Increased frequency of HLA-DR3 and DR4 in polymyalgia rheumatica-giant cell arteritis.
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Biomedical subjects
Publications and source records attributed to M B Lowenstein.
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We studied sera from 20 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA), 15 patients with systemic lupus erythematosus (SLE), 15 patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangietasia) and 33 age and sex matched controls for cytotoxicity against human endothelial cells using a 51Cr release assay. We observed increased levels of endothelial cytotoxic activity in the PMR/GCA sera compared with controls (P less than 0.001). This cytotoxicity was predominantly found in the GCA group, where 7 out of 10 patients (70%) demonstrated significant cytotoxicity. Sequential studies showed that the cytotoxic activity returned to normal when the disease was under control. Although 7 SLE and 3 CREST sera had significant cytotoxic activity, as a group they did not differ from controls (P less than 0.05). Pre-incubation with soybean trypsin inhibitor suppressed the cytotoxic activity in the positive sera suggesting the cytotoxicity is mediated via a protease mechanism. Our results demonstrate the presence of a cytotoxic factor in the serum of patients with PMR/GCA which may play an important role in the pathogenesis of the vascular lesions observed in these disorders.
An ovoid density was demonstrated by arthrography in the infrapatellar fat pad region of seven patients. In three patients, the density appeared demarcated from the fat pad, and arthrotomy in two of them disclosed a localized pigmented villonodular synovitis. In four patients the density appeared contiguous with the fat pad, and in two of these patients no infrapatellar abnormality was observed at arthrotomy. This arthrographic distinction may provide more specific criteria for the preoperative diagnosis of localized, infrapatellar pigmented villonodular synovitis and thereby prevent overdiagnosis.
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Immunofluorescent microscopy was performed on the clinically normal skin of 3 patients with infective endocarditis, 3 patients with bacteremia, and 6 normal subjects. Perivascular deposition of immunoglobulin and complement was demonstrated in two of the three patients with infective endocarditis and in none of the bacteremic or control subjects.
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The clinical history, deposition of IgG, IgM, IgA, C3, C4 and properdin at the dermal-epidermal junction (DEJ) of clinically normal skin, serum ANA, DNA-binding, C3, C4, Factor B, and properdin were compared in 27 systemic lupus erythematosus (SLE) probands, 21 first-degree household contact relatives (FDHCR), 19 first-degree nonhousehold contact relatives (FDNHCR), 15 spouses, 26 controls, and 16 chronic discoid lungs lupus erythematosus patients. Female consanguineous relatives of SLE patients had a higher incidence of rheumatic symptoms than male relatives (P less than 0.01). Female FDHCR and male spouses had a higher incidence of protein deposition at the DEJ than sex-matched controls (P = 0.026 and 0.0028). The incidence of protein deposition at the DEJ in FDNHCR did not differ from sex-matched controls. ANA titers of the consanguineous relatives were significantly higher than those of the spouses or sex-matched controls irrespective of household contact with their proband. The observation of protein deposition at the DEJ in normal appearing skin of FDHCR and spouses suggests the importance of environmental factors, whereas the elevations of ANA titers in consanguineous relatives suggests the importance of genetic factors in the pathogenesis of SLE.
In 182 patients with systemic lupus erythematosus (SLE), oral mucosal ulceration occurred in 47 patients (26%), was usually painless (82%), and most often involved the hard palate (89%). Oral ulceration was associated with an increase in overall clinical activity, although this was not accompanied by significant changes in the levels or titers of C3, anti-DNA antibodies, and anti-nuclear antibodies. Necrotizing vasculitis was not observed. Microscopic changes were similar to the skin lesions of SLE and immunoglobulin and complement were found in both the basement membrane and blood vessel walls.