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{{Short description|Viral disease caused by the varicella zoster virus}} {{Other uses|Shingle (disambiguation)}} {{Redirect|Zoster}} {{Good article}} {{Use dmy dates|date=May 2024}} {{Infobox medical condition (new) | name = Shingles | synonyms = Herpes zoster | image = Herpes zoster neck.png | caption = Herpes zoster blisters on the neck and shoulder | field = [[Dermatology]] | symptoms = Painful rash | complications = [[Meningitis]], [[facial nerve palsy]], [[keratitis]], [[postherpetic neuralgia]]<ref name=Pink2015/> | onset = | duration = 2–4 weeks<ref name=CDC2014Sym/> | causes = [[Varicella zoster virus]] (VZV)<ref name=Pink2015/> | risks = Old age, [[Immunosuppression|poor immune function]], having had chickenpox before 18 months of age<ref name=Pink2015/> | diagnosis = Based on symptoms<ref name=NEJM2013/> | differential = [[Herpes simplex]], chest pain, [[insect bite]]s, [[cutaneous leishmaniasis]]<ref>{{cite web | title=Herpes Zoster Diagnosis, Testing, Lab Methods | date=April 2022 | publisher=[[Centers for Disease Control and Prevention]] (CDC) | url=https://www.cdc.gov/shingles/hcp/diagnosis-testing.html | access-date=10 June 2022 | archive-date=3 June 2022 | archive-url=https://web.archive.org/web/20220603200709/https://www.cdc.gov/shingles/hcp/diagnosis-testing.html | url-status=live }} {{PD-notice}}</ref> | prevention = [[Shingles vaccine]]<ref name=Pink2015/> | treatment = | medication = [[Aciclovir]] (if given early), pain medication<ref name=NEJM2013/> | frequency = 33% (at some point)<ref name=Pink2015/> | deaths = 6,400 (with chickenpox)<ref name=GBD2015De>{{cite journal| vauthors = ((GBD 2015 Mortality and Causes of Death Collaborators)) |title=Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015|journal=Lancet|date=8 October 2016|volume=388|issue=10053|pages=1459–1544|pmid=27733281|pmc=5388903|doi=10.1016/s0140-6736(16)31012-1}}</ref> }} '''Shingles''', also known as '''herpes zoster''' or '''zona''',<ref>{{Cite web |date=2024-09-18 |title=Herpes zoster {{!}} Shingles, Varicella-Zoster, Pain Relief {{!}} Britannica |url=https://www.britannica.com/science/herpes-zoster |access-date=2024-10-26 |website=www.britannica.com |language=en}}</ref> is a [[viral disease]] characterized by a painful [[skin rash]] with blisters in a localized area.<ref name=CDC2014Sym/><ref>{{cite book | vauthors = Sivapathasundharam B, Gururaj N, Ranganathan K | chapter = Viral Infections of the Oral Cavity | veditors = Rajendran A, Sivapathasundharam B |title=Shafer's textbook of oral pathology|date=2014|isbn=978-8131238004|page=351|edition=Seventh| chapter-url = https://books.google.com/books?id=WnhtAwAAQBAJ&pg=PA351|publisher=Elsevier Health Sciences ]|access-date=11 September 2017|archive-date=17 December 2019|archive-url=https://web.archive.org/web/20191217060733/https://books.google.com/books?id=WnhtAwAAQBAJ&pg=PA351|url-status=live}}</ref> Typically the rash occurs in a single, wide mark either on the left or right side of the body or face.<ref name=Pink2015/> Two to four days before the rash occurs there may be [[paresthesia|tingling]] or local pain in the area.<ref name=Pink2015/><ref name=":1">{{Cite journal |last1=de Oliveira Gomes |first1=Juliana |last2=Gagliardi |first2=Anna Mz |last3=Andriolo |first3=Brenda Ng |last4=Torloni |first4=Maria Regina |last5=Andriolo |first5=Regis B. |last6=Puga |first6=Maria Eduarda Dos Santos |last7=Canteiro Cruz |first7=Eduardo |date=2 October 2023 |title=Vaccines for preventing herpes zoster in older adults |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=10 |pages=CD008858 |doi=10.1002/14651858.CD008858.pub5 |issn=1469-493X |pmc=10542961 |pmid=37781954}}</ref> Other common symptoms are fever, headache, and tiredness.<ref name=Pink2015/><ref name=Dwo2007/> The rash usually heals within two to four weeks,<ref name=CDC2014Sym>{{cite web|title=Shingles (Herpes Zoster) Signs & Symptoms|url=https://www.cdc.gov/shingles/about/symptoms.html|access-date=26 May 2015|date=1 May 2014|url-status=live|archive-url=https://web.archive.org/web/20150526151203/http://www.cdc.gov/shingles/about/symptoms.html|archive-date=26 May 2015| publisher=[[Centers for Disease Control and Prevention]] (CDC) }}{{PD-notice}}</ref> but some people develop ongoing [[neuropathy|nerve pain]] which can last for months or years, a condition called [[postherpetic neuralgia]] (PHN).<ref name=Pink2015/> In those with [[Immunosuppression|poor immune function]] the [[#Disseminated shingles|rash may occur widely]].<ref name=Pink2015/> If the rash involves the eye, [[vision loss]] may occur.<ref name=CDC2014Sym/><ref name=PMID26478818>{{cite journal | vauthors = Johnson RW, Alvarez-Pasquin MJ, Bijl M, Franco E, Gaillat J, Clara JG, Labetoulle M, Michel JP, Naldi L, Sanmarti LS, Weinke T | display-authors = 6 | title = Herpes zoster epidemiology, management, and disease and economic burden in Europe: a multidisciplinary perspective | journal = Therapeutic Advances in Vaccines | volume = 3 | issue = 4 | pages = 109–120 | date = July 2015 | pmid = 26478818 | pmc = 4591524 | doi = 10.1177/2051013615599151 }}</ref> Shingles is caused by the [[varicella zoster virus]] (VZV) that also causes [[chickenpox]]. In the case of chickenpox, also called varicella, the initial infection with the virus typically occurs during childhood or adolescence.<ref name=Pink2015/> Once the chickenpox has resolved, the virus can remain [[virus latency|dormant]] (inactive) in human [[nerve cell]]s ([[Dorsal root ganglion|dorsal root ganglia]] or [[cranial nerves]])<ref name="pmid35340552">{{cite journal | vauthors=Pan CX, Lee MS, Nambudiri VE | title=Global herpes zoster incidence, burden of disease, and vaccine availability: a narrative review | journal=[[SAGE Publishing|Therapeutic Advances in Vaccines and Immunotherapy]] | volume=10 | year=2022 | doi = 10.1177/25151355221084535 | pmc=8941701 | pmid=35340552 }}</ref> for years or decades, after which it may reactivate and travel along nerve bodies to nerve endings in the skin, producing blisters.<ref name=Pink2015/><ref name=":1" /> During an outbreak of shingles, exposure to the varicella virus found in shingles blisters can cause chickenpox in someone who has not yet had chickenpox, although that person will not suffer from shingles, at least on the first infection.<ref>{{cite web|title=Shingles (Herpes Zoster) Transmission |url=https://www.cdc.gov/shingles/about/transmission.html|access-date=26 May 2015|date=17 September 2014|url-status=live|archive-url=https://web.archive.org/web/20150506112409/http://www.cdc.gov/shingles/about/transmission.html|archive-date=6 May 2015| publisher=[[Centers for Disease Control and Prevention]] (CDC)}}{{PD-notice}}</ref> How the virus remains dormant in nerve cells or subsequently re-activates is not well understood.<ref name=Pink2015/><ref>{{Cite web |title=Researchers discover how chickenpox and shingles virus remains dormant |url=https://www.uclhospitals.brc.nihr.ac.uk/news/researchers-discover-how-chickenpox-and-shingles-virus-remains-dormant |access-date=25 April 2023 |website=UCLH Biomedical Research Centre |date=20 April 2018 |language=en}}</ref> The disease has been recognized since [[Ancient history|ancient times]].<ref name=Pink2015>{{cite book | vauthors = Lopez A, Harrington T, Marin M | chapter = Chapter 22: Varicella | publisher = U.S. [[Centers for Disease Control and Prevention]] (CDC) | veditors = Hamborsky J, Kroger A, Wolfe S | title = Epidemiology and Prevention of Vaccine-Preventable Diseases | edition = 13th | location = Washington D.C. | year = 2015 | chapter-url = https://www.cdc.gov/vaccines/pubs/pinkbook/varicella.html | isbn = 978-0990449119 | url = https://www.cdc.gov/vaccines/pubs/pinkbook/index.html | access-date = 9 January 2020 | archive-date = 30 December 2016 | archive-url = https://web.archive.org/web/20161230001534/https://www.cdc.gov/vaccines/pubs/pinkbook/index.html | url-status = live }}{{PD-notice}}</ref> Risk factors for reactivation of the dormant virus include old age, [[Immunodeficiency|poor immune function]], and having contracted chickenpox before 18 months of age.<ref name=Pink2015/> Diagnosis is typically based on the signs and symptoms presented.<ref name=NEJM2013/> ''Varicella zoster virus'' is not the same as ''[[herpes simplex virus]]'', although they both belong to the alpha subfamily of [[herpesvirus]]es.<ref name=CDC2014Over/> [[Shingles vaccine]]s reduce the risk of shingles by 50 to 90%, depending on the vaccine used.<ref name=Pink2015/><ref name=Cun2016>{{cite journal | vauthors = Cunningham AL | title = The herpes zoster subunit vaccine | journal = Expert Opinion on Biological Therapy | volume = 16 | issue = 2 | pages = 265–271 | date = 2016 | pmid = 26865048 | doi = 10.1517/14712598.2016.1134481 | name-list-style = vanc | s2cid = 46480440 }}</ref> Vaccination also decreases rates of [[postherpetic neuralgia]], and, if shingles occurs, its severity.<ref name=Pink2015/> If shingles develops, antiviral medications such as [[aciclovir]] can reduce the severity and duration of disease if started within 72 hours of the appearance of the rash.<ref name=NEJM2013>{{cite journal | vauthors = Cohen JI | title = Clinical practice: Herpes zoster | journal = The New England Journal of Medicine | volume = 369 | issue = 3 | pages = 255–263 | date = July 2013 | pmid = 23863052 | pmc = 4789101 | doi = 10.1056/NEJMcp1302674 | name-list-style = vanc }}</ref> Evidence does not show a significant effect of antivirals or [[Corticosteroid|steroids]] on rates of postherpetic neuralgia.