Varicella-zoster virus (VZV) causes two distinct clinical entities: varicella (chickenpox) and herpes zoster (shingles). 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.
A clinical association between varicella and herpes zoster has been recognized for nearly 100 years. Early in the twentieth century, similarities in the histopathologic features of skin lesions resulting from varicella and herpes zoster were demonstrated. Viral isolates from patients with chickenpox and herpes zoster produced similar alterations in tissue culture—specifically, the appearance of eosinophilic intranuclear inclusions and multinucleated giant cells. These results suggested that the viruses were biologically similar. Restriction endonuclease analyses of viral DNA from a patient with chickenpox who subsequently developed herpes zoster verified the molecular identity of the two viruses responsible for these different clinical presentations.
VZV is a member of the family Herpesviridae, sharing with other members such structural characteristics as a lipid envelope surrounding a nucleocapsid with icosahedral symmetry, a total diameter of ∼180–200 nm, and centrally located double-stranded DNA that is ∼125,000 bp in length.
Pathogenesis and Pathology
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 reticuloendothelial system and ultimately to the development of viremia. Viremia in patients with chickenpox is reflected in the diffuse and scattered nature of the skin lesions and can be verified in selected cases by the recovery of VZV from the blood or routinely by the detection of viral DNA in either blood or lesions by polymerase chain reaction (PCR). 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.
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, is uncommon in VZV infection.
Epidemiology and Clinical Manifestations
Humans are the only known reservoir for VZV. 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 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. VZV vaccination during the second year of life has dramatically changed the epidemiology of infection, causing a significant decrease in the annualized incidence of chickenpox.
The incubation period of chickenpox ranges from 10–21 days but is usually 14–17 days. Secondary attack rates in susceptible siblings within a household are 70–90%. 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.
Clinically, chickenpox presents with a rash, low-grade fever, and malaise, although a few patients develop a prodrome 1–2 days before onset of the exanthem. 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. The skin lesions—the hallmark of the infection—include maculopapules, vesicles, and scabs in various stages of evolution (Fig. 180-1). 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. Successive crops appear over a 2- to 4-day period. Lesions can also be found on the mucosa of the pharynx and/or the vagina. Their severity varies from one person to another. Some individuals have very few lesions, while others have as many as 2000. 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. 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. Immunocompromised individuals are also at greater risk for visceral complications, which occur in 30–50% of cases and are fatal ...