Systemic Vasculitis

Definition
A heterogeneous group of disorders linked by
the primary finding of inflammation within
blood vessel walls
Mimics of vasculitis should be excluded
 Components of a vasculitis diagnosis
1. Compatible clinical phenotype
2. Exclusion of mimics and secondary causes
3. Supported by specific serology (e.g. ANCA) or
radiology (e.g. angiography)
4. Confirmation by tissue biopsy
Type of vessels
Considerations in the Classifications of
Systemic Vasculitis
Size of predominant blood vessels affected
Pathologic features
Granulomatous inflammation
Immune complex deposition versus pauci-immune
histopathology
Linear staining along glomerular basement
membrane
Presence of antibodies : ANCA, anti-GBM Ab,
RF in serum
 ANCA-associated Small-vessel
vasculitis
Small-vessel vasculitis is defined as vasculitis
that affects vessels smaller than arteries

1. Microscopic polyagiitis
2. Granulomatosis with polyangiitis (Wegeners
granulomatosis)
3. Eosinophilic granulomatosis with polyangiitis
(Churg Strauss syndrome)
 What are ANCA?
Specific antibodies for antigens in cytoplasmic
granules of neutrophils and monocyte
lysosomes
 What are ANCA?
ANCAs were originally described based on their
immunofluorescence patterns
cytoplasmic (c-ANCA) and perinuclear (p-ANCA)

The antigens responsible for these patterns have also

been identified
proteinase 3 (PR3) for c-ANCA
myeloperoxidase (MPO) for p-ANCA
 Diagnosis of Small-Vessel Vasculitis
1. Is small-vessel vasculitis present?
2. Which specific type of small-vessel vasculitis
is present?
Is small-vessel vasculitis present?
Which specific type of small-vessel
vasculitis is present?
 Wegeners granulomatosis
Prevalence: 3 per 100.000
Age of onset: 40 years
Primary vasculitis syndrome damage of vessels
Immunopathogenic mechanisms
ANCA= antineutrophil cytoplasmic antibody
c-ANCA= cytoplasmic ANCA
(diffuse, granular cytoplasmic staining by
immunofluorescence microscopy)
Granuloma formation
 Clinical manifestations
ACR classification criteria for granulomatosis with polyangiitis
 Investigations
CBC, ESR/CRP, Cr, UA,CXR
ANCA: c-ANCA, anti PR-3
Tissue biopsy: granulomatous necrotizing
vasculitis
 Microscopic polyangiitis (MPA)
Average age at onset 50 years
M>F
Necrotizing vasculitis and granuloma is not
present
p-ANCA, anti MPO
 Eosinophilic granulomatosis with
polyangiitis (EGPA)
M = F , mean age 50 years
Asthma (esp. late onset, refractory)
Eosinophilia > 10%
Mono/polyneuropathy
Migratory/transient pulmonary opacities on
radiography
Paranasal abnormality: sinusitis, nasal polyp, rhinitis
Biopsy containing a blood vessel show eosinophils in
extravascular area
Skin : purpura, nodule, urticaria, ulcer
ANCA : pANCA > cANCA
 GPA and MPA treatment
Induction phase Maintenance of remission
High dose GC > 24 months
Plus
Cyclophosphamide or/and
Azathioprine (2 mg/kg/day)
Plasma exchange (may be Methotrexate (20-25
considered in patients with mg/wk) ( Cr < 1.5 mg/dL)
rapidly progressive renal
disease Leflunomide (20-30
or/and mg/day)
Rituximab
Methotrexate + high dose GC,
in nonorgan-threatening or
non life-threatening
 EGPA : treatment
Corticosteroid
Intra-nasal steroid , bronchodilator
Cyclophosphamide in fulminant/multisystem
cases