Varicella Zoster Virus (Chickenpox & Shingles)

1. Clinical Overview

Varicella Zoster Virus (VZV), also known as Human Herpesvirus 3 (HHV-3), is a neurotropic alphaherpesvirus that causes two clinically distinct syndromes separated by decades: varicella (chickenpox) as the primary infection, and herpes zoster (shingles) as viral reactivation. [1,2]

Primary infection with VZV typically occurs in childhood in non-vaccinated populations, resulting in the characteristic widespread pruritic vesicular exanthem. Following resolution, the virus establishes lifelong latency in dorsal root and cranial nerve ganglia through retrograde axonal transport. Reactivation, triggered by declining cell-mediated immunity, causes the painful dermatomal rash of herpes zoster, predominantly affecting older adults and immunocompromised individuals. [1,3]

While chickenpox is generally benign in healthy children, it carries significant morbidity and mortality in certain populations: adults (25-fold higher pneumonia risk), pregnant women (maternal pneumonitis and fetal varicella syndrome), neonates, and the immunocompromised (disseminated disease). Shingles affects approximately 30% of individuals during their lifetime, with post-herpetic neuralgia (PHN) representing the most debilitating chronic complication, affecting up to 20% of patients over age 50. [2,4]

Key Clinical Facts

• Infectivity: One of the most contagious viruses (R₀ = 10-12, comparable to measles). Transmission occurs via respiratory droplets and direct contact with vesicular fluid. [1]
• Infectious Period: 48 hours before rash onset until all lesions have crusted (typically 5-7 days).
• Chickenpox Rash: "Crops" of lesions in various stages (macules, papules, vesicles, pustules, crusts) appearing simultaneously - the classic "starry sky" appearance with centripetal distribution (trunk → face → extremities). [5]
• Shingles Rash: Strictly unilateral, dermatomal distribution that does not cross the midline. Preceded by 2-3 days of dermatomal pain (pre-herpetic neuralgia).
• Latency Site: Satellite cells of dorsal root ganglia and cranial nerve ganglia, where viral DNA persists episomally with minimal transcription (ORF63 and VLT transcripts). [3]

Critical Clinical Pearls

Hutchinson's Sign: Vesicles on the tip or side of the nose indicate nasociliary nerve involvement (branch of V1 trigeminal). This sign predicts ocular involvement (keratitis, uveitis, acute retinal necrosis) with 76% sensitivity. Requires urgent ophthalmology referral within 24 hours to prevent vision loss. [6,7]

Ramsay Hunt Syndrome (Herpes Zoster Oticus): Triad of (1) ipsilateral lower motor neuron facial palsy, (2) otalgia, and (3) vesicles in the auditory canal/concha/auricle. Caused by VZV reactivation in the geniculate ganglion. Facial nerve recovery is significantly worse than Bell's palsy (complete recovery 21% vs 71%), particularly if treatment delayed beyond 72 hours. [8]

Pregnancy Exposure Protocol: Non-immune pregnant women exposed to VZV require urgent serology. If IgG-negative, administer VZIG (Varicella Zoster Immunoglobulin) ideally within 96 hours, or up to 10 days post-exposure. Maternal infection less than 20 weeks gestation carries 0.4-2% risk of Fetal Varicella Syndrome (limb hypoplasia, cortical atrophy, chorioretinitis, skin scarring). [9]

Shingles Transmission: You cannot catch shingles from someone with shingles. However, a VZV-naive individual can develop chickenpox from exposure to shingles vesicular fluid (not airborne from shingles). Conversely, shingles is reactivation of endogenous latent virus, not re-infection.

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2. Epidemiology

Varicella (Chickenpox)

Herpes Zoster (Shingles)

High-Risk Populations

Severe Varicella Risk Factors:

1. Adults (> 15 years): 25x higher risk of varicella pneumonitis
2. Pregnancy: 10-20% develop pneumonitis; mortality 3-14% (especially third trimester)
3. Immunocompromised: HIV (CD4 less than 200), chemotherapy, high-dose steroids (> 20mg prednisolone > 14 days), biologics
4. Neonates: Maternal varicella 5 days before to 2 days after delivery = 17-30% severe neonatal varicella
5. Smokers: 3-4 fold increased pneumonitis risk

Herpes Zoster Risk Factors:

• Age: Incidence increases exponentially after age 50 (immunosenescence)
• Immunosuppression: Solid organ transplant (8-fold risk), haematological malignancy (20-fold), HIV
• Autoimmune disease: SLE, rheumatoid arthritis, IBD (2-3 fold increased risk)
• Female sex: 20-30% higher incidence than males

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3. Aetiology and Pathophysiology

Viral Structure and Classification

VZV is a double-stranded DNA virus (125 kb genome encoding ~70 proteins) of the Alphaherpesvirinae subfamily, closely related to Herpes Simplex Virus. The virion consists of:

• Core: Linear dsDNA genome
• Nucleocapsid: Icosahedral symmetry (162 capsomers)
• Tegument: Protein layer containing viral transactivators
• Envelope: Lipid bilayer with glycoproteins (gE, gI, gB, gH, gL) essential for cell entry and immune evasion

Primary Infection (Varicella): Pathogenesis

The pathogenesis of chickenpox follows a predictable temporal sequence: [1,3,5]

Day 0-2 (Inoculation and Replication)

• Entry via respiratory mucosa or conjunctival epithelium
• Initial replication in regional lymphoid tissue (tonsillar, cervical nodes)
• Dendritic cell infection enables immune evasion

Day 4-6 (Primary Viraemia)

• Cell-associated viraemia in T lymphocytes
• Dissemination to liver, spleen, reticuloendothelial system
• Extensive viral replication in these organs

Day 10-14 (Secondary Viraemia and Rash)

• High-titre viraemia (10³-10⁴ infectious units/mL)
• Seeding of skin via capillary endothelium
• Vesicle formation: focal dermal infection → ballooning degeneration of keratinocytes → intraepidermal vesicle
• Characteristic multinucleated giant cells (Tzanck cells) on cytology

Centripetal Distribution: Higher skin temperature on trunk favours viral replication; cooler extremities = fewer lesions.

