Giant cell arteritis and polymyalgia rheumatica.
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Aged↗
Biomedical subjects
G G Hunder
Publications and source records attributed to G G Hunder.
The HLA-DRB1 locus as a genetic component in giant cell arteritis. Mapping of a disease-linked sequence motif to the antigen binding site of the HLA-DR molecule.
Giant cell arteritis (GCA) is a granulomatous vasculitis affecting persons over 50 years of age. The inflammatory infiltrate, which is targeted at the aorta and its proximal branches, includes activated CD4+ helper T cells, histiocytes, and giant cells. To investigate whether the genetic polymorphism of the HLA-DRB1 genes contributes to the local accumulation of activated T cells, we have analyzed both HLA-DRB1 alleles in a cohort of 42 patients with biopsy-proven GCA. The majority of patients (60%) expressed the B1*0401 or B1*0404/8 variant of the HLA-DR4 haplotype, both of which also represent the major genetic factors underlying the disease association in RA. GCA patients negative for the disease-linked HLA-DR4 alleles were characterized by a nonrandom distribution of HLA-DRB1 alleles. Sequence comparison among the allelic products identified in the GCA cohort demonstrated heterogeneity for the sequence polymorphism of the third hypervariable region (HVR), but homology for the polymorphic residues within the HVR2 of the HLA-DRB1 gene. The GCA patients shared a sequence motif spanning amino acid positions 28-31 of the HLA-DR beta 1 chain. In the structural model for HLA-DR molecules, this sequence motif can be mapped to the antigen-binding site of the HLA complex, suggesting a crucial role of antigen selection and presentation in GCA. In contrast, the sequence polymorphism linked to RA has been mapped to the HVR3 of the HLA-DRB1 gene and translates into a distinct domain of the HLA-DR molecule, the alpha-helical loop surrounding the antigen-binding groove. A consecutive case series study demonstrated that GCA and RA rarely co-occurred, supporting the interpretation that distinct functional domains of the HLA-DR molecule are implicated in the pathomechanisms of these two autoimmune diseases.
Age Factors↗
Hypersensitivity vasculitis and Henoch-Schönlein purpura: a comparison between the 2 disorders.
Leukocytoclastic vasculitis of small vessels and predominant involvement of the skin are common features of both hypersensitivity vasculitis (HV) and Henoch-Schönlein purpura. In a study comparing 93 patients with HV and 85 patients with Henoch-Schönlein purpura we found major differences with respect to frequencies and type of organ involvement (gastrointestinal tract, kidneys, skin and joints) which were present in both younger and older patients when analyzed separately. To investigate which clinical criteria best differentiate between these 2 vasculitides, 2 methodologies were employed. A rule requiring 3 or more criteria to be present from a list of 6 yielded 87.1% of correctly classified Henoch-Schönlein purpura cases; and 2 or fewer criteria from the same list of 6 correctly classified 74.2% of HV cases. A classification tree was associated with respective values of 83.5 and 84.9%. The results indicate that HV and Henoch-Schönlein purpura are similar but separable clinical syndromes.
Adolescent↗
Inducible release of an endothelial cell-specific protein.
The authors investigated the release of an endothelial cell-specific protein (E92) by cultured porcine aortic endothelial cell cultures. Under normal culture conditions, endothelial cells released little or no E92 into the culture supernatant. Treatment with thrombin (0.01 to 10 units/ml), endotoxin (0.01 to 10 micrograms/ml), or interleukin-1 (0.01 to 3.0 units/ml), however, caused significant, dose-dependent increases in E92 detectable in the culture supernatants. Time-course experiments showed that maximum release of E92 into cellular supernatants occurred 24 hours after stimulation with all mediators. Parallel experiments used 51Cr-loaded endothelial cells as a measure of lethal cellular injury. None of the mediators caused significant injury at the doses observed to induce release of E92. These results suggest that the release of E92 into the supernatants of cultured endothelial cells is an inducible event. The data also support the hypothesis that detection of E92 antigen in sera from patients with rheumatic disease represents a marker of in vivo vascular endothelial cell activity.
Animals↗
Detection of circulating endothelial antigen.
