Varicella & Herpes Zoster (Chickenpox and Shingles)

Meet the patient

A 68-year-old woman arrives with three days of burning pain across the right side of her forehead and scalp, and this morning a cluster of tender vesicles appeared in the same band. She also has a single vesicle on the tip of her nose.[1]

Two questions decide the next hour, and they decide every zoster case: does that vesicle on the nose mean the cornea is at risk? and are we inside the 72-hour window where an antiviral still earns its keep? The nose vesicle is the Hutchinson sign, and it is the one bedside finding that turns a dermatomal rash into an ophthalmology emergency.[1][4]

Overview & Definition

Varicella-zoster virus (VZV) — formally human herpesvirus 3 (HHV-3) — is a neurotropic, enveloped, double-stranded DNA alpha-herpesvirus that, like its cousins HSV-1 and HSV-2, establishes lifelong latency in sensory ganglia after primary infection. It produces two clinically distinct diseases in the same host:[1][2]

1. Varicella (chickenpox) — the primary infection: a generalised, pruritic vesicular exanthem appearing in successive crops at different stages simultaneously (macules, papules, vesicles, pustules and crusts all present together), accompanied by fever and malaise. It is the archetypal childhood exanthem, spread by respiratory droplets and direct contact with vesicle fluid.
2. Herpes zoster (shingles) — reactivation of latent VZV: a painful, unilateral, dermatomal vesicular eruption (the rash does not cross the midline), preceded by prodromal pain in the same dermatome that is frequently misdiagnosed as cardiac, biliary, renal or musculoskeletal pain. [1]

The clinical skill in this disease is threefold: (a) recognising the generalised crops-of-different-stages pattern of varicella and distinguishing it from smallpox and other vesicular illnesses; (b) recognising the dermatomal, unilateral pattern of zoster — and specifically identifying ophthalmic zoster (Hutchinson sign) and Ramsay Hunt syndrome; and (c) treating early (within 72 hours) with antivirals to reduce severity and prevent postherpetic neuralgia, while escalating to IV aciclovir for severe, ophthalmic, disseminated, immunocompromised, pregnant and neonatal disease. Varicella in adults, pregnant women, smokers and the immunocompromised is far more severe than the childhood illness and carries a significant risk of life-threatening viral pneumonitis.[1][4]

Vaccination has transformed the epidemiology: live-attenuated varicella vaccine in childhood and the recombinant zoster vaccine (RZV, Shingrix) in older adults (over 90% efficacy) now prevent much of the disease burden — but VZV remains globally endemic, and a clinician must master both ends of the natural history.[2]

Classification

VZV disease is classified by phase of the viral life-cycle (primary vs reactivation), by anatomical distribution of zoster, and by severity/complication status. [1]

By phase of infection: [1]

• Primary infection (varicella / chickenpox) — generalised, occurs in non-immune hosts (usually children); confers lifelong immunity to varicella but not to reactivation.
• Reactivation (herpes zoster / shingles) — dermatomal, occurs in previously infected hosts when VZV-specific cell-mediated immunity (CMI) wanes (age, immunosuppression). A single episode of zoster does not give absolute immunity — recurrent zoster occurs in about 6%, and strongly suggests underlying immunodeficiency or malignancy. [1]

By anatomical distribution of zoster (an exam favourite):[1]

By severity / complication status: [1]

• Uncomplicated zoster — single dermatome, immunocompetent host.
• Complicated — ophthalmic zoster, Ramsay Hunt, disseminated, motor neuropathy/segmental paresis, CNS involvement (meningitis, encephalitis, myelitis), VZV vasculopathy/stroke, postherpetic neuralgia. [1]

Epidemiology & Risk Factors

Varicella is globally endemic with a strong winter-spring seasonality in temperate climates. In unvaccinated populations it is a disease of early childhood — over 90% of people acquire it before adolescence in endemic regions — but the age of infection shifts upward where universal childhood vaccination has reduced transmission (older children/adults get milder exposure but more severe primary disease). It is highly contagious: secondary attack rates of over 90% in susceptible household contacts. Transmission is by respiratory droplets, aerosols from vesicles, and direct contact with vesicle fluid.[2]

Incubation period: 10–21 days (mean 14–16 days). A patient is contagious from 1–2 days BEFORE the rash appears until all lesions have crusted (typically 5–7 days after rash onset). [1]

Herpes zoster cannot be acquired by exposure to another person with zoster (it is reactivation of endogenous latent virus) — but a person with zoster can cause primary varicella in a non-immune contact (vesicle fluid is infectious). The lifetime risk of zoster is about 1 in 3, rising to about 1 in 2 in those who live to age 85; incidence rises sharply with age. Recurrent zoster occurs in about 6% and should prompt a search for immunosuppression.[1]

Risk factors for herpes zoster (reactivation):[1]

Risk factors for severe/complicated varicella (the patients who need IV aciclovir, not paracetamol):[4]

• Adulthood (over 15) — the risk of varicella pneumonia rises sharply with age.
• Pregnancy (especially second and third trimester) — varicella pneumonia is particularly severe, with historically high maternal mortality before antivirals.
• Smoking — strongly predisposes to varicella pneumonia.
• Immunocompromise — dissemination, visceral and chronic disease.
• Chronic lung disease, neurological disease (aspiration risk).
• Neonatal infection (peripartum). [1]

Pathophysiology

VZV is a neurotropic alpha-herpesvirus: its defining biological signature is the capacity to invade sensory nerves, establish lifelong non-productive latency in sensory ganglia, and reactivate along a dermatome. The natural history unfolds in two mechanistically distinct phases.[2][3]

Phase 1 — Primary infection (varicella): [1]