Day 14-21 (Establishment of Latency)

• Virions enter sensory nerve terminals in skin
• Retrograde axonal transport via microtubule-dependent mechanism
• Virus reaches dorsal root ganglia and cranial nerve ganglia (especially trigeminal)
• Latency established: Viral genome persists as episomal DNA (not integrated)
• Minimal viral gene transcription: primarily ORF63 and VLT (VZV latency-associated transcript - antisense to ORF61)
• No viral replication; neurons remain undamaged during latency [3]

Exam Detail: Molecular Mechanisms of Latency

VZV latency is epigenetically regulated through histone modifications. During latency:

• Viral genome chromatinized with repressive histone marks (H3K9me3, H3K27me3)
• Polycomb repressive complexes (PRC2) silence lytic genes
• Only ORF63 (encodes IE63 regulatory protein) and VLT transcripts detected
• VLT is a long non-coding RNA (antisense to ORF61) that may regulate latency maintenance

Why doesn't VZV cause continuous reactivation? VZV-specific CD4+ and CD8+ T cells continuously surveil ganglia. Decline in T-cell immunity (age, immunosuppression, stress) allows viral gene transcription to proceed unchecked, leading to reactivation. [3,11]

Reactivation (Herpes Zoster): Pathogenesis

Zoster occurs when VZV-specific cell-mediated immunity wanes: [2,4,11]

Step 1: Immune Decline

• Age-related thymic involution → reduced naive T-cell generation
• Chronic inflammation ("inflammaging") → T-cell exhaustion
• Immunosuppressive medications, malignancy, HIV

Step 2: Viral Reactivation in Ganglion

• Loss of immune surveillance → viral gene transcription resumes
• Lytic viral replication in ganglion neurons
• Acute ganglionic inflammation: lymphocytic infiltration, neuronal necrosis, haemorrhage

Step 3: Anterograde Spread

• Virions travel down sensory nerve axon to skin
• Dermatomal distribution: vesicles limited to area innervated by affected ganglion
• Typically unilateral (occasionally involves adjacent dermatomes if multiple ganglia affected)

Step 4: Neuritis and Pain

• Active viral replication → neuronal destruction → neuropathic pain
• Pre-herpetic neuralgia: pain/dysaesthesia 2-3 days before rash (48-72 hours prodrome)
• Acute herpetic neuralgia: pain during active lesions
• Post-herpetic neuralgia: pain persisting > 90 days after rash crusting (see Complications)

Thoracic Dermatomes (T3-L2): Most common site (50-70%) - reflects greater number of thoracic ganglia Cranial Nerves: Trigeminal (V1 > V2 > V3) = 10-20%; Geniculate (facial) = 5-10%

Exam Detail: Why does zoster stop at the midline?

Dorsal root ganglia innervate ipsilateral dermatomes. The midline represents the boundary between contralateral ganglia. In disseminated zoster (seen in immunocompromised patients), haematogenous spread causes bilateral/multidermatomal lesions, indicating severely impaired immunity.

VZV Vasculopathy (Emerging Complication)

VZV can infect cerebral arteries via direct spread from ganglia or haematogenous dissemination, causing:

• Granulomatous arteritis → luminal narrowing → stroke (especially weeks to months post-zoster)
• Large and small vessel disease
• Diagnosed by VZV DNA PCR in CSF or brain biopsy (vessel wall biopsy if accessible)
• Treatment: IV aciclovir + corticosteroids (controversial but often used) [12]

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4. Clinical Presentation

A. Varicella (Chickenpox)

Prodrome (1-2 days before rash)

• Fever: 38-39°C (may be absent in young children)
• Malaise, headache, myalgia
• Anorexia, irritability in children

Exanthem (Rash)

• Onset: Face and trunk (centripetal) → spreads to proximal limbs

• Evolution (over 24 hours):

  • "Macule (1-2 hours): erythematous flat spot"
  • "Papule (2-4 hours): raised lesion"
  • Vesicle (4-6 hours): "dewdrop on rose petal"

• thin-walled, clear fluid on erythematous base

  • "Pustule (24-48 hours): clouding of vesicular fluid"
  • "Crust (48-72 hours): dried lesion (no longer infectious once all crusted)"

• Polymorphic: Lesions appear in successive crops (every 12-24 hours over 3-5 days) → all stages (macules, vesicles, crusts) present simultaneously = pathognomonic "starry sky"

• Distribution: Greatest density on trunk and scalp; sparse on distal limbs

• Number: Usually 200-500 lesions (range 10-1500)

• Pruritus: Intense itching (risk of secondary bacterial infection from scratching)

Mucosal Involvement (30-40%)

• Oropharyngeal: Vesicles → shallow ulcers (painful)
• Conjunctival: Vesicles on palpebral conjunctiva
• Genital: Vulvar or penile lesions (can be confused with HSV)

Duration

• New lesions stop appearing after 5-7 days
• Crusting complete by 10-14 days
• Fever resolves within 3-5 days in uncomplicated cases

Atypical Presentations

Modified Varicella (in vaccinated or partially immune individuals)

• Fewer lesions (less than 50)
• Milder systemic symptoms
• More rapid crusting
• Still infectious (though less so)

Breakthrough Varicella (post-vaccination)

• Occurs in 15-20% of vaccinated children upon exposure
• Predominantly maculopapular rash (fewer vesicles)
• Mild illness, fewer complications

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B. Herpes Zoster (Shingles)

Prodrome (2-3 days before rash): "Pre-herpetic Neuralgia"

• Dermatomal pain: burning, stabbing, or aching pain in affected dermatome
• Dysaesthesia/Hyperaesthesia: abnormal sensation to light touch
• Flu-like symptoms: fever, headache, malaise (in 5-10%)
• Diagnosis: Often mistaken for pleurisy, MI, cholecystitis, or appendicitis depending on dermatome

Exanthem (Rash)

