Varicella Zoster Virus (Lecture 2)

Slide 1 · Varicella-Zoster Virus

Latency, ganglion pathology, herpes zoster, and neurologic complications

Neuropathology and clinicopathologic correlations

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Explain how primary VZV infection establishes neuronal latency.

Relate viral reactivation to dermatomal vesicles and radicular pain.

Recognize ganglion, peripheral nerve, and CNS complications.

Integrate morphology, clinical patterns, PCR diagnosis, and prevention.

Slide 3 · One virus, two clinically distinct diseases

Primary VZV infection

Sensory ganglion latency

Later viral reactivation

Herpes zoster

Primary infection causes chickenpox; Recurrent disease causes shingles.

Slide 4 · Chickenpox versus herpes zoster

Chickenpox

Herpes zoster

Primary infection with VZV

Generalized vesicular eruption

Often milder in healthy children

May precede years of silent latency

Reactivation of latent VZV

One or several sensory dermatomes

Often pronounced neuropathic pain

Greater burden in older or immunosuppressed patients

Slide 5 · Neural tropism explains long-term disease

VZV involves mucosal epithelium, skin, and sensory neurons.

Primary illness may resolve while viral latency persists in ganglia.

Skin eruption and neural injury can therefore occur years apart.

The recurrent rash identifies the peripheral sensory territory involved.

Slide 6 · VZV and herpes simplex: Relevant distinctions

Varicella-zoster virus

Herpes simplex viruses

Respiratory aerosol spread emphasized

Hematogenous dissemination during primary infection

Generalized chickenpox is characteristic

Infrequent symptomatic reactivation relative to HSV

Related neurotropic herpesviruses

Classically localized mucocutaneous recurrence

Also establish latency in sensory neurons

Similar intranuclear cytopathic changes

Slide 7 · From respiratory exposure to chickenpox

Respiratory infection

Systemic dissemination

Widespread skin lesions

Respiratory aerosol transmission and hematogenous spread.

Slide 8 · Primary infection is usually a systemic exanthem

Chickenpox is the clinical expression of primary VZV infection.

The skin eruption is widespread rather than segmental.

In immunocompetent children, infection is often self-limited.

Adults and immunocompromised people may experience more severe illness.

Slide 9 · Distribution is a major diagnostic clue

Primary varicella

Reactivated zoster

Lesions arise on the torso and spread to head and extremities

Multiple waves of new lesions

No single nerve territory explains the rash

Groups of vesicles in a sensory dermatome

One or several adjacent dermatomes

Pain can localize to the same nerve territory

Slide 10 · Chickenpox rash: Lesion evolution

Macule

Vesicle

Rupture / crust

Regeneration

Individual lesions progress while additional crops may appear.

Slide 11 · Chickenpox vesicles are intraepithelial

Histologically, vesicular separation is located within the epithelium.

Infected epithelial cells occur around the base of the vesicle.

Viral cytopathic changes may include intranuclear inclusions.

These are histologic features, not a substitute for viral identification.

Slide 12 · Schematic: Intraepithelial skin vesicle

Intraepithelial

Vesicle

EPIDERMIS

DERMIS

SUBCUTIS

Original schematic — not an H&E micrograph

Slide 13 · Viral inclusions: Anatomic context

Herpesvirus-infected epithelial cells may show intranuclear inclusions.

Glassy inclusions in a herpesvirus blister.

Similar nuclear changes may occur with HSV; Morphology alone is not specific.

Interpret viral cytopathic effects together with clinical findings and PCR.

Slide 14 · Why uncomplicated lesions often heal without scars

Epidermal vesiculation

Crusting

Regeneration

Intact basal epidermis

Deep destruction is not a required feature of uncomplicated chickenpox.

Slide 15 · Healing versus scar formation

Uncomplicated lesion

Trauma or superinfection

Vesicle ruptures and crusts

Epithelial repair follows

Typically no permanent scar

Additional tissue destruction can occur

Basal epidermal layer may be damaged

Residual scarring can result

Slide 16 · The end of chickenpox is not viral eradication

Cutaneous lesions resolve while VZV enters a latent state.

Latent virus is retained in peripheral sensory ganglia.

The time between primary illness and reactivation may span decades.

The subsequent disease is zoster, not a new generalized chickenpox episode.

Slide 17 · Sensory ganglia as the reservoir of latency

Ganglion cell bodies

Latency in sensory

Ganglion cells

Reactivation:

Inflammation + injury

Latent virus persists in neural tissue after skin disease resolves.

Slide 18 · Dorsal root ganglia: Important neuronal reservoir

Cell bodies of spinal sensory neurons lie in dorsal root ganglia.