<ref>{{cite journal | vauthors = Chen N, Li Q, Yang J, Zhou M, Zhou D, He L | title = Antiviral treatment for preventing postherpetic neuralgia | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 2 | pages = CD006866 | date = February 2014 | pmid = 24500927 | pmc = 10583132 | doi = 10.1002/14651858.CD006866.pub3 }}</ref><ref name=":0">{{cite journal | vauthors = Jiang X, Li Y, Chen N, Zhou M, He L | title = Corticosteroids for preventing postherpetic neuralgia | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 12 | pages = CD005582 | date = December 2023 | pmid = 38050854 | pmc = 10696631 | doi = 10.1002/14651858.CD005582.pub5 }}</ref> [[Paracetamol]], [[NSAID]]s, or [[opioid]]s may be used to help with acute pain.<ref name=NEJM2013/> It is estimated that about a third of people develop shingles at some point in their lives.<ref name=Pink2015/> While shingles is more common among older people, children may also get the disease.<ref name=CDC2014Over>{{cite web|title=Overview|url=https://www.cdc.gov/shingles/about/overview.html|access-date=26 May 2015|date=17 September 2014|url-status=live|archive-url=https://web.archive.org/web/20150516220957/http://www.cdc.gov/shingles/about/overview.html|archive-date=16 May 2015| publisher=[[Centers for Disease Control and Prevention]] (CDC)}}{{PD-notice}}</ref> According to the US [[National Institutes of Health]], the [[Incidence (epidemiology)|number of new cases per year]] ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals to 3.9 to 11.8 per 1,000 person-years among those older than 65 years of age.<ref name=Dwo2007>{{cite journal |vauthors = Dworkin RH, Johnson RW, Breuer J, Gnann JW, Levin MJ, Backonja M, Betts RF, Gershon AA, Haanpaa ML, McKendrick MW, Nurmikko TJ, Oaklander AL, Oxman MN, Pavan-Langston D, Petersen KL, Rowbotham MC, Schmader KE, Stacey BR, Tyring SK, van Wijck AJ, Wallace MS, Wassilew SW, Whitley RJ | display-authors = 6 | title=Recommendations for the management of herpes zoster| journal=[[Clin. Infect. Dis.]]| volume=44| pages=S1–26| year=2007| issue = Suppl 1 | pmid=17143845| doi=10.1086/510206| doi-access=free}}</ref><ref name="Nair">{{cite book | vauthors = Nair PA, Patel BC | chapter =''Herpes zoster'' | title = StatPearls | via = NCBI Bookshelf | date=2 November 2021 | pmid=28722854 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK441824/ | access-date=10 June 2022 | archive-date=10 June 2022 | archive-url=https://web.archive.org/web/20220610043425/https://www.ncbi.nlm.nih.gov/books/NBK441824/ | url-status=live }}</ref> About half of those living to age 85 will have at least one attack, and fewer than 5% will have more than one attack.<ref name=Pink2015/><ref>{{cite book | vauthors = Schmader KE, Dworkin RH | chapter = Herpes Zoster and Postherpetic Neuralgia | veditors = Benzon HT |title=Essentials of Pain Medicine|date=2011|publisher=Elsevier Health Sciences|location=London|isbn=978-1437735932|page=358|edition=3rd| chapter-url = https://books.google.com/books?id=9UuAWD2FTFsC&pg=PA358|access-date=11 September 2017|archive-date=17 December 2019|archive-url=https://web.archive.org/web/20191217053808/https://books.google.com/books?id=9UuAWD2FTFsC&pg=PA358|url-status=live}}</ref> Although symptoms can be severe, risk of death is very low: 0.28 to 0.69 deaths per million.<ref name="pmid35340552"/> ==Signs and symptoms== [[File:Fox Plate XCVI.jpg|thumb|Shingles in various locations]] [[File:Shingles.JPG|thumb|upright=1.3|A case of shingles that demonstrates a typical [[dermatome (anatomy)#Important dermatomes and anatomical landmarks|dermatomal distribution, here C8/T1]].]] The earliest symptoms of shingles, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis.<ref name=Dwo2007/><ref name=pmid11458545>{{cite journal| author=Zamula E| title=Shingles: an unwelcome encore| journal=[[FDA Consumer]]| volume=35| issue=3| pages=21–25| date=May–June 2001| pmid=11458545| url=http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/2001/301_pox.html| access-date=5 January 2010| url-status=live| archive-url=https://web.archive.org/web/20091103045519/http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/2001/301_pox.html| archive-date=3 November 2009}} Revised June 2005.</ref> These symptoms are commonly followed by sensations of burning pain, itching, [[hyperesthesia]] (oversensitivity), or [[paresthesia]] ("pins and needles": tingling, pricking, or numbness).<ref name=pmid10794584>{{cite journal| vauthors=Stankus SJ, Dlugopolski M, Packer D| title=Management of herpes zoster (shingles) and postherpetic neuralgia| journal=[[Am. Fam. Physician]]| volume=61| issue=8| pages=2437–2444, 2447–2448| year=2000| pmid=10794584| url=http://www.aafp.org/afp/20000415/2437.html| url-status=dead| archive-url=https://web.archive.org/web/20070929083747/http://www.aafp.org/afp/20000415/2437.html| archive-date=29 September 2007}}</ref> Pain can be mild to severe in the affected [[dermatome (anatomy)|dermatome]], with sensations that are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.<ref name=pmid15307000>{{cite journal |vauthors=Katz J, Cooper EM, Walther RR, Sweeney EW, Dworkin RH |title=Acute pain in herpes zoster and its impact on health-related quality of life |journal=[[Clin. Infect. Dis.]] |volume=39 |issue=3 |pages=342–348 |year=2004 |pmid=15307000 |doi=10.1086/421942|doi-access=free }}</ref> Shingles in children is often painless, but people are more likely to get shingles as they age, and the disease tends to be more severe.<ref name="Hope-Simpson">{{cite journal|author=Hope-Simpson RE|title=The nature of herpes zoster: a long-term study and a new hypothesis|journal=[[Proceedings of the Royal Society of Medicine]]|year=1965|volume=58|pages=9–20|pmid=14267505|pmc=1898279|issue=1|doi=10.1177/003591576505800106}}</ref> In most cases, after one to two days—but sometimes as long as three weeks—the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occur on the torso but can appear on the face, eyes, or other parts of the body. At first, the rash appears similar to the first appearance of [[hives]]; however, unlike hives, shingles causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline.<ref name=pmid10794584/> <!-- Do not delete anchor, links from Bell's Palsy -->{{Anchor|Zoster sine herpete}} ''Zoster sine herpete'' ("zoster without herpes") describes a person who has all of the symptoms of shingles except this characteristic rash.<ref name=pmid10980741>{{cite journal |vauthors=Furuta Y, Ohtani F, Mesuda Y, Fukuda S, Inuyama Y |title=Early diagnosis of zoster sine herpete and antiviral therapy for the treatment of facial palsy |journal=[[Neurology (journal)|Neurology]] |volume=55 |issue=5 |pages=708–710 |year=2000 |pmid=10980741 |doi=10.1212/WNL.55.5.708| s2cid = 29270135 }}</ref> Later the rash becomes [[Vesicle (dermatology)|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, and crust over within seven to ten days; usually the crusts fall off and the skin heals, but sometimes, after severe blistering, scarring and discolored skin remain.<ref name=pmid10794584/> The blister fluid contains varicella zoster virus, which can be transmitted through contact or inhalation of fluid droplets until the lesions crust over, which may take up to four weeks.<ref>{{cite web|url=https://www.health.ny.gov/diseases/communicable/shingles/fact_sheet.htm|title=Shingles (herpes zoster)|date=January 2023|publisher=New York State|website=Department of Health|access-date=9 March 2023}}</ref> {| style="margin:auto;" |+ '''Development of the shingles rash''' ! Day 1 !! Day 2 !! Day 5 !! Day 6 |- valign="top" | [[Image:ShinglesDay1.JPG|143px]] | [[Image:ShinglesDay2 ed.JPG|120px]] | [[Image:ShinglesDay5 ed.JPG|145px]] | [[Image:ShinglesDay6 ed.JPG|149px]] |} ===Face=== Shingles may have additional symptoms, depending on the dermatome involved. The [[trigeminal nerve]] is the most commonly involved nerve,<!-- , accounting for 18–22% of shingles cases--><ref name=Gupta2015>{{cite journal| vauthors = Gupta S, Sreenivasan V, Patil PB |title = Dental complications of herpes zoster: Two case reports and review of literature |journal=[[Indian Journal of Dental Research]]|date=2015|volume=26|issue=2|pages=214–219|doi=10.4103/0970-9290.159175|pmid=26096121|doi-access=free}}</ref> of which the ophthalmic division is the most commonly involved branch.<ref name=Samaranayake2011>{{cite book|author=Samaranayake L|title=Essential Microbiology for Dentistry|url=https://books.google.com/books?id=xanRAQAAQBAJ&pg=PT638|edition=4th|year= 2011|publisher=Elsevier Health Sciences|isbn=978-0702046957|pages=638–642|url-status=live|archive-url=https://web.archive.org/web/20170908175310/https://books.google.com/books?id=xanRAQAAQBAJ&pg=PT638|archive-date=8 September 2017}}</ref> When the virus is reactivated in this nerve branch it is termed ''[[zoster ophthalmicus]]''. The skin of the forehead, upper eyelid and [[Orbit (anatomy)|orbit of the eye]] may be involved. Zoster ophthalmicus occurs in approximately 10% to 25% of cases. In some people, symptoms may include [[conjunctivitis]], [[keratitis]], [[uveitis]], and [[optic nerve]] [[:wikt:palsy|palsies]] that can sometimes cause chronic ocular inflammation, loss of vision, and debilitating pain.<ref name=pmid12449270>{{cite journal| vauthors=Shaikh S, Ta CN| title=Evaluation and management of herpes zoster ophthalmicus| journal=[[Am. Fam. Physician]]| year=2002| volume=66| issue=9| pages=1723–1730| pmid=12449270| url=http://www.aafp.org/afp/20021101/1723.html| url-status=live| archive-url=https://web.archive.org/web/20080514021237/http://www.aafp.org/afp/20021101/1723.html| archive-date=14 May 2008}}</ref> ''Shingles 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 (medical)|vertigo]] (rotational dizziness).