Chickenpox

Background

Chickenpox is an acute, systemic viral illness caused by infection with VZV (human herpesvirus type 3).^[1]  It afflicts approximately 84 million cases annually and is predominantly seen in pediatric populations.^[2]

The varicella-zoster virus (see the image below) is the etiologic agent of the clinical syndrome of chickenpox (varicella).^{[1, 3]}  Herpes zoster (shingles), a different clinical entity, is caused by reactivation of VZV after primary infection. Varicella-zoster virus is a double-stranded deoxyribonucleic acid virus included in the Alphaherpesvirinae subfamily. (See Etiology.)

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Vesicular eruption on the trunk demonstrating papules, vesicles, and crusts. Reprinted with permission from Cutis 65: 355, 2000.

Chickenpox primarily spreads through airborne respiratory droplets and can also transmit via direct contact with the vesicles, although this method poses a lower risk. (See Etiology) It predominantly affects children under 10 years, where it usually presents benignly, but it can lead to increased morbidity in adults and immunocompromised individuals. (See Epidemiology and Prognosis)

Since the introduction of the varicella vaccine in the United States in 1995, the incidence of chickenpox has decreased by nearly 90%. (See Epidemiology) Diagnosis is typically clinical, based on the characteristic rash and patient history of exposure within the 10-21 day incubation period. Adults may experience a more severe course with widespread rash and complications such as varicella pneumonia. (See Clinical Presentation)

Definitive diagnosis can be achieved through vesicular fluid cultures or direct immunofluorescence (See Workup). Treatment options include oral acyclovir for those at risk for severe infections, with valacyclovir and famciclovir as alternatives. Intravenous acyclovir is advised for immune-compromised patients, and varicella-zoster immune globulin (VZIG) is recommended for highly susceptible, exposed immunocompromised individuals. The live attenuated varicella vaccine (Oka strain) has been available since 1995 for prophylactic use in healthy children and adults. (See Treatment, Guidelines, and Medication)

See Pediatric Vaccinations: Do You Know the Recommended Schedules?, a Critical Images slideshow, to help stay current with the latest routine and catch-up immunization schedules for 16 vaccine-preventable diseases.

Also, see the 15 Rashes You Need to Know: Common Dermatologic Diagnoses slideshow for help identifying and treating various rashes.

Go to Pediatric Chickenpox for more complete information on this topic.

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Pathophysiology

Varicella-zoster virus is transmitted person to person primarily through the respiratory route by inhalation of aerosols from vesicular fluid of skin lesions of varicella or herpes zoster. It can also spread by direct contact with the vesicular fluid of skin lesions and possibly infected respiratory tract secretions.^{[4, 5]}  Varicella-zoster virus enters the host through the upper respiratory tract or the conjunctiva. After initial inhalation of contaminated respiratory droplets, the virus infects the conjunctivae or the mucosae of the upper respiratory tract,^[6]  with viral proliferation occurring in regional lymph nodes 2-4 days after infection. This is followed by primary viremia on days 4-6 post-infection, and a secondary round of viral replication in internal organs, notably the liver and spleen, leading to a secondary viremia 14-16 days post-infection, characterized by diffuse viral invasion of capillary endothelial cells and the epidermis.^[6]

Varicella is highly contagious with secondary attack ratios of approximately 85% (range 61%–100%) in susceptible household contacts, though it is less contagious after community exposure.^[4]  Herpes zoster is about 20% as infectious as varicella, and contact with herpes zoster rash in susceptible individuals results in varicella, not herpes zoster.^[4]  The communicability of varicella begins about 1-2 days before the onset of rash and ends when all lesions have crusted, typically 4-7 days after the onset of the rash in immunocompetent individuals; this period may be extended in immunocompromised individuals.^[4]  Vaccinated individuals who contract chickenpox may develop lesions that do not crust, and they are considered contagious until no new lesions have appeared for 24 hours. Patients with herpes zoster are contagious while they have active, vesicular lesions, usually for 7-10 days. In utero infection also can occur through transplacental passage of the virus during maternal varicella infection.^[4]

Exposure to VZV in a healthy child initiates the production of host immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies; IgG antibodies persist for life and confer immunity.^[6]  Cell-mediated immune responses are also crucial in limiting the scope and duration of primary varicella infection. After primary infection, VZV is hypothesized to spread from mucosal and epidermal lesions to local sensory nerves, remaining latent in the dorsal ganglion cells of the sensory nerves. Reactivation of VZV results in the clinically distinct syndrome of herpes zoster (shingles).^[6]

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Etiology

Chickenpox usually is acquired by the inhalation of airborne respiratory droplets from a VZV-infected host. High viral titers are found in the characteristic vesicles of chickenpox; thus, viral transmission also may occur through direct contact with these vesicles.

