Background

The varicella-zoster virus (VZV) 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.) 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.) 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 immunecompromised. 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 and Management and Medication.) Go to Pediatric Chickenpox for more complete information on this topic.

Pathophysiology
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

Europe). the virus infects the conjunctivae or the mucosae of the upper respiratory tract. Epidemiology Chickenpox is a common disease. Etiology Chickenpox is usually acquired by the inhalation of airborne respiratory droplets from a VZVinfected host. viral transmission may also occur through direct contact with these vesicles. VZV then remains latent in the dorsal ganglion cells of the sensory nerves. After initial inhalation of contaminated respiratory droplets. High viral titers are found in the characteristic vesicles of chickenpox. viral transmission may also occur through direct contact with these vesicles. Exposure to VZV in a healthy child initiates the production of host immunoglobulin G (IgG). thus. 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. Varicella has neither a racial nor a sexual predilection. the incidence of varicella has declined significantly. with most cases occurring in the pediatric population. with mortality decreasing by approximately 66%. immunoglobulin M (IgM). resulting in the characteristic vesicle. and immunoglobulin A (IgA) antibodies. A second round of viral replication occurs in the body's internal organs. approaching a decline of up to 90%. Reactivation of VZV results in the clinically distinct syndrome of herpes zoster (shingles).epidemics that spread quickly through schools. United States. . High viral titers are found in the characteristic vesicles of chickenpox.[1] United States statistics Since the introduction of widespread pediatric immunization in the United States in 1995. thus. Mortality from varicella has also declined since the initiation of the US vaccination program. this is followed by primary viremia on postinfection days 4-6. VZV infection of cells of the malpighian layer produces both intercellular edema and intracellular edema. Viral proliferation occurs in regional lymph nodes of the upper respiratory tract 2-4 days after initial infection. despite the lower associated risk. most notably the liver and the spleen. This secondary viremia is characterized by diffuse viral invasion of capillary endothelial cells and the epidermis. followed by a secondary viremia 14-16 days post infection. VZV is hypothesized to spread from mucosal and epidermal lesions to local sensory nerves.[2] International statistics Countries with tropical and semitropical climates have a higher incidence of adult chickenpox than do countries with a temperate climate (eg. After primary infection.

clear vesicles. manifesting as impetigo.[3] Staphylococci and streptococci are the most commonly implicated bacterial pathogens. shallow. by which time the last crop of vesicles has usually crusted over. For excellent patient education resources. together with painful. because the development of Reye syndrome is associated with salicylate administration in children with chickenpox. though the typical patient is infectious for 1-2 days prior to the development of rash. Lesions may be found in all stages of development and healing in affected sites. Secondary bacterial infection Secondary bacterial infection of skin lesions. Childhood chickenpox is usually not heralded by a prodrome. Localized bacterial superinfection rarely may manifest as septicemia. it begins with the onset of an exanthem. In adults and adolescents. face. myalgia. Intense pruritus commonly accompanies the vesicular stage of the rash. and pustules and subsequent central umbilication and crust formation. Also. Also. Bacterial superinfection may predispose to scarring. malaise. Vesicles may appear on the palms and the soles and on the mucous membranes. erythematous macules appear on the scalp. A history of exposure to an infected contact within the incubation period of 10-21 days is also an important clue in the diagnosis. and a low-grade fever can signal disease onset. and erysipelas. The triad of rash. culminating in . History Chickenpox is usually diagnosed clinically on the basis of the characteristic rash and successive crops of lesions. and proximal limbs. visit eMedicine's Bacterial and Viral Infections Center. chickenpox may be preceded by a prodrome of nausea. and headache. Increased morbidity occurs in adult and immunocompromised populations. it is important to advise parents not to use aspirin for fever control. The typical patient remains infectious for 4-5 days after the rash develops. with rapid sequential progression over 12-14 hours to papules.Prognosis Chickenpox that affects a healthy child is usually a self-limited disease. is the most frequent complication in otherwise healthy children. see eMedicine's patient education articles Chickenpox and Skin Rashes in Children. Small. trunk. cellulitis. anorexia. oropharyngeal or urogenital ulcers. 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.