In order to determine whether endothelial cell antigens are detectable in serum from patients with rheumatic disease characterized by vascular involvement, we developed an ELISA using a monoclonal antibody directed against a 92,000 molecular weight endothelial cell specific antigen designated E92. Sera were assayed from 191 patients and 34 healthy controls. E92 was undetectable or present in very low concentrations in healthy controls and was elevated in most patients with an active rheumatic disease. Our results indicate that circulating endothelial antigens are present in rheumatic vascular syndromes and may provide a measure of endothelial cell function.
Adolescent↗
The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction.
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Humans↗
The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods.
The American College of Rheumatology Subcommittee on Classification of Vasculitis of the Diagnostic and Therapeutic Criteria Committee developed classification criteria for 7 forms of vasculitis: polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Henoch-Schönlein purpura, giant cell (temporal) arteritis, and Takayasu arteritis. The data collection methods, quality control, and analytic procedures used to derive the classification rules are discussed herein.
Data Collection↗
The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa.
Criteria for the classification of polyarteritis nodosa were developed by comparing 118 patients who had this disease with 689 control patients who had other forms of vasculitis. For the traditional format classification, 10 criteria were selected: weight loss greater than or equal to 4 kg, livedo reticularis, testicular pain or tenderness, myalgias, mononeuropathy or polyneuropathy, diastolic blood pressure greater than 90 mm Hg, elevated blood urea nitrogen or serum creatinine levels, presence of hepatitis B reactants in serum, arteriographic abnormality, and presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy. The presence of 3 or more of these 10 criteria was associated with a sensitivity of 82.2% and specificity of 86.6%. A classification tree was also constructed, with 6 criteria being selected. Three of these, angiographic abnormality, biopsy-proven granulocyte or mixed leukocyte infiltrate in arterial wall, and neuropathy, were criteria used in the traditional format. The other 3 criteria used in the tree format included the patient's sex, weight loss greater than 6.5 kg, and elevated serum aspartate aminotransferase or alanine aminotransferase levels above the range of normal. The classification tree yielded a sensitivity of 87.3% and a specificity of 89.3%.
Diagnosis, Differential↗
The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis).
Criteria for the classification of Churg-Strauss syndrome (CSS) were developed by comparing 20 patients who had this diagnosis with 787 control patients with other forms of vasculitis. For the traditional format classification, 6 criteria were selected: asthma, eosinophilia greater than 10% on differential white blood cell count, mononeuropathy (including multiplex) or polyneuropathy, non-fixed pulmonary infiltrates on roentgenography, paranasal sinus abnormality, and biopsy containing a blood vessel with extravascular eosinophils. The presence of 4 or more of these 6 criteria yielded a sensitivity of 85% and a specificity of 99.7%. A classification tree was also constructed with 3 selected criteria: asthma, eosinophilia greater than 10% on differential white blood cell count, and history of documented allergy other than asthma or drug sensitivity. If a subject has eosinophilia and a documented history of either asthma or allergy, then that subject is classified as having CSS. For the tree classification, the sensitivity was 95% and the specificity was 99.2%. Advantages of the traditional format compared with the classification tree format, when applied to patients with systemic vasculitis, and their comparison with earlier work on CSS are discussed.
Adolescent↗
The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis.
Criteria for the classification of Wegener's granulomatosis (WG) were developed by comparing 85 patients who had this disease with 722 control patients with other forms of vasculitis. For the traditional format classification, 4 criteria were selected: abnormal urinary sediment (red cell casts or greater than 5 red blood cells per high power field), abnormal findings on chest radiograph (nodules, cavities, or fixed infiltrates), oral ulcers or nasal discharge, and granulomatous inflammation on biopsy. The presence of 2 or more of these 4 criteria was associated with a sensitivity of 88.2% and a specificity of 92.0%. A classification tree was also constructed with 5 criteria being selected. These criteria were the same as for the traditional format, but included hemoptysis. The classification tree was associated with a sensitivity of 87.1% and a specificity of 93.6%. We describe criteria which distinguish patients with WG from patients with other forms of vasculitis with a high level of sensitivity and specificity. This distinction is important because WG requires cyclophosphamide therapy, whereas many other forms of vasculitis can be treated with corticosteroids alone.
Biopsy↗
The American College of Rheumatology 1990 criteria for the classification of hypersensitivity vasculitis.
