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Corticosteroids for preventing postherpetic neuralgia

  1. Ying Han1,*,
  2. Jingjing Zhang2,
  3. Ning Chen2,
  4. Li He2,
  5. Muke Zhou2,
  6. Cairong Zhu3

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 16 APR 2012

DOI: 10.1002/14651858.CD005582.pub4


How to Cite

Han Y, Zhang J, Chen N, He L, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD005582. DOI: 10.1002/14651858.CD005582.pub4.

Author Information

  1. 1

    Xuanwu Hospital, Capital Medical University, Department of Neurology, Beijing, China

  2. 2

    West China Hospital, Sichuan University, Department of Neurology, Chengdu, Sichuan, China

  3. 3

    School of Public Health, Sichuan University, Epidemic Disease & Health Statistics Department, Sichuan, Chengdu, China

*Ying Han, Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng District, Beijing, 100053, China. sophiehanying@gmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 MAR 2013

SEARCH

 

Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 
Summary of findings for the main comparison. Corticosteroids for acute herpes zoster to prevent postherpetic neuralgia

Corticosteroids for acute herpes zoster to prevent postherpetic neuralgia

Patient or population: patients with acute herpes zoster to prevent postherpetic neuralgia
Settings: hospitals and clinics
Intervention: corticosteroids

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlCorticosteroids

Presence of PHN six months after the onset of the acute herpetic rash
Clinical manifestation
Follow-up: 6-23 months
193 per 1000183 per 1000
(87 to 384)
RR 0.95
(0.45 to 1.99)
114
(2 studies)
⊕⊕⊕⊝
moderate1

Serious adverse events
Clinical manifestation and laboratory examination
Follow-up: 6-23 months
8 per 100013 per 1000
(3 to 42)
RR 1.65
(0.38 to 5.29)
755
(5 studies)
⊕⊕⊕⊝
moderate1

Non-serious adverse events
Clinical manifestation and laboratory examination
Follow-up: 6-23 months
113 per 1000147 per 1000
(102 to 211)
RR 1.30
(0.9 to 1.87)
755
(5 studies)
⊕⊕⊕⊝
moderate1

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 There is a high risk of bias due to inadequately addressed incomplete outcome data of the Esmann 1987 trial, in which six participants were withdrawn, but the reasons and assigned groups of five cases were not specified.

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Postherpetic neuralgia (PHN) is a painful condition that occurs in people following an acute herpes zoster infection (commonly referred to as 'shingles'). Shingles is an acute vesicular eruption involving one or two adjacent dermatomes, with pain often preceding the eruption by days to weeks (Kost 1996). Herpes zoster results from reactivation of the varicella-zoster virus acquired during chicken pox, the primary varicella infection. Reactivation of latent varicella-zoster virus from dorsal root ganglia is responsible for the classic dermatomal rash and pain that occurs with herpes zoster (Kost 1996).

Herpes zoster is a sporadic disease with an estimated lifetime incidence of 10% to 20%. Its incidence increases sharply with advancing age, roughly doubling in each decade past the age of 50 years. Herpes zoster is uncommon in people less than 15 years old. The normal age-related decrease in cell-mediated immunity is thought to account for the increased incidence in older age (Stankus 2000). People with disease states that affect cell-mediated immunity, such as human immunodeficiency virus (HIV) infection and certain malignancies, are at increased risk. Chronic corticosteroid use, chemotherapy and radiation therapy may increase the risk of developing herpes zoster (Fillet 2002). Ethnic background may influence susceptibility to herpes zoster. Black people are one fourth less likely than white people to develop it. Although herpes zoster is not as contagious as primary varicella infection, people with reactivated infection can transmit varicella-zoster virus to non-immune contacts. There is no seasonal incidence and the areas of the body affected tend to be the chest and abdomen and the territory of the ophthalmic division of the trigeminal nerve.

PHN is one of the most common complications of herpes zoster. It may persist until death and has major implications for quality of life and use of healthcare resources. Although PHN has been defined in different ways, recent data support the distinction between acute (within 30 days of rash onset), subacute (30 to 120 days after rash onset) and PHN (defined as pain lasting at least 120 days from rash onset) (Desmond 2002; Dworkin 1994).

Although age, acute pain severity and rash severity appear to be correlated with incidence of PHN, accurate predictors for PHN have not been defined (Johnson 2003). About 20% of people with herpes zoster develop PHN. Its incidence is between 9% and 14% one month after the herpes zoster eruption. The most established risk factor is age. As age increases, the risk and duration of PHN also rise (Griffin 1998; Rosler 1996). The incidence of PHN after an outbreak of shingles is 10% in people over 40 years, and 20% to 50% in people over 60 years. PHN is rarely seen in people under 30 years. Other possible risk factors for the development of PHN are ophthalmic zoster, prodromal pain before the appearance of skin lesions and an immunocompromised state (Stankus 2000).

There is a tendency for PHN to improve with time and as few as 3% of people are left with severe PHN after one year. However, some series report that as many as 40% of people with PHN will continue to have long-term problems because of incomplete or no pain relief from treatments. There is no way of predicting who will recover (de Moragas 1957).

Varicella-zoster virus is a highly contagious DNA virus. It is thought that the varicella virus passes to the dorsal root ganglion via the skin during the initial infection (chicken pox) and lies dormant. The latent virus becomes reactivated when immune mechanisms are impaired and it is manifested by the rash and the pain. The pathophysiology of PHN remains unclear. However, pathologic studies have demonstrated damage to the sensory nerves, sensory dorsal root ganglia and dorsal horns of the spinal cord. The presence of PHN may reflect the persistence of more than the low amounts of varicella-zoster virus found during latency with continued inflammation. If this is the case, there may be a rationale for the aggressive treatment with aciclovir, and perhaps corticosteroids, of people who have zoster (Mahalingam 1993; Smith 1978).

The treatment of herpes zoster has three major objectives: (1) treatment of the acute viral infection, (2) treatment of the acute pain associated with herpes zoster, and (3) prevention of PHN. Antiviral agents, oral corticosteroids and adjunctive individualised pain-management modalities are used to achieve these objectives.

Treatment of PHN is difficult and a variety of treatments are offered without consensus about their effectiveness. The complexity of the underlying changes might account for the lack of efficacy of a single therapeutic approach (Alper 2002; Dworkin 2000; Johnson 2003). The effectiveness of antiviral agents in preventing PHN has been evaluated in a separate Cochrane review; it concluded that oral aciclovir was ineffective in reducing the incidence of PHN while insufficient evidence was found to recommend other antiviral treatments to prevent PHN (Li 2009).

Some older studies designed to evaluate the effectiveness of corticosteroids such as prednisolone or triamcinolone prednisone therapy in preventing PHN have suggested decreased pain at three and 12 months (Eaglstein 1970; Keczkes 1980). Other studies have demonstrated no significant benefit (Lancaster 1995; Volmink 1996). Another two large randomised, placebo-controlled trials evaluated the combination of corticosteroids and the antiviral agent aciclovir. One claimed that the addition of prednisone reduced the incidence and severity of acute pain but provided no additional benefit for long-term pain over aciclovir alone (Wood 1994b). The other suggested that aciclovir and a corticosteroid did not significantly alter the course of long-term zoster-associated pain but might improve quality of life (Whitley 1996). Despite the lack of clear evidence, corticosteroids are commonly used in the treatment of herpes zoster. A systematic review of corticosteroids for preventing PHN is needed to try and clarify the evidence and include in any meta-analysis the results of past and future trials.

The first version of this Cochrane review, published in 2008, indicated that there was insufficient evidence to draw any conclusion about the efficacy of corticosteroids in preventing PHN. In this update, which includes more up to date data analysis methodology, we conclude that there is moderate quality evidence that there is no benefit of corticosteroids in preventing postherpetic neuralgia, but that this evidence is limited.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

To examine the efficacy of corticosteroids in preventing PHN.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We searched for all randomised controlled trials (RCTs) for corticosteroids for preventing PHN after an acute herpes zoster infection, irrespective of any language restrictions. We did not include quasi-RCTs (trials in which a systematic method of randomisation such as alternation or hospital number was used).

