Clinical Overview

Herpes zoster, also known as shingles, is caused by the reactivation of the varicella-zoster virus (VZV), the same virus that causes varicella (chickenpox).

Primary infection with VZV causes varicella. Once the illness resolves, the virus remains latent in the dorsal root ganglia. VZV can reactive later in a person’s life and cause a painful, maculopapular rash called herpes zoster.

Clinical Features

People with herpes zoster most commonly have a rash in one or two adjacent dermatomes (localized zoster). The rash most commonly appears on the trunk along a thoracic dermatome. The rash does not usually cross the body’s midline. Less commonly, the rash can be more widespread and affect three or more dermatomes. This condition is called disseminated zoster. This generally occurs only in people with compromised or suppressed immune systems. Disseminated zoster can be difficult to distinguish from varicella.

The rash is usually painful, itchy, or tingly. These symptoms may precede rash onset by several days. Some people may also have headache, photophobia (sensitivity to bright light), and malaise in the prodromal phase.

The rash develops into clusters of vesicles. New vesicles continue to form over three to five days and progressively dry and crust over. They usually heal in two to four weeks. There may be permanent pigmentation changes and scarring on the skin.

Complications

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. PHN is pain that persists in the area where the rash once was for more than 90 days after rash onset. PHN can last for weeks or months, and occasionally, for years.

A person’s risk of having PHN after herpes zoster increases with age. Older adults are more likely to have longer lasting, more severe pain. Approximately 10 to 13% of people 60 years and older with herpes zoster will get PHN. PHN is rare in people younger than 40 years old. Other predictors of PHN include the level of pain and the size of rash.

Other complications of herpes zoster include:

• ophthalmic involvement (herpes zoster ophthalmicus) with acute or chronic ocular sequelae, including vision loss;
• bacterial superinfection of the lesions, usually due to Staphylococcus aureus and, less commonly, due to group A beta hemolytic streptococcus;
• cranial and peripheral nerve palsies; and
• visceral involvement, such as meningoencephalitis, pneumonitis, hepatitis, and acute retinal necrosis.

People with compromised or suppressed immune systems are more likely to have complications from herpes zoster. They are more likely to have a severe, long-lasting rash and develop disseminated herpes zoster.

Vaccination

Recombinant zoster vaccine (RZV, Shingrix) is the recommended vaccine to prevent shingles and its complications.

The Advisory Committee on Immunization Practices (ACIP) recommends Shingrix for adults 50 years and older. Immunocompetent adults 50 years and older should get two doses of Shingrix, 2 to 6 months apart, whether or not they have already had herpes zoster or previously received Zostavax^®, which is no longer in use in the United States.

Shingrix provides strong protection against herpes zoster and PHN. Two doses of Shingrix are more than 90% effective at preventing herpes zoster and PHN. Protection stays above 85% for at least the first four years after vaccination.

Transmission

People with active herpes zoster lesions can spread VZV infection and cause varicella in people who have never had varicella or received varicella vaccine. Once varicella resolves, these people would be at risk of herpes zoster.

Active herpes zoster lesions are infectious, through direct contact with vesicular fluid, until they dry and crust over. People with active herpes zoster lesions should cover their lesions and avoid contact with susceptible people in their household and in occupational settings until their lesions are dry and crusted.

Also see Managing People at High Risk for Severe Varicella.

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Epidemiology

Risk Factors

Anyone who has had natural infection with wild-type varicella zoster virus (VZV) or had varicella vaccination can develop herpes zoster. Children who get the varicella vaccine have a lower risk of herpes zoster compared with children who were infected with wild-type VZV. Many people do not remember having chickenpox; however, approximately 99.5% of people born before 1980 in the United States have been infected with wild-type VZV. As a result, almost all older adults in the United States are at risk for herpes zoster.

Approximately 1 out of 3 people in the United States will develop herpes zoster during their lifetime. Most people have only one episode of the illness in their lifetime, however, multiple episodes are possible. A person’s risk for herpes zoster, and complications, such as post herpetic neuralgia (PHN) and hospitalization, increases sharply after 50 years of age.

The reasons why VZV reactivates and causes herpes zoster are not well understood. However, a person’s risk for herpes zoster increases as their VZV-specific cell-mediated immunity declines. This decline in immunity can result from increasing age as well as from medical conditions or medications that suppress a person’s immune system.

People with the following conditions that compromise or suppress their immune system have an increased risk for herpes zoster:

• cancer, especially leukemia and lymphoma,
• human immunodeficiency virus (HIV),
• bone marrow or solid organ (renal, cardiac, liver, and lung) transplant recipients, or
• taking immunosuppressive medications, including steroids, chemotherapy, or transplant-related immunosuppressive medications.

