Chickenpox is usually acquired through inhalation of airborne respiratory droplets from an infected host. High viral titers are found in the characteristic vesicles of chickenpox; viral transmission may also occur through direct contact with these vesicles, though the risk of transmission is lower. (See Etiology.)
Chickenpox is largely a childhood disease, with more than 90% of cases occurring in children younger than 10 years. The disease is benign in the healthy child, and increased morbidity occurs in adults and immunocompromised patients. (See Epidemiology and Prognosis.) An outbreak of varicella was noted in a group of lymphoma patients treated with rituximab and was related to exposure to a patient with zoster.[1]
Since the introduction of widespread pediatric immunization in the United States in 1995, the incidence of varicella has declined significantly, approaching up to a 90% decline. (See Epidemiology.)
Chickenpox is usually diagnosed clinically on the basis of the characteristic rash and successive crops of lesions. These may be found in various developmental and healing stages in affected sites. Patient exposure to an infected contact within the incubation period of 10-21 days is an important diagnostic clue. The more complicated course in adults with chickenpox can be associated with a more widespread rash; prolonged fever; and an increased likelihood of complications, the most common being varicella pneumonia. (See Clinical Presentation.)
VZV can be isolated on vesicular fluid cultures, which provides a definitive diagnosis. Direct immunofluorescence has excellent sensitivity. (See Workup.)
Oral acyclovir should be considered for healthy persons at increased risk of severe varicella infections. Valacyclovir and famciclovir are other agents used in treatment. Intravenous acyclovir therapy is recommended for patients who are immune-suppressed or immune-compromised. Varicella-zoster immune globulin (VZIG) is indicated for use in highly susceptible, VZV-exposed immunocompromised or immunosuppressed populations. A live attenuated varicella vaccine (Oka strain) was approved by the US Food and Drug Administration in 1995 for prophylactic use in healthy children and adults. (See Treatment, Guidelines, and Medication.)
The varicella-zoster virus (VZV) (see the image below) is the etiologic agent of the clinical syndrome of chickenpox (varicella). Zoster, a different clinical entity, is caused by reactivation of VZV after primary infection. VZV is a double-stranded deoxyribonucleic acid virus included in the Alphaherpesvirinae subfamily. (See Etiology.)
View Image | Vesicular eruption on the trunk demonstrating papules, vesicles, and crusts. Reprinted with permission from Cutis 65: 355, 2000. |
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.
Chickenpox is usually acquired by the inhalation of airborne respiratory droplets from an infected host. The highly contagious nature of varicella-zoster virus (VZV) underlies the epidemics that spread quickly through schools.[2] High viral titers are found in the characteristic vesicles of chickenpox; thus, despite the lower associated risk, viral transmission may also occur through direct contact with these vesicles.
After initial inhalation of contaminated respiratory droplets, the virus infects the conjunctivae or the mucosae of the upper respiratory tract. Viral proliferation occurs in regional lymph nodes of the upper respiratory tract 2-4 days after initial infection; this is followed by primary viremia on postinfection days 4-6.
A second round of viral replication occurs in the body's internal organs, most notably the liver and the spleen, followed by a secondary viremia 14-16 days post infection. This secondary viremia is characterized by diffuse viral invasion of capillary endothelial cells and the epidermis. VZV infection of cells of the malpighian layer produces both intercellular edema and intracellular edema, resulting in the characteristic vesicle.
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. Cell-mediated immune responses are also important in limiting the scope and the duration of primary varicella infection. After primary infection, VZV is hypothesized to spread from mucosal and epidermal lesions to local sensory nerves. VZV then remains latent in the dorsal ganglion cells of the sensory nerves. Reactivation of VZV results in the clinically distinct syndrome of herpes zoster (shingles).
Chickenpox is usually 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 may also occur through direct contact with these vesicles.
Chickenpox is a common disease, with most cases occurring in the pediatric population. Varicella has neither a racial nor a sexual predilection.[3]
Since the introduction of widespread pediatric immunization in the United States in 1995, the incidence of varicella has declined significantly, approaching a decline of up to 90%. Mortality from varicella has also declined since the initiation of the US vaccination program, with mortality decreasing by approximately 66%.[4]
Countries with tropical and semitropical climates have a higher incidence of adult chickenpox than do countries with a temperate climate (eg, United States, Europe).
