- Email: [email protected]
Acute Herpes zoster in Tayside: Demographic and treatment details in immunocompetent patients 1989–1992
Journal of Infection(1998) 36, 209-214
Acute Herpes zoster in Tayside: Demographic and Treatment Details in Immunocompetent Patients 1989-1992 J. Torrens .1, D. N a t h w a n i t 1 T. M a c D o n a l d 2 a n d P. G. D a v e y 2 1Infection and Immunodeficiency Unit, Kings Cross Hospital, Dundee Teaching Hospitals NHS Trust, Dundee DD3 8EA, and 2Medicines Monitoring Unit (MEMO), Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. Medical records of 105 patients admitted to Tayside hospitals with acute Herpes zoster without underlying immunosuppression were examined retrospectively for the period 1984-1992. In this elderly population (median age: 79 years) there was a female preponderance (70,5%), most admissions were for trigeminal zoster (49.5%) and length of stay ranged from 1-70 days (median: 11 days), indicating significant morbidity. There was a wide variation in both pre-admission and inpatient treatment; 53.3% of patients did not receive any anti-viral therapy prior to admission, and prescribing patterns for in-patients revealed marked differences, according to the dermatome affected. Idoxuridine 5% solution was prescribed by 15.24% of General Practitioners. Given the significant morbidity and associated costs of Herpes zoster, and that existing anti-viral agents exert maximal benefit when administered early in the course of the disease, recommendations are made with respect to appropriate therapy, and auditing current management of this serious illness, which is expected to increase in prevalence as the population ages.
Introduction Acute Herpes zoster, resulting from reactivation of latent varicella zoster virus, is a serious and debilitating illness associated with significant morbidity and associated costs. 1 The overall annual incidence, variously estimated between 0 . 8 / 1 0 0 0 and 4 . 8 / 1 0 0 0 patients, rises to 10.1/ 1000 for those aged 80 or older. 2~ The elderly are more likely to suffer a serious form of the illness with increased morbidity, particularly with respect to post-hepetic neuralgia, which m a y affect up to 50% of this group. ~ Antiviral therapy in the form of aciclovir has been shown to be of benefit with respect to the acute pain experienced, and time to healing of the cutaneous lesions, but must be prescribed in the correct doses, and as soon as possible (ideally within 48 h) after the onset of the rash, to maximize its effect. 6-s The impact of aciclovir on postherpetic neuralgia remains controversial. 9 Our experience of patients with zoster admitted to the regional infectious diseases unit, either from the community or via other specialities, indicated that a wide variety of m a n a g e m e n t existed, and provided in part the stimulus to perform this study. In addition, with the increasing age of the population,l° Herpes zoster is likely to be an increasing problem, reflected in increased admission *Current address: PCEA, Chojoria Hospital, PO Box 35, Chojoria, Kenya. 1 To whom correspondence should be addressed. Accepted for publication 21 July 1997. 0163-4453/98/020209 +06 $12.00/0
rates to hospital with all the attendant resource implications. A retrospective study has therefore been performed of all immunocompetent patients admitted to Tayside hospitals over a 4-year period to analyse preadmission and in-patient treatment, length of stay and demographic details.
Materials and Methods The Tayside Medicines Monitoring (MEMO) Unit holds a computerized database containing details of all patients admitted to Tayside hospitals from January 1980.11 The information is collected from Scottish morbidity record (SMR) forms, which detail all discharge diagnoses of patients who leave hospital (or are transferred to another unit) following an episode of care. The last complete year for which data are currently available is 1992, and thus a 4-year period from January 1989 to December 1992 was examined. A programme was written to obtain a list of all patients, identified by their unique Community Health Index (CHI) number, discharged during the study period with acute Herpes zoster as a diagnosis. Synonyms such as shingles or ophthalmic shingles were also used to ensure as complete a cohort as possible, and patients with conditions indicating immunosuppression such as lymphoproliferative disease, malignancy, HIV infection and posttransplantation were excluded from analysis. The medical © 1998 The British Infection Society
210
J. Torrens et al.
records of this selected cohort were then retrieved and examined manually; any patient with an immunosuppressant condition or treatment not detailed on the SMR form was excluded from further analysis. From the resultant immunocompetent population, demographic details such as age, sex, year of admission, hospital and anatomical site affected were recorded. Length of stay was also recorded, as were pre-admission and in-patient treatment details. Statistical analysis was performed with Minitab for Windows.
