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Clinical Overview

Herpes zoster, also known as zoster and 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, and once the illness resolves, the virus remains dormant in the dorsal root ganglia. VZV can reactive later in a person’s life and cause a painful, maculopapular rash called herpes zoster.

Anyone who has had varicella or gotten varicella vaccine can develop herpes zoster. Most people typically have only one episode of herpes zoster in their lifetime. However, second and even third episodes are possible.

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. However, approximately 20% of people have rash that overlaps adjacent dermatomes. 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 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 days to weeks. Some people may also have headache, photophobia, and malaise in the prodromal phase.

The rash develops into clusters of clear 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. It is a persistent pain in the area where the rash once was. PHN is diagnosed in people who have pain that persists after their rash has resolved. Some define PHN as any duration of pain after the rash resolves; others define it as duration of pain for more than 30 days, or for more than 90 days after rash onset. PHN can last for weeks or months and occasionally, for many years.

A person's risk of having PHN after herpes zoster increases with age. Older adults are more likely to have PHN and to have longer lasting and more severe pain. Approximately 13% (and possibly more) of people 60 years of age 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 a person has when they have zoster rash and the size of their rash.

Other complications of herpes zoster include—

  • ophthalmic involvement with acute or chronic ocular sequelae (herpes zoster ophthalmicus);
  • 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, 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 severe rash that lasts longer. Also, they are at increased risk of developing disseminated herpes zoster.

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Transmission

People with active lesions caused by herpes zoster can spread VZV to susceptible people. People who have not had chickenpox and never received chickenpox vaccine can get infected with VZV from someone with herpes zoster. If this happens, they are at risk of developing varicella not herpes zoster.

The virus spreads when a person has direct contact with the lesions. The lesions are infectious until they dry and crust over. People with active herpes zoster lesions should avoid contact with susceptible people in their household who do not have evidence of VZV immunity and in occupational settings until their lesions dry and crusted.

Susceptible people at high risk for severe chickenpox include—

  • pregnant women,
  • all premature infants born to susceptible mothers,
  • infants born at less than 28 weeks gestation or who weigh less than 1000 grams, regardless of whether the mother had chickenpox or been vaccinated, and
  • people of all ages who have compromised or suppressed immune systems.

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Epidemiology

Risk Factors

Only people who were previously infected with VZV (through natural infection that caused varicella or varicella vaccination) can develop shingles. Although many people do not remember, approximately 99.5% of people born in the United States who are 40 years of age and older have had varicella. As a result, all older adults in the United States are at risk for herpes zoster.

The reasons why VZV reactivates and causes herpes zoster are not well understood. However, a person's risk for herpes zoster may increase as their VZV-specific cell-mediated immunity declines. This decline in immunity can result from increasing age and/or immunosuppressive medical conditions and medications.

A person's risk for herpes zoster increases sharply after 50 years of age. About 50% of people who live to 85 years of age will have had an episode of herpes zoster. A person’s risk for PHN also increases sharply with age. The oldest adults with herpes zoster are most likely to be hospitalized for complications from the disease and to develop PHN.

People with compromised or suppressed immune systems who have an increased risk for herpes zoster include those

  • with cancer, especially leukemia and lymphoma,
  • with human immunodeficiency virus,
  • who have undergone bone marrow or solid organ (renal, cardiac, liver, and lung) transplantation, or
  • who are 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 not consistent in all studies. For example-

  • Some studies found that more women than men develop herpes zoster, but other studies did not find a difference [1,2]; the reason for a possible difference between women and men is not known.
  • Some studies conducted in the United States and elsewhere found that herpes zoster is less common in African Americans (by at least 50%) than in whites.[3]

Rates

  • Disease occurrence:
    • The incidence for herpes zoster is approximately 4 cases per 1,000 U.S. population annually, age-adjusted to the 2000 U.S. population
    • The incidence among people 60 years of age and older is about 10 cases per 1,000 U.S. population annually.
    • There are an estimated one million cases of herpes zoster in the United States annually.
  • Repeat episodes:
    • Although 2nd and even 3rd episodes of herpes zoster can occur, the annual incidence of recurrence is not known.
  • Hospitalizations:
    • 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 are those with compromised or suppressed immune systems.
  • Deaths:
    • A recent study estimated that there are 96 deaths each year in which herpes zoster was the actual underlying cause (0.28-0.69 per 1 million population). Almost all the deaths occurred in elderly people or those with compromised or suppressed immune systems. [4]

Trends

Herpes zoster rates are increasing among adults in the United States. The increase has been gradual over a long period of time. We do not know the reason for this increase.[5,6,7]

Some experts suggest that exposure to varicella disease boosts a person’s immunity to VZV and reduces risk for VZV reactivation. Thus, they are concerned that routine childhood varicella vaccination, recommended in the United States in 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.[5,8]

Other countries, that do not have routine varicella vaccination programs, have also observed similar increases in herpes zoster rates.[9]

Herpes Zoster in People Who Received Varicella Vaccine

Although 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. The attenuated vaccine virus can reactivate and cause herpes zoster. Children vaccinated against varicella appear to have a lower risk of herpes zoster than people who were infected with wild-type VZV.[10] 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 is lower compared with reactivation of wild-type VZV.

  • In a study of children with leukemia, those who got varicella vaccine had a 67% lower risk of herpes zoster than children who had natural varicella disease.[11]
  • Data on healthy children show a similar pattern of reduced risk of herpes zoster in those vaccinated against varicella.
  • The number of older adults who have gotten 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 zoster vaccination programs.


References

  1. CDC. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(05):1-30.
  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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