Varicella Zoster Virus

Slide 1 · Varicella-Zoster Virus

Primary infection · varicella (chickenpox)

Latent infection · sensory ganglia

Reactivation · herpes zoster (shingles)

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Connect respiratory infection and hematogenous spread to the generalized varicella eruption.

Explain sensory-ganglion latency and subsequent dermatomal reactivation.

Recognize characteristic cutaneous and neural pathology and major complications.

Distinguish clinical presentations, diagnostic approach, and preventive strategies.

Slide 3 · One virus, two distinct clinical syndromes

Primary infection: Varicella

Disseminated vesicular exanthem

Rash develops in successive waves

Typically self-limited in immunocompetent children

Reactivation: Herpes zoster

Painful, dermatomal vesicular eruption

Virus travels along sensory nerves

Morbidity increases with age or immunosuppression

Slide 4 · VZV belongs to the α-herpesvirus group

α-Herpesviruses

HSV-1 · HSV-2 · VZV

Productive infection

Epithelial cells

Latent infection

Postmitotic neurons

Slide 5 · Epithelial–neural tropism shapes the disease

Epithelial infection

Skin and mucosal epithelium support productive infection and vesicle formation.

The primary exanthem reflects widespread cutaneous involvement.

Neural infection

Sensory ganglia provide a long-term latent reservoir.

Reactivation follows sensory pathways back toward skin.

Slide 6 · Latency is genome persistence without virion release

Herpesvirus latency retains viral genomes within host cells.

No infectious virus is produced during the latent state.

Reactivation resumes viral replication and permits tissue injury and transmission.

VZV’s latent reservoir lies in sensory ganglia.

Slide 7 · The natural history has three linked phases

Primary infection

Varicella

Latency

Sensory ganglia

Reactivation

Herpes zoster

Infection is not eliminated when the chickenpox lesions heal.

The interval before zoster may extend many years.

Slide 8 · Respiratory aerosols enable acquisition

Exposure

Respiratory aerosols

Infection

Respiratory tract

Dissemination

Bloodstream to skin

Epidemic VZV transmission with the more localized primary spread of HSV.

Slide 9 · Hematogenous dissemination produces a generalized rash

Following respiratory acquisition, VZV disseminates hematogenously.

Widespread skin infection creates vesicular lesions at anatomically separated sites.

This systemic route helps explain the different distribution of primary varicella and localized recurrent zoster.

Slide 10 · VZV and HSV have different patterns of spread

VZV

Spread via respiratory aerosols

Hematogenous dissemination in primary infection

Widespread primary cutaneous eruption

HSV (comparison)

Primary replication at mucosal or cutaneous entry site

Local epithelial lesions in characteristic distributions

Also becomes latent in sensory neurons

Slide 11 · Host immune status modifies severity

Immunocompetent child

Primary chickenpox is generally mild.

A primary infection usually resolves without permanent skin injury.

Adult or immunosuppressed host

Primary chickenpox can be more severe.

Severe or disseminated complications are more consequential.

Slide 12 · The varicella rash follows a respiratory incubation

Respiratory infection

Exposure and initial infection

~2 weeks later

Appearance of chickenpox rash

Following days

Vesicles rupture or crust and heal

“Approximately 2 weeks” is the interval specified in the Robbins morphology section.

Slide 13 · Varicella lesions arise in successive waves

New lesions appear in multiple crops rather than as one uniform eruption.

At a given examination, lesions may be at different stages of evolution.

This temporal heterogeneity is diagnostically informative when assessing a vesicular exanthem.

Slide 14 · The exanthem spreads centrifugally from the torso

Torso

Head

Extremities

Source pattern: Torso → head and extremities.

The eruption is generalized rather than confined to a single dermatome.

Distribution and lesion timing should be interpreted together.

Slide 15 · A varicella lesion progresses from macule to vesicle

Macule

Initial flat lesion

Vesicle

Fluid-filled blister

Crust

Rupture / drying

Healing

Regeneration

Most uncomplicated lesions heal without a scar.

Slide 16 · “Dewdrop on a rose petal” describes the vesicle

Visible lesion

A delicate vesicle becomes the dominant feature.

The phrase describes the clinical appearance, not a histologic diagnosis.

Histologic correlate

An intraepithelial cavity forms within infected epidermis.

Inclusion-bearing epithelial cells may line the vesicle base.

Slide 17 · Different lesion stages can coexist

Early lesions

Macules

Evolving lesions

Vesicles

Older lesions

Crusted lesions

Sequential crops account for coexistence of these morphologic stages.

