Herpes Zoster Infection in Adults

Publication: 20/10/2008  
Last review: 22/02/2017  
Next review: 22/02/2020  
Clinical Guideline
CURRENT 
ID: 1387 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the management of herpes zoster infection in adults

Summary
Herpes Zoster Infection in Adults

Criteria for use of guidelines:

  • Adults with suspected herpes zoster infection (shingles).

Non-Antimicrobial Management:

  • Paracetamol and ibuprofen are effective in relieving mild to moderate pain and pyrexia. In more severe pain these can be combined with opioid analgesia. If there is not a rapid response consider adding another agent such as gabapentin or amitriptyline
  • Chlorphenamine may relieve itch and reduce sleeplessness
  • Refer to the LTHT Infection Prevention and Control Policy [Please link to relevant section]

Antiviral treatment:

Immunocompetent patients

  • Patients who present within 72 hours of onset of rash treat with oral Aciclovir 800mg five times a day.
  • Consider antiviral treatment in patients presenting 72 hours after rash onset if on-going new vesicle formation.
  • Use antiviral treatment in patients with ocular or neurological complications. Some patients may require intravenous aciclovir [link to empirical antimicrobial therapy below]

Immunocompromised patients

Patients who are severely immunocompromised should be treated with intravenous aciclovir 10mg/kg body weight 8 hourly. Calculate dose on ideal body weight to avoid over dosage of obese patients and reduce in renal impairment (creatinine clearance <50ml /minute). When infection is controlled, i.e. the patient is systemically well and no new vesicles have appeared for 24 hours, treatment can be changed to oral valaciclovir 1gram three times a day.

Patients who are less severely immunocompromised can be treated with oral valaciclovir 1gram three times daily, along with close observation.

Duration of treatment:

Immunocompetent: 7 days
Immunocompromised:  10 days (however some patients may need longer duration)

Referral criteria
Patients who are immunocompromised or have complicated herpes zoster (e.g. Ramsay-Hunt syndrome (herpes zoster oticus) or neurological complications) - refer to infectious diseases.
Opthalmic involvement - refer to ophthalmology.

Back to top

Background
Herpes Zoster is a clinical manifestation of the reactivation of latent varicella zoster virus infection. It is characterized by a unilateral vesicular eruption in a dermatomal distribution. The most significant clinical symptoms are the associated acute neuritis and later, postherpetic neuralgia. It is a cause of considerable morbidity, especially in elderly patients, and can be fatal in immunosuppressed patients.

Back to top

Clinical Diagnosis
Once the rash has appeared, the diagnosis can usually be made clinically. Zosteriform herpes simplex in the sacral and cervical areas may be difficult to distinguish from herpes zoster. Atypical manifestations of herpes zoster may occur in immunocompromised patients. These include lesions that are intermittently recurrent, involvement of multiple dermatomes and lesions that appear as chronic crusts or nodules. When atypical lesions are present, or where there is doubt as to whether the pathogen is herpes simplex or zoster, diagnostic tests should be used.

Back to top

Investigation

Investigations required:

  • This is usually a clinical diagnosis.
  • In cases where there is doubt regarding the diagnosis, e.g. where the rash is atypical, then a swab can be taken for HSV, VZV and enterovirus PCR. Take a flock swab (provided in the pack containing Universal Transport Medium), remove the top from a lesion and swab. This swab should then be placed in the liquid medium provided. These packs can be obtained from the virology department. If a pack is not available, then a standard wound swab can be used, but the tip should be cut off and placed in a white topped sterile universal container.

PCR is the most sensitive and specific test. It is useful for old or crusted lesions but is expensive and takes at least 1 day to obtain a result. Culture of the virus is rarely undertaken.

Back to top

Treatment
Non-Antimicrobial Treatment

Corticosteroids

Two clinical trials showed a 3 week reducing course of prednisolone had some beneficial effect on acute pain and rash healing. [1, 2] In 1 of these studies, the time to return of normal activity and cessation of analgesics was accelerated in those receiving steroids. [1] However, there was no significant benefit with regard to treatment of chronic pain. [1, 2] Patients with contraindications to steroids were excluded from these trials, but despite this, adverse effects were reported. A subsequent meta-analysis of five placebo-controlled trials comparing aciclovir and steroid to aciclovir alone did not show a significant difference between the groups in preventing post-herpetic neuralgia [3]. Evidence level A

Analgesia

There is minimal data assessing oral analgesics for acute pain in herpes zoster, but it is hypothesized that the combination of antiviral therapy with the relief of acute pain may lessen the risk of post herpetic neuralgia beyond that of antiviral use alone. [4] Opioid analgesia in combination with analgesia such as paracetamol or NSAIDs is often used. A small randomised controlled trial comparing oxycodone or gabapentin to placebo in acute herpes zoster pain showed that oxycodone produced a significant reduction in acute pain in the first two weeks of the trial [5]. Drugs such as gabapentin and pregabalin have been shown to be effective in chronic pain syndromes including post herpetic neuralgia [6] and the use of these drugs in other acute pain conditions suggest they may also be effective in acute herpetic neuritis. Evidence level C

Recommendation:

  • Mild to moderate pain can be managed with paracetamol or ibuprofen alone or in combination with a weak opioid analgesic. Moderate to severe pain may require the addition of a strong opioid analgesic.
  • If moderate to severe pain is not controlled with opioid analgesia, then consideration should be given to addition of gabapentin or a tricyclic antidepressant such as amitriptyline. [13]
  • Corticosteroids should not be used routinely in uncomplicated herpes zoster.

