herpes zoster (shingles)

see also:

• varicella-zoster virus (chickenpox/shingles)

• reactivation of the latent varicella virus manifests as herpes zoster (HZ or shingles)
• neonates with congenital chickenpox are at high risk of HZ during infancy.
• 25% of unvaccinated people will develop zoster in their lifetime - mostly when their immune system becomes less effective when they age or become immunosuppressed ¹⁾
• patients with shingles should be regarded as being contagious for varicella and isolated from non-immune patients
• 60% of patients have varying degrees of dermatomal pain prior to rash eruption
• reported annual incidence of HZ varies from 1.5-3.4 cases per 1000 adults

• presentation depends upon age, health status and location of the shingles
• most common sites are: chest wall, neck, forehead (ophthalmic zoster), and lumbar/sacral nerve supplies. It may cause blisters in mouth, in ears (Ramsay Hunt) or on genitalia
• usually commences as unilateral local severe pain without any skin changes and then within 1-3 days develops into a localised unilateral dermatomal distributed red papular and then vesicular rash (+/- pustules) and there is usually a sharp cut-off at the anterior and posterior midlines with minimal if any crossing of the midline.
• there is usually malaise, fevers, headaches and may have lymphadenopathy
• pain and constitutional symptoms gradually improve
• the rash usually lasts 3-4 weeks but recovery may be complete in only 2-3 weeks in children and young adults
• many patients have persistent neuropathic pain in the region post-herpetic neauralgia which may continue for years

• atypical spread
  • less commonly, it may affect multiple dermatomes or have eruptions in bilateral dermazones
• herpes zoster “sine eruptione”
  • pain without the rash
  • most common in children
• Ramsay Hunt syndrome / herpes zoster oticus (see below)
  • involvement of the geniculate ganglion of cranial nerve VII resulting in facial nerve palsy and may have blisters in the ear canal
  • may involve cranial nerve VIII results in auditory (hearing) and/or vestibular symptoms (dizziness) or spread to cranial nerves III, IV, V, VI, IX, X, XI and XII
  • blisters may be absent
• ophthalmic zoster / herpes zoster ophthalmicus (see below)
  • involvement of the forehead has risk or involvement of the eye, especially the cornea which may cause scarring keratitis
  • the ophthalmic division of the trigeminal nerve divides into three main branches:
    • the frontal nerve
    • the lacrimal nerve
    • the nasociliary nerve which innervates the ciliary body, iris, cornea and conjunctiva.
      • its terminal branch is the anterior ethmoidal nerve, which innervates the sides of the tip of the nose (alae nasae) via the external nasal nerve
      • Hutchinson's sign: involvement of the alae nasae / tip of the nose is an early sign of possible ocular involvement
• muscle weakness
  • ~1 in 20 are said to develop muscle weakness
• healing by scarring
  • deep blisters may take weeks to heal and can result in scarring
• the pregnant patient
  • zoster in early pregnancy may harm the fetus but this is said to be rare
  • zoster in late pregnancy can cause chickenpox in the fetus or newborn and, later, shingles as an infant
  • exposure to a non-immune pregnant patient may cause chickenpox in the pregnant patient and involvement of the fetus
• internal organ involvements
  • rarely, involvement of internal organs, including the gastrointestinal tract, lungs, and brain (encephalitis) may occur