cortical atrophy. Disseminated primary varicella infection Disseminated primary varicella infection. Hemorrhagic complications Thrombocytopenia and purpura secondary to VZV infection have been described in more than 100 patients. 7] Primary maternal chickenpox during pregnancy may produce latency of VZV in the dorsal root ganglia of the fetus. Primary maternal chickenpox infection in early to mid-pregnancy is estimated to have a 1-2% risk of causing the congenital varicella syndrome. with febrile purpura being the most benign and having an uncomplicated outcome. usually seen in the immunocompromised or adult populations. These children may remain asymptomatic. although an autoimmune pathophysiologic mechanism has been implicated. and encephalitis have all been documented to occur after VZV infection. albeit very rarely. or they may develop zoster at a young age without a previous history of primary chickenpox infection.[6. cataract formation. Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations. otitis media.[5] Five major clinical syndromes have been described:      Febrile purpura Malignant chickenpox with purpura Postinfectious purpura Purpura fulminans Anaphylactoid purpura These syndromes have variable courses. and rudimentary digits. The latter represents significant. acute cerebellar ataxia. In utero VZV infection In utero infection with VZV is a concern. Guillain-Barré syndrome. . skin scarring. malignant chickenpox with purpura is a grave clinical condition that has a mortality exceeding 70%. Ninety percent of cases of varicella pneumonia occur in the adult population. may have high morbidity. gangrene. Rarer complications of disseminated chickenpox include myocarditis.[4] CNS complications Central nervous system complications of primary VZV infection may occur. potentially life-threatening morbidity. In contrast. Reye syndrome. muscular atrophy. which is characterized by limb hypoplasia.secondary bacterial pneumonia. and glomerulonephritis. The etiology of these hemorrhagic chickenpox syndromes is not known. hepatitis. or necrotizing fasciitis. microcephaly. although healthy children and adults have been affected.

Clinical variants of chickenpox infection also occur. 2000. Lesions characteristically heal without scarring.[8] Dewdrop on rose petal characteristic vesicle of chickenpox. although excoriation or secondary bacterial superinfection predisposes to scar formation. 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. Chickenpox is clinically characterized by the presence of active and healing lesions in all stages of development within affected locations. surrounded by an erythematous halo. Reprinted with permission from Cutis 65: 355. and an increased likelihood of complications.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. prolonged fever. Vesicular eruption on the trunk demonstrating papules. Adults with chickenpox have a more complicated course than that occurring in children. vesicles. which has substantial mortality. Peripartum infection of the fetus before sufficient maternal antibody has crossed the placenta to confer transient passive immunity to the fetus (ie. Hemorrhagic lesions are rare and are most commonly associated with patients who are immunocompromised or immunosuppressed. Adults may experience a more widespread rash. the most common being varicella pneumonia. 2000. Reprinted with permission from Cutis 65: 355. disseminated varicella infection. Physical Examination The characteristic chickenpox vesicle. is described as a dewdrop on a rose petal (see the images below). and crusts. .

Bullous chickenpox may affect both children and adults and must be differentiated from other bullous disorders (eg. which would be a concern in the event of biologic warfare. 10] The possibility of bullous impetigo from Staphylococcus aureus must be addressed. although a delay in diagnosis and treatment of elderly patients and immunocompromised patients may lead to serious morbidity. in which the characteristic eruption is primarily found on lichenified areas.[11. which can be prepared in an office setting. bullous pemphigoid. chest radiography. Tzanck Smear A Tzanck smear of vesicular fluid. serologic testing. demonstrates multinucleated giant cells and epithelial cells with eosinophilic intranuclear inclusion bodies. and histologic examination. disseminated herpes simplex virus infection. Chickenpox and other viral exanthems may appear concentrated in areas where intense sun exposure occurred during the incubation period. and neonatal syphilis. rickettsial disease. vesicular fluid culture. with the exception of smallpox. Differentials          Bullous Pemphigoid Dermatitis Herpetiformis Drug Eruptions Erythema Multiforme Herpes Simplex Impetigo Insect Bites Smallpox Syphilis Approach Considerations The workup for chickenpox includes a Tzanck smear.Bullous chickenpox is a rare variant in which bullae appear instead of the characteristic vesicles. The course of the disease is believed to be unchanged.[9. especially in a child with persistent fever or relapse after he or she appeared to be improving. pityriasis lichenoides et varioliformis acuta. 8] Diagnostic Considerations Diagnostic considerations in cases of suspected chickenpox include viral exanthems.[12] . Patients with atopic dermatitis may show an atypical distribution of varicella. pemphigus). All of the differential diagnoses listed are active considerations. atypical herpes zoster.

Adults and immunocompromised persons with chickenpox have a more complicated course than that occurring in children. and therefore. and indirect fluorescence are not widely available. culturing for VZV is technically difficult. Oral acyclovir should be considered for healthy persons at increased risk of severe varicella infections. Histologic Findings Histologic examination of skin lesions does not differentiate VZV from herpes simplex virus (HSV) infection. including the following:      Enzyme immunoassay Indirect fluorescent antibody Complement fixation Fluorescent antibody to membrane assay Latex agglutination test Enzyme immunoassay. Chest Radiography Chest radiography is indicated for adults who are experiencing pulmonary symptoms of chicken pox. however. and cultures are positive less than 40% of the time. The latex agglutination test is the most popular serologic assay for determining exposure and immunity to VZV. Polymerase chain reaction-based techniques are highly sensitive in identifying VZV. but they are not readily available. Approach Considerations Primary varicella infection in the healthy child is a rather benign disease that requires symptomatic therapy only. Intranuclear eosinophilic inclusion bodies are seen in epithelial cells in both infections. Direct immunofluorescence study offers excellent sensitivity and is more rapid than tissue culture. Leukocytoclastic vasculitis and hemorrhage are more common in VZV lesions than HSV.[13] Serology Serologic evidence of immunity (native immunoglobulin G formation) to VZV can be achieved through a number of different assays.Culture Isolation of the varicella-zoster virus (VZV) through culture of vesicular fluid provides a definitive diagnosis. and complement fixation is not highly sensitive for VZV. the condition necessitates a more aggressive . however. fluorescent antibody to membrane assay.

