Chickenpox (Varicella) : Causing Agent, Pathogenesis, Symptoms, Diagnosis, Treatment & Prevention
Introduction
- Chickenpox (Varicella) is caused by Varicella-zoster virus (VZV).
- Chickenpox, a ubiquitous and extremely contagious infection, is usually a benign illness of childhood characterized by an exanthematous vesicular rash.
- With reactivation of latent VZV (which is most common after the sixth decade of life), herpes zoster presents as a dermatomal vesicular rash, usually associated with severe pain.
- Chickenpox is highly contagious, with an attack rate of at least 90% among susceptible (seronegative) individuals. Persons of both sexes and all races are infected equally.
- The incubation period of chickenpox ranges from 10 to 21 days but is usually 14–17 days.
Causative Virus
- Causing agent : Varicella-zoster virus (VZV)
- Humans are the only known reservoir for VZV.
Epidemiology
- The virus is endemic in the population at large; however, it becomes epidemic among susceptible individuals during seasonal peaks—namely, late winter and early spring in the temperate zone.
- Much of our knowledge of the disease’s natural history and incidence predates the licensure of the chickenpox vaccine in 1995.
- Historically, children 5–9 years old are most commonly affected and account for 50% of all cases.
- Most other cases involve children 1–4 and 10–14 years old.
- Approximately 10% of the population of the United States over the age of 15 is susceptible to infection.
- Secondary attack rates in susceptible siblings within a household are 70–90%.
Mode of Infection
- Transmission is via droplets, aerosol or direct contact, or indirectly by touching freshly soiled contaminated items. Patients are usually contagious from a few days before onset of the rash until the rash has crusted over.
- Primary Infection Transmission occurs readily by the respiratory route; the subsequent localized replication of the virus at an undefined site (presumably the nasopharynx) leads to seeding of the lymphatic/reticuloendothelial system and ultimately to the development of viremia.
- Patients are infectious ~48 h before onset of the vesicular rash, during the period of vesicle formation (which generally lasts 4–5 days), and until all vesicles are crusted.
Pathogenesis
- Vesicles involve the corium and dermis, with degenerative changes characterized by ballooning, the presence of multinucleated giant cells, and eosinophilic intranuclear inclusions. Infection may involve localized blood vessels of the skin, resulting in necrosis and epidermal hemorrhage. With the evolution of disease, the vesicular fluid becomes cloudy because of the recruitment of polymorphonuclear leukocytes and the presence of degenerated cells and fibrin. Ultimately, the vesicles either rupture and release their fluid (which includes infectious virus) or are gradually reabsorbed.
- Recurrent Infection The mechanism of reactivation of VZV that results in herpes zoster is unknown. Presumably, the virus infects dorsal root ganglia during chickenpox, where it remains latent until reactivated.
- Histopathologic examination of representative dorsal root ganglia during active herpes zoster demonstrates hemorrhage, edema, and lymphocytic infiltration.
- Active replication of VZV in other organs, such as the lung or the brain, can occur during either chickenpox or herpes zoster but is uncommon in the immunocompetent host. Pulmonary involvement is characterized by interstitial pneumonitis, multinucleated giant cell formation, intranuclear inclusions, and pulmonary hemorrhage. Central nervous system (CNS) infection leads to histopathologic evidence of perivascular cuffing similar to that encountered in measles and other viral encephalitides. Focal hemorrhagic necrosis of the brain, characteristic of herpes simplex virus (HSV) encephalitis, develops infrequently in VZV infection.
Clinical Symptoms
Disease in children is usually well tolerated. Manifestations are more severe in adults, pregnant women and the immunocompromised.
Clinically, chickenpox menifested by following :
- Rash which progresses from small pink macules to vesicles and pustules within 24 hours. (Vesicular eruption begins, often on mucosal surfaces first, followed by rapid dissemination in a centripetal distribution; most dense on trunk and sparse on limbs),
- Low-grade fever,
- Malaise, although a few patients develop a prodrome 1–2 days before onset of the exanthem.
The skin lesions (rashes)—the hallmark of the infection—include maculopapules, vesicles, and scabs in various stages of evolution. These lesions, which evolve from maculopapules to vesicles over hours to days, appear on the trunk and face and rapidly spread to involve other areas of the body. Most are small and have an erythematous base with a diameter of 5–10 mm. New lesions occur every 2–4 days and each crop is associated with fever. Lesions can also be found on the mucosa of the pharynx and/or the vagina. Their severity varies from one person to another. Younger children tend to have fewer vesicles than older individuals. Secondary and tertiary cases within families are associated with a relatively large number of vesicles.
