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"Shingles" redirects here, for other uses of the term, see Shingle.
| Herpes zoster Classification & external resources | |
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| Herpes zoster blisters on the neck and shoulder | |
| ICD-10 | B02. |
| ICD-9 | 053 |
| DiseasesDB | 29119 |
| MedlinePlus | 000858 |
| eMedicine | med/1007 derm/180 emerg/823 oph/257 ped/996 |
Herpes zoster (or zoster), commonly known as shingles, is a viral disease characterised by a painful skin rash with blisters in a limited area on one side of the body. It is caused by varicella zoster virus (VZV), which is also the virus that causes chickenpox. After a chickenpox infection the virus can lodge permanently in ganglionic neurons, and less frequently in non-neuronal satellite cells, without causing any symptoms, although the mechanism is not understood. In an immunocompromised individual, perhaps years or decades after a chickenpox infection, the virus may break out of nerve cell bodies and travel down nerve axons to cause viral infection of the skin in the region of the nerve. The nerve cell bodies of dorsal root, cranial nerve or autonomic ganglion may contain the latent virus, and the virus may spread from one or more ganglia along nerves of an affected segment and infect the corresponding dermatome causing a rash, often referred to as shingles.Peterslund NA (1991). "Herpesvirus infection: an overview of the clinical manifestations". Scand J Infect Dis Suppl 80: 15–20. PMID 1666443. Although the rash usually heals within two to four weeks, some sufferers experience residual nerve pain for months or years, a condition called postherpetic neuralgia.
Throughout the world the incidence rate of herpes zoster ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years. Antiviral drug treatment can reduce the severity and duration of herpes zoster when a seven to ten day course is started within 72 hours of the appearance of the characteristic rash.Cunningham AL, Breuer J, Dwyer DE, Gronow DW, Helme RD, Litt JC, Levin MJ, Macintyre CR (2008). "The prevention and management of herpes zoster". Med. J. Aust. 188 (3): 171–6. PMID 18241179.
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The earliest symptoms of herpes zoster, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis.Zamula E (2001). "Shingles: An Unwelcome Encore". FDA Consum 35 (3): 21–5. PMID 11458545. Retrieved on 2007-12-15. Revised June 2005.Dworkin RH, Johnson RW, Breuer J et al. (2007). "Recommendations for the management of herpes zoster". Clin. Infect. Dis 44 Suppl 1: S1–26. doi:10.1086/510206. PMID 17143845. These symptoms are commonly followed by sensations of burning pain, itching, and hypersensitivity.Stankus SJ, Dlugopolski M, Packer D (2000). "Management of herpes zoster (shingles) and postherpetic neuralgia". Am Fam Physician 61 (8): 2437–44, 2447–8. PMID 10794584. The pain may be extreme in the affected nerve below. These sensations are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.Katz J, Cooper EM, Walther RR, Sweeney EW, Dworkin RH (2004). "Acute pain in herpes zoster and its impact on health-related quality of life". Clin. Infect. Dis 39 (3): 342–8. doi:10.1086/421942. PMID 15307000. In most cases, after 1-2 days (but sometimes as long as 3 weeks) the initial phase is followed by the addition of the characteristic skin rash. The pain and rash most commonly occurs on the torso, but can appear on the face, eyes or other parts of the body. At first, the rash is visually similar to the first appearance of hives; however, unlike hives, herpes zoster causes skin changes limited to a dermatome (an area of skin supplied by one spinal nerve), normally resulting in a stripe or belt-like pattern limited to one side of the body and not crossing the midline.
The rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever and general malaise continue. The painful vesicles eventually become cloudy or darkened as they fill with blood, crust over within seven to ten days, and usually the crusts fall off and the skin heals, but sometimes after severe blistering scarring and discolored skin remain.
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Herpes zoster may have additional symptoms, depending on the dermatome involved. Herpes zoster ophthalmicus involves the orbit of the eye and occurs in approximately 10–25% of cases. It is caused by the virus reactivating in the ophthalmic division of the trigeminal nerve. In a minority of patients, symptoms may include conjunctivitis, keratitis, uveitis, and optic nerve palsies that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain.Shaikh S, Ta CN (2002). "Evaluation and management of herpes zoster ophthalmicus". Am Fam Physician 66 (9): 1723–1730. PMID 12449270. Herpes zoster oticus, also known as Ramsay Hunt syndrome type II, involves the ear. It is thought to result from the virus spreading from the facial nerve to the vestibulocochlear nerve. Symptoms include hearing loss and vertigo (rotational dizziness).
