Herpes Zoster/Shingles
- Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or Human alphaherpesvirus
- Epidemiology
- Lifetime risk: 30%
- Age: Peak onset at 50-79 years old
- Gender predominance: Women account for 60% of cases
Pathophysiology of Varicella-Zoster Virus (VZV) Infection
Chickenpox (Primary VZV Infection):
Chickenpox is caused by the primary infection with Varicella-Zoster Virus (VZV). During the initial infection, the virus spreads throughout the body, primarily affecting the skin and respiratory tract. This results in the characteristic widespread vesicular rash of chickenpox. The virus is highly contagious, transmitted via respiratory droplets (from coughing or sneezing) and direct contact with the fluid from skin lesions.
Chickenpox is easily spread through close contact environments, such as schools and households, due to its respiratory route of transmission.
Shingles (Herpes Zoster – VZV Reactivation):
Herpes zoster, or shingles, occurs due to the reactivation of dormant VZV, which remains latent in the sensory nerve ganglia following the initial chickenpox infection. Reactivation typically happens in one or more dermatomes, leading to a localized vesicular rash confined to specific nerve distributions. Unlike chickenpox, shingles is not present in the respiratory tract, limiting its contagiousness.
Shingles is not transmitted through airborne droplets; it can only be spread via direct contact with the fluid from shingles blisters. However, a person with shingles cannot directly transmit shingles to others. Instead, the VZV virus can cause chickenpox in individuals who have not been previously infected with or vaccinated against VZV.
Varicella Zoster Virus (VZV) Reactivation:
- Initial Infection (Chickenpox): The primary infection causes chickenpox, after which the virus becomes dormant in the dorsal root ganglia and cranial nerve ganglia.
- Latency: Following chickenpox, VZV establishes latency within sensory ganglia.
- Reactivation (Herpes Zoster): Approximately 10-20% of individuals with a history of chickenpox will experience VZV reactivation, leading to shingles.
Mechanism of Reactivation:
- Triggering Factors: Reactivation typically occurs when there is a decline in T cell-mediated immunity or when the immune system is compromised.
- Nerve Involvement: The reactivated virus replicates in sensory neurons, and virions travel along the nerve axons to the skin supplied by the affected ganglion, producing a dermatome-specific rash.
- Immune Response: The local immune response leads to inflammation, pain, and vesicular lesions (blisters). When cranial nerves are involved, complications such as ocular involvement or facial paralysis (e.g., Ramsay Hunt syndrome) can occur.
- Perineuritis: Inflammation of the nerve sheath (perineuritis) contributes to the severe neuropathic pain often experienced along the affected dermatome.
Risk Factors for VZV Reactivation:
- Advancing Age: Individuals over 50 are at increased risk due to age-related decline in T-cell mediated immunity.
- Immunocompromised State: The risk of reactivation is heightened in people with compromised immune function, such as:
- HIV infection
- Malignancies (especially lymphoproliferative disorders like leukemia or lymphoma)
- Organ transplantation (due to immunosuppressive therapies)
- Immunosuppressant therapy (e.g., corticosteroids, chemotherapy)
- Early Exposure to VZV: Individuals who had chickenpox before 1 year of age are at a higher risk of developing shingles later in life.
- Specific Triggers: Several factors can precipitate VZV reactivation, including:
- Local trauma
- Systemic illness
- Emotional or physical stress
- Menstruation
- Fever
- Ultraviolet light exposure
- Cold wind
Precautions:
To prevent the spread of VZV, individuals with shingles should avoid contact with non-immune individuals (especially pregnant women, infants, and immunocompromised individuals) until the lesions have fully crusted over.