<ref name=pmid12676845/> Shingles may occur in the mouth if the maxillary or mandibular division of the trigeminal nerve is affected,<ref name=Neville2008/> in which the rash may appear on the [[mucous membrane]] of the upper jaw (usually the palate, sometimes the gums of the upper teeth) or the lower jaw (tongue or gums of the lower teeth) respectively.<ref name=Glick2014/> Oral involvement may occur alone or in combination with a rash on the skin over the cutaneous distribution of the same trigeminal branch.<ref name=Neville2008/> As with shingles of the skin, the lesions tend to only involve one side, distinguishing it from other oral blistering conditions.<ref name=Glick2014/> In the mouth, shingles appears initially as 1–4 mm opaque blisters (vesicles),<ref name=Neville2008/> which break down quickly to leave [[mouth ulcer|ulcers]] that heal within 10–14 days.<ref name=Glick2014/> The prodromal pain (before the rash) may be confused with [[toothache]].<ref name=Neville2008>{{cite book| vauthors = Chi AC, Damm DD, Neville BW, Allen CM, Bouquot J | chapter = Viral Infections |title=Oral and Maxillofacial Pathology|year=2008|publisher=Elsevier Health Sciences|isbn=978-1437721973|pages=250–253| chapter-url = https://books.google.com/books?id=5QIEAQAAQBAJ&pg=P250 |url-status=live|archive-url=https://web.archive.org/web/20170908175310/https://books.google.com/books?id=5QIEAQAAQBAJ&pg=P250|archive-date=8 September 2017}}</ref> Sometimes this leads to unnecessary dental treatment.<ref name=Glick2014>{{cite book|author=Glick M|title=Burket's oral medicine|url=https://books.google.com/books?id=cBEqCAAAQBAJ&pg=PA62|edition=12th|year=2015|publisher=coco|isbn=978-1607951889|pages=62–65}}</ref> Post-herpetic neuralgia uncommonly is associated with shingles in the mouth.<ref name=Glick2014/> Unusual complications may occur with intra-oral shingles that are not seen elsewhere. Due to the close relationship of blood vessels to nerves, the virus can spread to involve the blood vessels and compromise the blood supply, sometimes causing [[ischemia|ischemic]] [[necrosis]].<ref name=Neville2008/> In rare cases, oral involvement causes complications such as [[osteonecrosis]], [[tooth loss]], [[periodontitis]] (gum disease), pulp calcification, [[pulp necrosis]], [[periapical periodontitis|periapical lesions]] and tooth developmental anomalies.<ref name=Gupta2015/> ===Disseminated shingles=== {{anchor|Disseminated}}In those with deficits in immune function, ''disseminated shingles'' may occur (wide rash).<ref name=Pink2015/> It is defined as more than 20 [[skin lesion]]s appearing outside either the primarily affected dermatome or dermatomes directly adjacent to it. Besides the skin, other organs, such as the [[liver]] or [[brain]], may also be affected (causing [[hepatitis]] or [[encephalitis]],<ref>{{cite journal |vauthors=Chai W, Ho MG |title=Disseminated varicella zoster virus encephalitis |journal=Lancet |volume=384 |issue=9955 |pages=1698 |date=November 2014 |pmid=24999086 |doi=10.1016/S0140-6736(14)60755-8 |doi-access=free}}</ref><ref>{{cite journal| vauthors = Grahn A, Studahl M |title = Varicella-zoster virus infections of the central nervous system – Prognosis, diagnostics and treatment |journal=[[Journal of Infection]]|date=September 2015|volume=71|issue=3|pages=281–293|pmid=26073188|doi=10.1016/j.jinf.2015.06.004}}</ref> respectively), making the condition potentially lethal.<ref name="Andrews">{{cite book |vauthors=Elston DM, Berger TG, James WD |title=Andrews' Diseases of the Skin: Clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0721629216 }}</ref>{{rp|380}} ==Pathophysiology== [[Image:Varicella (Chickenpox) Virus PHIL 1878 lores.jpg|right|thumb|[[Electron microscope|Electron micrograph]] of [[varicella zoster virus]]. Approximately 150,000× magnification. The virus diameter is 150–200 nm.<ref>{{cite web |publisher=[[Public Health Agency of Canada]] |title=Pathogen Safety Data Sheets: Infectious Substances – Varicella-zoster virus |date=30 April 2012 |access-date=3 June 2022 |url=https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/varicella-zoster-virus.html |archive-date=22 March 2020 |archive-url=https://web.archive.org/web/20200322012121/https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/varicella-zoster-virus.html |url-status=live }}</ref>]] [[File:A Course of Shingles diagram.png|right|Progression of shingles. A cluster of small bumps (1) turns into blisters (2). The blisters fill with [[lymph]], break open (3), crust over (4), and finally disappear. [[Postherpetic neuralgia]] can sometimes occur due to nerve damage (5).|thumb]] The causative agent for shingles is the [[Human alphaherpesvirus 3|varicella zoster virus]] (VZV)—a double-stranded [[DNA virus]] related to the [[herpes simplex virus]]. Most individuals are infected with this virus as children which causes an episode of [[chickenpox]]. The immune system eventually eliminates the virus from most locations, but it remains dormant (or [[viral latency|latent]]) in the [[ganglion|ganglia]] adjacent to the spinal cord (called the [[dorsal root ganglion]]) or the [[trigeminal ganglion]] in the base of the skull.<ref name=pmid17945155>{{cite journal|vauthors=Steiner I, Kennedy PG, Pachner AR | title=The neurotropic herpes viruses: herpes simplex and varicella-zoster| journal=[[The Lancet Neurology]]| volume=6| issue=11| pages=1015–1028| year=2007| pmid=17945155| doi=10.1016/S1474-4422(07)70267-3 | s2cid=6691444}}</ref> Shingles occurs only in people who have been previously infected with VZV; although it can occur at any age, approximately half of the cases in the United States occur in those aged 50 years or older.<ref name=pmid18021864>{{cite journal| vauthors=Weinberg JM| title=Herpes zoster: epidemiology, natural history, and common complications| journal=[[Journal of the American Academy of Dermatology]]|volume=57| issue=6 Suppl| pages=S130–S135| year=2007| pmid=18021864| doi=10.1016/j.jaad.2007.08.046}}</ref> Shingles can recur.<ref name="MMWR mm6703a5"/> In contrast to the frequent recurrence of [[herpes simplex]] symptoms, repeated attacks of shingles are unusual.<ref name=Kennedy2015>{{cite journal |vauthors=Kennedy PG, Rovnak J, Badani H, Cohrs RJ |title=A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation |journal=The Journal of General Virology |volume=96 |issue=Pt 7 |pages=1581–1602 |date=2015 |pmid=25794504 |pmc=4635449 |doi=10.1099/vir.0.000128 |url=}}</ref> It is extremely rare for a person to have more than three recurrences.<ref name=pmid17945155/> The disease results from virus particles in a single sensory ganglion switching from their latent phase to their active phase.<ref name="pmid14583142">{{cite journal|vauthors=Gilden DH, Cohrs RJ, Mahalingam R | title=Clinical and molecular pathogenesis of varicella virus infection| journal=Viral Immunology| volume=16| issue=3| pages=243–258| year=2003| pmid=14583142| doi=10.1089/088282403322396073}}</ref> Due to difficulties in studying VZV reactivation directly in humans (leading to reliance on small-[[animal model]]s), its latency is less well understood than that of the herpes simplex virus.<ref name=Kennedy2015/> Virus-specific proteins continue to be made by the infected cells during the latent period, so true latency, as opposed to [[chronic (medical)|chronic]], low-level, active [[infectious disease|infection]], has not been proven to occur in VZV infections.<ref name=pmid12211045>{{cite journal |vauthors=Kennedy PG |title=Varicella-zoster virus latency in human ganglia |journal=Reviews in Medical Virology |volume=12 |issue=5 |pages=327–334 |year=2002 |pmid=12211045 |doi=10.1002/rmv.362|s2cid=34582060 }}</ref><ref name=pmid12491156>{{cite journal| vauthors=Kennedy PG| title=Key issues in varicella-zoster virus latency| journal=[[Journal of Neurovirology]]| volume=8 | issue = Suppl 2 | pages=80–84| year=2002| pmid=12491156| doi=10.1080/13550280290101058 | citeseerx=10.1.1.415.2755}}</ref> Although VZV has been detected in autopsies of nervous tissue,<ref name="pmid12707850">{{cite journal| vauthors=Mitchell BM, Bloom DC, Cohrs RJ, Gilden DH, Kennedy PG | title=Herpes simplex virus-1 and varicella-zoster virus latency in ganglia| journal=[[Journal of Neurovirology]]| volume=9| issue=2| pages=194–204| year=2003| pmid=12707850| doi=10.1080/13550280390194000| s2cid = 5964582 | url=http://www.jneurovirol.com/o_pdf/9(2)/194-204.pdf| url-status=live| archive-url=https://web.archive.org/web/20080517075513/http://www.jneurovirol.com/o_pdf/9(2)/194-204.pdf| archive-date=17 May 2008}}</ref> there are no methods to find dormant virus in the ganglia of living people. Unless the [[immune system]] is compromised, it suppresses reactivation of the virus and prevents shingles outbreaks. Why this suppression sometimes fails is poorly understood,<ref name=pmid7618983>{{cite journal|vauthors=Donahue JG, Choo PW, Manson JE, Platt R | title=The incidence of herpes zoster| journal=[[Archives of Internal Medicine]]| volume=155| issue=15| pages=1605–1609| year=1995| pmid=7618983| doi=10.1001/archinte.155.15.1605}}</ref> but shingles is more likely to occur in people whose immune systems are impaired due to aging, [[immunosuppressive therapy]], [[psychological stress]], or other factors.<ref name=pmid14720565>{{cite journal|vauthors=Thomas SL, Hall AJ | title=What does epidemiology tell us about risk factors for herpes zoster?