Chickenpox

Chickenpox (i.e., varicella) is an infection caused by the varicella zoster virus (VZV). The condition predominantly affects children. Transmission occurs via inhalation of airborne droplets and direct contact with respiratory secretions or skin lesion fluids. Chickenpox manifests with an intensely pruritic rash characterized by sequential clusters of papules, vesicles, and pustules in various stages of development; the rash may be preceded by a prodrome of constitutional symptoms. A clinical diagnosis is made based on the appearance of the rash; confirmatory testing may be obtained for atypical rashes or severe infection. In immunocompetent individuals, chickenpox is self-limiting and managed symptomatically. Antiviral therapy is reserved for patients with severe infection or at high risk for complications (e.g., bacterial superinfection, invasive infections). Following resolution, the virus remains latent in the sensory nerve root ganglia; it can reactivate (see “Shingles”) during episodes of stress or immunosuppression. Prevention includes routine vaccination and, when indicated, postexposure prophylaxis.

• Primarily occurs in children
• Before vaccines were widely introduced, ∼ 90% of all children had been infected by the age of 15.

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: : varicella zoster virus (VZV), a human herpesvirus type 3 (HHV-3) [2]
• Transmission [2]
  • Airborne droplets
  • Direct skin contact with VZV-infected vesicle fluid
  • Transplacental
• Infectivity
  • Highly contagious
  • Two days before and up to five days after the onset of exanthem (or until all the lesions have formed crusts) [3]
• Latency: can become latent after primary infection and reside inside the trigeminal and/or dorsal root ganglia [2]

Risk factors for severe VZV infection [3][4][5]

Individuals with any of the following factors are at risk of severe primary infection if they have no evidence of VZV immunity:

• Age > 12 years
• Immunosuppression
• Pregnancy
• Chronic skin or lung disease [3]
• Long-term salicylate therapy (e.g., aspirin)
• Infancy
  • < 28 days of age [6]
  • Premature infants during their initial hospitalization with any of the following:
    • Born at < 28 weeks gestation
    • Birth weight < 1 kg
    • Born at ≥ 28 weeks to a nonimmune mother
• Household exposure [3]

• Incubation period: ∼ 2 weeks [3]
• Prodrome phase (rare in children) [7]
  • Constitutional symptoms (e.g., fever, malaise, headache, muscle or joint pain)
  • 2–3 days prior to the onset of exanthem
• Exanthem phase: characterized by approx. 250–500 severely pruritic lesions in varying stages of development ; [3][7]
  • Lesion stages: papules→ superficial vesicles filled with clear fluid on an erythematous base (“dewdrop on rose petal” appearance) → umbilicated and crusted pustules → scabs fall off after 1–3 weeks, (often leaving a depressed base)
  • Skin involvement [3][7][8]
    • Lesions first manifest centrally (i.e., face, scalp, and trunk) and spread to the extremities.
    • The rash is ultimately distributed across the body, with the highest concentration of lesions in the central areas.
    • Mucous membranes may be affected (typically oropharyngeal, and possibly urogenital).
    • Ocular involvement may be present (see “VZV conjunctivitis”).
    • Palms and soles are typically spared.
  • Features of severe varicella infection may develop, e.g.: [3]
    • Prolonged high fever (> 1 week)
    • Prolonged eruption of vesicles (> 5 days) [2]
    • Signs of thrombocytopenia, including hemorrhagic skin lesions
    • Symptoms of visceral dissemination (e.g., encephalitis, pneumonia)
• Latent phase: Following resolution of active skin infection, VZV remains latent in the sensory root ganglia; it can later reactivate (see "Shingles”). [7] [3]

Severe varicella infection is characterized by the prolonged eruption of vesicles, which are sometimes hemorrhagic, high fever > 1 week, and dissemination of VZV to the brain (encephalitis), liver (hepatitis), and/or lungs (pneumonia). [3]

Breakthrough varicella infection [3][9]

• Definition: a wild-type VZV infection that occurs in individuals who have received ≥ 1 dose of the chickenpox vaccine ≥ 42 days prior to symptom onset [3][9][10]
• Infectivity: infectious to close contacts [9]
• Clinical features: generally mild compared to typical chickenpox infection [3]
  • Manifests ≥ 42 days following any dose of chickenpox immunization [9][10]
  • Shorter duration of illness and lower likelihood of fever
  • Typically < 50 skin lesions with few or no vesicles (predominantly maculopapular lesions)
• Diagnosis: PCR test confirms a wild-type strain of VZV; see “Diagnostics of chickenpox.” [11][12]
• Treatment: Usually supportive; follow varicella infection prevention measures to reduce spread.

