To describe disease expression and damage accrual in systemic lupus erythematosus (SLE), and determine the influence of ethnicity and socioeconomic factors on damage accrual in a large multiethnic Canadian cohort.
Adults with SLE were enrolled in a multicenter cohort. Data on sociodemographic factors, diagnostic criteria, disease activity, autoantibodies, treatment, and damage were collected using standardized tools, and results were compared across ethnic groups. We analyzed baseline data, testing for differences in sociodemographic and clinical factors, between the different ethnic groups, in univariate analyses; significant variables from univariate analyses were included in multivariate regression models examining for differences between ethnic groups, related to damage scores.
We studied 1416 patients, including 826 Caucasians, 249 Asians, 122 Afro-Caribbeans, and 73 Aboriginals. Although the overall number of American College of Rheumatology criteria in different ethnic groups was similar, there were differences in individual manifestations and autoantibody profiles. Asian and Afro-Caribbean patients had more frequent renal involvement and more exposure to immunosuppressives. Aboriginal patients had high frequencies of antiphospholipid antibodies and high rates of comorbidity, but disease manifestations similar to Caucasians. Asian patients had the youngest age at onset and the lowest damage scores. Aboriginals had the least education and lowest incomes. The final regression model (R2=0.27) for higher damage score included older age, longer disease duration, low income, prednisone treatment, higher disease activity, and cyclophosphamide treatment.
There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.
Arthritis mutilans is often described as the most severe form of psoriatic arthritis. However, a widely agreed on definition of the disease has not been developed. At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members hoped to agree on a definition of arthritis mutilans and thus facilitate clinical and molecular epidemiological research into the disease. Members discussed the clinical features of arthritis mutilans and definitions used by researchers to date; reviewed data from the ClASsification for Psoriatic ARthritis study, the Nordic psoriatic arthritis mutilans study, and the results of a premeeting survey; and participated in breakout group discussions. Through this exercise, GRAPPA members developed a broad consensus on the features of arthritis mutilans, which will help us develop a GRAPPA-endorsed definition of arthritis mutilans.
To investigate the association between smoking and psoriatic arthritis (PsA) among patients with psoriasis and its interaction with the HLA-C*06 allele.
In this exploratory case-control study, smoking status was determined at the time of the diagnosis of arthritis for PsA patients and at their first study visit for psoriasis patients, when they were confirmed not to have PsA. The proportions of patients exposed to smoking were compared in patients with PsA to those with psoriasis alone. A logistic regression model was constructed to test the independent association of smoking and PsA after adjusting for potential confounders. The statistical interaction between HLA-C*06 and smoking was tested through a regression model.
The proportions of current and past smokers were higher in the psoriasis group compared with the PsA group (30.2% vs 23.4% and 26.7% vs 22.3%, p=0.001, respectively). On multivariate analysis being a current smoker versus a lifetime non-smoker remained inversely associated with PsA (OR 0.57, p=0.002), while past smoker versus lifetime non-smoker status was no longer significant. In a subgroup analysis, smoking remained inversely associated with PsA only among patients who were HLA-C*06 negative. Regression analysis revealed that the interaction between smoking status (ever smoked vs lifetime non-smoker) and HLA-C*06 was statistically significant (p=0.01).
Smoking may be inversely associated with PsA among psoriasis patients. This association is not present among HLA-C*06-positive individuals.
Recent studies have shown that a nonsynonymous single-nucleotide polymorphism (SNP) (Arg381Gln; rs11209026) in the interleukin-23 receptor (IL-23R) gene on chromosome 1p31 is associated with Crohn's disease and psoriasis. Given the clinical and immunologic overlap between ankylosing spondylitis (AS) and these diseases, and the potential function of this candidate SNP, this study was undertaken to examine the association of IL-23R variants with AS in multiple Canadian populations.
We examined 3 cohorts of AS patients from established rheumatic disease centers in Canada. The majority of AS patients were Caucasians of northern European descent, and all patients satisfied the modified New York classification criteria for AS or for juvenile spondylarthritis. We examined 424 AS probands and 401 controls from Alberta, 251 AS probands and 122 controls from Toronto, and 121 AS probands and 219 controls from Newfoundland. Ten IL-23R SNPs were genotyped, 9 of which were incorporated in the haplotype analysis. Allele and haplotype associations were calculated using the WHAP software package. P values for haplotype associations were calculated using a permutation test.