 

Types of participants

We included people of all ages with herpes zoster of all degrees of severity, within seven days after the onset.

 

Types of interventions

We included all kinds of corticosteroids including hydrocortisone, prednisone, prednisolone, triamcinolone and dexamethasone given by an oral, intramuscular or intravenous route during the acute stage (starting within one week of the onset of the rash). We included trials which compared corticosteroids with no treatment or placebo but not with other treatments. It is intended that another review will include comparisons of corticosteroids with antiviral agents. We also included trials which compared corticosteroids plus routine treatment with placebo plus routine treatment. Other forms of administration of corticosteroids such as epidural injection or topical administration were not included.

 

Types of outcome measures

 

Primary outcomes

The primary outcome measure was the presence of PHN six months after the onset of the acute herpetic rash. PHN was defined according to clinical diagnostic criteria as persisting or recurring pain at the site of shingles at least one month after the onset of the acute rash (MacDonald 2000).

 

Secondary outcomes

Secondary outcome measures were as follows.

  1. Pain severity measured by a validated visual analogue scale or numerical descriptive scale after three, six and 12 months.
  2. Quality of life measured with the Short Form-36 Health Survey questionnaire (SF-36) (Ware 1998) after six months.
  3. Adverse events during or within two weeks after stopping treatment. Adverse events were categorised as serious or not serious. Serious adverse events were those which were life-threatening, required or prolonged hospitalisation, or caused death.

 

Outcomes for inclusion in a 'Summary of findings' table

We included a 'Summary of findings' table to illustrate the findings of the review and our assessment of the quality of the evidence for the key outcomes:

  • presence of PHN six months after the onset of the acute herpetic rash;
  • serious adverse events;
  • non-serious adverse events.

We graded the quality of the evidence from the included RCTs as high, moderate, low or very low based on the GRADE criteria. These start from a grading of high for RCTs. Reasons for downgrading are: study limitations, consistency of effect, imprecision, indirectness and publication bias. Evidence from downgraded RCTs can be upgraded for a large effect size in cases when all plausible confounding would tend to underestimate the size of the effect or when there is a dose-response gradient (GRADE working group 2004; Schünemann 2011; Schünemann 2011b).

 

Search methods for identification of studies

We searched for all RCTs of corticosteroids for preventing PHN after an acute herpes zoster infection irrespective of the language of publication.

We searched the Cochrane Neuromuscular Disease Group Specialized Register for RCTs (16 April 2012). The following search terms were used singly and in appropriate combinations: 'herpes zoster', 'shingles', 'postherpetic' or 'post-herpetic', 'neuralgia' or 'neuropathy' or 'pain', 'glucocorticoids', 'adrenal cortex hormones', 'corticosteroid', 'steroid', 'prednisolone', 'triamcinolone', 'dexamethasone', 'hydrocortisone' and 'prednisone'. We adapted this strategy to search CENTRAL (2012, Issue 3), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), LILACS (January 1982 to April 2012) and the Chinese Biomedical Retrieval System (January 1978 to February 2012). We also reviewed the bibliographies of the trials identified, contacted the authors and known experts in the field, and approached pharmaceutical companies to identify additional published or unpublished data.

The detailed search strategies are in the appendices: Appendix 1 (MEDLINE), Appendix 2 (EMBASE), Appendix 3 (CENTRAL), Appendix 4 (LILACS) and Appendix 5 (Chinese Medical Retrieval System).

 

Data collection and analysis

 

Selection of studies

Two review authors scrutinised titles and abstracts identified from the register. The review authors obtained the full text of all potentially relevant studies for independent assessment. Three review authors scrutinised all possible published and unpublished trials for inclusion. We resolved any disagreement by discussion.

 

Data extraction and management

Two review authors extracted data on participants, methods, interventions, outcomes and results independently and then entered the data into the Review Manager (RevMan 5) Cochrane authoring and statistical software. We obtained missing data from the study authors whenever possible. We extracted data on the number of participants with each outcome event, by allocated treatment group, irrespective of compliance with the protocol, and whether or not the participant was subsequently deemed ineligible or otherwise excluded from treatment or follow-up, so that the data could be analysed on an intention-to-treat basis. We resolved disagreement by discussion.

 

Assessment of risk of bias in included studies

Two review authors (YH, JZ) assessed the risk of bias in each trial. The assessment of risk of bias took into account security of randomisation, allocation concealment, blinding, completeness of outcome data, selective outcome reporting, and any other potential sources of bias. These items were assessed by two authors independently according to the Cochrane Collaboration standard scheme (Higgins 2011). All included trials were judged for each item as 'High risk of bias', 'Low risk of bias' or 'Unclear risk of bias'. We used 'Unclear risk of bias' if: there was insufficient detail to assess risk of bias, information was available but the risk of bias was unclear, or when the entry was not relevant to the study. We resolved any disagreement by discussion, with reference to a third author if necessary.

 

Data synthesis

We used RevMan 5 for the statistical analysis and reported data according to the Cochrane Collaboration criteria. Where meta-analysis was possible, we pooled results of clinically and statistically homogeneous trials to provide estimates of efficacy. We planned to analyse all the primary and secondary outcomes under consideration. For dichotomous outcomes we expressed the results as risk ratios (RRs) while for continuous outcomes we compared means and calculated mean differences (MDs), all with 95% confidence intervals (CIs).

To avoid unit-of-analysis error resulting from combining results of more than one time point for each study in a standard meta-analysis, we evaluated outcomes based on the periods of follow-up (six months after disease onset). For studies that compared more than two intervention groups, we selected the relevant pair of intervention groups to include in the analyses.

 

Subgroup analysis and investigation of heterogeneity

We performed the following subgroup analyses.

  1. Treatment started sooner or later after onset of herpes zoster (24 hours or less after onset; more than 24 hours up to 72 hours after onset; and more than 72 hours after onset).
  2. Younger and older (adults 49 years of age or less; adults aged 50 years or more).

 

Sensitivity analysis

We assessed heterogeneity among trials using the Chi2 test with a 10% level of statistical significance (P < 0.1) and I2 > 50% (Higgins 2002; Higgins 2003). When significant heterogeneity was present, we planned to undertake sensitivity analyses by repeating the calculation after omitting the trials which had a high risk of bias. We used a fixed-effect model for meta-analysis unless unexplained heterogeneity was identified when we planned to use a random-effects model analysis. For trials that were clinically heterogeneous or provided insufficient information for pooling, we performed a descriptive analysis.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

See tables: Characteristics of included studies and Characteristics of excluded studies.

 

Results of the search

For the 2012 update, the electronic searches retrieved a number of references: 20 from the Cochrane Neuromuscular Disease Group Specialized Register, 73 from CENTRAL, 760 from MEDLINE, 164 from EMBASE, 6 from LILACS, and 338 from the Chinese Biomedical Retrieval System. After scrutinising these titles and abstracts, we selected 43 possible RCTs, 35 of which were the same as those in the first version of this review. We found three additional potentially relevant trials (Brusco 1993; Huang 2010; Zeng 2011) during the search for the 2012 update, but these were found not to be RCTs on further checking. No other new trials were found by searching other sources. We excluded four trials that were awaiting assessment in the previous update as the participants' course of disease from onset to start of treatment exceeded seven days (Lin 2002; Wang 2004; Xu 1999; Zhang 2005); one study is still awaiting assessment (Hu 2001).

We excluded 37 trials (see Characteristics of excluded studies). Of these, two trials (Benoldi 1991; Keczkes 1980) compared corticosteroids with other treatment. Nineteen studies were found not to be RCTs by contacting the authors (Brusco 1993; Cui 2002; Hao 2002; Huang 2004; Huang 2010; Jiang 2008; Li 2000; Li 2002; Lin 2005; Ma 2000; Ma 2002; Shi 2008; Song 2009; Tang 2004; Yang 2010; Zeng 2011; Zhang 2003; Zhou 2000; Zhou 2008). In seven trials, participants received therapy that was mismatched in dosage, course of treatment or basal medication between corticosteroids and control groups (Guo 2001; Jiang 2005; Yang 2000; Yin 2004; Yin 2005; Zhang 2004; Zheng 2004). Four trials defined PHN as pain persisting at the site of shingles two weeks after the onset of the acute rash (Chang 2004; Liu 2003; Liu 2005; Yang 2002) and another trial defined PHN as pain persisting one week after total decrustation (Liao 2005); the follow-up of each of these studies was less than one month. As described above, four trials exceeded our seven days in the treatment criterion (Lin 2002; Wang 2004; Xu 1999; Zhang 2005).