Coronavirus disease 2019 (COVID-19) may rarely occur simultaneously with chickenpox, producing serious pulmonary disease even in a healthy immunocompetent individual.^[7] Reactivation may occur with immunosuppression and during coronavirus disease 2019 (COVID-19) infection. Some varicelliform eruptions during COVID-19 are actually varicella.^{[8, 9, 10]}

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Epidemiology

Varicella, commonly known as chickenpox, is endemic globally. In temperate climates, it predominantly affects children, with the highest incidence observed among preschool and elementary school-aged populations; less than 5% of adults are susceptible.^[4]  Seasonally, the disease typically manifests in late winter and early spring. In contrast, in tropical climates, varicella infection generally occurs later in childhood and is more prevalent among adults, particularly in sparsely populated areas. The disease incidence in these regions peaks during the driest and coolest months. Its incidence was reduced during the COVID pandemic. In Poland, the incidence of chickenpox by 2022 was found to be back at pre-COVID pandemic levels.^[11]  

The implementation of the childhood varicella vaccination program in the United States in 1996 has led to substantial reductions in the incidence of this disease.^[4] Although varicella remains endemic, the risk for VZV exposure in the United States now is comparatively lower than in most other regions globally. As of 2019, 18% of countries had integrated routine varicella vaccination into their national immunization schedules, and an additional 6% target vaccinations to specific high-risk groups.

Due to the worldwide prevalence of varicella, all travelers susceptible to the virus are at risk for infection during international travel.^[4] Additionally, exposure to herpes zoster can result in varicella among susceptible individuals, although it is significantly less transmissible than primary varicella infection. Infants, adults, and immunocompromised individuals lacking immunity are at the highest risk for severe varicella.

United States

In the early 1990s, before the introduction of the chickenpox vaccination program, chickenpox was extremely prevalent in the United States.^[12] Annually during this period, over 4 million cases of chickenpox were reported, leading to between 10,500 and 13,500 hospitalizations, and resulting in 100 to 150 deaths. Notably, a significant portion of these cases and hospitalizations, as well as half of the deaths, occurred among children. This underscores the substantial impact of chickenpox on pediatric populations prior to widespread immunization efforts.

International

Countries with tropical and semitropical climates have a higher incidence of adult chickenpox than do countries with a temperate climate (eg, United States, Europe).

In the United States, high vaccination rates are achieved across many states and jurisdictions, with mandates requiring children to be vaccinated against vaccine-preventable diseases before starting school.^[13] Conversely, in Japan, whereas the varicella vaccine was incorporated into routine immunization programs in 2014, it is not mandatory for school entry, resulting in lower vaccination rates compared to the United States. The basic reproduction number for varicella, estimated to be between 8 and 10, suggests that the current vaccination coverage in Japan is inadequate to control the spread of the disease, highlighting the need for increased vaccination efforts.

Additionally, although herpes zoster predominantly affects individuals older than 50 years, a decrease in varicella incidence could lead to an increase in herpes zoster cases among younger populations.^[13] This shift underscores the importance of herpes zoster vaccination, particularly for those with diminished cell-mediated immunity (CMI) against VZV. Developing methods to assess CMI activity is crucial for identifying individuals at risk and effectively targeting vaccination efforts.

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Prognosis

Chickenpox typically presents as a mild illness in children. However, severe or life-threatening cases are more likely to occur in the following groups^[1] :

• Adults
• Individuals with compromised T-cell immunity, such as those with lymphoreticular cancers
• Patients undergoing treatment with corticosteroids, chemotherapy, or other immunosuppressive therapies
• Patients receiving tumor necrosis factor (TNF) antagonists

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Patient Education

Parents of infected children should be instructed to trim their children’s fingernails to minimize skin damage from scratching and the associated complications of bacterial superinfection. Also, it is important to advise parents not to use aspirin for fever control, because the development of Reye syndrome is associated with salicylate administration in children with chickenpox.

Please see Pediatric Chickenpox.

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History

Chickenpox usually is diagnosed clinically on the basis of the characteristic rash and successive crops of lesions.^[1] Lesions may be found in all stages of development and healing in affected sites. A history of exposure to an infected contact within the incubation period of 10-21 days also is an important clue in the diagnosis.

Childhood chickenpox usually is not heralded by a prodrome; it begins with the onset of an exanthem. In adults and adolescents, chickenpox may be preceded by a prodrome of nausea, myalgia, anorexia, and headache. The triad of rash, malaise, and a low-grade fever can signal disease onset, though the typical patient is infectious for 1-2 days prior to the development of rash.

Small, erythematous macules appear on the scalp, face, trunk, and proximal limbs, with rapid sequential progression over 12-14 hours to papules, clear vesicles, and pustules and subsequent central umbilication and crust formation.

Vesicles may appear on the palms and the soles and on the mucous membranes, together with painful, shallow, oropharyngeal or urogenital ulcers. Intense pruritus commonly accompanies the vesicular stage of the rash.

The typical patient remains infectious for 4-5 days after the rash develops, by which time the last crop of vesicles usually has crusted over.

