Epidemiology

At least 90% of children have been exposed to chickenpox before they are aged 16. Shingles 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.

Chickenpox can rarely be acquired from a patient with active shingles, as the lesions shed virus (transmission is by direct contact or droplet spread) 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.
• Consider underlying immunodeficiency If anyone presents with shingles affecting more than one dermatome or if the patient is aged under 50 years.

Presentation

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

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 (resulting infection is chickenpox) until lesions are dried.
• 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 midline 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 PHN, is persistent or recurring pain lasting 30 days or more after the acute infection or after all lesions have crusted.

Variations

Ophthalmic shingles

Synonyms: herpes zoster ophthalmicus (HZO), ophthalmic herpes zoster

If the ophthalmic branch of the trigeminal nerve is involved this may affect the eye which is affected in only about half of cases (the likelihood of this occurring is not related to age or the severity of the rash)^[3] but this is a justly feared complication of this condition. If the tip of the nose has a rash, the nasociliary branch of the trigeminal nerve is involved. This branch supplies the globe and so it is very likely that the eye will be affected (at least 75% of cases). This is called Hutchinson's sign, as he described it in 1868. The eye can be seriously affected with little evidence of a shingles rash.

• Acute lesions of the orbit or globe develop within three weeks of the onset of the rash. They may resolve swiftly or linger and recur over years.
• Patients may have a red eye, decreased visual acuity, epiphora, photophobia and forehead tenderness.
• Other problems affect various parts of the eye:^[4] 
  • Lids - bilateral eyelid oedema can develop, as well as blepharitis and ptosis.
  • Conjunctiva - giving rise to a follicular conjunctivitis.
  • Episclera and sclera - resulting in inflammation (episcleritis and scleritis).
  • Cornea - keratitis; multiple features may occur - eg, multiple small epithelial dendrites (seen after instilling fluorescein), stromal and neurotrophic keratitis, raised mucous plaques and so on. This is one of the sites where significant visual loss can occur.
  • Anterior part of the eye - uveitis, paralysis ± atrophy of the iris and secondary glaucoma (about 10% of cases).
  • Posterior part of the eye - retinitis, choroiditis and optic neuritis.
• Nerve damage can include oculomotor palsies and neuralgia.
• Tissue scarring can include lid deformities, neuralgia, and lipid keratopathy.

Ramsay Hunt syndrome

See the separate article on Herpes Zoster Oticus (Ramsay Hunt Syndrome).

Differential diagnosis

• 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.
• Cluster headaches or migraine - consider in the prodromal phase.
• Ramsay 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.
• Consider the differentials of the acute red eye where there is no rash (eg, conjunctivitis, corneal abrasion, keratitis).
• If you strongly suspect HZO, look for a rash or evidence of a previous rash, such as pigmentary changes along the hairline or consider zoster sine herpete.

Investigation

The diagnosis is usually clinical, based on typical lesions in a single dermatome. Various techniques to detect the virus or antibody detection may be possible after consultation with a microbiologist. Scraping for smears and cultures are usually negative, as the viruses are difficult to recover from the scrapes. A direct immunofluorescence assay can be used; it is more sensitive than viral culture and can differentiate herpes simplex viral infections from varicella-zoster virus (VZV) infections.

Where the presentation is atypical (eg, a young patient, severe disease or a rash extending beyond one dermatome), the patient needs to be investigated for immunodeficiency.

Management

Topical therapy

Topical antiviral treatment is not recommended. Topical antibiotic treatment may be indicated for secondary bacterial infection.

Oral antiviral therapy

Oral aciclovir has been shown to shorten the duration of signs and symptoms, as well as to reduce the incidence and severity of HZO complications, notably PHN.

• The drugs that are used are aciclovir 800 mg five times a day (seven to ten days), valaciclovir 1000 mg three times a day or famciclovir 500 mg three times a day, both for seven days.^[5] 
• One review found a significant reduction in risk of pain with valaciclovir and famciclovir for management of herpes zoster including ophthalmicus. Valaciclovir or famciclovir were both shown to provide significant reduction in the risk of HZV-associated pain.^[6] 
• An oral antiviral drug should be started within 72 hours of rash onset for anyone over the age of 50 years with shingles, and for people of any age with non-truncal involvement (eg, affecting the neck, limbs, or perineum), or if there is moderate or severe pain or rash.
• If it is not possible to initiate treatment within 72 hours, consider starting an antiviral drug up to one week after rash onset, especially if the person is at higher risk of severe shingles or complications (eg, continued vesicle formation, older age, or severe pain).^[1] 
• A delayed start is also likely to confer some benefit in older patients who are likely to shed the virus for longer.
• Ophthalmic involvement:
  • Get immediate specialist advice or refer immediately (to be seen within 24 hours).
• Immunocompromised patients:
  • Get immediate specialist advice regarding treatment or refer immediately.
• For pregnant women:
  • Seek specialist advice regarding prescribing antiviral treatment in pregnancy.
• Children:^[5]  
  • Systemic antiviral treatment can reduce the severity and duration of pain, reduce complications, and reduce viral shedding.
  • Treatment with the antiviral should be started within 72 hours of the onset of rash and is usually continued for 7-10 days.
  • Immunocompromised patients at high risk of disseminated or severe infection should be treated with a parenteral antiviral drug.
• Longer and more intense (intravenous) treatments may be required in the elderly and the immunocompromised.
• Early and effective treatment reduces complications.^[1] 

Steroids^[7] 

The use of oral corticosteroids in the treatment of patients with zoster infection is controversial. As an adjuvant option in the treatment of patients with acute zoster infection, oral corticosteroids have been shown to ameliorate the inflammatory features and so reduce pain, and cosmetically improve the rash.