The study currently awaiting classification did not clarify the exact course of disease from onset of herpes zoster to receipt of treatment (Hu 2001). We contacted the study authors by mail but obtained no reply. Another article (Levinson 1985), which was classified as a study awaiting assessment in the first version of this Cochrane review, was a review of the previous studies. Although the authors said they were investigating the feasibility of a multicentre trial in this field, we did not find any subsequent trial report so we removed the reference from studies awaiting assessment.

Five trials (Clemmensen 1984; Eaglstein 1970; Esmann 1987; Whitley 1996; Wood 1994a) fulfilled the selection criteria (see Characteristics of included studies).

For the 2012 update we did not find any new trials for inclusion. Although we found two more trials published in the last two years in the Chinese databases (Huang 2010; Zeng 2011) and one trial in LILACS (Brusco 1993), we excluded all three because their participants were not truly randomly assigned to groups.

 

Trial design

The included trials were all randomised, double-blind, placebo-controlled parallel studies. Two of these were performed in a single centre (Clemmensen 1984 conducted in Denmark; Eaglstein 1970 conducted in a Miami dermatology inpatient service) and the others were performed in multiple centres (Esmann 1987 conducted in Aarhus and Copenhagen, Denmark; Whitley 1996 conducted in 15 university hospitals or affiliated clinics in USA; Wood 1994a conducted in four centres in the United Kingdom).

 

Participants

A total of 787 participants were enrolled in the five included studies. Four trials (Clemmensen 1984; Eaglstein 1970; Esmann 1987; Whitley 1996) reported the range of ages as 16 to 91 years old. Four trials (Clemmensen 1984; Esmann 1987; Whitley 1996; Wood 1994a) stated the gender distribution (male 307, female 427) and mean age of participants. All of the five trials defined explicit inclusion criteria. Among them, one trial (Eaglstein 1970) included participants with early, severely painful zoster; four trials (Clemmensen 1984; Esmann 1987; Whitley 1996; Wood 1994a) included participants with herpes or pain of different grades of severity. One trial (Esmann 1987) included participants aged at least 60 years and with onset of herpes zoster less than 96 hours before admission. One trial (Whitley 1996) included immunocompetent adults older than 50 years of age who fell ill less than 72 hours before study enrolment. One trial (Wood 1994a) included adults who fell ill less than 72 hours before study enrolment. All five included trials also defined explicit exclusion criteria. They excluded participants with peptic ulcer, psychosis, malignant disease, hypertension, diabetes, cardiac insufficiency, adrenocortical disease, tuberculosis, lymphomas, leukaemias, bacterial infections, pregnancy, or those who were on corticosteroid treatment. The time of onset to start of treatment was zero to seven days for four included trials (Clemmensen 1984; Esmann 1987; Whitley 1996; Wood 1994a). One trial (Eaglstein 1970) only stated that the mean time was five days, and more details could not be obtained.

 

Interventions

The treatment regimens varied between studies (see Characteristics of included studies). Two trials (Clemmensen 1984; Eaglstein 1970) compared corticosteroids with placebo. One trial used oral triamcinolone 16 mg three times daily for seven days, 8 mg three times daily for seven days, and 8 mg twice daily for seven days (Eaglstein 1970). One trial administered corticosteroid orally or adrenocorticotropic hormone (ACTH) intramuscularly (Clemmensen 1984). Prednisone was given in doses of 45 mg daily during the first week, 30 mg daily during the second week, and 15 mg daily tapered to zero during the third week. ACTH (Synacthen depot, 1 mg) was given intramuscularly three times a week (Monday, Wednesday, Friday) amounting to a total of seven injections. Placebo tablets or injections that were indistinguishable from the active medication were used (Clemmensen 1984). Three trials used aciclovir in combination with corticosteroids versus aciclovir in combination with placebo (Esmann 1987; Whitley 1996; Wood 1994a). One trial used 800 mg aciclovir orally five times daily for seven days and coded tablets containing either prednisolone or calcium lactate for 21 days. The dose of prednisolone was 40 mg daily for seven days, 30 mg for four days, 20 mg for three days, 10 mg for four days, and finally 5 mg for three days (Esmann 1987). One trial used prednisone or a matched placebo orally, 60 mg/day for days one to seven, 30 mg/day for days eight to 14, and 15 mg/day for days 15 to 21 (Whitley 1996). Aciclovir or a matched placebo was administered orally at 800 mg five times daily for 21 days. Matched medications were identical in taste and appearance. The four treatment regimens given were aciclovir plus prednisone, aciclovir plus prednisone placebo, prednisone plus aciclovir placebo, and placebos for both aciclovir and prednisone (Whitley 1996). Another trial administered aciclovir 800 mg orally five times daily, beginning on day zero (Wood 1994a). The participants in the groups assigned to seven days of aciclovir therapy (with or without corticosteroid) received matching placebo beginning on day seven. Prednisolone was administered according to the following schedule: on days zero through six, 40 mg per day; days seven through 10, 30 mg per day; days 11 through 14, 20 mg per day; days 15 through 18, 10 mg per day; and days 19 through 21, 5 mg per day (total dose 535 mg). Prednisolone was given as 5 mg tablets. The participants in the groups not receiving corticosteroid received matching placebo tablets. The four treatment regimens given were: aciclovir for seven days with corticosteroids, aciclovir for seven days without corticosteroids, aciclovir for 21 days with corticosteroids, and aciclovir for 21 days without corticosteroids (Wood 1994a). All trials followed the participants for at least six months or until the PHN ended or the participant no longer returned. One trial monitored all participants for three years (Eaglstein 1970).

 

Outcome measures

The outcome measures used differed between trials. Four trials reported the duration of PHN or presence of PHN at six months after the onset of the acute herpetic rash (Eaglstein 1970; Esmann 1987; Whitley 1996; Wood 1994a). Two trials did not provide separate information on the number of participants with PHN at six months and were therefore not included in the meta-analysis (Whitley 1996; Wood 1994a). All five included trials did not report, as a separate outcome, pain severity measured by a validated visual analogue scale or numerical descriptive scale after three, six and 12 months or the quality of life measured with the SF-36 Health Survey after six months. All five included trials reported adverse events during treatment or within two weeks after stopping treatment. Adverse events were categorised as serious or not serious.

 

Risk of bias in included studies

See: the 'Risk of bias' table of each included study in Characteristics of included studies.

All included trials were randomised, double-blind, placebo-controlled parallel studies. The method of randomisation was reported in three included trials (Eaglstein 1970; Whitley 1996; Wood 1994a). The Eaglstein study (Eaglstein 1970) used randomisation with a centralised code generated at a pharmacy. A supply of medication for each participant was assigned a different code number and distributed to the participants; the code of each participant was opened after a three-year follow-up. The Whitley and Wood studies both used a computer-generated randomisation code to randomly assign participants; in Wood 1994a the randomisation code was stratified by study centre to assign participants in blocks of eight to either group so that allocation concealment might be performed; the method of allocation concealment in Whitley 1996 was unclear. Clemmensen 1984 and Esmann 1987 did not describe the method of randomisation, and it was not clear from the reports if there was adequate allocation concealment in either study. The five included trials were all double-blind, using placebo in the control group. One of these trials used lactose as placebo (Eaglstein 1970), another used calcium lactate (Esmann 1987), and the other three studies only stated placebo tablets indistinguishable from the active medication but did not describe their composition (Clemmensen 1984; Whitley 1996; Wood 1994a). Three of the five trials (Esmann 1987; Whitley 1996; Wood 1994a) included aciclovir as routine treatment. All trials considered baseline clinical features. In four trials the baseline clinical features were similar between groups (Clemmensen 1984; Esmann 1987; Whitley 1996; Wood 1994a). In one trial baseline differences were not described (Eaglstein 1970) but the authors reported no serious imbalances in baseline prognostic factors between groups.