Secondary bacterial infection

Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most frequent complication in otherwise healthy children.^{[1, 4]}  Staphylococci and streptococci are the most commonly implicated bacterial pathogens. Bacterial superinfection may predispose to scarring. Localized bacterial superinfection rarely may manifest as septicemia, culminating in secondary bacterial pneumonia, otitis media, or necrotizing fasciitis. The latter represents significant, potentially life-threatening morbidity.

Disseminated primary varicella infection

Disseminated primary varicella infection, usually seen in the immunocompromised or adult populations, may have high morbidity.^{[1, 4]} Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, gangrene, hepatitis, and glomerulonephritis. Eczema varicellicum (mimicking eczema herpeticum) can occur.^[14]

CNS complications

Central nervous system complications of primary varicella-zoster virus (VZV) infection may occur, albeit very rarely.^{[1, 4]} Reye syndrome, Guillain-Barré syndrome, acute cerebellar ataxia, and encephalitis all have been documented to occur after VZV infection.

Hemorrhagic complications

Thrombocytopenia and purpura secondary to VZV infection have been described in more than 100 patients.^{[1, 4]} Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected.

Five major clinical syndromes have been described:

• Anaphylactoid purpura
• Febrile purpura
• Malignant chickenpox with purpura
• Postinfectious purpura
• Purpura fulminans

These syndromes have variable courses, with febrile purpura being the most benign and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality exceeding 70%.

The etiology of these hemorrhagic chickenpox syndromes is not known, although an autoimmune pathophysiologic mechanism has been implicated.

In utero VZV infection

In utero infection with VZV is a concern.^{[15, 16, 17]}  Primary maternal chickenpox during pregnancy may produce latency of VZV in the dorsal root ganglia of the fetus. These children may remain asymptomatic, or they may develop zoster at a young age without a previous history of primary chickenpox infection. Primary maternal chickenpox infection in early to mid-pregnancy is estimated to have a 1%-2% risk of causing the congenital varicella syndrome, which is characterized by limb hypoplasia, muscular atrophy, skin scarring, cortical atrophy, microcephaly, cataract formation, and rudimentary digits.

Antepartum infection with onset of chickenpox in the mother 5 or more days previous to delivery allows transplacental passage of sufficient maternal IgG antibody to protect the newborn from severe, disseminated varicella infection.^[18]

Peripartum infection of the fetus before sufficient maternal antibody has crossed the placenta to confer transient passive immunity to the fetus (ie, when the mother experiences onset of chickenpox < 5 d before delivery or within 2 d after delivery) often results in severe disseminated varicella in the newborn infant, which has substantial mortality.^[18]

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Physical Examination

The characteristic chickenpox vesicle, surrounded by an erythematous halo, is described as a dewdrop on a rose petal^[19] (see the images below).

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Dewdrop on rose petal characteristic vesicle of chickenpox. Reprinted with permission from Cutis 65: 355, 2000.

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Vesicular eruption on the trunk demonstrating papules, vesicles, and crusts. Reprinted with permission from Cutis 65: 355, 2000.

Chickenpox is clinically characterized by the presence of active and healing lesions in all stages of development within affected locations. Lesions characteristically heal without scarring, although excoriation or secondary bacterial superinfection predisposes to scar formation.

Adults with chickenpox have a more complicated course than that occurring in children. Adults may experience a more widespread rash; prolonged fever; and an increased likelihood of complications, the most common being varicella pneumonia.

Clinical variants of chickenpox infection also occur. Hemorrhagic lesions are rare and are most commonly associated with patients who are immunocompromised or immunosuppressed.

Bullous chickenpox is a rare variant in which bullae appear instead of the characteristic vesicles.^{[20, 21]} The possibility of bullous impetigo from Staphylococcus aureus must be addressed, especially in a child with persistent fever or relapse after they appeared to be improving.

Bullous chickenpox may affect both children and adults and must be differentiated from other bullous disorders (ie, bullous pemphigoid, pemphigus).^[22] The course of the disease is believed to be unchanged, although a delay in diagnosis and treatment of elderly patients and immunocompromised patients may lead to serious morbidity.

Chickenpox and other viral exanthems may appear concentrated in areas where intense sun exposure occurred during the incubation period. Patients with atopic dermatitis may show an atypical distribution of varicella, in which the characteristic eruption primarily is found on lichenified areas.^{[19, 23]}  An atypical presentation also may occur in areas of cutaneous irritation, such as sun exposure or pre-existing inflammation.^[24]  

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Approach Considerations

Chickenpox typically is suspected in patients who present with its distinctive rash, which is commonly used for clinical diagnosis.^[1]  However, this rash also may resemble those associated with other viral dermatoses,^[25]  necessitating laboratory confirmation in uncertain cases.

