Pathogenic Mechanisms in Systemic Vasculitis

The study of systemic vasculitis until now has consisted of clinical descriptive reports, disease associations, and the study of related immune complex mechanisms. Clinical features, the distribution of involvement, and certain disease associations have allowed a rough classification and some understanding. Whether or not this type of categorization has any bearing on etiology remains to be seen. Disease associations may provide some insight into pathogenic mechanisms. "Polyarteritis nodosa" is the term used to describe a pattern of disease of small and medium-sized arteries, which can affect many organs. This pattern of disease can be associated and presumably caused by hepatitis B surface antigen. This association accounts for only a small number of patients with polyarteritis. Hepatitis B surface antigen may be associated with other patterns of disease, including localized cutaneous vasculitis, localized glomerulonephritis, and mixed cryoglobulinemia. In these situations, the vasculitis is due to deposition of hepatitis B surface antigen and antibody complexes. The rare association of polyarteritis complicating hairy cell leukemia may provide a clue to other pathogenic mechanisms. Hairy cells are present in the involved vascular lesion and may contribute to the pathologic process. It is known that patients with hairy cell leukemia may make antibodies directed to certain determinates on the hairy cells, which cross-react with endothelial cells. It is possible that the vasculitis is due to these cross-reacting antibodies reacting with endothelial cells. Human T-cell leukemia virus-II (HTLV-II) has been found in two cases of hairy cell leukemia with involvement of T cells. It is possible that this retrovirus affects endothelial cells and could be responsible for the vasculitis. Vasculitic syndromes may be caused by other viruses. Viruses that have been shown to be associated with vasculitis are cytomegaloinclusion virus, HTLVI, human parvovirus, and herpes zoster. The vasculitis may be due to a direct attack on the vessel wall by the virus, or the vasculitis may be due to deposition of immune complexes triggered by the virus. In the rare disease of localized granulomatous vasculitis of the central nervous system, the vasculitis occasionally follows herpes zoster ophthalmicus. In such cases the herpes virus has been found in the involved cerebral arteries. A vasculitic neuropathy may accompany Lyme disease. The vasculitis in this situation may be due to direct invasion of the arterial wall by the Borrelia or due to deposition by induced immune complexes. The one mechanism that has been most commonly discussed and studied in the vasculitides is the immune complex mechanism of disease. Immune deposits may be found in involved tissue by immunopathologic techniques and by electron microscopy. Immune complexes may be detected in sera by a variety of immune complex assays. The problem with the immune complex assays is that they are too sensitive and may detect abnormalities in a wide variety of inflammatory, infectious, and malignant states. They may detect substances besides immune complexes. Many of the immune complex assays, particularly the Clq assay and the monoclonal immunoglobulin M assay, may detect just aggregates of the immunoglobulins. Consequently, most investigators require more than the presence of circulating immune complexes to substantiate immune complex disease. There are indirect indicators of ongoing immune complex disease. A diminished serum complement or a diminished C3 or C4 indicate complement activation, presumably as a result of immune complexes.