Vaccine-associated chickenpox rash [3][9][13]

• Definition: A vaccine-type VZV infection that occurs following chickenpox immunization. [11][14]
• Incidence: manifests in 5–10% of healthy individuals following chickenpox immunization [11]
• Infectivity: may rarely infect close contacts [9]
• Clinical features
  • A mild illness similar to breakthrough varicella infection [3][9][11]
  • Typically manifests 5– 42 days (21 days median) after varicella immunization [9][14]
  • Lesions are often present at the immunization injection site. [3]
• Diagnosis: PCR testing of lesions confirms vaccine-type strain (i.e., Oka strain); see “Diagnostics of chickenpox.” [11][12][13]
• Treatment: supportive

General principles

• Typically diagnosed clinically based on characteristic clinical features
• Confirmatory diagnostic studies are usually only considered in the following cases: [2][15]
  • Suspected VZV infection in patients with no rash or uncharacteristic rash
  • Vaccinated patients with suspected varicella
  • Patients with immunocompromised contacts
• Additional studies may be required for patients with severe infections.

Confirmatory studies [15][16]

• PCR (preferred test for active infection): detects VZV DNA [2][17][18]
• Direct fluorescent antibody testing on vesicular fluid
• Serology (IgM and IgG detection) can identify primary infection and serologic immunity. [3][15][17]
• Viral culture [7][17]
• Tzanck smear: not specific for VZV (may also be positive in HSV infections) [19]

Chickenpox is usually diagnosed clinically. Obtain laboratory testing in case of atypical rash or severe infections. [2]

Additional studies

Consider in severe varicella zoster infection, depending on clinical features.

• Bacterial superinfection of lesions: See “Diagnostics for sepsis" and "Diagnostics for pediatric sepsis."
• Pneumonia [20]
  • Chest imaging (CT or x-ray chest)
  • Advanced studies: PCR of bronchoalveolar lavage, biopsy of lung tissue
• Meningoencephalitis [21]
  • PCR of CSF
  • MRI brain [22]
• Thrombocytopenia: CBC

Visceral dissemination is more common in patients with HIV; consider HIV testing in patients with severe infection. [23]

Chickenpox may be confused with other conditions that involve widespread vesicles and/or crusting lesions, e.g.: [3][7]

• Disseminated herpes zoster (i.e., shingles)
• Herpes simplex virus: disseminated HSV, eczema herpeticum
• Enterovirus infection: atypical hand foot and mouth disease [24][25]
• Widespread bullous impetigo
• Monkeypox [7]
• Adverse reaction to smallpox vaccination: eczema vaccinatum, disseminated vaccinia [7][26][27]
• See also “Infectious rashes in childhood.”

The differential diagnoses listed here are not exhaustive.

Approach [2]

• Start supportive treatment for all patients.
• Assess for indications for antiviral therapy for varicella; if present, determine duration of symptoms.
  • Symptom duration ≤ 72 hours: Initiate immediate antiviral therapy. [3]
  • Symptom duration > 72 hours: Consult with infectious diseases; antiviral therapy may be appropriate in immunocompromised patients because of prolonged viral replication. [3]
• Provide treatment for complications and superinfections (e.g., treatment of pneumonia, treatment of skin and soft tissue infections).
• Start measures to prevent transmission of VZV.

Most otherwise healthy children < 13 years of age with chickenpox can be treated with symptomatic treatment alone, but advise caregivers to return in the event of prolonged or worsening symptoms and/or signs of secondary bacterial skin infection. [2]

Supportive treatment [2]

• Treat fever and pain with acetaminophen (see “Nonopioid oral analgesia in children”). [2]
• Pruritus ; [28]
  • General advice for caregivers
    • Apply cool compresses.
    • Take lukewarm oatmeal baths.
    • Trim fingernails or wear mitts to prevent scratching.
  • Medications
    • Topical: calamine lotion, pramoxine gel [28]
    • Oral antihistamines

Avoid use of aspirin and other salicylates (e.g., bismuth-subsalicylate) in children with chickenpox because of the risk of Reye syndrome. [3]

Avoid topical antihistamines and topical corticosteroids in patients with chickenpox because of the risk of systemic absorption when applied to large areas of skin. [29]

