Varicella Zoster Virus

Aka: Varicella Zoster Virus, Chickenpox, Chicken Pox, VZV, Human Herpesvirus 3, Varicella-Zoster Virus

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II. Epidemiology

  1. Peak onset ages 5 to 9 years old
  2. Outbreak time: January to May
  3. Incidence: 3.7 Million cases/year in U.S. 1980-1990
  4. Varicella Immunity
    1. Adults (U.S): 95% immune
    2. Adults (U.S.) without known VZV history: 75% immune

III. Etiology

  1. Herpes Varicella Zoster Virus
  2. Human Herpes Virus (Herpesviridae)

IV. Pathophysiology

  1. Incubation Period: 10-21 days (after respiratory transmission)
  2. Transmission
    1. Transplacental (vertical transmission)
    2. Direct contact or Respiratory droplet
      1. Household contact transmission: 90%
      2. Limited exposure: 10-35%

V. Symptoms

  1. Viral Prodrome (prodrome is often absent in children, who have rash at onset)
    1. Fever
    2. Anorexia
    3. Malaise
    4. Headache
    5. Myalgia
    6. Upper Respiratory Infection
  2. Pruritic rash
    1. See signs for description

VI. Signs

  1. Generalized Lymphadenopathy
  2. Rash (present in 100% of cases)
    1. Crops of small, Red Papules or Vesicles
      1. Start as Macules and transition to Papules, Vesicles and then Pustules
        1. In vaccinated patients, lesions remain maculopapular (not vesicular)
        2. If Immunocompromised, may develop progressive and extensive lesions
          1. May also appear septic, with multisystem organ involvement
      2. Lesions are in various stages of healing (contrast with Smallpox in which lesions at same stage)
      3. No longer contagious when all lesions have crusted (typically after 4-5 days)
    2. Develop into "Dew Drop on a rose petal" appearance
      1. Oval, "teardrop" Vesicles
      2. Erythematous base
    3. Spread centripetally from head to trunk
      1. Starts on face and scalp and spreads to trunk and back
      2. Minimal limb involvement
      3. May involve oral or vaginal mucosa
    4. Images
      1. DermVaricellaZoster.jpg

VII. Differential Diagnosis

  1. Herpes Simplex Virus
  2. Herpes Zoster Virus (Shingles)
  3. Impetigo
  4. Coxsackie virus
  5. Papular Urticaria
  6. Scabies
  7. Dermatitis Herpetiformis
  8. Drug rash
  9. Smallpox
    1. Vesicular lesions that are all in the same stage

VIII. Labs: Diagnosis

  1. Varicella is typically a clinical diagnosis (and formal testing is not typically needed)
    1. However, consider testing when diagnosis is unclear, especially in pregnancy, Immunocompromised patients
  2. Varicella PCR
    1. Preferred diagnostic test when needed
    2. Sample sources
      1. Vesicle (punture with needle or unroof and swab the base)
      2. Lesion crust
  3. Other tests
    1. Varicella tissue culture
      1. Lower Test Sensitivity than PCR, and longer wait
    2. Vesicular fluid exam (Tzanck Smear)
      1. Multinucleated giant cells
      2. Epithelial cells with Eosinophilic inclusion bodies
      3. Virus
    3. Varicella Serology
      1. Varicella IgG titers (obtain acute and convalescent titers)

IX. Labs: Other

  1. Complete Blood Count (CBC)
    1. Slight Leukocytosis
  2. IgG Antibody to VZV (ELISA)
    1. Immunity testing indicated in pregnancy

X. Management: General

  1. Reduction of Pruritus
    1. Calamine Lotion
    2. Oatmeal Bath (Aveeno)
    3. Atarax at bedtime
  2. Prevention of Superinfection
    1. Apply Bacitracin to denuded lesions until scab forms
  3. Hospitalization Indications
    1. Immunocompromised state or pregnancy <20 weeks gestation (see IV protocol below)
    2. Malignancy (e.g. Leukemia)
      1. Mortality rates are as high as 30%
    3. Varicella Complications (e.g. Pneumonia)
  4. Close observation and consider hospitalization
    1. Children <1 year old
    2. Adults with primary varicella (consider admission)
      1. Mortality >25 fold over that of children

