Varicella-Zoster Virus (Chickenpox, Shingles)

Definition

Primary infection with varicella-zoster virus results in the rash of varicella (chickenpox). The varicella-zoster virus establishes a latent infection in the nervous system and can reactivate later in life to cause zoster (shingles).

Epidemiology

Before the advent of an effective vaccine, more than 95% of children in temperate climates were infected with varicella-zoster virus. By comparison, infection is usually delayed until adulthood in tropical climates. Varicella usually occurs in children younger than 5 years. Zoster is less common in tropical areas, probably because of a delay in acquisition of varicella. Varicella is more common in the winter and spring, whereas zoster has no seasonal predilection.

Primary varicella infection can occur after exposure to either chickenpox or zoster. The virus is spread by droplets and aerosols from patients or by contact with vesicular lesions. Persons are infectious beginning about 2 days before the rash appears and continuing until all lesions have crusted. Although 60 to 90% of susceptible household contacts develop varicella, only 20 to 30% of susceptible persons exposed to zoster become infected. More than 95% of primary infections result in the symptoms of varicella, and second episodes of varicella are rare. Varicella is more severe in persons with impaired cellular immunity, including patients who are infected with human immunodeficiency virus (HIV) and infants whose mothers present with varicella 5 days before to 2 days after delivery.

In unvaccinated immunocompetent adults over age 50 years, the risk of herpes zoster is about 0.9% per 100 person-years. Before the introduction of an effective zoster vaccine, about 50% of persons who had varicella and lived to age 85 years developed zoster. The risk for zoster rises with increasing age (especially 50 years and older) and with increasing impairment of cellular immunity. ^, Perhaps because of advanced medical care and recognition by physicians, the reported incidence of zoster has increased by four-fold over the past six decades and continues to increase, although hospitalizations for zoster have decreased in adults since 2008, apparently related to the herpes zoster vaccine. ^, Men who are infected with HIV and who are not taking antiretroviral therapies have a 15-fold higher risk for development of zoster than age-matched controls. Less than 5% of persons have a second episode of zoster, but recurrent zoster is more common in persons with impaired cellular immunity.

Pathobiology

Varicella is transmitted by the respiratory route. The virus is thought to infect epithelial cells and lymphocytes in the oropharynx and upper respiratory tract or in the conjunctiva, and then infected lymphocytes subsequently spread the virus throughout the body. The virus then enters the skin through endothelial cells in blood vessels and spreads to epithelial cells, where it causes the vesicular rash of varicella. Lesions initially are vesicular but become pustular after the infiltration of inflammatory cells. Later the lesions break open and dry to form crusts that usually heal without scarring. During primary infection, neurons in cranial nerve ganglia and dorsal root ganglia become latently infected with the virus.

If varicella-zoster virus–specific cellular immunity declines, the virus can reactivate from a ganglion, travel down the axon, and replicate in epithelial cells to cause dermatomal zoster. In highly immunocompromised persons, high-grade viremia during reactivation causes disseminated zoster.

Antibodies, which usually are present at the time varicella presents clinically, persist for life. Antibody is important for protection against varicella, as evidenced by the ability of varicella immune globulin to attenuate the disease. Cytotoxic T cells are present within 2 to 3 days after the onset of varicella and limit its severity. Varicella and zoster are more severe in persons with impaired cellular immunity (e.g., HIV infection or genetic variants, particularly variants that affect interferon function) but not in patients with hypogammaglobulinemia. Cellular immunity is required to prevent reactivation of virus and zoster.

Clinical Manifestations

Varicella

Varicella begins with fever and malaise followed 1 to 2 days later by a disseminated, pruritic, vesicular rash ( Fig. 346-1 ). The usual incubation period for varicella is 2 weeks (range, 10 to 21 days) after exposure to an infected person. The lesions begin as papules that become vesicles, followed by pustules and then crusts. Lesions appear on the head and then spread to the trunk and then to the extremities; the mucosa also can be involved. There are typically 200 to 500 lesions in different stages on the skin. New lesions occur for up to 5 days in normal hosts, and crusting is complete within 2 weeks.

The most common complication of varicella is bacterial superinfection of skin lesions. Group A streptococcus ( Chapter 269 ) or Staphylococcus aureus ( Chapter 267 ) infections can cause cellulitis, bacteremia, and necrotizing fasciitis. Other complications include cerebellar ataxia, viral pneumonitis, hepatitis, and thrombocytopenia. Less frequent complications include viral meningitis, encephalitis, vasculopathy (which presents as a stroke), disseminated intravascular coagulopathy ( Chapter 161 ), and Reye syndrome (more common in children receiving aspirin) ( Chapter 136 ). Complications involving the lungs and liver are more common in children with impaired cellular immunity, including those receiving systemic steroids, children with chronic pulmonary or skin disease, adults, and pregnant women during the third trimester. The fetal varicella syndrome, which occurs in fetuses infected during the first trimester, is characterized by atrophy of limbs with scarring of skin, chorioretinitis or cataracts, and central nervous system abnormalities. HIV-infected patients who have moderately reduced CD4 cell counts may develop recurrent varicella lesions in the absence of new exposures, and patients who have CD4 cell counts below 200/µL may develop progressive varicella with new lesions occurring for at least 1 month or chronic verrucous lesions.