Admitting units The majority of patients (74) presented to the regional infectious diseases unit in Dundee, but the remaining 30 patients presented to other acute units, 14 in Dundee, 10 in Perth and four in Brechin. Trigeminal zoster tended to be admitted to the infectious diseases unit and accounted for 4 2 / 7 4 (56.8%) of their admissions vs. 10/30 (33.3%) of admissions to other units.
Treatment received before admission to hospital Results
Hospitalization for acute Herpes zoster infection Other information, such as time of initial diagnosis and duration of rash and presentation, were not recorded frequently enough to w a r r a n t meaningful analysis. Herpes zoster appeared in the discharge diagnosis list of patients without mention of underlying disease as specified in the methods. Of these, 173 sets of notes were available but 14 patient records were incomplete and did not contain sufficient information to analyse. Of the remaining 159 patients, 26 were found to have underlying immunosuppressive diseases which had not been recorded in the discharge sheet, 17 were admitted with post-herpetic neuralgia several weeks after the attack of acute zoster, and nine patients developed acute zoster as inpatients, having been admitted with other diagnoses. Thus, of the 156 complete records examined, only 105 were from patients who fulfilled the protocol definition of admission to hospital with acute herpes zoster in a patient without underlying immunosuppression.
Site of infection and basic demography One 78-year-old female was admitted to the regional infectious diseases unit with disseminated zoster which was treated with aciclovir po, 800 mg five times daily. This patient has been excluded from further analysis. Of the remaining 104 patients, the dermatomes involved were trigeminal in 52, thoracic in 27, lumbar in 16 and cervical in nine. The majority of patients (73) were female and the distribution of dermatomes involved was similar in males and females. For the remainder of the analysis the patients have been divided into those with zoster in the trigemina] dermatomes and those with zoster at other sites. The median age was 79 years, but lower in the patients with trigeminal zoster (77 vs. 81) mainly due to a higher proportion of patients aged > 8 9 : 1 6 / 5 2 (30.8%) vs. 6/52 (11.5%).
Pre-admission treatment was not recorded for three patients with non-trigeminal zoster. Of the remaining patients, just over half of those in either dermatome group received no antiviral treatment before admission (Fig. 1). In comparison with the other dermatomes, patients with trigeminal neuralgia received less idoxuridine (6/52 vs. 10/52) and more oral aciclovir at the recommended dose of 800 mg 5 times daily (12/52 vs. 4/52). Oral aciclovir was administered to five patients at the wrong dose ( 2 0 0 m g 5 times daily), one with trigeminal zoster and four with zoster in other dermatomes.
Inpatient treatment Length of stay was highly variable (Fig. 2), but the distribution was similar in patients with trigeminal zoster (median 10.5 days, range 1 - 6 3 days) vs. zoster in other dermatomes (median 12 days, range 1 - 7 0 days). There was an exponential relationship between age and length of stay (Fig. 3) and, on the basis of a simple regression analysis, age (natural logarithm) explained 31.3% of the observed variation in length of stay. There were striking differences between the two groups with respect to inpatient antiviral treatment (Fig. 4). Almost all of the patients with trigeminal neuralgia (43/ 52) received systemic aciclovir at effective doses (800 mg po or 5 mg/kg IV) vs 27/52 of the patients with zoster at other sites, of w h o m 16 received no antiviral treatment at all, two received topical idoxuridine and six received oral aciclovir in the wrong dose. The relationship between treatment and length of stay was examined by dividing the patients into two groups: those who received systemic aciclovir at an effective dose (800 mg po or 2 0 0 m g IV) vs. those who did not (no antiviral treatment, topical antiviral treatment and < 8 0 0 mg po). The median duration of treatment was 11.0 days for patients who received effective systemic treatment vs. 16.5 days for those who did not. The 95% confidence interval (CI) for the difference between the medians was from 0 days to 8 days. However, median
Acute Herpes zoster in Tayside
211
No t r e a t m e n t
Idoxuridine
.3 Aciclovir 800 m g po
Aciclovir topical 4~ ¢6
800 m g po + topical ~ 7 7 7 ~
200 m g po I 10%
0%
I 20%
I 30%
I 40%
I 50%
60%
P e r c e n t a g e of p a t i e n t s Figure 1. Pre-admission treatment of patients with zoster.