Zoster sine herpete describes a patient that has all symptoms of herpes zoster except the characteristic rash.Furuta Y, Ohtani F, Mesuda Y, Fukuda S, Inuyama Y (2000). "Early diagnosis of zoster sine herpete and antiviral therapy for the treatment of facial palsy". Neurology 55 (5): 708–10. PMID 10980741.
Herpes zoster on the chest
When the rash is present, a differential diagnosis is made on visual examination alone. Very few other diseases produce a rash in a dermatomal pattern (see map). Infrequently, herpes simplex virus (HSV) can produce a rash in such a pattern. The Tsanck smear is helpful for diagnosing acute infection with a herpes virus but does not distinguish between HSV and VZV.Oranje AP, Folkers E (1988). "The Tzanck smear: old, but still of inestimable value.". Pediatr Dermatol 5 (2): 127–9. PMID 2842739.
When the rash is absent (early or late in the disease, or in the case of zoster sine herpete), herpes zoster can be difficult to diagnose.Chan J, Bergstrom RT, Lanza DC, Oas JG (2004). "Lateral sinus thrombosis associated with zoster sine herpete". Am J Otolaryngol 25 (5): 357–60. PMID 15334402. Apart from the rash, most symptoms can occur also in other conditions.
Laboratory tests are available to diagnose herpes zoster. The most popular test detects VZV-specific IgM antibody in blood. This antibody is detectable only during chickenpox or herpes zoster, not while the virus is dormant.Arvin AM (1996). "Varicella-zoster virus" (PDF). Clin. Microbiol. Rev 9 (3): 361–81. PMID 8809466. In larger laboratories, lymph collected from a blister is tested with a polymerase chain reaction for VZV DNA or examined with an electron microscope for virus particles.Beards G, Graham C, Pillay D (1998). "Investigation of vesicular rashes for HSV and VZV by PCR". J. Med. Virol 54 (3): 155–7. PMID 9515761.
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The causative agent for herpes zoster is varicella zoster virus (VZV). Most people are infected with this virus as a child, as it causes chicken pox. The immune system eventually eliminates the virus from most locations, but it remains dormant in the ganglia adjacent to the spinal cord (called the dorsal root ganglion) or the ganglion semilunare (ganglion Gasseri) in the cranial base.
Herpes zoster occurs only in people who have had chickenpox, also caused by varicella zoster virus. It can occur at any age but the vast majority of patients diagnosed with it are more than 50 years old.Weinberg JM (2007). "Herpes zoster: epidemiology, natural history, and common complications". J Am Acad Dermatol 57 (6 Suppl): S130–5. doi:10.1016/j.jaad.2007.08.046. PMID 18021864. The virus survives latent in nerve cells of the nerve ganglia.Steiner I, Kennedy PG, Pachner AR (2007). "The neurotropic herpes viruses: herpes simplex and varicella-zoster". Lancet Neurol 6 (11): 1015–28. doi:10.1016/S1474-4422(07)70267-3. PMID 17945155. The disease results from the virus reactivating in a single sensory ganglion.Gilden DH, Cohrs RJ, Mahalingam R (2003). "Clinical and molecular pathogenesis of varicella virus infection". Viral Immunol 16 (3): 243–58. doi:10.1089/088282403322396073. PMID 14583142. In contrast to Herpes simplex virus the latency of VZV is poorly understood. The virus has not been recovered from human nerve cells by cell culture and the location and structure of the viral DNA is not known. Virus-specific proteins continue to be made by the infected cells during the latent period so true latency, as opposed to chronic infection, has not been proven.Kennedy PG (2002). "Varicella-zoster virus latency in human ganglia". Rev. Med. Virol. 12 (5): 327–34. doi:10.1002/rmv.362. PMID 12211045. Kennedy PG (2002). "Key issues in varicella-zoster virus latency". J. Neurovirol 8 Suppl 2: 80–4. doi:10.1080/13550280290101058. PMID 12491156.
Unless the immune system is compromised, it suppresses reactivation of the virus, so herpes zoster does not occur. Why this suppression sometimes fails is poorly understood,Donahue JG, Choo PW, Manson JE, Platt R (1995). "The incidence of herpes zoster". Arch. Intern. Med 155 (15): 1605–9. PMID 7618983. but herpes zoster is more likely to occur in people whose immune system is impaired due to aging, immunosuppressive therapy, psychological stress, or other factors.Thomas SL, Hall AJ (2004). "What does epidemiology tell us about risk factors for herpes zoster?". Lancet Infect Dis 4 (1): 26–33. doi:10.1016/S1473-3099(03)00857-0. PMID 14720565. Upon reactivation, the virus replicates in the nerve cells, and virions are shed from the cells and carried down the axons to the area of skin served by that ganglion. In the skin, the virus causes local inflammation with the formation of blisters. The pain caused by acute herpes zoster and the long-lasting nature of post herpetic neuralgia result from widespread growth of the virus in, and consequent inflammation of, the infected nerves.Schmader K (2007). "Herpes zoster and postherpetic neuralgia in older adults". Clin. Geriatr. Med. 23 (3): 615–32, vii–viii. doi:10.1016/j.cger.2007.03.003. PMID 17631237.
