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


METHODS
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.


METHODS
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
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.
Department of Neurology, University of Colorado School of Medicine, Aurora.
Maria A
MA
Nagel
Department of Neurology, University of Colorado School of Medicine, Aurora.
Teresa
T
White
Department of Neurology, University of Colorado School of Medicine, Aurora.
Nelly
N
Khmeleva
Department of Neurology, University of Colorado School of Medicine, Aurora.
April
A
Rempel
Department of Pathology, University of Colorado School of Medicine, Aurora.
Philip J
PJ
Boyer
Department of Neurology, University of Colorado School of Medicine, Aurora3Department of Ophthalmology, University of Colorado School of Medicine, Aurora.
Jeffrey L
JL
Bennett
Fort Wayne Neurological Center, Fort Wayne, Indiana.
Andrea
A
Haller
Arapahoe County Coroner's Office, Centennial, Colorado.
Kelly
K
Lear-Kaul
Department of Pathology, University of Colorado School of Medicine, Aurora.
Balasurbramaniyam
B
Kandasmy
Texas Oculoplastic Consultants, Austin.
Malena
M
Amato
Texas Oculoplastic Consultants, Austin7University of Texas Southwestern-Austin Transitional Year Program, Austin.
Edward
E
Wood
Texas Oculoplastic Consultants, Austin.
Vikram
V
Durairaj
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia.
Franz
F
Fogt
Scheie Eye Institute, University of Pennsylvania, Philadelphia.
Madhura A
MA
Tamhankar
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.
Hans E
HE
Grossniklaus
A. M. Rywlin Department of Pathology, Mount Sinai Medical Center and Florida International University, Miami.
Robert J
RJ
Poppiti
A. M. Rywlin Department of Pathology, Mount Sinai Medical Center and Florida International University, Miami.
Brian
B
Bockelman
Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany.
Kathy
K
Keyvani
Department of Neurology, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Lea
L
Pollak
Pathological Institute, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Sonia
S
Mendlovic
Department of Pathology, Icahn School of Medicine, Mount Sinai Health System, New York, New York.
Mary
M
Fowkes
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Charles G
CG
Eberhart
Department of Neurology, University of Würzburg, Würzburg, Germany.
Mathias
M
Buttmann
Department of Neurology, University of Würzburg, Würzburg, Germany.
Klaus V
KV
Toyka
Department of Ophthalmology, University of Würzburg, Würzburg, Germany.
Tobias
T
Meyer-ter-Vehn
Landspitali University Hospital, Reykjavik, Iceland.
Vigdis
V
Petursdottir
Department of Neurology, University of Colorado School of Medicine, Aurora20Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora.
Don
D
Gilden
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003430:Cross-Sectional Studies; D005260:Female; D013700:Giant Cell Arteritis / Q000276:immunology / Q000473:pathology / Q000821:virology; D006562:Herpes Zoster / Q000276:immunology / Q000473:pathology / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013699:Temporal Arteries / Q000276:immunology / Q000473:pathology / Q000821:virology