Varicella-zoster virus

Figure 193.1 Varicella. Note various stages of lesions in each area of eruption. (Courtesy of David Schlossberg, MD.)

Varicella vaccine was licensed in the United States in 1995 for individuals 12 months of age. A second dose was recommended in the United States in June 2006. Since the introduction of the vaccine, the age-unadjusted incidence of chickenpox has been approximately 3 cases per 1000 population, and the hospitalization rate for complications of varicella has decreased dramatically. Complications of varicella occur most frequently in those younger than 1 year and older than 15 years. These complications include bacterial superinfection of skin, dehydration, pneumonia, encephalitis, and hepatitis. With the availability of the vaccine, hospitalizations for chickenpox have significantly decreased and VZV-associated mortality is at an all-time low of less than 0.1 per million population.

Varicella zoster (shingles)

Although 10% to 20% of Americans overall will develop zoster in their lifetimes, 50% of persons reaching age 85 can be expected to do so; the incidence of herpes zoster rises dramatically, from a low of between 1.1 and 2.9 per 1000 person-years in people younger than 50 to 4.6 and 6.9 per 1000 person-years, respectively, in the age groups 50–59 and 60–69. The age groups 70–79 and 80 years old have the highest incidence, with 9.5 and 10.9 per 1000 person-years, respectively.

The principal risk factor for herpes zoster is prior history of VZV exposure. Any person who has had chickenpox or received the varicella vaccine as a child, which includes more than 90% of the US adult population, is at risk for herpes zoster. The association with advancing years, as previously described, is due to the age-related decline in VZV-specific cell-mediated immunity. Childhood zoster is rare but not unheard of, with cases reported in children as young as 4 months. The incidence of zoster in children younger than 10, however, is only 0.74 per 1000 person-years.

Immunocompromised people or those receiving immunosuppressive drugs are also at increased risk for zoster. Thus, human immunodeficiency virus (HIV) patients have a higher incidence of zoster disease than individuals with a healthy immune system, reported in one longitudinal study as 29.4 cases per 1000 patient-years. Patients undergoing bone marrow or organ transplant and treated with immunosuppressives are known to develop zoster with increased frequency.

Genetics may play a role in the development of herpes zoster, as suggested by the finding that elderly white men are four times more likely to develop zoster than elderly black men. Some reports have suggested that systemic steroid therapy can incite VZV reactivation as well, placing persons with conditions such as rheumatoid arthritis or lupus at increased risk. Finally, both trauma and stressful life circumstances have been suggested to play a role in development of herpes zoster, further increasing the population at risk.

The characteristic feature of herpes zoster is a vesicular rash of unilateral distribution limited to one to three adjacent dermatomes. The onset of the rash, however, often is preceded by a prodromal phase. Beginning 4 days to 2 weeks before lesions appear, patients often note pain and paresthesia in what will become the zoster-affected dermatome. The pain can be intermittent or continuous, and has been described by patients variously as throbbing, sharp, stabbing, burning, or shooting pain. Malaise, dysesthesia, and itching are frequent elements of the prodrome, as well.

The most common site of infection is the trigeminal nerve. Most patients exhibit thoracic distribution of zoster rash, with more than 50% of cases presenting with cutaneous lesions of the trunk. The rash generally appears proximally, then spreads distally along the affected dermatome. The initial lesions appear as erythematous maculopapules, which turn into vesicles within 12 to 24 hours. The vesicles become pustules in about 3 days, and form scabs 7 to 10 days later. New lesions generally appear over no more than 3 to 7 days, but the duration of the rash has been correlated with patient age (advancing age associated with longer duration) and site of infection (face healing more rapidly than other loci).

Zoster affecting the first division of the trigeminal nerve, as occurs in 10% to 15% of cases, can lead to herpes zoster ophthalmicus (HZO), which produces the characteristic zoster rash on the forehead, periocular area, and nose and can be accompanied by local pain. Ocular complications of HZO are among the most dangerous morbidity of zoster disease, placing patients at risk for sight impairment or vision loss due to nerve damage or ocular pathology.

Approximately 60% to 90% of zoster patients experience local neuritic pain and hypersensitivity in association with the acute herpetic rash. This pain is likely due to an immediate nociceptive response: local inflammation and tissue damage stimulate the primary afferent neurons of the skin and subcutaneous tissue, which neurologically manifests as pain. In addition, allodynia and hyperalgesia may be present, adding to patient discomfort during acute herpes zoster.

Pain associated with zoster disease resolves within several days for many patients, although the degree of pain can be variable; one report has suggested that more extensive pain during the acute phase might predict the prolonged pain of postherpetic neuralgia (PHN), and another indicates that early pain therapy might limit the central development of chronic PHN pain following herpes zoster.


