Giant cell arteritis - Epidemiology, etiology and pathogenesis

Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting lar ge and medium-sized arteries, which predominantly affects postmenopausal wo men. Its high incidence in populations with Scandinavian lineage, some fami lial accumulation, and the association with the HLA-DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symp tomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research i ndicates an antigen-driven disease with local T-cell and macrophage activat ion in the vessel wall. Morphologically, the inflammatory process appears t o be initiated by a foreign-body giant-cell attack on calcified internal el astic membrane in arteries and on calcified atrophic parts of the aortic me dia. The ensuing diffuse chronic inflammation leads to vessel dilatation an d extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis a nd 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) a. Cytoplasmic ER-a is also seen in media smooth-muscle cells in GCA and in non-GCA controls, b ut nucleotide sequence analysis of the ER alpha gene revealed no difference s between GCA patients and controls. In the future, comprehensive morpholog ical, cell biological and immunological research will be required for a bet ter understanding of the complex etiology and pathogenesis of GCA.