Slide 18 · VZV forms an intraepithelial vesicle

Epidermis

Dermis

Intraepithelial

Vesicle

The vesicle cavity lies within epidermal epithelium.

Adjacent infected epithelial cells remain part of the blister architecture.

This is a simplified structural schematic—not a tissue photomicrograph.

Slide 19 · Intranuclear inclusions identify infected epithelial cells

Epidermis

Dermis

Intraepithelial

Vesicle

Intranuclear inclusions (schematic)

Viral inclusion bodies are found in epithelial cells at the base of the vesicle.

The inclusion is intranuclear, not an extracellular blister component.

Other herpesviruses can produce similar cytopathic changes.

Slide 20 · Herpesvirus nuclear inclusions require context

Glassy intranuclear viral inclusions in a herpesvirus blister.

Herpetic cytopathic morphology supports the virus family but does not independently distinguish VZV from HSV.

Combine the distribution and clinical setting with pathogen-specific testing.

Slide 21 · Most varicella lesions heal by regeneration

Vesicle

Epithelial injury

Crusting

Short-lived surface defect

Regeneration

Healing without scar

Superficial lesions can resolve with preservation of regenerative epidermal structures.

Slide 22 · Bacterial superinfection may result in scarring

Ruptured vesicle

Often due to trauma

Secondary infection

Bacterial superinfection

Basal epidermal injury

Destructive damage

Scar

Residual fibrosis

The extent of tissue destruction—not the mere presence of a vesicle—determines scarring.

Slide 23 · Primary chickenpox and zoster have different origins

Chickenpox

Primary VZV infection

Respiratory exposure with bloodborne dissemination

Generalized eruption

Shingles

Reactivation of previously latent VZV

Sensory-nerve spread to skin

Localized dermatomal eruption

Slide 24 · Latency develops after the primary eruption

Primary epithelial infection

Generalized varicella

Sensory neurons

Viral entry into neural compartment

Ganglionic latency

Persistent viral genome

The skin’s visible healing does not imply clearance of latent viral genomes.

Slide 25 · Dorsal-root ganglia provide a latent reservoir

Sensory neuron

Satellite cells

Schematic — no diagnostic micrograph

Latent VZV in sensory ganglia.

Neurons and/or their surrounding satellite cells may harbor the virus.

Latency explains long asymptomatic intervals between clinical syndromes.

Slide 26 · Neurons and satellite cells are distinct ganglion compartments

Sensory neuron

Satellite cells

Schematic — no diagnostic micrograph

Large sensory neuronal cell bodies occupy the ganglion.

Satellite supporting cells surround neuronal somata.

The textbook recognizes latency in neurons and/or these neighboring cells.

Slide 27 · A latent genome is not the same as infectious shedding

Latency

Viral genome persists in the host cell

No production of infectious virus

Clinically silent reservoir

Reactivation

Productive viral replication resumes

Infectious virus may be released

Skin and nerve injury can reappear

Slide 28 · Reactivation may follow a long silent interval

Chickenpox

Primary acquisition

Years of latency

Viral persistence in ganglion

Shingles

Late reactivation

That zoster can develop many years after chickenpox.

Slide 29 · Reactivated virus reaches skin along sensory nerves

Sensory ganglion

Latent VZV reactivates

Sensory nerve

Spread toward periphery

Dermatome

Keratinocyte infection

Herpes zoster

Vesicles + neural symptoms

The nerve pathway links the lesion distribution to the neural site of disease.

Slide 30 · A dermatome maps cutaneous sensory innervation

One sensory

Territory

Schematic, not an anatomical dermatome map

Zoster is distributed in one or more dermatomes.

The involved territory reflects its sensory-nerve origin.

This is a localization schematic, not a precise dermatome atlas.

Slide 31 · VZV reactivation produces localized cutaneous lesions

One sensory

Territory

Schematic, not an anatomical dermatome map

The eruption is typically confined to one or several sensory territories.

Infected keratinocytes generate vesicular lesions.

The cutaneous pattern differs from widespread hematogenous varicella.

Slide 32 · Zoster produces neuropathic symptoms

Intense itching, burning, or sharp pain may accompany the vesicles.

Pain can be prominent because the sensory nerve roots are inflamed.

The cutaneous disease and the neural pathology are parts of one process.