XI. Management: Virus Suppression

  1. Antiviral therapy is routinely recommended only in patients at higher risk of complications
    1. Unvaccinated patients >12 years old
    2. Chronic skin conditions
    3. Chronic lung disease (e.g. Asthma, COPD, Cystic Fibrosis)
    4. Patients on Salicylates or Corticosteroids (including Inhaled Corticosteroids)
    5. Pregnancy (see protocol below)
    6. Immunocompromised patients (see protocol below)
  2. Normal host: Acyclovir (or Valacyclovir or Famciclovir)
    1. Dosing
      1. Acyclovir 20 mg/kg/dose (up to 800 mg/dose) 4 times per day for 5 days
    2. Efficacy
      1. Shortens time of viral shedding
      2. Most effective if started within 24 hours of rash (some effect up to 72 hours)
        1. Faster cessation of new lesions
        2. Fever duration reduced
        3. More rapid healing
    3. Indications
      1. Consider especially in large household
    4. Adverse effects
      1. Avoid if Dehydration present
      2. Not associated with short-term viral resistance
    5. References
      1. Balfour (2001) Pediatr Infect Dis J 20:219-26 [PubMed]
  3. Immunocompromised (including high dose Corticosteroids for >14 days) or pregnancy exposure <20 weeks gestation
    1. VZIG
      1. See postexposure protocol below
    2. Acyclovir
      1. Initiate as soon as possible with onset of rash
      2. Indicated within 10 days of rash onset
      3. Dose: 500 mg/m2/day IV divided q8 hours for 7 days

XII. Prevention: Preexposure

  1. Varicella Vaccine (Varivax)
    1. Vaccinated patients may become infected, but tend to have a milder course

XIII. Prevention: Postexposure Prophylaxis

  1. Indications
    1. Exposure between 2 days before rash onset and when all skin lesions have crusted (4 to 5 days) AND
    2. Not immune
      1. No history of Varicella Zoster Virus infection and negative Serology or
      2. Less than 2 doses of Varicella Zoster Virus Vaccine
  2. Healthy patients
    1. Varicella Vaccine within 3-5 days of exposure
  3. Immunocompromised, pregnant women, or newborns (mother with rash 5 days before or 2 days after delivery)
    1. Varicella zoster immune globulin (VZIG) 125 units per 10 kg IM
      1. Avoid delays (best within first 96 hours, but may be given up to 10 days postexposure)
    2. Immune globulin (IVIG) 400 mg/kg IV
      1. Give only if VZIG not available
  4. Oral Acyclovir
    1. Consider for 7-10 days after exposure in Immunocompromised children without Varicella Immunity
  5. References
    1. Marin (2007) MMWR Recomm Rep 56(RR-4): 1-40 [PubMed]

XIV. Course

  1. Incubation Period: 11-21 days
  2. Infectious
    1. Start: 1-3 days before rash
    2. End: Final lesion crusted (4-5 days after rash onset)

XV. Complications: General

  1. Highest complication rates are in infants age <1 year
    1. Teens and adults also have higher complication rates
    2. Lowest complication rates in young children and pre-teen (age 1 to 12 years)
  2. Progressive varicella (Immunocompromised patients)
    1. Extensive lesions developing over a longer course
    2. Sepsis and multiorgan involvement may occur
  3. Lung involvement (14-30% of adults)
    1. Viral PneumoniaIncidence 1 case per 400 adult cases
    2. Secondary Bacterial Pneumonia
  4. Encephalitis
    1. Occurs in 1.8 per 10,000 varicella infections
  5. Acute Cerebellar Ataxia
    1. Occurs in 1 per 4000 varicella infections in children <15 years old
  6. Herpes Zoster
    1. Unvaccinated children <18 years will develop zoster in 230 per 100,000 Varicella cases
  7. Secondary Bacterial Infection (superinfection) common (esp. if fever>5 days)
    1. Cellulitis
    2. Abscess
    3. Erysipelas
    4. Otitis Media
    5. Invasive Group A Beta-hemolytic Streptococcus
      1. Incidence: 5.2 cases per 100,000 VZV cases
      2. Increasing Incidence
      3. Suspect if fever persists >3-4 days after exanthem
    6. Septic Arthritis
    7. Osteomyelitis
    8. Staphylococcal pyomyositis
    9. Disseminated disease in Immunocompromised
  8. Reye's Syndrome
    1. Avoid concurrent Aspirin use in children
  9. Nephritis
  10. Varicella mortality
    1. Pre-Vaccine era (1987-1992)
      1. Deaths: 80-105 per year (mostly children), once every 4 days in U.S.
      2. Most deaths occur under age 20 years old, an often in otherwise healthy children
    2. Post-Vaccine era
      1. Deaths: 17 per year (2008 to 2011 in U.S.)