35.0%
30.0% ,iz111/, ,i11/1z~ iiiii//,
"///////
"z/////Z. 25.0%
V////// II/I//L ,llllzl,
7//////. V////// "///////
20.0%
,iii/ii,
i/iiiii,
15.0% (D
~/////z
P~
5.0%
0.0%
0-4
5-9
10-14
Figure 2. Percentage of patients with different lengths of stay.
15-19 L e n g t h of s t a y (days)
20-24
25-29
> 29
212
J. Torrens et al. 5
3
-
%
•
2-
• •
• • •
~
1-
0
/
"
I 10
I 20
I 30
I 40
i= 50 A g e (years)
• mm •
mn
•
i 60
i= 70
=
i 80
=
i 90
100
Figure 3. Exponential relationship between age and length of stay.
No t r e a t m e n t
Idoxuridine
Aciclovir 800 m g o
•~
Aeielovir topical
Aciclovir 1V
800 m g + topical
400 m g po 0%
10%
] 20%
Figure 4. Variation in treatment regimens for patients with zoster.
] 30% P e r c e n t a g e of p a t i e n t s
] 40%
I 50%
60%
Acute Herpes zoster in Tayside age was lower for patients who received effective systemic treatment (76.5 vs. 83.5). The 95% CI for the difference between the medicines was from 1.0 to 15.1 years.
Discussion The median age of 79 reflects an elderly population, which is to be expected with an immunocompetent cohort, and the predominance of females reflects the background sex ratio of this population. 1° Of all patients, 53.5% received no treatment prior to admission, but patients with trigeminal zoster were more likely to receive specific and effective antiviral therapy, both pre-admission and as inpatients. Idoxuridine use was mainly confined to the years 1989 and 1990 (14/16), perhaps reflecting a gradual increase in awareness and use of aciclovir following its licensing for zoster in 1988. Various studies of different designs have delivered conflicting results on the efficacy of idoxuridine, but for all practical purposes its use cannot be recommended for acute zoster. 12 A previous community-based survey of 1019 patients with acute shingles found that the thoracic dermatome was most commonly affected (56%), and that the trigeminal dermatome was affected in 12% of cases. 13 Therefore, the finding that 50% of our hospitalized patients had trigeminal zoster suggests that the risk of hospitalization is far greater with shingles affecting this dermatome in comparison with thoracic, lumbar or sacral shingles; this accords with previously published figures. ~4 The median length of stay of 11 days agrees with previous observations, ~4 but it is interesting to note the exponential relationship between this and the patient's age. The median length of stay was longer in those who did not receive effective doses of systemic aciclovir than in those who did. However, age m a y have been a confounding variable, because the patients who received systemic treatment were younger. Therefore, the association between treatment and length of stay m a y not be cause and effect. In a recent paper, Brennan et al. ~5 have reminded authors of observational studies of their responsibility to highlight possible areas of bias, and confounding factors, and to resist the temptation to draw "statistically significant" conclusions from retrospective analyses. It should be noted that data such as renal function, time of initial diagnosis, and duration of rash before treatment commenced or admission requested were not collected. In addition, it is not possible to say to w h a t degree social factors (particularly relevant in an elderly population) m a y have influenced admission rates, length of stay, and even pre-admission treatment, or how m a n y patients m a y have had undiagnosed malignancy or equivalent
213
