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dc.contributor.authorNagel, Maria A
dc.contributor.authorWhite, Teresa
dc.contributor.authorKhmeleva, Nelly
dc.contributor.authorRempel, April
dc.contributor.authorBoyer, Philip J
dc.contributor.authorBennett, Jeffrey L
dc.contributor.authorHaller, Andrea
dc.contributor.authorLear-Kaul, Kelly
dc.contributor.authorKandasmy, Balasurbramaniyam
dc.contributor.authorAmato, Malena
dc.contributor.authorWood, Edward
dc.contributor.authorDurairaj, Vikram
dc.contributor.authorFogt, Franz
dc.contributor.authorTamhankar, Madhura A
dc.contributor.authorGrossniklaus, Hans E
dc.contributor.authorPoppiti, Robert J
dc.contributor.authorBockelman, Brian
dc.contributor.authorKeyvani, Kathy
dc.contributor.authorPollak, Lea
dc.contributor.authorMendlovic, Sonia
dc.contributor.authorFowkes, Mary
dc.contributor.authorEberhart, Charles G
dc.contributor.authorButtmann, Mathias
dc.contributor.authorToyka, Klaus V
dc.contributor.authorMeyer-Ter-Vehn, Tobias
dc.contributor.authorPetursdottir, Vigdis
dc.contributor.authorGilden, Don
dc.date.accessioned2016-01-04T14:57:57Zen
dc.date.available2016-01-04T14:57:57Zen
dc.date.issued2015-11-01en
dc.date.submitted2015en
dc.identifier.citationAnalysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis. 2015, 72 (11):1281-7 JAMA Neurolen
dc.identifier.issn2168-6157en
dc.identifier.pmid26349037en
dc.identifier.doi10.1001/jamaneurol.2015.2101en
dc.identifier.urihttp://hdl.handle.net/2336/592779en
dc.descriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the pageen
dc.description.abstractGiant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV).
dc.description.abstractTo analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals.
dc.description.abstractA cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years.
dc.description.abstractPresence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers.
dc.description.abstractVaricella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs.
dc.description.abstractIn patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.
dc.description.sponsorshipNational Institutes of Health/AG032958 EY06360en
dc.language.isoenen
dc.publisherAmer Medical Assocen
dc.relation.urlhttp://dx.doi.org/ 10.1001/jamaneurol.2015.2101en
dc.rightsArchived with thanks to JAMA neurologyen
dc.subject.meshAged, 80 and overen
dc.subject.meshInfectionen
dc.subject.meshGiant Cell Arteritis/virology*en
dc.subject.meshEncephalitis, Varicella Zoster/epidemiologyen
dc.subject.meshCerebral Arterial Diseases/epidemiologyen
dc.subject.meshAgeden
dc.titleAnalysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis.en
dc.typeArticleen
dc.contributor.department[ 1 ] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA [ 2 ] Univ Colorado, Sch Med, Dept Pathol, Aurora, CO 80045 USA [ 3 ] Univ Colorado, Sch Med, Dept Ophthalmol, Aurora, CO 80045 USA [ 4 ] Ft Wayne Neurol Ctr, Ft Wayne, IN USA [ 5 ] Arapahoe Cty Coroners Off, Centennial, CO USA [ 6 ] Texas Oculoplast Consultants, Austin, TX USA [ 7 ] Univ Texas Southwestern, Austin Transit Year Program, Austin, TX USA [ 8 ] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA [ 9 ] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA [ 10 ] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA [ 11 ] Mt Sinai Med Ctr, AM Rywlin Dept Pathol, Miami, FL USA [ 12 ] Florida Int Univ, Miami, FL 33199 USA [ 13 ] Univ Duisburg Essen, Inst Neuropathol, Essen, Germany [ 14 ] Tel Aviv Univ, Sackler Fac Med, Assaf Harofeh Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel [ 15 ] Tel Aviv Univ, Sackler Fac Med, Assaf Harofeh Med Ctr, Inst Pathol, IL-69978 Tel Aviv, Israel [ 16 ] Mt Sinai Hlth Syst, Icahn Sch Med, Dept Pathol, New York, NY USA [ 17 ] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA [ 18 ] Univ Wurzburg, Dept Neurol, Wurzburg, Germany [ 19 ] Univ Wurzburg, Dept Ophthalmol, D-97070 Wurzburg, Germany [ 20 ] Landspitali Univ Hosp, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 21 ] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO 80045 USAen
dc.identifier.journalJAMA neurologyen
dc.rights.accessClosed - Lokaðen
html.description.abstractGiant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV).
html.description.abstractTo analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals.
html.description.abstractA cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years.
html.description.abstractPresence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers.
html.description.abstractVaricella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs.
html.description.abstractIn patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.


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