1. Portal of entry — VZV is inhaled in respiratory droplets or contacts the conjunctiva. It first replicates in the mucosa of the nasopharynx and oropharynx and in regional lymphoid tissue.
2. Primary viraemia (4–6 days) — virus spreads to reticuloendothelial organs (liver, spleen), where it replicates further.
3. Secondary viraemia — infected T-lymphocytes carry virus to the skin and mucosa. The characteristic rash appears.
4. Cutaneous lesion evolution — the virus replicates in capillary endothelial cells and keratinocytes, producing ballooning degeneration of epithelial cells → intercellular oedema → intraepidermal vesicle. The lesion passes through macule → papule → vesicle → pustule → crust. Because the viraemia seeds the skin in waves, successive crops of lesions at different stages appear simultaneously — the pathognomonic feature of varicella (and the key distinction from smallpox, where all lesions are at the same stage).
5. Centripetal distribution — the rash is denser on the trunk than the extremities, and also involves the face, scalp and mucous membranes (oral, sometimes vaginal/conjunctival).
6. Retrograde axonal transport to ganglia — during viraemia, VZV travels retrograde up sensory nerves to the dorsal root and cranial-nerve ganglia (especially trigeminal and thoracic dorsal root ganglia), where it establishes lifelong latent infection in the neuronal nuclei. The virus persists as episomal DNA with very limited gene expression. [1]

Resolution of primary infection is mediated by VZV-specific cell-mediated immunity (CMI) — CD4+ and CD8+ T cells and NK cells clear the virus from skin. Antibody (IgG) prevents reinfection with varicella but does not prevent reactivation — that requires intact CMI, which wanes with age and immunosuppression.[2]

Phase 2 — Reactivation (herpes zoster): [1]

1. Loss of containment — when VZV-specific CMI falls below a threshold (the dominant driver is age; also immunosuppression, malignancy, HIV, chemotherapy, biologic/steroid therapy), latent virus in a single sensory ganglion re-activates and begins to replicate.
2. Ganglionitis and neuritis — replication causes inflammatory destruction of neurons and supporting cells within the ganglion and along the nerve, producing the characteristic prodromal pain (burning, aching, lancinating) in the dermatome — days to a week before the rash appears. This pain is frequently misattributed to myocardial ischaemia, cholecystitis, renal colic, appendicitis or disc disease.
3. Anterograde spread to skin — virus travels down the sensory nerve (anterograde axonal transport) to the dermatome it supplies, producing the unilateral, dermatomal vesicular eruption that does not cross the midline. The vesicles follow the same morphology as varicella but are confined to the affected dermatome.
4. Why unilateral and dermatomal? Because reactivation originates from a single ganglion and travels along the sensory nerve supplying one dermatome on one side. (Rare bilateral or multidermatomal involvement implies profound immunosuppression.)
5. Resolution — the rash crusts and heals over 2–4 weeks; the ganglion/neuritis may persist as postherpetic neuralgia. [1]

Mechanism of postherpetic neuralgia (PHN): PHN results from a combination of peripheral sensitisation (reduced threshold of damaged nociceptors), central sensitisation (dorsal horn neuronal hyperexcitability from sustained C-fibre input), deafferentation (loss of primary afferent neurons, producing spontaneous ectopic firing), and anatomical destruction of the ganglion and nerve. These changes produce the allodynia, hyperalgesia and spontaneous burning/lancinating pain that define PHN and that are so difficult to treat.[4][5]

Mechanism of varicella pneumonia: VZV reaches the lung haematogenously during secondary viraemia, infecting alveolar epithelium and capillary endothelium, producing interstitial pneumonitis with mononuclear infiltrate, hyaline-membrane formation, and focal necrosis. Smokers, adults, pregnant women and the immunocompromised have an exaggerated inflammatory response and reduced clearance, explaining their disproportionate severity.[4]

Mechanism of VZV CNS disease and vasculopathy: VZV can spread to the CNS along trigeminal and other sensory afferents, producing meningitis, encephalitis, cerebellitis and myelitis. After ophthalmic zoster, VZV may spread along the trigeminal nerve to the cerebral arteries, producing a granulomatous arteritis (VZV vasculopathy) and ischaemic stroke — classically a contralateral hemiplegia weeks to months after ophthalmic zoster.[3]

Clinical Presentation

Varicella (chickenpox)

• Prodrome (1–2 days): fever, malaise, headache, anorexia, sometimes mild abdominal pain — most pronounced in adults.
• Rash — the hallmark: a generalised, pruritic vesicular exanthem.
  • Evolution: macule → papule → vesicle ("dewdrop on a rose petal") → pustule → crust.
  • Crops at different stages simultaneously — the cardinal feature (pathognomonic for varicella; distinguishes it from smallpox).
  • Distribution: centripetal — denser on the trunk than the limbs; also scalp, face; mucous membranes (palate, occasionally conjunctiva/vulva).
  • Pruritus is intense — scratching drives secondary bacterial infection (the commonest complication).
  • Lesions crust over 5–7 days; the patient is contagious until all lesions are crusted.
• Lymphadenopathy may be present.
• Atypical / severe presentations:
  • Adults, pregnant women, smokers, immunocompromised — higher fever, more profuse rash, significant risk of varicella pneumonia (cough, dyspnoea, hypoxia, haemoptysis), hepatitis, encephalitis.
  • Immunocompromised — progressive, chronic, or haemorrhagic lesions; visceral dissemination.
  • Neonate (maternal varicella around delivery) — severe, disseminated, high mortality without VZIG + aciclovir.
  • Breakthrough varicella in vaccinated children — milder, fewer lesions, often maculopapular rather than vesicular, still contagious but less so. [1]

Herpes zoster (shingles)