Symptoms:
- Timing
- May be precede rash by 1-5 days
- Most common symptoms
- Fever (variably present)
- Headache
- Photophobia
- Paresthesias
- Pain within Dermatome occurs first
- Examples: itching, burning, hyperesthesia
- Malaise
- Rash
- Develops after 48-72 hours (up to 5 days before rash)
- Lesions heal within 2-4 weeks
- Distribution
- Follows 1-2 Dermatomes and uncommonly crosses the mid-line (although may occur on back)
- Lesions appear proximally first, then distally
- Most common regions
- Back (esp. T1 to L2)
- Face (esp. ophthalmic branch of Trigeminal Nerve, accounting for 15% of cases)
- Characteristics
- Starts as erythematous, maculopapular rash
- Clear Vesicles develop
- Vessicles turn cloudy within 3-5 days
- Crust over within 7-10 days
- Residual scar or pigmentation changes are common
Variants:
- Zoster Sine Herpete (zoster without a rash)
- Zoster without rash is uncommon but does occur
- Hutchinson’s Sign (Vesicle on the tip of nose)
- Associated with Herpes Zoster Ophthalmicus
- Stain the eye for Fluorescein and observe for Dendrites
- Exercise high level of suspicion for ocular involvement
- Ramsay Hunt Syndrome (Vesicle in ear)
- Associated with Bell’s Palsy
- Rapid onset with facial pain
- Signs:
- Unilateral herpetic rash of pinna
-
- Tinnitus and Vertigo may occur if Cranial Nerve 8 is involved
- hearing Loss
- Peripheral Facial Nerve Paralysis (Bells Palsy)
- Course may be more prolonged
Complications
- Hospitalization in 2-3% of cases
- Postherpetic Neuralgia
- Herpes Zoster Ophthalmicus
- Herpes Zoster Oticus (Ramsay Hunt Syndrome)
- Meningitis
- Encephalitis
- Granulomatous Angiitis with contralateral Hemiplegia
- Cutaneous dissemination in Lymphoma (40%)
- Longterm increased cardiovascular and Cerebrovascular Disease risk – Growing evidence for association – Erskine (2017) PLoS One 12(7):e0181565 +PMID: 28749981 [PubMed]
Management:
- Relative indications for antivirals (maximal benefit):
- Onset within 72 hours of starting treatment, Age 50 years and older, More than 50 lesions
- Acyclovir
- Dose: 800 mg orally five times daily for 7-10 days
- Reduces healing time, pain, and rash dissemination
- Least expensive of all antiviral options by an order of magnitude
- Valacyclovir
- appeared more effective in over age 50
- Dose: 1000 mg orally three times daily for 7 days
- Equivalent efficacy to Famciclovir
- Famciclovir
- Dose: 500 mg orally three times daily for 7 days, Lesions healed faster, more brief virus shedding, Reduces Postherpetic Neuralgia duration by 2 months
- Pain Management
Postherpetic Neuralgia
- Pain in Dermatomal Distribution persists >90 days after Herpes Zoster rash resolves
- C/O of
- Burning or electric-shock pain
- Hyperalgesia
- Allodynia
- Typical duration: 30 days to 6 months -Some cases may persist years
- Management
- Topical – Lidocaine 5% patch, Capsaicin cream (Zostrix) 0.075% cream
- TCAs (Amitriptyline more effective than Gabapentin, but adverse effects limits tricyclic use)
- SNRI: Cymbalta, Venlafaxine
- Anticonvulsants: Gabapentin, Pregabalin
- Transcutaneous Electric Nerve Stimulation (TENS)
- Nerve Block
- Opioid Analgesics
- Intrathecal Methylprednisolone 60 mg at L2-L3
- Analgesics
- NSAIDs
- Opioid Analgesics
- agents used in Postherpetic Neuralgia – No evidence that these agents reduce acute Shingles pain or that they prevent Postherpetic Neuralgia
- Systemic Corticosteroids
- May reduce acute pain, inflammation and speed up healing
- Does not reduce risk of Postherpetic Neuralgia
- Prophylaxis: Varicella Immune Globulin (VZIG) Indications
- Immunodeficient under age 15 years
- Newborn of infected mother – Exposure 5 days before delivery or 2 days after
Prevention
- Avoid contact with active Shingles or Chicken Pox
- Consider prophylaxis if exposure in high-risk groups
- Varicella Vaccine routinely in children, teens, and adults
- Varivax
- live attenuated vaccine used to protect against varicella (chickenpox). Oka/Merck strain vaccine
- Primarily used for children aged 18 months as part of routine immunization.
- Also recommended for older children, adolescents, and adults who are non-immune to varicella.
- Immunity may not be lifelong, vaccine is effective for over 10 years in preventing varicella infection in healthy individuals, and when breakthrough infections do occur, illness is typically mild
- should not be given to immunocompromised individuals, pregnant women, or those with contraindications to live vaccines.