• Onset: Erythematous plaque → grouped vesicles on erythematous base ("cluster of grapes")
• Distribution: Strictly unilateral, dermatomal (rarely crosses midline)
• Evolution: Vesicles → pustules (3-5 days) → crusting (7-10 days) → healing (2-4 weeks)
• Scarring: Hypopigmentation or hyperpigmentation common; pitted scarring in severe cases

Common Dermatomes:

• Thoracic (T1-L2): 50-70% - horizontal band around chest/abdomen
• Trigeminal (V1): 10-15% - forehead, scalp, eye (Ophthalmic zoster)
• Trigeminal (V2/V3): 5% - mid-face, lower face
• Cervical: 10-15% - neck, upper limb
• Lumbar/Sacral: 10% - lower limb, perineum

Special Presentations

Herpes Zoster Ophthalmicus (HZO) [6,7]

• Incidence: 10-20% of all zoster cases
• V1 trigeminal nerve involvement (ophthalmic division)
• Hutchinson's Sign: Vesicles on tip/side of nose (nasociliary branch) → 76% risk of ocular involvement
• Ocular Complications:
  • Conjunctivitis (40-50%)
  • "Keratitis (25-35%): punctate epithelial → dendritic → stromal"
  • Uveitis (anterior 30-40%; posterior 5-10%)
  • "Acute retinal necrosis (rare, less than 1%): vision-threatening"
  • Optic neuritis, scleritis (rare)
• Management: URGENT ophthalmology referral + oral antivirals (or IV if severe)

Ramsay Hunt Syndrome (Herpes Zoster Oticus) [8]

• Incidence: 5% of zoster cases
• Pathophysiology: VZV reactivation in geniculate ganglion (facial nerve)
• Classic Triad:
  1. LMN facial palsy (ipsilateral)
  2. Ear pain (otalgia)
  3. Vesicles in external auditory canal, concha, or anterior two-thirds of tongue
• Additional features: Hearing loss (20-30%), vertigo (15-20%), hyperacusis, loss of taste
• Prognosis: Complete facial nerve recovery only 21% (vs 71% in Bell's palsy) - worse if elderly or delayed treatment > 72h
• Management: Oral antivirals + corticosteroids (controversial but widely used) within 72 hours

Disseminated Zoster

• Definition: > 20 lesions outside primary and adjacent dermatomes OR involvement of multiple non-contiguous dermatomes
• Indicates: Severe immunosuppression (HIV CD4 less than 200, haematological malignancy, transplant)
• Risk: Visceral involvement (pneumonitis, hepatitis, encephalitis, disseminated intravascular coagulation)
• Management: IV aciclovir (10mg/kg TDS) + investigate underlying immunodeficiency

Zoster Sine Herpete (Zoster Without Rash)

• Dermatomal pain without visible rash
• Diagnosis: VZV DNA PCR in CSF (if neurological symptoms) or rising VZV IgG titres
• Relatively common cause of radicular pain in elderly

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Red Flag Features

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5. Differential Diagnosis

For Varicella (Chickenpox)

For Herpes Zoster (Shingles)

Clinical Pearl: Thoracic Zoster vs Cardiac/Pulmonary Pathology

Pre-herpetic neuralgia (2-3 days of dermatomal pain before rash) can mimic:

• Left T4-T6 zoster: Acute coronary syndrome (perform ECG, troponin)
• Right T7-T9 zoster: Cholecystitis (check RUQ ultrasound)
• Lower thoracic zoster: Pancreatitis, renal colic

Key clue: Hyperaesthesia to light touch along dermatome before rash appears (this does not occur in referred visceral pain).

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6. Investigations

Clinical Diagnosis (Usually Sufficient)

In immunocompetent patients with classic presentations:

• Varicella: Widespread polymorphic vesicular rash in crops = clinical diagnosis
• Zoster: Unilateral dermatomal vesicular rash + pain = clinical diagnosis

Laboratory confirmation NOT routinely required but indicated in:

• Atypical presentations
• Immunocompromised patients
• Pregnancy
• Severe complications (encephalitis, pneumonitis, vasculopathy)
• Public health/epidemiological purposes

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Laboratory Confirmation

1. VZV DNA PCR (Polymerase Chain Reaction) - GOLD STANDARD

• Sample: Vesicle fluid (unroof vesicle, swab base), crusted lesion, or CSF
• Sensitivity: 95-100% (higher than viral culture)
• Turnaround: 24-48 hours
• Use: Diagnosis in immunocompromised, CNS involvement, atypical cases

2. Direct Immunofluorescence (DFA)

• Sample: Vesicle scrapings
• Principle: Fluorescent antibodies bind VZV antigens
• Sensitivity: 80-90% (lower than PCR)
• Turnaround: 2-4 hours
• Use: Rapid diagnosis when PCR unavailable

3. Viral Culture

• Sensitivity: 30-60% (VZV is cell-associated and labile)
• Turnaround: 5-10 days (slow growth)
• Use: Rarely used now (superseded by PCR)

4. Tzanck Smear (Historical)

• Method: Scrape vesicle base → Giemsa stain → look for multinucleated giant cells
• Sensitivity: 60-70%
• Specificity: Cannot distinguish VZV from HSV
• Use: Largely obsolete; replaced by PCR

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Serology (IgG and IgM)

VZV IgG

• Use: Determine immune status (past infection or vaccination)
• Interpretation:
  • "Positive: Immune to varicella (> 95% protective)"
  • "Negative: Susceptible; requires VZIG if exposed and high-risk (pregnancy, immunocompromised)"
• Indications:
  • Pregnant women exposed to varicella (check urgently)
  • Healthcare workers (occupational health screening)
  • Pre-transplant/chemotherapy assessment

VZV IgM

• Use: Acute infection diagnosis (primary or reactivation)
• Limitations:
  • False positives (cross-reactivity with other herpesviruses)
  • False negatives (immunocompromised may not mount IgM response)
  • Not reliable for distinguishing primary from reactivation
• Use: Limited; PCR preferred

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Investigations for Complications