• Prodrome (days to ~1 week before rash): pain, burning, paraesthesia or hyperaesthesia in a single dermatome — unilateral, often severe; commonly misattributed to cardiac, biliary, renal, musculoskeletal or dental disease. Fever, malaise and headache may accompany.
• Rash:
  • Unilateral, dermatomal, vesicular, does not cross the midline.
  • Evolves erythematous patch/macule → grouped papules → clustered vesicles → pustules → crusts over 7–10 days.
  • All lesions in the affected dermatome are at roughly the same stage (in contrast to varicella's crops of different stages).
  • May involve adjacent dermatomes (1–2) but rarely widespread in the immunocompetent.
  • May leave post-inflammatory hyperpigmentation and scarring.
• Acute pain (acute neuritis / herpetic neuralgia): present during the rash; may be severe.
• Regional lymphadenopathy is common. [1]

Specific clinical syndromes (exam-critical)

• Ophthalmic zoster (V1): zoster of the ophthalmic division of the trigeminal nerve (forehead, upper eyelid, periorbital). The Hutchinson sign — a vesicle on the tip or side of the nose (inervated by the nasociliary nerve, a branch of V1 that also supplies the cornea) — is a powerful predictor of ocular involvement. Ocular complications include episcleritis, scleritis, keratitis (punctate, dendritic, disciform, neurotrophic), uveitis, glaucoma, optic neuritis, and acute retinal necrosis. Any ophthalmic involvement is an ophthalmology emergency.[1]
• Ramsay Hunt syndrome (herpes zoster oticus): VZV reactivation in the geniculate ganglion of the facial nerve (CN VII). The triad is (1) vesicles in the ear / external auditory canal / concha / palate, (2) lower motor neuron (LMN) facial palsy (ipsilateral), and (3) vestibulocochlear symptoms — sensorineural hearing loss, tinnitus, vertigo. The facial palsy is often complete and recovers less well than Bell palsy. Treatment is antiviral + corticosteroid.[1]
• Disseminated zoster: defined as more than 20 vesicles outside the primary dermatome, or involvement of 3 or more non-contiguous dermatomes. Implies immunosuppression — search for HIV, malignancy, immunosuppressive therapy. Manage with IV aciclovir and isolation.
• Zoster sine herpete: dermatomal pain without a rash — a difficult diagnosis confirmed by VZV PCR of blood/CSF; consider in otherwise unexplained segmental radicular pain.
• Motor zoster: segmental motor weakness in the myotome corresponding to the affected dermatome (e.g. limb paresis with thoracic zoster, or diaphragmatic paralysis with cervical zoster) — occurs in ~1–5%.
• Sacral zoster: may cause urinary retention (sacral autonomic involvement).

Differential Diagnosis

Differential of a generalised vesicular rash

[1]

Key exam rule — varicella vs smallpox: in varicella the lesions are in crops at different stages simultaneously (papules, vesicles, pustules, crusts together) and are centripetal; in smallpox all lesions are at the same stage, progress synchronously, and are centrifugal (denser on face and extremities). The febrile prodrome precedes the smallpox rash but accompanies varicella. [1]

Differential of a dermatomal painful/vesicular eruption

Clinical & Bedside Assessment

• Inspect the rash: distribution (generalised/centripetal vs unilateral/dermatomal), stage of individual lesions, presence of crops at different stages (varicella) vs same-stage lesions in one dermatome (zoster), and whether the eruption crosses the midline (zoster does not).
• Examine mucous membranes (oral palate, conjunctiva, genital).
• Map the dermatome in zoster — thoracic (commonest, ~50%), trigeminal (V1 > V2 > V3, ~20%), cervical (~15%), lumbosacral (~10%).
• In suspected ophthalmic zoster, perform a focused eye examination:
  • Hutchinson sign — vesicles on tip/side of nose (nasociliary nerve → cornea at risk).
  • Visual acuity (each eye separately).
  • Fluorescein staining with cobalt-blue light for dendritic / punctate epithelial keratitis.
  • Slit-lamp for anterior chamber inflammation (uveitis), keratic precipitates.
  • Intraocular pressure (secondary glaucoma).
  • Red reflex / fundus (acute retinal necrosis, optic neuritis).
  • Any V1 involvement = urgent ophthalmology referral.
• Assess for complications:
  • Respiratory: rate, oxygen saturation — look for varicella pneumonia (cough, dyspnoea, hypoxia).
  • Neurological: GCS, meningism, cerebellar signs (ataxia in varicella children), LMN facial palsy / hearing (Ramsay Hunt), focal deficit (VZV vasculopathy/stroke), motor weakness (motor zoster).
  • Skin: secondary bacterial superinfection (expanding erythema, pus, necrotising fasciitis).
  • Bladder/bowel in sacral zoster (urinary retention).
• Assess immune status, pregnancy status, and immunosuppression — these drive the decision to use IV aciclovir and VZIG, and the need for isolation.
• Assess vaccination history (childhood varicella vaccine, recombinant zoster vaccine) and exposure history (household/school contacts, timing since exposure — relevant for VZIG). [1]

Investigations

Varicella and uncomplicated zoster are clinical diagnoses. Laboratory confirmation is needed only in selected situations.[1][2]

When to investigate:

• Atypical, severe or disseminated disease
• Immunocompromised host (atypical chronic/ulcerative lesions)
• Pregnant woman (confirmation influences management)
• Suspected smallpox / bioterrorism concern (urgent Public Health referral)
• CNS involvement (CSF analysis)
• Pneumonia / visceral disease [1]

Diagnostic methods (in order of yield): [1]

Investigations for severe / complicated disease: [1]