All five included studies reported the time of follow-up; three used six months (Esmann 1987; Whitley 1996; Wood 1994a), one 10 months (Clemmensen 1984), and one three years (Eaglstein 1970). In one study (Esmann 1987) six participants were withdrawn but it was unclear whether the lack of compliance was due to inefficacy or side effects. The group that those participants were first assigned to was not specified so bias from incomplete outcome data was possibly an issue in this study. The other four studies all reported information about follow-up and dropouts and described the reasons for dropping out clearly. Only one study claimed that an intention-to-treat analysis was used (Whitley 1996); the other four included studies did not state whether, or not, the analysis was by intention to treat, but there was sufficient information in three trial reports (Clemmensen 1984; Eaglstein 1970; Wood 1994a) to restore them to the correct group and perform an intention-to-treat analysis in our review.

For each included study, outcomes listed in the methods section were all reported. Publication bias should be taken into account since most of the included and excluded studies were published in English or Chinese, although we have attempted to do our best to search all probable literature without any language restrictions and have contacted investigators to get more information. The included studies used different cut-off times to definite PHN so, although we clearly stated that PHN was pain persisting, or recurring, at the site of shingles at least one month after the onset of the acute rash, we have not restricted inclusion to studies using the same definition in order not to introduce more missing data.

For this update, according to the new 'Risk of bias' assessments (Higgins 2011), we updated 'blinding' and performed the analyses in two parts: blinding of participants and personnel, and blinding of outcome assessment. Two (Eaglstein 1970; Wood 1994a) of the trials were rated as at low risk of bias, two (Clemmensen 1984; Whitley 1996) as unclear risk of bias, and one (Esmann 1987) as at high risk of bias (Figure 1).

 FigureFigure 1. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Effects of interventions

See:  Summary of findings for the main comparison Corticosteroids for acute herpes zoster to prevent postherpetic neuralgia

 

Primary outcome measure

 

Presence of PHN six months after the onset of the acute herpetic rash

One trial comparing triamcinolone with placebo (Eaglstein 1970) provided data on the presence of PHN six months after the onset of the acute herpetic rash. There was no significant difference in the number of participants with PHN six months after the onset of the acute herpetic rash between those in the corticosteroids group (2/15,13.3%) and those in the placebo group (2/20, 10.0%). However, the wide CIs meant we could not rule out significant benefit or harm (RR 1.33, 95% CI 0.21 to 8.41). This study also reported the presence of PHN at other time points during follow-up, including one and four months after the onset, which are also commonly used to evaluate incidence of PHN. The presence of PHN was not statistically different between groups (9/15 versus 14/20 at one month, P = 0.55; 2/15 versus 4/20 at four months, P = 0.61). Another trial comparing prednisolone plus routine treatment with placebo plus routine treatment (Esmann 1987) provided data for our primary outcome. The trial compared aciclovir plus corticosteroids with aciclovir plus placebo. The presence of PHN six months after the onset of the acute herpetic rash following corticosteroids plus antiviral agents (9/42, 21.4%) was not significantly different from its presence following placebo plus antiviral agents (9/37, 24.3%) (RR 0.88, 95% CI 0.39 to 1.98).

We conducted a meta-analysis combining relevant data from the above two trials, with a total of 114 participants, and the results showed that oral corticosteroids did not play a part in preventing PHN six months after the onset of herpes (RR 0.95, 95% CI 0.45 to 1.99, P = 0.89) ( Analysis 1.1; Figure 2). The Clemmensen study (Clemmensen 1984) used a cut-off time of six weeks for defining PHN, concluding that prednisone did not decrease the incidence of PHN. Since the numbers of participants with PHN six months after the rash onset could not be obtained, these data were not included in any meta-analysis for effects of corticosteroids ( Summary of findings for the main comparison).

 FigureFigure 2. Forest plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.1 The presence of PHN six months after the onset of the acute herpetic rash.

Two other trials provided relevant data for this outcome although not in a format which permitted inclusion in our meta-analysis. In a trial with 201 participants (Whitley 1996), a Cox regression model analysis of the main effect of prednisone compared with no prednisone showed no significant difference in the time to cessation of zoster-associated pain (RR 1.26, 95% CI 0.91 to 1.75). From their Cox regression model, we used the generic inverse variance approach to calculate the main effect of prednisone compared with no prednisone and confirmed that there was no significant difference in the time to cessation of zoster-associated pain (RR 1.11, 95% CI 0.96 to 1.27) ( Analysis 1.2; Figure 3). In the trial with 400 participants, of whom 349 completed the study (Wood 1994a), the investigators did not detect significant differences between any of the treatment groups in the time to complete cessation of pain. The median time to cessation of pain was 147 and 120 days in the groups receiving 7-day and 21-day aciclovir without a corticosteroid and 146 and 120 days in the two groups who received aciclovir with corticosteroids. Thus, the results of both these large trials agreed with the conclusion from the meta-analysis of the two smaller trials that corticosteroids did not significantly affect the presence of PHN after six months.

 FigureFigure 3. Forest plot of comparison: 1 Corticosteroids versus placebo or no treatment, outcome: 1.2 The main effect of prednisone compared with no prednisone on six months evaluation of pain (generic inverse variance).

 

Secondary outcome measures

 

(1) Pain severity measured by a validated visual analogue scale or numerical descriptive scale after three, six and 12 months

Four included trials (Clemmensen 1984; Eaglstein 1970; Esmann 1987; Wood 1994a) evaluated pain intensity after using corticosteroids to treat acute herpes zoster, but three of them (Clemmensen 1984; Eaglstein 1970; Wood 1994a) recorded the data only during the first month and they used different pain evaluation methods; so we were not able to include the data in a meta-analysis even when attempting to convert outcomes to dichotomous data. The Clemmensen study graded pain from zero (no pain) to three (insufferable pain). There was no significant difference in mean pain score between prednisone and placebo during the 21-day treatment period, and the score was significantly lower in the ACTH group during the first four days of the trial (P = 0.02 to 0.03) but not after (Clemmensen 1984). One trial reported that in participants more than 60 years old, pain resolved spontaneously but more rapidly with corticosteroids (Eaglstein 1970). In the Wood trial (Wood 1994a) the reduction in pain score was significantly larger in the corticosteroids groups than the no-corticosteroids groups on days 7 and 14 (P < 0.01). Only one trial reported pain at six months: 18 participants had pain, of whom 15 had light pain; two had moderate pain; and one had severe pain. Among them nine had received prednisone and nine placebo but the severity of pain was not reported by group (Esmann 1987).

 

(2) Quality of life measured with the SF-36 Health Survey after six months

None of the trials reported separate data on quality of life measured with the SF-36 Health Survey after six months.

 

(3) Adverse events during or within two weeks after stopping treatment

Adverse events were categorised as serious or not serious. Serious adverse events were those which were life-threatening, required or prolonged hospitalisation, or caused death. Details for individual studies have been given in the Characteristics of included studies table.

 
(a) Serious adverse events

Two of the included trials explicitly recorded the absence of serious adverse effects attributable to the experimental treatment (Clemmensen 1984; Eaglstein 1970). The other three trials all reported several serious adverse events during or within two weeks after stopping treatment, including acute cardiac insufficiency (Esmann 1987), myocardial infarction (Whitley 1996), pneumonia or bronchopneumonia (Whitley 1996; Wood 1994a), chest infection (Wood 1994a), haematemesis (Wood 1994a) and death from other unspecified causes (Wood 1994a). In the meta-analysis, the incidence of serious adverse events for corticosteroids (6/376, 1.6%) was not significantly different from that for placebo (3/379, 0.8%) (RR 1.65, 95% CI 0.51 to 5.29, P = 0.40) ( Analysis 1.3; Figure 4).

 FigureFigure 4. Forest plot of comparison: 1 Corticosteroids versus placebo, outcome: 1.3 Serious adverse events.

