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D D Gladman

Publications and source records attributed to D D Gladman.

At least 37 records · Page 2Linked to original sources
PubMed2004

Dactylitis in psoriatic arthritis: a marker for disease severity?

AIM: To describe dactylitis in a large cohort of patients with psoriatic arthritis followed prospectively in a specialist clinic, and identify whether it is associated with a worse prognosis. METHODS: Between 1979 and 1999, 537 patients were registered in the psoriatic arthritis clinic and entered onto a longitudinal database. Patients were followed prospectively at six to 12 month intervals according to a standard protocol, and all information was entered onto a database. The database was searched for patients with dactylitis. Descriptive statistics were used to describe the population and chi(2) tests to relate dactylitis to radiographic changes. RESULTS: Dactylitis was documented in 260 patients (48%); 69% of the episodes were recorded at presentation to the clinic. Dactylitis affected feet only in 65% of cases, hands only in 24%, and both hands and feet in 12%. Recurrent dactylitis occurred in 44% of the patients. Increased radiological progression was noted in digits showing dactylitis compared with those without dactylitis (50% v 38%, respectively; p<0.0001). CONCLUSIONS: Dactylitis is common among patients with psoriatic arthritis. It most often affects the feet, in an asymmetrical distribution. It is associated with a greater degree of radiological damage than occurs in digits not affected by dactylitis.

Acute Disease↗
PubMed2004

Treatment of refractory psoriatic arthritis with infliximab: a 12 month observational study of 16 patients.

OBJECTIVE: To evaluate the effectiveness and toxicity of infliximab in patients with recalcitrant psoriatic arthritis (PsA). METHODS: Patients with treatment resistant PsA and at least six actively inflamed joints, who had failed to respond to at least two disease modifying agents, were included. Infliximab (5 mg/kg) was given at weeks 0, 2, 6, and every 6-8 weeks pending response. Clinical and laboratory measures included actively inflamed joint count (AJC), swollen joint count (SJC), psoriasis severity (PASI), HAQ, and SF-36. Response was defined as at least a 30% reduction in AJC and PASI. Differences from baseline were analysed using the signed rank test. RESULTS: Sixteen patients (12 male, 4 female), mean age 48 and disease duration 14 years, were included. At baseline the mean AJC was 22.5 and mean PASI 4.5. Eleven patients continued receiving methotrexate. The AJC did not show a statistically significant response. SJC improved significantly at week 54 (p = 0.01). The PASI improved significantly at weeks 14 (p = 0.001) and 30 (p = 0.002) and CRP was reduced significantly at week 30 (p = 0.02). The HAQ score improved at week 30 (p = 0.02). Six patients became positive for dsDNA without clinical features of a connective tissue disease. Six patients discontinued treatment owing to lack of efficacy (1) and toxicity (5). Other serious adverse events included: urticaria (3); thrombocytopenia (1); lower gastrointestinal bleeding (2); severe diarrhoea (2); serious infections (6). Raised transaminases, at least 1.5x normal, occurred in four patients. CONCLUSION: In refractory PsA, infliximab led to a marked improvement in psoriasis but modest response in joint disease. Toxicity and rate of treatment termination was high.

Adult↗
PubMed2004

Osteoporosis in systemic lupus erythematosus: factors associated with referral for bone mineral density studies, prevalence of osteoporosis and factors associated with reduced bone density.

The purpose of this study was to evaluate the clinical characteristics of women with systemic lupus erythematosus (SLE) sent for a dual energy X-ray absorptiometry (DEXA) study, and to analyse the factors associated with a lower bone mineral density in these patients. Women with SLE who had a DEXA done between 1 January 1995 and 31 December 2000 were compared with those who did not have DEXA scans performed. SLE patients with osteoporosis (OP) were compared with those with a normal bone density. Of 516 women with SLE, 205 had a DEXA done. These patients had more traditional risk factors for osteoporosis, higher lupus disease activity, renal involvement, increased damage, higher mean steroid dose, increased use of immunosuppressants and occurrence of avascular necrosis. Of the 205 patients with DEXA, 18% had osteoporosis, 48.8% had osteopenia and 33.2% had normal bone mineral density. The two statistically significant predictors of a low bone density were a higher age at time of DEXA (P = 0.0003) and a higher SDI score (P = 0.0019). Osteoporosis is a significant comorbidity in SLE. Lupus patients referred for a DEXA have more traditional risk factors and use more corticosteroids. The main factors associated with a low bone density were however found to be age and increased damage. Interestingly, disease activity and corticosteroid use were not associated with osteoporosis in this study which may suggest other potential causes such as decreased physical activity associated with damage.

