Australian Herpes Management Forum

Managing Herpes Zoster

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Compiled by the Board of the Australian Herpes Management Forum (AHMF)

Defining shingles

Shingles is caused by a reactivation of the varicella-zoster virus (VZV). Chickenpox is the clinical manifestation of primary infection with VZV. After recovery from primary infection, VZV is not eliminated from the body but rather, the virus lies dormant in the sensory nervous system. When latent infection reactivates, the result is an episode of shingles, which is characterised by localised rash and pain along a dermatomal distribution.

This can involve any dermatome, including the lower sacral dermatome. However, as lower sacral dermatomal zoster is much less common than genital herpes, so-called "recurrent zoster" is usually recurrent HSV infection. Prodromal neurological symptoms of herpes zoster comprise pain rather than the typical paraesthesiae of recurrent herpes simplex. The rash of zoster is often intensely pruritic and spreads throughout the dermatome, evolving through papular, vesicular and crusting stages (Figure 1). It usually lasts two to four weeks. The most troubling symptom is usually pain, which ranges from mild to severe, and from burning to lancinating. Paraesthesiae, or anaesthesia and allodynia (pain induced by touch, often from trivial stimuli), can accompany severe pain. The pain may be self-limited or persist beyond the rash for up to a year ("post herpetic neuralgia").1,2 Another relatively common complication is zoster ophthalmicus (2%-4%), which follows involvement of the first division of the fifth cranial (trigeminal) nerve. It ranges from keratitis to the more severe iritis.3 In about 1% of immunocompromised people with herpes zoster, the virus spreads to the eye, brain or liver. Prolonged pain is uncommon. People with AIDS may have recurrent or prolonged zoster or multiple dermatomal involvement, and zoster in a person at risk of HIV may be an indicator of unrecognised HIV infection.4 Herpes zoster during pregnancy is not associated with intrauterine infection.2

Figure 1: Herpes Zoster, Typical papulovesicular rash of herpes zoster affecting thoracic dermatomes. Figure 2: Shingles lesions

Managing Herpes Zoster

Early and adequate antiviral treatment of shingles pain will help to reduce its severity and duration

The principal challenge in the management of shingles is the rapid resolution of pain. Prompt management with antiviral agents is clearly beneficial.

Three factors independently increase the risk of persistent shingles pain (post herpetic neuralgia)

They are:

• Advancing age (particularly in patients over 50 years)
• Severe or moderately severe pain (in the patient's estimation) at the time the rash appears
• Pain before the rash appears (prodromal pain)

Pain, particularly persistent pain, is thought to be largely the result of virus-induced damage (and scarring) to the affected sensory nerve ganglion, nerve and nerve root. The rationale behind the use of antiviral agents is simple: by stopping virus replication as quickly as possible, nerve damage is minimised. Three antiviral compounds, namely aciclovir, famciclovir and valaciclovir, have been assessed for their ability to speed the resolution of shingles pain when administered within 72 hours of rash onset. All are available in Australia. Immunosuppression, per se, is not a risk factor for the development of post-herpetic neuralgia.

The role of antiviral drugs can be summarised as follows

• Failure to obtain adequate antiviral treatment using either aciclovir, famciclovir or valaciclovir within 72 hours of rash onset increases the likelihood of persistent pain
• The total duration of zoster-associated pain is reduced by aciclovir
• Valaciclovir speeds pain resolution significantly faster than aciclovir
• Controlled trials have shown no difference between famciclovir and valaciclovir in resolution of pain

Recommendations on antiviral therapy in shingles

Based on the above information, the recommendations for treatment are:

• Antiviral therapy is appropriate for all patients presenting with shingles within 72 hours of rash onset (and may be useful beyond this point as new lesions are continuing to appear).
• On current evidence, valaciclovir is probably the most effective agent available, based on the knowledge that it speeds pain resolution faster than aciclovir.
• Both famciclovir and valaciclovir offer more convenient dosing than aciclovir.

Ophthalimic Zoster

Opthalmic zoster potentially involving the eye should be referred to an ophthalmic specialist.

Managing Pain

 Severe pain during the early stages of shingles is associated with the development of persistent pain, by permanently sensitising the nerves to even the mildest stimulation. Therefore it is important that severe acute pain is managed aggressively from the outset with appropriate analgesic agents in addition to an antiviral compound. Early referral to a pain specialist should be considered.

Table 1: Guide to assessing severity of acute zoster pain and neurological dysfunction

* Also assess level of disability (impact on sleep, mood and activities of daily living) caused by pain and/or neurological dysfunction. † Dysaesthesia is an unpleasant abnormal sensation that can be spontaneous or evoked. Special cases of dysaesthesia include hyperalgesia and allodynia.⁹

Is there a role for oral corticosteroids?

