Neurology 2015 May 18;84(19):1948-55. Epub 2015 Feb 18.
From the Departments of Neurology (D.G., T.W., N.K., A.H., A.C., A.R., N.B., J.L.B., R.J.C., R.M., M.A.N.), Microbiology (D.G., R.J.C.), Pathology (P.J.B., B.K.), and Ophthalmology (J.L.B., N.M.), University of Colorado School of Medicine, Aurora; Children's Hospital (C.G., J.E.C.), University of Iowa, Iowa City; Arapahoe County Coroner's Office (K.L.-K.), Aurora, CO; Denver Office of the Medical Examiner (D.B.H.), Denver, CO; Department of Pathology (C.G.E.), Johns Hopkins University School of Medicine, Baltimore, MD; A.M. Rywlin Department of Pathology (B.B., R.J.P.), Mount Sinai Medical Center, Miami Beach, FL; Florida International University (B.B., R.J.P.), Miami Beach; Scheie Eye Institute (M.A.T.) and Department of Pathology and Laboratory Medicine (F.F.), University of Pennsylvania, Philadelphia; Texas Oculoplastic Consultants (M.A., E.W., V.D.), Austin; University of Texas, Southwestern - Austin Transitional Year Program (E.W.), Austin; Departments of Pathology and Laboratory Medicine, Ophthalmology, and Visual Sciences (S.R.), University of British Columbia, Vancouver, Canada; Landspitali University Hospital (V.P.), Reykjavik, Iceland; Department of Neurology (L.P.) and Pathological Institute (S.M.), Assaf Harofeh Medical Center, Zerifin, University of Tel Aviv, Israel; Department of Pathology (D.C.), Centre Hospitalier Universitaire du Nord and RECIP, Amiens, France; Institute of Neuropathology (K.K.), University of Duisburg-Essen, Germany; and Department of Neuropathology (W.B.), University Medical Center Gottingen, Germany.
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.