Absorptiometry, Photon↗
PubMed2004

Pulmonary hypertension in systemic lupus.

Pulmonary arterial hypertension (PAH) has devastating consequences in the rheumatic diseases; however, the prevalence in lupus is not well delineated. We searched the University of Toronto lupus database to ascertain the first echocardiogram ordered at their physician's discretion between 1995 and 2002. We reviewed the echocardiogram reports for right ventricular systolic pressure (RVSP), valvular disease, and atrial and ventricular function. The PAH was defined as RVSP > or = 40 mmHg. Patients were divided into three groups: RVSP > or = 40 mmHg, RVSP = 30-39 mmHg and RVSP < 30 mmHg. We analysed potential associations between presence of PAH and lupus including disease activity, organ involvement and anticardiolipin antibodies, both at the time of and any time prior to echocardiography. In total, 129 patients underwent echocardiography. Nine patients' echocardiograms were not obtainable, and three patients were excluded from analysis, as their visit was more than six months from the date of echocardiography. Sixteen patients (14%) had RVSP > or = 40 mmHg, 43 (37%) patients had RVSP of 30-39, and 60 (51%) patients had RVSP < 30 mmHg. There was no statistical difference in disease activity, organ involvement or serology among all three groups. In conclusion, the prevalence of PAH (RVSP > or = 40 mmHg) on first echocardiogram ordered at physician discretion in our cohort was 14%. An RVSP of 30-39 mmHg was found in 37% of patients. Although abnormal, the clinical significance of this finding is unknown. Disease activity, organ involvement and anticardiolipin antibodies were not associated with PAH. Further research is needed to identify the mechanism, response to immunosuppression and impact on quality of life in these patients.

Atrial Function↗
PubMed2004

Impaired brachial artery endothelium dependent flow mediated dilation in systemic lupus erythematosus: preliminary observations.

Our objective was to compare brachial artery endothelium dependent and independent vasodilation in lupus patients and healthy females, by means of high-resolution noninvasive brachial artery ultrasound. Endothelially mediated vasodilation was estimated noninvasively by examination of brachial artery responses to postischemic reactive hyperemia and endothelial independent vasodilation from response to sublingual glycerlynitrate (GTN) using high-resolution external vascular ultrasound. Five patients with known coronary artery disease (CAD), five with subclinical CAD, five with no CAD and five control subjects were assessed. Endothelium dependent vasodilation was significantly blunted in lupus patients with CAD as compared with healthy female controls (0.11 versus 11.1%, P = 0.018). Corresponding values for lupus patients with subclinical CAD and no CAD were 11 and 9.6%, respectively. For each subject, endothelium dependent vasodilation (EDV) was related to endothelium independent vasodilation (EIV) to adjust for varying vascular smooth muscle responses to GTN in individual subjects. This ratio was markedly depressed in lupus patients with CAD as compared with control subjects (0.12 versus 1.15). The corresponding EDV/EIV ratios for patients with subclinical CAD and no CAD were similar at 0.69 and 0.65, respectively. The conclusion was that flow mediated vasodilation in lupus patients with coronary artery disease is markedly depressed as compared to healthy subjects.

Adult↗
PubMed2003

CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis.

A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA.

Adult↗
PubMed2002

The nature and outcome of infection in systemic lupus erythematosus.

