Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis.
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Authors
Gilden, DonWhite, Teresa
Khmeleva, Nelly
Heintzman, Anna
Choe, Alexander
Boyer, Philip J
Grose, Charles
Carpenter, John E
Rempel, April
Bos, Nathan
Kandasamy, Balasubramaniyam
Lear-Kaul, Kelly
Holmes, Dawn B
Bennett, Jeffrey L
Cohrs, Randall J
Mahalingam, Ravi
Mandava, Naresh
Eberhart, Charles G
Bockelman, Brian
Poppiti, Robert J
Tamhankar, Madhura A
Fogt, Franz
Amato, Malena
Wood, Edward
Durairaj, Vikram
Rasmussen, Steve
Petursdottir, Vigdis
Pollak, Lea
Mendlovic, Sonia
Chatelain, Denis
Keyvani, Kathy
Brueck, Wolfgang
Nagel, Maria A
Issue Date
2015-05-12
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Neurology 2015, 84 (19):1948-55Abstract
Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA).Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen-positive slides were analyzed by PCR for VZV DNA.
VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen-positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen-positive TAs, in 6/10 (60%) VZV antigen-positive skeletal muscles, and in one VZV antigen-positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs.
Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.
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10.1212/WNL.0000000000001409
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