Back to top

Empirical Antimicrobial Treatment

The principal goals of treatment of herpes zoster are reduction of pain in immunocompetent patients and inhibition of viral replication in immunocompromised patients.

Oral antiviral agents

The results of meta-analysis [8-10] and many - but not all - randomized control trials have demonstrated that antiviral therapy significantly reduces the incidence and duration of prolonged pain. Evidence level A

Aciclovir electronic Medicines Compendium information on Aciclovir   800mg 5 times daily, valaciclovir 1gram 3 times daily and Famciclovir electronic Medicines Compendium information on Famciclovir  500mg 3 times daily are all licensed for use in the treatment of herpes zoster.

Aciclovir electronic Medicines Compendium information on Aciclovir   the first antiviral agent to be used, was studied in four clinical trials [11-15] and at a dose of 800mg 5 times daily started within 72 hours of the rash was shown to reduce the severity and duration of acute pain.  Two clinical trials were conducted to compare Famciclovir electronic Medicines Compendium information on Famciclovir to placebo, [16, 17] and a single clinical trial of two different doses of valaciclovir compared with aciclovir. [18] These showed famciclovir and valaciclovir to be effective in accelerating the resolution of post herpetic neuralgia. Evidence level A

There is some but no definite evidence that Famciclovir electronic Medicines Compendium information on Famciclovir and valaciclovir may be more effective than Aciclovir electronic Medicines Compendium information on Aciclovir  , particularly with respect to speed of pain resolution. [18-20] These agents provide higher antiviral activity in blood and may promote patient adherence because they are dosed three rather than five times daily. Evidence level C

There is no clinical trial evidence available on starting antiviral treatment more than 72 hours after the onset of rash. However it may be beneficial in patients who have new vesicle formation, suggesting on-going viral replication, and in those patients with complications. Since the risks of treatment with antiviral drugs is minimal, it is recommended to consider treatment in patients with new vesicle formation more than 72 hours after onset of rash and in patients with neurological or ocular complications.[7] Evidence level C

Recommendation: (Immunocompetent patients)

Treat with oral Aciclovir electronic Medicines Compendium information on Aciclovir 800mg five times a day

  • Patients who present within 72 hours of onset of rash
  • Consider antiviral treatment in patients presenting 72 hours after rash onset if new vesicle formation is ongoing

Neurological or ocular complications:
Intravenous aciclovir should be used for patients with complications such as acute retinal necrosis, herpes zoster opthalmicus with sight threatening disease and neurological complications such as encephalitis and myelitis.

Treatment duration is 7 days but longer courses may be required with ocular or neurological complications

Immunocompromised patients

Patients with disorders of cell mediated immunity such as lymphoproliferative malignancy, solid organ transplants, advanced HIV and those receiving steroid treatment are at highest risk for the development of herpes zoster. Those with the greatest degree of immunosuppression are at highest risk of virus dissemination and visceral organ involvement. [7] Evidence level A

Initial clinical trials of IV aciclovir in immunocompromised patients showed that treatment halts disease progression and reduces the duration of viral replication. [21] Subsequent trials showed that IV aciclovir is also effective at preventing virus dissemination. [22,23]

Intravenousaciclovir 10mg/kg 8 hourly remains the treatment of choice for severely immunocompromised patients. Evidence level C

The dose should be calculated on ideal body weight to avoid over dosage of obese patients and is reduced in renal impairment (creatinine clearance <50ml /minute). When infection is controlled, i.e. the patient is systemically well and no new vesicles have appeared for 24 hours, then oral medication can be substituted for the duration of the course. There is limited clinical trial data on the use of Famciclovir electronic Medicines Compendium information on Famciclovir and valaciclovir in immunocompromised patients, but growing clinical experience suggests that these medications are safe and effective in this setting. [24,25]

For patients who are less severely immunosuppressed, oral antiviral therapy with close observation is a reasonable option. The higher plasma concentrations of Famciclovir electronic Medicines Compendium information on Famciclovir   and valaciclovir along with simpler dose regime favours their use over oral aciclovir.

Recommendation (immunocompromised patients):

  • Patients who are severely immunocompromised should be treated with intravenous aciclovir 10mg/kg body weight 8hrly. When infection is controlled, i.e. the patient is systemically well and no new vesicles have appeared for 24 hours, treatment can be changed to oral valaciclovir 1gram three times a day. Evidence level C
  • Patients who are less severely immunocompromised can be treated with valaciclovir 1gram three times daily along with close observation.
  • Treatment should be at least 10 days duration though some patients may require a longer course.