risk factors for zoster affecting morbidity and outcome. However, we believe several comments m a y be made on the basis of this study. Firstly, given the nature of current antiviral agents, I2' ~6.17 it is necessary to ensure early treatment with correct doses to achieve m a x i m u m benefit; doctors should be educated to this end. Secondly, elderly patients should not be excluded from active treatment, given that they m a y benefit more in terms of alleviation of acute symptoms and morbidity, including possibly post-herpetic neuralgia. 9' 17 Thirdly, there should be recognition of the significant morbidity and associated costs in those with post-herpetic neuralgia I and that any antiviral treatments should be assessed in terms of reducing hospital outpatient consultations, admission rates and length of stay, as well as alleviation of acute symptoms, time to healing of rash, and the incidence of post-herpetic neuralgia. Fourthly, we would recommend the instigation of audit of the m a n a g e m e n t of zoster, both in the community and in hospitals, and for further studies monitoring the efficacy of newer antiviral agents to be performed. Acute Herpes zoster remains an important cause of misery and suffering for a substantial minority of the elderly populations, as the prevalence of the elderly increases in the U.K. It is imperative that safe, beneficial, and effective treatment is offered as efficiently as possible to achieve the m a x i m u m outcome.
Acknowledgements We would like to thank Tayside Medicines Monitoring Unit for their help with this study.
References 1 Davies L, Cossins L, Bowsher D, Drummond M. The cost of treatment for post-herpetic neuralgia in the UK. PharmacoEconomics 1994; 6: 142-148. 2 Miller E, Marshall R, Vurdien J. Epidemiology, outcome and control of varicella-zoster infection. Rev Med Microbiol 1993; 4 : 2 2 2 - 2 3 0 . 3 Ragozzino MW, Melton III LJ, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine 1982; 61: 310-316. 4 Jolleys JV. Treatment of shingles and post-herpetic neuralgia: relieves shingles but does not prevent neuralgia. Br Med J 1989; 298: 1537-1538. 5 Wood MJ. Herpes zoster in immunocompetent patients. Res Clin For 1994; 8: 61-68. 6 Wood MJ, Johnson RW, McKendrick MWM, Taylor J, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N Eng J Med 1994; 330: 896-900. 7 McKendrick MW, McGill JI, White JE, Wood MJ. Oral acyclovir in acute herpes zoster. Br Med J 1986; 293: 1529-1532. 8 Wood MJ, Ogan PH, McKendrick MW, Care C, McGill WM. Efficacy
214
9 10 11
12
J. Torrens et al.
of oral acyclovir treatment of acute herpes zoster. Am J Med 1988; 85 (Suppl. 2A): 79-83. Gilden DH. Herpes zoster with postherpetic neuralgia-persisting pain and frustration. New Engl J Med 1994; 330: 932-933. Registrar General Scotland, Annual Report. Edinburgh. Scottish Office. 1993; 139. Beardon OHG, Brown SV, McDevitt DG. Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: a controlled study using record linkage in Tayside. Quart J Med 1989; 71: 497-505. Wood MJ. Current experience with antiviral therapy for acute herpes zoster. Annals of Neurology 1994; 35 (Suppl.): $65-68.
13 Glynn C, Crockford G, Gavaghan D, Cardno P, Price D, Miller J. Epidemiology of shingles. J Roy Soc Med 1990; 83: 617-619. 14 Bannister P, Crosse B. Severe herpes zoster infection in the United Kingdom: experience in a regional infectious disease unit. J Roy Soc Med 1989; 82: 145-146. 15 Brennan P, Croft P. Interpreting the results of observational research: chance is not such a fine thing. Br MedJ 1994; 309: 727-730. 16 Whitley R]. Therapeutic approaches to varicella-zoster virus infections. J InfDis 1992; 166 (Suppl. 1): $51-57. 17 Whitley RJ, Straus SE. Therapy for varicella-zoster virus infections: where do we stand? Infect Dis Clin Pract 1993; 2: 100-108.
