Varicella zoster virus triggers the immunopathology of giant cell arteritis

Abstract

Purpose of review: Giant cell arteritis (GCA) is a severe form of vasculitis in the elderly. The recent discovery of varicella zoster virus (VZV) in the temporal arteries and adjacent skeletal muscle of patients with GCA, and the rationale and strategy for antiviral and corticosteroid treatment for GCA are reviewed.

Recent findings: The clinical features of GCA include excruciating headache/head pain, often with scalp tenderness, a nodular temporal arteries and decreased temporal artery pulsations. Jaw claudication, night sweats, fever, malaise, and a history of polymyalgia rheumatica (aching and stiffness of large muscles primarily in the shoulder girdle, upper back, and pelvis without objective signs of weakness) are common. ESR and CRP are usually elevated. Diagnosis is confirmed by temporal artery biopsy which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. This review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA, but whose temporal artery biopsies (Bx) are pathologically negative for GCA (Bx-negative GCA). Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, mostly in skip areas that correlate with adjacent GCA pathology.

Summary: The presence of VZV in Bx-positive and Bx-negative GCA temporal arteries indicates that VZV triggers the immunopathology of GCA. However, the presence of VZV in about 20% of temporal artery biopsies from non-GCA postmortem controls also suggests that VZV alone is not sufficient to produce disease. Treatment trials should be performed to determine if antiviral agents confer additional benefits to corticosteroids in both Bx-positive and Bx-negative GCA patients. These studies should also examine whether oral antiviral agents and corticosteroids are as effective as intravenous acyclovir and corticosteroids. Appropriate dosage and duration of treatment also remain to be determined.

FIGURE 1

Varicella zoster virus (VZV) antigen in giant cell arteritis (GCA)-positive and GCA-Bx-negative temporal arteries (TAs). Immunohistochemical analysis with mouse anti-VZV gE IgG1 antibody shows VZV antigen in the adventitia of a GCA-positive TA (A) and in the adventitia, media and intima of a GCA-Bx-negative TA (B). No staining was seen when mouse anti-IgG1 isotype control antibody was substituted for the primary antibody (C & D). Magnification 600×.

FIGURE 2

Varicella zoster virus (VZV) antigen in pathologically verified granulomatous aortitis. Immunostaining with a monoclonal mouse anti-VZV gE IgG1 antibody revealed VZV antigen in the adventitia of an aorta from a patient with pathologically verified granulomatous aortitis (A, pink color). No staining was seen when mouse IgG1 isotype control antibody was substituted for the primary anti-VZV antibody (B). Hematoxylin and eosin staining of another aorta that contained VZV antigen showed classic granulomatous aortitis pathology: inflammation in the adventitia and media with medial necrosis (C) and giant cells (C, arrow & inset). Magnification 600× (A and B) and 100× (C).