Chickenpox that affects a healthy child is usually a self-limited disease. Increased morbidity occurs in adult and immunocompromised populations.
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.
For patient education resources, see the Infections Center. Also, see the patient education articles Chickenpox and Skin Rashes in Children.
Chickenpox is usually diagnosed clinically on the basis of the characteristic rash and successive crops of lesions. 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 is also an important clue in the diagnosis.
Childhood chickenpox is usually 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 has usually crusted over.
Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most frequent complication in otherwise healthy children.[5] 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, usually seen in the immunocompromised or adult populations, may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, gangrene, hepatitis, and glomerulonephritis.[6] Eczema varicellicum (mimicking eczema herpeticum) can occur.[7]
Central nervous system complications of primary VZV infection may occur, albeit very rarely. Reye syndrome, Guillain-Barré syndrome, acute cerebellar ataxia, and encephalitis have all been documented to occur after VZV infection.
Thrombocytopenia and purpura secondary to VZV infection have been described in more than 100 patients. Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected.[8]
Five major clinical syndromes have been described:
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 infection with VZV is a concern.[9, 10] 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.
Prepartum 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.
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.
The characteristic chickenpox vesicle, surrounded by an erythematous halo, is described as a dewdrop on a rose petal[11] (see the images below).
View Image | Dewdrop on rose petal characteristic vesicle of chickenpox. Reprinted with permission from Cutis 65: 355, 2000. |
View Image | 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.[12, 13] The possibility of bullous impetigo from Staphylococcus aureus must be addressed, especially in a child with persistent fever or relapse after he or she appeared to be improving.
Bullous chickenpox may affect both children and adults and must be differentiated from other bullous disorders (eg, bullous pemphigoid, pemphigus). 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 is primarily found on lichenified areas.[11, 14]
The workup for chickenpox includes a Tzanck smear, vesicular fluid culture, serologic testing, chest radiography, and histologic examination.
A Tzanck smear of vesicular fluid, which can be prepared in an office setting, demonstrates multinucleated giant cells and epithelial cells with eosinophilic intranuclear inclusion bodies.[15]
Isolation of the varicella-zoster virus (VZV) through culture of vesicular fluid provides a definitive diagnosis; however, culturing for VZV is technically difficult, and cultures are positive less than 40% of the time. Direct immunofluorescence study offers excellent sensitivity and is more rapid than tissue culture. Polymerase chain reaction-based techniques are highly sensitive in identifying VZV, but they are not readily available.[16]
Serologic evidence of immunity (native immunoglobulin G formation) to VZV can be achieved through a number of different assays, including the following:
Enzyme immunoassay, fluorescent antibody to membrane assay, and indirect fluorescence are not widely available, and complement fixation is not highly sensitive for VZV. The latex agglutination test is the most popular serologic assay for determining exposure and immunity to VZV.
Chest radiography is indicated for adults who are experiencing pulmonary symptoms of chicken pox.
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.[17]
Primary varicella infection in the healthy child is a rather benign disease that requires symptomatic therapy only. Oral acyclovir should be considered for healthy persons at increased risk of severe varicella infections.
Adults and immunocompromised persons with chickenpox have a more complicated course than that occurring in children, and therefore, the condition necessitates a more aggressive pharmacotherapeutic approach. Intravenous acyclovir therapy is recommended for patients who are immunosuppressed or immunocompromised.
Varicella-zoster immune globulin (VariZIG) is indicated for use in highly susceptible, VZV-exposed immunocompromised or immunosuppressed populations. A live attenuated varicella vaccine (Oka strain) was approved by the FDA in 1995 for prophylactic use in healthy children and adults.[18, 19, 20, 21, 22]
While the current standard of care is with the antiviral agents discussed below, Lysimachia mauritiana extract appears promising as a potential agent.[23]
Also see the Guidelines section.
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.[24]
Given the high risk of varicella-related complications, children should be treated if any of the following conditions are a medical concern:
Go to Pediatric Chickenpox for more complete information on this topic.