 
(b) Non-serious adverse events

All five trials reported details of non-serious adverse events, including clinical manifestation or laboratory results, the number of participants experiencing each adverse event, and their distribution between groups. The most frequently reported non-serious adverse events were gastrointestinal symptoms (such as dyspepsia, nausea, vomiting and diarrhoea), dizziness, headache, sweats, rash, oedema, hyperglycaemia, and increase of serum aspartate glutamyltransferase. In our meta-analysis of data from the five trials ( Analysis 1.4; Figure 5), the overall incidence of non-serious adverse events for corticosteroids (55/376, 14.6%) was not statistically significant compared to placebo (43/379, 11.3%) (RR 1.30, 95% CI 0.90 to 1.87, P = 0.16).

 FigureFigure 5. Forest plot of comparison: 1 Corticosteroids versus placebo, outcome: 1.4 Non-serious adverse events.

 

Subgroup analyses

 

Time from onset of herpes zoster to start of treatment (24 hours or less after onset, more than 24 hours up to 72 hours after onset, and more than 72 hours after onset)

This information was not available from the published reports.

 

Younger and older (adults 49 years of age or less, adults aged 50 years or more)

 
(a) Adults aged 50 years or more

The Eaglstein study (Eaglstein 1970) reported duration of pain for each participant in bar charts which clearly showed the age of each participant. Two other trials (Esmann 1987; Whitley 1996) only enrolled participants aged more than 60 or 50 years old, respectively. So a subgroup analysis involving only adults aged 50 years or more was potentially possible for these three trials. Unfortunately the Whitley study was not included in the meta-analysis since detailed numbers of events could not be extracted from this article. Thus in two trials (Eaglstein 1970; Esmann 1987) including 107 participants aged 50 years or more, the presence of PHN six months after the onset of the acute herpetic rash was similar in the corticosteroids group (11/53, 20.8%) to that in the placebo group (11/54, 20.4%) (RR 0.97, 95% CI 0.47 to 2.04) ( Analysis 2.1; Figure 6).

 FigureFigure 6. Forest plot of comparison: 2 Subgroup analysis, outcome: 2.1 The presence of postherpetic neuralgia six months after the onset of the acute herpetic rash.

The Clemmensen study (Clemmensen 1984) reported 33 participants in the group of participants aged over 55 years, of whom nine developed PHN (four in the prednisone group, one in the placebo group, and four in the other treatment group) without significant differences between groups. However, the study defined PHN using a six-week cut-off time and only reported the mean duration of PHN as 4.2 months (range 1.5 to 10.0 months), so we were not able to obtain the separate data on participants with PHN after six months follow-up.

 
(b) Adults 49 years of age or less

In one trial with six participants (Eaglstein 1970), none developed PHN after six months follow-up. In the Clemmensen study (Clemmensen 1984) none of the 22 participants aged 55 years or less developed PHN (the mean duration of PHN was 4.2 months). Relevant data could not be obtained from the other trials.

One of the participants in the Eaglstein study was not included in either the younger or older subgroup as she was withdrawn because of possible side effects. Her age was not reported in the article (Eaglstein 1970).

 

Sensitivity analyses

Heterogeneity amongst trials was assessed for each comparison, but no significant heterogeneity ( I2 > 50%) was present. Furthermore, although a trial of poor quality was included in the meta-analyses the results of each included trial were all similar with no significant differences in the outcomes relevant to this review. Therefore, we did not undertake any sensitivity analysis.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Clinical therapeutic effect

Our aim was to review the evidence from RCTs on the effectiveness and safety of corticosteroids in preventing PHN. Only five studies examining the prevention effects of corticosteroids in a total of 787 participants were suitable for this review. This is a relatively small number in relation to the known variability in the outcome of PHN.

The meta-analysis of two trials which provided data for our primary outcome measure showed no significant difference between the corticosteroid group and the placebo group in the number of participants with PHN six months after the onset of the acute herpetic rash. There was no significant difference in time to cessation of pain in two larger trials, one with 201 and one with 359 participants (Whitley 1996; Wood 1994a).

Established PHN may be intractable and lead to considerable disability in social and domestic activities. Pain evaluation is the key step to controlling neuropathic pain. Doctors must make a detailed and full-scale pain evaluation during the period of treatment and follow-up, including pain character, intensity, position and scope. The most used evaluation methods are the validated visual analogue scale (VAS) or numerical descriptive scales (NRS). Four of the trials included in this review evaluated pain intensity changes but used different pain evaluation methods, so we were unable to combine the data in our meta-analysis. Two trials (Clemmensen 1984; Esmann 1987) reported that corticosteroid treatment did not give additional pain relief during the three or six months of follow-up. One trial (Eaglstein 1970) reported that pain tended to resolve spontaneously without therapy but more rapidly with corticosteroid therapy, but this trial only included 35 participants.

Despite the lack of benefit in terms of reduction of PHN, which was the focus of this review, there is some evidence of a beneficial effect on short-term outcomes. A trial with 359 participants (Wood 1994a) showed that pain intensity after two and three weeks had reduced from baseline significantly more in those who received corticosteroids than in those who did not. Another trial with 201 participants (Whitley 1996) showed significantly faster recovery with corticosteroids than without. On evaluation after one month, with the Cox regression model, the main effect of prednisone compared with no prednisone was significant for all four outcomes reported:

  1. time to cessation of acute neuritis (RR 2.28, 95% CI 1.35 to 3.86);
  2. time to return to uninterrupted sleep (RR 1.65, 95% CI 1.14 to 2.41);
  3. time to return to 100% usual daily activity (RR 1.74, 95% CI 1.21 to 2.51);
  4. time to total cessation of analgesic therapy (RR 2.25, 95% CI 1.42 to 3.54).

The results of these two papers suggest that corticosteroids may have a significant effect in accelerating healing and reducing acute zoster pain. This conclusion differs from the lack of effect of corticosteroids on the persistence of PHN and suggests that the relationship between acute inflammation, pain and PHN is not simple.

 

Adverse events

All five included trials reported adverse events, but these were not significantly more common in corticosteroid than in placebo participants.

 

Subgroup analyses

Although the most established risk factor for PHN is age, accurate predictors for PHN have not been defined (Johnson 2003). We conducted subgroup analyses according to age of participants but did not find a significant benefit either in those older than 50 years or those younger. Small numbers make this conclusion very uncertain. There was a lack of sufficient detail to permit extraction of all required data concerning most subgroups of interest. In the absence of a significant effect in the primary outcome measures, and the fact that individual trials were too small to detect moderate effects, more extensive subgroup analysis would have been unreliable. We hope that publication of this review will encourage authors of future PHN prevention trials to collect and publish data which will allow the analysis of subgroups in subsequent systematic reviews.

 

Outcome measures

In the trials reviewed, the outcome measures involved crude clinical endpoints or a simple pain scale which may be insufficiently responsive to detect meaningful clinical effects. None of the trials reported separate data on pain severity measured by validated visual analogue scales or numerical descriptive scales after three, six or 12 months. However, even the results using these scales are affected by difficulties in standardisation, which make it difficult to draw useful conclusions.

None of the trials reported separate data on quality of life measured with the SF-36 questionnaire after six months.The SF-36 questionnaire is used to assess physical functioning, bodily pain, vitality, social functioning, emotional role and mental health, but can also be used for evaluating quality of life among pain patients (Ware 1998). None of the four trials used this questionnaire to assess the quality of life among participants with pain, and only one trial evaluated aspects of quality of life (Whitley 1996). Future randomised controlled trials (RCTs) should monitor long-term quality of life regularly, which could allow better evaluation of the efficacy of corticosteroids. Regular monitoring of participants' quality of life would improve understanding of the natural progression of PHN with respect to its impact on the physical, emotional and social well-being of those affected.

No trial has incorporated cost-effectiveness calculations.

 

Future trials

The meta-analysis of two small studies (Eaglstein 1970; Esmann 1987) and the analysis of another two large studies (Wood 1994a; Whitley 1996) showed that corticosteroids did not reduce pain at six months after the onset of the acute rash more than the control group. However, the results of the Wood and Whitley studies suggested that corticosteroids may reduce the acute pain in herpes zoster and may improve quality of life.

