Giant cell arteritis. Epidemiology, etiology and pathogenesis.

Abstract

Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting large and medium-sized arteries, which predominantly affects postmenopausal women. Its high incidence in populations with Scandinavian lineage, some familial accumulation, and the association with the HLA-DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symptomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research indicates an antigen-driven disease with local T-cell and macrophage activation in the vessel wall. Morphologically, the inflammatory process appears to be initiated by a foreign-body giant-cell attack on calcified internal elastic membrane in arteries and on calcified atrophic parts of the aortic media. The ensuing diffuse chronic inflammation leads to vessel dilatation and extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis and ischemic complications. The possible role of female sex hormones in GCA requires further investigation. Mononuclear and giant cells in GCA display the cytoplasmic accumulation of estrogen receptor (ER) alpha. Cytoplasmic ER-alpha is also seen in media smooth-muscle cells in GCA and in non-GCA controls, but nucleotide sequence analysis of the ER-alpha gene revealed no differences between GCA patients and controls. In the future, comprehensive morphological, cell biological and immunological research will be required for a better understanding of the complex etiology and pathogenesis of GCA.