Acute Herpes zoster in Tayside: Demographic and Treatment Details in Immunocompetent Patients 1989-1992 J. Torrens .1, D. N a t h w a n i t 1 T. M a c D o n a l d 2 a n d P. G. D a v e y 2 1Infection and Immunodeficiency Unit, Kings Cross Hospital, Dundee Teaching Hospitals NHS Trust, Dundee DD3 8EA, and 2Medicines Monitoring Unit (MEMO), Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. Medical records of 105 patients admitted to Tayside hospitals with acute Herpes zoster without underlying immunosuppression were examined retrospectively for the period 1984-1992. In this elderly population (median age: 79 years) there was a female preponderance (70,5%), most admissions were for trigeminal zoster (49.5%) and length of stay ranged from 1-70 days (median: 11 days), indicating significant morbidity. There was a wide variation in both pre-admission and inpatient treatment; 53.3% of patients did not receive any anti-viral therapy prior to admission, and prescribing patterns for in-patients revealed marked differences, according to the dermatome affected. Idoxuridine 5% solution was prescribed by 15.24% of General Practitioners. Given the significant morbidity and associated costs of Herpes zoster, and that existing anti-viral agents exert maximal benefit when administered early in the course of the disease, recommendations are made with respect to appropriate therapy, and auditing current management of this serious illness, which is expected to increase in prevalence as the population ages.
Introduction Acute Herpes zoster, resulting from reactivation of latent varicella zoster virus, is a serious and debilitating illness associated with significant morbidity and associated costs. 1 The overall annual incidence, variously estimated between 0 . 8 / 1 0 0 0 and 4 . 8 / 1 0 0 0 patients, rises to 10.1/ 1000 for those aged 80 or older. 2~ The elderly are more likely to suffer a serious form of the illness with increased morbidity, particularly with respect to post-hepetic neuralgia, which m a y affect up to 50% of this group. ~ Antiviral therapy in the form of aciclovir has been shown to be of benefit with respect to the acute pain experienced, and time to healing of the cutaneous lesions, but must be prescribed in the correct doses, and as soon as possible (ideally within 48 h) after the onset of the rash, to maximize its effect. 6-s The impact of aciclovir on postherpetic neuralgia remains controversial. 9 Our experience of patients with zoster admitted to the regional infectious diseases unit, either from the community or via other specialities, indicated that a wide variety of m a n a g e m e n t existed, and provided in part the stimulus to perform this study. In addition, with the increasing age of the population,l° Herpes zoster is likely to be an increasing problem, reflected in increased admission *Current address: PCEA, Chojoria Hospital, PO Box 35, Chojoria, Kenya. 1 To whom correspondence should be addressed. Accepted for publication 21 July 1997. 0163-4453/98/020209 +06 $12.00/0
rates to hospital with all the attendant resource implications. A retrospective study has therefore been performed of all immunocompetent patients admitted to Tayside hospitals over a 4-year period to analyse preadmission and in-patient treatment, length of stay and demographic details.
Materials and Methods The Tayside Medicines Monitoring (MEMO) Unit holds a computerized database containing details of all patients admitted to Tayside hospitals from January 1980.11 The information is collected from Scottish morbidity record (SMR) forms, which detail all discharge diagnoses of patients who leave hospital (or are transferred to another unit) following an episode of care. The last complete year for which data are currently available is 1992, and thus a 4-year period from January 1989 to December 1992 was examined. A programme was written to obtain a list of all patients, identified by their unique Community Health Index (CHI) number, discharged during the study period with acute Herpes zoster as a diagnosis. Synonyms such as shingles or ophthalmic shingles were also used to ensure as complete a cohort as possible, and patients with conditions indicating immunosuppression such as lymphoproliferative disease, malignancy, HIV infection and posttransplantation were excluded from analysis. The medical © 1998 The British Infection Society
210
J. Torrens et al.
records of this selected cohort were then retrieved and examined manually; any patient with an immunosuppressant condition or treatment not detailed on the SMR form was excluded from further analysis. From the resultant immunocompetent population, demographic details such as age, sex, year of admission, hospital and anatomical site affected were recorded. Length of stay was also recorded, as were pre-admission and in-patient treatment details. Statistical analysis was performed with Minitab for Windows.
