Page 289 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Systemic Vasculitis and the Kidney 263

to be less common in patients with GPA in Japan than in the UK. AAV is also recognized in
China [4] and India [5], as well as regions of the Middle East [6], but there are no data
regarding incidence and prevalence in these areas. There are rare case reports of AAV from
Africa [7]. It is important to note that while PAN, a medium-vessel vasculitis, is not classified
as an AAV; it has historically been included in most of these data. Collectively, there is
believed to be an overall incidence of approximately 10 to 20 cases per million individuals
annually in Caucasian patients of European descent [8].

Strikingly, multiple examples exist of differences in incidence of AAV that appear to be
dependent upon geographic milieu. For example, in northern Saskatchewan, Canada, a 2.69
odds ratio (OR) of developing AAV was reported in a rural versus urban setting [9]. A study
from the Australian Capital Territory of New South Wales found the annual incidence of
MPA to be significantly higher in rural versus urban areas (13.9 vs 1.6 cases per million
individuals), with a similar trend seen in the incidence of GPA [10].

There are also multiple reports that demonstrate differences in incidence relative to
latitude. A north-to-south positive gradient was observed in the Southern Hemisphere, and a
south-to-north positive gradient is seen in the Northern Hemisphere. In other words, incidence
of AAV appears to correlate with latitudinal equatorial proximity. This association was
apparent in one study from New Zealand [2], located in the Southern Hemisphere, where an
increase in incidence of GPA was noted moving from north to south. A second study
comparing incidence of AAV in two regions of Europe, including Norwich, UK, latitude
52°N; and Lugo, Spain, 43°N, both in the Northern Hemisphere, found a higher incidence of
GPA in Norwich, the more northerly latitude, than in Lugo, even though the overall incidence
of AAV was nearly identical [11]. Interestingly, no such difference has been noted in MPA or
EGPA. Similar observations regarding incidence relative to latitude have been reported
elsewhere [12]. The average age of disease-onset varies somewhat within populations, but
occurs predominantly in the sixth and seventh decades of life. The relationship of disease to
this demographic may be somewhat skewed since, when evaluated retrospectively, a number
of patients arguably hade evidence of disease years prior to diagnosis. Diagnostic delays are
well-substantiated in the literature [13, 14]. Furthermore, most studies of disease do not
include pediatric patients, and it is important to remain cognizant that AAV can occur at any
age [15, 16].

Pathogenesis

Since the initial discovery of AAV and glomerulonephritis [17], incredible strides have
been made in understanding the etiology and pathogenesis of these diseases. It is well known
that ANCA are pathogenic antibodies that cause disease through an ability to activate
neutrophils and monocytes prematurely within small vessels [18]. Rather than describe this
entire body of investigation, this chapter will henceforth focus on highlighting notable
findings of late that represent key breakthroughs in the field in humans.

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