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PODIUM PRESENTATIONS
1 ETHNIC VARIATION IN SYSTEMIC LUPUS ERYTHEMATOSUS Sindhu R. Johnson, Dafna D. Gladman, Dominique Ibanez, Murray B. Urowitz (Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, University of Toronto, ON, Canada) Disease severity has been reported to be greater in lupus patients of African and Chinese origin. The prevalence of renal and central nervous system (CNS) manifestations appears to be higher in Chinese patients, while the severity of renal manifestations in patients of African origin compared to Caucasians is controversial. We have a unique opportunity to assess variation in disease manifestations, and patient outcomes (damage and mortality), and their relationship to ethnic origin since the environment is uniform in our clinic. Objective: To investigate the prevalence of renal and CNS lupus; renal, CNS and overall end organ damage and mortality, in a single centre multiethnic lupus cohort. Methods: Clinical features (renal and CNS disease ever, and adjusted for disease duration), end organ damage measured by the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI), and mortality were compared by ethnic origin (Caucasian, African and Chinese) among prospectively followed patients in a longitudinal lupus clinic over a 32 year period. Statistical analysis included t-test, linear and logistic regressions with all 3 groups adjusting for disease duration and age at diagnosis. Kaplan-Meir survival analysis was also performed. Results: There were a total of 1017 patients: 853 Caucasian, 88 African-Canadian and 76 Chinese patients. Age at diagnosis was younger (p = 0.007), and disease duration was shorter (p = 0.05) for Chinese patients compared to Caucasians, but not dissimilar between African-Canadians and Caucasians. There was no significant difference in mortality by survival analysis among the 3 groups (p = 0.87). There was no significant difference in CNS disease, with and without adjustment for disease duration, when comparing Caucasians to Chinese and African-Canadians. However, CNS disease was greater in African-Canadians than Chinese patients (p = 0.02). Renal disease, with and without adjustment for disease duration, was more common in African-Canadian than Caucasian and Chinese patients (p = 0.03) with no significant difference between Caucasian and Chinese patients. There was also a higher prevalence of renal damage among African-Canadians than Caucasians (p = 0.04). There was no significant difference between races in CNS damage (p = 0.91) and overall end organ damage (p = 0.11) using SDI. Conclusion: There is no significant difference in overall end organ damage, CNS damage, or mortality among the three ethnic groups. African-Canadians have a higher prevalence of renal disease and damage. Further investigation into other determinants such as genetic predisposition, co-morbid illness, treatment and cultural perceptions are needed. 2 QUALITY OF LIFE IN SCLERODERMA: COMPARED TO PSORIATIC ARTHRITIS, SLE, RHEUMATOID ARTHRITIS AND HEALTHY CONTROLS Sindhu R. Johnson, Dafna D. Gladman, Catherine T. Schentag, Peter Lee (Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto, ON, Canada, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto, ON, Canada, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto, ON, Canada, Scleroderma Clinic, Mount Sinai Hospital, Toronto, ON, Canada) Objective: To assess clinical and laboratory factors associated with quality of life in patients with systemic sclerosis (SSc)compared to psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. Methods: Patients were recruited from the university rheumatology clinics based on ACR classification criteria for SSc, PsA, SLE and RA and compared to healthy controls. Eighty-two SSc patients, 82 PsA, 74 SLE, 42 RA and 60 controls underwent physical examination, tender point count, erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ) and Short Form Health Survey (SF-36). SSc patients also had assessment of a skin score. Data was analyzed using descriptive statistics, t-tests, ANOVA and Pearson correlation, as appropriate. A p<0.05 was considered statistically significant. Results: There were 71 female and 9 male SSc patients, with an average age of 48.2 years and disease duration 7.1 years. SSc patients were younger and had shorter disease duration than the comparator groups. The SF-36 physical component summary and HAQ in SSc patients were adversely affected by arthritis, > 10 tender points, gastrointestinal involvement and high skin score. There was no correlation between tender points and SF-36 mental component summary, mental health and emotional domains, gender or age. All four patient groups has significantly poorer HAQ, VAS pain and SF-36 physical component summary scores than controls. Although SSc patients overall were no different from PsA, SLE and RA patients in these measures, those with arthritis has significantly poorer HAQ scores than patients with PsA (1.43 vs 0.84), and had higher VAS pain scores than RA patients (1.37 vs 1.01). Conclusions: Quality of life is adversely affected in SSc with a strong correlation between disability and the presence of > 10 tender points, arthritis, high skin score and GI involvement. SSc patients with arthritis are more disabled than those with PsA and experience more severe pain than RA patients. 