Infectivity lasts from up to 4 days (but usually 48 hours) before the lesions appear until the last vesicles crust over.
In the immunocompetent patient, chickenpox is usually a benign illness associated with lassitude and with body temperatures of 37.8°–39.4°C (100°–103°F) of 3–5 days’ duration.
Immunocompromised patients— both children and adults, particularly those with leukemia—have lesions (often with a hemorrhagic base) that are more numerous and take longer to heal than those of immunocompetent patients.
Complications
- The most common infectious complication of varicella is secondary bacterial superinfection of the skin, which is usually caused by Streptococcus pyogenes or Staphylococcus aureus, including strains that are methicillin-resistant. Skin infection results from excoriation of lesions after scratching.
- The most common extracutaneous site of involvement in children is the CNS. The syndrome of acute cerebellar ataxia and meningeal inflammation generally appears ~21 days after onset of the rash and rarely develops in the pre-eruptive phase. The cerebrospinal fluid (CSF) contains lymphocytes and elevated levels of protein. CNS involvement is a benign complication of VZV infection in children and generally does not require hospitalization. Aseptic meningitis, encephalitis, transverse myelitis, and Guillain-Barré syndrome can also occur. Reye’s syndrome has been reported in children concomitantly treated with aspirin.
- Varicella pneumonia, the most serious complication following chickenpox, develops more often in adults (up to 20% of cases) than in children and is particularly severe in pregnant women. Pneumonia due to VZV usually has its onset 3–5 days into the illness and is associated with tachypnea, cough, dyspnea, and fever. Cyanosis, pleuritic chest pain, and hemoptysis are frequently noted. Roentgenographic evidence of disease consists of nodular infiltrates and interstitial pneumonitis. Resolution of pneumonitis parallels improvement of the skin rash; however, patients may have persistent fever and compromised pulmonary function for weeks.
- Other complications of chickenpox include myocarditis, corneal lesions, nephritis, arthritis, bleeding diatheses, acute glomerulonephritis, and hepatitis. Hepatic involvement, distinct from Reye’s syndrome and usually asymptomatic, is common in chickenpox and is generally characterized by elevated levels of liver enzymes, particularly aspartate and alanine aminotransferases.
- Perinatal varicella is associated with mortality rates as high as 30% when maternal disease develops within 5 days before delivery or within 48 h thereafter. Illness in this setting is unusually severe because the newborn does not receive protective transplacental antibodies and has an immature immune system. Congenital varicella, with clinical manifestations of limb hypoplasia, cicatricial skin lesions, and microcephaly at birth, is extremely uncommon.
Diagnosis
Chickenpox can be diagnosed by following methods :
- Clinically by recognition of the rash (primarily) and a history of recent exposure,
- Detection of antigen (direct immunofluorescence),
- PCR technology by DNA of aspirated vesicular fluid,
- Serology.
Diagnosis is primarily clinical, by recognition of the rash. If necessary, this can be confirmed by detection of antigen (direct immunofluorescence) or DNA (PCR) of aspirated vesicular fluid. Serology is used to identify seronegative individuals at risk of infection.
Other viral infections that can mimic chickenpox include disseminated HSV infection in patients with atopic dermatitis and the disseminated vesiculopapular lesions sometimes associated with coxsackievirus infection, echovirus infection, or atypical measles. However, these rashes are more commonly morbilliform with a hemorrhagic component rather than vesicular or vesiculopustular.
Rickettsialpox is sometimes confused with chickenpox; however, rickettsialpox can be distinguished easily by detection of the “herald spot” at the site of the mite bite and the development of a more pronounced headache. Serologic testing is also useful in differentiating rickettsialpox from varicella and can confirm susceptibility in adults unsure of their chickenpox history.
The lesions of smallpox are larger than those of chickenpox and are all at the same stage of evolution at any given time.
Lab findings
- Unequivocal confirmation of the diagnosis is possible only through the isolation of VZV in susceptible tissue-culture cell lines, the demonstration of either seroconversion or a fourfold or greater rise in antibody titer between acute-phase and convalescent-phase serum specimens, or the detection of VZV DNA by PCR. A rapid impression can be obtained by a Tzanck smear, with scraping of the base of the lesions in an attempt to demonstrate multinucleated giant cells; however, the sensitivity of this method is low (~60%).
