HZ arises from the reactivation of the VZV after latent infection in the trigeminal and dorsal root ganglia and results in the virus being transferred along nerves to the skin. The exact mechanisms for reactivation are unknown but correlate with a reduction in controlling T cell immunity. A prodromal period of dermatomal pain often precedes the acute eruption by several days, occasionally longer. The character of the acute pain (neuritis) in the affected dermatome has been variously described as burning, deep aching, tingling, itching or stabbing.
Patients not uncommonly experience neuropathic pain. Depending on the degree of neuritis/ganglionitis, this includes:
- paraesthesia (burning and tingling)
- anaesthesia/dysaesthesia (reduced or altered sensation)
- debilitating allodynia (pain induced by nonpainful stimuli such as touch)
- hyperaesthesia (exaggerated or prolonged response to pain).
Although such symptoms usually start during the acute phase, they may also be associated with ongoing pain (for 30 to 90 days after onset) or chronic pain (beyond 90 days after onset). Moderate- to-severe pain persisting for more than 90 days is known as postherpetic neuralgia (PHN).
The acute rash of HZ is often pruritic as well as tender, and spreads throughout the affected dermatome (Figure). It evolves through a papular stage to a vesicular stage (lasting three to five days) and then crusts over five to seven days. Acute HZ takes two to four weeks to heal.
Acute HZ has a significant impact on patients’ quality of life. In one recent study, three-quarters of the patients were experiencing significant pain within the first two weeks of onset, more than half had problems with their usual activities, 36% had issues with either mobility or anxiety and almost one in five had problems with self-care. The patients’ doctors were more likely to underestimate rather than overestimate the patients’ pain.11
HZ is usually diagnosed clinically. Laboratory diagnosis (involving the detection of VZV antigens or nucleic acid from swabs of lesions, or by VZV-specific immunogloblin [Ig] M antibody tests) is recommended when the clinical picture is atypical or complicated. Examples include when there is persistent or recurrent rash, atypical rash such as a single lesion, central nervous system (CNS) involvement or disseminated rash with immunosuppression.12,13
The most frequent and important complication of VZV reactivation is PHN. One in five patients aged over 50 years with HZ will still report pain six months after HZ onset despite adequate antiviral therapy, and the incidence rises with age.14,15
The pathogenesis of PHN in the CNS is still being defined. It often leads to impairment of quality of life and prolonged hospitalisation, particularly in older people,16 and treatment is difficult. Although oral aciclovir given within 72 hours of the onset of HZ rash does reduce the severity and duration of acute HZ, it does not reduce significantly the incidence of PHN.17 Thirty to fifty percent of patients who have pain three months after the onset of zoster still have pain four years later.14
Risk factors for PHN include:
- older age
- greater prodromal pain
- severe pain and rash
- ophthalmic involvement.18
Severe immunosuppression and diabetes have also been shown to be significantly associated with PHN.18
Severity of disease at presentation and depression are the major correlates of pain burden in patients with acute HZ and PHN.19
The case study in Box 1 illustrates some of the issues in the management of patients with acute HZ and significant pain.
VZV reactivation may also cause ophthalmic disease (1.5%), dissemination (1.3%), a wide variety of neurological symptoms (0.6%) including motor neuropathy, and vasculitis (0.2%).20
Box 2 lists the complications of VZV reactivation.9,20-22