• lifetime risk of HZ is ~30% with incidence substantially rising with age > 60 years
• whites have 2x risk compared to blacks²⁾
• risk factor for the development of HZ is reduced cell-mediated immune system function:
  • the normal aging process
    • incident rates/1000person-yrs (IR):
      • 21-30yrs old: 2.7
      • 31-40yrs old: 3.3
      • 41-50yrs old: 3.9
      • 51-60yrs old: 5.8
      • 61-70yrs old: 8.5
      • 71-85+ : 10.6
  • family history zoster gives 3.6x risk
  • chronic renal failure
    • immune dysfunction may be due to poor nutrition, uraemic toxins, and immunosuppressive therapies
    • previous immunosuppressants administration gave odds ratio of 10.9 of developing HZ, while dialysis gave an odds ratio of 3.3 in patients with ESRF ³⁾
    • these patients have higher incidence of post-herpetic neuralgia, and higher overall risk of adverse cardiovascular events after the zoster attack, are more at risk of progression to ESRD and in those with lupus, seem to be associated with increased risk of lupus disease flares within 3 months⁴⁾.
  • immunosuppressive Rx
    • systemic lupus erythematosus (SLE)
      • 1.7-3.9x risk; IR 15-25 across age groups with highest in 21-30yr olds at 24.6
      • 18% of lupus nephritis pts developed HZ within 2yrs of starting Rx⁵⁾
    • solid organ transplants (SOT)
      • HZ incidence and severity in SOT recipients are most pronounced after heart and lung transplantation, in older patients, and when CMV prophylaxis is lacking ⁶⁾
    • dermatomyositis and polymyositis gives a hazard ratio of 3.9 in developing HZ ⁷⁾
  • HIV/AIDS (15x risk)
  • neoplasia / cancer / tumours
    • lymphoma 8x risk; oesophageal Ca 4.2x risk; brain tumour 3.8x risk; gynae cancer 3.5x risk; lung Ca 2.3x risk; gastric or colorectal Ca ~1.9x risk;
  • inflammatory bowel disease (IBD) or rheumatoid arthritis
    • 2-3x risk in older adults;
  • psoriatic arthritis:
    • 2-3x risk in older adults; 1.5-2x risk in those with psoriasis without psoriatic arthritis;
  • ankylosing spondylitis (AS)
    • 1.5-2x risk
  • hypertension
    • 2x risk
  • lumbar disc prolapse
    • 2x risk ⁸⁾
  • diabetes mellitus
    • mod. risk factor ~`1.3-1.6x risk⁹⁾
  • gout
    • ~1.3x risk
  • asthma or COPD ~1.3x risk
  • women ~1.3x risk
  • major depression

• the US has started a program to reduce zoster in the elderly by offering vaccination to those over age 50yrs as it appears to reduce the incidence of zoster by 96% if one gives two doses of Shingrix between two and six months apart to adults who are at least 50 years old - this is far more effective and longer lasting than the older Zostavax.¹⁰⁾
  • unfortunately in Australia we still only have subsidised access to Zostavax as of 2022 ¹¹⁾, Shingrix is available to those aged over 55yrs but the two doses will cost around $AU560 in total

• complications of shingles may include post-herpetic neuralgia, and disseminated zoster with visceral, central nervous system and pulmonary involvement
  • 1-4% will need hospital admission esp. if immuncompromised, 30% of patients needing admission have immunocompromise
  • postherpetic neuralgia is more common in patients older than 50 years and overall affects 10%
  • immunosuppressed patients may develop disseminated disease with viraemia and haematogenous spread:
    • eg. infection of lungs, liver, brain or neurologic (eg, motor neuropathies of the cranial and peripheral nervous system, encephalitis, meningoencephalitis, myelitis, Guillain-Barré syndrome)
• increased risk of cardiovascular events
  • 1.4x risk of stroke in next 90 days (2x risk if cranial nerves involved) - this can be reduced with antiviral Rx¹²⁾
  • increased risk of progression to ESRF in patients with chronic renal failure

• see also below for additional HZ ophthalmicus Mx
• isolate from non-immune contacts
• aciclovir if within 72hrs of onset 800mg 5/day for 10 days (Aust. PBS Auth)
  • or famciclovir 250mg tds for 10 days (500mg dose if immunocompromised)
  • or valaciclovir 1g tds for 10 days
• analgesia - consider controlled-release oxycodone in the acute phase
• consider post-exposure vaccination for non-immune contacts - see varicella-zoster virus (chickenpox/shingles)