Antiviral therapy for VZV infection (high-risk patients only)

• Indications for antiviral therapy
  • Severe VZV infection
  • Risk factors for severe VZV infection
• Recommended treatment: Begin antiviral therapy as soon as possible (ideally within 24 hours of rash onset). ; [3]
  • Immunocompromised individuals, neonates, and/or those with severe infection: IV acyclovir [2][3]
  • Immunocompetent individuals, individuals with nonsevere infection: oral acyclovir or valacyclovir [3][8][30]

Patients with nonsevere infections and no risk factors for severe VZV infection do not require antiviral therapy and can be managed with supportive treatment only. [2]

Neonates, immunocompromised patients, and patients with severe infection should not receive oral acyclovir because of poor oral bioavailability. [3]

Adults have higher rates of complications from varicella compared to children. [2]

Skin [3]

• Bacterial superinfection; (including impetigo, phlegmon, necrotizing fasciitis), which often leads to scarring and is managed with systemic antibiotics
• Reactivation of latent VZV results in shingles (herpes zoster).
• Scarring

Central nervous system [3][31]

• Acute cerebellar ataxia: good prognosis, mainly self-limiting after several weeks
• Encephalitis (very rare): cramps, coma, poor prognosis

Lungs [3]

• Pneumonia (viral or bacterial)

Fetus (chickenpox during pregnancy) [3]

• Congenital varicella syndrome

We list the most important complications. The selection is not exhaustive.

• In healthy children, chickenpox infection generally has a benign course and heals without any consequences.
• Residual scarring may occur because of excessive scratching or bacterial superinfection.
• Immunosuppressed individuals are at a greater risk of the disease taking a generalized or even fatal course.

References:[2]

Approach

• Provide primary prevention against varicella infection.
  • Ensure children receive varicella vaccination as part of the routine immunization schedule.
  • Offer catch-up vaccinations to individuals without evidence of VZV immunity.
• For infected patients: Initiate measures to limit transmission.
  • Tell patients to avoid school/work until all lesions have scabbed over and no new lesions appear. [3]
  • If hospitalized, start infection control measures to prevent nosocomial spread of varicella.
  • If required by law, notify the health department for possible contact tracing.
• For close contacts:
  • Assess for evidence of VZV immunity.
  • Offer postexposure prophylaxis for chickenpox to individuals with no evidence of immunity.

Most US states mandate reporting cases of chickenpox to local and/or state health departments. [32]

Evidence of VZV immunity [3][8][9]

Any of the following constitutes evidence of immunity to chickenpox: [9][33]

• Documentation of age-appropriate varicella immunization
• Laboratory findings that confirm prior wild-type disease or serologic evidence of immunity (see “Diagnostics of chickenpox”)
• Attestation of past varicella or herpes zoster infection by a healthcare provider

Varicella vaccine [34][35][36]

• General principles
  • Consists of 2 doses of a live attenuated vaccine
  • Available vaccines include: [3][5][37]
    • A single-antigen varicella vaccine
    • A combined measles, mumps, rubella, varicella (MMRV) vaccine [38]
  • Recommended for all individuals without evidence of VZV immunity who have no contraindications to live vaccines
• Schedule: See “ACIP immunization schedule” for details on routine and catch-up schedules.
• Adverse effects [3]
  • Minor injection-site reaction and fever
  • If MMRV is given at 12– 23 months of age: increased risk of febrile seizures
  • Vaccine-associated chickenpox rash
  • Future development of shingles [3]

Recommend the varicella vaccine to all nonimmune children and adults who do not have contraindications to live vaccination. [37][39]

Postexposure prophylaxis for chickenpox [4][9]

General principles

• Postexposure prophylaxis is recommended for nonimmune individuals exposed to chickenpox or shingles to prevent disease onset or mitigate disease course. [3][40]
• Eligibility is determined by assessing for evidence of VZV immunity and verifying exposure.
• High-risk interactions include:
  • Indoor face-to-face contact with an infected individual for ≥ 5 minutes [3][9]
  • Sharing a hospital room or living arrangements with an infected individual
• Active or passive immunization is given depending on risk factors.
• For patients who are ineligible for active immunization and cannot receive passive immunization: Consult infectious disease about possible chemoprophylaxis. [3]
• Passive immunization may prolong the incubation period of VZV; monitor patients for 28 days following exposure. [3][41]
• If symptoms develop following exposure, initiate treatment for varicella infection regardless of whether the patient received postexposure prophylaxis.

