Shingles

Synonyms: herpes zoster and varicella zoster.

It is caused by the human herpesvirus-3 (HHV3).

Primary infection usually occurs in childhood, producing chickenpox (varicella) although it can be subclinical. After this the virus lays dormant in the sensory nervous system in the geniculate, trigeminal or dorsal root ganglia. It may lay dormant for many years or many decades before flaring up in a single dermatome segment.

At least 90% of children have been exposed to chickenpox before they are 16. Herpes zoster is seen as a disease of older people but it can affect all ages including children. The incidence and severity increase with age. This may be due to a decline in cellular rather than humoral immunity.¹ Figures available are unreliable and in those quoted below there are no figures for the those aged between 50 and 80. They do at least show the expected upward trend with age.

• Under 20 years - 0.4 to 1.6 cases per 1000 persons.
• Age 20 to 50 years - 2.0 to 3.0 cases per 1000 persons.
• Over 80 years - 4.5 to 11.0 cases per 1000 persons.
• About 20% of people will have shingles at some stage in their lives.

There is no sex difference in incidence but women are more susceptible to post-herpetic neuralgia.

Typically affected dermatomes include:

• Thoracic (56%)
• Cervical (17%)
• Trigeminal nerve (12%)
• Lumbar (10%)
• Sacral (5%)

Post-herpetic neuralgia and intractable pain increase with age, from 27% of untreated adults aged 55 years to 47% of untreated adults aged 60 years to 73% of untreated adults aged 70 years.

Pain lasting for more than 1 year occurs in 48% of patients older than 70 years.

Ophthalmic herpes is more common in elderly males.²

Patients will often suggest that elderly people should be kept away from children with chickenpox in case they catch shingles. This is a misconception. Chickenpox can rarely be acquired from a patient with active shingles as the lesions shed virus, but shingles is not caught from contact with a person with chickenpox.

Risk factors

• Increasing age increases the incidence and morbidity of shingles.
• Incidence and risk are increased in the immunocompromised patient.
• Diseases such as HIV, Hodgkin's lymphoma and bone marrow transplants all have a high risk.
• If anyone presents with shingles affecting more than one dermatome, think of immune compromise.

The disease can be divided into the pre-eruptive phase, acute eruptive phase, and chronic phase (post-herpetic neuralgia).

Pre-eruptive phase

• In the pre-eruptive phase there is no skin lesion to see but 80% of patients complain of burning, itching, or paraesthesia in one dermatome.
• This usually lasts for a day or two but it can be over a week before the characteristic eruption appears.
• The patient may feel unwell with malaise, myalgia, headache, and fever but these symptoms may abate as the eruption appears.
• In the pre-eruptive phase the skin may be tender but there are no lesions to see. There may be lymphadenopathy.
• Diagnosis is difficult before the characteristic rash appears.

Eruptive phase

• The eruptive phase is when the skin lesions appear. Most, but not all adults have acute, neuritic pain in this phase. A few have severe pain without any eruption called zoster sine herpete. Young adults and children are most likely to be free of pain.
• Crust formation and drying occurs over 7 to 10 days and is followed by resolution at 14 to 21 days.
• Patients are infectious until lesions are dried.
• Pregnant women and immunosuppressed patients have the highest risk of serious sequelae.
• In the eruptive phase the rash first appears as a patch of erythematous, swollen plaques with clusters of small vesicles. This eruption is virtually diagnostic of shingles. It may not affect the whole dermatome but it will not extend outside it. Hence any rash that crosses the mid-line is not shingles.
• More vesicles may erupt over the next 5 to 7 days. They form crusts that fall off inside 3 weeks.
• In elderly and immunocompromised patients, the eruptive phase is longer and more extensive. It occasionally results in haemorrhagic blisters, skin necrosis, and secondary bacterial infections.

Chronic phase

• Chronic phase or post-herpetic neuralgia is persistent or reoccurring pain lasting 30 days or more after the acute infection or after all lesions have crusted.

• Trigeminal herpes zoster represents 7 to 10% of shingles. If the ophthalmic branch of the trigeminal nerve is involved this may affect the eye. The eye is not always involved at this level but if it is, the patient should see an ophthalmologist the same day. About 25% will develop long-term sequelae.
• Complications from inflammatory changes include keratitis, episcleritis, iritis, ischaemic papillitis, and orbital vasculitis.
• Nerve damage can include oculomotor palsies and neuralgia.
• Tissue scarring can include lid deformities, neuralgia, and lipid keratopathy.
• The Ramsey-Hunt Syndrome is caused by zoster of the geniculate ganglion. Whilst it is a general tenet of shingles that it affects the sensory and not the motor system, this is the notable exception. It may present as a Bell's palsy and it is not until the rash appears that the diagnosis is apparent. Involvement of the auditory nerve can impair hearing or paralysis of the tensor tympani can cause hyperacusis. Vesicular eruptions may appear on the pinna, in the auditory canal, on the tympanic membrane, or occasionally on the hard palate. There may be unilateral loss of taste of the anterior two thirds of the tongue.
• CNS involvement is uncommon in those with normal immunity but it can be devastating.³ Direct invasion of adjacent structures may occur leading to involvement of the anterior horn neurons, resulting in muscular weakness, cranial nerve palsies, diaphragmatic paralysis, neurogenic bladder, and pseudo-obstruction of the colon. In the absence of a rash diagnosis can be very difficult.
• The cerebrospinal fluid may have pleocytosis and increased protein content suggestive of CNS inflammation. Some patients may have very mild encephalitis but most have only a headache. Significant meningoencephalitis is rare but has a 20% mortality.