Oral acyclovir should be considered for healthy persons at increased risk of severe varicella infections, most notably patients older than 12 years. 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.
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.[25]
Secondary complications (eg, bacterial pneumonia, meningitis) caused by bacterial superinfection of cutaneous lesions with subsequent septicemia, are also 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.[26]
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.
Varicella-zoster immune globulin (VariZIG), a human immunoglobulin preparation, is indicated for use in highly susceptible, VZV-exposed immunocompromised or immunosuppressed populations.
High risk groups include:
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.[27]
A live attenuated varicella vaccine (Oka strain) was approved by the US Food and Drug Administration in 1995 for prophylactic use in healthy children and adults. Vaccination recommendations consist of 1 dose for healthy children aged 12-18 months and 2 doses, in a 4- to 8-week interval, in susceptible persons older than 13 years. Studies in Japan point to high seroconversion rates and long-term immunity in children after vaccination.[18, 19, 20, 21, 22, 28] The need for revaccination, or a booster immunization, will be addressed after more long-term studies have been completed.
The effectiveness of the vaccine wanes over time, ranging from 97% in the first year after vaccination to 84% at 8 years post vaccination.
Breakthrough varicella, which is seen in previously immunized persons, is a well-known clinical entity.[29] The disease course is typically 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 has also been reported, though it is a rare phenomenon. 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.
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.
Clinical guidelines for immunization against chickenpox have been published by the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) Committee on Infectious Diseases.
In 2006, the CDC reported on VariZIG for postexposure prophylaxis of varicella (provided under an investigational new drug application expanded access protocol).[30] In 2008, the CDC Advisory Committee on Immunization Practices (ACIP) published recommendations for the administration of combination measles, mumps, rubella, and varicella (MMRV) vaccine.[31] The ACIP updated the MMRV guideline in 2010.[32] Yearly updates to the ACIP recommended immunization schedule for adults include guidelines for immunization to varicella, as in 2009[33] and 2011; adults aged 60 years or older are candidates for immunization to herpes zoster.[34]
The AAP Committee on Infectious Diseases has published recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule, issued in 2007 and reaffirmed in 2010.[35] Yearly AAP schedules for immunization of children and adolescents provide recommendations for the use of combined MMRV or MMR with varicella given separately.[36, 37, 38]
The Royal College of Obstetricians and Gynaecologists recently released their 2014 guidelines for treating chickenpox in pregnancy, summarized below.[39]
Clinicians should ask women presenting for antenatal care about previous chickenpox or shingles infection.
Pregnant women who have not had chickenpox, or who are known to be seronegative for chickenpox, should avoid contact with persons who have chickenpox or shingles and should promptly inform their clinician of potential exposure.
Clinicians should confirm potential exposure by careful history to confirm the significance of the contact and the susceptibility of the patient, as well as by blood test to determine varicella-zoster virus (VZV) immunity or nonimmunity.
Pregnant women may need a second dose of varicella-zoster immunoglobulin if there is further exposure and 3 weeks have elapsed since the last dose.
Pregnant women who develop the characteristic rash should immediately inform their clinician, and they should be isolated from other pregnant women and neonates until the lesions have crusted over (usually about 5 days after rash onset).
Symptomatic treatment and hygiene are helpful to prevent secondary bacterial infection.
Clinicians should consider hospital assessment of women at high risk for severe or complicated chickenpox, regardless of clinical status.
Clinicians should refer pregnant women who develop chickenpox to a fetal medicine specialist, virologist, and neonatologist for decision regarding treatment.
Clinicians should individualize the timing and mode of delivery of the pregnant woman with chickenpox.
Women with chickenpox should breast-feed if they so desire and are in sufficiently good health.
The goals of pharmacotherapy are to reduce morbidity and to prevent complications, especially in individuals who are immunocompromised/immunosuppressed.[40]
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.
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.
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.
Clinical Context: Famciclovir is a prodrug that, when biotransformed into the active metabolite, penciclovir, may inhibit viral deoxyribonucleic acid synthesis/replication.
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.
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.
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.
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.
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).