Original Investigation
November 2015

Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis

Author Affiliations
  • 1Department of Neurology, University of Colorado School of Medicine, Aurora
  • 2Department of Pathology, University of Colorado School of Medicine, Aurora
  • 3Department of Ophthalmology, University of Colorado School of Medicine, Aurora
  • 4Fort Wayne Neurological Center, Fort Wayne, Indiana
  • 5Arapahoe County Coroner’s Office, Centennial, Colorado
  • 6Texas Oculoplastic Consultants, Austin
  • 7University of Texas Southwestern–Austin Transitional Year Program, Austin
  • 8Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia
  • 9Scheie Eye Institute, University of Pennsylvania, Philadelphia
  • 10Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia
  • 11A. M. Rywlin Department of Pathology, Mount Sinai Medical Center and Florida International University, Miami
  • 12Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany
  • 13Department of Neurology, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • 14Pathological Institute, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • 15Department of Pathology, Icahn School of Medicine, Mount Sinai Health System, New York, New York
  • 16Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 17Department of Neurology, University of Würzburg, Würzburg, Germany
  • 18Department of Ophthalmology, University of Würzburg, Würzburg, Germany
  • 19Landspitali University Hospital, Reykjavik, Iceland
  • 20Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora

Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Neurol. 2015;72(11):1281-1287. doi:10.1001/jamaneurol.2015.2101

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 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.

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 < .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.

Conclusions and Relevance  In 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.