| journal=[[The Lancet Infectious Diseases]]| volume=4| issue=1| pages=26–33| year=2004| doi=10.1016/S1473-3099(03)00857-0| pmid=14720565}}</ref><ref>{{cite web|title=Shingles|url=https://beta.nhs.uk/conditions/shingles/|website=NHS.UK|access-date=25 September 2017|archive-url=https://web.archive.org/web/20170926042439/https://beta.nhs.uk/conditions/shingles/|archive-date=26 September 2017|url-status=dead}}</ref> Upon reactivation, the virus replicates in neuronal cell bodies, and [[virion]]s are shed from the cells and carried down the [[axon]]s to the area of skin innervated by that ganglion. In the skin, the virus causes local [[inflammation]] and blistering. The short- and long-term pain caused by shingles outbreaks originates from inflammation of affected nerves due to the widespread growth of the virus in those areas.<ref name=pmid17631237>{{cite journal |author=Schmader K |title=Herpes zoster and postherpetic neuralgia in older adults |journal=Clinics in Geriatric Medicine |volume=23 |issue=3 |pages=615–632, vii–viii |year=2007 |pmid=17631237 |pmc=4859150 |doi=10.1016/j.cger.2007.03.003 }}</ref> As with chickenpox and other forms of alpha-herpesvirus infection, direct contact with an active rash can spread the virus to a person who lacks immunity to it. This newly infected individual may then develop chickenpox, but will not immediately develop shingles.<ref name=pmid10794584/> The complete sequence of the viral [[genome]] was published in 1986.<ref name="pmid3018124">{{cite journal| vauthors=Davison, AJ, Scott, JE | title=The complete DNA sequence of varicella-zoster virus| journal=[[Journal of General Virology]]| volume=67| issue=9| pages=1759–1816| year=1986| pmid=3018124| doi=10.1099/0022-1317-67-9-1759| doi-access=free}}</ref> ==Diagnosis== [[Image:Herpes zoster chest.png|right|thumb|Shingles on the chest]] If the rash has appeared, identifying this disease (making a [[differential diagnosis]]) requires only a visual examination, since very few diseases produce a rash in a [[Dermatome (anatomy)|dermatomal pattern]] (sometimes called by doctors on TV "a dermatonal map").{{Citation needed|date=July 2024|reason=This statement is very vague and could benefit from specific examples.}} However, [[herpes simplex virus]] (HSV) can occasionally produce a rash in such a pattern (zosteriform herpes simplex).<ref name=Koh>{{cite journal| vauthors = Koh MJ, Seah PP, Teo RY |title=Zosteriform herpes simplex|journal=[[Singapore Med. J.]]|date=Feb 2008|volume=49|pages=e59–60|pmid=18301829|url=http://smj.sma.org.sg/4902/4902cr9.pdf|issue=2|url-status=live|archive-url=https://web.archive.org/web/20140602213312/http://smj.sma.org.sg/4902/4902cr9.pdf|archive-date=2 June 2014}}</ref><ref name=Kalman>{{cite journal| vauthors = Kalman CM, Laskin OL |title=Herpes zoster and zosteriform herpes simplex virus infections in immunocompetent adults|journal=[[Am. J. Med.]]|date=Nov 1986|volume=81 |pages=775–778|pmid=3022586|issue=5|doi=10.1016/0002-9343(86)90343-8}}</ref> When the rash is absent (early or late in the disease, or in the case of {{lang|la|zoster sine herpete}}), shingles can be difficult to diagnose.<ref name=pmid15334402>{{cite journal|vauthors=Chan J, Bergstrom RT, Lanza DC, Oas JG | title=Lateral sinus thrombosis associated with zoster sine herpete| journal=Am. J. Otolaryngol.| volume=25| issue=5| pages=357–360| year=2004| pmid=15334402| doi=10.1016/j.amjoto.2004.03.007}}</ref> Apart from the rash, most symptoms can occur also in other conditions. Laboratory tests are available to diagnose shingles. The most popular test detects VZV-specific [[IgM]] [[antibody]] in blood; this appears only during chickenpox or shingles and not while the virus is dormant.<ref name=pmid8809466>{{cite journal| author=Arvin AM| title=Varicella-zoster virus| journal=[[Clin. Microbiol. Rev.]]| volume=9| issue=3| pages=361–381| year=1996| pmid=8809466| url= http://cmr.asm.org/cgi/reprint/9/3/361.pdf| pmc=172899| url-status=live| archive-url=https://web.archive.org/web/20080625213222/http://cmr.asm.org/cgi/reprint/9/3/361.pdf| archive-date=25 June 2008| doi=10.1128/CMR.9.3.361}}</ref> In larger laboratories, [[lymph]] collected from a blister is tested by [[polymerase chain reaction]] (PCR) for VZV DNA, or examined with an electron microscope for virus particles.<ref name="pmid9515761">{{cite journal|vauthors=Beards G, Graham C, Pillay D | title=Investigation of vesicular rashes for HSV and VZV by PCR| journal=[[J. Med. Virol.]]| volume=54| issue=3| pages=155–157| year=1998| pmid=9515761 |doi=10.1002/(SICI)1096-9071(199803)54:3<155::AID-JMV1>3.0.CO;2-4| s2cid=24215093}}</ref> Molecular biology tests based on ''in vitro'' nucleic acid amplification (PCR tests) are currently considered the most reliable. [[Nested PCR]] test has high [[sensitivity and specificity|sensitivity]], but is susceptible to contamination leading to [[False positives and false negatives#False positive error|false positive results]]. The latest [[real-time polymerase chain reaction|real-time PCR]] tests are rapid, easy to perform, and as sensitive as nested PCR, and have a lower risk of contamination. They also have more sensitivity than [[viral culture]]s.<ref name=DePaschaleClerici2016>{{cite journal| vauthors=De Paschale M, Clerici P| title=Microbiology laboratory and the management of mother-child varicella-zoster virus infection. | journal=World J Virol | year= 2016 | volume= 5 | issue= 3 | pages= 97–124 | pmid=27563537 | doi=10.5501/wjv.v5.i3.97 | pmc=4981827 | type= Review | doi-access=free }}</ref> === Differential diagnosis === Shingles can be confused with [[herpes simplex]], [[dermatitis herpetiformis]] and [[impetigo]], and skin reactions caused by [[contact dermatitis]], [[candidiasis]], certain drugs and insect bites.<ref name=SampathkumarDrage2009>{{cite journal| vauthors=Sampathkumar P, Drage LA, Martin DP| title=Herpes zoster (shingles) and postherpetic neuralgia | journal=Mayo Clin Proc | year= 2009 | volume= 84 | issue= 3 | pages= 274–280 | pmid=19252116 | doi=10.4065/84.3.274 | pmc=2664599 | type= Review }}</ref> == Prevention == {{Main|Zoster vaccine}} Shingles risk can be reduced in children by the [[Varicella vaccine|chickenpox vaccine]] if the vaccine is administered before the individual gets chickenpox.<ref>{{cite journal |vauthors=Weinmann S, Naleway AL, Koppolu P, Baxter R, Belongia EA, Hambidge SJ, Irving SA, Jackson ML, Klein NP, Lewin B, Liles E, Marin M, Smith N, Weintraub E, Chun C |display-authors = 6 |title=Incidence of Herpes Zoster Among Children: 2003–2014 |journal=Pediatrics |volume=144 |issue=1 |pages= e20182917|date=July 2019 |pmid=31182552 |doi=10.1542/peds.2018-2917 |pmc = 7748320 |s2cid = 184486904|doi-access=free }}*{{lay source |template=cite web|date=11 June 2019|url=https://www.scientificamerican.com/article/two-for-one-chickenpox-vaccine-lowers-shingles-risk-in-children |title=Two-for-One: Chickenpox Vaccine Lowers Shingles Risk in Children|website = Scientific American}}</ref> If primary infection has already occurred, there are [[shingles vaccine]]s that reduce the risk of developing shingles or developing severe shingles if the disease occurs.<ref name=Pink2015/><ref name=Cun2016/> They include a [[live attenuated virus]] vaccine, Zostavax, and an [[immunologic adjuvant|adjuvanted]] [[subunit vaccine|subunit]] vaccine, Shingrix.<ref name="MMWR mm6703a5">{{cite journal |vauthors=Dooling KL, Guo A, Patel M, Lee GM, Moore K, Belongia EA, Harpaz R |display-authors=6 |title=Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=67 |issue=3 |pages=103–108 |date=January 2018 |pmid=29370152 |pmc=5812314 |doi=10.15585/mmwr.mm6703a5 |url=https://www.cdc.gov/mmwr/volumes/67/wr/pdfs/mm6703a5-H.pdf |access-date=9 January 2020 |archive-date=29 August 2021 |archive-url=https://web.archive.org/web/20210829055010/https://www.cdc.gov/mmwr/volumes/67/wr/pdfs/mm6703a5-H.pdf |url-status=live }}</ref><ref name="MMWR_57(05)">{{cite journal| vauthors = Harpaz R, Ortega-Sanchez IR, Seward JF| title = Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP)| journal = [[MMWR Recomm. Rep.]]| volume = 57| issue = RR–5| pages = 1–30; quiz CE2–4| date = 6 June 2008| pmid = 18528318| url = https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5705a1.htm| access-date = 4 January 2010| url-status=live| archive-url = https://web.archive.org/web/20091117154208/http://www.cdc.gov/mmWR/preview/mmwrhtml/rr5705a1.htm| archive-date = 17 November 2009}}{{PD-notice}}</ref><ref name="pmid27626517"/> A review by [[Cochrane (organisation)|Cochrane]] concluded that Zostavax was useful for preventing shingles for at least three years.<ref name=":1" /> This equates to about 50% [[relative risk reduction]]. The vaccine reduced rates of persistent, severe pain after shingles by 66% in people who contracted shingles despite vaccination.<ref name=shapiro>{{cite journal |vauthors=Shapiro M, Kvern B, Watson P, Guenther L, McElhaney J, McGeer A |title=Update on herpes zoster vaccination: a family practitioner's guide |journal=[[Can. Fam. Physician]] |volume=57 |issue=10 |pages=1127–1131 |date=October 2011 |pmid=21998225 |pmc=3192074 }}</ref> Vaccine efficacy was maintained through four years of follow-up.<ref name=shapiro/> It has been recommended that people with primary or acquired immunodeficiency should not receive the live vaccine.<ref name=shapiro/> Two doses of Shingrix are recommended, which provide about 90% protection at 3.5 years.