Laboratory confirmation techniques

For definitive diagnosis, several laboratory techniques are available^[1] :

• Immunofluorescence identifies viral antigens in lesion samples.
• Polymerase chain reaction (PCR) is highly recommended for its sensitivity in detecting viral DNA.
• Serologic assay tests measure IgM antibodies specific to varicella-zoster virus (VZV) or demonstrate seroconversion from negative to positive VZV antibody titers, indicating an acute infection.
• Tzanck smear is useful for visualizing cellular changes associated with herpes virus infections but does not differentiate between VZV and HSV.
• Viral culture, although definitive, is less sensitive than PCR and has a longer turnaround time.

Specimen collection and handling

Diagnostic specimens typically are obtained by scraping the base of the lesion and should be transported to the laboratory in appropriate viral transport media.^[1] Alternative specimens such as nasopharyngeal secretions, saliva, urine, bronchial washings, and cerebrospinal fluid are generally less ideal for VZV detection, often leading to suboptimal samples and a higher likelihood of false-negative results.^[29]

Additional diagnostic considerations

Histologic examination of skin lesions provides limited differentiation between VZV and HSV. However, specific histologic features such as leukocytoclastic vasculitis and hemorrhage may suggest VZV. Immunohistochemistry and direct fluorescent antibody (DFA) testing can further aid in differentiating between these infections.^[30]  Other methods like DFA and additional viral cultures generally are less recommended due to their lower sensitivity compared to PCR.^[29]

In a 12-month study focusing on the diagnostic accuracy of PCR compared to viral cultures and Tzanck smears, researchers analyzed samples from patients with suspected HSV or VZV infections.^[31] The final analysis included 77 patients: 30 with HSV, 32 with VZV, and 15 controls without evidence of viral infection.

The results showed that PCR was highly effective in detecting viral DNA. For HSV, PCR identified DNA sequences in 73% of stained smears and 83% of unstained smears. In cases of VZV, the detection rates were even higher, with 88% for stained smears and 97% for unstained smears.

In contrast, viral cultures showed a lower detection rate, particularly for VZV, with positive results in 83% of HSV cases and only 44% of VZV cases. The Tzanck smear method had a positivity rate of 60% for HSV and 75% for VZV.

The study concluded that PCR is a more reliable and effective method for diagnosing both HSV and VZV infections compared to traditional viral cultures, especially for VZV. This suggests that PCR should be considered a preferred diagnostic tool in clinical settings for its higher sensitivity and specificity.

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Polymerase chain reaction (PCR)

PCR testing is highly sensitive for detecting varicella-zoster virus (VZV) DNA and is considered the gold standard for laboratory confirmation. Optimal specimens for PCR include vesicular lesions or scabs. Challenges may arise when collecting specimens from maculopapular lesions in vaccinated individuals; however, proper collection techniques can yield reliable results. PCR-based techniques, while highly sensitive, may not be universally available.

Virus Strain Identification

PCR testing and genotyping are critical tools for distinguishing between wild-type VZV and vaccine-type (Oka/Merck) strains of VZV.^{[29, 32, 33]} This differentiation is particularly important in cases where identifying the specific strain of VZV can inform clinical decisions, such as in suspected vaccine adverse events.

Examples of potential vaccine-related adverse events include:

• Occurrence of varicella or a varicella-related complication in a vaccinated individual 7 to 42 days post-vaccination.
• Development of herpes zoster in a vaccinated individual.
• Suspected secondary transmission of vaccine-strain VZV.

To confirm the etiology and identify a vaccine-related adverse event, samples such as blood, cerebrospinal fluid, biopsies, or autopsy specimens may be tested to differentiate between vaccine-strain and wild-type VZV. However, it is important to note that these specimens might yield false negative results, which can complicate the diagnostic process.

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Tzanck Smear

The Tzanck smear involves a superficial scraping from a freshly ruptured vesicle, stained with Wright-Giemsa or toluidine blue. This method reveals multinucleated giant cells and epithelial cells with eosinophilic intranuclear inclusion bodies, indicative of herpes simplex and herpes zoster infections. However, it does not differentiate between these viruses.^[1]

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Culture

Viral culture can provide a definitive diagnosis of VZV but is technically challenging and less sensitive than PCR, with positive results in less than 40% of cases. Cultures also have a longer turnaround time, typically 1 to 2 weeks, which may delay diagnosis and treatment.^[1]

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Serology

Serologic testing is utilized to identify VZV-specific antibodies (IgM and IgG) and can indicate acute infection through seroconversion.^[1] Various assays are employed, including complement fixation, enzyme immunoassay, fluorescent antibody to membrane assay, indirect fluorescent antibody, and latex agglutination test. Among these, the latex agglutination test is most commonly used for assessing exposure and immunity due to its practicality, although it and other serologic tests may not be as sensitive as molecular methods.

