Aciclovir

Findings differ from earlier results

EDITOR--The article by Helgason et al provides new data about the prevalence of postherpetic neuralgia in Iceland.[1] Their findings differ markedly in some respects from earlier retrospective findings. Two points in particular are at variance with British and American studies. The first is the proportion of patients with herpes zoster who develop postherpetic neuralgia and its duration. The Icelandic values are lower in both categories than those previously published from other countries.

A datum that is unfortunately missing from all studies is the age at which chickenpox, and therefore immunity, was acquired. It is well known anecdotally that postherpetic neuralgia is both rarer and less severe in people born on the Indian subcontinent; and there is considerable evidence that chickenpox occurs at a later age in this population.[2] Most doctors working in pain clinics have seen patients with severe postherpetic neuralgia of 20 or more years' duration. Most such patients have had their herpes zoster when they were younger than 50 years.

The second point is that the intensity of postherpetic neuralgia pain is rated as considerably more severe by most European and North American sources than it is by Helgason et al. The mean visual analogue pain intensity score of 246 successive patients attending our centre for pain relief was 86.2 at presentation, with 142 patients having a score of over 90 (L Cossins et al, fifth international congress on the pain clinic, Jerusalem, 1992). Although herpes antibody titres are probably a guide to the severity of herpes zoster and postherpetic neuralgia, this cannot be performed on whole populations. It would be interesting to speculate, especially in view of the evidence from the Indian subcontinent, whether the age at which chickenpox occurs might give some prognostic indication of the incidence and severity of postherpetic neuralgia. Might this differ in the isolated Icelandic community in comparison with western Europe and North America?

The associated editorial by Cunningham and Dworkin advocates the pre-emptive use of low dose tricyclic antidepressants along with one of the newer antiviral drugs in the treatment of herpes zoster and prevention of postherpetic neuralgia.[3 4] Since we have urged primary care doctors in our area to prescribe low dose tricyclic antidepressants from the onset of herpes zoster, referrals to our pain clinic for postherpetic neuralgia have dropped from more than 100 per year to fewer than 30 per year.

David Bowsher honorary senior research fellow Pain Research Institute, University Hospital Aintree, Liverpool L9 1AE

Competing interests: None declared.

[1] Helgason S, Petursson G, Gudmundsson S, Sigurdsson J. Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long term follow up. BMJ 2000;321:794-6. (30 September.)

[2] Lee BW Review of varicella zoster seroepidemiology in India and Southeast Asia. Trop Med Int Health 1998;3: 886-90.

[3] Cunningham AL, Dworkin RH. The management of postherpetic neuralgia. BMJ 2000; 321:778-9. (30 September.)

[4] Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage 1997;13:327-31.

Authors' reply

EDITOR--Bowsher's suggestions regarding the pathogenesis of the severity of pain after zoster are interesting. Our study was not designed ,to answer these questions, which therefore warrant further studies. The age at which children in Iceland acquire chickenpox is generally thought to be low and similar to northern Europe and the United States. Most children acquire chickenpox during the preschool years (aged from about 18 months to five years). We have no accurate data on this for most of our study subjects. In another study (by us) into young people who developed herpes zoster at a younger age than 20 years, information on age at time of chickenpox was available for 77 children.[1] Their mean age at the time of chickenpox was 3.1 years.

Contracting chickenpox late in life may be protective against postherpetic neuralgia, but that is not likely to have been the case for our study population. We share with Bowsher his recommendation of prescribing a low dose tricyclic antidepressant from the onset of herpes zoster but point out that these recommendations are based on only one study.[2] Further research is thus needed on the protective effects of tricyclic antidepressants on the development of postherpetic neuralgia.

Sigurdur Helgason general practitioner

Johann A Sigurdsson professor johsig@hi.is

Department of Family Medicine, University of Iceland, IS- 105 Reykjavik, Iceland

Competing interests: SH has received honoraria from GlaxoWellcome for lecturing on herpes zoster.

[1] Petursson G, Helgason S, Gudmundsson S, Sigurdsson JA. Herpes zoster in children and adolescents. Pediatr Infect Dis J 1998;17:905-8.

[2] McQuay HJ. Antidepressants and chronic pain. Effective analgesia in neuropathic pain and other syndromes. BMJ 1997;314:763-4.

Pathogenesis of postherpetic neuralgia should be determined

EDITOR--The article by Helgason et al suggests that postherpetic neuralgia is infrequent and benign.[1] This has not been our experience. In a community based study conducted over the past two years, general practitioners in East London referred acute cases of shingles for evaluation. Of 247 cases referred, 202 (84%) were confirmed as shingles by immunofluorescence and polymerase chain reaction. A total of 136 patients with a laboratory diagnosis have been followed up for six months and 134 for a year. Most patients (68%) were treated with aciclovir or analogues in therapeutic doses by their general practitioners. Patients were asked to report the presence of pain at six weeks, three months, six months, and 12 months, and the severity was assessed by subjective evaluation including interference with daily activities, visual analogue scores, and McGill questionnaires.

