Basics
Description
Varicella-zoster virus (VZV) is a highly contagious herpesvirus. Primary infection with the virus results in varicella (chickenpox), whereas reactivation from latency results in herpes zoster (shingles).
Epidemiology
- Transmission occurs by droplet and airborne transmission of infectious respiratory secretions or direct contact with vesicles and respiratory secretions.
- Incubation 10-21 days (usually 14-16 days) after exposure; cases most contagious 2 days before the rash appears until skin lesions have fully crusted.
- Immunocompromised patients may have longer or shorter incubation.
- Post-intravenous immunoglobulin (IVIG), incubation may be up to 28 days.
- The incidence of chickenpox has declined by 90% since the introduction of universal varicella vaccination.
- The attack rate for susceptible household contacts exposed to varicella is 90%.
- Disease is more severe in immunocompromised persons, infants >3 months of age, adolescents, adults, persons with pulmonary disorders (asthma), persons with chronic skin disorders (eczema), and persons on oral and/or intravenous (IV) steroids or long-term aspirin therapy.
- Congenital varicella embryopathy: Risk is 1-2% when maternal primary VZV infection occurs before the 20th week of gestation.
- The rate of complications from varicella has declined dramatically since the licensure of the varicella vaccine.
General Prevention
- Varicella vaccine
- Live attenuated vaccine (Oka strain)
- 2-dose series for routine immunization of all healthy, susceptible children; adolescents; and adults
- Immunogenicity: ~85% of immunized children developed protective levels of humoral and cellular immunity after 1 dose, ~100% with 2 doses; 3 less likely to have breakthrough disease when 2 doses of vaccine were administered
- Effectiveness: 70-90% effective against all VZV disease; >97% effective against severe disease (e.g., median number of vesicles was 50 in vaccinated children vs. 250 in unvaccinated children)
- Herpes zoster can occur following varicella vaccination, but clinical severity of the zoster is milder and the risk of acquiring zoster following immunization is lower than following wild-type chickenpox.
- Contraindications
- Anaphylaxis to vaccine components (e.g., neomycin, gelatin)
- Pregnant, immunocompromised, or <12 months of age
- HIV is an exception: It is recommended to vaccinate HIV-positive children if CD4+ T-cell counts are ≥15%. Give doses 3 months apart.
- High-dose corticosteroid doses of >2 mg/kg/day or >20 mg/day of prednisone, or its equivalent, for ≥14 days are considered immunosuppressive doses: VZV vaccine should not be given until systemic corticosteroid therapy has been discontinued for at least 1 month.
- Postexposure prophylaxis
- If no contraindication to VZV vaccine: Administer VZV vaccine to susceptible hosts (1st or 2nd dose) within 72 hours (up to 120 hours) of exposure.
- If with contraindications to VZV vaccine: Consider passive immunization.
- Passive immunization if
- (i) No evidence of immunity in exposed person, (ii) probability that exposure will result in infection, and (iii) likelihood of complications of VZV in the exposed person due to risk factors
- Susceptible immunocompromised people, pregnant women, and neonates whose mothers develop varicella infection 5 days prior to 2 days after delivery should be especially considered for passive immunization upon exposure.
- Administer varicella immunoglobulin (VariZIG) or IVIG as per protocol within 96 hours of exposure.
- If VariZIG or IVIG is unavailable, or >96 hours have passed, some experts recommend postexposure prophylaxis with oral acyclovir (20 mg/kg q6h for 7 days) beginning 7-10 days after exposure.
Pathophysiology
- After primary infection, the virus establishes latency in dorsal root ganglia cells.
- Immunity from natural disease is usually lifelong, but symptomatic and asymptomatic reinfections do occur, boosting antibody levels.
Diagnosis
History
- Chickenpox
- Fever, malaise; decreased appetite common prior to onset of rash
- Fever low grade to moderate and persists after rash appears
- Pruritic rash begins on scalp, face, or trunk.
- New lesions appear as some begin to crust; all stages (macules, vesicles, crusted lesions) apparent at one time.
- Vesicles may appear in the mouth, conjunctiva, vagina, and urethra.
- Zoster
- Prodrome of pain, pruritus, hyperesthesias
- Vesicular lesions are clustered unilaterally in a dermatomal distribution of one or more adjacent sensory nerves.
- Mildly painful in children
Physical Exam
- Chickenpox
- Evolution of rash from macules to vesicles, which appear as "dewdrop on a rose petal," then crust
- Lesions in multiple stages of formation is pathognomonic.
