Editing Shingles (section)

==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&nbsp;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>