• CXR in varicella pneumonia: bilateral, diffuse reticulonodular / nodular infiltrates (peribronchial, lower-zone), which may calcify on resolution as tiny miliary densities. Hypoxaemia may be disproportionate to CXR.
• LFTs — hepatitis (transaminitis) in visceral varicella.
• CSF analysis for CNS involvement — lymphocytic pleocytosis, mildly raised protein, normal/mildly low glucose; CSF VZV PCR is diagnostic and more sensitive than antibody (the syndrome of VZV meningitis/encephalitis, cerebellitis and myelitis).
• FBC — thrombocytopenia in severe varicella; leukocytosis may indicate bacterial superinfection.
• Renal function before IV aciclovir (renal dosing; hydration to prevent crystalline nephropathy).
• HIV testing if dissemination, recurrent or unusual zoster in a young adult. [1]

[15] [7] [14] [10] [6]

Management — Resuscitation

Most varicella and zoster are managed in the community. Resuscitative intervention is reserved for the severe spectrum: varicella pneumonia, encephalitis, disseminated/visceral disease, and the immunocompromised or neonate.[4]

ABCDE:

• Airway/Breathing — oxygen to target SpO2 94–98% (or 88–92% in chronic CO2 retainers); escalate to high-flow nasal cannula / NIV / intubation for varicella pneumonitis with respiratory failure.
• Circulation — IV access, fluids for dehydration/sepsis; treat secondary bacterial sepsis (fluids, empirical antibiotics).
• Disability — GCS, glucose; treat seizures; lumbar puncture if meningoencephalitis suspected.
• Exposure — examine the whole skin, map the rash. [1]

Time-critical drug — IV aciclovir for: varicella pneumonia, varicella/encephalitis, disseminated zoster, immunocompromised hosts, ophthalmic zoster with ocular involvement, Ramsay Hunt, varicella in pregnancy with systemic involvement, and neonatal varicella.[4][6][8]

• Aciclovir 10 mg/kg IV every 8 hours (or 500 mg/m² per dose); for varicella pneumonitis the recommended course is 5–10 days, started within 24–72 hours of rash onset. Because VZV is less sensitive to aciclovir than HSV, these high doses are required; at these doses adequate hydration and urine flow must be maintained and impaired renal function requires the dosage to be regulated downward.[6][8]
• Start promptly — early recognition and treatment reduces acute symptoms and may also reduce postherpetic neuralgia. [18]

Isolation / infection control — the most-often-missed resuscitative measure:

• Varicella, disseminated zoster, or zoster in the immunocompromised: airborne + contact precautions in a negative-pressure room until all lesions crusted.
• Localised zoster in an immunocompetent host: contact precautions only, with lesions covered.
• Protect non-immune staff and patients — exclude pregnant/immunocompromised non-immune contacts; offer VZIG to high-risk susceptible contacts, ideally within 96 hours and up to 10 days after exposure. [9]

Management — Definitive & Stepwise

Varicella (chickenpox)

1. Uncomplicated childhood varicella — supportive care.[2][4]

• Hydration, rest, antipyresis with paracetamol.
  • AVOID aspirin in children with acute viral illness — Reye syndrome (hepatic encephalopathy).
  • Avoid NSAIDs (ibuprofen) in children with varicella — concern over increased risk of severe invasive group A streptococcal skin/soft-tissue infection (UK MHRA advice; some controversy, but caution is prudent).
• Antihistamine (e.g. chlorphenamine / cetirizine) and cool compresses / calamine for pruritus.
• Hygiene — keep nails short, daily bathing — to prevent secondary bacterial infection.
• Return to school/daycare only once all lesions are crusted (typically day 5–7). [1]

2. Oral antiviral therapy (selected cases). [6][8]

• Oral aciclovir 800 mg five times daily is the recommended oral dose for varicella-zoster virus disease: it is effective in varicella and zoster in immunocompromised patients, and also in otherwise normal patients — but there the effect is less dramatic and the drug must be given early.[6]
• Pregnant women with significant (e.g. pneumonitic) varicella — treat with oral acyclovir 800 mg five times daily; if varicella pneumonitis develops or progresses, admission to hospital should be seriously considered and intravenous acyclovir given (usually 10–15 mg/kg, or 500 mg/m², IV every 8 h for 5–10 days, started within 24–72 h of rash onset).[8]

3. IV aciclovir — high-risk / severe varicella. [6][8]

• IV aciclovir 10 mg/kg every 8 hours (or 500 mg/m² per dose) — intravenous aciclovir is effective for varicella in adults and immunocompromised children, producing more rapid resolution of the illness and fewer complications.[6]
• Severe varicella in pregnancy (pneumonitis) — IV aciclovir within 24–72 h of rash onset; maternal admission to hospital should be seriously considered.[8]
• Varicella may spread from 1–2 days before the rash until all lesions are crusted over — admit and isolate accordingly. [15]

Herpes zoster (shingles)

1. Antiviral therapy — the cornerstone (within 72 hours of rash onset).[1][4]

[12] [7]

• Antivirals given early (ideally within 72 hours of rash onset): early recognition and treatment can reduce acute symptoms and may also reduce postherpetic neuralgia; early antiviral use reduces pain across all stages of the disease.[18][7]
• Acyclovir, valacyclovir and famciclovir are first-line antiviral therapy for herpes zoster; treatments used in combination with antiviral therapy may further reduce pain and other complications.[4]
• Diagnosis is usually clinical — treatment need not await PCR confirmation when the rash has the characteristic appearance. [18]

2. IV aciclovir — severe/complicated zoster. [6][14]

• IV aciclovir 10 mg/kg every 8 hours (or 500 mg/m² per dose), with adequate hydration and urine flow maintained and the dose reduced when renal function is impaired.[6]
• Indications: immunocompromised hosts (intravenous aciclovir decreases new lesion formation, halts dissemination and lessens visceral complications in immunocompromised zoster), disseminated or visceral disease, zoster encephalitis, and severe disease.[6]
• Ophthalmic zoster — eye disease develops in approximately half of cases, and HZO is an ophthalmologic emergency because of the high risk of vision loss if not promptly recognised and treated: refer urgently.[14]