- Direct immunofluorescent staining of cells from the lesion base or detection of viral antigens by other assays (such as the immunoperoxidase assay) is also useful, although these tests are not commercially available. The most frequently employed serologic tools for assessing host response are the immunofluorescent detection of antibodies to VZV membrane antigens, the fluorescent antibody to membrane antigen (FAMA) test, immune adherence hemagglutination, and enzyme-linked immunosorbent assay (ELISA).
- The FAMA test and the ELISA appear to be most sensitive.
Treatment
Chickenpox in adult or child (with chickenpox of ≤24 h duration) managed as following :
- Oral aciclovir (Acyclovir) 800 mg 5 times daily for 5 days (acyclovir therapy may be of benefit to children <12 years of age if initiated early in the disease (<24 h) at a dose of 20 mg/kg every 6 h.)
- Famciclovir 250 or 500 mg 3 times daily for 5 days (Famciclovir is recommended but not licensed for varicella.)
- Valaciclovir (valacyclovir) 1 g 3 times daily for 5 days (Valacyclovir is licensed for use in children and adolescents.)
Chickenpox in Immunocompromised host (e.g., transplant recipients, patients with lymphoproliferative malignancies) / pregnant woman managed as following :
- Aciclovir 5 mg/kg 3 times daily IV until patient is improving (or 10 mg/kg every 8 h for 7 days), then complete therapy with oral therapy until all lesions crusting over. If medically feasible, it is desirable to decrease immunosuppressive treatment concomitant with the administration of IV acyclovir.
Chickenpox with complications is managed as following :
- Visceral involvement (non-CNS) in VZV : Aciclovir IV 5 mg/kg 3 times daily for 7 days
- Severe complications (encephalitis, disseminated infection) : Aciclovir IV 10 mg/kg 3 times daily (up to 20 mg/kg in neonates) for 14–21 days
Pruritus can be decreased with topical dressings or the administration of antipruritic drugs. Tepid water baths and wet compresses are better than drying lotions for the relief of itching.
Patients with varicella pneumonia often require ventilatory support.
Persons with zoster ophthalmicus should be referred immediately to an ophthalmologist. Therapy for this condition consists of the administration of analgesics for severe pain and the use of atropine. Acyclovir, valacyclovir, and famciclovir all accelerate healing. Decisions about the use of glucocorticoids should be made by the ophthalmologist.
The management of acute neuritis and/or postherpetic neuralgia can be particularly difficult. In addition to the judicious use of analgesics ranging from nonnarcotics to narcotic derivatives, drugs such as gabapentin, pregabalin, amitriptyline hydrochloride, lidocaine (patches), and fluphenazine hydrochloride are reportedly beneficial for pain relief. In one study, glucocorticoid therapy administered early in the course of localized herpes zoster significantly accelerated such quality-of-life improvements as a return to usual activity and termination of analgesic medications. The dose of prednisone administered orally was 60 mg/d on days 1–7, 30 mg/d on days 8–14, and 15 mg/d on days 15–21. This regimen is appropriate only for relatively healthy elderly persons with moderate or severe pain at presentation.
Patients with osteoporosis, diabetes mellitus, glycosuria, or hypertension may not be appropriate candidates. Glucocorticoids should not be used without concomitant antiviral therapy.
Medical management of chickenpox in the immunologically normal host is directed toward the prevention of avoidable complications. Obviously, good hygiene includes daily bathing and soaks. Secondary bacterial infection of the skin can be avoided by meticulous skin care, particularly with close cropping of fingernails.
Administration of aspirin to children with chickenpox should be avoided because of the association of aspirin derivatives with the development of Reye’s syndrome.
Control & Prevention
Three methods are used for the prevention of VZV infections.
- First, a live attenuated varicella vaccine (Oka) is recommended for all children >1 year of age (up to 12 years of age) who have not had chickenpox and for adults known to be seronegative for VZV. Two doses are recommended for all children: the first at 12–15 months of age and the second at ~4–6 years of age. VZV-seronegative persons >13 years of age should receive two doses of vaccine at least 1 month apart. The vaccine is both safe and efficacious.
- A second approach is to administer varicella-zoster immune globulin (VZIG) to individuals who are susceptible, are at high risk for developing complications of varicella, and have had a significant exposure. This product should be given within 96 h (preferably within 72 h) of the exposure.
- Lastly, antiviral therapy can be given as prophylaxis to individuals at high risk who are ineligible for vaccine or who are beyond the 96-h window after direct contact. While the initial studies have used acyclovir, similar benefit can be anticipated with either valacyclovir or famciclovir. Therapy is instituted 7 days after intense exposure. At this time, the host is midway into the incubation period. This approach significantly decreases disease severity, if not totally preventing disease.