Varicella Pneumonitis

• CXR: Diffuse bilateral nodular infiltrates or interstitial pattern (may lag clinical symptoms by 24-48h)
• ABG: Hypoxaemia (PaO₂ less than 8 kPa on room air = severe)
• High-Resolution CT: "Miliary" nodules (2-5mm); ground-glass opacification

CNS Involvement (Encephalitis, Meningitis, Vasculopathy)

• Lumbar Puncture:
  • Lymphocytic pleocytosis (10-1000 cells/μL)
  • Mildly elevated protein
  • Normal or low glucose
  • VZV DNA PCR in CSF (sensitivity 80% for encephalitis; lower for vasculopathy)
• Brain MRI:
  • "Cerebellar ataxia: Cerebellar swelling (children)"
  • "Vasculopathy: Ischaemic strokes in basal ganglia, internal capsule"
  • "Encephalitis: T2/FLAIR hyperintensities in cortical/subcortical regions"
• EEG: Non-specific slowing; periodic discharges rare

Secondary Bacterial Infection

• Blood cultures: If systemically unwell (Group A Streptococcus, Staphylococcus aureus)
• Wound swab: Culture from erythematous/purulent lesions
• Inflammatory markers: CRP, WCC (neutrophilia)

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7. Classification and Staging

Clinical Severity Classification

Varicella (Chickenpox)

• Mild: less than 100 lesions, no systemic upset, immunocompetent
• Moderate: 100-500 lesions, fever less than 39°C, mucosal involvement
• Severe: > 500 lesions, high fever, complications (pneumonitis, encephalitis), immunocompromised

Herpes Zoster (Shingles)

• Uncomplicated: Single dermatome, age less than 50, immunocompetent, no cranial nerve involvement
• Complicated: Multiple dermatomes, cranial nerve involvement (HZO, Ramsay Hunt), immunocompromised, disseminated zoster

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8. Management

A. Management of Varicella (Chickenpox)

Uncomplicated Varicella in Healthy Children

Supportive Care (Mainstay)

• Antipyretics: Paracetamol 15mg/kg QDS (max 4g/day in adults)
  • AVOID IBUPROFEN/NSAIDs ❌ - case-control studies link to increased risk of necrotising fasciitis (Group A Strep superinfection) [13]
  • AVOID ASPIRIN ❌ - risk of Reye's syndrome (acute encephalopathy + hepatic dysfunction)
• Antihistamines: Chlorphenamine 0.1mg/kg QDS or cetirizine 5-10mg OD (reduce pruritus, prevent scratching)
• Emollients: Calamine lotion, cooling gels (soothing)
• Hygiene: Short fingernails; daily baths (reduce secondary bacterial infection)

Isolation

• Exclude from school/nursery until all lesions crusted (usually 5 days from rash onset)
• Avoid contact with immunocompromised, pregnant women, neonates

No Antiviral Therapy: Not recommended for healthy children (marginal benefit; chickenpox is self-limiting)

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Varicella in Adults and Adolescents (> 14 years)

Oral Antivirals (reduces duration and severity if started within 24 hours of rash onset)

• Aciclovir: 800mg five times daily (PO) for 7 days
• Valaciclovir: 1g TDS (PO) for 7 days (better bioavailability; more convenient)
• Mechanism: Guanosine analogue; phosphorylated by viral thymidine kinase → inhibits viral DNA polymerase

Indications: All adults with chickenpox (higher complication risk than children)

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Severe/Complicated Varicella (High-Risk Groups)

IV Aciclovir - 10mg/kg TDS (over 1 hour infusion) for 7-10 days

Indications:

• Varicella pneumonitis
• Varicella encephalitis/meningoencephalitis
• Haemorrhagic or necrotising varicella
• Immunocompromised patients (HIV, chemotherapy, steroids > 20mg prednisolone > 14 days, transplant)
• Neonatal varicella (maternal infection -5 to +2 days of delivery)
• Pregnancy with severe disease or complications

Monitoring: Renal function (aciclovir nephrotoxicity - ensure adequate hydration); FBC, LFTs

Adjunctive:

• Oxygen: If hypoxic (varicella pneumonitis)
• Mechanical ventilation: Severe pneumonitis with respiratory failure
• IV immunoglobulin (IVIG): 1-2g/kg in immunocompromised with severe disease (controversial; limited evidence)

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Varicella in Pregnancy [9]

First/Second Trimester (less than 20 weeks)

• Risk: Fetal Varicella Syndrome (0.4-2% if infected less than 20 weeks)
  • Limb hypoplasia, cortical atrophy, chorioretinitis, cataracts, cutaneous scarring
• Management:
  • "If mild maternal disease: Oral aciclovir 800mg 5x/day for 7 days (safety data reassuring)"
  • "If severe (pneumonitis): IV aciclovir 10mg/kg TDS"
  • Fetal ultrasound at 5 weeks and 20 weeks gestation (assess structural abnormalities)

Third Trimester

• Risk: Maternal pneumonitis (10-20% of pregnant women with varicella)
• Management: Low threshold for IV aciclovir (mortality 3-14% if pneumonitis develops)

Peripartum Varicella (-5 to +2 days of delivery)

• Risk: Severe neonatal varicella (17-30% mortality if untreated) - insufficient time for maternal IgG transfer
• Management:
  • "Neonate: VZIG 125 units IM (within 96h of birth) + monitor closely"
  • "If neonatal varicella develops: IV aciclovir 10-20mg/kg TDS for 10-14 days"

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Post-Exposure Prophylaxis (PEP)

For non-immune high-risk individuals exposed to varicella:

1. Varicella Zoster Immunoglobulin (VZIG)

• Dose: 125 units/10kg IM (max 625 units)
• Timing: Ideally within 96 hours of exposure (up to 10 days)
• Indications:
  • Immunocompromised (no VZV immunity)
  • Pregnant women (IgG-negative)
  • Neonates (maternal infection -5 to +2 days of delivery)
• Effect: Attenuates disease severity (does not always prevent infection)

2. Aciclovir Prophylaxis (if VZIG unavailable or delayed)

• Dose: 800mg QDS (PO) for 7 days, starting day 7-10 post-exposure (during incubation period)
• Evidence: Less established than VZIG; used when VZIG unavailable