Criteria for the classification of hypersensitivity vasculitis were developed by comparing 93 patients who had this disease with 714 control patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than 16 at disease onset, history of taking a medication at onset that may have been a precipitating factor, the presence of palpable purpura, the presence of maculopapular rash, and a biopsy demonstrating granulocytes around an arteriole or venule. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 71.0% and a specificity of 83.9%. A classification tree was also constructed. The criteria appearing in the tree structure were the same as for the traditional format, except there were 2 pathology criteria: one required the presence of granulocytes in the wall of an arteriole or venule, and the other required the presence of eosinophils in the inflammatory exudate. The classification tree was associated with a sensitivity of 78.5% and a specificity of 78.7%.
Adolescent↗
The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura.
Criteria for identifying Henoch-Schönlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%.
Adolescent↗
The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis.
Criteria for the classification of giant cell (temporal) arteritis were developed by comparing 214 patients who had this disease with 593 patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than or equal to 50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated erythrocyte sedimentation rate (Westergren) greater than or equal to 50 mm/hour, and biopsy sample including an artery, showing necrotizing arteritis, characterized by a predominance of mononuclear cell infiltrates or a granulomatous process with multinucleated giant cells. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%. A classification tree was also constructed using 6 criteria. These criteria were the same as for the traditional format, except that elevated erythrocyte sedimentation rate was excluded, and 2 other variables were included: scalp tenderness and claudication of the jaw or tongue or on deglutition. The classification tree was associated with a sensitivity of 95.3% and specificity of 90.7%.
Aged↗
The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis.
Criteria for the classification of Takayasu arteritis were developed by comparing 63 patients who had this disease with 744 control patients with other forms of vasculitis. Six criteria were selected for the traditional format classification: onset at age less than or equal to 40 years, claudication of an extremity, decreased brachial artery pulse, greater than 10 mm Hg difference in systolic blood pressure between arms, a bruit over the subclavian arteries or the aorta, and arteriographic evidence of narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities. The presence of 3 or more of these 6 criteria demonstrated a sensitivity of 90.5% and a specificity of 97.8%. A classification tree also was constructed with 5 of these 6 criteria, omitting claudication of an extremity. The classification tree demonstrated a sensitivity of 92.1% and a specificity of 97.0%.
Adult↗
The American College of Rheumatology 1990 criteria for the classification of vasculitis. Summary.
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Biopsy↗
Relationship of glucocorticoid dosage to serum bone Gla-protein concentration in patients with rheumatologic disorders.
Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = -0.71, P less than 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R2 = 0.72, P less than 0.001) between serum BGP1/2 and prednisone dosage, dosage2, serum creatinine, age, and an age-creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20-25 mg/day.
Adolescent↗
Giant cell (temporal) arteritis.
Giant cell arteritis is becoming recognized as one of the most common forms of vasculitis. However, its variable presentations and multiple features may make recognition difficult. Early diagnosis and treatment with cortico-steroids can prevent vascular occlusions. The challenge for the clinician is to use the lowest dose that suppresses the disease but also results in the fewest drug-related adverse effects.
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Trends in incidence and clinical presentation of temporal arteritis in Olmsted County, Minnesota, 1950-1985.
Ninety-four Olmsted County, Minnesota residents with temporal arteritis (TA) initially diagnosed between 1950 and 1985 (incidence cohort) were identified. The age- and sex-adjusted incidence of TA per 100,000 population age 50 years or older was 17.0 (95% confidence interval [CI] 13.6-20.5), with a marked increase in incidence with age and a threefold greater incidence in women (23.4, 95% CI 18.2-28.7) than in men (7.4, 95% CI 3.7-11.0). The previously described secular increase in TA incidence in Olmsted County women continued from 1970 through 1985, while TA incidence in men declined in this latter time period. Although the frequency of classic clinical manifestations of TA declined over time, the percentage of patients undergoing biopsy who have positive specimens remained relatively constant (women 41%, men 26%). The incidence rate of temporal artery biopsy also increased for women during this period, but declined for men, suggesting that the differing trends in TA incidence by sex may be partially attributable to a detection bias. Future research in TA etiology and epidemiology should focus on possible causal factors linked to the differential TA incidence by sex.
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