Varicella Zoster Virus and Granulomatous Arteritis
By Dean L. Winslow, MD, FACP, FIDSA
Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine
Dr. Winslow reports no financial relationships relevant to this field of study.
SYNOPSIS: Varicella zoster virus antigen was identified in 11 of 11 aortas with pathologically verified granulomatous arteritis and in only five of 18 control aortas from surgical or autopsy specimens.
SOURCE: Gilden D, White T, Boyer PJ, et al. Varicella zoster virus infection in granulomatous arteritis of the aorta. J Infect Dis 2016;213:1866-1871.
Researchers examined surgical pathology databases at Massachusetts General Hospital from 1990 to present and identified 11 cases that met criteria for granulomatous arteritis of the aorta. The cases included five men and six women who ranged from 32-87 years of age. Eighteen control aortas were studied and included specimens from eight men and 10 women ranging from 23-66 years of age. No control aortas had evidence of inflammation or giant cell arteritis (GCA). Formalin-fixed tissue blocks were examined for varicella zoster virus (VZV) by immunohistochemistry and polymerase chain reaction (PCR).
Immunohistochemical analysis using three different antibodies identified VZV antigen in the cytoplasm of all 11 aortas with pathologically confirmed granulomatous arteritis. Antigen was present in all arterial layers. VZV antigen also was identified in one case of nongranulomatous arteritis and in five of 18 control aortas. Ten of the aortas with granulomatous arteritis contained amplifiable DNA and, of those, seven (70%) contained VZV DNA detected by PCR. A records review of the 11 patients who underwent surgical repair of an aortic aneurysm suggested a diagnosis of giant cell arteritis in five cases, whereas none had evidence of Takayasu arteritis.
COMMENTARY
This study expands on an earlier study by this same group, which demonstrated VZV in most temporal arteries of patients with GCA, but in only 18% of normal extracranial temporal arteries.1 Since no inflammation was present in the normal aortas that contained VZV antigen, it is likely that this represented asymptomatic reactivation. It is also unlikely that the VZV in the aortas with either granulomatous arteritis or temporal arteries with GCA represents a nonspecific “bystander” result of tissue inflammation, since VZV is not detected in tissue sections or CSF from patients with a variety of other inflammatory/infectious diseases.2 In addition, the identification of VZV in all of the arterial layers of the aorta (intima, media, and adventitia) in this study is consistent with findings seen in patients with VZV vasculopathy3 and GCA.2
While strict demonstration of VZV causation in these cases of granulomatous arteritis and GCA has not been proven, it certainly provides a plausible biological linkage. The common temporal association of stroke with recent herpes zoster also has been recognized recently.4 The potential protective effect of zoster vaccination on prevention of vasculopathy and stroke in adults has yet to be determined, yet seems worthy of study, as well as that of potential antiviral intervention.
REFERENCES
- Gilden D, White T, Khmeleva N, et al. Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Neurology 2015;84:1948-1955.
- Nagel MA, White T, Khmeleva N, et al. Analysis of varicella zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis. JAMA Neurol 2015;72:1281-1287.
- Nagel MA, Traktinskiy I, Azarkh Y, et al. Varicella zoster virus vasculopathy. Analysis of virus-infected arteries. Neurology 2011;77:364-370.
- Kang JH, Ho JD, Chen YH, et al. Increased risk of stroke after a herpes zoster attack: A population-based follow-up study. Stroke 2009;40:3443–3448.
Varicella zoster virus antigen was identified in 11 of 11 aortas with pathologically verified granulomatous arteritis and in only five of 18 control aortas from surgical or autopsy specimens.
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