Admitting units The majority of patients (74) presented to the regional infectious diseases unit in Dundee, but the remaining 30 patients presented to other acute units, 14 in Dundee, 10 in Perth and four in Brechin. Trigeminal zoster tended to be admitted to the infectious diseases unit and accounted for 4 2 / 7 4 (56.8%) of their admissions vs. 10/30 (33.3%) of admissions to other units.
Treatment received before admission to hospital Results
Hospitalization for acute Herpes zoster infection Other information, such as time of initial diagnosis and duration of rash and presentation, were not recorded frequently enough to w a r r a n t meaningful analysis. Herpes zoster appeared in the discharge diagnosis list of patients without mention of underlying disease as specified in the methods. Of these, 173 sets of notes were available but 14 patient records were incomplete and did not contain sufficient information to analyse. Of the remaining 159 patients, 26 were found to have underlying immunosuppressive diseases which had not been recorded in the discharge sheet, 17 were admitted with post-herpetic neuralgia several weeks after the attack of acute zoster, and nine patients developed acute zoster as inpatients, having been admitted with other diagnoses. Thus, of the 156 complete records examined, only 105 were from patients who fulfilled the protocol definition of admission to hospital with acute herpes zoster in a patient without underlying immunosuppression.
Site of infection and basic demography One 78-year-old female was admitted to the regional infectious diseases unit with disseminated zoster which was treated with aciclovir po, 800 mg five times daily. This patient has been excluded from further analysis. Of the remaining 104 patients, the dermatomes involved were trigeminal in 52, thoracic in 27, lumbar in 16 and cervical in nine. The majority of patients (73) were female and the distribution of dermatomes involved was similar in males and females. For the remainder of the analysis the patients have been divided into those with zoster in the trigemina] dermatomes and those with zoster at other sites. The median age was 79 years, but lower in the patients with trigeminal zoster (77 vs. 81) mainly due to a higher proportion of patients aged > 8 9 : 1 6 / 5 2 (30.8%) vs. 6/52 (11.5%).
Pre-admission treatment was not recorded for three patients with non-trigeminal zoster. Of the remaining patients, just over half of those in either dermatome group received no antiviral treatment before admission (Fig. 1). In comparison with the other dermatomes, patients with trigeminal neuralgia received less idoxuridine (6/52 vs. 10/52) and more oral aciclovir at the recommended dose of 800 mg 5 times daily (12/52 vs. 4/52). Oral aciclovir was administered to five patients at the wrong dose ( 2 0 0 m g 5 times daily), one with trigeminal zoster and four with zoster in other dermatomes.
Inpatient treatment Length of stay was highly variable (Fig. 2), but the distribution was similar in patients with trigeminal zoster (median 10.5 days, range 1 - 6 3 days) vs. zoster in other dermatomes (median 12 days, range 1 - 7 0 days). There was an exponential relationship between age and length of stay (Fig. 3) and, on the basis of a simple regression analysis, age (natural logarithm) explained 31.3% of the observed variation in length of stay. There were striking differences between the two groups with respect to inpatient antiviral treatment (Fig. 4). Almost all of the patients with trigeminal neuralgia (43/ 52) received systemic aciclovir at effective doses (800 mg po or 5 mg/kg IV) vs 27/52 of the patients with zoster at other sites, of w h o m 16 received no antiviral treatment at all, two received topical idoxuridine and six received oral aciclovir in the wrong dose. The relationship between treatment and length of stay was examined by dividing the patients into two groups: those who received systemic aciclovir at an effective dose (800 mg po or 2 0 0 m g IV) vs. those who did not (no antiviral treatment, topical antiviral treatment and < 8 0 0 mg po). The median duration of treatment was 11.0 days for patients who received effective systemic treatment vs. 16.5 days for those who did not. The 95% confidence interval (CI) for the difference between the medians was from 0 days to 8 days. However, median
Acute Herpes zoster in Tayside
211
No t r e a t m e n t
Idoxuridine
.3 Aciclovir 800 m g po
Aciclovir topical 4~ ¢6
800 m g po + topical ~ 7 7 7 ~
200 m g po I 10%
0%
I 20%
I 30%
I 40%
I 50%
60%
P e r c e n t a g e of p a t i e n t s Figure 1. Pre-admission treatment of patients with zoster.