<ref name="MMWR mm6703a5"/><ref name="pmid27626517">{{cite journal |vauthors=Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Díez-Domingo J, Godeaux O, Levin MJ, McElhaney JE, Puig-Barberà J, Vanden Abeele C, Vesikari T, Watanabe D, Zahaf T, Ahonen A, Athan E, Barba-Gomez JF, Campora L, de Looze F, Downey HJ, Ghesquiere W, Gorfinkel I, Korhonen T, Leung E, McNeil SA, Oostvogels L, Rombo L, Smetana J, Weckx L, Yeo W, Heineman TC |display-authors = 6 |title=Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older |journal=N. Engl. J. Med. |volume=375 |issue=11 |pages=1019–1032 |date=September 2016 |pmid=27626517 |doi=10.1056/NEJMoa1603800 |doi-access=free |hdl=10536/DRO/DU:30086550 |hdl-access=free }}</ref> As of 2016, it had been studied only in people with an intact immune system.<ref name=Cun2016/> It appears to also be effective in the very old.<ref name=Cun2016/> In the UK, shingles vaccination is offered by the [[National Health Service]] (NHS) to all people in their 70s. {{As of|2021}} Zostavax is the usual vaccine, but Shingrix vaccine is recommended if Zostavax is unsuitable, for example for those with immune system issues. Vaccination is not available to people over 80 as "it seems to be less effective in this age group".<ref>{{Cite web |title=Shingles vaccine overview |author= |website=NHS (UK) |date=31 August 2021 |url=https://www.nhs.uk/conditions/vaccinations/shingles-vaccination/ |access-date=9 October 2021 |archive-date=2 June 2014 |archive-url=https://web.archive.org/web/20140602024601/https://www.nhs.uk/Conditions/vaccinations/Pages/shingles-vaccination.aspx |url-status=live }} Overview to be reviewed 31 August 2024.</ref><ref>{{cite web | url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/697963/Shingles_vaccination_prgramme_letter_April2018.pdf | title=The shingles immunisation programme: evaluation of the programme and implementation in 2018 | publisher=[[Public Health England]] (PHE) | date=9 April 2018 | access-date=9 January 2020 | archive-date=9 January 2020 | archive-url=https://web.archive.org/web/20200109161256/https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/697963/Shingles_vaccination_prgramme_letter_April2018.pdf | url-status=live }}</ref> By August 2017, just under half of eligible 70–78 year olds had been vaccinated.<ref>{{cite web | title=Herpes zoster (shingles) immunisation programme 2016 to 2017: evaluation report | website=GOV.UK | date=15 December 2017 | url=https://www.gov.uk/government/publications/herpes-zoster-shingles-immunisation-programme-2016-to-2017-evaluation-report | access-date=9 January 2020 | archive-date=9 January 2020 | archive-url=https://web.archive.org/web/20200109161228/https://www.gov.uk/government/publications/herpes-zoster-shingles-immunisation-programme-2016-to-2017-evaluation-report | url-status=live }}</ref> About 3% of those eligible by age have conditions that suppress their immune system, and should not receive Zostavax.<ref name=HSJ/> There had been 1,104 adverse reaction reports by April 2018.<ref name=HSJ>{{cite news |title=NHS England warning as vaccine programme extended |url=https://www.hsj.co.uk/policy-and-regulation/nhs-england-warning-as-vaccine-programme-extended/7022175.article |url-access=registration |author=Shaun Linter |work=Health Service Journal |date=18 April 2018 |access-date=10 June 2018 |archive-date=15 November 2019 |archive-url=https://web.archive.org/web/20191115234845/https://www.hsj.co.uk/policy-and-regulation/nhs-england-warning-as-vaccine-programme-extended/7022175.article |url-status=live }}</ref> In the US, it is recommended that healthy adults 50 years and older receive two doses of Shingrix, two to six months apart.<ref name="MMWR mm6703a5"/><ref name=CDC2019Sym>{{cite web|title=Shingles (Herpes Zoster) Vaccination|url=https://www.cdc.gov/shingles/vaccination.html|access-date=18 January 2019|date=25 October 2018|publisher=[[Centers for Disease Control and Prevention]] (CDC)|archive-date=16 January 2020|archive-url=https://web.archive.org/web/20200116090840/https://www.cdc.gov/shingles/vaccination.html|url-status=live}}{{PD-notice}}</ref> ==Treatment== The aims of treatment are to limit the severity and duration of pain, shorten the duration of a shingles episode, and reduce complications. Symptomatic treatment is often needed for the complication of [[postherpetic neuralgia]].<ref name=pmid18021865>{{cite journal |journal= [[J. Am. Acad. Dermatol.]] |year=2007 |volume=57 |issue= 6 Suppl |pages=S136–S142 |title= Management of herpes zoster and postherpetic neuralgia |author= Tyring SK |doi=10.1016/j.jaad.2007.09.016 |pmid=18021865}}</ref> However, a study on untreated shingles shows that, once the rash has cleared, postherpetic neuralgia is very rare in people under 50 and wears off in time; in older people, the pain wore off more slowly, but even in people over 70, 85% were free from pain a year after their shingles outbreak.<ref name=pmid11009518>{{cite journal | vauthors = Helgason S, Petursson G, Gudmundsson S, Sigurdsson JA | title= Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long term follow up | journal= [[British Medical Journal]] | volume= 321 | year= 2000 | pmid= 11009518 | doi= 10.1136/bmj.321.7264.794 | issue= 7264 | pages= 794–796 | pmc= 27491 }}</ref> ===Analgesics=== People with mild to moderate pain can be treated with [[Over-the-counter drug|over-the-counter]] [[analgesics|pain medications]]. 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) can be used. Topical [[lidocaine]] and nerve blocks may also reduce pain.<ref name=pmid15061819>{{cite journal| author=Baron R| title=Post-herpetic neuralgia case study: optimizing pain control| journal=[[Eur. J. Neurol.]] | volume=11| pages=3–11| year=2004| issue=Suppl 1| pmid=15061819| doi=10.1111/j.1471-0552.2004.00794.x| s2cid=24555396}}</ref> Administering [[gabapentin]] along with antivirals may offer relief of postherpetic neuralgia.<ref name=pmid18021865/> ===Antivirals=== [[Antiviral drugs]] may reduce the severity and duration of shingles;<ref name=Bad2013>{{cite journal| vauthors = Bader MS |title = Herpes zoster: diagnostic, therapeutic, and preventive approaches |journal=[[Postgraduate Medicine]]|date=Sep 2013|volume=125|issue=5|pages=78–91|pmid=24113666|doi=10.3810/pgm.2013.09.2703 |s2cid = 5296437 }}</ref> however, they do not prevent [[postherpetic neuralgia]].<ref name=Han2014>{{cite journal |vauthors=Chen N, Li Q, Yang J, Zhou M, Zhou D, He |title=Antiviral treatment for preventing postherpetic neuralgia |journal=[[Cochrane Database of Systematic Reviews]] |volume= 2014|issue=2 |pages=CD006866 |year=2014 |pmid=24500927 |doi=10.1002/14651858.CD006866.pub3 | veditors = He L |pmc=10583132 }}</ref> Of these drugs, [[aciclovir]] has been the standard treatment, but the newer drugs [[valaciclovir]] and [[famciclovir]] demonstrate similar or superior efficacy and good safety and tolerability.<ref name=pmid18021865/> The drugs are used both for [[prophylaxis|prevention]] (for example in people with [[HIV/AIDS]]) and as therapy during the [[Acute (medical)|acute phase]]. Complications in [[immunocompromised]] individuals with shingles may be reduced with [[intravenous]] aciclovir. In people who are at a high risk for repeated attacks of shingles, five daily oral doses of aciclovir are usually effective.<ref name=pmid12676845>{{cite journal| journal=[[BMJ]]| year=2003| volume=326| issue=7392| pages=748–750| doi=10.1136/bmj.326.7392.748| vauthors=Johnson RW, Dworkin RH| title=Clinical review: Treatment of herpes zoster and postherpetic neuralgia| pmid=12676845| pmc=1125653}}</ref> ===Steroids=== [[glucocorticoid|Corticosteroids]] do not appear to decrease the risk of [[postherpetic neuralgia|long-term pain]].<ref name=":0" /> Side effects however appear to be minimal. Their use in [[Ramsay Hunt syndrome type 2|Ramsay Hunt syndrome]] had not been properly studied as of 2008.<ref>{{cite journal| vauthors = Uscategui T, Doree C, Chamberlain IJ, Burton MJ |title=Corticosteroids as adjuvant to antiviral treatment in Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults|journal=[[Cochrane Database of Systematic Reviews]]|date=16 July 2008|issue=3|pages=CD006852|pmid=18646170|doi=10.1002/14651858.CD006852.pub2}}</ref> ===Zoster ophthalmicus=== [[File:Herpes zoster ophthalmicus.2.jpg|right|thumb|Zoster ophthalmicus. Labels in [[Serbian language|Serbian]], from top: [[Exudate|exudative]] [[erythema]], scabs, blister, eyelid swelling]] Treatment for [[Ophthalmic zoster|zoster ophthalmicus]] is similar to standard treatment for shingles at other sites.{{medcn|date=May 2023}} A trial comparing aciclovir with its [[prodrug]], valaciclovir, demonstrated similar efficacies in treating this form of the disease.<ref name="pmid10919899">{{cite journal| vauthors=Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T | title=Comparison of the Efficacy and Safety of Valaciclovir and Acyclovir for the Treatment of Herpes zoster Ophthalmicus|journal=[[Ophthalmology (journal)|Ophthalmology]] | volume=107| issue = 8| pages=1507–1511| year=2000| pmid=10919899| doi=10.1016/S0161-6420(00)00222-0}}</ref> ==Prognosis == The rash and pain usually subside within three to five weeks, but about one in five people develop a painful condition called [[postherpetic neuralgia]], which is often difficult to manage. In some people, shingles 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 many [[brain|cranial]] [[neuropathy|neuropathies]], [[neuritis|polyneuritis]], [[myelitis]], or [[aseptic meningitis]]. Other serious effects that may occur in some cases include partial [[Bell's palsy|facial paralysis]] (usually temporary), ear damage, or [[encephalitis]].<ref name=pmid12676845/> Although initial infections with VZV during pregnancy, causing chickenpox, may lead to infection of the fetus and complications in the newborn, chronic infection or reactivation in shingles are not associated with fetal infection.