3 SHOULD PROPHYLACTIC SURGICAL FUSION BE OFFERED TO PATIENTS WITH RHEUMATOID ARTHRITIS AND CERVICAL INSTABILITY BEFORE DEVELOPMENT OF NEUROLOGICAL SYMPTOMS? A DECISION ANALYSIS. Yan Liu (Trainee PGY5), Beate Sander, Andreas Maetzel (Dept. of Medicine, Division of Rheumatology, University of Toronto, University Health Network, Division of Clinical Decision Making, University Health Network, Division of Clinical Decision Making, Dept. of Health Policy Management and Evaluation, University of Toronto) Background: Surgical fusion is routinely proposed to patients with rheumatoid involvement of the cervical spine in the presence of neurological symptoms. However, successful outcomes of surgery have prompted surgeons to advocate intervention in patients with pain alone in the absence of neurological signs. Objective: To evaluate the benefits of surgery as a prophylactic measure for patients with painful cervical instability in the absence of neurological signs (Ranawat I) [PROPH], versus surgery only for those whose disease progresses to neurological involvement (Ranawat ≥II) [NEURO]. Methods: We developed a decision analysis model with a comprehensive representation of the transitions of patients with cervical instability between Ranawat stages, surgical complications and death. A systematic search of Medline (1966 - 09/2003) was performed to obtain estimates of events in the model. We excluded studies that contained less than 10 patients and were published before 1985, when CT and MRI imaging modalities were routinely used. Primary outcomes considered were the progression from Ranawat I to Ranawat ≥II and mortality. We adopted a time horizon of 5 years. Sensitivity analysis was performed on key clinical variables. Results: Eight studies met eligibility criteria, providing key input to the following baseline variables: 1) progression from Ranawat I to ≥II with NEURO - 55%; 2) progression from Ranawat I to ≥II with PROPH - 0%; 3) chance of non-permanent surgical complications 17% (PROPH) vs. 11% (NEURO); 4) improvement to Ranawat I with NEURO - 72%. Neither strategy was associated with increased mortality directly related to surgery. Adopting PROPH would lead to a higher proportion of patients remaining in Ranawat I or 0 (free of pain) (100%) as compared to NEURO (79%). Sensitivity analysis shows that preference of PROPH over NEURO is robust to changes in the probability of progression to Ranawat ≥II, however, NEURO would be the preferred strategy if ≥20 % of patients worsen to Ranawat ≥II under PROPH. Conclusion: Results of this decision analysis indicate that prophylactic surgery is a reasonable management option for patients with cervical instability related to RA. These findings are influenced by the very good outcomes reported in the surgical literature. 4 CLINICAL ASSOCIATIONS AND EPITOPES BOUND BY AUTOANTIBODIES TO GW BODIES AND THE CYTOPLASMIC AUTOANTIGEN GW182 Theophany Eystathioy, LeeAnne Luft, Edward K.L. Chan, Marvin Fritzler (University of Calgary, Calgary, Alberta, University of Florida, Gainseville, FL, USA) A human autoimmune serum was used to identify an autoantigen named GW182 and novel cytoplasmic structures referred to as GW bodies (GWBs). Unique features of the GW182 protein include >35 repeats of a glycine (G) and tryptophan (W) motif, a RNA recognition motif (RRM) that bound to messenger RNAs (mRNA), and a nuclear localization signal (NLS). The goal of the study was to determine the frequency of anti-GWB in a clinical service laboratory, to elucidate the clinical features of patients with anti-GW182 antibodies, and to characterize the anti-GW182 autoantibody response by defining the epitopes bound by human autoantibodies. Out of 5000 sequential, unselected serum samples studies in a clinical service laboratory, ~200 sera showed a cytoplasmic speckled staining pattern on HEp-2 cells. Of these 200 sera, 18 (9%) had autoantibodies to the GWBs as determined by co-localization with a monoclonal antibody (4B6) that reacts with the GW182 protein and stains the GWBs. The anti-GWB titres as determined by IIF on commercially prepared HEp-2 cells ranged from 1/320 - 1/5120. Seventeen of the eighteen patients (39%) with autoantibodies to the GWBs were female with an age range from 46 to 85 years (mean age 58 yr). The clinical diagnoses could be stratified into three groups: group A composed of 9 patients had predominantly mixed motor and/or sensory neuropathy, although other disease manifestations were also noted; 3 patients comprising group B had Sjögren's syndrome (SjS) in addition to some neurological features that overlapped with group A; in group 3, 6 patients had SLE and/or SjS without documented evidence of neurological disease. When the various diagnoses or clinical conditions were tabulated individually, SjS was the most common, seen in 7/18 (39%), followed by patients with neurological disease (motor and sensory neuropathy and/or ataxia) in 6/18 (33%), followed by SLE in 4/18 (22%). Of interest, 5/18 (28%), 9/18 (50%) and 3/18 (17%) of the sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens respectively. When overlapping 15mer peptides representing the full length GW182 were synthesized on nitrocellulose membranes, the human autoantibodies bound to peptides that mapped to the GW-rich mid-part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens that can be classified as messenger RNA ribonucleoprotein (mRNP) complexes. 