3. Pain management — stepwise (acute herpetic neuralgia and PHN).[4][5]

[19] [7]

• Acute zoster pain: pain management is an essential part of herpes zoster treatment; early use of antiviral medications reduces pain across all stages of the disease.[1]
• Postherpetic neuralgia (PHN): treatment focuses on symptom control — topical lidocaine or capsaicin and oral gabapentin, pregabalin, or a tricyclic antidepressant; tramadol and capsaicin creams and patches are second- or third-line therapies.[7][19]
• Add-on therapy: treatments used in combination with antiviral therapy may further reduce pain and other complications of herpes zoster.[4]

4. Secondary bacterial skin infection. [15]

• Bacterial skin infection is a recognised complication of varicella — treat promptly with antibiotics chosen by local policy and severity, and escalate quickly for rapidly spreading or necrotising soft-tissue infection. [15]

Infection control & return-to-work/school

• Varicella / disseminated zoster / immunocompromised localised zoster: airborne + contact isolation until all lesions crusted.
• Immunocompetent localised zoster: cover lesions, contact precautions until dry/crusted.
• Return to school/work: once all lesions crusted and dry. [1]

Specific Subtypes & Scenarios

Ophthalmic zoster (V1)

• Hutchinson sign — vesicle on tip/side of nose (nasociliary nerve, supplying cornea) — predicts ocular involvement.
• Ocular complications: punctate/dendritic/disciform/neurotrophic keratitis, uveitis, scleritis/episcleritis, secondary glaucoma, optic neuritis, acute retinal necrosis (vision-threatening).
• Management: systemic antiviral (oral valaciclovir 1 g TDS if no ocular signs; IV aciclovir if ocular involvement, immunocompromised, or severe); urgent ophthalmology referral; topical steroids only on ophthalmology instruction (never in active epithelial keratitis).[1]

Ramsay Hunt syndrome (herpes zoster oticus)

• VZV of the geniculate ganglion (CN VII).
• Triad: ear/concha/palate vesicles + LMN facial palsy + vestibulocochlear symptoms (sensorineural hearing loss, vertigo, tinnitus).
• Management: valaciclovir + high-dose prednisolone (started early) — best chance of facial-nerve recovery.
• Prognosis: facial recovery worse than Bell palsy — incomplete recovery in up to half; eye protection (lubrication, taping) to prevent exposure keratopathy.[1]

Disseminated zoster

• Definition: more than 20 vesicles outside the primary dermatome, or involvement of 3 or more non-contiguous dermatomes.
• Implication: immunosuppression — screen for HIV, malignancy, transplant, immunosuppressive/biologic therapy.
• Management: IV aciclovir, airborne + contact isolation, consider long-term suppression (oral aciclovir/valaciclovir) in recurrent disease.[1]

Varicella in pregnancy

• Varicella pneumonia in pregnancy is severe (historically high maternal mortality) — admit and treat with IV aciclovir; it is safe in pregnancy.
• Congenital varicella syndrome (CVS): risk if maternal primary varicella occurs in the first or early second trimester (up to ~20–28 weeks); highest risk at 13–20 weeks (~0.4–2%); features: limb hypoplasia, cutaneous scarring in a dermatomal distribution, eye abnormalities (chorioretinitis, cataract, microphthalmia), cortical atrophy, microcephaly, autonomic/psychomotor delay. Ultrasound for limb/eye/CNS anomalies; amniotic fluid VZV PCR after 17–21 weeks.
• Neonatal varicella: maternal varicella from 5 days before to 2 days after delivery — minimal maternal antibody transfer, severe neonatal disseminated disease (pneumonia, hepatitis, encephalitis, up to 30% mortality untreated). Management: VZIG to the neonate + IV aciclovir; isolate mother-neonate. Maternal varicella more than 5–7 days before delivery allows antibody transfer and is usually protective.[2]

Postherpetic neuralgia (PHN)

• Definition: pain persisting beyond 90 days (some use 120 days) after rash onset (after the acute zoster has healed).
• Risk factors: age over 50–60, severe acute rash, severe acute (prodromal) pain, ophthalmic site, immunocompromise, female sex.
• Mechanism: peripheral and central sensitisation, deafferentation, ganglion/nerve destruction.
• Prevention: antivirals within 72 h (reduces PHN risk), aggressive acute pain control, and recombinant zoster vaccine (primary prevention of zoster itself).
• Management: neuropathic pain ladder (TCA, gabapentinoid, topical lidocaine/capsaicin, opioids, pain clinic).[4][5]

Varicella / zoster in the immunocompromised

• Atypical: chronic, ulcerative, hyperkeratotic, or verrucous lesions; disseminated disease; visceral involvement (pneumonia, hepatitis, encephalitis, retinitis — progressive outer retinal necrosis in HIV/AIDS).
• Management: IV aciclovir (higher threshold, longer course); long-term suppression (oral aciclovir 400 mg BD–TDS, or valaciclovir/famciclovir) in HIV/AIDS with recurrent disease until immune reconstitution (CD4 over 200); isolation.
• Prevention: vaccinate (live varicella/zoster vaccine) before immunosuppression, when immunity is intact; avoid live vaccines when severely immunocompromised (CD4 under 200) — use recombinant zoster vaccine (non-live) in immunocompromised adults.[2]

Neurological complications

• Cerebellar ataxia — the commonest neurological complication of varicella in children; self-limiting over weeks.
• Encephalitis, transverse myelitis, aseptic meningitis, Guillain-Barré syndrome — rare but serious; CSF VZV PCR; IV aciclovir.
• VZV vasculopathy / stroke — granulomatous arteritis after ophthalmic zoster → contralateral hemiplegia weeks to months later; MRI/MRA/DSA; treat with IV aciclovir + corticosteroid; antiplatelet/anticoagulation per stroke pathway.[3]

