**4. Environmental factors**

6] The prevalence of aortic inflammation, in unselected patients with GCA, has not been fully estimated, although in a systematic necropsy study of 13 patients, large artery involvement was demonstrated in over 90% of them. [7] In more recent studies, an increased prevalence of aortic aneurysm (compared to the general population), was observed in GCA patients. [8]

Retrospective surveys, over extended time periods (20-50 years), confirmed that aortic aneurysm occurs in 9.5-22.5% of these patients and, particularly, in the first 5 years of follow up. [9, 10] These findings indicate that large vessel involvement in GCA may be more frequent than anticipated. Based on these data, a recent prospective study from Prieto-Gonzalez et al, using non-invasive techniques (CT angiography), concluded that large vessel vasculitis occurs in two thirds of patients with GCA, while aortic dilatation is already present in 15% of them

Large vessel involvement represents a significant cause of death in GCA and it may be asymptomatic and lead to aortic dissection and/or rupture. [12] These findings underline the importance of elucidating the pathophysiologic basis of the disease, in which the immune

In this chapter, a thorough review of the current evidence for disease immunopathophysiol‐

In accordance with the pathophysiology of many immune-mediated diseases, GCA is believed to represent the final result of the complex interactions between three distinct factors, namely the host (by means of the individual genetic background), the environment (pathogens, physicochemical exposures etc.) and the unique immune system response. However, the exact

Several studies have demonstrated that GCA is a complex disease, where multiple genes confer susceptibility. In most surveys, the allele HLA-DRB1\*04 has been shown to be related to disease and its severity. [13] More recent studies have implied the role of genetic variants in the evolution of the immune and inflammatory pathways in GCA and its clinical expression. Polymorphisms include the rs20541 (R130Q) polymorphism of the IL-13 gene [14], the rs2779251 in the NOS2 gene, the rs1885657 and the rs2010963 in the VEGF gene [15] and, also,

ogy, in regard to disease phenotype and response to treatment, is presented.

at the time of diagnosis. [11]

system seems to play a central role.

94 Updates in the Diagnosis and Treatment of Vasculitis

**2. The pathophysiologic basis of GCA**

etiology of the disease remains unknown.

**3. Genetic predisposition**

the TLR-4 (+896A/G) gene. [16]

Several experimental studies, using DNA analysis, have shown a possible relation of GCA with certain infectious agents, such as the human papilloma virus (HPV) [17], *Chlamydia spp,* herpes viruses and PARVO B19 among others. [18] Older epidemiological studies have also demonstrated that increased incidence of GCA was observed in close relation to two inde‐ pendent epidemics of *Mycoplasma pneumoniae* infection. [19] However, not all studies con‐ firmed these associations and GCA initiation is not definitely considered to be triggered by infectious agents. [20]