5 ASSOCIATION OF COLLAGEN GENES AND PRIMARY IDIOPATHIC OA Tara Snelgrove, Lynette Peddle, Yvonne Tobin, Craig Stone, Frank Noftall, Peter Rockwood, Daniel Squires, Donna Hefferton, Proton Rahman (Graduate student Memorial University, St. John's, Newfoundland and Labrador, Newfound Genomics, St. John's, Newfoundland and Labrador, Health Care Corporation, St. John's, Newfoundland and Labrador, Memorial University, St. John's, Newfoundland and Labrador) Introduction: Mutations in the collagen genes COL1A2, COL2A1, and COL9A1 are potential candidates in osteoarthritis (OA) as these genes have all been implicated in osteochondrodysplasias, which often have OA as a principal phenotype. However all these genes lack clear associations with primary, idiopathic OA. Objective: Our primary objective is to test if mutations in genes involved in cartilage homeostasis, that are known to produce a spectrum of chondrodyplasias, are associated with idiopathic OA from a founder population, where there is an enhanced signal to noise ratio. Methods: Mutations in COL1A2 (rs3216902), COL2A1 (rs2276454), and COL9A1 (rs2076816) were tested in generalized, idiopathic OA. Genotyping was performed by time-of-flight mass spectrometry, using the Sequenom platform. In brief, PCR primer pairs were amplified around the SNP, as well as extension primers, which were designed using Sequenom SpectroDesigner software. Unincorporated nucleotides were removed from the products of the PCR, using shrimp alkaline phosphatase treatment. The homogeneous mass extend reaction were then performed. The extension reaction was then purified using Sequenom SpectroClean resin. The chip was run through a mass spectrometry workstation (Bruker), and the resulting spectra were analyzed using the Sequenom Spectro TYPER-RT software. Results: The allele frequencies obtained from our study were 200/566 (35%) vs 30/118 (25%) (p=0.04) for the deletion in COL1A2; 316/560 (56%) vs 83/126 (65%) (p=0.06) for the C allele in COL2A1; and 360/574 (63%) vs 89/132 (67%) (p=0.37) for the C allele in COL9A1. For the COL1A2 deletion, the allele frequency for OA of the knee (31%), hip (42%), and hand (32%)were numerically higher than controls (25%), but were not significant due to the smaller number of patients in each sub-category. The age of onset of OA and frequency of joint replacement were not significantly different in homozygotes for the deletion of COL1A2. Conclusions: Thus we conclude that COL1A2 may be associated with idiopathic OA in the Newfoundland population and our finding needs to be replicated in other Caucasian populations. 6 THE INCIDENCE RATE OF THROMBOSIS AFTER DIAGNOSIS OF SYSTEMIC LUPUS ERYTHEMATOSUS FOLLOWS A BIMODAL PATTERN. Zhaleh Shariati, Raja Bobba, Dominique Ibanez, Dafna Gladman, Murray Urowitz, Paul R. Fortin (Toronto Western Hospital, University Health Network, Toronto, Ontario) Objective: Our objective was to describe the risk of thrombosis in SLE over time. Methods: Population. An inception cohort of patients from the University of Toronto Lupus Database was created with all patients diagnosed with SLE <1 year before their first clinic visit and no previous thrombosis. The database has used a standard prospective lupus data collection protocol since 1970. Outcome variables. Thrombotic events (TE), arterial TE (ATE), and venous TE (VTE) since diagnosis of SLE were studied. ATE was defined as angina, myocardial infarction, angiography, bypass, stroke, or peripheral arterial thrombosis, and VTE as deep venous thrombosis or pulmonary emboli. Statistics. Incidence rates and 95% confidence intervals of TE, ATE, and VTE were calculated for each year of follow-up. Only first events were included. Results: Five hundred and fifty-three patients were eligible and contributed 4,155 person-years of follow-up. Of 103 patients (18.6%) with thromboembolic events after SLE diagnosis, 67 (12.1%) had ATE and 36 (6.5%) had VTE. The incidence rates [95% CI] per 100 py of TE since SLE ranged from 0.00 [0.00 - 7.13] to 7.26 [5.08 - 10.05], and suggested a bimodal pattern with peaks within the first year and also at 13 years after SLE diagnosis (Table 1). Incidence rates [95% CI] for ATE showed a pattern similar to that of overall TE, being highest within the first year of diagnosis and also 15 years after SLE diagnosis, and ranged from 0.00 [0.00-3.82] to 5.28 [1.94 -11.49] events/100py. For VTE, the incidence rates [95% CI] were higher within the first year of diagnosis (range from 0.00 [0.00 - 0.97] to 3.23 [1.84 - 5.24] events/100py) and decreased in later time periods.
Conclusion: We conclude that there is a bimodal pattern of thrombosis incidence in SLE. Although previous studies have suggested a later mode of TE in SLE, the observation of an early mode is new. The first mode is found within the first year after diagnosis and may reflect lupus disease activity while the later mode is observed 10 years after diagnosis and may reflect overall damage. Strategies to prevent TE may derive from a better understanding of this pattern of thrombosis in SLE.  Figure 1. Palmoplantar pustulosis. Dr. Claude Blier. CRA slide competition
 Figure 2. Eye maculopathy. Dr. Joseph B. Houpt. CRA slide competition
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