Analysis of varicella-zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis

Maria A. Nagel, Teresa White, Nelly Khmeleva, April Rempel, Philip J. Boyer, Jeffrey L. Bennett, Andrea Haller, Kelly Lear-Kaul, Balasurbramaniyam Kandasmy, Malena Amato, Edward Wood, Vikram Durairaj, Franz Fogt, Madhura A. Tamhankar, Hans E. Grossniklaus, Robert J. Poppiti, Brian Bockelman, Kathy Keyvani, Lea Pollak, Sonia MendlovicMary Fowkes, Charles G Eberhart, Mathias Buttmann, Klaus V. Toyka, Tobias Meyer-Ter-Vehn, Vigdis Petursdottir, Don Gilden

Research output: Contribution to journalArticle

Abstract

IMPORTANCE: Giant 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). OBJECTIVE: To 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. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study for VZV antigenwas 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. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: Varicella-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

Original languageEnglish (US)
Pages (from-to)1281-1287
Number of pages7
JournalJAMA Neurology
Volume72
Issue number11
DOIs
StatePublished - Nov 1 2015

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Temporal Arteries
Giant Cell Arteritis
Human Herpesvirus 3
Biopsy
Antigens
Systemic Vasculitis
Private Practice
Virus Diseases
Hematoxylin
Eosine Yellowish-(YS)
Tertiary Care Centers
Paraffin
Formaldehyde
Adrenal Cortex Hormones
Cross-Sectional Studies
Immunohistochemistry
Staining and Labeling
Neurons

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Nagel, M. A., White, T., Khmeleva, N., Rempel, A., Boyer, P. J., Bennett, J. L., ... Gilden, D. (2015). Analysis of varicella-zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis. JAMA Neurology, 72(11), 1281-1287. https://doi.org/10.1001/jamaneurol.2015.2101

Analysis of varicella-zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis. / Nagel, Maria A.; White, Teresa; Khmeleva, Nelly; Rempel, April; Boyer, Philip J.; Bennett, Jeffrey L.; Haller, Andrea; Lear-Kaul, Kelly; Kandasmy, Balasurbramaniyam; Amato, Malena; Wood, Edward; Durairaj, Vikram; Fogt, Franz; Tamhankar, Madhura A.; Grossniklaus, Hans E.; Poppiti, Robert J.; Bockelman, Brian; Keyvani, Kathy; Pollak, Lea; Mendlovic, Sonia; Fowkes, Mary; Eberhart, Charles G; Buttmann, Mathias; Toyka, Klaus V.; Meyer-Ter-Vehn, Tobias; Petursdottir, Vigdis; Gilden, Don.

In: JAMA Neurology, Vol. 72, No. 11, 01.11.2015, p. 1281-1287.

Research output: Contribution to journalArticle

Nagel, MA, White, T, Khmeleva, N, Rempel, A, Boyer, PJ, Bennett, JL, Haller, A, Lear-Kaul, K, Kandasmy, B, Amato, M, Wood, E, Durairaj, V, Fogt, F, Tamhankar, MA, Grossniklaus, HE, Poppiti, RJ, Bockelman, B, Keyvani, K, Pollak, L, Mendlovic, S, Fowkes, M, Eberhart, CG, Buttmann, M, Toyka, KV, Meyer-Ter-Vehn, T, Petursdottir, V & Gilden, D 2015, 'Analysis of varicella-zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis', JAMA Neurology, vol. 72, no. 11, pp. 1281-1287. https://doi.org/10.1001/jamaneurol.2015.2101
Nagel, Maria A. ; White, Teresa ; Khmeleva, Nelly ; Rempel, April ; Boyer, Philip J. ; Bennett, Jeffrey L. ; Haller, Andrea ; Lear-Kaul, Kelly ; Kandasmy, Balasurbramaniyam ; Amato, Malena ; Wood, Edward ; Durairaj, Vikram ; Fogt, Franz ; Tamhankar, Madhura A. ; Grossniklaus, Hans E. ; Poppiti, Robert J. ; Bockelman, Brian ; Keyvani, Kathy ; Pollak, Lea ; Mendlovic, Sonia ; Fowkes, Mary ; Eberhart, Charles G ; Buttmann, Mathias ; Toyka, Klaus V. ; Meyer-Ter-Vehn, Tobias ; Petursdottir, Vigdis ; Gilden, Don. / Analysis of varicella-zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis. In: JAMA Neurology. 2015 ; Vol. 72, No. 11. pp. 1281-1287.
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AU - Nagel, Maria A.

AU - White, Teresa

AU - Khmeleva, Nelly

AU - Rempel, April

AU - Boyer, Philip J.

AU - Bennett, Jeffrey L.

AU - Haller, Andrea

AU - Lear-Kaul, Kelly

AU - Kandasmy, Balasurbramaniyam

AU - Amato, Malena

AU - Wood, Edward

AU - Durairaj, Vikram

AU - Fogt, Franz

AU - Tamhankar, Madhura A.

AU - Grossniklaus, Hans E.

AU - Poppiti, Robert J.

AU - Bockelman, Brian

AU - Keyvani, Kathy

AU - Pollak, Lea

AU - Mendlovic, Sonia

AU - Fowkes, Mary

AU - Eberhart, Charles G

AU - Buttmann, Mathias

AU - Toyka, Klaus V.

AU - Meyer-Ter-Vehn, Tobias

AU - Petursdottir, Vigdis

AU - Gilden, Don

PY - 2015/11/1

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N2 - IMPORTANCE: Giant 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). OBJECTIVE: To 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. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study for VZV antigenwas 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. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: Varicella-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

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