The relationship between acute inflammation, pain and PHN is complicated. The effect of corticosteroids is not clear at different stages in the transition from acute pain to PHN. Dworkin et al have recommended the use of systemic corticosteroids as soon as possible after diagnosis of herpes zoster for people with at least moderately severe pain and no contraindications, and that these should be initiated only in combination with antiviral therapy (Dworkin 2007). However, this recommendation is based on expert opinion and the evidence for the effect of corticosteroids on preventing PHN at six months would not support this recommendation. Trials addressing short-term pain relief with corticosteroids are lacking. If they were performed they should also include a long-term follow-up to assess the transition from short-term to long-term pain. Further high quality RCTs using validated and generally accepted outcome measures should be considered for both short and long-term pain prevention and treatment in PHN. In a condition where the natural course is spontaneous recovery in the majority of cases, the number of participants has to be large enough to give the study the power to detect clinically relevant improvements.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 

Implications for practice

Short courses of corticosteroids do not result in significantly more adverse events in participants with acute herpes zoster but they are ineffective in preventing PHN persisting at six months.

 
Implications for research

Moderate quality evidence does not support the use of corticosteroids in acute herpes zoster infection for preventing PHN. However, large trials with sufficient power to detect a meaningful difference and which include validated and approved pain outcomes have not been performed. Further high quality studies to assess the effect of corticosteroids on both short-term pain and longer-term PHN are required. This may provide information about the mechanisms of transition from acute pain to long-term PHN.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

We would like to acknowledge the Chinese Evidence-Based Medicine Center and the Cochrane Neuromuscular Disease Group for their technical support. We thank Professor Richard Hughes, Kate Jewitt, Janice Fernandes, Ruth Brassington, Rachel Barton and Dr Tony Swan for their advice and encouragement in the preparation of this review.

The editorial base of the Cochrane Neuromuscular Disease Group is supported by the MRC Centre for Neuromuscular Diseases.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
Download statistical data

 
Comparison 1. Corticosteroids versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 The presence of PHN six months after the onset of the acute herpetic rash2114Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.45, 1.99]

 2 The main effect of prednisone compared with no prednisone on six months evaluation of pain (generic inverse variance)1RR Ratios (Fixed, 95% CI)Totals not selected

 3 Serious adverse events5755Risk Ratio (M-H, Fixed, 95% CI)1.65 [0.51, 5.29]

 4 Non-serious adverse events5755Risk Ratio (M-H, Fixed, 95% CI)1.30 [0.90, 1.87]

 
Comparison 2. Subgroup analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 The presence of PHN six months after the onset of the acute herpetic rash2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Adults aged 50 years or more
2107Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.47, 2.04]

    1.2 Adults 49 years of age or less
16Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Appendix 1. MEDLINE (OvidSP) search strategy

Database: Ovid MEDLINE(R) <1946 to April Week 1 2012>
Search Strategy:
--------------------------------------------------------------------------------
1 randomized controlled trial.pt. (324061)
2 controlled clinical trial.pt. (83872)
3 randomized.ab. (228422)
4 placebo.ab. (130165)
5 drug therapy.fs. (1520746)
6 randomly.ab. (165133)
7 trial.ab. (236319)
8 groups.ab. (1087415)
9 or/1-8 (2821643)
10 exp animals/ not humans.sh. (3698513)
11 9 not 10 (2395603)
12 exp Herpes Zoster/ (8963)
13 herpes zoster.mp. (10273)
14 shingle$.mp. (710)
15 neuralgia/ (6430)
16 (postherpetic or post herpetic).mp. (1817)
17 15 and 16 (724)
18 PHN.tw. (944)
19 postherpetic neuralgia.mp. (1109)
20 post herpetic neuralgia.mp. (465)
21 post-herpetic neuralgia.mp. (465)
22 or/12-14,17-21 (11470)
23 Glucocorticoids/ (43624)
24 glucocorticoid$.mp. (75141)
25 adrenal cortex hormone/ (49254)
26 adrenal cortex hormone$.mp. (49446)
27 corticosteroid$.mp. (65614)
28 exp Steroids/ (658271)
29 steroid$.mp. (236281)
30 Prednisolone/ (27327)
31 prednisolone$.mp. (35082)
32 TRIAMCINOLONE/ (3003)
33 triamcinalone$.mp. (25)
34 DEXAMETHASONE/ (41472)
35 dexamethasone$.mp. (52796)
36 triamcinolone$.mp. (8540)
37 HYDROCORTISONE/ (58559)
38 hydrocortisone$.mp. (62689)
39 PREDNISONE/ (32495)
40 prednisone$.mp. (41193)
41 or/23-40 (883394)
42 11 and 22 and 41 (760)

 

Appendix 2. EMBASE (OvidSP) search strategy

Database: Embase <1980 to 2012 Week 15>
Search Strategy:
--------------------------------------------------------------------------------
1 crossover-procedure.sh. (33524)
2 double-blind procedure.sh. (108172)
3 single-blind procedure.sh. (15702)
4 randomized controlled trial.sh. (319715)
5 (random$ or crossover$ or cross over$ or placebo$ or (doubl$ adj blind$) or allocat$).tw,ot. (856935)
6 trial.ti. (128545)
7 or/1-6 (982129)
8 (animal/ or nonhuman/ or animal experiment/) and human/ (1169403)
9 animal/ or nonanimal/ or animal experiment/ (3254561)
10 9 not 8 (2698485)
11 7 not 10 (899899)
12 limit 11 to embase (696033)
13 exp *Herpes Zoster/ or exp herpes zoster/pc (9000)
14 herpes zoster.tw. (7301)
15 shingle$.tw. (971)
16 neuralgia/ (5689)
17 (postherpetic or post herpetic).tw. (2648)
18 16 and 17 (371)
19 PHN.tw. (1278)
20 postherpetic neuralgia.tw. (1698)
21 post herpetic neuralgia.tw. (756)
22 post-herpetic neuralgia.tw. (756)
23 or/13-15,18-22 (13391)
24 Glucocorticoid/ (56327)
25 glucocorticoid$.tw. (53251)
26 adrenal cortex hormone/ (153885)
27 adrenal cortex hormone$.tw. (475)
28 corticosteroid$.tw. (84499)
29 exp Steroid/ (987285)
30 steroid$.mp. (270140)
31 Prednisolone/ (81643)
32 prednisolone$.tw. (21934)
33 TRIAMCINOLONE/ (9114)
34 triamcinalone$.tw. (27)
35 DEXAMETHASONE/ (92367)
36 dexamethasone$.tw. (45944)
37 triamcinolone$.tw. (6002)
38 HYDROCORTISONE/ (85948)
39 hydrocortisone$.tw. (14239)
40 PREDNISONE/ (112202)
41 prednisone$.tw. (23775)
42 or/24-41 (1087022)
43 12 and 23 and 42 (166)
44 remove duplicates from 43 (164)

 

Appendix 3. The Cochrane Library CENTRAL search strategy

#1 MeSH descriptor Herpes Zoster explode all trees
#2 "herpes zoster"
#3 shingle*
#4 MeSH descriptor Neuralgia, Postherpetic, this term only
#5 PHN
#6 (postherpetic or "post herpetic" or "post-herpetic") and neuralgia
#7 (#1 OR #2 OR #3 OR #4 OR #5 OR #6)
#8 MeSH descriptor Glucocorticoids explode all trees
#9 glucocorticoid*
#10 MeSH descriptor Adrenal Cortex Hormones explode all trees
#11 "adrenal cortex hormone"
#12 corticosteroid*
#13 MeSH descriptor Steroids explode all trees
#14 steroid*
#15 MeSH descriptor Prednisolone explode all trees
#16 prednisolone
#17 MeSH descriptor Triamcinolone explode all trees
#18 triamcinalone
#19 MeSH descriptor Dexamethasone explode all trees
#20 dexamethasone
#21 triamcinolone
#22 MeSH descriptor Hydrocortisone explode all trees
#23 hydrocortisone
#24 MeSH descriptor Prednisone explode all trees
#25 prednisone
#26 (#8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25)
#27 (#7 AND #26)

 

