Biomedical subjects
D Gladman
Publications and source records attributed to D Gladman.
The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.
OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.
Systemic Lupus International Collaborating Clinics conference on assessment of lupus flare and quality of life measures in SLE. Systemic Lupus International Collaborating Clinics Group.
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Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus.
OBJECTIVE: To evaluate the prevalence of cytoplasmic (c) and peripheral (p) antineutrophil cytoplasmic antibodies (ANCA) using the indirect immunofluorescence (IIF) slide kit (INOVA) in patients with systemic lupus erythematosus (SLE) to correlate the presence of ANCA with disease activity and to determine if ANCA is associated with specific clinical manifestations. METHODS: One hundred and fourteen consecutive patients with SLE seen at The Wellesley Hospital Lupus Clinic, Toronto, Ontario in May and June, 1992 were assessed clinically, and blood drawn for routine serology and ANCA. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). ANCA was measured by IIF. RESULTS: Of the 114 patients, 12 (10.5%) had c-ANCA and 29 patients (25.4%) had p-ANCA. The titers of ANCA varied from 1:20 to 1:160. SLEDAI was 0 in 6 patients (5%), and 108 patients had some disease activity. Eighty-eight patients (77%) had mild to moderate active disease (SLEDAI < 10), and 20 (18%) patients had severe active disease (SLEDAI > or = 10). CONCLUSION: No correlation was found between the presence of ANCA and SLEDAI either when analyzed as active-inactive (p = 0.75) or when correlated with degrees of disease activity (1-10: > 10) (p = 0.77). No correlation was found between p and c ANCA and the presence of vasculitis, renal, or CNS disease at the time of the assessment or at any time during the course of the disease. Thus ANCA was not associated with SLE disease activity or the presence of vasculitis in SLE.
Performance of scored palpation, a point count, and dolorimetry in assessing unsuspected nonarticular tenderness.
Nonarticular tenderness was measured in 152 patients, 51 with rheumatoid arthritis, 50 with psoriatic arthritis, and 51 with human immunodeficiency virus infection. Three methods for assessing tenderness were used: a 14-site point count, scored tenderness at 10 sites (6 fibrositic and 4 control), and dolorimetry at the same 10 sites. The data from the 3 separate measures were converted into a common scale of standard deviation units for further analysis. There were strong correlations among the 3 measures. In particular, the scored tenderness at just 6 fibrositic sites provided as much information about the presence and severity of widespread tenderness as the other 2, more complex measures. At the interface between nontender and tender, the 2 methods based on palpation were significantly more sensitive to differences among individuals, than was dolorimetry. However, the palpation scales used did not evaluate different degrees of nontenderness. In 102 of the 152 subjects, there were 842 sites scored zero by palpation, and which showed widely different thresholds of tenderness by dolorimetry, significantly associated with diagnosis and sex. For screening and epidemiological purposes, scored tenderness at a limited number of accessible sites may be adequate and feasible, using the 18 point count of the new standard criteria as a gold standard for confirmation. For the assessment of generally acting factors affecting tenderness, dolorimetry is currently superior.
A reliability study of SLEDAI: a disease activity index for systemic lupus erythematosus.
SLEDAI, a disease activity index for systemic lupus erythematosus (SLE) has been validated against other such indices and its reliability has been shown by specialists in SLE. To assess its reliability among less experienced clinicians, we conducted a reliability study with 3 rheumatology trainees and 9 patients with SLE according to a Latin square design. SLEDAI easily distinguished between patients (p = 0.0009), and physician variability was not statistically significant (p = 0.27). Inter and intraobserver agreement were 78.7 and 98.0%, respectively. SLEDAI was thus shown to be a reliable instrument among less experienced observers for the assessment of disease activity in SLE.
Systemic lupus international collaborative clinics: development of a damage index in systemic lupus erythematosus.
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Gastrointestinal-related arthritis and psoriatic arthritis.
Psoriatic arthritis and the enteropathic arthropathies are included among the seronegative spondyloarthropathies. The concept of psoriatic arthritis as a specific entity continues to be challenged by some investigators, while others report on additional findings in this condition, such as temporomandibular joint disease. The etiopathogenesis of the condition continues to be investigated by the exploration of genetic and immunologic factors. Treatment options include dietary manipulations. The prevalence of arthritis among patients with bowel disease seems to be increasing, while the presence of gut lesions among patients with spondyloarthropathy is noted to be associated with disease activity.