VZV latency has been described in neurons and associated satellite cells.

A ganglion is anatomically linked to a defined cutaneous sensory territory.

This link provides the anatomical basis of a dermatomal recurrence.

Slide 19 · Sensory pathway: Ganglion to the skin

Spinal

Cord

Dorsal root

Ganglion

Skin /

Dermatome

Sensory neuron soma

Peripheral sensory axon

The affected ganglion connects the spinal sensory pathway to a dermatome.

Slide 20 · Trigeminal ganglia: A second major reservoir

The trigeminal system contains sensory neurons serving the face.

Reactivation in this system can produce severe zoster pain.

Trigeminal involvement is prominent among recurrent presentations.

Clinical consequences depend on the neural distribution affected.

Slide 21 · Reactivation begins inside a latent reservoir

Persistent latent VZV

Reduced immune control

Neural viral reactivation

Spread toward skin

Decreased cell-mediated immunity is suspected; Determinants are not fully understood.

Slide 22 · Cell-mediated immunity is clinically relevant

VZV persistence and clinical reactivation reflect host–virus interaction.

Robbins implicates decreased cell-mediated immune control in reactivation.

Risk rises with older age or immunosuppression.

Not every latent infection leads to clinically apparent zoster.

Slide 23 · Who is more vulnerable to zoster morbidity?

Older adults

Immunocompromised people

Reactivation and pain complications are clinically important

Postherpetic neuralgia is emphasized particularly after age 60

Recurrent episodes may occur

Reactivation may be recurrent or extensive

Neural and visceral complications are important

Disseminated infection requires particular attention

Slide 24 · Axonal spread creates a dermatome-specific eruption

Latent sensory ganglion

Spread along sensory nerve

Keratinocyte infection

Localized vesicular rash

The neural projection determines the skin territory involved.

Slide 25 · Dermatomal localization: Schematic

Other sensory territory

Other sensory territory

Affected sensory dermatome

Other sensory territory

Other sensory territory

Schematic banded organization — not an anatomical atlas

Slide 26 · Thoracic and trigeminal dermatomes are common

Thoracic segments frequently produce a unilateral truncal eruption.

Trigeminal sensory territories can produce facial zoster.

Symptoms and vesicles usually share the same distribution.

The dermatome pattern helps localize the infected sensory pathway.

Slide 27 · A generalized rash is not the same as a dermatomal rash

Generalized distribution

Segmental distribution

More characteristic of primary varicella

Crops distributed across the body

Hematogenous dissemination is central

More characteristic of reactivated zoster

Grouped vesicles follow sensory innervation

Neural transport links ganglion to skin

Slide 28 · Zoster skin lesions are more than cutaneous infection

VZV infection of keratinocytes produces vesicular lesions.

Concomitant radiculoneuritis can generate intense neuropathic pain.

Burning, sharp pain, or itching may accompany the rash.

Painful skin findings thus indicate possible sensory neural injury.

Slide 29 · Three connected components of shingles

Reactivated VZV

Sensory ganglion

Sensory axon

Radiculoneuritis

Cutaneous vesicles

Slide 30 · Localized zoster is usually self-limited

The vesicular eruption commonly resolves as infection subsides.

The course is not always free of lasting neural complications.

Persistent pain can outlast the visible skin lesions.

Older age is an important context when assessing this possibility.

Slide 31 · Affected ganglia show inflammatory destruction

Sensory ganglia may contain a dense mononuclear infiltrate.

Infected ganglion neurons can undergo cell death.

Focal necrosis and hemorrhage may accompany severe lesions.

Inflammatory injury provides a structural basis for neural dysfunction.

Slide 32 · Ganglion injury: Illustrated cellular pattern

Ganglion cell bodies

Latency in sensory

Ganglion cells

Reactivation:

Inflammation + injury

Schematic of the sensory neuronal compartment; Not a micrograph.

Slide 33 · Neuronal loss and inflammatory infiltration

Ganglion cell injury

Inflammatory response

Neuronal death can occur

Focal necrosis and hemorrhage may be present

Damaged neurons no longer maintain normal axons

Mononuclear inflammatory cells can be abundant

Inflammation involves the sensory ganglion

The process can extend into associated neural pathways

Slide 34 · Peripheral axons degenerate after neuron loss

Peripheral sensory fibers arise from ganglion neurons.

Death of the neuronal cell body can produce axonal degeneration.

Degenerating axons belonging to injured sensory neurons.

This creates a link from viral ganglionitis to persistent sensory symptoms.