XVI. Complications: Congenital Syndrome (Pregnancy related)

  1. General
    1. Non-immune Mother exposed to Varicella Zoster Virus
    2. Congenital syndrome risk 13-20 weeks gestation (2% risk if mother has varicella)
    3. Not associated with Pregnancy loss
    4. Not associated with Preterm Labor
  2. Infant Findings
    1. Skin lesions
    2. Short limbs and digits
    3. Ocular abnormalities
    4. Muscular atrophy
    5. Intrauterine Growth Retardation

XVII. References

  1. Harrison and Ruttan (2019) Crit Dec Emerg Med 33(7): 3-12
  2. Harrison and Ruttan (2023) Crit Dec Emerg Med 38(2): 23-31
  3. Doctor (1995) Pediatrics 96:428-33 [PubMed]
  4. Spencer (2017) Am Fam Physician 95(12): 786-94 [PubMed]

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Related Studies

Ontology: Chickenpox (C0008049)

Definition (MSHFRE) Maladie très contagieuse provoquée par le virus de la varicelle et du zona (herpèsvirus 3 humain). Elle touche en général les enfants et se propage par contact direct ou par voie respiratoire, par l’intermédiaire de gouttelettes. Elle se caractérise par l’apparition sur la peau et les muqueuses de vagues successives de lésions vésiculaires prurigineuses typiques qui se rompent facilement et forment des croûtes. Relativement bénigne chez l’enfant, elle peut être compliquée par une pneumonie ou une encéphalite chez l’adulte. (Dorland, 27e éd.)
Definition (MEDLINEPLUS)

Chickenpox is an infection caused by the varicella-zoster virus. Most cases are in children under age 15, but older children and adults can get it. It spreads very easily from one person to another.

The classic symptom of chickenpox is an uncomfortable, itchy rash. The rash turns into fluid-filled blisters and eventually into scabs. It usually shows up on the face, chest, and back and then spreads to the rest of the body. Other symptoms include

  • Fever
  • Headache
  • Tiredness
  • Loss of appetite

Chickenpox is usually mild and lasts 5 to 10 days. Calamine lotions and oatmeal baths can help with itching. Acetaminophen can treat the fever. Do not use aspirin for chickenpox; that combination can cause Reye syndrome.

Chickenpox can sometimes causes serious problems. Adults, babies, teenagers, pregnant women, and those with weak immune systems tend to get sicker from it. They may need to take antiviral medicines.

Once you catch chickenpox, the virus usually stays in your body. You probably will not get chickenpox again, but the virus can cause shingles in adults. A chickenpox vaccine can help prevent most cases of chickenpox, or make it less severe if you do get it.

