Page 100 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

76 David S. Younger

Small-Size Vessel Vasculitis

ANCA-Associated Vasculitis

Background
The classification of the ANCA-associated vasculitides (AAV) has been controversial

[97] with existing systems developed by the ACR [98, 99], the CHCC [58] and the European
Medicines Agency algorithm [100] to provide a standardized method for their application in
epidemiological studies, each with separate deficiencies, especially when applied to
unselected patients. These systems were developed as classification criteria and not as
diagnostic criteria. As there were no validated diagnostic criteria for AAV, the Diagnostic and
Classification Criteria for Vasculitis Study (DCVAS), developed by Watts and colleagues
[100] led to the consensus development and validation of diagnostic criteria by an algorithm
to avoid inclusion of patients with other conditions. So defined, Watts and colleagues noted
an annual incidence of 11.3 for GPA and 5.9 per million for MPA, with respective prevalence
at the end of calendar year 2008 of 145.9 for GPA and 63.1 per million for MPA. Lyons and
colleagues [101] conducted a GWAS in a cohort of 1233 UK subjects with AAV and 5884
controls noting both MHC and non-MHC associations with AAV, with the strongest genetic
association with the antigenic specificity of ANCA, not with the clinical syndrome.

Those with anti–proteinase 3 (PR3) ANCA were associated with HLA-DP (rs3117242) at
the 6p21.32 chromosome locus, as well as those encoding ?1-antitrypsin (SERPINA1–
SERPINA11) (rs7151526) at the 14q32 chromosome locus and proteinase 3 (PRTN3)
(rs62132295) at the 19p13.3 chromosome locus, while anti–myeloperoxidase ANCA (MPO)
was associated with HLA-DQ (rs5000634) at the 6p21.32 chromosome locus. These studies
confirmed that the pathogenesis of AAV had a genetic component and that the genetic
distinction between GPA and MPA was associated with ANCA specificity.

Moreover, the response against the PR3 auto antigen was a central pathogenic feature of
PR3-AAV, distinct from MPO-AAV.

Epidemiology
The global incidence and prevalence is summarized in Table 6. Watts [65, 102], Ormerod

[103], Mohammad [104], and Mahr and colleagues [60] evaluated the epidemiological
aspects of AAV globally in adults. In two regions of Europe, Norwich, UK and Lugo, Spain,
the incidence rate of GPA in Norwich was 10.6 per million compared to that in Lugo of 4.9
per million for 2008 with virtually equal age distribution of 34.1 per million between age 45
and 74 years, suggesting that environmental factors might be important in the their
etiopathogenesis [65].

In a ten year study of primary systemic vasculitis in the UK [102] in the NHA from 1988
to 1997, the annual incidence of GPA was 9.7, EGPA 2.7, and MPA 8.0 per million during
the entire study period, however a comparison of the period from 1988 to 1992 with 1993 to
1997, showed respective annual incidences toward an increase in all conditions (8.7 for GPA,
1.5 for EGPA, and 6.8 for MPA, compared to 10.3 for GPA, 3.7 for EGPA, and 8.9 for
MPA).

Complimentary Contributor Copy