Cortisol catabolism by lymphocytes of patients with systemic lupus erythematosus and rheumatoid arthritis.
We have shown that low cortisol catabolism by lymphocytes correlates with a high sensitivity of the cells to the steroid. In the present study, we aimed to assess whether high resistance to corticosteroid treatment correlates with a high rate of cortisol catabolism by lymphocytes. Since patients with systemic lupus erythematosus (SLE) usually require high doses of corticosteroids, while patients with rheumatoid arthritis (RA) respond to relatively low doses of steroids, we compared the capability of lymphocytes of patients with SLE and RA to catabolize cortisol. The rate of cortisol catabolism obtained with the RA group was not significantly different from that obtained with the control group. The catabolism of cortisol by lymphocytes of the SLE group was significantly higher than both the control group (p less than 0.05) and the RA group (p less than 0.01). A significant correlation was demonstrated between the SLE disease activity index and rates of cortisol catabolism attained by lymphocytes of SLE patients (p less than 0.001).
Atlantoaxial subluxation in a patient with psoriatic arthritis.
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Criteria for assessing disease activity in systemic lupus erythematosus.
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Reactivity of T-cells from patients with rheumatoid arthritis to anti-CD3 antibody.
The ability of an anti-CD3 monoclonal antibody (OKT3) to induce proliferation was examined in peripheral blood mononuclear cells (PBM) from 30 patients with rheumatoid arthritis (RA). Controls consisted of 10 patients with osteoarthritis, 12 patients with psoriatic arthritis, and 12 healthy subjects. The results revealed enhanced PBM reactivity in patients with active RA relative to inactive RA patients and all control groups. PBM of patients with mild/moderate clinical disease activity exhibited augmented anti-CD3 reactivity while those with severe disease demonstrated impaired reactivity. Enhanced reactivity was also observed in the active RA group using another anti-CD3 monoclonal antibody (Leu-4). Differences in anti-CD3 dose-response or time kinetics could not account for the results. Studies of enriched T-cell preparations revealed a markedly enhanced anti-CD3 reactivity of RA T-cells relative to normal control T-cells. Monocyte/T-cell mixing experiments revealed no enhanced reactivity of RA monocytes in the anti-CD3 response. RA T-cell preparations depleted of monocytes by limiting dilution reacted significantly more to anti-CD3 in the presence of IL-2 relative to controls. The enhanced reactivity could be accounted for in part by hyperreactivity of the OKT8-bearing subpopulation of T-cells.
Antithyroid microsomal autoantibodies and HLA-DR5 are associated with postpartum thyroid dysfunction: evidence supporting an autoimmune pathogenesis.
Antithyroid microsomal antibodies (AMA) and human leukocyte antigen (HLA) haplotypes were assessed as markers for the occurrence of postpartum thyroid dysfunction (all forms) and postpartum painless thyroiditis with transient hyperthyroidism, respectively. AMA titers and thyroid function tests were measured sequentially in 261 mothers from delivery to up to 1 yr postpartum. To test for the association of HLA haplotypes in the subgroup of women with postpartum painless thyroiditis with hyperthyroidism, typing for HLA-A, -B, -C, -DR, and -DQ antigens was carried out in a selected group of 38 mothers with this syndrome. Their results were compared to those in 60 women with hypothyroid goitrous autoimmune thyroiditis and 98 regional controls. In the AMA study, 40 (15%) of the 261 mothers had positive AMA titers (titer, less than or equal to 1:80) at delivery, 54 (21%) 2-4 months postpartum, 69 (26%) 5-7 months postpartum, and 60 (23%) 1 yr postpartum. Among 55 mothers who developed postpartum thyroid dysfunction, 25 (47%) had positive AMA at delivery [relative risk (RR), 10.0; P less than 0.001; sensitivity, 45%; specificity, 95%]. Two to 4 months postpartum, 46 mothers had thyroid dysfunction, of whom 35 (76%) had positive AMA, while only 19 of the 215 euthyroid mothers (9%) had positive tests for AMA. Positive AMA tests at these times resulted in a RR for postpartum thyroid dysfunction of 32.8 (P less than 0.0001; sensitivity, 76%; specificity, 91%). Five to 7 months postpartum, 55 mothers had thyroid dysfunction, of whom 47 (86%) had positive AMA, while only 22 of 206 euthyroid mothers (11%) were positive (RR, 59.0; P less than 0.0001; sensitivity, 86%; specificity, 90%). In the HLA studies, DR5 occurred in 11 of 38 (29%) women with postpartum painless thyroiditis with hyperthyroidism vs. 12 of 98 (12%) controls, resulting in a RR of 2.9 (P less than 0.05). HLA-DR5 was present in 22 of 60 (37%) patients with goitrous autoimmune thyroiditis (RR, 4.2; P less than 0.01). HLA-DR4 and HLA-DQw3 were slightly but not significantly increased in women with postpartum painless thyroiditis with hyperthyroidism and goitrous autoimmune thyroiditis compared to those in normal controls. DQw1 was reciprocally decreased (P less than 0.025) in the women with goitrous autoimmune thyroiditis, but not in the women with postpartum painless thyroiditis with hyperthyroidism compared to that in normal controls...