<ref name=pmid3012334>{{cite journal |vauthors=Paryani SG, Arvin AM |title=Intrauterine infection with varicella-zoster virus after maternal varicella |journal=[[The New England Journal of Medicine]] |volume=314 |issue=24 |pages=1542–1546 |year=1986 |pmid=3012334 |doi=10.1056/NEJM198606123142403 }}</ref><ref name=Enders>{{cite journal |vauthors=Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M |title=Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases |journal=[[The Lancet]] |volume=343 |issue=8912 |pages=1548–1551 |year=1994 |pmid=7802767 |doi=10.1016/S0140-6736(94)92943-2 | s2cid = 476280 }}</ref> There is a slightly increased risk of developing [[cancer]] after a shingles episode. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus.<ref name=pmid15328522>{{cite journal |vauthors=Sørensen HT, Olsen JH, Jepsen P, Johnsen SP, Schønheyder HC, Mellemkjaer |title=The risk and prognosis of cancer after hospitalisation for herpes zoster: a population-based follow-up study |journal=[[Br. J. Cancer]] |volume=91 |issue=7 |pages=1275–1279 |year=2004 |pmid=15328522 |doi=10.1038/sj.bjc.6602120 |pmc=2409892}}</ref> Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.<ref name=pmid6979711>{{cite journal |doi=10.1056/NEJM198208123070701 |vauthors=Ragozzino MW, Melton LJ, Kurland LT, Chu CP, Perry HO |title=Risk of cancer after herpes zoster: a population-based study |journal=[[The New England Journal of Medicine]] |volume=307 |issue=7 |pages=393–397 |year=1982 |pmid=6979711}}</ref> Although shingles typically resolves within 3–5 weeks, certain complications may arise: * Secondary bacterial infection.<ref name=PMID26478818/> * Motor involvement,<ref name=PMID26478818/> including weakness especially in "motor herpes zoster".<ref>{{cite journal|doi=10.1007/s00415-009-5149-8|pmid=19434442|title=Pure motor Herpes Zoster induced brachial plexopathy.|journal=Journal of Neurology|volume=256|issue=8|pages=1343–1345|year=2009| vauthors = Ismail A, Rao DG, Sharrack B|s2cid=26443976}}</ref> * Eye involvement: [[trigeminal nerve]] involvement (as seen in herpes ophthalmicus) should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus.<ref>{{cite web|url=http://www.merckmanuals.com/professional/eye-disorders/corneal-disorders/herpes-zoster-ophthalmicus|title=Herpes Zoster Ophthalmicus|work=Merck Manual|date=September 2014|access-date=14 August 2016|author=Roat MI|url-status=live|archive-url=https://web.archive.org/web/20160812031812/http://www.merckmanuals.com/professional/eye-disorders/corneal-disorders/herpes-zoster-ophthalmicus|archive-date=12 August 2016}}</ref> * [[Postherpetic neuralgia]], a condition of chronic pain following shingles. ==Epidemiology== {{See also|Chickenpox#Epidemiology|l1=Chickenpox epidemiology}} Varicella zoster virus (VZV) has a high level of [[infectivity]] and has a worldwide prevalence.<ref>{{cite journal |vauthors=Apisarnthanarak A, Kitphati R, Tawatsupha P, Thongphubeth K, Apisarnthanarak P, Mundy LM |title=Outbreak of varicella-zoster virus infection among Thai healthcare workers |journal=[[Infect. Control Hosp. Epidemiol.]] |volume=28 |issue=4 |pages=430–434 |year=2007 |pmid=17385149 |doi=10.1086/512639 |s2cid=20844136 }}</ref> Shingles is a re-activation of latent VZV infection: zoster can only occur in someone who has previously had chickenpox (varicella). Shingles has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age.<ref name="Hope-Simpson"/><ref name=pmid14720565/> The incidence rate of shingles ranges from 1.2 to 3.4 per 1,000 person‐years among younger healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years,<ref name=Dwo2007/><ref name="Hope-Simpson"/> and incidence rates worldwide are similar.<ref name=Dwo2007/><ref name=pmid17939895>{{cite journal| vauthors=Araújo LQ, Macintyre CR, Vujacich C| title=Epidemiology and burden of herpes zoster and post-herpetic neuralgia in Australia, Asia and South America| journal=[[Herpes (journal)|Herpes]]| volume=14| issue=Suppl 2| pages=40A–44A| year=2007| pmid=17939895| url=http://www.ihmf.org/journal/download/5%20-%20Herpes%2014.2%20suppl%20Araujo.pdf| access-date=16 December 2007| archive-url=https://web.archive.org/web/20191205132432/http://www.ihmf.org/journal/download/5%20-%20Herpes%2014.2%20suppl%20Araujo.pdf| archive-date=5 December 2019| url-status=dead}}</ref> This relationship with age has been demonstrated in many countries,<ref name=Dwo2007/><ref name="pmid17939895"/><ref>{{cite journal|vauthors=Brisson M, Edmunds WJ, Law B, Gay NJ, Walld R, Brownell M, Roos LL, De Serres G | display-authors = 6 | title = Epidemiology of varicella zoster virus infection in Canada and the United Kingdom| journal = [[Epidemiol. Infect.]] | year = 2001| volume = 127| issue = 2| pages = 305–314| pmid = 11693508| doi = 10.1017/S0950268801005921| pmc = 2869750}}</ref><ref>{{cite journal| vauthors = Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA | title = The incidence of herpes zoster in a United States administrative database| journal = [[J. Gen. Intern. Med.]] | year = 2005| volume = 20| issue = 8| pages = 748–753| pmid = 16050886| doi = 10.1111/j.1525-1497.2005.0150.x| pmc = 1490195}}</ref><ref>{{cite journal| vauthors = Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS | title = A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction| journal = [[Mayo Clin. Proc.]]| year = 2007| volume = 82| issue = 11| pages = 1341–1349| pmid = 17976353| doi=10.4065/82.11.1341}}</ref><ref>{{cite journal| vauthors = de Melker H, Berbers G, Hahné S, Rümke H, van den Hof S, de Wit A, Boot H| display-authors = 6| title = The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination| journal = [[Vaccine (journal)|Vaccine]]| year = 2006| volume = 24| issue = 18| pages = 3946–3952| pmid = 16564115| doi = 10.1016/j.vaccine.2006.02.017| hdl = 10029/5604| url = http://rivm.openrepository.com/rivm/bitstream/10029/5604/1/melker2006.pdf| hdl-access = free| access-date = 3 September 2019| archive-date = 8 August 2017| archive-url = https://web.archive.org/web/20170808211650/http://rivm.openrepository.com/rivm/bitstream/10029/5604/1/melker2006.pdf| url-status = live}}</ref> and is attributed to the fact that cellular immunity declines as people grow older. Another important risk factor is [[immunosuppression]].<ref>{{cite journal|vauthors = Colebunders R, Mann JM, Francis H, Bila K, Izaley L, Ilwaya M, Kakonde N, Quinn TC, Curran JW, Piot P | display-authors = 6 | title = Herpes zoster in African patients: a clinical predictor of human immunodeficiency virus infection| journal = [[J. Infect. Dis.]]| volume = 157| issue = 2| pages = 314–318| doi = 10.1093/infdis/157.2.314| year = 1988| pmid = 3335810}}</ref><ref>{{cite journal|vauthors=Buchbinder SP, Katz MH, Hessol NA, Liu JY, O'Malley PM, Underwood R, Holmberg SD | display-authors = 6 | title = Herpes zoster and human immunodeficiency virus infection| journal = [[J. Infect. Dis.]]| year = 1992| volume = 166| issue = 5| pages = 1153–1156| doi = 10.1093/infdis/166.5.1153| pmid = 1308664}}</ref><ref>{{Cite journal| vauthors = Tsai SY, Chen HJ, Lio CF, Ho HP, Kuo CF, Jia X, Chen C, Chen YT, Chou YT, Yang TY, Sun FJ, Shi L | display-authors = 6 |date=22 August 2017|title=Increased risk of herpes zoster in patients with psoriasis: A population-based retrospective cohort study|journal=PLOS ONE|volume=12|issue=8|pages=e0179447|doi=10.1371/journal.pone.0179447|pmid=28829784|issn=1932-6203|bibcode=2017PLoSO..1279447T|pmc=5567491| doi-access = free }}</ref> Other risk factors include [[Stress (medicine)|psychological stress]].<ref name=pmid15307000/><ref>{{cite journal| author = Livengood JM| title = The role of stress in the development of herpes zoster and postherpetic neuralgia| journal = [[Curr. Rev. Pain]]| year = 2000| volume = 4| issue = 1| pages = 7–11| pmid = 10998709| doi = 10.1007/s11916-000-0003-9 | s2cid = 37086354}}</ref><ref name="Gatti2010">{{cite journal| vauthors = Gatti A, Pica F, Boccia MT, De Antoni F, Sabato AF, Volpi A | title = No evidence of family history as a risk factor for herpes zoster in patients with post-herpetic neuralgia| journal = [[J. Med. Virol.]]| year = 2010| volume = 82| issue = 6| pages = 1007–1011| pmid = 20419815| doi = 10.1002/jmv.21748| hdl = 2108/15842| s2cid = 31667542 | hdl-access = free}}</ref> According to a study in North Carolina, "black subjects were significantly less likely to develop zoster than were white subjects."<ref>{{cite journal| vauthors = Schmader K, George LK, Burchett BM, Pieper CF | title = Racial and psychosocial risk factors for herpes zoster in the elderly| journal = [[J. Infect. Dis.]]| year = 1998| volume = 178| issue = Suppl 1| pages = S67–S70| pmid = 9852978| doi = 10.1086/514254| doi-access = free}}</ref><ref>{{cite journal| vauthors = Schmader K, George LK, Burchett BM, Hamilton JD, Pieper CF | title = Race and stress in the incidence of herpes zoster in older adults| journal = [[J. Am. Geriatr. Soc.]]| year = 1998| volume = 46| issue = 8| pages = 973–977| pmid = 9706885| doi=10.1111/j.1532-5415.1998.tb02751.x| s2cid = 7583608 }}</ref> It is unclear whether the risk is different by sex. Other potential risk factors include [[Physical trauma|mechanical trauma]] and exposure to [[immunotoxin]]s.<ref name=pmid14720565/><ref name="Gatti2010"/> There is no strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who had shingles were twice as likely to develop it themselves,<ref>{{cite journal| vauthors = Hicks LD, Cook-Norris RH, Mendoza N, Madkan V, Arora A, Tyring SK | title = Family history as a risk factor for herpes zoster: a case-control study| journal = [[Arch. Dermatol.]]