Back to top

Treatment Failure

Please contact microbiology if the patient is not responding to the recommended antimicrobial regimens.

Vaccination:
A national herpes zoster immunisation programme was introduced in 2013 with the aim of lowering the incidence and severity of herpes zoster in older people.  It is offered routinely to all people at age 70 years.  The vaccine is a live attenuated form and should not be given to immunosuppressed individuals without a prior clinical risk assessment. In immunocompetent individuals who develop herpes zoster, vaccination should be delayed for one year. [26]

Back to top

Provenance

Record: 1387
Objective:

To improve the diagnosis and management of herpes zoster virus (HZ) infection in adults

Clinical condition:

Herpes zoster

Target patient group: Adults with suspected herpes zoster infection (shingles)
Target professional group(s): Secondary Care Doctors
Pharmacists
Adapted from:

Evidence base

Evidence base:

  1. Whitley RJ, Weiss H, Gnann JW Jr, et al. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med 1996; 125:376–83.
  2. 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. N Engl J Med 1994; 330:896–900
  3. He L, Zhang D, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2008
  4. Dworkin RH, Schmader KE. Treatment and prevention of postherpetic neuralgia. Clin Infect Dis 2003; 36:877–82.
  5. Dworkin RH, Barbano RL, Tyring SK, Betts RF, McDermott MP, Pennella-Vaughan J, et al. A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster. Pain. 2009 Apr;142(3):209-17
  6. Rice ASC, Maton S. Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study. Pain 2001; 94:215–24.
  7. Dworkin RH, Johnson RW et al. Recommendations for the management of herpes zoster. Clin infect Dis 2007;44:S1-26
  8. Wood MJ, Kay R, Dworkin RH, Soong SJ, Whitley RJ. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta-analysis of placebo-controlled trials. Clin Infect Dis 1996; 22:341–7.
  9. Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia: a meta-analysis. Arch Intern Med 1997; 157:909–12.
  10. Crooks RJ, Jones DA, Fiddian AP. Zoster-associated chronic pain: an overview of clinical trials with acyclovir. Scand J Infect Dis Suppl 1991; 78:62–8.
  11. McKendrick MW, McGill JI, White JE, Wood MJ. Oral acyclovir in acute herpes zoster. BMJ 1986; 293: 1529 – 32.
  12. Huff JC, Bean B, Balfour HH Jr, et al. Therapy of herpes zoster with oral acyclovir. Am J Med 1988; 85 (Suppl 2A): 84 – 9.
  13. Huff JC, Drucker JL, Clemmer A, et al. Effect of oral acyclovir on pain resolution in herpes zoster: a reanalysis. J Med Virol 1993; Suppl 1:93 – 6.
  14. Wood MJ, Organ PH, McKendrick MW, Care CD, McGill JI, Webb EM. Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med 1988; 85(Suppl 2A): 79 – 83.
  15. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J 1989; 102: 93 – 5.
  16. Tyring S, Barbarash RA, Nahlik JE, et al.Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123:89–96.
  17. Dworkin RH, Boon RJ, Griffin DR, Phung D. Postherpetic neuralgia: impact of Famciclovir, age, rash severity and acute pain in herpes zoster patients. J Infect Dis 1998; 178(Suppl 1):S76–80.
  18. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39:1546–53.
  19. Degreef H. Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. Int J Antimicrob Agents 1994; 4:241–6.
  20. Shafran SD, Tyring SK, Ashton R, Decroix J, Forszpaniak C, Wade A, Paulet C, Candaele D. Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial. J Clin Virol. 2004;29(4):248
  21. Serota FT, Starr SE, Bryan CK, Koch PA, Plotkin SA, August CS. Acyclovir treatment of herpes zoster infections use in children undergoing bone marrow transplant. JAMA 1982; 247:2132–6.
  22. Shepp DH, Dandliker PS, Meyers JD. Treatment of varicella-zoster infection in severely immunocompromised patients: a randomized comparison of acyclovir and vidarabine. N Engl J Med 1986; 314:208–12.
  23. Meyers JD, Wade JC, Shepp DH, Newton B. Acyclovir treatment of varicella-zoster virus infection in the compromised host. Transplantation 1984; 37:571–4.
  24. Tyring S, Belanger R, Bezwoda W, Ljungman P, Boon R, Saltzman RL. A randomized, double-blind trial of Famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients. Cancer Invest 2001; 19:13–22
  25. Brentjens MH, Torres G, He J, Lee PC, Tyring SK. A double-blind randomized study of the use of 2 grams vs. 1 gram valacyclovir TID for 7 days in the treatment of acute herpes zoster in immunocompromised individuals. Presented at: Annual Meeting of the American Academy of Dermatology (San Francisco, March 2003).
  26. Public Health England. The Green Book: Chapter 28a Shingles (herpes zoster). February 2016

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.