Diagnosis and management of polyarteritis nodosa.
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Biomedical subjects
Publications and source records attributed to D L Conn.
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Fifty-three patients with polyarteritis who were followed up for at least 2 years were defined clinically and studied retrospectively to determine the influence of clinical factors and treatment on the prognosis. There was a spectrum of severity of disease, and the 5-year survival in the group was 55%. A small number of patients had evidence of ongoing immune-complex disease, as indicated by the presence of cryoglobulins or hepatitis Bs antigen or by diminished serum complement. These markers were not associated with distinct clinical features and did not influence prognosis. Organ involvement that most adversely affected prognosis was that of the gut and the kidneys. Six of 8 patients with bowel infarction or serious gastrointestinal bleeding died, and 6 of 10 patients with renal insufficiency died. Hypertension and peripheral neuropathy did not influence the prognosis. Thirty-six patients were treated with corticosteroids alone and 14 with a combination of corticosteroids and cytotoxic agents (3 received no treatment); the outcome was the same in both groups. Twenty-two in the steroid-alone group and six in the combination group were alive when last seen. Early deaths were usually due to complications directly related to the vasculitis, and late deaths were often due to cerebrovascular or cardiovascular complications. At the last follow-up, 18 patients were in remission, and 13 had inactive vasculitic disease and were on maintenance treatment.
Glucocorticoids are potent anti-inflammatory agents that play an important role in the therapy of many patients with connective tissue diseases, including systemic lupus erythematosus, polymyalgia rheumatica, various types of vasculitis, and complications of rheumatoid arthritis. Glucocorticoids reduce the number and influence the function of lymphocytes, monocytes, and eosinophils in peripheral blood. Prolonged high doses of glucocorticoids result in decreased levels of immunoglobulins, particularly IgG. Granulocytes are increased in the peripheral blood, but their migration to sites of inflammation is diminished. Glucocorticoids inhibit release of lysosomal enzymes. Although they have no effect on the factor or factors that initiate inflammation, glucocorticoids have proved to be effective in the treatment of inflammatory manifestations of disease. Among significant adverse effects of glucocorticoid therapy are osteoporosis, aseptic necrosis of bone, and steroid myopathy.
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A retrospective review was undertaken to ascertain whether there are distinctive histopathologic features of the lymphoid neoplasms that occur in patients with previous connective tissue disease. Of 29 patients studied, 12 had malignant lymphoma with diffuse large-cell cytomorphology. Only 1 of these 12 had an immunoblastic cell type. The remaining 17 patients had neoplasia of a widely diverse nature. Six had lymphocytic lymphoma (one nodular poorly differentiated, three diffuse poorly differentiated, and three diffuse well differentiated), two had Hodgkin's disease, three had plasma cell myeloma, and six had chronic lymphocytic leukemia. Data fail to confirm a relationship between lymphoid proliferations with immunoblastic morphology and connective tissue diseases.
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In the three major morphologic groups of lupus nephritis--diffuse, focal proliferative, and membranous--glomerular deposition of immunoglobulins is usually a combination of IgG, IgM, and IgA and is not a good indicator of initial renal severity or outcome. In this study of 60 patients with systemic lupus erythematosus and nephritis, patients with exclusive or predominant glomerular deposition of IgG did not have more severe renal disease or a worse prognosis than those with combined IgG-IgM deposition.
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Rheumatoid arthritis (RA) was differentiated from systemic lupus erythematosus (SLE) by direct immunofluorescent techniques on skin specimens, using monospecific antisera for IgG, IgM, C3, C1q, properdin, and fibrin. Of 30 patients with RA studied, 20 had dermal vessel deposits of immunoglobulins and complement components in unaffected skin without the characteristic dermal-epidermal junctional fluorescence of SLE. Of 24 SLE patients studied, 24 had granular deposits of immunoglobulins and complement components in unaffected skin at the dermal-epidermal junction.
Five patients with Wegner's granulomatosis were found to have significantly raised serum immunoglobulin E (IgE) levels. The rise in IgE was not related to the extent of clinical involvement, was not part of a generalized serum immunoglobulin rise, and was not associated with eosinophilia. Raised serum IgE may be a clue to the pathogenesis of this disease.
Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.
Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.
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