Pathologic features of diabetic thick skin.
Skin thickening simulating scleroderma, or progressive systemic sclerosis, has previously been reported in children and adults with insulin-dependent diabetes mellitus. We have studied eighty-nine patients with insulin-dependent diabetes mellitus and twenty-five normal control subjects. Clinical evidence of skin thickening (diabetic thick skin) was found in 22% of patients with insulin-dependent diabetes mellitus and in 4% of control subjects (p less than 0.05). Full-thickness skin biopsy specimens were taken from the forearm of nine patients with insulin-dependent diabetes mellitus and diabetic thick skin, four patients with insulin-dependent diabetes mellitus and clinically normal skin, four patients with progressive systemic sclerosis, and four normal control subjects. The sections stained with hematoxylin and eosin showed increased thickness of the dermis of the forearm skin in all diabetic patients. In diabetic thick skin the collagen bundles were large, disorganized, and separated by clear spaces. Small amounts of acid mucopolysaccharides were present in the upper reticular dermis of five patients with diabetic thick skin. Electron microscopy of the dermis showed capillary basement membrane thickening in Groups 1, 2, and 3. All patients with diabetic thick skin showed active fibroblasts and extensive collagen polymerization in the rough endoplasmic reticulum. Occasional collagen flowers were noted in all patients with diabetic thick skin. Measurements of 100 collagen fibers in the upper and lower reticular dermis of each biopsy specimen showed predominance of large fibers (greater than 60 nm) in Groups 1 and 2. Unlike scleroderma, diabetic thick skin resulted in small fiber sizes (less than 60 nm) only rarely, and bimodality of fiber sizes was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo activation of lymphocytes in rheumatoid arthritis.
Spontaneous in vivo proliferation of peripheral blood mononuclear cells (PBM) and T and B lymphocytes from 28 patients with rheumatoid arthritis (RA), 20 healthy individuals and 13 patients with psoriatic arthritis was evaluated. PBM, T (E+) and non-T (E-) cells from patients with active RA proliferated significantly more than the same populations from healthy individuals and patients with inactive RA. In contrast, only E+ cells from PSA patients showed a trend to increased proliferation relative to healthy individuals. AET treated sheep red blood cells (SRBC) inhibited 3HTdR incorporation of highly profilerating PBM of active RA patients. The data suggest in vivo activation of both B and T cells in patients with clinically active RA.
Severe reflex neurovascular dystrophy in childhood.
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Malakoplakia and immunosuppressive therapy. Reversal of clinical and leukocyte abnormalities after withdrawal of prednisone and azathioprine.
Malakoplakia is a chronic granulomatous inflammatory disorder. It is suspected clinically by the presence of chronic infection and diagnosed by histologic examination of affected tissues. Studies of 4 patients with malakoplakia--2 renal transplant recipients, 1 patient with systemic lupus erythematosus, and 1 patient with polymyositis--are reported. All patients were receiving prednisone and azathioprine at the time of diagnosis and had an infection caused by Escherichia coli. Leukocytes from all patients failed to kill Staphylococcus aureus and E coli normally in vitro. Cholinergic agonists had no apparent effect on bacterial killing in vitro or in vivo in the 2 patients examined. Clinically, malakoplakia improved significantly when immunosuppressive therapy was tapered or discontinued, and leukocyte function returned to normal in all 4 patients. The cases reported here and those documented previously suggest that the pathogenesis of malakoplakia and its treatment may not be the same for all patients. Malakoplakia may be more common than previously thought, particularly with the increased use of immunosuppressive therapy.
HLA-DR antigens and gold-induced enterocolitis.
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