Infection remains a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). To describe the nature and outcomes of infection and determine their associated risk factors in patients with SLE, we performed a nested case-control study at the University of Toronto Lupus Clinic, with prospective follow-up according to a standard protocol since 1970. Cases were SLE patients seen between January 1987 and January 1992 who had documented infections and controls were patients without infection from the same cohort matched for age, gender and time of visit. The type, site and outcome of infection were recorded for each case. A conditional logistic regression analysis was performed to compare factors associated with infection in cases and their controls. Ninety-three patients had 148 infection episodes; the majority were bacterial, but viral, fungal and protozoan organisms were also identified (multiple organisms in seven). Forty-eight patients required hospital admission and three patients died. Steroids at time of infection, as well as use ever, duration and dose, immunosuppressives at time of infection and use ever, active renal disease, CNS damage, SLEDAI at the time of infection, adjusted mean SLEDAI and variability measure were significantly associated with infection by univariate analysis. By multivariate analysis one factor remained statistically significant: use of steroids ever (P = 0.029). Infection carries a large burden for SLE patients. Until new medications which will control disease activity without predisposing to infection are developed, careful titration of steroids and cytotoxic drugs to control disease activity will remain crucial.

Age Factors↗
PubMed2001

Health-related quality of life of patients with psoriatic arthritis: a comparison with patients with rheumatoid arthritis.

OBJECTIVE: To compare health-related quality of life (QOL) between patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA), using the Medical Outcomes Study Short Form health survey (SF-36) and the Health Assessment Questionnaire (HAQ). METHODS: Both the SF-36 and the HAQ were administered to 107 PsA patients attending the University of Toronto Psoriatic Arthritis Clinic between January 1 and December 31, 1994, and to 43 RA patients attending a University of Toronto-affiliated RA clinic during the same period. Standardized assessments of disease activity and severity were also performed at each clinic visit. Logistic regression analysis was used to compare health-related QOL between PsA and RA. RESULTS: Both patient populations experienced lower physical health compared with that of a general population sample. The RA patients demonstrated more active inflammatory disease at the time of assessment than the PsA patients. The PsA patients were younger, and more were men. Logistic regression analyses showed that patients with PsA reported higher levels of vitality than patients with RA, even after adjusting for the observed differences in clinical and demographic characteristics. PsA patients, however, reported more role limitations due to emotional problems and more bodily pain after adjusting for the difference in vitality and other covariates. CONCLUSIONS: Although both patient populations experienced reduced QOL, there were some meaningful differences in how the 2 conditions affect health-related QOL. Further, it appeared that there may be unique disabilities associated with the psoriasis dimension of PsA.

Adult↗
PubMed2001

HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

Adult↗
PubMed2001

The long-term use of azathioprine in patients with psoriatic arthritis.

Despite the widespread use of methotrexate in the treatment of psoriatic arthritis (PsA), there are patients who are either refractory, develop toxicity to, or refuse to take methotrexate. In search of an alternative, we studied long-term tolerability of and clinical response to azathioprine (AZA) in PsA patients in comparison with matched controls and followed them in a longitudinal clinic. Twenty-eight of 485 patients followed prospectively between 1978 and 1998 took AZA during their clinic follow-ups. Eighteen of the 28 took AZA for 12 months and were included in the study. AZA was well tolerated by most patients, even in the long-term. Although there was no statistically significant difference in the reduction in number of actively inflamed joints between AZA-treated patients and controls, and AZA was no better in preventing progression of damage, AZA was still as good as the other medications. Consequently, AZA was often given to individuals who had not responded to other medications in the past. We provide illustrative case reports in which AZA also controlled psoriasis, and we conclude that, whereas AZA is not superior to other medications in the treatment of PsA, it may be safely used and it provides an alternative therapy for patients with PsA.

Journal Article↗
PubMed2001

Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus.

The aim of this study was to determine whether early damage accrued in SLE as measured by the SLICC/ACR Damage Index predicts mortality in an inception cohort of lupus patients that have been followed prospectively in a single centre. SLE patients from the University of Toronto Lupus Clinic presenting within 1 y of their diagnosis prior to 1988 were included. This enabled all patients to be potentially followed for at least 10 y. Yearly SLICC/ACR Damage Index scores were determined for each patient. Early damage was defined as a score > or = 1 and no damage as a score of 0 at the initial assessment. Log rank test was used to compare the survival experience between those with and without damage, with all patients being censored at 10 y. Two-hundred and sixty-three patients were identified in this inception cohort who were followed for 10 y. One-hundred and ninety patients (72%) had a SLICC/ACR Damage Index score of 0 (no damage) while 73 patients (28%) had at least one SLICC/ACR Damage Index item scored (early damage). Twenty-five percent of lupus patients who exhibited damage at their first SLICC/ACR Damage Index assessment died within 10 y of their illness as compared to only 7.3% who had no early damage (log rank P-value = 0.0002). SLE patients who died within 10 y were more likely to have renal damage (P = 0.013), and a trend toward more cardiovascular disease (P = 0.056), compared to patients who were alive. Early damage as reflected by the initial SLICC/ACR Damage Index is associated with a higher rate of mortality.