- Most children have less than 300 lesions; higher numbers are found among children who develop varicella after household contact.
- New lesions appear for up to 7 days in otherwise healthy children.
- Assess for complications: interstitial pneumonia, encephalitis, secondary bacterial infection (especially group A Streptococcus).
- Zoster
- Discrete vesicles appear first, then enlarge and coalesce.
- New lesions cease to form after 3-7 days and crusting occurs within 2 weeks.
- Severe local dermatomal infection, cutaneous dissemination, and visceral dissemination may occur in immunocompromised children.
Diagnostic Tests & Interpretation
Lab
- Not needed for typical cases in healthy children
- VZV is difficult to isolate in cell culture.
- Immunohistochemical staining of epithelial cells from cutaneous lesions may provide a rapid diagnosis.
- PCR testing of clinical specimens must be done by experienced laboratory personnel.
- Serology is used to determine susceptibility to infection.
- Acute and convalescent sera can determine acute infection: enzyme immunoassay (EIA), immunofluorescence assay (IFA), latex agglutination (LA), fluorescent antibody to membrane antigen (FAMA), and enzyme-linked immunosorbent assay (ELISA).
Differential Diagnosis
The differential diagnosis includes other causes of vesicular rash:
- Coxsackievirus infection (hand, foot, mouth)
- Eczema herpeticum
- Herpes zoster with dissemination
- Impetigo
- Insect bites
- Monkeypox
- Mycoplasma (erythema multiforme)
- Pseudomonas (ecthyma gangrenosum)
- Rickettsial pox
- Scabies
- Toxic epidermal necrosis, Stevens-Johnson, and various noninfectious vesicular conditions of the skin
Treatment
Medication
- Acyclovir is the drug of choice for varicella or zoster in children.
- IV acyclovir is indicated for infected immunocompromised hosts and neonates and those with associated pneumonia or encephalitis:
- <1 year old: 10-20 mg/kg q8h
- ≥1 year old: 500 mg/m2 q8h or 10-20 mg/kg q8h
- ≥12 years old: 10 mg/kg q8h
- Treat for 7-10 days or until no new lesions for 48 hours.
- Oral acyclovir may be considered for those with increased risk of severe infection, including those with cutaneous disorders, chronic diseases that may be exacerbated by acute varicella infection, adolescents, and those who acquire infection after household contact.
- Acyclovir (PO): 20 mg/kg q6h to max of 800 mg q6h, for 5 days
- Valacyclovir (PO): (≥2 years old) 20 mg/kg (max 1,000 mg) q8h for 5 days; better bioavailability
- Children with VZV should not receive salicylates because of the risk of Reye syndrome. Use acetaminophen to control fever.
Additional Treatment
General Measures
- Isolation of hospitalized patients with chickenpox:
- Contact and airborne precautions of the index case for the duration of vesicular eruption and all vesicles crusted (usually 5 days, longer in immunocompromised patients)
- Use negative-pressure rooms, if possible.
- Exposed susceptible persons should be in contact and airborne precautions from day 8 to 21 after the onset of rash in the index patient.
- Neonates born to mother with VZV: contact and airborne precautions until day 28
- Embryopathy does not require precautions if there are no active lesions.
- Persons who received VariZIG or IVIG should be kept in contact and airborne precautions for 28 days after exposure.
- Isolation of hospitalized patients with zoster:
- Immunocompromised patients who have zoster (localized or generalized) and immunocompetent patients with disseminated zoster should remain in contact and airborne precautions for the duration of the illness, as above.
- Immunocompetent patients with localized zoster: contact precautions until all lesions crusted.
- Isolation of outpatients with chickenpox:
- Child should remain at home, away from susceptible and high-risk persons, until no new eruptions and all vesicles have crusted.
- Isolation of outpatients with zoster:
- For immunocompetent patients with localized zoster, contact precautions are recommended until all lesions are crusted.
- If lesions can remain completely covered, child may return to school; however, active lesions are infectious.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
For normal healthy individuals, follow-up is not necessary.
Prognosis
- For most children, this childhood exanthema is a benign disease that lasts 6-8 days.
- Postherpetic neuralgia can cause significant morbidity following zoster in adults but is very rare in children.