The symptoms of herpes zoster cannot be transmitted to another person.Schmader K (1999). "Herpes zoster in the elderly: issues related to geriatrics". Clin. Infect. Dis 28 (4): 736–9. PMID 10825029. However, during the blister phase, direct contact with the rash can spread VZV to a person who has no immunity to the virus. This newly-infected individual may then develop chickenpox, but they will not immediately develop shingles. Once the rash has developed crusts, a person is no longer contagious. A person is also not infectious before blisters appear, or during postherpetic neuralgia (pain after the rash is gone).
Although VZV has been detected in autopsies of nervous tissue,Mitchell BM, Bloom DC, Cohrs RJ, Gilden DH, Kennedy PG (2003). "Herpes simplex virus-1 and varicella-zoster virus latency in ganglia" (PDF). J. Neurovirol 9 (2): 194–204. doi:10.1080/13550280390194000. PMID 12707850. there are no methods to find dormant virus in the ganglia in live people.
The pain characteristic of herpes zoster is thought to be due to irritation of the sensory nerve fibers in which the virus reproduces.
The aims of treatment are to limit the severity and duration of pain, shorten the duration of a shingles episode, and reduce complications. After a shingles episode the herpes zoster virus will again become dormant in the nerve cell bodies of ganglia, and occasionally the virus may become reactivated to cause subsequent attacks of shingles. Symptomatic treatment is often needed for the complication of postherpetic neuralgia.Tyring SK (2007). "Management of herpes zoster and postherpetic neuralgia". J Am Acad Dermatol 57 (6 Suppl): S136–42. doi:10.1016/j.jaad.2007.09.016. PMID 18021865.
Antiviral drugs inhibit VZV replication and reduce the severity and duration of herpes zoster with minimal side effects, but do not reliably prevent postherpetic neuralgia. Of these drugs, aciclovir had been the standard of care; the new drugs valaciclovir and famciclovir demonstrate similar or superior efficacy or safety/tolerability. The drugs are used both as prophylaxis (for example, AIDS patients) and as therapy during the acute phase. Antiviral treatment is recommended for all immunocompetent individuals with herpes zoster over 50 years old, preferably within 72 hours of the appearance of the rash.Breuer J, Whitley R (2007). "Varicella zoster virus: natural history and current therapies of varicella and herpes zoster". Herpes 14 (Supplement 2): 25-9.. PMID 17939892. Complications in immunocompromised individuals with herpes zoster may be reduced with treatment of intravenous aciclovir. In people who are at high risk for recurrences, five daily oral doses of aciclovir are usually effective.Johnson, RW & Dworkin, RH (2003). "Clinical review: Treatment of herpes zoster and postherpetic neuralgia". BMJ 326 (7392): 748. doi:10.1136/bmj.326.7392.748. PMID 12676845. Administering gabapentin along with antivirals may offer further protection against postherpetic neuralgia.
Patients with mild to moderate pain can be treated with over-the-counter analgesics. Topical lotions containing calamine can be used on the rash or blisters and may be soothing. Occasionally, severe pain may require an opioid medication, such as morphine. Once the lesions have crusted over, capsaicin cream (Zostrix) may be applied. Topical lidocaine and nerve blocks may also be effective in reducing pain.Baron R (2004). "Post-herpetic neuralgia case study: optimizing pain control". Eur. J. Neurol 11 Suppl 1: 3–11. doi:10.1111/j.1471-0552.2004.00794.x. PMID 15061819.
Orally administered corticosteroids are frequently used in treatment of the infection, despite the results of clinical trials of this treatment being unconvincing. Prednisone administered with aciclovir reduces the pain associated with herpes zoster and improves the quality of life. In addition, because of the risks of corticosteroid treatment, it is recommended that this combination of drugs only be used in people more than 50 years of age, due to their greater risk of postherpetic neuralgia.Whitley RJ, Weiss H, Gnann JW, Tyring S, Mertz GJ, Pappas PG, Schleupner CJ, Hayden F, Wolf J, Soong SJ (1996). "Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group". Ann. Intern. Med. 125 (5): 376–83. PMID 8702088.