3. Post-Exposure Varicella Vaccination

• Timing: Within 3-5 days of exposure
• Efficacy: 70-90% protection if given within 3 days
• Not suitable: Immunocompromised, pregnancy (live vaccine contraindicated)

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B. Management of Herpes Zoster (Shingles)

Antiviral Therapy

Oral Antivirals - Start within 72 hours of rash onset (maximum benefit)

Indications for Antiviral Treatment: [2,4]

• Age > 50 years (all patients) - reduces acute pain and PHN risk by 20-30%
• Immunocompromised (any age)
• Moderate-severe pain
• Moderate-severe rash
• Non-truncal involvement (especially cranial nerve)
• Ophthalmic zoster (HZO)

Can treat > 72 hours if:

• New vesicles still forming
• Ophthalmic or Ramsay Hunt syndrome
• Immunocompromised

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IV Aciclovir (Severe Zoster)

Dose: 10mg/kg TDS IV (over 1 hour) for 7-10 days

Indications:

• Disseminated zoster
• Immunocompromised with severe disease
• CNS involvement (encephalitis, myelitis, vasculopathy)
• Acute retinal necrosis
• Visceral involvement (hepatitis, pneumonitis)

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Analgesia

Pain management is ESSENTIAL - zoster is one of the most painful conditions in medicine.

Acute Pain (During Active Rash)

1. Simple Analgesia

• Paracetamol: 1g QDS (first-line)
• NSAIDs: Ibuprofen 400mg TDS or naproxen 500mg BD (if no contraindications)

2. Weak Opioids (if inadequate control)

• Codeine: 30-60mg QDS
• Tramadol: 50-100mg QDS (max 400mg/day)

3. Neuropathic Agents (early initiation may prevent PHN)

• Gabapentin: Start 300mg OD → titrate to 300-600mg TDS (max 3.6g/day)
• Pregabalin: Start 75mg BD → titrate to 150-300mg BD (max 600mg/day)
• Amitriptyline: Start 10mg ON → titrate to 50-75mg ON (off-label but effective)

4. Topical Agents

• Lidocaine gel 5%: Apply to painful area QDS (avoid broken skin)
• Capsaicin cream: Use once lesions crusted (may worsen pain initially)

5. Strong Opioids (severe pain only; short-term)

• Morphine sulphate (immediate-release): 5-10mg PRN
• Seek specialist pain advice if escalating

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Post-Herpetic Neuralgia (PHN) - See Complications section below

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Corticosteroids (Controversial)

Oral Prednisolone: 60mg OD for 7 days, then taper over 2 weeks

Proposed Benefits: Reduce acute pain, faster rash healing

Evidence: Cochrane review shows no reduction in PHN incidence; modest reduction in acute pain. [14]

Use Limited To:

• Ramsay Hunt syndrome (may improve facial nerve recovery - though evidence weak)
• Severe inflammation (e.g., periorbital oedema in HZO)

Contraindications: Diabetes, immunosuppression, hypertension (relative)

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Ophthalmic Zoster (HZO) - Specific Management [6,7]

Urgent Ophthalmology Review (within 24 hours)

1. Antivirals

• Oral aciclovir 800mg 5x/day for 7-10 days (sufficient for most cases)
• IV aciclovir if: Acute retinal necrosis, severe keratitis, immunocompromised

2. Topical Ophthalmic Treatment (prescribed by ophthalmologist)

• Topical steroids: Prednisolone 1% (if uveitis or keratitis) - ONLY under ophthalmology guidance
• Cycloplegics: Cyclopentolate 1% (relieve pain from ciliary spasm)
• Lubricants: Preserve cornea

3. Monitor Complications

• Intraocular pressure (steroid-induced glaucoma)
• Corneal scarring
• Chronic/recurrent uveitis

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Ramsay Hunt Syndrome - Specific Management [8]

1. Antivirals

• Oral aciclovir 800mg 5x/day for 7 days (or valaciclovir 1g TDS)
• Start within 72 hours for best facial nerve recovery

2. Corticosteroids (commonly used, though evidence limited)

• Prednisolone 60mg OD for 7 days, then taper over 2 weeks
• Aim: Reduce inflammation/oedema in facial canal

3. Eye Protection (if incomplete eye closure)

• Artificial tears during day
• Lubricating ointment (lacri-lube) at night
• Tape eye shut at night (prevent corneal exposure keratitis)

4. Specialist Referral

• ENT for audiometry, vestibular assessment
• Facial nerve assessment: House-Brackmann grading
• Consider surgical decompression if complete paralysis (controversial; rarely performed)

Prognosis: Complete recovery 21% (vs 71% Bell's palsy); older age and delayed treatment = worse outcome

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C. Isolation and Infection Control

Varicella (Chickenpox)

• Highly contagious: Airborne + contact precautions
• Isolation: Until all lesions crusted (5-7 days from rash onset)
• Healthcare Setting: Negative pressure room if available; HCWs must be immune (check VZV IgG)

Herpes Zoster (Shingles)

• Less contagious: Contact precautions (cover lesions; transmission only via direct contact with vesicular fluid)
• Immunocompetent with localized zoster: Standard precautions + cover rash
• Disseminated zoster or immunocompromised: Airborne + contact precautions (treat as varicella)

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9. Complications

Varicella Complications

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Herpes Zoster Complications

1. Post-Herpetic Neuralgia (PHN) [4,11]

Definition: Dermatomal pain persisting > 90 days after rash onset (some define as > 3 months; others > 6 months)

Incidence:

• 10-15% overall
• 20% in age > 50
• 30-50% in age > 80

Pathophysiology:

• Viral-induced neuronal destruction → aberrant nerve regeneration
• Central sensitization → neuropathic pain
• Deafferentation pain (loss of sensory input)

Clinical Features:

• Pain types: Constant burning, lancinating/stabbing, allodynia (pain from light touch)
• Location: Follows original zoster dermatome
• Duration: Can last months to years (20-30% have pain > 1 year)
• Impact: Severe functional impairment; depression; suicidal ideation