Complications
Complications are associated with significant morbidity and may occur regardless of the use of acyclovir:
- Secondary bacterial infection-especially group A streptococcal infections and Staphylococcus aureus
- CNS (1 in 4,000): transverse myelitis, myelopathy, encephalitis (60 cases/year prevaccine), meningoencephalitis, acute cerebellar ataxia, necrotizing retinitis
- Varicella interstitial pneumonitis (more common in adults and infants)
- GI: pancreatitis, appendicitis, and hepatitis
- Heme: idiopathic thrombocytopenia, disseminated intravascular coagulation (hemorrhagic VZV)
- Nephritis
- Vasculopathy of small and large cerebral vessels, causing strokes
- Zoster sine herpete: radicular pain without rash but virologic confirmation of reactivation; can be dermatomal or CNS; very rare in the pediatric population
- Individuals with AIDS may have chronic VZV, including progressive myelopathy.
- Congenital varicella syndrome: characterized by limb atrophy and scarring of the extremity (cicatrices), CNS and eye manifestations
- Postherpetic neuralgia: Neuropathic pain is more common in zoster patients >60 years.
- Death: Varicella-related deaths continue to occur despite the recommended vaccine. Secondary bacterial infections and pneumonia are most frequent causes of death.
Additional Reading
- American Academy of Pediatrics. Varicella- zoster infections. In: Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:774-789.
- American Academy of Pediatrics, Committee on Infectious Diseases. Prevention of varicella: update of recommendations for use of quadrivalent and monovalent varicella vaccines in children. Pediatrics. 2011;128(3):630-632. [View Abstract]
- Macartney K, McIntyre P. Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults. Cochrane Database Syst Rev. 2008;(3):CD001833. [View Abstract]
- Marin M, G Œris D, Chaves SS, Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40. [View Abstract]
- Seward JF, Marin M, V Ązquez M. Varicella vaccine effectiveness in the US vaccination program: a review. J Infect Dis. 2008;197(Suppl 2):S82-S89. [View Abstract]
- Vazquez M, LaRussa PS, Gershon AA, et al. The effectiveness of varicella vaccine in clinical practice. N Engl J Med. 2001;344(13):955. [View Abstract]
Codes
ICD09
- 052.9 Varicella without mention of complication
- 053.9 Herpes zoster without mention of complication
- 052.8 Chickenpox with unspecified complication
- 052.9 Varicella without mention of complication
- V05.4 Need for prophylactic vaccination and inoculation against varicella
ICD10
- B01.9 Varicella without complication
- B02.9 Zoster without complications
- B01.89 Other varicella complications
SNOMED
- 38907003 varicella (disorder)
- 4740000 Herpes zoster (disorder)
- 23737006 Chickenpox with complication (disorder)
FAQ
- Q: What do you do for a patient on corticosteroids who has not had VZV and is exposed to VZV?
- A: Patients receiving ≥2 mg/kg/day or ≥20 mg/day of prednisone or its equivalent cannot be immunized with VZV vaccine. If the child is susceptible, has had sufficient exposure, and deemed at risk for serious infection, passive immunization with VariZIG or IVIG can be given.
- Q: Can children receiving inhaled steroids for asthma be immunized safely with VZV vaccine?
- A: Yes. Asthmatics on inhaled steroids can be safely immunized because the dose of inhaled steroid is not immunosuppressive.
- Q: For whom is VZV vaccine contraindicated?
- A: Immunosuppressed individuals, pregnant patients, infants <1 year old, and anyone who has a history of an allergic reaction to a vaccine component such as neomycin should not receive the VZV vaccine. Additionally, any child with a moderate to severe acute illness should have his or her VZV vaccination deferred until his or her illness has resolved. Patients with HIV infection can be vaccinated with VZV vaccine if their CD4+ T-cell percentages are ≥15%.
- Q: Can a child get shingles after vaccination with VZV vaccine?
- A: Yes. Zoster can occur following VZV vaccination. However, cases of shingles following vaccination tend to be milder and less frequent than after wild-type varicella.
- Q: What are the most common adverse effects of VZV vaccination?
- A: Mild local reactions are most common, occurring in 20-25% of vaccine recipients. 1-3% of children will develop a localized rash after vaccination, whereas 3-5% will develop a more generalized varicella-like rash. These rashes typically consist of 2-5 maculopapular or vesicular lesions and occur 5-26 days after vaccination.
- Q: What are the characteristics of breakthrough infection in a child who has been immunized with VZV vaccine?
- A: Breakthrough varicella can occur in children who have been appropriately immunized with VZV vaccine. Breakthrough infection is usually milder than that occurring in unimmunized children, often with fewer than 50 lesions, lower fever, and faster recovery. Although these children are less contagious than those with wild virus infection, they can transmit the virus to susceptible individuals.