• see also emedicine
• refers to HZ involving the trigeminal ganglion, first division (ophthalmic) of the trigeminal nerve and nasociliary nerve
• 10-25% of all cases of shingles
• 50% of patients with HZO develop complications
• sequelae can be devastating including blindness as well as post-herpetic neuralgia
• prodromal phase of influenza-like illness with fatigue, malaise, and low-grade fever that may last up to 1 week prior to the development of unilateral rash over the forehead, upper eyelid, and nose.
• Hutchinson sign is the appearance of typical HZ lesions at the tip, side, or root of the nose and indicates nasocilary nerve involvement and increased risk of corneal involvement
• ocular complications include:
  • periorbital and conjunctival edema (1 wk)
  • secondary Staphylococcus aureus infection (1-2 wk)
  • focal scleral atrophy (late)
  • punctate epithelial keratitis (swollen epithelium, 1-2 d)
  • dendritic keratitis (tree branch–like epithelial defects, 4-6 d)
  • stromal keratitis (fine infiltrates beneath the surface, 1-2 wk)
  • deep stromal keratitis (lipid infiltrates and corneal neovascularization, 1 month to years)
  • neurotrophic keratopathy (erosions, persistent defects, corneal ulcers; months to years)
  • uveitis, with inflammation and iris scarring leading to glaucoma and cataract (2 weeks to years)
  • acute retinal necrosis/progressive outer retinal necrosis

• examine for nasociliary nerve involvement and ocular involvement
• examine for the blinking reflex and if compromised, an eye lubricant is needed to prevent corneal desiccation injury.
• oral antivirals ASAP (Aust. PBS Authority) as per HZ Rx but can be started irrespective of onset duration given benefits are likely to outweigh risks
  • as VZV DNA may persist in cornea for up to 30 days, prolonged antiviral Rx should be considered if ocular involvement, the elderly or immunocompromised
  • iv antiviral Rx should be considered for evidence of retinal involvement which may then require months of oral Rx
• oral corticosteroids:
  • may reduce immediate pain but not post-herpetic neuralgia
  • ONLY prescribe if concurrent antiviral Rx AND only if low risk patient (eg. non-diabetic, no PH gastritis)
• do NOT start ophthalmic topical steroids without ophthalmology consultation, but this may be indicated for Rx of stromal keratitis, episcleritis or uveitis
• early ophthalmology review

• an acute peripheral facial neuropathy associated with erythematous vesicular rash of the skin of the ear canal, auricle (also termed herpes zoster oticus), and/or mucous membrane of the oropharynx as a result of reactivation of varicella virus within the geniculate ganglion.
• aka geniculate neuralgia or nervus intermedius neuralgia
• may involve CN VIII, IX, V, and VI in order of frequency, as well as the facial nerve
• accounts for 16% of unilateral facial nerve palsy in children over age 6yrs, and 18% of facial palsies in adults
• it is rare in children under 6 yrs age
• facial palsy recover rate is < 50%

• see emedicine
• patients usually present with paroxysmal pain deep within the ear which precedes onset of rash by hours or days.
• zoster lesions in one of the facial zones:
  • auricularis (ie. around the ear or inside the external auditory canal)
  • facial (ie. lower half of face)
  • occipito-collairs
  • ipsilateral anterior two thirds of the tongue or soft palate (lingual nerve)
• +/- facial nerve palsy (Bell's palsy like)
  • +/- auditory symptoms such as tinnitus, deafness (in 50%), vertigo, nystagmus and ataxia

• ocular lubricants and eyelid management to prevent corneal erosions from dehydration as per Bell's palsy
• oral aciclovir as per shingles
• oral corticosteroids are often used as per Bell's palsy but little evidence for long term benefits
• analgesics - consider controlled-release oxycodone
• vestibular suppressants if severe vertigo
• consider topical local anaesthetics to auditory canal lesions if otalgia problematic