The features of varicella and varicella zoster are so characteristic that a diagnosis is generally made clinically. In chickenpox, lesions in all stages of development (macules, vesicles, pustules, and crusted lesions) may be a suggestive finding. The differential diagnosis of varicella includes the following: herpes simplex virus, Coxsackie and other enteroviruses, mycoplasma, streptococcal impetigo, rickettsialpox, insect bites, and allergic contact dermatitis.

For herpes zoster, the diagnosis can be made based on the presence of prodromal pain and/or itching, and the defining zoster rash. For patients presenting in the prodromal period, the pain and dysesthesia may require differentiation from other pain sources, such as trauma, myocardial ischemia, renal colic, gallbladder disease, or dental pain. Atypical lesions, furthermore, may require laboratory confirmation, which sometimes is obtained from viral culture (often difficult to recover from swabs) or more readily from direct immunofluorescence assay. Recently, nested and real-time polymerase chain reaction (PCR) testing of samples from skin lesions have proved valuable for identifying VZV, with more rapid amplification than other methods and high sensitivity. These laboratory techniques are most valuable for differentiating VZV from zosteriform herpes simplex, a herpes simplex viral infection that mimics zoster disease.

Prevention and therapy

Varicella vaccine

The live, attenuated varicella vaccine (Varivax) was approved in the United States in 1995 and is recommended for persons older than 12 months. Every person in the United States who does not have indicators for VZV immunity should have two doses of varicella vaccine. The first dose should be administered at the age of 12 to 15 months. The second dose should be given between the ages of 4 and 6 years. People 13 years of age and older who have never had chickenpox or received chickenpox vaccine should get two doses, at least 28 days apart.

Each dose, for infants and adults, is 0.5 mL administered subcutaneously.

Other populations may benefit from varicella vaccine, including eligible healthcare and day-care workers, college students, prisoners, military recruits, nonpregnant women of childbearing age, and international travelers.

Prior to the introduction of the vaccine, about 11 000 people were hospitalized for chickenpox each year in the United States, and about 100 people died each year as a result of chickenpox in the United States. As noted previously, since the introduction of the vaccine, the incidence of chickenpox and the hospitalization rate for complications of varicella has decreased dramatically.

The vaccine is not recommended for infants <1 year old, for those on salicylate therapy, for pregnant women, or those allergic to components of the vaccine, including neomycin, gelatin, and monosodium glutamate. Immunosuppressed individuals should confer with their physician about the risks and benefits of vaccination.

Zoster vaccine

The herpes zoster vaccine is a live attenuated preparation of the Oka/Merck strain of VZV that boosts the recipient’s immunity to VZV, thus increasing the chance that their latent VZV will remain dormant and that they will not develop herpes zoster. Its efficacy and safety in reducing the risk of herpes zoster disease in adults over age 60 were established in a pivotal trial, on the basis of which the US Food and Drug Administration (FDA) approved the vaccine in May 2006 for clinical use. On March 24, 2011, the FDA approved Zostavax for individuals 50 to 59 years of age.


Overall assessment

The goal in management is to treat the symptoms of primary VZV infection and to prevent complications if possible. The three stages of management are (1) establishing the likelihood of the diagnosis, (2) determining whether antiviral therapy is indicated, and (3) ruling out secondary bacterial infection, other complications, and failure of previous antiviral treatment.

Symptomatic therapy

Itching is the major symptom of chickenpox, and antipyretic management is important. Warm baths containing baking soda (1/3 cup per bathtub) or emulsified oatmeal (Aveno) can temporarily relieve pruritus. This can be combined with the oral administration of either diphenhydramine (Benadryl), 1.25 mg/kg every 6 hours, or hydroxyzine (Atarax, Vistaril), 0.5 mg/kg every 6 hours. In older children, cold pramoxine HCl 1% lotion with calamine 8% (Caladryl) can be used, but this should be avoided in infants because of the risk of excessive surface exposure and absorption of drug or vehicle (alcohol 2.2%). Fever should be controlled with acetaminophen, but salicylates should not be used because administration of certain salicylates to children with chickenpox increases the risk of subsequent Reye’s syndrome. For severe dysuria, a cold compress on the genital area during urination will ease the pain and minimize the likelihood of a functional bladder obstruction.

Antiviral therapy

Acyclovir (Zovirax) is the only agent licensed in the United States for the treatment of chickenpox. It is indicated for treatment of chickenpox in certain normal persons, for disseminated VZV infection in immunosuppressed persons, and for treatment of shingles. Oral acyclovir should be used in otherwise healthy persons with chickenpox who are at risk for moderate to severe disease, such as those older than 12 years, those with chronic cutaneous or pulmonary disorders, those receiving chronic salicylate therapy, and those receiving short, intermittent, or aerosolized courses of corticosteroids or aerosolized corticosteroids (Table 193.1

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Jun 18, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on Varicella-zoster virus

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