Complications & Pitfalls

Complications of varicella:[2][4]

• Secondary bacterial skin infection — the commonest complication (group A streptococcus, S. aureus): cellulitis, impetigo, necrotising fasciitis, staphylococcal scalded skin.
• Varicella pneumonia — adults (especially smokers), pregnant, immunocompromised; cough, dyspnoea, hypoxia, haemoptysis; bilateral reticulonodular CXR, may leave miliary calcification.
• Neurological — cerebellar ataxia (children, self-limiting), encephalitis, transverse myelitis, aseptic meningitis, Reye syndrome (if aspirin given), Guillain-Barré.
• Hepatitis, thrombocytopenia, purpura fulminans/DIC, glomerulonephritis, arthritis, myocarditis.
• Congenital varicella syndrome and neonatal varicella (see above). [1]

Complications of herpes zoster:[1][4]

• Postherpetic neuralgia (PHN) — the commonest and most disabling complication, especially in the elderly; the leading cause of zoster-related morbidity and health-care expenditure.[5]
• Ophthalmic complications — keratitis, uveitis, scleritis, optic neuritis, acute retinal necrosis; potential blindness.
• Ramsay Hunt syndrome — facial palsy, hearing loss.
• Motor neuropathy / segmental zoster paresis (limb or diaphragmatic weakness in the affected myotome).
• Bacterial superinfection of the rash.
• Meningoencephalitis, myelitis, VZV vasculopathy/stroke (especially after ophthalmic zoster).
• Dissemination (immunocompromised).
• Postherpetic itch (rare, can be severe and refractory).

Classic pitfalls:

• Missing ophthalmic zoster — not checking for the Hutchinson sign (vesicle on the nose) and not referring to ophthalmology; corneal blindness is preventable.
• Giving aspirin to a child with varicella — Reye syndrome.
• Giving NSAIDs (ibuprofen) to a child with varicella — risk of severe group A streptococcal skin/soft-tissue infection (UK caution).
• Delaying antivirals beyond 72 hours in a patient who would have benefited (and not treating high-risk groups regardless of timing).
• Not using IV aciclovir for varicella pneumonia, disseminated/visceral, immunocompromised, ophthalmic, Ramsay Hunt, pregnant-pneumonia, neonatal disease.
• Failing to isolate — nosocomial varicella outbreak; not protecting pregnant/immunocompromised non-immune staff and patients.
• Missing dissemination in an apparently localised case — and not screening for HIV/malignancy in recurrent or disseminated zoster.
• Misdiagnosing pre-herpetic pain as myocardial ischaemia, cholecystitis, renal colic, appendicitis or disc disease — leading to inappropriate cardiac/biliary/abdominal workup before the rash appears.
• Treating the rash but not the pain — under-treating PHN, the most disabling sequela.
• Missing VZV vasculopathy — a stroke weeks after ophthalmic zoster.
• Not offering VZIG to high-risk susceptible contacts within the window (10 days; ideally 96 hours). [1]

Prognosis & Disposition

• Uncomplicated childhood varicella: excellent, self-limiting over 5–7 days; scarring uncommon unless secondarily infected.
• Adult / pregnant / immunocompromised varicella: significant morbidity and mortality from pneumonia/encephalitis — admit for IV aciclovir if any systemic involvement.
• Uncomplicated zoster (immunocompetent): rash heals over 2–4 weeks; risk of PHN rises sharply with age — up to 20–35% in those over 60; much lower (under 5%) under age 50.
• Disposition:
  • Community management: uncomplicated varicella in children; uncomplicated thoracic/cervical/lumbosacral zoster in immunocompetent adults under 50–60 with mild pain.
  • Admit: varicella pneumonia/encephalitis/disseminated, immunocompromised varicella/zoster, neonatal varicella, severe ophthalmic zoster, Ramsay Hunt with severe palsy, severe pain, social factors, pregnancy with varicella.
  • ICU: respiratory failure (varicella pneumonitis/ARDS), meningoencephalitis with coma, severe sepsis from secondary bacterial infection.
• Return to school/work: once all lesions crusted and dry (no new lesions for ~48 h).
• Ramsay Hunt facial recovery: incomplete in up to half; worse than Bell palsy.
• VZV vasculopathy/stroke: significant morbidity; outcome depends on prompt antiviral + stroke-pathway management. [1]

Special Populations

• Pregnancy — varicella in pregnancy demands awareness of the maternal and fetal sequelae: detailed ultrasound and appropriate follow-up to screen for fetal consequences, and for significant (e.g. pneumonitic) varicella, oral acyclovir 800 mg five times daily, escalating to IV acyclovir (10–15 mg/kg, or 500 mg/m², every 8 h for 5–10 days, within 24–72 h of rash onset) if pneumonitis develops or progresses.[8]
• Neonate — VZIG to the neonate whenever maternal varicella onset falls between 5 days before and 2 days after delivery; newborns in this window, premature infants and infants under 1 year are the recognised high-risk groups for post-exposure VZIG.[8][9]
• Immunocompromised (HIV, transplant, chemotherapy, biologics, high-dose steroids) — varicella and zoster can follow a serious course with permanent central nervous system damage; the recombinant adjuvanted glycoprotein E vaccine allows vaccination also in severely immunosuppressed patients — ACIP recommends 2 doses for immunodeficient or immunosuppressed adults 19 years and older.[2][11]
• Children — varicella is generally a mild, self-limiting illness; routine immunisation is recommended (live attenuated vaccine around the first year of age with a school-age booster, preventing about 70–90% of infections and 95% of severe disease).[2][15]
• Elderly — the highest burden of zoster and PHN (individual lifetime risk ~30%; PHN in about one in five patients); the recombinant zoster vaccine is approved for adults 50 years and older with 97% efficacy in ZOE-50.[7][10]
• Susceptible women and contacts — varicella immunisation is recommended for all non-immune women as part of pre-pregnancy and postpartum care; document antenatal immunity (previous infection, vaccination or IgG serology), and on exposure test serum — if negative or unavailable within 96 hours, give VZIG.[8]

