Inflammation of the walls of vessels called vasculitis, is encountered in diverse disease and clinical settings. Vessels of any type in virtually any organ can be affected; this leads to a wide spectrum of clinical manifestations, which often includes constitutional signs and syumptoms , such as fever, myalgias, artralgias, and malaise. The two most common mechanisms of vasculitis are immune-mediated inflammation and direct invasion of vascular walls by infectious pathogens. Infections can directly induce a noninfectious vasculitis , for example by generating immune complexes or triggering cross-reactivity. In a particular patient, it is critical to distinguish between directly infectious and immunologic mechanisms because the treatment approaches differ widely for example the immunosuppressive therapy appropriate for immune mediated vasculitis would be potentially harmful for infectious vasculitis. Physical and chemical injury, such as irradiation , mechanical trauma and toxins, can also cause vascular damage. In such cases one or a relatively few vessels may be affected, as for example in a localized area of infection , irradiation, or mechanical trauma.

Most noninfectious vasculitides appear to be initiated by one of several immunologic mechanisms. Such process often induce relatively distinctive clinicopathologic entities, in which the vasculitis is widespread. Of these so called systemic necrotizing vasculitides, several types affect the aorta and medium sized vessels; most affect vessels smaller than arteries, such arterioles, venules and capillaries

Immune Complexes

The evidence for involvement of immune complexes in vasculitides can be summarized as follows:

The vascular lesions resumble those found in experimental immune complex- mediated conditions, such as the local Arthus phenomenon and serum sickness. Immune reactants and complement can be detected in the serum or vessels of patients with vasculitis. For example, DNA anti DNA complexes are present in the vascular lesions of systemic lupus erythematosus associated vasculitis; Igg IgM and complement in cryoglobulinemic vasculitis and a number of other antigens in isloated cases.

Hypersensitivity to drugs causes approximaately 10% of vasculitic skin lesions. Some such as penicilin conjugate serum proteins, whereas others such as streptokinase are foreign proteins; both can lead to vascular deposits of immune complexes.

The most impressive evidence comes from vasculitis associated with viral infections particularly hepatitis. There is a high incidence of hapatitis B antigen and HbsAg immune complexes in the serum and with complement in the vascular lesions of some patients with vasculitis particularly those with large vessel polyarteritis nodosa dn less commonly in those with membranous or membrano proliferative glomerulonephritis or leukocytoclastic vasculitis. Improtantly, immunosuppressive treatment results in a remission of the vasculitis. Importantly, immunosuppressive treatment results in a remission of the vasculitis but perpetuates the hepatitis B virus infection. Chronic hepatitis C virus infection leads to glomerulonephritis in which HCV/RNA and cryoprecipitates containing anti- HCV antibodies are detected in glomeruli.

Whether complexes accrue in vessel walls by deposition from the circulation by in situ formation or by a combination of these mechanisms is not known. Moreover many small vessel vasculitides show a paucity of vascular immune deposits and therefore other mechanisms have been sought for these co called pauci immune vasculitides.

Antineutrophil Cytoplasmic Antibodies

Serum from many patients with vasculitis in small vessels reacts with cytoplasmic antigens in neutrophils indicating the presence of antineutrophil cytoplasmic autoantibodies ANCA comprise a heterogeneous group of autoantibodies against enzymes mainly found within the azurophil or primary granules in neutrophils but also found in the lysosomes of monocytes and in endothelial cells. ANCA can be detected in serum by immunoflurscent microscopy of ethanol fixed neutrophils and by immunochemical assays.

Classification

The systemic vasculitides are classified on the basis of the size of the involved blood vessels the anatomic site and histologic characteristics of the lesion and the clinical manifestations. There is considerable clinical and pathologic overlap among these disorders. The nomenclature used here is that developed at the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitides and sequence of entities