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GENERAL PRACTICE:
Sigurdur Helgason, Gunnar Petursson, Sigurdur Gudmundsson, and Johann A Sigurdsson
Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up
BMJ 2000; 321: 794 [Abstract] [Full text]

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Prevalence of post-herpetic neuralgia after a first episode of herpes zoster: David Bowsher (26 October 2000)

Comments by authors: Johann A Sigurdsson (7 November 2000)

Clinical Relevance of Zoster Associated Pain (ZAP): Paul M Coplan, Monique Bulotsky, Alexander Nikas, Karen M Kaplan (19 April 2001)

Prevalence of post-herpetic neuralgia after a first episode of herpes zoster 26 October 2000

David Bowsher
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Re: Prevalence of post-herpetic neuralgia after a first episode of herpes zoster

The interesting article by Helgason and colleagues (BMJ 2000; 321: 794-6) provides new data about the prevalence of postherpetic neuralgia (PHN) in Iceland. Their findings differ significantly in some respects from earlier (retrospective) studies. Two points in particular are at variance with British and American studies:
1. The proportion of herpes zoster (HZ) patients who develop PHN and its duration. The Icelandic values are lower in both categories than those previously published. A datum which is unfortunately missing from all studies is the age at which chickenpox (and therefore immunity) was acquired. It is well-known anecdotally that PHN is both rarer and less severe in people born in the Indian sub-continent; and there is considerable evidence that chickenpox occurs at a later age in this population1,2,3.
Most physicians working in pain clinics have seen patients with severe PHN of 20 or more years duration. The majority of such individuals have perforce had their HZ at less than 50 years of age.
2. The intensity of PHN pain is rated as considerably more severe by most European and North American sources than it is by Helgason and his colleagues. The mean Visual Analogue pain intensity score of 246 successive PHN patients attending our Centre for Pain Relief was 86.2, with 142 (57.6%) of them having a VAS score of over 904. While it is obvious that herpes antibody titres are probably a guide to the severity of HZ and PHN, this obviously cannot be performed on whole populations. It would be interesting to speculate, especially in view of the evidence from the Indian sub-continent, whether the age at which chickenpox occurs might give some prognostic indication on the incidence and severity of PHN. Might this differ in the relatively isolated Icelandic community in comparison with Western Europe and North America?
The associated leader by Cunningham and Dworkin (BMJ 2000; 321:778-9) advocates the pre-emptive use of low-dose tricyclic antidepressant5 along with one of the newer antivirals in the treatment of HZ and prevention of PHN. Since we have persuaded primary care physicians in our area to prescribe low-dose tricyclic antidepressant from the onset of HZ, referrals to our pain clinic for PHN have dropped from >100 p.a. to <30 p.a.
1. Seetaram K. Ind J Med Sci 1969; 23: 210-213
2. Sinha DP. Internat J Epidemiol 1976; 5: 367-374
3. Lee BW. Trop Med Internat Health, 1998; 3: 886-890
4. Cossins L, Bowsher D, Wells C, Wiles JR. The Pain Clinic, 5th Internat Cong, Jerusalem 1992, Abstracts S61
5. Bowsher D. J Pain Sympt Man, 1997; 13: 327-331

Comments by authors 7 November 2000

Johann A Sigurdsson,
professor
Department of Family Medicine, Iceland
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Re: Comments by authors

Dr Bowsher 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 Northen Europa and USA. The vast majority of children aquire chickenpox during the pre school years (from about age one and a half to five years). We have no accurate data on this for the majority of our study subjects. In another study (by us) on young people who developed herpes zoster at a younger age than 20 years 1), information on age at time of chickenpox was available for 77 children. Their mean age at the time of chickenpox was 3.1 years.
Contracting chickenpox late in life may be protective against PHN, but that is not likely to have been the case for our study population. We share with Dr Bowsher his recommendation of prescribing a low-dose tricyclic antidepressant from the onset of HZ, but point out that these recommendatons are only based on one study 2). Further research is thus needed regarding the protective effects of tricyclic antidepressants on PHN development.
1. Petursson G, Helgason S, Gudmundsson S, Sigurdsson JA. Herpes zoster in children and adolescents. Pediatr Infect Dis J 1998;17:905-908
2. McQuay HJ. Antidepressants and chronic pain. Effective analgesia in neuropathic pain and other syndromes. BMJ 1997;314:763-4.
Sigur�ur Helgason MD
Johann A. Sigurdsson Ph.d. professor

Clinical Relevance of Zoster Associated Pain (ZAP) 19 April 2001

Paul M Coplan,
Associate Director, Scientific Staff
Merck Research Laboratories,
Monique Bulotsky, Alexander Nikas, Karen M Kaplan
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Re: Clinical Relevance of Zoster Associated Pain (ZAP)