Slide 35 · Neuropathic pain: A pathologic sequence

Ganglion inflammation

Sensory neuron injury

Abnormal sensory signaling

Pain / dysesthesia

The sequence illustrates clinicopathologic interpretation, not a measured pathway.

Slide 36 · Radiculoneuritis explains severe zoster pain

Pain can arise from the inflamed sensory root and associated nerve.

It may be described as burning, sharp, or intense.

Pain distribution often corresponds to the rash distribution.

Trigeminal zoster may be especially painful.

Slide 37 · Postherpetic neuralgia: Persistence after eruption

Pain can persist after the acute zoster eruption resolves.

The syndrome is especially important in people older than 60 years.

The involved sensory territory remains the clinical focus.

Persistent pain demonstrates that neural damage can outlast skin infection.

Slide 38 · Pain from active zoster versus postherpetic neuralgia

Acute zoster pain

Postherpetic neuralgia

Associated with vesicular skin disease

Radiculoneuritis accompanies active neural infection

Burning or sharp pain and itching may occur

Pain persists beyond cutaneous healing

Often more important in older adults

Stimuli ordinarily not painful may evoke pain

Slide 39 · Allodynia is a relevant clinical descriptor

Allodynia is pain evoked by a stimulus that is normally not painful.

Robbins explicitly identifies this phenomenon in postherpetic neuralgia.

It indicates abnormal sensory processing in an injured pathway.

A healed rash does not exclude ongoing neuropathic pain.

Slide 40 · Why a healed rash may leave ongoing disability

Acute sensory ganglionitis

Neuronal / axonal injury

Residual sensory dysfunction

Persistent pain syndrome

Postherpetic neuralgia is a neural complication rather than a persistent vesicular eruption.

Slide 41 · Motor weakness is possible but less common

Although VZV predominantly involves sensory ganglia, motor symptoms can occur.

Weakness may follow a distribution related to the involved segment.

Corresponding anterior horn motor neurons can be damaged.

Cranial motor nuclei may also be affected at related levels.

Slide 42 · From sensory ganglionitis to segmental weakness

Sensory ganglion inflammation

Adjacent neural structures

Segmental weakness (subset)

Motor involvement occurs in a subset; Do not assume it in every patient.

Slide 43 · Ramsay Hunt syndrome: Cranial nerve correlation

VZV can involve the geniculate ganglion region.

Associated facial nerve dysfunction may produce facial paralysis.

This is a distinctive cranial neuropathic complication of zoster.

A concurrent vesicular eruption and facial weakness should prompt consideration.

Slide 44 · Neurologic disease extends beyond sensory ganglia

VZV can cause encephalitis involving brain tissue.

Transverse myelitis can involve spinal cord tissue.

VZV vasculopathy is also a recognized complication.

These are complications, not the usual course of primary chickenpox.

Slide 45 · Neurologic complications: Site of injury

VZV-associated disease

Sensory ganglion

Peripheral nerve

Brain / spinal cord

Zoster pain

Weakness or CNS deficits

Slide 46 · Encephalitis is a documented VZV complication

Encephalitis among potential VZV manifestations.

Central nervous system involvement is especially important in susceptible hosts.

Such disease is conceptually distinct from uncomplicated dermatomal shingles.

The source does not give a VZV-specific encephalitis morphology or frequency.

Slide 47 · Transverse myelitis: Spinal cord involvement

VZV can cause inflammatory disease of the spinal cord.

Cord injury differs from peripheral sensory ganglionitis.

Clinical localization helps separate cord syndromes from radiculopathy.

Specific diagnostic criteria are not supplied in the selected Robbins excerpt.

Slide 48 · VZV vasculopathy: Vascular nervous-system disease

VZV vasculopathy is listed as a possible complication.

Vascular involvement should not be conflated with ordinary radicular pain.

The source establishes the association but gives no subtype classification.

Avoid assuming every neurologic deficit reflects ganglionitis alone.

Slide 49 · Two neurologic compartments to distinguish

Peripheral sensory system

Central nervous system

Sensory ganglion inflammation

Axonal degeneration / radiculoneuritis

Dermatomal pain, sometimes weakness

Encephalitis

Transverse myelitis

Vasculopathy affecting neurologic function

Slide 50 · Immunosuppression changes the severity spectrum

Severe primary infection and zoster may occur in immunocompromised people.

Complications can extend beyond skin and peripheral nerves.

Interstitial pneumonia and necrotizing visceral lesions.

Encephalitis, myelitis, and vasculopathy are also recognized.

Slide 51 · Beyond skin: Distribution of complicated infection

Complicated VZV

Neural tissues

Visceral tissues

Encephalitis / myelitis

Interstitial pneumonia / necrosis

Slide 52 · Host susceptibility: TLR3 is an example

Certain TLR3 mutations with greater susceptibility to VZV encephalitis.