The primary SNP of interest in a previous study of inflammatory bowel disease (IBD) (Arg381Gln; rs11209026) was found to be protective against AS in the Newfoundland population (P=0.04) and in the Toronto population (P=0.04) in single-marker univariate analysis. The strongest association, however, was with SNP rs11465804 (P=0.007 for the Newfoundland population and P=0.0007 for the Toronto population). A 3-marker sliding window omnibus test revealed a significant association with markers rs10489629, rs2201841, and rs11465804 in both the Newfoundland population (P=0.04) and the Alberta population (P=0.034). Our results were independent of the IBD and psoriasis status of the AS patients.
This concurrent analysis of 3 distinct AS populations and their regional controls demonstrates a disease association with the IL-23R locus and implicates the same polymorphisms associated with IBD and psoriasis.
A recent genome-wide pooling study noted a significant association of interleukin 23 receptor (IL-23R) and psoriasis. Overxpression of IL-23 has been detected in lesional psoriatic skin, and induces epidermal proliferation. Given the interplay between psoriasis and PsA, we examined the association of IL-23R variants in 2 independent Canadian Caucasian cohorts of patients with psoriatic arthritis (PsA).
We examined 496 PsA probands and 476 controls. Cases and controls were genotyped for a panel of 11 single-nucleotide polymorphisms (SNP) in IL-23R. Allele and haplotype associations were calculated using WHAP software. P values for haplotype associations were calculated using a permutation test.
The 381Gln allele of the coding SNP Arg381Gln (rs11209026) was found to be protective in the Canadian population (p=0.004; corrected p=0.044). A 2-marker haplotype from SNP rs7530511 and rs11209026 was associated with PsA (p=0.011). All 3-marker sliding windows containing SNP rs11209026 were associated with PsA (p=0.02 for all 3 windows). The magnitude of effect of IL-23R association in PsA appears to be similar to that reported in uncomplicated psoriasis.
Significant associations between Arg381Gln SNP and haplotypes encoding this variant were noted in PsA. It remains to be determined what contribution of this association, if any, is specifically due to the inflammatory arthritis (PsA) rather than psoriasis.
To examine the association between the IL1 gene cluster and susceptibility to ankylosing spondylitis (AS) in 3 independent case-control cohorts.
We analyzed 394 patients and 446 controls from Alberta, Newfoundland, and Toronto, Canada. Samples were genotyped using a panel of 38 single-nucleotide polymorphism (SNP) markers within the IL1 gene cluster. Data from 20 informative and nonredundant SNP markers were analyzed using several association test strategies. First, we used the program WHAP to identify single-marker associations. Second, we used WHAP to analyze "sliding windows" of 3 contiguous markers along the entire extent of the IL1 gene cluster in order to identify haplotypic associations. Third, we used the linkage disequilibrium mapping program DMLE to estimate the posterior probability distribution of a disease locus.
A total of 14 SNP markers showed significant single-locus disease associations, the most significant being rs3783526 (IL1A) (P = 0.0009 in the Alberta cohort, P = 0.04 in the Newfoundland cohort) and rs1143627 (IL1B) (P = 0.0005 in the Alberta cohort, P = 0.02 in the Newfoundland cohort). Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/rs3917356/rs3917354 (P = 0.006-0.0001). With DMLE, a strong peak in the probability distribution was estimated near IL1A in both the Alberta and the Newfoundland populations.
These results indicate that the IL1 locus, or a locus close to IL1, is associated with susceptibility to AS.
To determine prevalence and type of atherosclerotic vascular events (AVE) occurring after entry to the University of Toronto Lupus Clinic; and to compare risk factors in patients with systemic lupus erythematosus (SLE) with AVE to matched SLE controls without AVE.
Patients with SLE attending the University of Toronto Lupus Clinic who did not have AVE prior to clinic entry were included. Patients have been followed at 2-6 months since 1970 according to a standard protocol. Cases with AVE were matched for sex, era at first clinic visit (1970s, 1980s, 1990s +), inception status, age at first visit, and duration of followup. Chi-square, Fisher's exact, paired T test, and McNemar test were used. Comparison of risk factors for the development of AVE was done using a stepwise conditional logistic regression model for matched pairs.