Serologic tests can retrospectively confirm a diagnosis through a substantial rise in serum varicella IgG titers from acute- and convalescent-phase samples by any standard serologic assay. However, these antibody tests might not be reliable in immunocompromised individuals. In vaccinated individuals, baseline IgG levels might be high, potentially preventing a 4-fold increase in convalescent serum samples.^[4]  Testing for varicella-zoster IgM using commercial kits is not recommended due to the lack of sensitivity and specificity of available methods; false-positive IgM results are common in the presence of high IgG levels, and a positive IgM does not distinguish between primary infection and reactivation.^[4]

This consolidation highlights that whereas serologic tests are useful for assessing exposure and immunity, they are less reliable than PCR or direct fluorescent antibody methods for virus identification, especially in certain populations such as the immunocompromised or previously vaccinated.^[4]

Evaluating VZV susceptibility

IgG ELISA

IgG ELISA is utilized to determine if an individual has antibodies to VZV from previous varicella infection or vaccination.^[29] This test is crucial for identifying candidates for varicella-zoster immune globulin (VZIG), with VariZIG being the product available in the United States.^{[34, 35]} The whole infected cell (wc) ELISA, commonly used in commercial settings, effectively detects seroconversion to natural VZV infection from blood samples. However, routine testing for varicella immunity post-vaccination is not recommended, as commercial VZV IgG assays lack the sensitivity to detect all seroconversions following vaccination. In research settings, the more sensitive purified glycoprotein ELISA (gpELISA) is used to detect seroconversion post-vaccination, but it is not commercially available.

IgG avidity

IgG avidity testing, primarily conducted in research settings, helps determine whether an individual with IgG positivity for VZV was infected recently or in the past.^[29] The CDC has developed an IgG avidity assay to ascertain whether the most recent VZV rash resulted from a primary infection (varicella) or reactivation (herpes zoster). High avidity indicates a remote infection, whereas low avidity suggests a primary VZV infection. Following vaccination, individuals undergo antibody affinity maturation, leading to moderate to high IgG avidity VZV antibody levels. However, measuring VZV avidity in vaccinated individuals does not effectively distinguish between remote and recent infections. This test is not available commercially.

Establishing laboratory evidence of immunity to varicella

A positive IgG ELISA result confirms the presence of antibodies to VZV from past disease or vaccination, but it cannot differentiate between antibodies developed from natural infection or vaccination.^[29] Whereas many commercial VZV IgG ELISAs are adequate for detecting seroconversion from wild-type virus infections, their performance specifications, including specificity and sensitivity, vary significantly. Some commercially available VZV IgG assays are unreliable for detecting a natural disease history, and currently, there are no commercial methods sensitive and specific enough to reliably detect seroconversion to the vaccine.

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Chest Radiography

Chest radiography is indicated for adults who are experiencing pulmonary symptoms of chickenpox.

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Histologic Findings

Histologic examination of skin lesions does not differentiate VZV from herpes simplex virus (HSV) infection. Intranuclear eosinophilic inclusion bodies are seen in epithelial cells in both infections. Leukocytoclastic vasculitis and hemorrhage are more common in VZV lesions than HSV, however, and both immunohistochemistry and direct fluorescent antibody testing can be used to differentiate between the infections.^[30]

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Approach Considerations

In mild cases of chickenpox in children, symptomatic treatment ypically sufficient.^[1] Managing itching and preventing scratching, which can lead to secondary bacterial infections, is crucial. Wet compresses, systemic antihistamines, and colloidal oatmeal baths can be effective for severe itching.

To minimize the risk for secondary bacterial infections, regular bathing, maintaining clean underclothing and hands, and keeping nails trimmed are recommended. Antiseptics only should be used if lesions become infected, at which point bacterial superinfections may require antibiotic treatment.

Patients should avoid returning to school or work until all lesions have crusted over.

Antivirals and chickenpox

Oral antivirals can slightly reduce the duration and severity of symptoms if administered to immunocompetent patients within 24 hours of the onset of the rash.^{[1, 4]} However, antiviral treatment is not routinely recommended for healthy children younger than 12 years owing to the generally benign nature of the disease in this age group.

Oral valacyclovir, famciclovir, or acyclovir should be considered for individuals at risk for moderate to severe disease, including those who are unvaccinated and older than 12 years (older than 18 years for famciclovir), have skin disorders such as eczema, suffer from chronic lung disease, are on long-term salicylate therapy, are undergoing current corticosteroid therapy, or have contracted a secondary case from household contacts, which tend to be more severe than primary cases.

For adults who are immunocompetent, famciclovir or valacyclovir are preferred due to better oral bioavailability compared to acyclovir. Immunocompromised patients aged 1 year and older should receive IV acyclovir.

Pregnant individuals, who are at increased risk for severe varicella complications, may be prescribed oral acyclovir or valacyclovir, although the safety of antiviral therapy during pregnancy is not conclusively established. Acyclovir and valacyclovir are classified as pregnancy category B drugs. IV acyclovir is advised for serious varicella cases in pregnant people. Due to limited safety data, famciclovir generally is not recommended during pregnancy.

