Page 156 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

132 J. Charles Jennette, Ronald J. Falk and Adil. H. M. Gasim

All of the lesions observed in MPA can occur in patients with GPA and EGPA.
Thus, among patients with AAV, a diagnosis of MPA is a diagnosis of exclusion, once GPA
and EGPA are ruled out. Of course, in a clinical setting this is never unequivocal, because a
patient thought to have MPA may in fact have an occult focus of necrotizing granulomatosis.
This may not be a major problem because the presentation at that time may be primarily as
MPA, and if the GPA features become overt, the working diagnosis would change to GPA.

The histopathologic lesions of immune complex SVV can be indistinguishable from
those of AAV. For example, leukocytoclastic angiitis or vasculitis (LCV) (Figure 4B) in the
skin can be caused by any of the systemic variants of AAV including MPA, GPA, and EGPA,
as well as, most if not all forms of immune complex SVV, including but not limited to IgAV,
cryoglobulinemic vasculitis (CV) and serum sickness.

Light microscopy alone is not sufficient to identify the cause of LCV. Additional data are
required, such as serologic findings and tissue immunostaining.

GPA is defined as necrotizing granulomatous inflammation usually involving the upper
and lower respiratory tract, and necrotizing vasculitis affecting predominantly small to
medium vessels such as capillaries, venules, arterioles, arteries and veins [1]. Necrotizing
glomerulonephritis is common. The defining granulomatosis of GPA is a very destructive
lesion that in the acute phase resembles an abscess (Figure 7A) more than a typical
granuloma. In the acute phase, neutrophils predominate at the sites of granulomatosis, and a
few scattered multinucleated giant cells are the only histologic features justifying a
designation of granulomatosis.

However, as the lesions evolve, the neutrophils in the central zone of necrosis lyse and
are replaced by amorphous necrotic debris, and epithelioid macrophages form palisades that
wall of the zone of necrosis in a typical granulomatous pattern (Figure 7B).

EGPA is defined as eosinophil-rich and necrotizing granulomatous inflammation often
involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to
medium vessels, and associated with asthma and eosinophilia. ANCA is more frequent when
glomerulonephritis is present. The asthma the precedes EGPA typically is late onset, and
affected patients often have a prodromal phase of eosinophil rich inflammatory disease for
example eosinophilic pneumonia or eosinophilic gastroenteritis, prior to the onset of
definitive manifestations for vasculitis or glomerulonephritis [15]. Eosinophils are
conspicuous at sites of tissue inflammation, including sites of vasculitis (Figure 8).

However, similar prominence of eosinophils can be observed in lesion of MPA and GPA,
thus this is not diagnostic in the absence of the asthma and blood eosinophilia.

With sensitive clinical assays, 90% or more of patients with active untreated MPA and
GPA are ANCA positive, with PR3-ANCA more frequent in GPA and MPA in Europe and
North America [16].

However, <50% of patients with EGPA are positive for ANCA, almost always MPO-
ANCA [16]. Interestingly, more than 75% of EGPA patients with renal disease are ANCA-
positive compared to approximately 25% of EGPA patients with no clinical evidence for
kidney disease [17].

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