This is a genetic susceptibility observation, not a universal mechanism.

VZV risk still depends on broader host immune competence.

The excerpt does not define a clinical genetic-testing algorithm.

Slide 53 · PCR is the primary method cited for VZV diagnosis

Polymerase chain reaction as the primary diagnostic method.

PCR detects viral nucleic acid rather than inferring the organism from morphology.

Interpret results in the context of the clinical syndrome and sampled site.

The excerpt does not specify specimen protocols, test thresholds, or sensitivities.

Slide 54 · Morphologic clues and their limitations

Finding

What it supports

What it cannot prove

Intraepithelial vesicle

Viral vesicular cytopathic injury

VZV species on its own

Intranuclear inclusions

Herpesvirus-type cell injury

VZV versus HSV identification

Ganglion neuron loss

Neural damage in zoster context

A unique cause without testing

Mononuclear ganglionitis

Inflammatory response in ganglion

Viral identity without corroboration

Slide 55 · Distinguishing VZV from HSV clinically

Evidence favoring VZV

Potential overlap with HSV

Primary generalized chickenpox history

Later painful dermatomal shingles

Latency in sensory ganglia

VZV PCR for confirmation

Both are neurotropic herpesviruses

Both may produce vesicular skin lesions

Both may cause intranuclear inclusions

Morphology alone may not distinguish the agents

Slide 56 · A practical diagnosis framework

Recognize pattern

Localize neural or cutaneous site

Consider host immune status

Use VZV PCR when indicated

Clinical interpretation remains essential; No sensitivity or algorithmic cutoff is claimed.

Slide 57 · Prevention targets two phases of VZV disease

Primary infection prevention

Reactivation complication prevention

Live attenuated varicella vaccination in childhood

Aims to prevent chickenpox and its sequelae

Exact local schedules vary

Recombinant zoster vaccination in adults over 50

Also for younger adults at increased risk

Targets zoster and related complications

Slide 58 · Vaccination relevance to neuropathology

Latent infection makes the burden of VZV extend beyond childhood.

Preventing reactivation reduces potential neural morbidity.

Postherpetic neuralgia is a particularly relevant outcome.

The selected text does not supply country-specific vaccine schedules.

Slide 59 · Clinical application: Generalized vesicles

A previously healthy child develops crops of widespread vesicular lesions after a respiratory illness. Lesions at different stages are present across the torso and extremities.

What is the most likely infection phase?

Primary varicella (chickenpox), with systemic cutaneous dissemination.

Slide 60 · Clinical application: Dermatomal pain

An older adult develops a painful band of grouped vesicles along one side of the trunk. Burning pain localizes to the same region.

What makes this a neural disorder as well as a skin disease?

Reactivated VZV travels along a sensory pathway and may cause radiculoneuritis.

Slide 61 · Clinical application: Pain after healing

After a shingles rash resolves, a person reports persistent pain when light clothing contacts the previously affected skin.

Name the key complication and sensory phenomenon.

Postherpetic neuralgia with allodynia.

Slide 62 · Clinical application: Facial paralysis

A patient with shingles develops facial weakness associated with cranial nerve-region vesicular disease.

Which named zoster-related neurologic syndrome is relevant?

Ramsay Hunt syndrome: VZV-associated facial nerve involvement.

Slide 63 · Clinical application: Immune compromise

An immunosuppressed adult with vesicular VZV disease develops systemic and neurologic symptoms rather than a limited cutaneous eruption.

What complications must be kept conceptually separate from simple zoster?

Visceral disease, encephalitis, myelitis, and vasculopathy.

Slide 64 · Integrated pathology: Skin and nervous system

Cutaneous pathology

Neural pathology

Macules evolve into intraepithelial vesicles

Viral nuclear inclusions may be present

Uncomplicated lesions crust and regenerate

Latency persists in sensory ganglia

Reactivation causes inflammatory neuronal injury

Radiculoneuritis, axonal injury, and PHN can follow

Slide 65 · Five clinicopathologic conclusions

Primary varicella and herpes zoster are two phases of one infection.

Sensory ganglion latency is the bridge between those phases.

The neural distribution determines the recurrent skin eruption.

Ganglion injury explains acute pain and possible persistent neuralgia.

PCR and preventive vaccination complement morphologic understanding.

Slide 66 · Selected textbook reading

Core reference

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th edition (2026).

Relevant sections

Varicella-Zoster Virus — infections and neuropathology.

Peripheral nerve infections and viral diseases of the central nervous system.