The rash and pain usually subside within three to five weeks, but about one in five patients develops a painful condition called postherpetic neuralgia, which is often difficult to manage. In some patients, herpes zoster can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve (a dermatomal distribution), but without an accompanying rash. This condition may involve complications that affect several levels of the nervous system and cause multiple cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary), ear damage, or encephalitis.
During pregnancy, first infections with VZV, causing chickenpox, may lead to infection of the fetus and complications in the newborn, but chronic infection or reactivation in shingles are not associated with fetal infection.Paryani SG, Arvin AM (1986). "Intrauterine infection with varicella-zoster virus after maternal varicella". N. Engl. J. Med. 314 (24): 1542–6. PMID 3012334. Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M (1994). "Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases". Lancet 343 (8912): 1548–51. PMID 7802767.
There is a slightly increased risk of developing cancer after a herpes zoster infection. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus.Sørensen HT, Olsen JH, Jepsen P, Johnsen SP, Schønheyder HC, Mellemkjaer L (2004). "The risk and prognosis of cancer after hospitalisation for herpes zoster: a population-based follow-up study". Br. J. Cancer 91 (7): 1275–9. doi:10.1038/sj.bjc.6602120. PMID 15328522. Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.Ragozzino MW, Melton LJ, Kurland LT, Chu CP, Perry HO (1982). "Risk of cancer after herpes zoster: a population-based study". N. Engl. J. Med. 307 (7): 393–7. PMID 6979711.
Repeat attacks of herpes zoster are rare. It is extremely rare for patients to suffer more than three recurrences.
A live vaccine for VZV exists, marketed as Zostavax. In a 2005 study of 38,000 older adults it prevented half the cases of herpes zoster and reduced the number of cases of postherpetic neuralgia by two-thirds.Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD et al. (2005). "A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults". N Engl J Med 253 (22): 2271–84. PMID 15930418. A 2007 study found that the zoster vaccine is likely to be cost-effective in the U.S., projecting an annual savings of $82 to $103 million in healthcare costs with cost-effectiveness ratios ranging from $16,229 to $27,609 per quality-adjusted life year gained.Pellissier JM, Brisson M, Levin MJ (2007). "Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults". Vaccine 25 (49): 8326–37. doi:10.1016/j.vaccine.2007.09.066. PMID 17980938. In October 2007 the vaccine became recommended in the U.S. for healthy adults aged 60 and over.Advisory Committee on Immunization Practices (2007). "Recommended adult immunization schedule: United States, October 2007–September 2008". Ann Intern Med 147 (10): 725–9. PMID 17947396. Adults also receive an immune boost from contact with children infected with varicella, a boosting method that prevents about a quarter of herpes zoster cases among unvaccinated adults, but which is becoming less common in the U.S. now that children are routinely vaccinated against varicella.Brisson M, Gay N, Edmunds W, Andrews N (2002). "Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox". Vaccine 20 (19–20): 2500–7. doi:10.1016/S0264-410X(02)00180-9. PMID 12057605.
A 2006 study of 243 cases and 483 matched controls found that fresh fruit may reduce the risk of developing shingles: people who consumed less than one serving of fruit a day had three times the risk as those who consumed over three servings, after adjusting for other factors such as total energy intake. For those aged 60 or more, vitamins and vegetable intake had a similar lowering of risk.Thomas SL, Wheeler JG, Hall AJ (2006). "Micronutrient intake and the risk of herpes zoster: a case-control study". Int J Epidemiol 35 (2): 307–14. doi:10.1093/ije/dyi270. PMID 16330478.
Varicella zoster virus is an extremely contagious virus that is prevalent worldwide. VZV has an almost 100% rate of consistent prevalence from generation to generation.Abendroth A, Arvin AM (2001). "Immune evasion as a pathogenic mechanism of varicella zoster virus". Semin. Immunol. 13 (1): 27–39. doi:10.1006/smim.2001.0293. PMID 11289797. Retrieved on 2007-12-19. Varicella zoster epidemics result from the transmission of VZV through respiratory secretions and from the virus filled lesions of infected people to individuals who lack immunity to the virus. VZV is a benign disease in a healthy child in the United States. To those individuals who are infected later in life or who have altered immune states or deficiencies, however, varicella can be lethal. The number of people in this high-risk group grows with the increase in HIV incidence and the increase in immunosuppressive therapies. Nosocomial infections of varicella are a significant problem, especially in hospitals caring for high-risk populations.Weller TH (1997). Varicella-herpes zoster virus. In: Viral Infections of Humans: Epidemiology and Control. Evans AS, Kaslow RA, eds.. Plenum Press, 865-892. ISBN 978-0306448553.