Management:

First-Line:

• Gabapentin: Start 300mg OD → titrate to 1800-3600mg/day (in divided doses)
• Pregabalin: Start 75mg BD → titrate to 300mg BD (max 600mg/day)
• Tricyclic Antidepressants: Amitriptyline 10mg ON → titrate to 75mg ON (or nortriptyline if sedation problematic)

Second-Line:

• Topical Lidocaine 5% patches: Apply to affected area for 12 hours/day (evidence for localized PHN)
• Capsaicin 8% patches: Single application for 30-60 minutes (specialist application); depletes substance P
• Duloxetine: 60mg OD (SNRI; alternative to TCAs)

Third-Line (Specialist Pain Clinic):

• Opioids: Tramadol, morphine, oxycodone (short-term; high side-effect burden in elderly)
• Nerve blocks: Epidural, paravertebral, stellate ganglion (temporary relief)
• Spinal cord stimulation: Refractory cases

Prevention:

• Early antiviral therapy (less than 72h) reduces PHN risk by 20-30%
• Shingles vaccination (Shingrix) reduces PHN incidence by > 90% in vaccinated individuals who develop zoster

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2. Herpes Zoster Ophthalmicus (HZO) Complications [6,7]

• Keratitis: Punctate epithelial → dendritic → stromal (can cause corneal scarring/blindness)
• Uveitis: Anterior (30-40%); posterior (5-10%) with vasculitis/retinitis
• Acute Retinal Necrosis (ARN): Rapidly progressive necrotising retinitis → retinal detachment → blindness (rare less than 1%)
• Optic Neuropathy: Ischaemic or inflammatory (rare)
• Chronic/Recurrent Disease: 25% develop chronic or recurrent ocular inflammation

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3. Neurological Complications

• VZV Vasculopathy: Granulomatous arteritis → ischaemic or haemorrhagic stroke (weeks to months post-zoster)
• Myelitis: Transverse myelitis (motor/sensory deficits below lesion level)
• Meningoencephalitis: Altered consciousness, seizures, focal neurology
• Guillain-Barré Syndrome: Rare post-infectious complication
• Motor Neuropathy: Zoster paresis (weakness in affected myotome; e.g., arm weakness with cervical zoster)

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4. Disseminated Zoster

• Definition: > 20 lesions outside primary dermatome OR multidermatomal involvement
• Populations: HIV (CD4 less than 200), haematological malignancy, transplant, high-dose immunosuppression
• Complications: Visceral dissemination (hepatitis, pneumonitis, encephalitis), DIC
• Management: IV aciclovir; investigate underlying immunodeficiency

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10. Prognosis and Prevention

Prognosis

Varicella (Chickenpox)

• Healthy children: Self-limiting; full recovery in 10-14 days
• Adults: Higher complication rate (25x pneumonitis risk); longer recovery
• Immunocompromised: Prolonged viraemia; risk of disseminated disease and death (mortality 7-17% if untreated)
• Pregnancy: Maternal pneumonitis mortality 3-14%; fetal varicella syndrome 0.4-2% if less than 20 weeks

Herpes Zoster (Shingles)

• Uncomplicated zoster: Pain resolves within 3 months in 50-75% (higher in younger patients)
• Post-Herpetic Neuralgia: Major determinant of long-term morbidity (see above)
• Ramsay Hunt: Permanent facial palsy in 50-70%
• Ophthalmic Zoster: Chronic ocular disease in 25%

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Prevention

1. Varicella Vaccination (Primary Prevention)

Live Attenuated Varicella Vaccine (Oka/Merck Strain)

Schedule:

• USA/Australia: Routine childhood immunisation (2 doses: 12-15 months, 4-6 years)
• UK: Selective use (healthcare workers, close contacts of immunocompromised, seronegative individuals)

Efficacy:

• Protection against varicella: 85-90% (any disease); 95-100% (severe disease)
• Herd immunity: Reduces circulation in community

Contraindications:

• Immunocompromised (except HIV with CD4 > 200 and stable disease)
• Pregnancy
• Severe immunosuppression (chemotherapy, high-dose steroids)

Post-Vaccination Zoster Risk:

• Lower than wild-type VZV (vaccine strain less likely to reactivate)

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2. Shingles Vaccination (Preventing Reactivation)

Two vaccines available:

A. Shingrix (Recombinant Zoster Vaccine - RZV) [15]

Composition: Recombinant VZV glycoprotein E + AS01B adjuvant (non-live)

Schedule: 2 doses IM (deltoid), 2-6 months apart

Efficacy (Pivotal Trials: ZOE-50, ZOE-70):

• Prevention of HZ: > 90% efficacy (age 50-69); > 90% (age ≥70)
• Prevention of PHN: > 90% efficacy
• Duration: Sustained > 7 years (ongoing studies)

Indications:

• ≥50 years (USA, Australia, Europe)
• ≥60 years (UK NHS - free on NHS from September 2023)
• Immunocompromised (≥18 years): HIV, transplant, autoimmune on biologics (safe - non-live)

Advantages:

• Non-live → safe in immunocompromised
• Superior efficacy to Zostavax
• Sustained protection

Adverse Effects:

• Local reactions (80-90%): pain, redness, swelling at injection site
• Systemic: Myalgia, fatigue, headache, fever (common but transient)

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B. Zostavax (Live Attenuated Zoster Vaccine - ZVL) (Being Phased Out)

Composition: Live attenuated VZV (Oka strain, 14x higher titre than varicella vaccine)

Schedule: Single dose SC

Efficacy:

• Prevention of HZ: 51% (age 60-69); 38% (≥70) - waning over 5 years
• Prevention of PHN: 67%

Contraindications: Immunocompromised (live vaccine)

Replaced by Shingrix in most countries (superior efficacy, non-live)

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Vaccine Recommendations (UK - JCVI Guidance 2023)

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Can You Vaccinate After Having Shingles?

Yes - but wait ≥12 months after acute episode. Shingrix can prevent recurrent zoster.

