Multifocal VZV vasculopathy with temporal artery infection mimics giant cell arteritis

Abstract

Objective: To address the incidence of varicella-zoster virus (VZV) infection in patients with biopsy-negative giant cell arteritis (GCA), we examined archived biopsy-negative temporal arteries from subjects with clinically suspected GCA for the presence of VZV antigen.

Methods: Formalin-fixed, paraffin-embedded temporal arteries that were pathologically negative for GCA and normal temporal arteries were analyzed immunohistochemically for VZV and herpes simplex virus-1 (HSV-1) antigen.

Results: Five (21%) of 24 temporal arteries from patients who were clinically suspect but biopsy negative for GCA revealed VZV but not HSV-1 by immunohistochemical analysis. Thirteen normal temporal arteries did not contain VZV or HSV-1 antigen. All 5 subjects whose temporal arteries contained VZV antigen presented with clinical and laboratory features of GCA and early visual disturbances.

Conclusion: Multifocal VZV vasculopathy can present with the full spectrum of clinical features and laboratory abnormalities characteristically seen in GCA.

Figure 1. VZV antigen in biopsy-negative temporal arteries from subjects with clinically suspected GCA

Positive control VZV-infected cadaveric human cerebral artery (A, arrows) shows VZV antigen (pink color). Five (21%) of 24 subjects with suspected GCA, but whose temporal arteries were pathologically GCA negative, contained VZV antigen. Subjects 1 and 2 had VZV antigen exclusively in the adventitia (C and F, respectively, arrows). Subject 3 had VZV antigen exclusively in the media (I, arrows). Subject 4 had VZV antigen in the media (L, thick arrow) and in the intima (L, arrowhead) adjacent to the internal elastic lamina (L, thin arrow). Subject 5 had VZV antigen exclusively in the media (O, thick arrow) adjacent to the internal elastic lamina (O, thin arrow). HSV-1 antigen was present in the positive control HSV-1–infected cadaveric cerebral artery (B, arrows), but not in any human temporal arteries, including those that contained VZV antigen (D, G, J, M, and P). No staining was seen when NRS was used as primary antibody on temporal arteries (E, H, K, N, and Q). None of 13 temporal arteries from 7 normal subjects contained VZV antigen (data not shown). Original magnification ×600. GCA = giant cell arteritis; HSV-1 = herpes simplex virus-1; NRS = normal rabbit serum; VZV = varicella-zoster virus.

Figure 2. Multiple areas of VZV antigen in a biopsy-negative temporal artery of a subject with clinically suspected giant cell arteritis

In a temporal artery that was found to contain VZV antigen, 95 consecutive 5-μm sections from that artery were further stained to determine how many sections contained VZV antigen. Arrows show 4 positive areas along a 500-μm length of temporal artery at position 20, 160, 250, and 480 μm (A–D, respectively). Original magnification ×600. VZV = varicella-zoster virus.