Also see the Guidelines section.

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Treatment in Healthy Children

The symptoms of chickenpox in the pediatric population can be treated topically and with oral agents. Pruritus can be treated with calamine lotion or pramoxine gel; powdered oatmeal baths; or oral antihistamines.

The nucleoside analogue acyclovir (20 mg/kg PO qid for 5 d), though shown to decrease the symptoms and duration of primary varicella infection when administered within 24 hours of onset of symptoms, is not commonly prescribed for otherwise healthy children.^{[4, 36]}

Given the high risk for varicella-related complications, children should be treated if any of the following conditions are a medical concern:

• Chronic asthma
• Chronic atopic dermatitis
• Defects in cell-mediated immunity
• Iatrogenic immunosuppression
• Long-term systemic steroid use
• Nephrotic syndrome
• Splenic dysfunction

Go to Pediatric Chickenpox for more complete information on this topic.

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Treatment in Immunocompetent Adults

Oral acyclovir should be considered for healthy persons at increased risk for severe varicella infections, most notably patients older than 12 years.^{[1, 4]} Oral acyclovir therapy in this population (800 mg 5 times/d for 7 d), begun within 24 hours of onset of symptoms, has been shown to decrease the duration of lesions and pyrexia, while reducing other symptoms and disease duration.

Valacyclovir, the L-valyl ester of acyclovir, is a prodrug that has higher oral bioavailability than acyclovir. Valacyclovir is used in the treatment of herpes zoster, but no large-based clinical trials yet have demonstrated its efficacy in primary varicella infection of healthy, immunocompetent individuals.

Famciclovir is a prodrug of penciclovir, which is a nucleoside analogue similar to acyclovir. Like valacyclovir, famciclovir has demonstrated efficacy in the treatment of herpes zoster, but it has not been extensively studied for use in primary varicella infection of healthy populations.

A few case reports also have found sorivudine, a nucleoside analogue that is a potent in vivo inhibitor of varicella-zoster virus (VZV) replication, to be effective in the treatment of primary varicella in healthy adults. Larger scale clinical trials are needed to demonstrate the efficacy of this medication.

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Treatment in the Immunocompromised or Immunosuppressed

Intravenous acyclovir therapy is recommended for patients who are immunosuppressed or immunocompromised, because of the life-threatening complications of primary varicella infection to which they are particularly susceptible. Severe disseminated disease, with the development of varicella pneumonia, encephalitis, hepatitis, and hemorrhagic complications, is much more common in this population than in other populations.^[37]

Secondary complications (eg, bacterial pneumonia, meningitis) caused by bacterial superinfection of cutaneous lesions with subsequent septicemia, are more common and dangerous among those who are immunocompromised.

Case reports have described vidarabine, a purine nucleoside analogue, and interferon-alpha to be effective in the treatment of primary varicella infection of immunocompromised hosts. Acyclovir-resistant strains of VZV have been reported in patients with AIDS.

Foscarnet, an inorganic pyrophosphate analogue that acts as a selective inhibitor of viral deoxyribonucleic acid polymerases and reverse transcriptases, is a potentially efficacious drug in patients with acyclovir-resistant VZV strains. Optimal dosage, duration of therapy, and efficacy in primary varicella infection need further investigation. Treatment of primary varicella in these populations is difficult and necessitates an integrated team approach.^[38]

Continuing research into new antiviral agents and ongoing clinical trials are constantly adding new information relative to the pharmacotherapeutic options in the fight against VZV infections.

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Chickenpox in Pregnancy

Clinicians should inquire about previous chickenpox or shingles infections when women present for antenatal care.^[39] Pregnant individuals who have not had chickenpox or who are known to be seronegative should avoid contact with infected individuals and promptly inform their clinician of any potential exposure. Clinicians must then confirm the exposure through a detailed history to assess the significance of the contact and the patient's susceptibility, supplemented by a blood test to determine immunity to the varicella-zoster virus (VZV). If a significant exposure is confirmed and the patient is not immune, post exposure prophylaxis (PEP) should be considered. The first choice for PEP is oral antiviral therapy, such as aciclovir or valaciclovir, recommended to be given from Day 7 to 14 post-exposure. If there are contraindications or adverse effects to antivirals, varicella-zoster immune globulin (VZIG) may be used, effective up to 10 days after contact.

If exposed again, pregnant women may require a second dose of VZIG 3 weeks after the initial dose.^[39] Should pregnant individuals develop the characteristic rash, they must immediately contact their clinician and isolate from other pregnant people and neonates until the lesions have crusted over, typically about 5 days post-rash onset. Symptomatic treatment and maintaining hygiene are crucial to prevent secondary bacterial infections. Clinicians should consider a hospital assessment for patients at high risk for severe or complicated chickenpox, regardless of their clinical status, and refer those who develop chickenpox to a fetal medicine specialist, virologist, and neonatologist to decide on treatment. The timing and mode of delivery should be individualized for pregnant patients with chickenpox. Lastly, mothers with chickenpox should continue to breastfeed if they wish and are in good health.