Slide 33 · Radiculoneuritis explains the pain of shingles

Viral reactivation

Sensory ganglion

Neural inflammation

Radiculoneuritis

Clinical expression

Burning / sharp pain

Pain is not explained solely by the visible epidermal vesicles.

Slide 34 · Trigeminal involvement can be especially painful

Ganglion location

VZV latency may involve trigeminal sensory ganglia.

Reactivation affects the sensory territory supplied by involved branches.

Clinical consequence

Severe pain with trigeminal zoster.

The site of neural involvement modifies morbidity.

Slide 35 · Ramsay Hunt syndrome reflects facial-nerve involvement

Reactivation

VZV in neural tissues

Facial pathway

Uncommon involvement

Clinical complication

Facial paralysis

This as an uncommon complication.

Slide 36 · Sensory ganglia develop inflammatory injury

Sensory neuron

Satellite cells

Schematic — no diagnostic micrograph

Zoster may produce a dense inflammatory infiltrate within sensory ganglia.

The cells are predominantly mononuclear.

Ganglionic pathology provides the anatomic basis for radicular pain.

Slide 37 · Herpetic inclusions occur in ganglionic cells

Sensory neuron

Satellite cells

Schematic — no diagnostic micrograph

Intranuclear inclusions occur in neurons and supporting cells.

This indicates cytopathic infection beyond the skin.

Tissue observations complement the cutaneous distribution and symptoms.

Slide 38 · Ganglion-cell necrosis is a recognized lesion

Sensory neuron

Satellite cells

Schematic — no diagnostic micrograph

Robbins Figure 8.14 identifies ganglion-cell necrosis with inflammation.

Neuronal injury links viral reactivation to nerve dysfunction.

The diagram shows relationships only; It is not the textbook micrograph.

Slide 39 · Varicella and zoster differ in topography

Feature

Varicella

Herpes zoster

Timing

Primary infection

Reactivation after latency

Distribution

Generalized, multiple crops

One or several dermatomes

Symptoms

Vesicular exanthem

Neural pain + vesicles

Pathway

Bloodborne dissemination

Sensory-nerve spread

Slide 40 · Their skin lesions share a herpetic pattern

Finding

Varicella

Herpes zoster

Vesicles

Intraepithelial

Keratinocyte infection causes vesicles

Nuclear inclusions

At base of vesicle

Herpetic changes in affected cells

Neural association

Latency follows primary episode

Radiculoneuritis accompanies lesions

Distribution

Generalized

Dermatomal

Slide 41 · Recurrence is uncommon in immunocompetent hosts

Repeat episodes of shingles in only approximately 1%–4% of infected immunocompetent individuals.

Recurrence may occur more than once in older or immunosuppressed hosts.

The quantitative statement is textbook-specific, not an updated contemporary population estimate.

Slide 42 · Age and immunosuppression alter zoster morbidity

Older patients

Herpes zoster can be a substantial source of morbidity.

Postherpetic neuralgia is highlighted in the CNS chapter.

Immunosuppressed patients

Multiple recurrences may occur.

Severe organ complications and visceral injury are more concerning.

Slide 43 · VZV complications extend beyond the skin

Varicella-zoster infection

Cutaneous disease

Neural tissues

Encephalitis · myelitis

Vessels / viscera

Vasculopathy · necrotizing injury

The importance of these complications in immunosuppressed hosts.

Slide 44 · Interstitial pneumonia is a visceral manifestation

VZV can cause interstitial pneumonia.

This establishes that disease may extend beyond the cutaneous and neural compartments.

The possibility is particularly important in an immunosuppressed patient with VZV infection.

Slide 45 · Encephalitis represents central nervous system involvement

VZV is among the viral causes of encephalitis.

Risk is influenced by host susceptibility, including TLR3 mutations.

Severe neurological symptoms should not be interpreted as ordinary uncomplicated shingles.

Slide 46 · Transverse myelitis is another neural complication

The spinal cord can be affected during VZV infection.

Transverse myelitis among possible complications.

This differs anatomically from inflammation restricted to a peripheral sensory root.

Slide 47 · VZV-associated vasculopathy affects blood vessels

Primary tissue target

The vascular compartment can be involved in VZV disease.

Vasculopathy among the recognized complications.

Clinicopathologic implication

A neurologic syndrome may involve mechanisms beyond direct ganglion infection.

Pathology must be interpreted in the full clinical context.

Slide 48 · Visceral lesions may undergo necrosis

VZV can produce necrotizing visceral lesions.

Robbins especially associates severe visceral complications with immunosuppression.

