Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis

Don Gilden, Teresa White, Nelly Khmeleva, Anna Heintzman, Alexander Choe, Philip J. Boyer, Charles Grose, John E. Carpenter, April Rempel, Nathan Bos, Balasubramaniyam Kandasamy, Kelly Lear-Kaul, Dawn B. Holmes, Jeffrey L. Bennett, Randall J. Cohrs, Ravi Mahalingam, Naresh Mandava, Charles G. Eberhart, Brian Bockelman, Robert J. PoppitiMadhura A. Tamhankar, Franz Fogt, Malena Amato, Edward Wood, Vikram Durairaj, Steve Rasmussen, Vigdis Petursdottir, Lea Pollak, Sonia Mendlovic, Denis Chatelain, Kathy Keyvani, Wolfgang Brueck, Maria A. Nagel

Research output: Contribution to journalArticle

Abstract

Objective: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1948-1955
Number of pages8
JournalNeurology
Volume84
Issue number19
DOIs
StatePublished - May 12 2015

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ASJC Scopus subject areas

  • Clinical Neurology

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Gilden, D., White, T., Khmeleva, N., Heintzman, A., Choe, A., Boyer, P. J., Grose, C., Carpenter, J. E., Rempel, A., Bos, N., Kandasamy, B., Lear-Kaul, K., Holmes, D. B., Bennett, J. L., Cohrs, R. J., Mahalingam, R., Mandava, N., Eberhart, C. G., Bockelman, B., ... Nagel, M. A. (2015). Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Neurology, 84(19), 1948-1955. https://doi.org/10.1212/WNL.0000000000001409