Adolescent↗
PubMed2001

Significance of isolated hematuria and isolated pyuria in systemic lupus erythematosus.

Hematuria or sterile pyuria as isolated urinary findings present a clinical dilemma for the treating physician. Our objective was to determine whether isolated hematuria and isolated sterile pyuria are associated with active systemic lupus erythematosus (SLE) with respect to renal and non-renal disease activity. This is a descriptive study from a large SLE cohort followed prospectively at the University of Toronto Lupus Clinic. All episodes of isolated hematuria and isolated pyuria between 1970 and 2000 were identified from our database. Isolated hematuria was defined as > 5 red blood cells per high power field; isolated sterile pyuria was defined as > 5 white blood cells per high power field in the absence of urinary infection and other renal manifestations. Non-renal disease activity (defined as nrSLEDAI > 1) was determined at first episode of isolated hematuria and pyuria. Renal disease activity was assessed by scoring renal biopsies within 3 months of detecting isolated hematuria or sterile pyuria. Thirty-four percent (323/946) of our cohort had at least one episode of isolated hematuria. Seventy-seven percent of these patients had concurrent non-renal disease activity. Of the 22 biopsies scored with isolated hematuria, 96% were abnormal (WHO > class I), including 52% with active nephritis. Twenty-three percent (215/946) had at least one episode of isolated sterile pyuria. Seventy-eight percent of these patients had concurrent non-renal disease activity. All 12 biopsies scored with isolated pyuria were abnormal (WHO Class > 1), including 75% with active nephritis. The appearance of isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. An ongoing debate has emerged regarding the significance of isolated hematuria and isolated pyuria with respect to SLE disease activity. The results of this study suggest that isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. Thus isolated hematuria and isolated sterile pyuria should be considered manifestations of active SLE.

Biopsy↗
PubMed2001

Predictive factors for symptomatic osteonecrosis in patients with systemic lupus erythematosus.

OBJECTIVE: To analyze predictive factors for the development of osteonecrosis (ON) in a large cohort of patients with systemic lupus erythematosus (SLE) followed in a single center. METHODS: A nested matched case control design was used. Patients with SLE who developed ON during followup were identified from the University of Toronto Lupus Clinic database. The diagnosis of ON was confirmed by either radiographs, bone scans, tomograms, or magnetic resonance imaging. A comparison group of patients with SLE without ON was selected from the same database, matched by year of birth. sex, and year of entry to the clinic to the patients with ON. Clinical, laboratory, and therapeutic factors thought to be relevant to the development of ON were compared between the 2 groups. RESULTS: Seventy patients with SLE developed ON in the course of followup at the clinic. In univariate analysis, arthritis was the only clinical feature predictive of the development of ON. Use of glucocorticosteroid therapy, dose and duration, as well as Cushingoid appearance and cytotoxic therapy were also predictive for the development of ON. Multivariate analysis revealed that glucocorticosteroid use, the presence of arthritis, and the use of cytotoxic medications remained significant. CONCLUSION: Glucocorticosteroid therapy, the presence of arthritis, and use of cytotoxic medication are independent risk factors for development of ON in patients with SLE.

Adolescent↗
PubMed2001

Comparison of radiological severity in psoriatic arthritis and rheumatoid arthritis.

OBJECTIVE: To compare the radiological severity of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Patients were identified from the University of Toronto PsA and RA databases. Using the earliest available radiographs, each RA patient was matched to a single PsA patient on the basis of sex, age, and disease duration. Two rheumatologists blinded to the patient's diagnosis scored the radiographs using the modified Steinbrocker method. RESULTS: PsA and RA groups were similar with respect to demographics as well as the use of disease modifying antirheumatic medications. No significant difference in Steinbrocker score for the hands and feet or the hands only was noted. Patients with RA had a higher radiological score in the feet. The 2 groups were similar in the number of joints with significant radiological damage (Steinbrocker 3 and 4). CONCLUSION; Overall the radiological severity in the hands and feet of patients with PsA was comparable to that of patients with RA.