16.pharmacotherapeutic approach. Valacyclovir. has been shown to decrease the duration of lesions and pyrexia. is not commonly prescribed for otherwise healthy children. Pruritus can be treated with calamine lotion or pramoxine gel. A live attenuated varicella vaccine (Oka strain) was approved by the FDA in 1995 for prophylactic use in healthy children and adults. or oral antihistamines. Varicella-zoster immune globulin (VZIG) is indicated for use in highly susceptible. 18] Treatment in Healthy Children The symptoms of chickenpox in the pediatric population can be treated topically and with oral agents.[14. Treatment in Immunocompetent Adults Oral acyclovir should be considered for healthy persons at increased risk of severe varicella infections. 17. Oral acyclovir therapy in this population (800 mg 5 times/d for 7 d). Intravenous acyclovir therapy is recommended for patients who are immunosuppressed or immunocompromised. though shown to decrease the symptoms and duration of primary varicella infection when administered within 24 hours of onset of symptoms.[19] Given the high risk of varicella-related complications. children should be treated if any of the following conditions are a medical concern:        Defects in cell-mediated immunity Chronic atopic dermatitis Chronic asthma Iatrogenic immunosuppression Long-term systemic steroid use Splenic dysfunction Nephrotic syndrome Go to Pediatric Chickenpox for more complete information on this topic. begun within 24 hours of onset of symptoms. most notably patients older than 12 years. the L-valyl ester of acyclovir. powdered oatmeal baths. The nucleoside analogue acyclovir (20 mg/kg PO qid for 5 d). while reducing other symptoms and disease duration. VZVexposed immunocompromised or immunosuppressed populations. immunocompetent individuals. Valacyclovir is used in the treatment of herpes zoster. is a prodrug that has higher oral bioavailability than acyclovir. but no large-based clinical trials yet have demonstrated its efficacy in primary varicella infection of healthy. . 15.

and interferon-alpha to be effective in the treatment of primary varicella infection of immunocompromised hosts. Passive Immunization Varicella-zoster immune globulin (VZIG). a human immunoglobulin preparation. and hemorrhagic complications. . patients undergoing immunosuppressive therapy for transplant procedures. patients with congenital or acquired immunodeficiency syndromes.[20] Secondary complications (eg. 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. Treatment of primary varicella in these populations is difficult and necessitates an integrated team approach. bacterial pneumonia. Acyclovir-resistant strains of VZV have been reported in patients with AIDS. with the development of varicella pneumonia. Foscarnet. Case reports have described vidarabine. because of the life-threatening complications of primary varicella infection to which they are particularly susceptible.[21] 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. is indicated for use in highly susceptible. meningitis) caused by bacterial superinfection of cutaneous lesions with subsequent septicemia. Treatment in the Immunocompromised or Immunosuppressed Intravenous acyclovir therapy is recommended for patients who are immunosuppressed or immunocompromised. and infants born to mothers who experience onset of chickenpox within 5 days prior to delivery or within 2 days after delivery. and efficacy in primary varicella infection need further investigation. is a potentially efficacious drug in patients with acyclovir-resistant VZV strains. VZV-exposed immunocompromised or immunosuppressed populations. is much more common in this population than in other populations. an inorganic pyrophosphate analogue that acts as a selective inhibitor of viral deoxyribonucleic acid polymerases and reverse transcriptases. These populations would comprise. those with leukemia. encephalitis. A few case reports also have found sorivudine. famciclovir has demonstrated efficacy in the treatment of herpes zoster. Optimal dosage. hepatitis. are also more common and dangerous among those who are immunocompromised. which is a nucleoside analogue similar to acyclovir. duration of therapy. patients who have undergone bone marrow transplantation. Severe disseminated disease.Famciclovir is a prodrug of penciclovir. but it has not been extensively studied for use in primary varicella infection of healthy populations. Like valacyclovir. Larger scale clinical trials are needed to demonstrate the efficacy of this medication. a purine nucleoside analogue. for example.

