Giant-cell arteritis and polymyalgia rheumatica

Abstract

Giant-cell arteritis is an immune-mediated disease characterized by granulomatous infiltrates in the wall of medium-size and large arteries. The immunopathology consists of 2 components. Excessive cytokine production (for example, of interleukin-1 and interleukin-6) induces systemic inflammation with an exuberant acute-phase response. In parallel, interferon-gamma, which is released by T cells captured in the arterial wall, activates tissue-injurious macrophages. In response to the immune injury, the artery generates hyperplasia of the intima that leads to luminal occlusion and subsequent tissue ischemia. Despite the systemic character of the disease, distinct vascular territories are preferentially affected. On the basis of the predominant involvement, clinical subtypes can be distinguished: cranial giant-cell arteritis with ischemic complications in the eye, the face, and the central nervous system; large-vessel giant-cell arteritis with occlusions in the subclavian or axillary vessels; aortic giant-cell arteritis; giant-cell arteritis presenting as an intense systemic inflammatory syndrome with nonstenosing vasculitis; and "isolated" polymyalgia rheumatica with myalgias, systemic inflammation, and subclinical vasculitis. Temporal artery biopsy remains the diagnostic procedure of choice to detect arteritis in cranial vessels. In other vascular territories, giant-cell arteritis is most commonly diagnosed by vascular imaging. Laboratory studies characteristically document the marked elevations of nonspecific acute-phase reactants, such as C-reactive protein and erythrocyte sedimentation rate. Cytokines, such as interleukin-6, that induce the acute-phase reaction are currently being explored as more sensitive biological markers of disease activity. Corticosteroids are highly effective in suppressing systemic inflammation, but they do not eliminate the immune responses in the vessel wall. In general, the clinical outcome of giant-cell arteritis is excellent, and efforts must now concentrate on tailoring therapies to the needs of the individual patient.