In February 2010, an 80-year-old man developed left ophthalmic distribution zoster that was treated with oral valacyclovir (1 g, 3 times daily for 1 week). One month later, he developed sudden painless loss of vision in the left eye. He denied headache, scalp tenderness, or jaw claudication. Findings of neurological examination were normal except for left eye visual acuity, which was reduced to counting fingers at 1-foot distance, an afferent pupillary defect, and 50% reduction in red saturation. Funduscopic examination showed no cherry-red spots, optic nerve pallor, retinal edema, or increased intraocular pressure. The erythrocyte sedimentation rate was 32 mm/h, and the C-reactive protein level was 16 mg/L (to convert to nanomoles per liter, multiply by 9.524). The cerebrospinal fluid (CSF) contained 5 white blood cells; the level of CSF protein was 51 mg/100 mL; the IgG index was 0.3 (reference range, 0.3–0.7); and there were no oligoclonal bands. Polymerase chain reaction analysis of CSF did not reveal amplifiable VZV or herpes simplex virus DNA; the CSF was also sent for testing for anti-VZV antibody. Brain magnetic resonance imaging with sections at multiple levels of the optic nerve revealed occlusion of the left ophthalmic artery without evidence of restricted diffusion or subacute infarction. Fluorescein angiography revealed left optic disc leakage with no choroidal perfusion nasally. Magnetic resonance angiography revealed no flow in the left ophthalmic artery; all other intracranial and extracranial arteries were normal. The patient was immediately treated empirically for GCA with a single dose of methylprednisolone (250 mg intravenously). Owing to his recent history of left-sided ophthalmic-distribution zoster, the diagnosis of VZV vasculopathy with acute occlusion of the ipsilateral ophthalmic artery was also considered; the next day, he was also treated with oral prednisone (80 mg daily) and intravenous acyclovir (10 mg/kg every 8 hours).
On the third hospital day, a temporal artery biopsy revealed inflammation of the intima and adventitia () with eosinophils, lymphocytes, and multinucleated giant cells; the adventitia contained a lymphocytic infiltrate, with focal granulomatous inflammation of the vasa vasorum. Necrosis and vascular thrombosis were absent. The intima was thickened in areas with the most severe inflammation. The internal elastic lamina was almost completely intact (), with less than 5% to 10% of the circumferential diameter disrupted despite adjacent severe intimal inflammation. No phagocytosis of elastic lamina fragments was identified. Because some of these findings were consistent with GCA, intravenous acyclovir was discontinued after an initial 4-day course, although he continued to take oral prednisone (80 mg daily). Ten days later, analysis of CSF for antiviral antibody revealed anti-VZV IgM and IgG antibody but not anti–herpes simplex virus antibody. The serum to CSF ratio of anti-VZV IgM antibody was markedly reduced (4.6), as was the serum to CSF ratio of anti-VZV IgG antibody (3.6) compared with ratios for total IgG (344) and albumin (86), indicative of intrathecal synthesis of both anti-VZV IgM and anti-VZV IgG. Oral prednisone treatment was immediately reduced to 40 mg daily and tapered by 10 mg per week, and the patient received a 14-day course of intravenous acyclovir (10 mg/kg every 8 hours) followed by oral valacyclovir (1 g twice daily). Eight weeks after acute vision loss, the patient’s visual acuity had improved to 20/50. Oral valacyclovir was continued with planned close observation. The erythrocyte sedimentation rate was now 16 and C-reactive protein was 2.0. Subsequent immunohistochemistry on the temporal artery biopsy specimen revealed abundant VZV antigen in the adventitia () and lesser amounts in the media ().
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 (more ...)
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) (more ...)
Figure 3 Immunohistochemical analysis of the temporal artery as described in . 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 (more ...)