Varicella-Zoster Virus

Varicella-zoster virus (VZV) is the cause of chickenpox in children and herpes zoster (shingles) in adults.

Epidemiology

Incidence – 1,000,000 estimated new cases annually in the U.S.
Age
- Varicella zoster– children (usually 1-9 years)
- Herpes zoster – >60 years
Sex – M:F, equal
Climate variation
- Temperate climates – 90% have infection before adolescence
- Tropical climates – adults are more susceptible than in temperate climates

Organism

DNA virus
Member of the Herpesviridae family
Establishes latency in sensory ganglia

Risk Factors

Varicella
- Direct contact with large-particle droplets (for non-immune individuals)
Herpes zoster
- Immune deficiency, psychological stress and localized physical trauma

Clinical Presentation

Varicella (chickenpox)
- Fever and generalized vesicular exanthem
  - Rash begins as macules and rapidly progresses from papules to vesicles
  - Successive crops of lesions
Complications
- Secondary bacterial infections
- Invasive infections – pneumonia, osteomyelitis
- Central nervous system – strokes (vasculopathy), cerebellar ataxia, meningitis, transverse myelitis
Herpes zoster (reactivation of VZV)
- Skin eruption (shingles)
  - Unilateral, painful maculopapular lesions followed by vesicular eruptions with dermatomal distribution (1-3 dermatomes is usual) that do not cross the midline
- Facial nerve involvement (seventh cranial nerve) – Ramsey-Hunt syndrome
  - Pain from inflammation of sensory nerve ganglia
  - May mimic other serious medical conditions (eg, myocardial infarction, appendicitis, acute cholecystitis, renal colic, pulmonary embolism, glaucoma)
  - Less common manifestations include pneumonitis, acute retinal necrosis, myelitis, vasculopathy, hepatitis and meningitis/encephalitis
  - Complications
    - Postherpetic neuralgia (PHN)
    - Secondary skin infection from Streptococcus pyogenes or Staphylococcus aureus
Congenital VZV
- Transmission (0.4-2% of children when mother had VZV during first 20 weeks of pregnancy) may cause severe disseminated neonatal infection with the following
  - Pneumonia
  - Skin lesions
  - Hemorrhages
  - Death
  - Developmental problems, including hypoplastic limbs, cataracts, chorioretinitis, microphthalmos

Treatment

Early treatment of zoster with antivirals accelerates resolution and may lessen post-herpetic pain

Prevention

Childhood vaccination preventive for VZV in most cases
Universal vaccination has decreased outbreaks and severity of secondary complications
New vaccine recently approved for adults >60 years to prevent herpes zoster
- Vaccine shown to reduce incidence of PHN by 66.5%
Passive immunization with varicella-zoster immune globulin (VZIG) can prevent severe disease in certain susceptible pediatric populations after exposure

Indications for Testing

Rash of VZV primary or as shingles is usually a clinical diagnosis
- Chickenpox – skin lesions are in different stages of development (papule, vesicle, pustule, umbilication, and crusting) concurrently
- Shingles – painful vesicles in a dermatomal distribution
Most common indication is to confirm severe or atypical disease

Laboratory Testing

DFA or PCR – rapid identification of the virus
- Performed on lesion swabs
- Sensitivity and specificity exceed 90%
- PCR is recommended in VZV-CNS syndromes where viral recovery of organisms from CSF is poor
Tzanck smear – rapid but not specific for VZV; performed on swabs from lesions
Viral culture
- Takes >1 week
- Only 60-70% sensitive
- Difficult to grow organisms
Antibody testing
- Significant change in titer from paired sera or a single high titer IgM is indicative of acute infection
- IgG titer is useful in assessing immunity to VZV

Differential Diagnosis

Cutaneous skin lesions (varicella-zoster)
- HSV
- Smallpox
- Rickettsial pox (Rickettsia rickettsii)
- Enterovirus
- Bullous impetigo
- Eczema with secondary superinfection
Cutaneous skin lesions (herpes zoster)
- HSV
- Contact dermatitis
- Poison ivy
- Poison oak
- Bullous impetigo
Meningitis/encephalitis
- Viral encephalitis
- Fungal meningitis
- Bacterial meningitis
Congenital
- Treponema pallidum (syphilis)
- Congenital histocytosis
- Toxoplasma gondii
- Cytomegalovirus
- HSV
- Rubella virus
Vasculitis
Autoimmune bullous disease

Tests generally appear in the order most useful for common clinical situations

Test name: Varicella-Zoster Virus DFA with Reflex to Varicella-Zoster Virus Culture

ARUP #: 0060282

Methodology: Direct Fluorescent Antibody Stain

Use:

Confirm VZV, especially in active skin lesions

Culture considered gold standard

Limitations:

Not recommended for CSF samples

Test name: Varicella-Zoster Virus DFA

ARUP #: 0060290

Methodology: Direct Fluorescent Antibody Stain

Use:

Rapid confirmation of VZV

High sensitivity and specificity

Limitations:

~20% of samples submitted for VZV are positive for HSV; HSV testing is NOT included in this test

Test name: Varicella-Zoster Virus & Herpes Simplex Virus DFA with Reflex to Varicella-Zoster Virus Culture & Herpes Simplex Virus Culture

ARUP #: 0060283

Methodology: Direct Fluorescent Antibody Stain

Use:

Confirm VZV or HSV especially in active skin lesions

Limitations:

Not recommended for CSF samples

Test name: Varicella-Zoster Virus by PCR

ARUP #: 0060042

Methodology: Qualitative Polymerase Chain Reaction

Use:

PCR is the most sensitive and rapid test, but because of assay expense, some laboratories may limit testing to

CNS syndromes
Body fluids or tissues from unusual varicella or herpes zoster infections
Vesicle fluid specimens negative for VZV by culture and/or DFA negative for HSV by culture where definitive etiologic determination clinically important

Test name: Varicella-Zoster Virus Antibodies, IgG & IgM

ARUP #: 0050162

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Diagnose clinical infections with varicella or herpes zoster

Identify hospitalized children with varicella

Assess immune status of individuals exposed to varicella, especially pregnant women

Follow-up: Repeat testing in 10-14 days if results equivocal

Test name: Varicella-Zoster Virus Antibody, IgM by ELISA (CSF)

ARUP #: 0054445

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Confirm VZV in acute infections

Limitations:

Antibody detection in CSF may reflect contamination by blood or antibody transfer across blood-brain barrier rather than VZV infection

Follow-up:

Repeat in 10-14 days if results equivocal

Additional Tests Available

Test name: Varicella-Zoster Virus Antibody, IgM

ARUP #: 0099314

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Varicella-Zoster Virus Antibody, IgG

ARUP #: 0050167

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Varicella-Zoster Virus Antibody, IgG by ELISA (CSF)

ARUP #: 0054444

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Encephalitis Panel, CSF with Reflex to HSV Type 1 & 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001741

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001742

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001765

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Comments:

Test name: Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG

ARUP #: 2001764

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Chemiluminescent Immunoassay

Comments:

General

Comprehensive Review: April 2011
Last Update: April 2011

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