However, studies have shown conflicting results and many consider that any limited benefit is outweighed by the adverse effects of corticosteroids, especially in the elderly.

Management of ocular problems

• Where there is intraocular involvement, various agents are used depending on which tissue is involved. An ophthalmologist should be involved to carry out a detailed assessment and tailor a management plan accordingly.
• Patients may benefit from long-term application of ocular lubricants, and cool compresses are advised for the conjunctivitis in the acute phase. Epithelial defects are sometimes treated with additional chloramphenicol ointment.
• Patients may also require cycloplegics to help pain relief and intraocular pressure-lowering drugs.
• Where there is retinitis, choroiditis or optic neuritis, admission for intravenous antivirals may be required.
• Topical steroids may only be started under ophthalmic supervision (these are beneficial in certain specific cases and harmful in others).
• Where neurotrophic ulcers develop, botulinum toxin administration to produce a protective ptosis may be considered (the effects wear off after about three months). Other options available to manage these ulcers include bandage contact lenses, tissue glue and tarsorrhaphy (the lids are sutured together; depending on the type of procedure, this may or may not be irreversible).
• Treatment may go on for many months or even years.
• Corneal scarring may require penetrating keratoplasty (corneal transplant).

Analgesia

It may be necessary to give quite strong analgesia if there is pain. Corticosteroids, tricyclic antidepressants, gabapentin, and opioids reduce acute pain and may have additional effects on the reduction of PHN.^[2] 

If the pain is severe beyond the moment that the vesicles have crusted over, then PHN has probably developed.

Referral^[1]

• Refer all patients with a red eye or reduced visual acuity within the same day or, at the very latest, the next morning.
• If the eye is not red but Hutchinson's sign is present, refer the patient to be seen within one to two weeks, as there is a high risk of eventual ocular involvement.
• Refer patients with cranial nerve palsies for urgent assessment.
• Any patient with known immunodeficiency (including those with organ transplants and patients on systemic immunosuppression or chemotherapy) should be seen urgently by physicians in an infectious disease unit.
• More severe disease, recurrence or multiple dermatomal involvement should raise suspicions of underlying immunosuppression; actively look for causes. Consider HIV in patients under 65 years of age.^[8]
• Patients with extensive associated cellulitis need to be admitted for intravenous antibiotics.
• Patients with more severe or persistent neuralgia should be referred early to a pain clinic before the condition becomes chronic.

Complications

General complications

• Bone marrow recipients with visceral dissemination have a mortality rate of approximately 10%.
• Morbidity associated with PHN increases with age.
• Haematogenous dissemination to the viscera occurs in 1 or 2% of immunocompetent patients but is more frequent in immunocompromised patients.

Complications of ophthalmic shingles

• Ocular complications include pain, anterior uveitis and varieties of keratitis. Possible long-term complications include chronic uveitis, keratitis, and neuropathic ulceration.
• Lid complications include ptosis, trichiasis, scarring of the skin and madarosis (loss of lashes).
• Rare ocular complications include optic neuritis, retinitis and ocular cranial nerve palsies. There is a complete or near resolution of ophthalmoplegia in about 65% of cases.^[9] Sight is threatened by neuropathic keratitis, perforation, secondary glaucoma, posterior scleritis, optic neuritis, and acute retinal necrosis. Neurological complications are rare (one series reported this in 5.5% of patients) with meningoencephalitis being noted in a few patients.^[10]
• Long-term complications may be related to poor sensation of the cornea and poor motor function of the eyelid. This may put the eye at risk during episodes of impaired consciousness. There is risk of neuropathic ulceration and exposure keratopathy. There is also a risk of complications common to the disease elsewhere, like PHN. The risk of long-term problems is such that it is recommended that a history of ophthalmic herpes zoster should remain in the problems section of the medical record. There is a 6-14% chance of recurrence.^[3]
• Permanent sequelae of ophthalmic zoster infection may include chronic ocular inflammation, loss of vision, and debilitating pain.^[4] Gradual clouding of the cornea may occur.

Postherpetic neuralgia (PHN)

See related separate article on Postherpetic Neuralgia.

Prognosis

• The prognosis for younger and otherwise healthy patients is excellent.
• Pregnant women and immunosuppressed patients have the highest risk of serious sequelae.
• Elderly people have a significantly increased risk of complications, including PHN, bacterial infections, and scarring.
• Immune compromise carries poorer prognosis.

Prevention

Studies have shown that giving older people (adults aged over 60) varicella-zoster vaccine boosts their waning immunity and significantly reduces the morbidity due to HZV and PHN.^[11] Herpes zoster vaccine is effective in preventing herpes zoster disease. The vaccine is well tolerated and produces few systemic adverse events.^[12] 

In the UK, there will be a shingles vaccination programme for people aged 70, with a catch-up programme for those aged up to, and including, 79. The programme begins in September 2013.^[13]

The introduction of a childhood varicella-zoster vaccine (as in the USA) would reduce the risk of HZV, and therefore PHN, when this cohort of children becomes elderly. However, there is concern that reducing the number of children with VZV by introducing a vaccine could lead to a short-term increase in HZV in those who are latently infected.