ANCA disease: pathology (PPT / 13136.5 KB)

ANCA disease: pathology Dušan Ferluga Institute of Pathology, Faculty of Medicine, University of Ljubljana Ljubljana, Slovenia

Systemic vasculitides International Consensus Conference, Chapel Hill, USA, 1993 (proposal in Arthritis&Rheumatism 1994, 37: 187-192) - Terminology (names of diseases = diagnostic terms) - Definition of diseases (abnormalities that warrant assignement of the diagnostic terms) - Diagnostic criteria? (not yet defined)

Small vessel vasculitides • Frequent affection of kidneys (up to 100%) Glomerulonephritis, extraglomerular vasculitis, tubulointerstitial involvement • Important contribution of kidney biopsy to establish diagnosis and to evaluate activity, chronicity and severity (extent) • Final diagnosis clinical (immunoserology!)pathological

Necrotizing crescentic glomerulonephritis (NC-GN) • Focal (50%) • Isolated (primary), in systemic vasculitides, in autoimmune connective tissuee diseases • Immunopathogenetic categories: 1. Immune complex NC-GN 2. Anti-GBM NC-GN 3. Pauci-immune ANCA NC-GN

98/285 – 34,4% 40/285 – 14,0% 147/285 – 51,6%

Significance of kidney biopsy in ANCA disease To confirm diagnosis - why? ANCA specificity and sensitivity are not absolute. Not all ANCA positive patients have ANCA vasculitis and ANCA negative results do not exclude ANCA disease.

Histopathologic hallmarks of ANCA glomerulonephritis / vasculitis • Pauci-immune pattern by immunofluorescence • Fibrinoid necrosis • Extracapillary crescents without significant glomerular proliferation • Residual scarring glomerulosclerosis (segmental, global)

CD68

Clinico-pathologic diagnosis in 135 patients with ANCA renal disease PR3-ANCA

MPO-ANCA

(n=55)

(n=74)

Other ANCA antigens (n=6)

Wegener’s granulomatosis

47/56

8/56

1/56

Microscopic polyangiitis

6/50

42/50

2/50

Renal limited vasculitis

2/28

23/28

3/28

Churg Strauss syndrome

0/1

1/1

0/1

Diagnosis

Significance of kidney biopsy in differential diagnosis of ANCA vasculitides • Underdiagnosed extraglomerular focal necrotizing vasculitis (5 - 35%), suggesting systemic vasculitides, because of biopsy sampling inspite of serial sections • Limited significance of kidney biopsy in distinguishing between MPA, WG and CS (limited specificities of eosinophilic infiltration, absence of true interstitial geographic type granulomas as typically seen in respiratory tract)

Renal histologic changes in 135 patients with ANCA-associated GN PR3-ANCA

MPO-ANCA

(n=55)

(n=74)

Other ANCA antigens (n=6)

GN focal - diffuse

31 - 24*

18 - 56*

4-2

Glom necrosis Glom exud react Crescents Glob GSCL

1.8 ± 1.3* 1.2 ± 1.2 38.5% 11.5%*

1.3 ± 1.2* 0.8 ± 0.9 43.6% 24.0%*

0.8 ± 0.9 0.5 ± 0.8 37.5% 17.7%

7.0%*

13.9%*

4.2%

1.3 ± 1.1*

2.2 ± 1.2*

2.2 ± 1.0

Histologic changes

Seg GSCL Interst fibrosis •P