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11. Key Guidelines and Evidence

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12. Examination Focus

Common Exam Scenarios (MRCP/MRCPCH/GP)

1. "38-year-old pregnant woman (28 weeks) exposed to chickenpox. She is unsure if she had chickenpox as a child. What is your immediate management?"

Model Answer: "This is a potentially serious scenario. I would:

1. Urgent VZV IgG serology to determine immune status
2. If IgG-negative (non-immune): Administer VZIG (Varicella Zoster Immunoglobulin) within 96 hours of exposure (ideally; up to 10 days)
3. Counsel regarding risk of varicella pneumonitis (10-20% in pregnancy) - advise urgent review if develops respiratory symptoms
4. If develops varicella: Low threshold for IV aciclovir (10mg/kg TDS) given high pneumonitis risk in third trimester
5. Fetal surveillance: Ultrasound at 5 weeks and 20 weeks post-infection (though risk of fetal varicella syndrome less than 0.5% in third trimester)
6. Inform neonatology if develops varicella near delivery (neonate may require VZIG/monitoring)"

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2. "72-year-old with unilateral vesicular rash on left forehead extending to the tip of the nose. What is your diagnosis and immediate action?"

Model Answer: "This is Herpes Zoster Ophthalmicus with Hutchinson's sign.

• Hutchinson's sign (vesicles on nasal tip) indicates nasociliary nerve involvement (branch of ophthalmic V1) and predicts ocular involvement in 76% of cases.
• Immediate action:
  1. Urgent ophthalmology referral (same-day or next-day)
  2. Start oral aciclovir 800mg five times daily for 7-10 days immediately (do not wait for ophthalmology review)
  3. Examine eyes for conjunctivitis, keratitis (fluorescein staining), uveitis (anterior chamber cells, photophobia)
  4. Warn patient of risk of vision loss if untreated
  5. Adequate analgesia (neuropathic agents: gabapentin/pregabalin)
• Ophthalmology will assess for keratitis, uveitis, and may start topical steroids (contraindicated without ophthalmology input due to risk of worsening dendritic ulcers)."

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3. "5-year-old with chickenpox for 3 days, now developing severe pain and rapidly spreading erythema around one lesion on the leg. What is the concern?"

Model Answer: "I am concerned about secondary bacterial superinfection, specifically Group A Streptococcal cellulitis or necrotising fasciitis.

• Varicella lesions breach skin barrier → entry point for bacteria (GAS, S. aureus)
• Necrotising fasciitis is rare but life-threatening; presents with severe pain disproportionate to appearance, rapidly spreading erythema, systemic toxicity
• Management:
  1. Urgent assessment: Vital signs (tachycardia, fever, hypotension suggest sepsis)
  2. Blood tests: FBC (WCC), CRP, blood cultures, lactate
  3. IV antibiotics immediately (do not wait for microbiology): Flucloxacillin 50mg/kg QDS + Clindamycin 10mg/kg TDS (clindamycin inhibits toxin production)
  4. Urgent surgical review if suspected necrotising fasciitis (requires surgical debridement)
  5. Admit for IV antibiotics and monitoring"

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4. "60-year-old with left-sided facial weakness, ear pain, and vesicles in the ear canal. Diagnosis and management?"

Model Answer: "This is Ramsay Hunt Syndrome (Herpes Zoster Oticus) - VZV reactivation in the geniculate ganglion of the facial nerve.

• Classic triad: (1) LMN facial palsy, (2) ear pain, (3) vesicles in external auditory canal/concha
• May also have hearing loss, vertigo, loss of taste (anterior 2/3 tongue)
• Prognosis worse than Bell's palsy (complete recovery only 21% vs 71%)
• Management:
  1. Oral aciclovir 800mg 5x/day for 7 days (or valaciclovir 1g TDS) - start within 72 hours
  2. Oral prednisolone 60mg OD for 7 days, then taper (controversial but commonly used)
  3. Eye protection (if incomplete eye closure): artificial tears, lacri-lube ointment at night, tape eye shut at night
  4. ENT referral: Audiometry, vestibular testing, facial nerve grading (House-Brackmann)
  5. Analgesia: Neuropathic agents (gabapentin/pregabalin) + simple analgesia
• Counsel regarding prognosis (50-70% residual facial weakness)"

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Viva Points (High-Yield Facts)

VZV Epidemiology:

• R₀ of 10-12 (one of most contagious viruses - comparable to measles)
• Lifetime zoster risk 30% (increases to 50% if live to 85)
• Post-herpetic neuralgia affects 20% of zoster patients > 50 years

Pathophysiology:

• VZV establishes latency in dorsal root ganglia and cranial nerve ganglia (not peripheral nerves)
• During latency: minimal viral gene transcription (ORF63, VLT transcripts only)
• Reactivation triggered by decline in VZV-specific cell-mediated immunity (age, immunosuppression)

Clinical Diagnosis:

• Varicella: Polymorphic rash (all stages present) in crops; centripetal distribution
• Zoster: Unilateral dermatomal rash; does not cross midline (unless disseminated)

Management Pearls:

• AVOID NSAIDs in chickenpox (risk of necrotising fasciitis)
• AVOID aspirin in children (risk of Reye's syndrome)
• Oral antivirals (aciclovir 800mg 5x/day) reduce zoster pain and PHN risk if started less than 72h
• Hutchinson's sign = ophthalmology emergency (76% develop ocular complications)

Vaccination:

• Shingrix (recombinant VZV gE + adjuvant): > 90% efficacy preventing zoster and PHN; non-live (safe in immunocompromised)
• Zostavax (live attenuated): 50% efficacy; being replaced by Shingrix

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Common Mistakes in Exams

❌ Mistake 1: Treating uncomplicated chickenpox in healthy children with aciclovir ✅ Correct: Supportive care only; antivirals not indicated (marginal benefit, self-limiting disease)

❌ Mistake 2: Prescribing ibuprofen for fever in chickenpox ✅ Correct: Paracetamol only (ibuprofen linked to necrotising fasciitis)

❌ Mistake 3: Failing to recognize Hutchinson's sign → delayed ophthalmology referral ✅ Correct: Vesicles on nasal tip = urgent same-day ophthalmology review (risk of blindness)

❌ Mistake 4: Giving VZIG to pregnant woman with positive VZV IgG ✅ Correct: VZIG only for IgG-negative (non-immune) pregnant women

❌ Mistake 5: Not starting antivirals in Ramsay Hunt beyond 72 hours ✅ Correct: Still treat if diagnosed late (facial nerve outcomes better with treatment even if delayed)

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13. Patient and Layperson Explanation

What is the difference between Chickenpox and Shingles?