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Prevention

Varicella vaccine

The varicella vaccine is proven to be safe, effective, and cost-efficient for healthy children, adolescents, and adults.^[40] Breakthrough cases of MVLS are notably less severe than infections with wild-type varicella.

In the United States, two formulations of the live attenuated varicella vaccine are available^[1] :

• Standard two-dose varicella vaccine
• Combination measles-mumps-rubella-varicella (MMRV) vaccine^{[41, 42]}

According to the Centers for Disease Control and Prevention (CDC), all healthy children and susceptible individuals should receive two doses of the live attenuated varicella vaccine, as outlined in the CDC's Child and Adolescent Immunization Schedule by Age.^[1] Vaccination is particularly important for individuals of reproductive age, those at high risk for exposure, and those who have contact with individuals at higher risk for severe disease. This includes healthcare professionals, educators, childcare workers, and residents and staff of nursing homes or other institutional settings such as correctional facilities. Routine serologic testing to assess immune status before vaccination typically is unnecessary in adults. Although infrequent, the vaccine may induce mild chickenpox lesions in immunocompetent individuals, usually presenting with fewer than 10 papules or vesicles and causing minimal systemic symptoms.^[43]

It is recommended that healthcare workers lacking evidence of varicella immunity receive vaccination. Exposed healthcare workers should be vaccinated immediately and may need to be excluded from duty for 21 days to prevent disease transmission.

Vaccination is contraindicated in individuals who^[1] :

• Have had a severe allergic reaction (ie, anaphylaxis) to a previous dose of the vaccine or any of its components
• Are experiencing moderate to severe acute illnesses (vaccination should be deferred until recovery)
• Are immunocompromised
• Are pregnant or planning to conceive within 1 month of vaccination (per CDC guidelines) or within 3 months (per vaccine labeling)
• Are undergoing high-dose systemic corticosteroid therapy
• Are children receiving salicylate therapy

Postexposure prophylaxis

Varicella-zoster immune globulin (VariZIG) administered intramuscularly (IM) can prevent or attenuate chickenpox following exposure. Eligible candidates include the following^{[1, 4]} :

• Individuals with leukemia, immunodeficiencies, or other severe debilitating illnesses without immunity
• Pregnant individuals without immunity
• Neonates whose parent developed chickenpox shortly before or after delivery
• Neonates born at less than 28 weeks gestation exposed to a non-maternal source, even if the parent is immune (exposed neonates born at 28 weeks or later should receive immune globulin if the parent lacks immunity)

VariZIG should be administered as soon as possible, ideally within 10 days of exposure, to modify or prevent the disease. Exposed, susceptible individuals eligible for vaccination (ie, age ≥ 1 year without contraindications) should be vaccinated as soon as possible after exposure. Vaccination can be effective in preventing or mitigating the disease if administered within 3 to 5 days post-exposure.

To prevent nosocomial transmission, the CDC recommends postexposure prophylaxis with either vaccination or varicella-zoster immunoglobulin, depending on the immune status, for exposed healthcare workers and patients without evidence of immunity.

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Passive Immunization

Varicella-zoster immune globulin (VariZIG), a human immunoglobulin preparation, is indicated for use in highly susceptible, VZV-exposed immunocompromised or immunosuppressed populations.^[4]

High risk groups include:

• Adults without evidence of immunity
• Immunocompromised children and adults
• Infants less than 1 year of age
• Newborns of mothers with varicella shortly before or after delivery
• Premature infants
• Pregnant individuals

VZIG given within 10 days (ideally within 96 hours) of exposure can modify the course of disease but does not prevent it. Maximal effectiveness is seen with administration as soon as possible after exposure.^[34]

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Varicella-Zoster Virus Vaccination

Updated guidelines were issued in June 2009 by the CDC's Advisory Committee on Immunization Practices (ACIP) for the use of the combined measles, mumps, rubella, and varicella vaccine (MMRV, ProQuad, Merck & Co, Inc).^{[4, 44]}  The MMRV vaccine, which was approved in the United States in September 2005, can be used as an alternative to the separate measles, mumps, rubella vaccine (MMR, M-M-RII, Merck & Co., Inc) and varicella vaccine (VARIVAX, Merck & Co, Inc) to fulfill the recommended two-dose vaccination schedule aimed at preventing these diseases in children aged 12 months to 12 years.^[45] Initially, the MMRV vaccine was the preferred choice for both the first and second doses instead of individual injections of the MMR and varicella vaccines. This preference aligned with the ACIP's 2006 general recommendations on the use of combination vaccines.