In a total cohort of 1087 SLE patients followed from 1970 until 2004, the prevalence of AVE was 10.9%, and in 561 inception patients it was 9.6%. In multivariate analyses, neuropsychiatric involvement was significantly associated with AVE in both the total and inception cohorts. Smoking was also associated with AVE in the inception cohort, whereas the number of coronary artery disease (CAD) risk factors and vasculitis were significant in the total cohort.
AVE are major contributors to the clinical presentation of late-stage lupus. A combination of lupus related factors and classic CAD risk factors contributed to the development of AVE.
It has been reported that influenza vaccination increases autoantibody production and/or disease activity in a significant proportion of patients with systemic lupus erythematosus (SLE). During the recent H1N1 epidemic, we investigated whether the use of adjuvant- and nonadjuvant-containing H1N1 vaccine induced increased autoantibody production in patients with SLE.
Patients with SLE who received H1N1 vaccination and had a battery of 9 autoantibodies tested before and 1 and 3 months after vaccination were included. Antibodies tested included rheumatoid factor (nephelometry), antinuclear antibody (immunofluorescence), anti-DNA (Farr), anti-RNP, anti-Sm, anti-Ro, anti-La, anti-Scl-70, and anti-Jo-1 (enzyme-linked immunosorbent assay). Patients were evaluated by standard protocol, including items necessary to calculate the Systemic Lupus Erythematosus Disease Activity Index 2000 and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Descriptive statistics and McNemar's test were performed to evaluate change in antibody positivity. Multivariate logistic regression was performed to adjust for repeated measures in the comparisons of autoantibodies over visits and vaccine types.
One hundred three patients (94 women, 9 men) with a mean ± SD age at vaccination of 43.9 ± 15.2 years and a mean ± SD disease duration of 14.2 ± 11.0 years were included. Fifty-one patients received adjuvant and 52 received nonadjuvant vaccines. Antibody testing was performed a mean of 1.9 months prior to the vaccination. The first postvaccination sample was taken a mean of 1 month after vaccination and the second a mean of 3.5 months after vaccination. The percentage of patients with changes in antibodies following vaccination was not statistically significant for most antibodies. After adjusting for the number of tests performed, none of the associations was significant.
H1N1 vaccination (both adjuvant and nonadjuvant) did not increase the levels of autoantibodies in patients with SLE.
To determine whether the presence of psoriatic arthritis (PsA) is associated with greater comorbidity, in particular cardiovascular morbidity, compared to psoriasis without arthritis.
Six hundred eleven patients with PsA were recruited from the University of Toronto Psoriatic Arthritis Clinic and 449 psoriasis without arthritis patients were recruited from the University of Toronto Psoriasis Cohort. The clinical database was used to identify the prevalence of cardiovascular and other comorbidities in both PsA and psoriasis without arthritis patients. Univariate and multivariate logistic regression analyses were conducted to estimate odds ratios (ORs), comparing the odds of ever having a given comorbid disease in PsA patients with those in psoriasis without arthritis patients. Covariates included age, sex, education, smoking status, severity and duration of psoriasis, medication status, and other comorbidities.
The prevalence of hypertension, obesity, hyperlipidemia, type 2 diabetes mellitus, and at least 1 cardiovascular event in PsA patients was 37.1%, 30.0%, 20.7%, 12.0%, and 8.2%, respectively. This was significantly higher than in psoriasis without arthritis patients, with unadjusted ORs ranging from 1.54 to 2.59. In the multivariate analyses, hypertension remained significantly elevated (adjusted OR 2.17). PsA was also significantly associated with infections not treated with antibiotics (presumably viral), neurologic conditions, gastrointestinal disorders, and liver disease (adjusted ORs 2.83, 4.76, 21.53, and 7.74, respectively). Infections treated with antibiotics and depression/anxiety were relatively common in PsA, with a prevalence of 30.5% and 20.7%, respectively. However, this was not significantly different from psoriasis without arthritis after multivariate adjustments.
The results suggest that inflammatory joint disease may play a role in both cardiovascular and noncardiovascular morbidity in PsA.
Psoriasis is often associated with other diseases, substantially adding to the patient's burden of disease. Recent epidemiologic studies have demonstrated an increased cardiovascular morbidity among patients with psoriasis and psoriatic arthritis (PsA), which contributes to their reduced life expectancy. At the meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) adjacent to the International Federation of Psoriasis Associations (IFPA) congress, members discussed the pathogenetic aspects of this association and resulting consequences for the management of patients with psoriasis and PsA. A future research agenda was considered.