They are caused by the same virus (Varicella Zoster Virus). When you catch it for the first time (usually as a child), you get chickenpox - lots of itchy blisters all over your body. After you recover, the virus doesn't leave your body completely. It "goes to sleep" in the nerves near your spine and remains there for decades.

Later in life (often when you're older or your immune system is weaker), the virus can "wake up" and travel down a nerve to the skin, causing shingles - a painful rash in a band or stripe on one side of your body.

Can I catch shingles from someone?

No, you cannot catch shingles from someone else. Shingles is the virus reactivating from inside your own body. However, if you have never had chickenpox, you can catch chickenpox from someone with shingles if you touch their blisters (not from the air). Once the blisters are crusted over, shingles is no longer contagious.

How do I manage chickenpox at home?

• Keep cool: Heat makes itching worse. Use cool baths or wet flannels.
• Cut fingernails short: Prevent scratching (scratching can cause scarring and infection).
• Calamine lotion: Soothing for itchy skin.
• Paracetamol for fever: Do NOT use ibuprofen (Nurofen) in chickenpox - it can increase the risk of serious skin infections.
• Avoid school/nursery: Until all blisters have crusted over (usually about 5 days).
• Stay away from: Pregnant women, newborn babies, and anyone with a weak immune system.

What is Post-Herpetic Neuralgia (PHN)?

This is nerve pain that continues long after the shingles rash has healed (usually defined as pain lasting more than 3 months). It happens because the virus damaged the nerves. The pain can feel like:

• Constant burning or aching
• Sharp, stabbing pains
• Extreme sensitivity to touch (even light clothing can hurt)

PHN is more common in older people and can last months or even years. Medications like gabapentin or amitriptyline help calm the nerves and reduce pain.

Should I get the shingles vaccine?

If you are over 60 (or over 50 if you have a weak immune system), the Shingrix vaccine is recommended. It is very effective (> 90% protection) at preventing shingles and post-herpetic neuralgia. It is not a live vaccine, so it is safe even if your immune system is weak. You need two doses, 2-6 months apart.

Even if you've had shingles before, you can still benefit from the vaccine (wait 12 months after your shingles episode before getting vaccinated).

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14. References

1. Gershon AA, Breuer J, Cohen JI, et al. Varicella zoster virus infection. Nat Rev Dis Primers. 2015;1:15016. doi:10.1038/nrdp.2015.16

2. Patil A, Goldust M, Wollina U. Herpes zoster: A Review of Clinical Manifestations and Management. Viruses. 2022;14(2):192. doi:10.3390/v14020192

3. Kennedy PGE, Mogensen TH, Cohrs RJ. Recent Issues in Varicella-Zoster Virus Latency. Viruses. 2021;13(10):2018. doi:10.3390/v13102018

4. Cohen JI. Herpes Zoster. N Engl J Med. 2013;369(3):255-263. doi:10.1056/NEJMcp1302674

5. Arvin AM. Varicella-zoster virus. Clin Microbiol Rev. 1996;9(3):361-381. doi:10.1128/CMR.9.3.361

6. Litt J, Cunningham AL, Arnalich-Montiel F, Parikh R. Herpes Zoster Ophthalmicus: Presentation, Complications, Treatment, and Prevention. Infect Dis Ther. 2024;13(7):1439-1459. doi:10.1007/s40121-024-00990-7

7. Yawn BP, Wollan PC, Kurland MJ, et al. Herpes zoster eye complications: rates and trends. Mayo Clin Proc. 2013;88(6):562-570. doi:10.1016/j.mayocp.2013.03.014

8. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. 2001;71(2):149-154. doi:10.1136/jnnp.71.2.149

9. Royal College of Obstetricians and Gynaecologists. Chickenpox in Pregnancy (Green-top Guideline No. 13). London: RCOG; 2015.

10. Brisson M, Edmunds WJ, Law B, et al. Epidemiology of varicella zoster virus infection in Canada and the United Kingdom. Epidemiol Infect. 2001;127(2):305-314. doi:10.1017/s0950268801005921

11. Johnson RW, Rice ASC. Clinical practice: Postherpetic neuralgia. N Engl J Med. 2014;371(16):1526-1533. doi:10.1056/NEJMcp1403062

12. Nagel MA, Gilden D. Complications of varicella zoster virus reactivation. Curr Treat Options Neurol. 2013;15(4):439-453. doi:10.1007/s11940-013-0246-5

13. Souyris C, Léauté-Labrèze C, Chauvel A, et al. Severe necrotizing soft-tissue infections and nonsteroidal anti-inflammatory drugs. Clin Exp Dermatol. 2008;33(3):249-255. doi:10.1111/j.1365-2230.2007.02652.x

14. Chen N, Li Q, Yang J, et al. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev. 2014;(2):CD006866. doi:10.1002/14651858.CD006866.pub3

15. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep. 2018;67(3):103-108. doi:10.15585/mmwr.mm6703a5

16. National Institute for Health and Care Excellence. Shingles. Clinical Knowledge Summary. NICE; 2023. https://cks.nice.org.uk/topics/shingles/

17. Sauerbrei A. Diagnosis, antiviral therapy, and prophylaxis of varicella-zoster virus infections. Eur J Clin Microbiol Infect Dis. 2016;35(5):723-734. doi:10.1007/s10096-016-2605-0

18. National Institute for Health and Care Excellence. Neuropathic pain in adults: pharmacological management in non-specialist settings (NG193). NICE; 2020. https://www.nice.org.uk/guidance/ng193

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current local/national guidelines.