We found that of those aged 50 years and over, 15% (12/79) still had pain at six months and 12% (9/77) at one year. This is comparable with the Icelandic study, in which 8% of patients over age 50 still had pain at 12 months. The fact that 16% of patients with shingles in our study were wrongly diagnosed suggests that the figure for postherpetic neuralgia reported by Helgason et al is low. In contrast to the findings of the Icelandic study, our data suggest considerable morbidity from postherpetic neuralgia. Ten per cent of older patients (8/79) still required analgesia at six months and 8% at one year (table).

Postherpetic neuralgia was severe enough to interfere with daily activities, including sleep, in 9% (12/136) of our cohort at three months and 7% (9/136) at six months. The incidence of prolonged postherpetic neuralgia in our cohort, most of whom received antiviral treatment, is comparable with that in treated groups reported in other studies and lower than is seen in most untreated groups.[2 3] This would tend to support a role for antivirals in prevention of postherpetic neuralgia, and we therefore caution against abandoning their use in vulnerable groups. We agree with the editorial and commentary that more work is now needed to determine the pathogenesis of postherpetic neuralgia and to improve early identification of those at most risk of prolonged pain.

Judith Breuer consultant in virology breuer@mds.qmw.ac.uk

Fiona Scott research nurse in virology

Mary Leedham-Green data manager in virology Department of Medical Microbiology, St Bartholomew's and the London Hospital Medical School, London E1 1BB

Competing interests: FS is supported in part by an educational grant from GlaxoWellcome.

[1] Helgason S, Petursson G, Gudmundsson S, Sigurdsson J. Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long term follow up. BMJ 2000;321:794-6. (30 September.)

[2] Kost RG, Strauss SE. Post herpetic neuralgia pathogenesis treatment and prevention. N Engl J Med 1996;335:33-43.

[3] Cunningham AL, Dworkin RH. The management of postherpetic neuralgia. BMJ 2000;321:778-9. (30 September.)

Treatment with amitriptyline is cheaper than with aciclovir

EDITOR--Helgason et al report a low incidence of postherpetic neuralgia and suggest that as the absolute benefits of antiviral drugs are small, they may not be necessary.[1] They do not, however, mention evidence that the antidepressant amitriptyline also prevents postherpetic neuralgia[2]; neither do they estimate the cost of treatment. Our best estimate of the effectiveness of antiviral drugs is that oral aciclovir started within 72 hours of the onset of symptoms, reduces the incidence of pain at six months by 46%.[3] Our best estimate of the effectiveness of amitriptyline 25 mg a day in postherpetic neuralgia is that it reduces the incidence of postherpetic neuralgia at six months by 55% if started at presentation and continued for 90 days.[2] Consideration of the resource implications may clarify the relative merits of the interventions. A course of aciclovir costs 93.12 [pounds sterling] and 90 days' treatment with amitriptyline 0.77 [pounds sterling].

Using the estimates of Helgason et al of the incidence of postherpetic neuralgia at one year, we can calculate the numbers needed to treat to prevent a case of postherpetic neuralgia and the prescribing costs per case prevented (table). About 130 patients aged 70 or over will have to be treated with aciclovir to prevent one case of postherpetic neuralgia: a cost per case prevented of 12 146 [pounds sterling]. About 109 patients aged 70 or older will have to be treated with amitriptyline to prevent one case of postherpetic neuralgia: a cost per case prevented of 83 [pounds sterling].

Tom Marshall lecturer in public health medicine Department of Public Health and Epidemiology, University of Birmingham, Birmingham B15 2TT

Competing interests: None declared.

[1] Helgason S, Petursson G, Gudmundsson S, Sigurdsson J. Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long term follow up. BM J 2000;321:794-6. (30 September.)

[2] Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage 1997; 13:327-31.

[3] Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A meta-analysis. Arch Intern Med 1997;157:909-12.

Why burden the pain clinic?

EDITOR--Cunningham and Dworkin's advice is stark and unequivocal: patients who get troublesome postherpetic neuralgia should attend pain clinics.[1] They have mentioned antidepressants in passing, but only as possible prophylactic drugs; they have not mentioned gabapentin at all. Yet these two drugs can be used in a general practice setting. Antidepressants for postherpetic neuralgia were comprehensively dealt with in an editorial in the BMJ three years ago.[2] Gabapentin is effective and improves mood, sleep quality, and quality of life.[3] It is licensed and has few side effects. Pain clinics are overstretched, waiting lists ridiculously long, and many consultants who run them read the BMJ. Such a journal should not be making out that the pain clinic is a sort of "black box" into which readers can pass specific troubles: it should be disseminating evidence based knowledge to a wide readership.

Rory Greet specialist registrar

Andrew Severn consultant asevern@ageanaesthesia.demon.co.uk Pain Clinic, Royal Lancaster Infirmary, Lancaster LA1 4RP

Competing interests: None declared.

[1] Cunningham AL, Dworkin RH. The management of postherpetic neuralgia. BMJ 2000;321:778-9. (30 September.)

[2] McQuay HJ. Antidepressants and chronic pain. BMJ 1997;314:763-4.

[3] Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998;280:1837-42.

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