- Varivax
- Herpes Zoster Vaccine (Shingles Vaccine, Zostavax)
- Reduces risk of Herpes Zoster Incidence by 60% and Post-herpetic Neuralgia by 65%
- Administered to adults, especially those aged 50 years and over or immunocompromised adults aged 18 years and over, as it is not a live vaccine.
- Zostavax
- Developed in 1970, live attenuated vaccine
- is a more concentrated formulation of the Varivax vaccine, designed to elicit an immune response in older adults whose immunity to VZV wanes with advancing age
- 51% effective against shingles
- contraindicated in people who are immunocompromised
- Shingrix
- Developed in 2017, recommended Shingrix for adults over the age of 50, including those who have already received Zostavax.
- Shingrix is the preferred vaccine for use in people who are immunocompromised.
- 97% effective against shingles for people aged 50-69
- 91% effective against shingles for people >70
- Eligible for Free Shingrix® (Two-dose Course):
- People aged 65 years and over
- Aboriginal and Torres Strait Islander people aged 50 years and over
- Certain immunocompromised individuals aged 18 years and over (detailed list available in Appendix A of the NIP document)
Shingles Vaccine
General Recommendations:
- All individuals aged 50 years and over
- Individuals aged 18 years and over who are immunocompromised
Vaccine Details:
- Shingrix® vaccine is recommended for both immunocompromised and immunocompetent individuals because it is not a live vaccine.
Eligibility for Free Vaccine Under the National Immunisation Program (NIP)
Eligible for Free Shingrix® (Two-dose Course):
- People aged 65 years and over
- Aboriginal and Torres Strait Islander people aged 50 years and over
- Certain immunocompromised individuals aged 18 years and over (detailed list available in Appendix A of the NIP document)
Shingles Vaccine Doses
Shingrix®:
- Two doses: 2–6 months apart for immunocompetent individuals
- 1–2 months apart for immunocompromised individuals
- Each dose is 0.5 mL given intramuscularly (preferably in the deltoid)
Zostavax®:
- Administered as a single 0.65 mL dose by subcutaneous injection
Booster Doses
- No booster doses are currently recommended for shingles vaccines.
Common Side Effects of Shingles Vaccines
Injection Site Reactions (Shingrix® and Zostavax®):
- Pain, swelling, and redness
- Common in up to 82% of Shingrix® recipients and 50% of Zostavax® recipients
Generalized Symptoms (More Common with Shingrix®):
- Fatigue, muscle aches, headache, shivering, fever, and gastrointestinal symptoms (typically mild and resolving in a few days)
Rare Side Effects of Zostavax®:
- 0.1% may develop a chickenpox-like rash locally
- Widespread rash may indicate disseminated infection and requires prompt review
Co-administration with Other Vaccines
- Shingrix® or Zostavax® can be given with most other vaccines, including influenza, COVID-19, and respiratory syncytial virus vaccines.
- Providers may consider separate visits to reduce reaction risk, but timely vaccination should not be delayed.
Options for Non-Eligible Individuals
- Adults aged 50–64 years can purchase Shingrix® or Zostavax® through private prescription.
- Immunocompromised adults aged 18 years and over not eligible for NIP-funded vaccine can also access Shingrix® through private prescription.
Missed Doses
- If it has been more than 6 months since Dose 1 of Shingrix®, give Dose 2 as soon as practical. No need to repeat Dose 1.
Vaccination After Previous Shingles
- People who have had shingles are recommended to wait 12 months before receiving a shingles vaccine (Shingrix®). Immunocompromised individuals can receive it after 3 months.
Shingles Management After Vaccination
- Suspected shingles after vaccination should be reviewed, with antiviral treatment and analgesics used as appropriate.
Use in Immunocompromised Individuals
- Shingrix® is preferred for immunocompromised people.
- Zostavax® is contraindicated in severely immunocompromised individuals.
- If immunocompromise is uncertain, avoid Zostavax®.
Vaccination for Those with Prior Chickenpox Vaccine
- People with no history of chickenpox but who received a chickenpox vaccine may not require a shingles vaccine.
- If chickenpox history is unknown, Shingrix® is safe and recommended.
Blood Test Before Vaccination
- Generally, no blood test is needed before administering Shingrix®. Most Australians by age 30 have had the varicella-zoster virus.
Free Shingrix® After Zostavax®
- A person can receive Shingrix® if they previously had Zostavax®, with a waiting period of at least 12 months between the two vaccines.