Page 326 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

300 Elana J. Bernstein and Robert F. Spiera

RA. In an incident RA cohort in Olmsted County, Minnesota, from 1955 to 1994 [12], the 10-
year cumulative incidence rate of severe RV, defined as major cutaneous vasculitis and
neuropathy due to vasculitis, remained stable by decade of RA diagnosis (2.1% for 1955-
1964, 3.5% for 1965-1974, 2.5% for 1975-1984, 4.3% for 1985-1994, p-value = 0.72).
However, looking at more recent data from Olmsted County, Minnesota [13] , the 10-year
cumulative incidence of RV decreased from 3.6% in the 1985-1994 RA cohort to 0.6% in the
1995-2007 RA cohort on (p = 0.011). In a retrospective study of the prevalence of RV among
US veterans [14], the prevalence of RV decreased significantly between 2000 and 2001 for
both inpatient and outpatient US veterans. The prevalence decreased by 31% (41/1000 RA
cases to 28/1000 RA cases, p < 0.003) among ambulatory US veterans and by 53% (32/1000
RA cases to 15/1000 RA cases, p < 0.001) among hospitalized US veterans. Moreover, an
extension of the Norwich Health Authority studies from 1988 to 1994 [10] to 2002 showed a
decline in the annual incidence rate of RV over the period 1988 to 2002 [15]. The annual
incidence rate of RV in 1988-1992 was 11.6 per million (95% CI 7.4-17.0); in 1993-1997 it
was 8.9 per million (95% CI 5.3 to 13.6); and in 1998-2002 it was 3.6 per million (95% CI
1.6 to 7.1) [15]. The overall annual incidence rate of RV during the time period 1988 to 2002
in the former Norwich Health Authority in the UK was 7.9 per million (95% CI 5.9 to 10.4)
[15]. Data from a population-based database of hospitalizations in California compiled by the
California Office of Statewide Health Planning and Development indicated that the risk of
hospitalization for RV was 33% lower in the period 1998 to 2001 than 1983 to 1987 (adjusted
rate ratio 0.67, 95% CI 0.61–0.74; p=value < 0.0001). Adjusting for age, sex, and ethnicity,
the rate decreased from 170 per 100,000 persons with RA in 1983 to 99 per 100,000 persons
with RA in 2001 [16].

Patients who develop RV typically have longer-standing RA, lasting 10 years or more
[17, 18]. In a retrospective study of 50 patients with RV, the mean duration or RA prior to the
onset of RV was 13.6 years [19]. Although women are more frequently affected by RA than
men [17], men with RA may be more likely to develop RV than women with RA [10, 18]. In
a population-based study of patients living within the Norwich Health Authority in the United
Kingdom from 1988 to 1994, the annual incidence rate of RV in men was 15.8 per million
(95% CI 9.5-24.7) compared to 9.4 per million (95% CI 4.8-16.4) in women [10]. Patients
with erosive, seropositive disease are also more likely to develop RV than those without
destructive disease who are seronegative [18, 20]. Moreover, the presence of certain other
extra-articular manifestations of RA, such as rheumatoid nodules and Felty syndrome, has
been associated with the development of RV [18, 20, 21]. Smoking is a major risk factor for
later development of both RA in general and RV in particular [22-24]. In a case-control study
of 45 RA patients with RV and 211 RA patients without RV, a significantly greater
percentage of RV patients were current smokers (p-value < 0.02) [23]. In a case-control study
of patients with severe RA with and without ExRA from the Mayo Clinic in Rochester,
Minnesota, and 3 RA cohorts in Sweden, smoking was an independent predictor of RV in a
multivariate model [24].

Genetic factors likely also contribute to the development of RV. In a meta-analysis of
individual patient data from 1,568 patients with RA (129 of whom had RV), patients with RV
were significantly more likely than RA patients without RV to have a "double dose" of the
shared epitope: HLA-DRB1*0401/*0401 (odds ratio [OR] 6.2, 95% CI 1.01–37.9),
*0401/*0404 (OR 4.1, 95% CI 1.1–16.2), and *0101/*0401 (OR 4.0, 95% CI 1.4–11.6) [25].
In a case-control study of 46 patients with RV and 178 RA without ExRA from the Mayo

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