• Before the rash appears the pain may be thought to originate from under that dermatome and so it must be considered as a possible cause of chest or abdominal pain.
• The Ramsey-Hunt syndrome may present as Bell's palsy before the rash appears.
• The rash, especially if without pain, may be mistaken for atopic eczema, contact dermatitis, herpes simplex or impetigo. This may lead to this viral infection being treated with steroid cream.

Diagnosis is usually purely clinical. Viral culture is available but rarely necessary.

Topically applied cool compresses or calamine lotion may offer limited relief.

Drugs

• If there is pain, analgesics will be required. Especially in the elderly, a combination approach is required.⁵
• The main purpose of treatment with anti-viral agents is to reduce the risk of post-herpetic neuralgia. Topical idoxuridine does not seem to be any better than placebo.⁶ Oral therapy should be started within 72 hours of the onset of pain. It does seem to reduce the duration of post-herpetic neuralgia.⁷ There is no significant difference in the efficacy of the various agents available. A systematic review confirmed the benefit of antiviral agents but found no benefit from steroids.⁸ However, a 4-arm trial of patients with and without aciclovir and prednisolone⁹ showed some benefit from adding steroid to antiviral therapy in healthy people over 50.
• Considering the low incidence of post-herpetic neuralgia in young people, antiviral therapy is probably not of value in this group but if there is immune compromise or if there is ocular involvement¹⁰ it must be considered mandatory.
• A systematic review¹¹ of the treatment of established post-herpetic neuralgia found that no single best treatment is known. Tricyclic antidepressants, topical capsaicin, gabapentin, and oxycodone are effective for alleviating pain but long-term, clinically meaningful benefits are uncertain and side effects are common. If pain is refractory to these therapies there may benefit from intrathecal methylprednisolone.¹²
• Little evidence is available regarding treatment of post-herpetic neuralgia of less than 6 months duration.
• Although a RCT found benefit from administration of amitriptyline from the onset of shingles,¹³ instead of waiting for the neuralgia, it has been criticised as being of poor quality as there was no control about the simultaneous administration of antiviral therapy.

Surgical

Intrathecal steroids and nerve blocks are sometimes used in PHN.

• Bone marrow recipients with visceral dissemination have a mortality rate of approximately 10%.
• Long-term complications of ophthalmic zoster with corneal involvement occur in over 20% of such patients and may result in blindness.
• Morbidity associated with post-herpetic neuralgia increases with age.
• Haematogenous dissemination to the viscera occurs in 1 or 2% of immunocompetent patients but is more frequent in immunocompromised patients.

Post-herpetic neuralgia

Pain gradually resolves in most patients but it can persist for years. It is described as a deep, burning or aching pain, paraesthesia, dysaesthesia, hyperaesthesia, or electric shock-like pains.

If pain lasts for more than 3 months it is defined as post-herpetic neuralgia. It can be long-lasting, refractory to treatment and even lead the sufferer to suicide. The most important risk factor for PHN is age. At age 60, approximately 60% of patients with shingles develop PHN, and at age 70, 75% develop PHN. The affected area may show evidence of scarring and sensation may be different. The risk is greatest in the trigeminal area, especially the ophthalmic division.

• The prognosis for younger and otherwise healthy patients is excellent.
• Elderly people have a significantly increased risk of complications, including post-herpetic neuralgia, bacterial infections, and scarring.
• Immune compromise carries poorer prognosis.

In the USA, vaccination against chickenpox has become routine and cases have dropped by 80%. It is a very effective vaccine.¹⁴ It reduces the incidence of herpes zoster in children with leukaemia.¹⁵ In the UK, a vaccine is available to at risk groups, including those who are not immune but work in a setting where they may be infected.

There are two causes of concern about vaccination in the UK. One is that immunisation of children may result in a susceptible adult population later on and if adults contract the wild disease, it is far more serious than in children. The other is concern that there may be a temporary increase in the incidence of shingles.¹⁶ In view of these concerns, current policy is to wait and see what happens elsewhere, especially in the USA that has had routine immunisation for a number of years.¹⁷