Page 92 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

68 David S. Younger

granulomatosis with polyangiitis (GPA) with a prevalence rate of 98 per million inhabitants.
The prevalence rate of GCA doubled in northern Germany for those age 50 years or more
from 240 to 440 per million inhabitants between 1994 to 2006, and from 87 to 171 per
million population overall. There was both a difference in period prevalence and incidence
rates between the urban and rural areas, with an incidence of GCA of 27.1 /million/year in
urban Luebeck compared to 14.7/million/year in rural Segeberg (p=0.2), while respective
prevalence rates were 237 and 116 per million population overall, and 586 and 311 per
million inhabitants of age 50 year or more.

Differences in incidence between regional populations of the world may be explained in
part by immunogenetic and environmental factors that account for differences in
susceptibility and may contribute to severity and outcome [24].

In 1980 Kemp and coworkers [25] performed HLA tissue-type antigen determinations for
A-B, C-antigens in the sera of eighty-eight mixed cases of clinical GCA and polymyalgia
rheumatica (PMR) with an overwhelming representation of women and only sporadic familial
occurrence, demonstrating no significant deviation from a sample compared to 3164 blood
donor controls. In 1983, Armstrong and colleagues [26] studied fifty-five patients with GCA
and PMR, typed for HLA A, B, C and DR loci, noting a significantly increased frequency of
DR4, Cw3 and Cw6, with the rise in Cw3 possibly attributed to linkage disequilibrium to
DR4.

Among 128 DNA samples for 128 patients and 145 ethnically matched controls in a case-
control association study to determine whether those with patients with GCA and PMR
sample from Lugo in northwestern Spain exhibited identical HLA class II associations,
Dababneh and colleagues [27] found that the association of HLA-DRB 1*0401 and GCA
reached statistical significance in the total GCA group of patients, less so for DRG1*0101
and *0102. An association was also observed between the RA DRB1 shared epitope (SE) and
GCA that was primarily accounted for by the presence of a single copy of the SE, moreover a
SE-bearing allele of DRB1 was observed in those with jaw claudication and visual
manifestations. The genetic susceptibility to GCA was supported by reports of the
contribution of shared HLA class II gene polymorphisms in mannose-binding lectin variant
alleles by Jacobsen and coworkers [28]; in DR4 by Jacobson [28-30], Richardson [31], and
Barrier and colleagues [32]; in DR3 by Lowenstein and colleagues [33]; in DRB1 by
Martinez-Taboda [34], Weyland [35, 36] and Gonzalez-Gay and colleagues [37], Cw3 [38];
and in MHC class I MICA and HLA-B gene polymorphisms by Gonzalez-Gay [39].

Takayasu Disease

Background
In contrast to GCA, Takayasu arteritis (TAK) occurs in those <40 years of age and

presents with large vessel-sized vasculitis of the aorta and its branches. For the purpose of
epidemiological studies, the case definition has generally followed the ACR 1990 criteria for
the classification of TAK [40]. The evolution and characterization of pediatric-specific
vasculitis classification criteria and the associated clinical syndromes have been reviewed [41,
42]. An understanding of the inflammatory lesions in TAK, like that of GCA, has been
advanced by immunological studies, revealing a clearer understand of the pathophysiology,
which may be impacted by the genetic background of different global regions.

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