35.0%
30.0% ,iz111/, ,i11/1z~ iiiii//,
"///////
"z/////Z. 25.0%
V////// II/I//L ,llllzl,
7//////. V////// "///////
20.0%
,iii/ii,
i/iiiii,
15.0% (D
~/////z
P~
5.0%
0.0%
0-4
5-9
10-14
Figure 2. Percentage of patients with different lengths of stay.
15-19 L e n g t h of s t a y (days)
20-24
25-29
> 29
212
J. Torrens et al. 5
3
-
%
•
2-
• •
• • •
~
1-
0
/
"
I 10
I 20
I 30
I 40
i= 50 A g e (years)
• mm •
mn
•
i 60
i= 70
=
i 80
=
i 90
100
Figure 3. Exponential relationship between age and length of stay.
No t r e a t m e n t
Idoxuridine
Aciclovir 800 m g o
•~
Aeielovir topical
Aciclovir 1V
800 m g + topical
400 m g po 0%
10%
] 20%
Figure 4. Variation in treatment regimens for patients with zoster.
] 30% P e r c e n t a g e of p a t i e n t s
] 40%
I 50%
60%
Acute Herpes zoster in Tayside age was lower for patients who received effective systemic treatment (76.5 vs. 83.5). The 95% CI for the difference between the medicines was from 1.0 to 15.1 years.
Discussion The median age of 79 reflects an elderly population, which is to be expected with an immunocompetent cohort, and the predominance of females reflects the background sex ratio of this population. 1° Of all patients, 53.5% received no treatment prior to admission, but patients with trigeminal zoster were more likely to receive specific and effective antiviral therapy, both pre-admission and as inpatients. Idoxuridine use was mainly confined to the years 1989 and 1990 (14/16), perhaps reflecting a gradual increase in awareness and use of aciclovir following its licensing for zoster in 1988. Various studies of different designs have delivered conflicting results on the efficacy of idoxuridine, but for all practical purposes its use cannot be recommended for acute zoster. 12 A previous community-based survey of 1019 patients with acute shingles found that the thoracic dermatome was most commonly affected (56%), and that the trigeminal dermatome was affected in 12% of cases. 13 Therefore, the finding that 50% of our hospitalized patients had trigeminal zoster suggests that the risk of hospitalization is far greater with shingles affecting this dermatome in comparison with thoracic, lumbar or sacral shingles; this accords with previously published figures. ~4 The median length of stay of 11 days agrees with previous observations, ~4 but it is interesting to note the exponential relationship between this and the patient's age. The median length of stay was longer in those who did not receive effective doses of systemic aciclovir than in those who did. However, age m a y have been a confounding variable, because the patients who received systemic treatment were younger. Therefore, the association between treatment and length of stay m a y not be cause and effect. In a recent paper, Brennan et al. ~5 have reminded authors of observational studies of their responsibility to highlight possible areas of bias, and confounding factors, and to resist the temptation to draw "statistically significant" conclusions from retrospective analyses. It should be noted that data such as renal function, time of initial diagnosis, and duration of rash before treatment commenced or admission requested were not collected. In addition, it is not possible to say to w h a t degree social factors (particularly relevant in an elderly population) m a y have influenced admission rates, length of stay, and even pre-admission treatment, or how m a n y patients m a y have had undiagnosed malignancy or equivalent
213