Determining postexposure prophylaxis

Active immunization

• Indications: immunocompetent patients ≥ 12 months of age with no evidence of VZV immunity [3]
• Recommended prophylaxis
  • Chickenpox immunization
  • Give within 5 days following exposure (ideally within 3 days). [9]
• Follow-up vaccination: Complete the age-appropriate vaccination series per the immunization schedule.

Prophylaxis is not recommended for healthy individuals who are either too young for vaccination or who were exposed to VZV > 5 days prior to evaluation. [3]

Passive immunization

• Indications
  • Individuals with no evidence of VZV immunity who are:
    • Immunocompromised
    • Pregnant
  • Patients who have undergone bone marrow transplantation [9]
  • Neonates, if the mother was symptomatic 5 days before or up to 2 days after birth [3][9]
  • Hospitalized premature babies if:
    • Born < 28 weeks or with a birth weight ≤ 1 kg [41]
    • Born ≥ 28 weeks to a mother without evidence of VZV immunity [41]
• Recommended prophylaxis: Give as soon as possible within 10 days following exposure (ideally within 4 days). [41]
  • Preferred: varicella-zoster immune globulin (VZIG) [3][41]
  • If VZIG is unavailable within 10 days postexposure: intravenous immunoglobulin (IVIG) [3]
• Follow-up vaccination
  • Recommended for all patients without contraindications to live vaccination.
  • Give 5–8 months after immunoglobulin therapy. [42]

Controlling varicella transmission in healthcare settings [43]

• Place patients with chickenpox on contact and airborne precautions (see “Infection prevention and control”). [3]
• All health care workers should have evidence of immunity to chickenpox.
• If a health care worker with no evidence of immunity is exposed, notify their supervisor and the occupational health department. [3]

Varicella in pregnancy [6][9]

Overview

• Infection during pregnancy and the peripartum period is associated with significant complications.
• Pregnant woman: increased risk of varicella pneumonia [6]
• Fetus: congenital varicella syndrome [3][6]
• Neonate: neonatal varicella [3][6]

Diagnostics

• No modifications are required in pregnant patients.
• See “Diagnostics of chickenpox.”

Treatment

• VZV diagnosed in pregnancy [18]
  • Evaluate for evidence of fetal VZV infection with:
    • Fetal imaging (i.e., ultrasound, MRI) [6][18]
    • Amniocentesis for VZV PCR [18]
  • Initiate antiviral therapy (see “Treatment of chickenpox”). [3][6][18]
• VZV diagnosed in the peripartum period:
  • Administer postexposure VZV prophylaxis to the neonate. [3]
  • Separate the mother and child until the mother is no longer infectious. [3]

Prevention of varicella in pregnancy [6][9]

• Prior to pregnancy: Offer vaccination to patients with no evidence of VZV immunity who are willing to delay conception for 3 months. [6][9]
• During pregnancy:
  • Screening for varicella immunity is a routine part of prenatal care.
  • Offer nonimmune patients vaccination after pregnancy and postexposure VZV prophylaxis if an exposure occurs during pregnancy.
• See also “Prevention of chickenpox.”

Pregnant women should not receive the varicella vaccine. Nonimmune women should be vaccinated after delivery. [9]

Varicella in adults [1]

Overview

• Adults are more likely than children to have a prodrome of fever and malaise prior to rash. [7]
• Adult patients are more likely to experience complications of varicella. [2]

Management

• No modifications to diagnostics of chickenpox are required.
• For treatment of chickenpox in nonimmune adults, antiviral therapy is recommended.

Varicella in patients with HIV [23]

Overview

• Most adults with HIV have acquired varicella immunity prior to HIV infection.
• If infected, adults and adolescents with HIV are more likely to develop disseminated infection.
• See also “Cutaneous complications in HIV infection.”

Diagnostics

• No modifications are required in patients with HIV.
• See “Diagnostics of chickenpox.”

Treatment

• Antiviral treatment is recommended. [23]
• Discuss route of antiviral treatment with infectious diseases. [23]
  • Uncomplicated infection is usually treated with oral antivirals
  • Severe or complicated infection is usually treated with IV antivirals
• See also “Treatment of chickenpox.”

Prevention

• Discuss vaccination with infectious diseases; typically recommended for individuals with a well-preserved immune system. [23]
• Patients with no evidence of VZV immunity require passive immunization for postexposure prophylaxis. [23]