Appendix 4. LILACS search strategy

(Mh Herpes Zoster OR Tw herpes zoster OR Tw shingle$ OR (Mh neuralgia AND (postherpetic OR post herpetic)) OR Tw PHN OR Tw postherpetic neuralgia OR Tw post herpetic neuralgia OR post-herpetic neuralgia) [Words] and 

(Mh Glucocorticoids OR Tw glucocorticoid$ OR Mh adrenal cortex hormone OR Tw adrenal cortex hormone$ OR Tw corticosteroid$ OR Mh Steroids OR Tw steroid$ OR Mh Prednisolone OR Tw prednisolone$ OR  Mh TRIAMCINOLONE OR Tw  triamcinalone$ OR Mh DEXAMETHASONE Or Tw dexamethasone$ OR Tw triamcinolone$ OR Mh HYDROCORTISONE OR Tw hydrocortisone$ OR Mh PREDNISONE OR Tw prednisone$) [Words] and 

((Pt randomised controlled trial OR Pt controlled clinical trial OR Mh randomised controlled trials OR Mh random allocation OR Mh double-blind method OR Mh single-blind method) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Pt clinical trial OR Ex E05.318.760.535$ OR (Tw clin$ AND (Tw trial$ OR Tw ensa$ OR Tw estud$ OR Tw experim$ OR Tw investiga$)) OR ((Tw singl$ OR Tw simple$ OR Tw doubl$ OR Tw doble$ OR Tw duplo$ OR Tw trebl$ OR Tw trip$) AND (Tw blind$ OR Tw cego$ OR Tw ciego$ OR Tw mask$ OR Tw mascar$)) OR Mh placebos OR Tw placebo$ OR (Tw random$ OR Tw randon$ OR Tw casual$ OR Tw acaso$ OR Tw azar OR Tw aleator$) OR Mh research design) AND NOT (Ct animal AND NOT (Ct human and Ct animal)) OR (Ct comparative study OR Ex E05.337$ OR Mh follow-up studies OR Mh prospective studies OR Tw control$ OR Tw prospectiv$ OR Tw volunt$ OR Tw volunteer$) AND NOT (Ct animal AND NOT (Ct human and Ct animal))) [Words]

 

Appendix 5. Chinese Biomedical Retrieval System Database search strategy

(NB. all of the search terms were translated to Chinese terms when we conducted the searches)
1. herpes zoster
2. postherpetic neuralgia
3. PHN
4. shingle
5. 1-4/or
6. herpes
7. neuralgia
8. 6 and 7
9. 5 or 8
10.corticorsteroid
11.hormone
12.steroid
13.prednisone
14.prednisolone
15.triamcinolone
16.dexamethasone
17.hydrocortisone
18.10-17/or
19.random
20.control
21.clinical trial
22.blind procedure
23.placebo
24.19-23/or
25.9 and 18 and 24

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Last assessed as up-to-date: 16 April 2012.


DateEventDescription

23 October 2012New citation required but conclusions have not changedUpdated searches integrated but no new trials identified. Change in first author.

3 September 2012New search has been performedSearches updated to April 2012. We also updated the methods of assessment of risk of bias. Some edits throughout; abstract and plain language summary revised.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Protocol first published: Issue 1, 2006
Review first published: Issue 1, 2008


DateEventDescription

8 November 2010New citation required but conclusions have not changedNew authors have joined the review update team

17 July 2010New search has been performedFor the 2010 update we updated the searches, but found no new trials. We assessed risk of bias using the new methods, added a 'Summary of findings' table and revised the review.

14 November 2007New citation required and conclusions have changedSubstantive amendment



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Ying Han and Jingjing Zhang identified the studies, reassessed their risk of bias and made a revision for the new version. Ning Chen and Mi Yang performed the previous update of the review in 2010. Li He is a consultant and expert in this field. She is the contact author, originally suggested the review and contributed to writing the final version of the protocol and review. She also contributed to updating the review and offering expert advice. Dongping Zhang developed and wrote the protocol and first review, and entered the text into Review Manager. Muke Zhou contributed to developing and writing the final version of the protocol and review. Cairong Zhu contributed to writing the section of the manuscript that refers to the planned statistical analysis.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

None known

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Internal sources

  • None, Not specified.

 

External sources

  • None, Not specified.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

In the 2010 update we assessed risk of bias using new methods and added a 'Summary of findings' table. We introduced a change from the protocol (He 2006) to exclude quasi-RCTs, because RCTs are thought to be the only way to prevent systematic differences in baseline characteristics between intervention groups, according to the latest Cochrane Handbook for Systematic Reviews of Interventions. However, no quasi-RCTs were found.

In the 2012 update we split 'blinding' into assessments of blinding of participants and personnel (performance bias) and blinding of outcome assessors (assessment bias) and revised the wording of assessments to high, low or unclear (Higgins 2011). We added information about the 'Summary of findings' table to the methods section.

Changes to the team of authors have taken place. See Other published versions of this review.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to studies awaiting assessment
  23. Additional references
  24. References to other published versions of this review
Clemmensen 1984 {published data only}
Eaglstein 1970 {published data only}
  • Eaglstein WH, Katz R, Brown JA. The effects of early corticosteroid therapy on the skin eruption and pain of herpes zoster. JAMA 1970;211(10):1681-3. [PUBMED: 4905733]
Esmann 1987 {published data only}
  • Esmann V, Geil JP, Kroon S, Fogh H, Peterslund NA, Petersen CS, et al. Prednisolone does not prevent post-herpetic neuralgia. Lancet 1987;2(8551):126-9. [PUBMED: 2885599]
Whitley 1996 {published data only}
  • Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, Pappas PG, et al. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Annals of Internal Medicine 1996;125(5):376-83. [PUBMED: 8702088]
Wood 1994a {published data only}
  • Wood MJ, Johnson RW, Mckendrick MW, Taylor J, Mandal BK, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. New England Journal of Medicine 1994;330(13):896-900. [PUBMED: 8114860]