Evidence, Guidelines & Regional Differences

Vaccines (the prevention that examiners reward):[2]

• Live-attenuated varicella vaccine (Oka strain): childhood primary prevention; 2-dose schedule (12–15 months and 4–6 years in the US ACIP schedule); ~90% efficacy against any varicella and over 95% against severe varicella; breakthrough varicella (in vaccinated children) is milder, with fewer (often maculopapular) lesions.
• Live attenuated zoster vaccine (Zostavax, high-dose Oka): the first-generation zoster vaccine; reduced zoster incidence by ~50–70% and PHN by ~67%; a single dose for adults over 60; efficacy waned over time. Now largely withdrawn from many markets in favour of recombinant zoster vaccine.
• Recombinant zoster vaccine (RZV, Shingrix): glycoprotein E antigen + AS01B adjuvant; 2-dose intramuscular schedule (0 and 2–6 months); over 90% efficacy against both herpes zoster and PHN in adults over 50 (ZOE-50), with sustained protection for at least a decade; efficacy remains high (over 85%) in adults over 70. Recommended by ACIP for all immunocompetent adults over 50 and for immunocompromised adults over 19 (non-live — safe in immunosuppression). Now the preferred zoster vaccine.[2]

Regional vaccine schedules: [1]

[17] [11] [9] [1] [1]

Post-exposure prophylaxis with VZIG (VARIZIG): [9]

• Indications: high-risk individuals exposed to varicella — immunocompromised children and adults, pregnant women, and infants (preterm infants, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and infants under 1 year).[9]
• Dose: 125 IU per 10 kg body weight, up to a maximum of 625 IU, intramuscularly.[9]
• Timing: ideally within 96 hours, but up to 10 days, after exposure; varicella outcomes were similar whether VARIZIG was given within or beyond 96 hours in the expanded-access programme.[9]
• Pregnant contacts with unknown immune status: test serum on exposure — if results are negative or unavailable within 96 hours, administer VZIG.[8]

Controversy — the exogenous boosting hypothesis: universal childhood varicella vaccination reduces circulating wild-type virus, removing the natural "boosting" of CMI in latently infected adults that is thought to suppress zoster reactivation. Mathematical models predicted a temporary rise in zoster incidence after introduction of universal childhood vaccination — a key historical argument against routine varicella vaccination (notably in the UK). Subsequent empirical data show the rise in zoster has been smaller and briefer than feared, and that the recombinant zoster vaccine now directly prevents zoster in older adults regardless — which has tipped policy toward universal childhood varicella vaccination plus zoster vaccination of older adults.[2]

Corticosteroids — evidence: a short course in acute zoster modestly improves acute pain and quality of life but does not prevent PHN; reserved for immunocompetent adults over 50 with moderate–severe acute zoster, with no contraindication. In Ramsay Hunt, high-dose steroids with antiviral give the best facial-nerve recovery. There is no role for topical or systemic corticosteroids in preventing PHN.[4]

Exam Pearls

• Hutchinson sign — skin lesions at the tip, side or root of the nose (nasociliary dermatomes) are a powerful predictor of ocular inflammation and corneal denervation in zoster ophthalmicus: urgent ophthalmology.[13]
• Herpes zoster ophthalmicus — reactivation in the ophthalmic division (V1); eye disease in approximately 50% of cases; an ophthalmologic emergency; 10–25% of all zoster cases.[14]
• Antiviral within 72 h of the zoster rash — acyclovir, valacyclovir or famciclovir, ideally within 72 hours of rash onset; early treatment reduces acute symptoms and may also reduce PHN.[7][18]
• PHN = dermatomal pain sustained for at least 90 days after acute zoster; occurs in about one in five patients; first-line tricyclics, gabapentin/pregabalin, lidocaine patches, then tramadol and capsaicin.[7][19]
• IV aciclovir 10 mg/kg every 8 hours (or 500 mg/m²) — high dose because VZV is less sensitive to acyclovir than HSV; maintain hydration and urine flow, and reduce the dose in renal impairment.[6]
• Recombinant zoster vaccine — 97% efficacy against herpes zoster in adults 50 and over (ZOE-50); two doses intramuscularly, 2 months apart.[10]
• VZIG: 125 IU per 10 kg, up to 625 IU IM — ideally within 96 hours and up to 10 days after exposure, for high-risk contacts.[9]
• Incubation 10–21 days (average about 2 weeks); contagious from 1–2 days before the rash until all lesions are crusted over.[15]
• Lifetime zoster risk is about 30% (roughly 1 in 3); conditions that decrease cell-mediated immunity make herpes zoster 20–100 times more likely.[7]
• PHN risk varies from 5% to more than 30% (age distribution and definition dependent); recurrent zoster risk 1–6%.[16]
• Zoster is usually unilateral and confined to a single dermatome, with vesicles that crust over in 7–10 days; prodromal abnormal skin sensations may precede the rash by 2–3 days.[7]
• Varicella is more severe in adults than in children; immunocompromised subjects risk permanent CNS damage.[15][2]
• VZV vasculitis is associated with morbidity and mortality — a recognised, treatable-in-principle complication of zoster.[1]

[1] [1]