risk factors for zoster affecting morbidity and outcome. However, we believe several comments m a y be made on the basis of this study. Firstly, given the nature of current antiviral agents, I2' ~6.17 it is necessary to ensure early treatment with correct doses to achieve m a x i m u m benefit; doctors should be educated to this end. Secondly, elderly patients should not be excluded from active treatment, given that they m a y benefit more in terms of alleviation of acute symptoms and morbidity, including possibly post-herpetic neuralgia. 9' 17 Thirdly, there should be recognition of the significant morbidity and associated costs in those with post-herpetic neuralgia I and that any antiviral treatments should be assessed in terms of reducing hospital outpatient consultations, admission rates and length of stay, as well as alleviation of acute symptoms, time to healing of rash, and the incidence of post-herpetic neuralgia. Fourthly, we would recommend the instigation of audit of the m a n a g e m e n t of zoster, both in the community and in hospitals, and for further studies monitoring the efficacy of newer antiviral agents to be performed. Acute Herpes zoster remains an important cause of misery and suffering for a substantial minority of the elderly populations, as the prevalence of the elderly increases in the U.K. It is imperative that safe, beneficial, and effective treatment is offered as efficiently as possible to achieve the m a x i m u m outcome.
Acknowledgements We would like to thank Tayside Medicines Monitoring Unit for their help with this study.
References 1 Davies L, Cossins L, Bowsher D, Drummond M. The cost of treatment for post-herpetic neuralgia in the UK. PharmacoEconomics 1994; 6: 142-148. 2 Miller E, Marshall R, Vurdien J. Epidemiology, outcome and control of varicella-zoster infection. Rev Med Microbiol 1993; 4 : 2 2 2 - 2 3 0 . 3 Ragozzino MW, Melton III LJ, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine 1982; 61: 310-316. 4 Jolleys JV. Treatment of shingles and post-herpetic neuralgia: relieves shingles but does not prevent neuralgia. Br Med J 1989; 298: 1537-1538. 5 Wood MJ. Herpes zoster in immunocompetent patients. Res Clin For 1994; 8: 61-68. 6 Wood MJ, Johnson RW, McKendrick MWM, Taylor J, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N Eng J Med 1994; 330: 896-900. 7 McKendrick MW, McGill JI, White JE, Wood MJ. Oral acyclovir in acute herpes zoster. Br Med J 1986; 293: 1529-1532. 8 Wood MJ, Ogan PH, McKendrick MW, Care C, McGill WM. Efficacy
214
9 10 11
12
J. Torrens et al.
of oral acyclovir treatment of acute herpes zoster. Am J Med 1988; 85 (Suppl. 2A): 79-83. Gilden DH. Herpes zoster with postherpetic neuralgia-persisting pain and frustration. New Engl J Med 1994; 330: 932-933. Registrar General Scotland, Annual Report. Edinburgh. Scottish Office. 1993; 139. Beardon OHG, Brown SV, McDevitt DG. Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: a controlled study using record linkage in Tayside. Quart J Med 1989; 71: 497-505. Wood MJ. Current experience with antiviral therapy for acute herpes zoster. Annals of Neurology 1994; 35 (Suppl.): $65-68.
13 Glynn C, Crockford G, Gavaghan D, Cardno P, Price D, Miller J. Epidemiology of shingles. J Roy Soc Med 1990; 83: 617-619. 14 Bannister P, Crosse B. Severe herpes zoster infection in the United Kingdom: experience in a regional infectious disease unit. J Roy Soc Med 1989; 82: 145-146. 15 Brennan P, Croft P. Interpreting the results of observational research: chance is not such a fine thing. Br MedJ 1994; 309: 727-730. 16 Whitley R]. Therapeutic approaches to varicella-zoster virus infections. J InfDis 1992; 166 (Suppl. 1): $51-57. 17 Whitley RJ, Straus SE. Therapy for varicella-zoster virus infections: where do we stand? Infect Dis Clin Pract 1993; 2: 100-108.