Breakthrough varicella, which is seen in previously immunized persons, is a well-known clinical entity.^[46] The disease course typically is much milder than conventional primary varicella and is characterized by an atypical clinical presentation in which only a few papules or papulovesicles are present, but severe disease with pneumonitis or other organ involvement can occur. Transmission of VZV to other individuals may occur, although at lower rates than in nonimmunized people with primary varicella.

Adverse effects of the vaccination include pain and erythema at the site of injection, allergic reactions to gelatin, and the development of a localized chickenpox. Vaccine-induced herpes zoster infection in immunocompetent and immunocompromised populations also has been reported, though it is a rare phenomenon.^[47] Rarer still is the transmission of vaccine-associated virus from vaccinated individuals to susceptible contacts.

Go to Pediatric Chickenpox for more complete information on this topic.

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Consultations

For most patients in the pediatric population, a pediatrician can provide treatment. Adults without severe complications can be seen by a primary care physician or internal medicine specialist. In those patients who are immunocompromised, consultation with an infectious disease specialist with knowledge of the most recent pharmacotherapeutic advances is highly advised.

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Clinical Guidelines for Immunization

The following organizations have released guidelines for the management of varicella-zoster virus. Key diagnostic and treatment recommendations have been reviewed and integrated throughout the article.  

• US Centers for Disease Control and Prevention (2024): Clinical guidance for people at risk for severe varicella.^[48]
• Advisory Committee on Immunization Practices (2024): Varicella (chickenpox) vaccine.^[49]
• Royal College of Obstetricians and Gynaecologists (Updated 2024): Treatment of chickenpox in pregnancy.^[39]
• Advisory Committee on Immunization Practices (2018): Use of herpes zoster vaccines.^[50]
• US Centers for Disease Control and Prevention (2018): Recommended immunization schedule for adults aged 19 years and older in the United States.^[51]
• US Centers for Disease Control and Prevention (updated in 2013): Use of VariZIG in the United States.^[34]
• Advisory Committee on Immunization Practices (2010): Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine.^[44]

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Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications, especially in individuals who are immunocompromised/immunosuppressed.^[52]

• References

Varicella zoster immune globulin, human (VariZIG)

• Dosing, Interactions, etc.

Clinical Context:  When given within 10 days (ideally within 96 hours) of exposure, this agent modifies the course of disease but does not prevent it. Maximal effectiveness is seen with administration as soon as possible after exposure. It provides passive immunization to exposed individuals at high risk of complications from varicella. High-risk groups include immunocompromised children and adults, newborns of mothers with varicella shortly before or after delivery, premature infants, infants younger than 1 year, adults without evidence of immunity, and pregnant women. Administer by deep intramuscular injection in the deltoid muscle or in another large muscle mass. For neonates or infants, administer intramuscularly in anterolateral aspect of the thigh.

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Class Summary

For passive immunization, use varicella-zoster immune globulin, human (VariZIG), a human immunoglobulin preparation. This agent is indicated for use in highly susceptible, VZV-exposed immunocompromised or immunosuppressed populations.

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Acyclovir (Zovirax)

• Dosing, Interactions, etc.

Clinical Context:  Acyclovir inhibits activity of both herpes simplex virus (HSV)-1 and HSV-2. It has affinity for viral thymidine kinase and, once phosphorylated, causes deoxyribonucleic acid (DNA) chain termination when acted on by DNA polymerase. Patients experience less pain and faster resolution of cutaneous lesions when acyclovir is given within 48 hours from rash onset. It may prevent recurrent outbreaks. Early initiation of therapy is imperative.

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Famciclovir (Famvir)

• Dosing, Interactions, etc.

Clinical Context:  Famciclovir is a prodrug that, when biotransformed into the active metabolite, penciclovir, may inhibit viral deoxyribonucleic acid synthesis/replication.

• References

Valacyclovir (Valtrex)

• Dosing, Interactions, etc.

Clinical Context:  Valacyclovir is a prodrug that is rapidly converted to the active drug acyclovir. It is more expensive than acyclovir but has a more convenient dosing regimen.

• References

Class Summary

Nucleoside analogues are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit herpes virus polymerase 30-50 times more than the human host cells alpha-DNA polymerase.

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Diphenhydramine (Benadryl)

• Dosing, Interactions, etc.

Clinical Context:  Diphenhydramine is a first-generation antihistamine with anticholinergic effects that binds to H1 receptors in the CNS and the body. It is often used for symptomatic relief of pruritus caused by the release of histamine in inflammatory reactions. Diphenhydramine may cause drowsiness.

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Loratadine (Claritin, Alavert)

• Dosing, Interactions, etc.

Clinical Context:  Loratadine selectively inhibits peripheral histamine H1-receptors. It provides relief of pruritus and has a decreased incidence of sedation compared with first-generation antihistamines.

• References

Class Summary

The symptoms of chickenpox such as pruritus in the pediatric population can be treated with oral antihistamines. Examples of antihistamines are diphenhydramine (Benadryl) and loratadine (Claritin, Alavert).

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