17. Clinical Guidelines for Immunization 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.[24] The ACIP updated the MMRV guideline in 2010. Vaccination recommendations consist of 1 dose for healthy children aged 12-18 months and 2 doses. 22] The need for revaccination.[27] . which is seen in previously immunized persons. Vaccine-induced herpes zoster infection in immunocompetent and immunocompromised populations has also been reported. Go to Pediatric Chickenpox for more complete information on this topic. allergic reactions to gelatin. mumps. adults aged 60 years or older are candidates for immunization to herpes zoster. or a booster immunization. as in 2009[26] and 2011. will be addressed after more long-term studies have been completed. The disease course 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.[25] Yearly updates to the ACIP recommended immunization schedule for adults include guidelines for immunization to varicella. in a 4to 8-week interval. ranging from 97% in the first year after vaccination to 84% at 8 years post vaccination. Transmission of VZV to other individuals may occur.VZIG given within 96 hours of exposure can modify the course of disease but does not prevent it. Varicella-Zoster Virus Vaccination 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. is a well-known clinical entity. and the development of a localized chickenpox. in susceptible persons older than 13 years.[23] In 2008. Breakthrough varicella. Maximal effectiveness is seen with administration as soon as possible after exposure. Adverse effects of the vaccination include pain and erythema at the site of injection. rubella. 18. although at lower rates than in nonimmunized people with primary varicella. Rarer still is the transmission of vaccine-associated virus from vaccinated individuals to susceptible contacts. the CDC Advisory Committee on Immunization Practices (ACIP) published recommendations for the administration of combination measles. and varicella (MMRV) vaccine. the CDC reported on VariZIG for postexposure prophylaxis of varicella (provided under an investigational new drug application expanded access protocol). In 2006. 16. 15.[14. The effectiveness of the vaccine wanes over time. Studies in Japan point to high seroconversion rates and long-term immunity in children after vaccination. though it is a rare phenomenon.

[31] Immune globulins Class Summary For passive immunization. Antiviral agents Class Summary . VZV-exposed immunocompromised or immunosuppressed populations. In those patients who are immunocompromised. 30] Consultations For most patients in the pediatric population. including a recommendation for a routine 2-dose varicella immunization schedule. This agent is indicated for use in highly susceptible. VZIG can modify the course of disease but does not prevent it. Adults without severe complications can be seen by a primary care physician or internal medicine specialist. use varicella-zoster immune globulin. View full drug information Varicella zoster immune globulin. consultation with an infectious disease specialist with knowledge of the most recent pharmacotherapeutic advances is highly advised.[28] Yearly AAP schedules for immunization of children and adolescents provide recommendations for the use of combined MMRV or MMR with varicella given separately. issued in 2007 and reaffirmed in 2010. Medication Summary The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Maximal effectiveness is seen with administration as soon as possible after exposure.The AAP Committee on Infectious Diseases has published recommendations for use of varicella vaccines in children. a human immunoglobulin preparation. a pediatrician can provide treatment. human (VZIG) When given within 96 hours of exposure.[29. especially in individuals who are immunocompromised/immunosuppressed. human (VZIG). Administer by deep intramuscular injection in the gluteal muscle or in another large muscle mass.

View full drug information Acyclovir (Zovirax) Acyclovir inhibits activity of both herpes simplex virus (HSV)-1 and HSV-2.Nucleoside analogues are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. Patients experience less pain and faster resolution of cutaneous lesions when acyclovir is given within 48 hours from rash onset. Examples of antihistamines are diphenhydramine (Benadryl) and loratadine (Claritin. Early initiation of therapy is imperative. View full drug information Diphenhydramine (Benadryl) . may inhibit viral deoxyribonucleic acid synthesis/replication. It has affinity for viral thymidine kinase and. It is more expensive than acyclovir but has a more convenient dosing regimen. Alavert). Antihistamines Class Summary The symptoms of chickenpox such as pruritus in the pediatric population can be treated with oral antihistamines. It may prevent recurrent outbreaks. View full drug information Valacyclovir (Valtrex) Valacyclovir is a prodrug that is rapidly converted to the active drug acyclovir. causes deoxyribonucleic acid (DNA) chain termination when acted on by DNA polymerase. View full drug information Famciclovir (Famvir) Famciclovir is a prodrug that. when biotransformed into the active metabolite. penciclovir. once phosphorylated. These molecules inhibit herpes virus polymerase 30-50 times more than the human host cells alpha-DNA polymerase.

View full drug information Loratadine (Claritin. Alavert) Loratadine selectively inhibits peripheral histamine H1-receptors. Diphenhydramine may cause drowsiness. . It is often used for symptomatic relief of pruritus caused by the release of histamine in inflammatory reactions.First-generation antihistamine with anticholinergic effects that binds to H1 receptors in the CNS and the body. It provides relief of pruritus and has a decreased incidence of sedation compared with first-generation antihistamines.

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