| volume = 144| issue = 5| pages = 603–608|date=May 2008| pmid = 18490586| doi = 10.1001/archderm.144.5.603| doi-access = free}}</ref> but a 2010 study found no such link.<ref name="Gatti2010"/> Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost.<ref name="Hope-Simpson"/><ref name="Gatti2010"/> This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the United States, there was concern that, because older adults would no longer receive this natural periodic boost, there would be an increase in the incidence of shingles. Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995.<ref>{{cite journal |journal=[[MMWR Recomm. Rep.]] |date=22 June 2007 |volume=56 |issue=RR–4 |pages=1–40 |title=Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP) |vauthors=Marin M, Güris D, Chaves SS, Schmid S, Seward JF |pmid=17585291 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5604a1.htm | collaboration = Advisory Committee On Immunization Practices |url-status=live |archive-url=https://web.archive.org/web/20110904022547/http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5604a1.htm |archive-date=4 September 2011 }}{{PD-notice}}</ref> However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community.<ref>{{cite journal |journal=[[J. Infect. Dis.]] |year=2005 |volume=191 |issue=12 |pages=2002–2007 |title=Incidence of herpes zoster, before and after varicella-vaccination-associated decreases in the incidence of varicella, 1992–2002 |vauthors= Jumaan AO, Yu O, Jackson LA, Bohlke K, Galil K, Seward JF |pmid=15897984 |doi=10.1086/430325|doi-access=free }}</ref><ref>{{cite journal |journal=[[J. Infect. Dis.]] |year=2005 |volume=191 |issue=12 |pages=1999–2001 |title=Changing dynamics of varicella-zoster virus infections in the 21st century: the impact of vaccination |author= Whitley RJ |pmid=15897983 |doi=10.1086/430328|doi-access=free }}</ref> A later study by Patel ''et al.'' concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles increased by more than $700 million annually for those over age 60.<ref>{{cite journal|vauthors=Patel MS, Gebremariam A, Davis MM|title=Herpes zoster-related hospitalizations and expenditures before and after introduction of the varicella vaccine in the United States|journal=[[Infect. Control Hosp. Epidemiol.]] |volume=29|issue=12|pages=1157–1163|date=December 2008|pmid=18999945|doi=10.1086/591975|s2cid=21934553}}</ref> Another study by Yih ''et al.'' reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased, and the occurrence of shingles among adults increased by 90%.<ref>{{cite journal| journal = [[BMC Public Health]] | year = 2005| volume = 5| page = 68| title = 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, 1998–2003| vauthors = Yih WK, Brooks DR, Lett SM, Jumaan AO, Zhang Z, Clements KM, Seward JF| display-authors = 6 | pmid = 15960856| doi = 10.1186/1471-2458-5-68| pmc = 1177968| doi-access = free}}</ref> The results of a further study by Yawn ''et al.'' showed a 28% increase in shingles incidence from 1996 to 2001.<ref>{{cite journal| journal = [[Mayo Clin. Proc.]] | year = 2007| volume = 82| issue = 11| pages = 1341–1349| title = A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction| vauthors = Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS | pmid = 17976353| doi = 10.4065/82.11.1341}}</ref> 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.<ref name=Dwo2007/> In one study, it was estimated that 26% of those who contract shingles eventually present complications. Postherpetic neuralgia arises in approximately 20% of people with shingles.<ref name=pmid17939894>{{cite journal |author=Volpi A |title=Severe complications of herpes zoster |journal=[[Herpes (journal)|Herpes]] |volume=14 |issue=Suppl 2 |pages=35A–39A |year=2007 |pmid=17939894 |url=http://www.ihmf.org/journal/download/4%20-%20Herpes%2014.2%20suppl%20Volpi.pdf |access-date=18 December 2007 |archive-date=27 January 2019 |archive-url=https://web.archive.org/web/20190127051057/http://www.ihmf.org/journal/download/4%20-%20Herpes%2014.2%20suppl%20Volpi.pdf |url-status=live }}</ref> 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.<ref>{{cite journal |journal=[[Pediatr. Infect. Dis. J.]] |year=2001 |volume=20 |issue=7 |pages=641–645 |title= Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction: a baseline assessment of the shifting epidemiology of varicella disease |vauthors= Coplan P, Black S, Rojas C, Shinefield H, Ray P, Lewis E, Guess H | display-authors = 6 | pmid=11465834 |doi=10.1097/00006454-200107000-00002 |s2cid=25626718 }}</ref> 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.<ref>{{cite journal |journal=[[J. Am. Osteopath. Assoc.]] |date=1 March 2007 |volume=107 |issue=3 Suppl |pages=S2–57 |title=The burden of herpes zoster and postherpetic neuralgia in the United States |author=Weaver BA |pmid=17488884 |url=http://www.jaoa.org/cgi/content/full/107/suppl_1/S2 |url-status=dead |archive-url=https://web.archive.org/web/20080113020412/http://www.jaoa.org/cgi/content/full/107/suppl_1/S2 |archive-date=13 January 2008 }}</ref> ==History== Shingles has a long recorded history, although historical accounts fail to distinguish the blistering caused by VZV and those caused by [[smallpox]],<ref name=pmid18021864/> [[ergotism]], and [[erysipelas]]. [[Aulus Cornelius Celsus]], around 25 BC to 50 AD, first used the term herpes zoster.<ref>{{citation |url=https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-23-zoster.html |chapter=Chapter 23: Zoster |title= Epidemiology and Prevention of Vaccine-Preventable Diseases |last1=Leung |first1=Jessica |last2=Harrington |first2=Theresa |last3=Dooling |first3=Kathleen |date=2024 |publisher=Center for Disease Control |access-date=31 March 2025}}</ref> In the late 18th century [[William Heberden]] established a way to differentiate shingles and smallpox,<ref>{{cite book|author=Weller TH |year=2000 |chapter=Chapter 1. Historical perspective |title=Varicella-Zoster Virus: Virology and Clinical Management |veditors=Arvin AM, Gershon AA |publisher= Cambridge University Press |isbn= 978-0521660242}}</ref> and in the late 19th century, shingles was differentiated from erysipelas. In 1831 [[Richard Bright (physician)|Richard Bright]] hypothesized that the disease arose from the dorsal root ganglion, and an 1861 paper by [[Friedrich Wilhelm Felix von Bärensprung|Felix von Bärensprung]] confirmed this.<ref>{{cite journal |author= Oaklander AL |title= The pathology of shingles: Head and Campbell's 1900 monograph |journal= [[Arch. Neurol.]] |volume= 56 |issue= 10 |pages= 1292–1294 |date= October 1999 |pmid= 10520948 |doi= 10.1001/archneur.56.10.1292}}</ref> Recognition that chickenpox and shingles were caused by the same virus came at the beginning of the 20th century. Physicians began to report that cases of shingles were often followed by chickenpox in younger people who lived with the person with shingles. The idea of an association between the two diseases gained strength when it was shown that lymph from a person with shingles 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 Huckle Weller]], in 1953.<ref name=pmid13064265>{{cite journal |author= Weller TH |title=Serial propagation in vitro of agents producing inclusion bodies derived from varicella and herpes zoster |journal=[[Proc. Soc. Exp. Biol. Med.]] |volume=83 |issue=2 |pages=340–346 |year=1953 |pmid=13064265 |doi=10.3181/00379727-83-20354 |s2cid=28771357 }}</ref> Some sources also attribute the first isolation of the herpes zoster virus to [[Evelyn Nicol]].<ref>{{Cite web|title=Evelyn Nicol 1930 - 2020 - Obituary|url=https://www.legacy.com/amp/obituaries/chicagotribune/196328986|access-date=28 August 2020|website=legacy.com|language=en|archive-date=27 May 2022|archive-url=https://web.archive.org/web/20220527064140/https://www.legacy.com/amp/obituaries/chicagotribune/196328986|url-status=live}}</ref> Until the 1940s the disease was considered benign, and serious complications were thought to be very rare.<ref>{{cite book |vauthors=Holt LE, McIntosh R |title= Holt's Diseases of Infancy and Childhood |url=https://archive.org/details/b31351554 |year=1936 |publisher=D Appleton Century Company |pages=931–933}}</ref> However, by 1942, it was recognized that shingles was a more serious disease in adults than in children and that it 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.<ref name="Weller">{{cite book |author=Weller TH |chapter-url=https://archive.org/details/viralinfectionso0004unse_v7u2/page/865/mode/2up |title=Viral Infections of Humans: Epidemiology and Control |publisher=Plenum Press |year=1997 |isbn=978-0306448553 |veditors=Evans AS, Kaslow RA |pages=865–892 |chapter=Varicella-herpes zoster virus |chapter-url-access=registration}}</ref> 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 (i.e., 50%) would have at least one attack of shingles, and 10 (i.e., 1%) would have at least two attacks.<ref name="hopesimpson65">{{cite journal |author=Hope-Simpson RE |year=1965 |title=The nature of herpes zoster; a long-term study and a new hypothesis |journal=[[Proceedings of the Royal Society of Medicine]] |volume=58 | pages=9–20 |pmid=14267505 |pmc=1898279 |issue=1|doi=10.1177/003591576505800106 }}</ref> In historical shingles studies, shingles incidence generally increased with age. However, in his 1965 paper, [[Robert Edgar Hope-Simpson|Hope-Simpson]] suggested that the "peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed".<ref name="Hope-Simpson"/> Lending support to this hypothesis that contact with children with chickenpox boosts adult cell-mediated immunity to help postpone or suppress shingles, a study by Thomas ''et al.'' reported that adults in households with children had lower rates of shingles than households without children.