VasculitisPATHOLOGY

• Characterised by Inflammation and damage to blood vessels.

• Vessel lumen is usually compromised .• Leads to ishemia of the tissues supplied.

• It may involve a single organ(skin) or it may involve multiple organs.

Vasculitis

Vasculitis may be primary-I. The primary vasculitis syndromes.

It may be secondary to1. Infections(Rickettsia, Neisseria,Syphilis,

Varicella)2. Other Autoimmune diseases(SLE, Rheum.

Arthritis)

3. Malignancy

Immune complex formation and/or deposition

Anti Neutrophil Cytoplasmic Antibodies production.(ANCA)

T lymphocyte activation with granuloma formation

Direct Antibody mediated.

Potential mechanisms

Immune complexes get deposited in vessel wall

Activation of Complement components (C5a which is strongly chemotactic for neutrophils)

Neutrophils phagocytose immune complexes and release their intracytoplasmic enzymes that damage the vessel wall.

As the process becomes sub acute or chronic, mononuclear cells infiltrate the vessel wall.

Immune complex mediated

Many patients with active vasculitis do not have demonstrable circulating or deposited immune complexes

The Antigens present in the complexes are rarely identified.

Exeptions are most cases of PAN (hepatitis B antigen) and Cryoglobulinemic vasculitis (Hepatitis C antigen)

So the causal role of immune complexes has not been established in most of the vasculitis syndromes.

BUT….

Henoch Shonlein purpura. Polyarteritis Nodosa( Hepatitis B Ag-Ab) Collagen vascular diseases(SLE,

Rheumatoid Arthrits) Cryoglobulinemic vasculitis.(Hepatitis C

Ag-Ab) Serum sickness.

Antibodies against certain protiens in the cytoplasmic granules of neutrophils and monocytes are present in the serum of certain patients with vasculitis.

These are the ANCA associated vasculitis syndromes.

cANCA is directed against cytoplasmic protienase 3

p ANCA is directed against perinuclear myeloperoxidase.

ANCA

Either ANCA may be present in any of the ANCA associated vasculitides.

c ANCA is typically seen in Wegners granulamatosis with polyangitis(90%)

p ANCA is seen in most cases of Microscopic polyangitis and

Churg Strauss Syndrome.

Patients may have Wegners granulamatosis with polyangitis in the absence of ANCA

Titer of antibodies does not correlate with disease severity.

Patients who are in remission from Wegners may continue to have high cANCA titers.

Thus the role of these auto antibodies in pathogenesis of systemic vasculitis remains unclear.

BUT….

Endothelial cells may express HLA II molecules at their surface similar to antigen presenting cells. ( following activation by cytokines)

CD4+ T cells get activated following interaction with these endothelial cells.

Propogation of immunological processes resulting in cell mediated injury, granuloma formation, delayed hypersensitivity.

T lymphocyte mediated

Giant Cell (Temporal)Artritis Takayashus Arteritis Wegners Granulamatosis Churg- Strauss Syndrome.

In Kawasaki disease (Mucocutaneous Lymph Node syndrome), 25% cases are associated with coronary artery aneurism.

Vasculitis of the coronary arteries are found in virtually all cases that had been autopsied.

Anti- Endothelial Cell antibodies are believed to play the central role.

Antibody Mediated

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