Ward-round test — three stems, thirty seconds each

Stem 1 — the vesicle on the nose (answer)

The woman from the top of the topic: right-sided forehead pain, a dermatomal vesicular band, and a vesicle on the tip of her nose. What does the nose lesion mean, and what must happen today? Model: The nose vesicle is the Hutchinson sign — lesions at the tip, side and root of the nose map to the dermatomes of the external nasal and infratrochlear branches of the nasociliary nerve, and in acute zoster ophthalmicus they are a powerful predictor of ocular inflammation and corneal denervation (relative risks 3.35 and 4.02 respectively).[13] Eye disease develops in approximately half of HZO cases, and because of the high risk of vision loss if not promptly recognised and treated, HZO is an ophthalmologic emergency — urgent ophthalmology referral today.[14] Start an oral antiviral now: valacyclovir 1000 mg three times daily for 7 days, famciclovir 500 mg three times daily for 7 days, or acyclovir 800 mg five times daily — regimens with comparable ocular outcomes — and ideally within 72 hours of rash onset, since early treatment reduces acute symptoms and may also reduce postherpetic neuralgia.[12][7]

Stem 2 — the pregnant woman with chickenpox and a cough (answer)

A 30-year-old at 28 weeks' gestation develops a classic generalised vesicular rash in crops at different stages, and within 24 hours a dry cough and breathlessness; her oxygen saturation is 92 per cent. What is the dangerous complication, and what changes about her antiviral? Model: This is varicella pneumonitis — varicella is more severe in adults than in children, and pregnancy guideline management is explicit: for significant (e.g. pneumonitic) varicella infection, treat with oral acyclovir 800 mg five times daily; when varicella pneumonitis develops or progresses, maternal admission to hospital should be seriously considered and intravenous acyclovir given — usually 10–15 mg/kg (or 500 mg/m²) every 8 hours for 5–10 days, started within 24–72 hours of the onset of rash.[8] In immunocompromised subjects and adults, varicella can cause permanent damage of the central nervous system — admit, isolate and involve obstetrics early.[2]

Stem 3 — the rash that could be smallpox (answer)

A febrile, unwell patient has a widespread vesicular rash. You are asked at the bedside: how do you tell varicella from smallpox in the five seconds before you reach for the textbook? Model: Look at the stages and the distribution. In varicella the lesions are in crops at different stages simultaneously — papules, vesicles, pustules and crusts all sitting next to each other — and the rash is centripetal (denser on the trunk than the limbs); the fever accompanies the rash. In smallpox every lesion is at the same stage and progresses synchronously, and the rash is centrifugal (denser on the face and extremities), preceded by a severe febrile prodrome. Smallpox was eradicated in 1980, so a truly synchronous centrifugal vesicular rash with a high prodromal fever is a public-health emergency — isolate and notify immediately. For the everyday case, crops of different stages, centripetal, with the fever is varicella every time.[1][2]

References

1. [1]Patil A, Goldust M, Wollina U. Herpes zoster: A Review of Clinical Manifestations and Management Viruses, 2022.PMID 35215786
2. [2]Freer G, Pistello M. Varicella-zoster virus infection: natural history, clinical manifestations, immunity and current and future vaccination strategies New Microbiol, 2018.PMID 29498740
3. [3]Ogunjimi B, et al. Varicella zoster virus and the central nervous system Nat Rev Microbiol, 2026.PMID 41735628
4. [4]Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of herpes zoster Clin Infect Dis, 2007.PMID 17143845
5. [5]Dworkin RH, White R, O'Connor AB, et al. Health care expenditure burden of persisting herpes zoster pain Pain Med, 2008.PMID 18366512
6. [6]Huff JC. Antiviral treatment in chickenpox and herpes zoster J Am Acad Dermatol, 1988.PMID 3339143
7. [7]Saguil A, Kane S, Mercado M, Lauters R. Herpes Zoster and Postherpetic Neuralgia: Prevention and Management Am Fam Physician, 2017.PMID 29431387
8. [8]Shrim A, Koren G, Yudin MH, et al. Management of varicella infection (chickenpox) in pregnancy J Obstet Gynaecol Can, 2012.PMID 22385673
9. [9]Levin MJ, Duchon JM, Swamy GK, Gershon AA. Varicella zoster immune globulin (VARIZIG) administration up to 10 days after varicella exposure in pregnant women, immunocompromised participants, and infants PLoS One, 2019.PMID 31269033
10. [10]Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults N Engl J Med, 2015.PMID 25916341
11. [11]Anderson TC, Masters NB, Guo A, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged 19 Years and Older: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022 MMWR Morb Mortal Wkly Rep, 2022.PMID 35051134
12. [12]Fan S, Stojanovic D, Malvankar-Mehta MS, Hutnik C. Treatment of herpes zoster ophthalmicus: a systematic review and Canadian cost-comparison Can J Ophthalmol, 2018.PMID 29631821
13. [13]Zaal MJ, Völker-Dieben HJ, D'Amaro J. Prognostic value of Hutchinson's sign in acute herpes zoster ophthalmicus Graefes Arch Clin Exp Ophthalmol, 2003.PMID 12644941
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17. [17]Lopez AS, Cardemil C, Pabst LJ, et al. Two-dose varicella vaccination coverage among children aged 7 years--six sentinel sites, United States, 2006-2012 MMWR Morb Mortal Wkly Rep, 2014.PMID 24572613
18. [18]Sampathkumar P, Drage LA, Martin DP. Herpes zoster (shingles) and postherpetic neuralgia Mayo Clin Proc, 2009.PMID 19252116
19. [19]Lin CS, Lin YC, Lao HC, Chen CC. Interventional Treatments for Postherpetic Neuralgia: A Systematic Review Pain Physician, 2019.PMID 31151330