromised state. With reactivation, the virus replicates in neurons and spreads retrogradely to the skin through peripheral nerves.
With viral replication and the resulting neuropathic damage, especially to myelinated fibres and nonmyelinated peripheral nerve cells, the activation thresholds are lowered. The clinical results are an exaggerated response to stimuli, and pain due to nerve damage.'
Treatment
The principal objective of intervention is to initiate antiviral therapy rapidly within 72 hours of a zoster episode to inhibit viral replication and reduce virus-associated nerve damage.
The initial therapy for herpes zoster was with acyclovir, which exhibited a short intracellular half life (0.8 hours or 48 minutes in vitro) and low bioavailability( 10-20%). The prodrug form of acyclovir. valacyclovir, has improved bioavailability(57%) but the same shon intracellular half life.
In contrast, the antiviral famciclovir (Famvir©) has a long intracellular half-life (7.2 hours in vitro) and high bioavailability (77%). Famciclovir is converted to the active agent penciclovir, which is incorporated into infected nerve cells, where it inhibits viral replication.
The recommended dose is Famvir 500 mg three times a day for seven days, administered within 72 hours of a herpes zoster rash."
It should be noted that neither acyclovir nor valacyclovir is indicated for PHN. In contrast famciclovir is indicated in Canada to reduce the duration of PHN pain
In a muticentre, placebo-controlled study by Tyring and colleagues of 419 patients with herpes zoster patients were treated with famciclovir 500 mg or 750 mg three times a day for seven days. Among patients over age 50 who experienced PHN, loss of PHN occurred 2.6 times more quickly with famciclovir versus placebo. The mean duration of PHN in these patients
was 100 days shorter for the famciclovir 500 mg three times a day group versus the placebo group (63 days vs 163 days).
In a subsequent analysis, Siegfried and colleagues found that compared to famciclovir-treated patients, placebo-treated patients had a 60-80% increased risk of still having pain at six months following therapy.
Famvir is recommended only in immunocompetent patients. The most common adverse effects with famciclovir are headache and nausea. A reduced dose is recommended in patients with reduced renal function.
A number of additional therapies have been employed for pain management Analgesics (e.g. ASA) have limited value; ibuprofen has been shown to be ineffective. Topical analgesics have been found to have some usefulness in uncontrolled trials.
Due to the limited success in alleviating chronic PHN pain, early intervention with famciclovir is important to reduce the duration of the pain episode and to reduce patients' suffering.
References:
1. Degreef H, Famciclovir Herpes Zoster Clinical Study Group.
Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocomptent patients. Int J Antimicrob Agents 1994; 4:241-246
2. Wood MJ, Easterbrook p. Shingles scourge of the elderly. In: Sacks SL, Straus SE, Whitley RJ, Griffiths PD, eds. Clinical Management of Herpes Viruses. Oxford: IOS PRESS, 1995; 193-207.
3. Tyring S, Barabarash RS, Nahlik JE, et al. Famciclovir for the trratment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. Ann Inter Med 1995; 123:89-96.
4. Kost RG, Straus SE, Postherpetic neuralgia- pathogenesis, treatment and prevention. N Engl J Med 1996; 335:32-42.
5. Portenoy RK, Duma C, Foley KM. Acute herpetic and post herpetic neuralgia: clinical review ant current management. Ann Neurol 1986; 20: 651-664.
6. Whitley RJ. Varicella-zoster virus infections. In: Galasso GJ, Whitley RJ, Merigan TC, eds. Antiviral Agents and Viral Diseases of Man, 3rd edition. New York, Raven Press, 1990; 235-263.
7. Beutner KR, Friedman, DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39: 1546-1553.
8. Famvir (famciclovir) Product Monograph.
9. Sigfried RN, Dworkin RH, the Collaborative Famciclovir Herpes Zoster Study Group. Postherpetic neuralgia: impact of famciclovir treatment, age, lesion severity, and pain severity in acute herpes zoster patients. Presented at the 8th World Congress on Pain, Vancouver, British Columbia, August 17-22, 1996; abstract 167.