To the Editor,
In "Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long term follow up," Helgason et. al. report the results of a prospective cohort study of 421 patients with a first episode of zoster, identified from 62 selected general practices in Iceland and followed 1, 3, 6, and 12 months after rash onset for the development of postherpetic neuralgia (PHN) (1). The authors intended "to estimate the frequency, duration, and clinical importance of PHN after a single episode of herpes zoster," and "gathered information on the clinical course of PHN, with emphasis on the patient's report of the clinical importance of pain and its impact on daily life." The authors found rates of PHN lower than those previously reported (2-4).
Culture, HLA type, and other factors are believed to influence the interpretation of pain; thus we do not take issue with the frequency of PHN reported in the Icelandic study population. Nevertheless, the manuscript states no measure by which clinical importance or impact on daily life were evaluated nor are there any patient reports of impact on daily life. We believe therefore that their conclusion that "the probability of longstanding pain of clinical importance� is low" is unjustified.
In a prospective observational study that investigated the severity, natural history, and clinical relevance of zoster associated pain (ZAP), 121 immunocompetent patients � 60 years of age enrolled within 14 days of a clinically diagnosed zoster rash onset were interviewed in person or by telephone at regular intervals (5). Patients were followed for 6 months (182 days) or until they reported no pain for two consecutive interviews, whichever came first. A total of 110 patients completed the study and are included in the analysis.
At each interview, patients rated their pain intensity in the previous 24 hours using pain categories from the McGill Pain Questionnaire Present Pain Intensity Scale (no pain, mild, discomforting, distressing, horrible, excruciating) (6-7). They also rated their ability to perform activities of daily living (ADL) for the period of pain during the previous 24 hours, using a 10-point scale, where 0 = "pain does not interfere" and 10 = "pain completely interferes". We converted the ADL scale to a mean percent interference by multiplying the mean interference scores by 10. Patients recorded their quality of life (QoL) as measured by the SF-12 questionnaire and summarized as the Mental and Physical Health Summary scales and the EuroQoL rating scale, from 0 to 100, (i.e. from worst to best imaginable personal health state) (8, 9).
Patients' worst pain scores for the time intervals 31-182 and 91-182 days after rash onset were selected for this analysis. If a patient's worst pain score was consistent between interviews, we report data from the earliest interview date. Mean scores for ADL and QoL measures are reported by category of pain rating.
Mean percent interference in ADL increased markedly with increasing McGill Pain Scores in both the 31-182 and 91-182 day intervals (Table). Higher levels of interference in general activity were evident even with mild and discomforting pain (8 and 32% respectively) and increased substantially with distressing (45%) and horrible/excruciating (83%) pain during the 31-182 day interval. Pain interfered >50% with both sleep and enjoyment of life for patients with pain rated as distressing or worse during both time intervals. Trends for the other ADLs in both time intervals followed similar patterns. A previous validation study had shown a similar degree of interference with activities of daily living at ZAP levels rated mild to moderate and similar trends with increasing pain (10). Higher pain scores also were associated with lower quality of life scores: in the 31-182 day interval, patients with no pain or mild pain both had EuroQol scores of 84, while those with pain rated as discomforting, distressing, or horrible/excruciating had EuroQol scores of 71, 59, and 51 respectively (Table).
ZAP increases with increasing age (11, 2-4). In persons >60 years of age, Helgason et al. (1) report that the incidence of moderate to severe pain after 1 month was 24.2% (24/99), after 3 months was 7% (8/115), and after 12 months was 1.6% (2/127). The estimated annual incidence rate of herpes zoster is at least 5-10 per 1,000 persons >60 years of age (3,12-13). The Scandinavian countries have a total population of approximately 24 million people, with 5 million people 60 years or older; thus, a minimum of 25,000 cases of zoster in this age group can be expected in these countries annually. Based on the findings of Helgason et al, each year, approximately 6,050 Scandinavians would be expected to experience moderate to severe ZAP for at least one month, 1,750 for at least 3 months, and 400 for at least 12 months, leading to 45 -90% interference in general activity, 55-73% interference with sleep, and 50-93% interference with the enjoyment of life.
Although the frequency and severity of ZAP may vary among populations, the impact of the pain on patients' lives may be substantial, even at pain rated as moderate in intensity, and particularly if pain lasts 3 months or more. We believe that given the clinical relevance of ZAP, particularly in persons over 60 years of age, the prevention of herpes zoster is an important public health goal.
Paul M. Coplan, DSc.
Monique Bulotsky, MPH
Alexander Nikas, MPH
Karen M. Kaplan, MD
Merck Research Laboratories, Merck and Co, Inc., West Point, PA 19486
Competing interests: The authors are employees of Merck and Co, Inc, and potentially own stock and/or hold stock options in the company.
References
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Table. Association between pain intensity, interference with activities of daily living, and quality of life (reported as mean percent interference). No Pain Mild Discomforting Distressing Horrible/ Excruciating Days 31-182 (N = 86) (N = 28) (N = 23) (N = 18) ( N = 13) (N = 4) Activities of Daily Living General Activity 3 8 32 45 83 Walking Ability 0 5 19 23 60 Work 0 5 28 48 65 Relations with Others 2 5 25 42 70 Sleep 3 9 28 58 63 Enjoyment of Life 2 9 41 57 78 Get out of the house 1 2 27 45 70 Participate in leisure activities 3 5 41 55 73 Concentrate on mental tasks 1 6 27 44 60 Quality of Life EuroQol (0 to 100 scale) 84 84 71 59 51 SF-12 Mental Health Summary 51 52 45 37 34 SF-12 Physical Health Summary 49 44 39 35 30 Days 91-182 (N = 34) (N = 18) (N = 7) (N = 4) (N = 2) (N = 3) Activities of Daily Living General Activity 1 9 23 55 90 Walking Ability 1 11 8 15 73 Work 1 9 8 50 80 Relations with Others 0 1 15 20 83 Sleep 1 14 18 55 73 Enjoyment of Life 1 10 15 50 93 Get out of the house 1 3 8 40 70 Participate in leisure activities 1 3 15 60 87 Concentrate on mental tasks 1 11 5 50 47 Quality of Life EuroQol (0 to 100 scale) 89 66 52 63 42 SF-12 Mental Health Summary 55 52 46 37 31 SF-12 Physical Health Summary 52 42 31 33 26 N= Number of patients