Other potential risk factors for herpes zoster have been identified, but the findings are either inconsistent or unexplained. For example:

• more women than men develop herpes zoster
• herpes zoster is less common in blacks (by at least 50%) than in whites

 Disease Rates

• An estimated one million cases of herpes zoster occur annually in the United States.
• The incidence for herpes zoster is approximately 4 cases per 1,000 U.S. population annually.
• The incidence among people 60 years and older is about 1 case per 100 U.S. population annually.

• Repeat episodes:
  • Multiple episodes of herpes zoster can occur, but the precise incidence of recurrence is not known. Most people have only one episode of herpes zoster in their lifetime.
• Complications:
  • Approximately 1 to 4% of people with herpes zoster get hospitalized for complications.
  • Older adults and people with compromised or suppressed immune systems are more likely to get hospitalized. About 30% of all people hospitalized with herpes zoster have compromised or suppressed immune systems.
  • About 1 in 10 adults with herpes zoster develop PHN.
• Deaths:
  • One study estimated that 96 deaths occur each year in which herpes zoster was the actual underlying cause (0.28 to 0.69 per 1 million population). Almost all the deaths occurred in elderly people or those with compromised or suppressed immune systems.

Trends

Herpes zoster rates are increasing among adults in the United States, especially among younger adults. The increase has been gradual over a long period of time. We do not know the reason for this increase. The rates among older adults are plateauing.

Some experts suggest that exposure to varicella boosts a person’s immunity to VZV and reduces the risk for VZV reactivation. Thus, they are concerned that routine childhood varicella vaccination, recommended in the United States in since 1996, could lead to an increase in herpes zoster in adults due to reduced opportunities for being exposed to varicella. However, two CDC studies have found that herpes zoster rates:

• started increasing before varicella vaccine was introduced in the United States, and
• did not accelerate after the routine varicella vaccination program started.

Other countries, that do not have routine varicella vaccination programs, have also observed similar increases in herpes zoster rates.

Herpes Zoster in People Who Received Varicella Vaccine

Although herpes zoster has always been uncommon among children, the rate of herpes zoster in U.S. children has been declining since the routine varicella vaccination program started. Varicella vaccine contains live attenuated VZV, which causes latent infection.

• Children (healthy and immunocompromised) who have been vaccinated against varicella have lower rates of herpes zoster compared to children who had natural infection with varicella. The reason for this is that vaccinated children are less likely to become infected with wild-type VZV, and the risk of reactivation of vaccine-strain VZV appears lower compared with reactivation of wild-type VZV.
• The number of older adults who have received varicella vaccine since it was licensed in 1995 is quite small. There is very little information on the risk of herpes zoster in people who got varicella vaccine as adults.

CDC continues to study the epidemiology of herpes zoster among adults and children and to monitor the effects of the U.S. varicella and herpes zoster vaccination programs.

References

1. CDC. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP) Recommendations for use of Herpes Zoster Vaccines. MMWR Recomm Rep. 2018;67(03):103-108.
2. Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis. 2004;4(1):26-33.
3. Tseng HF, Smith N, Harpaz R, Bialek SR, Sy LS, Jacobsen SJ. Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease. JAMA. 2011 Jan 12;305(2):160-6.
4. Mahamud A, Marin M, Nickell SP, Shoemaker T, Zhang JX, Bialek SR. Herpes zoster-related deaths in the United States: validity of death certificates and mortality rates, 1979-2007. Clin Infect Dis.2012 Oct;55(7):960-6.
5. Leung J, Harpaz R, Molinari NA, Jumaan A, Zhou F. Herpes zoster incidence among insured persons in the United States, 1993-2006: evaluation of impact of varicella vaccination. Clinical Infectious Diseases. 2011;52(3):332-340.
6. Yih W, Brooks D, Lett S, Jumaan A, Zhang Z, Clements K, Seward J. The Incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage. BMC Public Health. 2005;5(68).
7. Jumaan AO, Yu O, Jackson LA, Bohlke K, Galil K, Seward JF. Incidence of herpes zoster, before and after varicella vaccination-associated decreases in the incidence of varicella. Journal of Infectious Diseases. 2005;191:2002-7.
8. Hales CM, Harpaz R, Joesoef MR, Bialek SR (2013). Examination of links between herpes zoster incidence and childhood varicella vaccination. Annals of Internal Medicine. 159(11):739-45
9. Russell ML, Dover DC, Simmonds KA, Svenson LW. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. DOI 10.1016/j.vaccine.2013.09.018.
10. Weinmann S, Chun C, Schmid DS, Roberts M, Vandermeer M, Riedlinger K, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005–2009. Journal of Infection Diseases. 2013;208(11):1859-68.
11. Hardy I, Gershon AA, Steinberg SP, LaRussa P. The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group. N Engl J Med. 1991;325(22):1545-50.

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