Varicella zoster virus ischemic optic neuropathy and subclinical temporal artery involvement

Abstract

Objective: To demonstrate varicella zoster virus (VZV) infection in an asymptomatic extracranial (temporal) artery in a patient with ischemic optic neuropathy produced by VZV vasculopathy in whom the pathological changes were mistakenly identified as giant cell arteritis.

Design: Case report.

Setting: Teaching hospital, pathology and virology laboratory.

Patient: An 80-year-old man with left ophthalmic distribution zoster who developed left ischemic optic neuropathy.

Intervention: An ipsilateral temporal artery biopsy revealed inflammation that was mistakenly identified as giant cell arteritis. The patient was initially treated with steroids but his condition did not improve. When the diagnosis of VZV vasculopathy was confirmed virologically and the patient was treated with intravenous acyclovir, his vision improved.

Results: Pathological and virological studies provided proof of VZV vasculopathy in the asymptomatic temporal artery. Varicella zoster virus antigen was abundant in arterial adventitia and scattered throughout the media. With intravenous antiviral therapy, the patient's vision improved.

Conclusion: Although in previously studied patients who died of chronic VZV vasculopathy after 10 to 12 months, VZV antigen was present exclusively in the intima, collective analyses of chronic cases and the asymptomatic VZV-infected temporal artery suggest that virus enters arteries through the adventitia and spreads transmurally to the intima.

Figure 1

Cross-section of the temporal artery examined on day 3 of patient’s hospitalization. Note the maximal inflammation in the intima (short arrow) and adventitia (long arrow), with relative sparing of the media (hematoxylin-eosin, original magnification ×200) (A) and the nearly intact, black-colored internal elastic lamina (arrow), despite the nearby intense intimal and adventitial inflammation (Verhoeff van Gieson stain for elastic fibers, original magnification ×100) (B).

Figure 2

Immunohistochemical analysis of the temporal artery. Note varicella zoster virus (VZV) antigen (red) in the nucleus and cytoplasm (solid arrows) and cytoplasm alone (dashed arrow) of cells in the arterial adventitia (A; original magnification ×200) not seen with normal rabbit serum (B). Sections of the temporal artery were deparaffinized and incubated with 10% normal sheep serum in phosphate-buffered saline (PBS) for 1 hour at room temperature. To prevent nonspecific binding, primary antibodies were adsorbed with normal human liver powder for 30 minutes and again for 20 hours at 4°C. Sections were then incubated with polyclonal antibodies raised against VZV open reading frame 63 protein (1:1000 dilution) or normal rabbit serum (1:1000 dilution), rinsed with PBS and incubated with a 1:300 dilution of biotinylated goat antirabbit IgG in PBS containing 5% normal sheep serum, washed 3 times in PBS, incubated with alkaline phosphatase–conjugated streptavidin (1:100 dilution), and washed 3 times with PBS. The color reaction was developed for 5 to 30 minutes with fresh fuchsin substrate system. Levamisole was added to the color reaction to block endogenous phosphatase. Uninfected and VZV-infected BSC-1 cells were used as controls (not shown).

Figure 3

Immunohistochemical analysis of the temporal artery as described in Figure 2. Note varicella zoster virus antigen scattered throughout the nucleus and cytoplasm of cells in the arterial wall (media) (A; original magnification ×400) not seen with normal rabbit serum (B).