In temperate zones chickenpox is a disease of children, with most cases occurring during the winter and spring, most likely due to school contact; there is no evidence for regular epidemics. In the tropics chickenpox typically occurs among older people.Wharton M (1996). "The epidemiology of varicella-zoster virus infections". Infect Dis Clin North Am 10 (3): 571–81. PMID 8856352. Herpes zoster has no seasonal incidence and does not occur in epidemics. Incidence is highest in people who are over age 55, as well as in immunocompromised patients regardless of age group, and in individuals undergoing psychological stress. Non-whites may be at lower risk; it is unclear whether the risk is increased in females. Other potential risk factors include mechanical trauma, genetic susceptibility, and exposure to immunotoxins.
The incidence rate of herpes zoster ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years. Similar incidence rates have been observed worldwide.Araújo LQ, Macintyre CR, Vujacich C (2007). "Epidemiology and burden of herpes zoster and post-herpetic neuralgia in Australia, Asia and South America" (PDF). Herpes 14 (Suppl 2): 40A–4A. PMID 17939895. Herpes zoster develops in an estimated 500,000 Americans each year.Insinga RP (2005). "The incidence of herpes zoster in a United States administrative database". J Gen Intern Med 20 (6): 748–753. doi:10.1111/j.1525-1497.2005.0150.x. PMID 16050886. Multiple studies and surveillance data demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995.Marin M, Güris D, Chaves SS, Schmid S, Seward JF (2007). "Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 56 (RR-4): 1–40. PMID 17585291. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.
In one study, it was estimated that 26% of patients who contract herpes zoster eventually present with complications. Postherpetic neuralgia arises in approximately 20% of patients.Volpi A (2007). "Severe complications of herpes zoster" (PDF). Herpes 14 (Suppl 2): 35A–9A. PMID 17939894. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up.Coplan P, Black S, Rojas C (2001). "Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction: a baseline assessment of the shifting epidemiology of varicella disease". Pediatr Infect Dis J 20 (7): 641-5. PMID 11465834. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV in the earlier study, or to the introduction of antivirals in California before 1994.Weaver BA (2007). "The burden of herpes zoster and postherpetic neuralgia in the United States". J Am Osteopath Assoc 107 (3 Suppl): S2–7. PMID 17488884.
Electron micrograph of Varicella zoster virus
Herpes zoster has a long recorded history, although historical accounts fail to distinguish the blistering caused by VZV and those caused by smallpox, ergotism, and erysipelas. It was only in the late eighteenth century that William Heberden established a way to differentiate between herpes zoster and smallpox,Weller TH (2000). Chapter 1. Historical perspective in: Varicella-Zoster Virus: Virology and Clinical Management (Arvin AM & Gershon AA, editors). Cambridge University Press. ISBN 0521660246. and only in the late nineteenth century that herpes zoster was differentiated from erysipelas. The first indications that chickenpox and herpes zoster were caused by the same virus were noticed at the beginning of the 20th century. Physicians began to report that cases of herpes zoster were often followed by chickenpox in the younger people who lived with the shingles patients. The idea of an association between the two diseases gained strength when it was shown that lymph from a sufferer of herpes zoster could induce chickenpox in young volunteers. This was finally proved by the first isolation of the virus in cell cultures, by the Nobel laureate Thomas H. Weller in 1953.Weller TH (1953). "Serial propagation in vitro of agents producing inclusion bodies derived from varicella and herpes zoster". Proc. Soc. Exp. Biol. Med. 83 (2): 340–6. PMID 13064265.
Until the 1940s, the disease was considered benign, and it was believed that serious complications were very rare.Holt LE & McIntosh R (1936). Holt\'s Diseases of Infancy and Childhood. D Appleton Century Company, 931–3. However, by 1942, it was recognized that zoster was a more serious disease in adults than in children and that herpes zoster increased in frequency with advancing age. Further studies during the 1950s on immunosuppressed individuals showed that the disease was not as benign as once thought, and the search for various therapeutic and preventive measures began. By the mid-1960s, several studies identified the gradual reduction in cellular immunity in old age, observing that in a cohort of 1,000 people who lived to the age of 85, approximately 500 would have one attack of herpes zoster and 10 would have two attacks.Hope-Simpson RE (1965). "The nature of herpes zoster; a long-term study and a new hypothesis". Proc R Soc Med 58: 9–20. PMID 14267505.
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