Centers for Disease Control and Prevention
Definition (NCI) A contagious childhood disorder caused by the varicella zoster virus. It is transmitted via respiratory secretions and contact with chickenpox blister contents. It presents with a vesicular skin rush, usually associated with fever, headache, and myalgias. The pruritic fluid-filled vesicles occur 10-21 days after exposure and last for 3-4 days. An additional 3-4 days of malaise follows before the affected individual feels better. An individual is contagious 1-2 days prior to the appearance of the blisters until all blisters are crusted over. Generally, healthy individuals recover without complications.
Definition (MSH) A highly contagious infectious disease caused by the varicella-zoster virus (HERPESVIRUS 3, HUMAN). It usually affects children, is spread by direct contact or respiratory route via droplet nuclei, and is characterized by the appearance on the skin and mucous membranes of successive crops of typical pruritic vesicular lesions that are easily broken and become scabbed. Chickenpox is relatively benign in children, but may be complicated by pneumonia and encephalitis in adults. (From Dorland, 27th ed)
Definition (CSP) highly contagious infectious disease caused by the varicella-zoster virus (Herpesvirus 3); usually affects children, is spread by direct contact or respiratory route via droplet nuclei, and is characterized by the appearance on the skin and mucous membranes of successive crops of typical pruritic vesicular lesions that are easily broken and become scabbed; chickenpox is relatively benign in children, but may be complicated by pneumonia and encephalitis in adults.
Concepts Disease or Syndrome (T047)
MSH D002644
ICD9 052
ICD10 B01 , B01.9
SnomedCT 186508005, 154325003, 38907003
LNC LA10517-3, LA17013-6
English Chicken Pox, Chickenpox, Varicella, VARICELLA, varicella infection (diagnosis), varicella infection, Varicella [chickenpox], Varicella NOS, Chickenpox [Disease/Finding], chicken pox, Chicken Pox Infection, Varicella infection (& [chickenpox]) (disorder), Chickenpox - varicella, Varicella infection (& [chickenpox]), Varicella infection (disorder), Varicella (Chickenpox), Varicella infection, Chicken pox, Varicella (disorder), chickenpox, varicella, Chickenpox, NOS, Varicella, NOS, Chickenpox NOS
French VARICELLE, Varicelle
Portuguese VARICELA, Varicela, Catapora
German WINDPOCKEN, Varizellen [Windpocken], Varizellen, Wasserpocken, Windpocken
Dutch waterpokken, Waterpokken (Vlaanderen ook: windpokken), varicella, Varicella [waterpokken], Waterpokken, Varicella
Swedish Vattkoppor
Japanese ｽｲﾄｳ, 水痘, 水疱瘡
Czech varicela, neštovice plané, varicella, Plané neštovice, Varicella, plané neštovice
Finnish Vesirokko
Russian VETRIANAIA OSPA, ВЕТРЯНАЯ ОСПА
Korean 수두
Croatian VARIČELA
Polish Ospa wietrzna
Hungarian varicella, Bárányhimlő
Norwegian Varicella, Vannkopper
Spanish varicela (trastorno), varicela, viruela de las aves, Varicela, Varicella
Italian Varicella
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Human herpesvirus 3 (C0042338)