<ref>{{cite journal |vauthors= Thomas SL, Wheeler JG, Hall AJ |year=2002 |title=Contacts with varicella or with children and protection against herpes zoster in adults: a case-control study |journal=[[The Lancet]] |volume=360 | pages=678–682 |pmid=12241874 |doi=10.1016/S0140-6736(02)09837-9 |issue=9334 |s2cid=28385365 }}</ref> Also, the study by Terada ''et al.'' indicated that pediatricians reflected incidence rates from 1/2 to 1/8 that of the general population their age.<ref>{{cite journal |vauthors=Terada K, Hiraga Y, Kawano S, Kataoka N |year=1995 |title=Incidence of herpes zoster in pediatricians and history of reexposure to varicella-zoster virus in patients with herpes zoster | journal=Kansenshogaku Zasshi | volume=69 | issue=8 | issn=0387-5911 | pmid=7594784 | pages=908–912 |doi=10.11150/kansenshogakuzasshi1970.69.908 | doi-access=free }}</ref> ==Etymology== The family name of all the [[herpesvirus]]es derives from the Greek word {{lang|el|έρπης herpēs}},<ref>{{LSJ|e(/rphs|ἕρπης|ref}}.</ref> from {{lang|el|έρπω herpein}} ("to creep"),<ref>{{LSJ|e(/rpw|ἕρπειν|shortref}}.</ref><ref>{{OEtymD|herpes}}</ref><ref>{{cite web|url=http://dictionary.reference.com/browse/herpes|title=Herpes | Define Herpes at Dictionary.com|access-date=14 March 2011|url-status=live|archive-url=https://web.archive.org/web/20110225123419/http://dictionary.reference.com/browse/herpes|archive-date=25 February 2011}}</ref> referring to the latent, recurring infections typical of this group of viruses. ''Zoster'' comes from Greek {{lang|el|ζωστήρ zōstēr}},<ref>{{LSJ|zwsth/r|ζωστήρ|shortref}}.</ref> meaning "belt" or "girdle", after the characteristic belt-like dermatomal rash.<ref>{{OEtymD|zoster}}</ref> The common name for the disease, ''shingles'', derives from the Latin {{lang|la|cingulus}}, a variant of Latin {{lang|la|cingulum}},<ref>{{L&S|cingulus|lL&S}}, {{L&S|cingulum1|cingulum|ref}}</ref> meaning "girdle".<ref>{{OEtymD|shingles}}</ref><ref>{{cite journal| vauthors = Yawn BP, Gilden D |title=The global epidemiology of herpes zoster |journal=[[Neurology (journal)|Neurology]]|date=3 September 2013|volume=81|issue=10|pages=928–930|pmid=23999562|doi=10.1212/wnl.0b013e3182a3516e|pmc=3885217}}</ref> ==Research== Until the mid-1990s, infectious complications of the [[central nervous system]] (CNS) caused by VZV reactivation were regarded as rare. The presence of rash, as well as specific neurological symptoms, were required to diagnose a CNS infection caused by VZV. Since 2000, PCR testing has become more widely used, and the number of diagnosed cases of CNS infection has increased.<ref name="ijidonline.com">{{cite journal |title = Infection of the central nervous system caused by varicella zoster virus reactivation: a retrospective case series study |url = http://www.ijidonline.com/article/S1201-9712(13)00096-9/abstract |journal = [[International Journal of Infectious Diseases]] |date = July 2013 |doi = 10.1016/j.ijid.2013.01.031 |volume = 17 |issue = 7 |pages = e529–534 |vauthors = Becerra JC, Sieber R, Martinetti G, Costa ST, Meylan P, Bernasconi E |pmid = 23566589 |doi-access = free |access-date = 2 March 2016 |archive-date = 17 December 2019 |archive-url = https://web.archive.org/web/20191217063234/https://www.ijidonline.com/article/S1201-9712(13)00096-9/abstract |url-status = live }}</ref> Classic textbook descriptions state that VZV reactivation in the CNS is restricted to immunocompromised individuals and the elderly; however, studies have found that most participants are immunocompetent, and younger than 60 years old. Historically, vesicular rash was considered a characteristic finding, but studies have found that rash is only present in 45% of cases.<ref name="ijidonline.com"/> In addition, systemic inflammation is not as reliable an indicator as previously thought: the mean level of C-reactive protein and mean white blood cell count are within the normal range in participants with VZV meningitis.<ref>{{cite journal | vauthors = Ihekwaba UK, Kudesia G, McKendrick MW |title = Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections | journal=Clinical Infectious Diseases | volume=47 | issue=6 | date=15 September 2008 | issn=1058-4838 | pmid=18680414 | doi=10.1086/591129 | pages=783–789 | doi-access=free }}</ref> MRI and CT scans are usually normal in cases of VZV reactivation in the CNS. CSF pleocytosis, previously thought to be a strong indicator of VZV encephalitis, was absent in half of a group of people diagnosed with VZV encephalitis by PCR.<ref name="ijidonline.com"/> The frequency of CNS infections presented at the emergency room of a community hospital is not negligible, so a means of diagnosing cases is needed. PCR is not a foolproof method of diagnosis, but because so many other indicators have turned out not to be reliable in diagnosing VZV infections in the CNS, PCR is the recommended method of testing for VZV. Negative PCR does not rule out VZV involvement, but a positive PCR can be used for diagnosis, and appropriate treatment started (for example, antivirals can be prescribed rather than antibiotics).<ref name="ijidonline.com"/> The introduction of DNA analysis techniques has shown some complications of varicella-zoster to be more common than previously thought. For example, sporadic meningoencephalitis (ME) caused by varicella-zoster was regarded as rare disease, mostly related to childhood chickenpox. However, meningoencephalitis caused by varicella-zoster is increasingly recognized as a predominant cause of ME among immunocompetent adults in non-epidemic circumstances.<ref name="ncbi.nlm.nih.gov">{{cite journal |title = Varicella zoster vs. herpes simplex meningoencephalitis in the PCR era. A single center study |journal= [[Journal of the Neurological Sciences]] |date=August 2011 |pmid=22138027 |doi=10.1016/j.jns.2011.11.004 |volume=314 |issue= 1–2 |pages=29–36| vauthors = Pollak L, Dovrat S, Book M, Mendelson E, Weinberger M |s2cid= 3321888 }}</ref> Diagnosis of complications of varicella-zoster, particularly in cases where the disease reactivates after years or decades of latency, is difficult. A rash (shingles) can be present or absent. Symptoms vary, and there is a significant overlap in symptoms with herpes-simplex symptoms.<ref name="ncbi.nlm.nih.gov"/> Although DNA analysis techniques such as [[polymerase chain reaction]] (PCR) can be used to look for DNA of herpesviruses in spinal fluid or blood, the results may be negative, even in cases where other definitive symptoms exist.<ref>{{cite journal | vauthors = Kojima Y, Hashiguchi H, Hashimoto T, Tsuji S, Shoji H, Kazuyama Y |title = Recurrent Herpes Simplex Virus Type 2 Meningitis: A Case Report of Mollaret's Meningitis |url = http://www0.nih.go.jp/JJID/SC-29.pdf | journal=Japanese Journal of Infectious Diseases | volume=55 | issue=3 | date=15 September 2008 | issn=1344-6304 | pmid=12195049 | pages=85–88 |url-status=live |archive-url = https://web.archive.org/web/20130122201650/http://www0.nih.go.jp/JJID/SC-29.pdf |archive-date = 22 January 2013 }}</ref> Notwithstanding these limitations, the use of PCR has resulted in an advance in the state of the art in our understanding of herpesviruses, including VZV, during the 1990s and 2000s. For example, in the past, [[clinician]]s believed that [[encephalitis]] was caused by [[herpes simplex]] and that people always died or developed serious long-term function problems. People were diagnosed at [[autopsy]] or by [[brain biopsy]]. Brain biopsy is not undertaken lightly: it is reserved only for serious cases that cannot be diagnosed by less invasive methods. For this reason, knowledge of these herpes virus conditions was limited to severe cases. DNA techniques have made it possible to diagnose "mild" cases, caused by VZV or HSV, in which the symptoms include fever, headache, and altered mental status. Mortality rates in treated people are decreasing.<ref name="ncbi.nlm.nih.gov"/> == References == {{Reflist}} == Further reading == * {{Cite journal |author=Saguil A |title=Herpes Zoster and Postherpetic Neuralgia: Prevention and Management |url=https://www.aafp.org/pubs/afp/issues/2017/1115/p656.html |journal=American Family Physician |volume=96 |issue=10 |date=November 2017 |pages=656–663 |pmid=29431387 }} ==External links== {{Commons category|Herpes zoster}} {{Offline|med}} * [https://www.ninds.nih.gov/Disorders/All-Disorders/Shingles-Information-Page NINDS Shingles Information Page] – [[National Institute of Neurological Disorders and Stroke]] {{Medical condition classification and resources | ICD11 = {{ICD11|1E91}} | ICD10 = {{ICD10|B|02||b|00}} | ICD9 = {{ICD9|053}} | ICDO = | OMIM = | MedlinePlus = 000858 | eMedicineSubj = med | eMedicineTopic = 1007 | eMedicine_mult = {{eMedicine2|derm|180}} {{eMedicine2|emerg|823}} {{eMedicine2|oph|257}} {{eMedicine2|ped|996}} | DiseasesDB = 29119 }} {{Diseases of the skin and appendages by morphology}} {{Viral cutaneous conditions}} {{Varicella zoster}} {{Oral pathology}} {{Portal bar|Viruses|Medicine}} {{Authority control}} [[Category:Betaherpesvirinae]] [[Category:Chickenpox]] [[Category:Oral mucosal pathology]] [[Category:Viral diseases]] [[Category:Varicella zoster virus-associated diseases]] [[Category:Virus-related cutaneous conditions]] [[Category:Wikipedia emergency medicine articles ready to translate]] [[Category:Wikipedia medicine articles ready to translate]] [[Category:Vaccine-preventable diseases]]
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