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to studies awaiting assessment
  23. Additional references
  24. References to other published versions of this review
Benoldi 1991 {published data only}
Brusco 1993 {published data only}
  • Brusco JE, JaimovichCB, Bacchiocchi MF. Herpes zoster, study of 96 patients: postherpetic neuralgia and corticoids [Herpes zoster, estudio de 96 pacientes: neuralgia postherpética y corticoides]. Archivos Argentinos de Dermatología 1993;43(3):175-83.
Chang 2004 {published data only}
  • Chang JF. Corticosteroids for the treatment of postherpetic neuralgia. Chinese Journal of Practical Medicine 2004;4(9):830.
Cui 2002 {published data only}
  • Cui SS, Cheng XH. Evaluation of the effect of corticosteroids for the prevention of PHN in the elderly people. Journal of DaLian Medical University 2002;24(2):116-7.
Guo 2001 {published data only}
  • Guo QJ. Corticosteroids plus combined therapy for the treatment of 57 cases with herpes zoster. ShanDong Medical Journal 2001;41(1):53.
Hao 2002 {published data only}
  • Hao SZ. Clinical efficacy of acyclovir combined with prednisone for the treatment of 48 cases with herpes zoster in aged persons. Journal of JinZhou Medical College 2002;23(5):57.
Huang 2004 {published data only}
  • Huang YZ. Clincial efficacy of acyclovir combined prednisone given by intravenous routes for the treatment of herpes zoster in middle-aged persons. International Medical & Heath Guidance News 2004;10(2-3):81-2.
Huang 2010 {published data only}
  • Huang ZF, Huang YZ, Ma DX. Combined treatment of famciclovir and compound betamethasone for herpes zoster in middle-aged and aged population [泛昔洛韦联合复方倍他米松注射液治疗中老年带状疱疹疗效观察]. Guangdong Medical Journal 2010;31(13):1746-7.
Jiang 2005 {published data only}
  • Jiang MB, Jiang JY, Wang SJ. Clinical efficacy of ribaviron combined with dexamethasone for the treatment of 38 cases with herpes zoster in middle-aged persons. Theory and Practice of Chinese Medicine 2005;15(2):163.
Jiang 2008 {published data only}
  • Jiang CH. [Short-term combined treatment with small dose of corticosteroids and acyclovir for herpes zoster]. China Journal of Leprosy and Skin Disease 2008;4:255.
Keczkes 1980 {published data only}
Li 2000 {published data only}
  • Li YF. Clinical observation of acyclovir combined with prednisone for the treatment of herpes zoster. Journal of Zhejiang Medicine. Science 2000;22(7):441-2.
Li 2002 {published data only}
  • Li QH, Shi X, Li B. Clinical efficacy of acyclovir combined with prednisone for the treatment of herpes zoster in middle-aged persons. The Chinese Journal of Dermatovenereology 2002;16(3):2.
Liao 2005 {published data only}
  • Liao JY, Yan ZQ, Liu GT. Acyclovir plus prednisone was applied to the treatment of senile herpes zoster. Clinical Journal of Military Surgeon 2005;33(4):413-4.
Lin 2002 {published data only}
  • Lin LZ. A combination oral therapy with prednisone and acyclovir in treatment of 34 cases with herpes zoster. Journal of Clinical Dermatology 2002;31(1):30-1.
Lin 2005 {published data only}
  • Lin BS. Clinical efficacy of valacyclovir combined with low dosage of prednisone for the treatment of herpes zoster in aged persons. Southern China Journal of Dermato-Venereology 2005;12(1):21-2.
Liu 2003 {published data only}
  • Liu Y, Dun SH. Aciclovir combined with prednisone for the treatment of herpes zoster neuralgia in aged persons. Chinese Journal of Clinical Rehabilitation 2003;7(11):1727.
Liu 2005 {published data only}
  • Liu YB. Clinical observation of acyclovir combined with prednisone for the treatment of herpes zoster neuralgia in middle-aged persons. Journal of LiaoNing College of Traditional Chinese Medicine 2005;7(3):251.
Ma 2000 {published data only}
  • Ma WY. Clincial observation of antiviral agents combined with dexamethasone for the treatment of herpes zoster. QingHai Medical Journal 2000;30(10):44.
Ma 2002 {published data only}
  • Ma J, Cai AH, Cao MR. Glucocorticoid alleviates postherpetic neuralgia. Journal of China Clinical Medicine 2002;9(5):578-9.
Shi 2008 {published data only}
  • Shi RY, Liu FZ. Acyclovir combined with prednisone for 24 patients with herpes zoster. Chinese Coummunity Doctors 2008;12:37.
Song 2009 {published data only}
  • Song KT. Combined treatment with interferon, acyclovir and steroid for patients with herpes zoster. Chinese Journal of Misdiagnosis 2009;9(6):1344-5.
Tang 2004 {published data only}
  • Tang JC. Andrographolide combined with prednisone for the treatment of herpes zoster in middle-aged persons. JiLin Journal of Traditional Chinese Medicine 2004;24(6):34.
Wang 2004 {published data only}
  • Wang HQ. Clinical observation of valaciclovir combined with prednisone for the treatment of herpes zoster in middle-aged persons. Chinese of Celiopathy 2004;4(5):344-5.
Xu 1999 {published data only}
  • Xu YC. Clinical observation of acyclovir combined with prednisone for the treatment of herpes zoster. Journal of Clinical Dermatology 1999;28(3):181.
Yang 2000 {published data only}
  • Yang J, Huang XY, Hou J. Control study of prednisone in prevention of senile postherpetic neuralgia. Journal of Clincial Dermatology 2000;29(2):99-100.
Yang 2002 {published data only}
  • Yang JL, Hu YY. Clinical observation of acyclovir combined with prednisone for the treatment of herpes zoster. Practical Clinical Medicine 2002;3(6):128.
Yang 2010 {published data only}
  • Yang XM. [Acyclovir combined with prednisone for herpes zoster]. Chinese Journal of Clinical Rational Drug Use 2010;3(6):31.
Yin 2004 {published data only}
  • Ying GW, He QB, Li DQ, Yu JB. Clinical Observation of low dosage of corticosteroids for the prevention of PHN in elderly people. Chinese Journal of Geriatrics 2004;23(8):579.
Yin 2005 {published data only}
  • Yin GW, He QB, Li DQ, Yu JB. The observation of efficacy and safety of glucocorticoids for the treatment of herpes zoster. Chinese Journal of Practitioner 2005;4(3):187.
Zeng 2011 {published data only}
  • Zeng C. Corticosteroids for the treatment of postherpetic neuralgia [糖皮质激素治疗带状疱诊对防治后遗神经痛的疗效观察]. Zhong Guo Jian Kang Yue Kan (China Health Monthly) 2011;30(5):49-50.
Zhang 2003 {published data only}
  • Zhang JM. A clinical comprehend of Virmax combined prednisone in the treatment of 30 cases with herpes zoster in aged persons. Journal of HanDan Medical College 2003;16(2):115.
Zhang 2004 {published data only}
  • Zhang CM, Wang FF, Zhu YM, Ren Y. Control study of prednisone in prevention of senile postherpetic neuralgia. Journal of ChengDe Medical College 2004;21(3):199-200.
Zhang 2005 {published data only}
  • Zhang JQ. Acyclovir combined with low dosage prednisone for the treatment of 30 cases with herpes zoster. Clinical Journal of Integrated Traditional and Western Medicine 2005;5(3):44.
Zheng 2004 {published data only}
  • Zheng HY, Han J. Clinical study of early combination treatment for patients with herpes zoster. Journal of Jingangshan Medical College 2004;11(3):66.
Zhou 2000 {published data only}
  • Zhou XY. Famciclovir combined with prednisone for the treatment of herpes zoster in aged persons. Journal of BaiQiuEn Medical College 2000;26(6):647.
Zhou 2008 {published data only}
  • Zhou J. [Clinical effect investigation of herpes zoster with glucocorticosteroids and acyclovir in old patients]. Journal of North Sichuan Medical College 2008;23(3):255-6.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to studies awaiting assessment
  23. Additional references
  24. References to other published versions of this review
Alper 2002
de Moragas 1957
  • de Moragas JM, Kierland RR. The outcome of patients with herpes zoster. A.M.A. Archives of Dermatology 1957;75(2):193-6.
Desmond 2002
  • Desmond RA, Weiss HL, Arani RB, Soong SJ, Wood MJ, Fiddian PA, et al. Clinical applications for change-point analysis of herpes zoster pain. Journal of Pain and Symptom Management 2002;23(6):510-6.
Dworkin 1994
Dworkin 2000
  • Dworkin RH, Perkins FM, Nagasako EM. Prospects for the prevention of postherpetic neuralgia in herpes zoster patients. The Clinical Journal of Pain 2000;16(2 Suppl):S90-100.
Dworkin 2007
Fillet 2002
GRADE working group 2004
  • GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490-4.
Griffin 1998
Higgins 2002
Higgins 2003
Higgins 2011
  • Julian PT Higgins, Douglas G Altman, Jonathan AC Sterne (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Intervention Version 5.1.0 ( updated March 2011). The Cochrane Collaboration, 2011.
Johnson 2003
Kost 1996
  • Kost RG, Straus SE. Postherpetic neuralgia - pathogenesis, treatment, and prevention. The New England Journal of Medicine 1996;335(1):32-42.
Lancaster 1995
  • Lancaster T, Silagy C, Gray S. Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials. British Journal of General Practice 1995;45(390):39-45.
Levinson 1985
Li 2009
MacDonald 2000
  • MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 2000;123(Pt 4):665-76.
Mahalingam 1993
  • Mahalingam R, Wellish M, Lederer D, Forghani B, Cohrs R, Gilden DH. Quantitation of latent varicella-zoster virus DNA in human trigeminal ganglia by polymerase chain reaction. Journal of Virology 1993;67(4):2381-4.
Rosler 1996
Schünemann 2011
  • Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, et al. Chapter 11: Presenting results and ‘Summary of findings' tables. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Schünemann 2011b
  • Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Smith 1978
Stankus 2000
  • Stankus SJ, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. American Family Physician 2000;61(8):2437-44, 2447-8.
Volmink 1996
Ware 1998
Wood 1994b

References to other published versions of this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to studies awaiting assessment
  23. Additional references
  24. References to other published versions of this review
He 2006
  • He L, Zhang D, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD005582]
He 2008
He 2010