Vasculitis

Vasculitis is a condition which involves the inflammation of the blood vessels. Vessels of any type and in any organ can be affected. Clinical manifestations include constitutional signs and symptoms like:
1) fever
2) myalgias
3) arthralgias
4) malaise
5) downstream tissue ischemia

Of these several systemic vasculitides, several affect the aorta and medium sized vessels, but most affect small vessels, such as arterioles, venules and capillaries (called small vessel vasculitis). Although some patients might have overlap between the vessels involved.

The two most common mechanisms of vasculitis are:
1) direct infection by pathogens
2) immune mediated mechanisms
But, it is important to know that pathogens can also induce an indirect vasculitis of the immune-mediated kind by formation of immune complexes or by causing cross-reactivity between pathogenic and self antigens. It is important to distinguish between both types of vascuilitis as immunosuppresive therapy is profitable in the immune-mediated type of vasculitis whereas, it can be potentially lethal in the infectious form of the disease. Physical and chemical injury such as irradiation, mechanical trauma and toxins can also cause vascular damage.

Pathogenesis of Noninfectious Vasculitis:
Three main mechanisms are reported to cause the immune-mediated type of vasculitis. These are:
1) immune complex deposition
2) antinuetrophil anitbodies
3) anti-endothelial cell antibodies

1) Immune complexes:
The evidence for involvement of immune complexes is as follows:
a) The lesions resemble those found in other immune-complex mediated reactions, eg: Arthus phenomenon and serum sickness. Immune reactants and complement can be detected in the patients with vasculitis (DNA anti-DNA complexes in SLE vasculitis)

b) Some drugs can cause Hypersensitivity reactions and are responsible for 10% of vasculitic lesions, mostly immune-complex deposits. The types can cary from small vessel involvement and leukocytoclastic vascultis to polyarteritis nodosa. Identification of this type is important as removal of the drug leads to rapid improvement in condition of the patient

c) Vasculitis associated with viral infections, immune complexes can be found in the serum and vascular lesions of some patients

2) Antineutrophil Cytoplasmic Antibodies:
Serum from many patients with vasculitis reacts with cytoplasmic antigens in neutrophils, indicating the presence of antineutrophil cytoplasmic antibodies (ANCAs). ANCAs are a heterogenous group of autoantibodies directed against enzymes mainly found within the aurophil or primary granules in neutrophils, in the lysosomes of monocytes and in Endothelial cells. Staining of these antibodies shows two types:
i - cytoplasmic or c-ANCA
ii - perinuclear or p-ANCA
c-ANCA is found in Wegener granulomatosis and p-ANCA in most cases of microscopic polyangiitis. These disorders are called ANCA-associated vasculitides.

These antibodies serve as good diagnostic markers for the conditions mentioned and their levels may reflect the extent of disease. Also the close association between these titers and disease activity suggest a role of ANCAs in the pathogenesis of vasculitic lesions. However, the exact mechanism and the role of ANCAs is not known.

3) Anti-Endothelial Cells Antibodies:
Antibodies to endothelial cells might be produced by a defect or abnormality in the immune response or might be generated in repsonse to molecular mimicry by certain pathogens. As a result these immunoglobulins predispose to certain vasculitides such as those associated with SLE and Kawasaki disease.

Some examples of different types of Vasculitis are as follows:
1) Large Vessel Vasculitis: Giant cell (temporal) arteritis; Takayasu arteritis
2) Medium Vessel Vasculitis: poly arteritis nodosa; Kawasaki disease
3) Small Vessel Vasculitis: Wegener granulomatosis; Churg-Strauss syndrome; microscopic Angiitis


Pathogenesis of Infectious Vasculitis:
Localized arteritis may be caused by a direct invasion of infectious agents, usually bacteria or fungi, especially Aspergillosis or mucormycosis. Lesions normally accompany bacterial pneumonia or occur alongwith tuberculous abscesses or in superficial cerebral vessels in cases of meningitis. Less common but other possible causes include hematogenous spread during septicemia or embolization from infective endocarditis.
Vascular infections may weaken or damage the arterial wall to result in a mycotic aneurysm. They might also induce thrombosis and infarction. For example, vasculitis of superficial brain vessels lead to thrombosis, with subsequent brain infarction and extension of subarachnoid infection to the brain.