Adult↗
PubMed2001

Remission in psoriatic arthritis.

OBJECTIVE: To determine the frequency of remission in psoriatic arthritis (PsA), to describe the characteristics of remission in PsA, and to identify features associated with remission in PsA. METHODS: Patients with PsA are followed prospectively according to a standard protocol. Only patients with > or =3 visits and those with peripheral arthritis were included in this study. Patients who sustained remission, defined as no actively inflamed joints on at least 3 consecutive visits, were compared to patients with persistent inflammation throughout the followup period (nonremission). RESULTS: Among 391 patients with peripheral arthritis and > or =3 visits, 69 patients sustained remission and 178 had persistent inflammatory activity. The frequency of remission was thus 17.6%. The average duration of remission was 2.6 years. However, 52% of the patients experienced flare after a mean of 1.8 years. Univariate analyses revealed that male sex, fewer actively inflamed and damaged joints, and better functional class at presentation to clinic were associated with remission. CONCLUSION: Remission does occur in PsA and may be prolonged. There are clinical characteristics of patients at their first clinic visit that are associated with future remission.

Adult↗
PubMed2001

Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus.

OBJECTIVE: To describe the frequency and type of symptomatic osteonecrosis (ON) in a large cohort of patients with systemic lupus erythematosus (SLE) followed in a single center and to describe the outcome in terms of mortality and disability compared to SLE patients without ON. METHODS: Patients with ON were identified from the University of Toronto Lupus Clinic Database. The diagnosis of ON was confirmed by radiographs, bone scans, tomograms, or magnetic resonance images. A comparison group of patients with SLE without ON was selected from the same database, matched by year of birth, sex, and year of entry to the clinic. Mortality, disability, and health related quality of life were compared between patients with and without ON. RESULTS: Ninety-nine patients with ON were identified with 217 affected joints, the majority hips and knees, often in a bilateral distribution. There was no increase in mortality. Patients with ON had higher Health Assessment Questionnaire scores and lower SF-20 scores of physical functioning, suggesting increased disability. Hip joints that underwent surgery were more likely to have higher grades of ON at diagnosis. CONCLUSION: Symptomatic ON occurred in 12.8% of 744 patients with SLE and often involved multiple joints. ON was not associated with increased mortality but was associated with physical disability. Radiological class of the hip jointsat diagnosis of ON was predictive of subsequent surgery.

Adolescent↗
PubMed2000

Premature atherosclerosis in systemic lupus erythematosus.

SLE is a multifaceted disease; over the past 20 years, as survival has improved dramatically, new challenges have emerged. It is now clear from the results of studies at several centers that SLE is associated with at least a fivefold increased risk of CAD, which is accelerated at its onset and seems to abolish a female premenopausal protection against CAD. Several groups have also found by various techniques that subclinical disease occurs at a frequency of about 35% to 40%. The pathogenesis of atherosclerosis in this context seems to be a complex interaction of factors associated with the disease, its therapy, and traditional risk factors. Indeed, experimental models suggest a synergy of these different dimensions in plaque formation. Hypercholesterolemia has been identified as predictive of both future CAD events and sub-clinical disease. This is mainly the case in those patients in whom hypercholesterolemia is a sustained phenomenon. In addition, SLE itself seems to be a strong risk factor for CAD over and above the effects of the known traditional CAD risk factors. There is a lot that is still unknown about the pathogenesis of CAD in SLE. Current knowledge is sufficient to justify the belief that an aggressive approach to management of traditional CAD risk factors in patients with SLE is likely to have a major impact on morbidity and mortality in this population. For this to happen, patients must be educated about this issue and be encouraged to play an active role in lifestyle modifications. In addition, clinicians who care for patients with SLE need to assume a primary role in screening and coordinating the management of CAD risk factors in these high-risk patients.

Arteriosclerosis↗