Definition (NCI_CDISC) Any viral organism that can be assigned to the species Human Herpesvirus 3.
Definition (NCI) An icosahedral, enveloped virus containing a single molecule of linear double-stranded DNA of 125000 nucleotides that infects only humans. It is the causative agent of chickenpox and shingles.
Definition (CSP) primary infection causes chickenpox; reactivation causes herpes zoster.
Definition (MSH) The type species of VARICELLOVIRUS causing CHICKENPOX (varicella) and HERPES ZOSTER (shingles) in humans.
Concepts Virus (T005)
MSH D014645
SnomedCT 19551004
LNC LP14853-3, MTHU002144
English Chickenpox Virus, Chickenpox Viruses, Herpes zoster Virus, Herpes zoster Viruses, Herpesvirus varicellae, Ocular Herpes zoster Virus, Varicella-Zoster Virus, Varicella-Zoster Viruses, VZ Virus, VZ Viruses, Herpesvirus 3 (alpha), Human, Herpesvirus 3, Human, varicella zoster virus, HHV-3, HHV 3, HERPESVIRUS 3 ALPHA HUMAN, HUMAN HERPESVIRUS 03, HERPESVIRUS HUMAN 03, VARICELLA, human alphaherpesvirus 3, chickenpox virus, varicella virus, Human Herpesvirus 3, Varicella-Zoster Virus 1, Herpes Zoster Virus, HHV3, herpesvirus 3, human, herpes zoster, varicella-zoster virus, herpes zoster virus, HUMAN HERPESVIRUS 3, Human alphaherpesvirus 3, varicella zoster virus VZV, varicella-zoster virus VZV, Varicella zoster virus, VZV, Varicella Zoster Virus, Herpes zoster, Varicella-zoster virus, Human (alpha) herpes virus 3, VZV - Varicella-zoster virus, HZ - Herpes zoster virus, HZ - Herpes zoster, Human herpesvirus 3 (organism), Human herpesvirus 3
French Virus varicelle-zona, Herpesvirus varicellae, Herpèsvirus humain de type 3, VZV (Varicella-Zoster Virus), Herpes zoster virus, VVZ (Virus Varicelle-Zona), Varicella-zoster virus, Virus de la varicelle et du zona, Virus du zona, HHV-3 (Human HerpesVirus 3), Ocular herpes zoster virus, Virus du zona oculaire, Human herpesvirus 3, Virus de la varicelle, Chickenpox virus
Swedish Herpesvirus 3, humant
Czech virus varicella zoster
Portuguese Herpesvirus Humano Tipo 3, Herpesvirus Humano 3, Herpesvirus varicellae, Vírus da Varicela, Vírus da Varicela-Zoster, Vírus do Herpes Zoster Ocular, Vírus do Herpes Zoster, Vírus VZ
Spanish Herpesvirus Humano 3, Herpesvirus Humano Tipo 3, virus varicela zóster, virus de la varicela zóster, Virus del Herpes Zóster Ocular, Virus de la Varicella-Zóster, Virus del Herpes Zóster, virus del herpes humano 3 (organismo), virus del herpes humano 3, Herpesvirus varicellae, Virus de la Varicela, Virus VZ
Finnish Ihmisen herpesvirus 3
Italian Virus VZ, Virus della varicella zoster, Virus herpes zoster, HHV-3, Virus herpes zoster oculare, Virus della varicella, Herpesvirus 3 (alfa) umano, Herpesvirus varicellae, Herpesvirus 3 umano
Russian GERPESVIRUS 3 CHELOVEKA, LISHAI OPOIASYVAIUSHCHII, VIRUS, VARICELLA-ZOSTER VIRUS, OPOIASYVAIUSHCHII LISHAI, VIRUS, VETRIANAIA OSPA, VIRUS, VZ VIRUS, HERPES ZOSTER VIRUS, HERPES ZOSTER ВИРУС, VARICELLA-ZOSTER ВИРУС, VZ ВИРУС, ВЕТРЯНАЯ ОСПА, ВИРУС, ГЕРПЕСВИРУС 3 ЧЕЛОВЕКА, ЛИШАЙ ОПОЯСЫВАЮЩИЙ, ВИРУС, ОПОЯСЫВАЮЩИЙ ЛИШАЙ, ВИРУС
German HUMANES HERPESVIRUS 03, HERPESVIRUS HUMANES 03, Herpes-Zostervirus, Herpesvirus 3, humanes, Ophthalmisches Herpes-Zoster-Virus, VZ-Virus, Varizellen-Zostervirus, Herpesvirus varicellae, Humanes Herpesvirus 3, Windpocken-Virus
Croatian HERPESVIRUS 3, HUMANI, VARICELA-ZOSTER VIRUS
Polish Wirusy ospy wietrznej i półpaśca, Herpesvirus Varicellae zoster, Wirusy VZ, Herpeswirus 3 ludzki
Japanese ヒトヘルペスウイルス3型, VZウイルス, ヒトヘルペスウイルス3(アルファ), ヒトヘルペスウイルス3, 帯状ヘルペスウイルス, 水痘-帯状疱疹ウイルス, 水痘ウイルス, 水痘ヘルペスウイルス, 水痘帯状疱疹ウイルス, 眼球帯状ヘルペスウイルス, ヘルペスウイルス3(アルファ)-ヒト, ヘルペスウイルス3-ヒト, ヘルペスウイルス3型-ヒト, 帯状疱疹ウイルス, 眼部帯状疱疹ウイルス
Dutch Herpes-zoster-ophtalmicus-virus, Herpes-zoster-virus, Herpesvirus varicellae, VZ-virus, Varicella-zoster-virus, Waterpokkenvirus, Herpesvirus 3, humaan, Humaan herpesvirus 3, Virus 3, humaan herpes-
Derived from the NIH UMLS (Unified Medical Language System)

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