This is a major reason not to regard VZV exclusively as a cutaneous infection.

Slide 49 · TLR3-associated susceptibility is relevant to encephalitis

Host factor

TLR3 mutation

Susceptibility

Increased risk of VZV encephalitis

Clinical expression

CNS infection

The source describes an association, not a deterministic outcome for carriers.

Slide 50 · Postherpetic neuralgia persists after zoster

Acute zoster

Painful vesicular eruption

Cutaneous healing

Visible lesions resolve

Postherpetic neuralgia

Pain persists beyond skin healing

Robbins Chapter 28 particularly emphasizes this complication in people older than 60 years.

Slide 51 · Postherpetic neuralgia may include allodynia

Persisting pain

Pain can continue after the acute eruption resolves.

It contributes to long-term morbidity after reactivation.

Stimulus sensitivity

A normally nonpainful stimulus may provoke pain.

This is a neuropathic clinical feature, not continued vesicular formation.

Slide 52 · PCR is the principal diagnostic method described

Clinical syndrome

Varicella or zoster suspected

Viral detection

PCR for VZV

Interpretation

Correlate with presentation

PCR as the primary diagnostic approach; Specimen-level protocols are not supplied in this excerpt.

Slide 53 · Clinical context distinguishes VZV from HSV

Feature

VZV

HSV

Primary spread

Respiratory / hematogenous

Replicates at entry epithelium

Primary rash

Widespread crops

Often localized mucocutaneous

Reactivation

Often dermatomal zoster

Recurrent mucocutaneous disease

Latency

Sensory ganglia

Sensory neurons

Slide 54 · Diagnosis integrates localization and viral detection

Pattern recognition

Generalized lesions in multiple stages suggest primary varicella.

Dermatomal painful vesicles suggest herpes zoster.

Etiologic confirmation

VZV PCR is the principal method named.

Herpetic inclusions alone are not uniquely VZV-specific.

Slide 55 · Varicella vaccination prevents primary disease

Robbins recommends a live attenuated VZV vaccine for children.

The strategy addresses infection before later latency and reactivation.

This presentation follows the textbook description, not a jurisdiction-specific vaccination schedule.

Slide 56 · Recombinant vaccination targets shingles risk

Robbins recommends recombinant zoster vaccination for adults older than 50 years.

It also identifies younger adults at increased risk due to immunodeficiency or immunosuppression.

Current local eligibility and schedules should be checked against local health-authority guidance.

Slide 57 · Case 1 · generalized vesicular eruption

Hypothetical teaching case

A previously well child develops successive crops of vesicles after a respiratory illness.

Some lesions are early macules while others have crusted.

The lesions occupy the torso, head, and extremities.

Clinical reasoning question

What mechanism explains the generalized, asynchronous eruption?

Slide 58 · Case 2 · localized painful eruption

Hypothetical teaching case

An older adult develops burning pain followed by vesicles in a localized sensory territory.

The eruption is not generalized.

The presentation occurs years after a childhood chickenpox episode.

Clinical reasoning question

Which tissue reservoir and route explain this pattern?

Slide 59 · Case 3 · pain after visible lesions resolve

Hypothetical teaching case

An individual older than 60 years had a painful dermatomal vesicular eruption.

The skin has healed, but pain continues.

Light touch can now provoke discomfort.

Clinical reasoning question

What persistent complication best explains the symptoms?

Slide 60 · Case 4 · beyond cutaneous zoster

Hypothetical teaching case

An immunosuppressed patient with VZV develops progressive systemic or neurologic findings.

Localized skin morphology alone is insufficient to characterize the illness.

Several noncutaneous VZV complications.

Clinical reasoning question

Which organ complications merit consideration?

Slide 61 · Clinicopathologic synthesis

Entry / dissemination

Respiratory → blood → skin

Latency

Sensory ganglia

Reactivation

Nerve → dermatome

Consequences

Skin + neural / visceral injury

Disease distribution is best explained by the changing anatomical route of viral spread.

Slide 62 · What should the pathologist recognize?

Cutaneous VZV creates intraepithelial vesicles with infected epithelial cells and intranuclear inclusions.

Ganglionic VZV can show mononuclear inflammation, herpetic inclusions, and neuronal injury.

Morphology is interpreted together with distribution, host status, neurologic findings, and PCR.

Slide 63 · Principal source

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

Infectious Diseases: herpesvirus latency and varicella-zoster virus.

The Central Nervous System: varicella-zoster virus and postherpetic neuralgia.