Studies with small numbers of patients suggested that treatment of acute herpes zoster with steroids such as prednisolone or triamcinolone might decrease the incidence of post-herpetic neuralgia. More recently, a study involving over 400 patients, compared aciclovir treatment with aciclovir plus steroids^5,6.

Addition of steroids conferred a slight benefit in reducing the incidence and severity of acute pain but provided no additional benefit for long-term pain over aciclovir alone. A further trial comparing aciclovir with or without prednisolone and measuring quality of life endpoints has been completed⁷. It concluded that aciclovir plus a steroid does not alter the course of long-term zoster associated pain, but it may have a quality of life benefit.

Due to this effect on quality of life, which may be important to the patient, it could be appropriate to consider using a combination of antiviral treatment and a steroid in individuals over the age of 50 in whom steroids are not contraindicated. However, in general, the complications of steroid therapy tend to outweigh the benefits.

Post-herpetic neuralgia

The most common and widely feared complication is persistent pain in the affected area of the body after the rash has healed (in approximately 10% of cases over 50 years). This is usually called post-herpetic neuralgia, which may be very severe and prolonged, particularly in older patients (> 55 years). Unfortunately it can be very resistant to treatment but, by treating shingles with an antiviral agent within 72 hours of the rash appearing, it may be possible either to reduce the likelihood of developing prolonged pain or, put another way, reduce the overall duration of pain associated with the condition⁸.

Persistent pain should be managed by low dose amitriptyline in the first instance and referred to a pain clinic if still resistant. 40% of pain is resistant to all treatment, which highlights the need for timely antiviral therapy in zoster.

Table 2: An algorithm for the pharmacological management of established post herpetic neuralgia (PHN)*†

• Trial the medications outlined below in a stepwise fashion.
• Trial combination therapy where appropriate.
• Consider early referral to a pain specialist.

* Defined as pain persisting 90 days after onset of pain or rash. † Drug doses cited assume normal renal and hepatic function. ‡ Medications lacking evidence and not recommended in the treatment of PHN include NSAIDs, oral steroids, carbamazepine, phenytoin, sodium valproate, selective serotonin reuptake inhibitors and N-methyl-D-aspartate antagonists.^2,10
NSAID = non-steroidal anti-inflammatory drug.
Algorithm adapted from: Neurology Expert Group. Postherpetic neuralgia.²³

Preventing Herpes Zoster

Zoster Vaccine

A recent study, the Shingles Prevention Study, trialled a live, attenuated VZV vaccine (Zostavax™) in over 38,000 patients aged 60 years of age. Zostavax significantly reduced the likelihood of developing both herpes zoster and post-herpetic neuralgia. Compared with placebo, the vaccine demonstrated a 51% reduction in herpes zoster and a 67% reduction in post-herpetic neuralgia. The vaccine is licensed for use in Australia in individuals aged ≥ 50 years. The PBAC has recommended listing of Zostavax on the National Immunisation program (NIP) for the prevention of herpes zoster and post-herpetic neuralgia and for the reduction of acute and chronic zoster-associated pain in immunocompetent persons aged 60 to 79 years⁹.

In summary

• Quick antiviral treatment is the key to effective management for herpes zoster;
• Severe acute pain should be managed aggressively from the outset with appropriate analgesic agents because research suggests it reduces the risk of severe long-term pain;
• Oral corticosteroids should be considered as an adjunct to antiviral therapy only in individuals over the age of 50 in whom steroids are not contraindicated.

References

1. Cunningham AL, Dworkin RH. The management of post-herpetic neuralgia. BMJ 2000; 321: 778-779
2. Dworkin RH, Carrington D, Cunningham AL, et al. Assessment of pain in herpes zoster: lessons learned from antiviral trials. Antiviral Res 1997; 33: 73-85
3. Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Ann Intern Med 1999; 130: 922-932
4. Whitley RJ, Gnann JW Jr. Herpes zoster in patients with human immunodeficiency virus infection - an ever expanding spectrum of disease. Clin Infect Dis 1995; 21: 989-990
5. Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, et al. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. NEJM 1994,330(13);896-900
6. Wood M. Understanding pain in herpes zoster: an essential for optimizing treatment. J Infect Dis 2002,186 (Suppl 1);S78-82
7. Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, et al. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial. Ann Intern Med 1996;125;376-383
8. Cunningham AL, Dworkin RH. The management of post-herpetic neuralgia. BMJ 2000; (321); 778-779

Disclaimer

The AHMF have made considerable efforts to ensure the information upon which this guideline is based reproduces the evidence as accurately as possible. Users of this guideline are strongly recommended to confirm that the information contained within it, especially drug indications, is correct by way of independent sources, as this guideline does not indicate an exclusive course of action or serve as a standard of medical care. The AHMF accepts no responsibility for any inaccuracies, information perceived as misleading, or success of any treatment regime detailed in this guideline.