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Psoriasis: HELP
Articles by Vinod Chandran
Based on 129 articles published since 2008
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Between 2008 and 2019, V. Chandran wrote the following 129 articles about Psoriasis.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
76 Article Diffuse idiopathic skeletal hyperostosis in psoriatic arthritis. 2013

Haddad, Amir / Thavaneswaran, Arane / Toloza, Sergio / Chandran, Vinod / Gladman, Dafna D. ·Centre for Prognosis Studies in the Rheumatic Diseases University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada. ·J Rheumatol · Pubmed #23772085.

ABSTRACT: OBJECTIVE: To determine the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in patients with psoriatic arthritis (PsA) and to identify the features associated with its occurrence. METHODS: Patients were recruited from the University of Toronto PsA observational cohort initiated in 1978. All patients fulfilled the CASPAR criteria. Radiographs of peripheral joints and spine were obtained every 2 years. DISH was defined as flowing bony bridges in at least 4 contiguous thoracic vertebrae. Each PsA patient with DISH was matched by sex to 3 PsA patients without DISH. Demographics, disease characteristics, and radiographic features were compared using McNemar test, Fisher's exact test, chi-square test, and paired t test as appropriate. Logistic regression analyses models with stepwise regression were conducted. RESULTS: DISH was observed in 78 (8.3%) of 938 patients with PsA. Patients with DISH were older and had longer disease duration, higher body mass index (BMI), and higher uric acid levels. Diabetes and hypertension were more prevalent in patients with DISH than in those without. The severity of radiographic damage to peripheral joints was also greater in patients with DISH. The presence of inflammatory back pain, HLA-B*27 allele, and sacroiliitis was similar in both groups. Patients with DISH had more syndesmophytes and calcaneal spurs. Older age, higher BMI, and the presence of radiographic damage to peripheral joints were associated with DISH in multivariate analysis. CONCLUSION: The diagnosis of DISH is possible in the presence of axial PsA. DISH was associated with known DISH-related factors including older age and high BMI, as well as the presence of radiographic damage to peripheral joints.

77 Article Incremental effects of comorbidity on quality of life in patients with psoriatic arthritis. 2013

Husted, Janice A / Thavaneswaran, Arane / Chandran, Vinod / Gladman, Dafna D. ·Department of Health Studies and Gerontology, University of Waterloo, Waterloo, Ontario, Canada. ·J Rheumatol · Pubmed #23772076.

ABSTRACT: OBJECTIVE: To assess the added effect of comorbidity on quality of life (QOL) in psoriatic arthritis (PsA). METHODS: Between 2006 and 2012, 631 patients were recruited from the University of Toronto PsA Clinic. Using the clinical database, we ascertained the frequency of 15 comorbidities. The Medical Outcomes Study Short Form-36 (SF-36) physical (PCS) and mental component (MCS) summary scales were used to assess QOL. Linear regression analyses were conducted to estimate the magnitude of the association between number and type of comorbidities and PCS and MCS scores, after adjustment for disease-related and sociodemographic variables. RESULTS: Prevalence of comorbidity was high, with 42% of patients having 3 or more comorbid conditions. After adjustment for inflammatory disease-related and sociodemographic factors, a history of 3 or more comorbid conditions accounted for only 2% and 1% of the R(2) value explained in PCS and MCS scores, respectively. In terms of added burden, type of comorbid condition was more significant than number of comorbidities. After adjustment for disease-related and sociodemographic factors, fibromyalgia (FM), neurological disorders, and obesity jointly accounted for 6% of R(2) value explained in PCS scores, while FM and depression/anxiety jointly accounted for about 9% of the R(2) explained in MCS scores. The point decrease in PCS and MCS scores associated with each of these disorders was clinically significant. The 11 other comorbid conditions failed to achieve statistical significance in the models. CONCLUSION: The added effect of comorbidity on patient-reported physical and mental health in PsA was more related to type of comorbidity than number of comorbidities.

78 Article Soluble biomarkers associated with response to treatment with tumor necrosis factor inhibitors in psoriatic arthritis. 2013

Chandran, Vinod / Shen, Hua / Pollock, Remy A / Pellett, Fawnda J / Carty, Adele / Cook, Richard J / Gladman, Dafna D. ·Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, Canada. ·J Rheumatol · Pubmed #23637322.

ABSTRACT: OBJECTIVE: To identify soluble biomarkers associated with response to therapy with tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA). METHODS: The study was conducted at a PsA clinic where patients are assessed every 6 months, and serum samples are collected and stored once a year at the time of clinical assessment. Forty patients with active PsA who gave serum samples prior to treatment with TNFi and after at least 3 months of therapy were identified. Patients were classified as TNFi responders if tender joint count was < 3, swollen joint count was 0, and Psoriasis Area and Severity Index score was < 4 at the time the second sample was collected. The following biomarkers were tested by ELISA: TNF superfamily 14, matrix metalloprotease-3 (MMP-3), receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, cartilage oligomeric matrix protein (COMP), CPII, C2C and C1-2C, CS-846, and highly sensitive C-reactive protein. Paired t tests and logistic regression was used for statistical analyses. RESULTS: After a mean treatment duration of 11 months with TNFi (etanercept 28 patients, adalimumab 6, golimumab 4, infliximab 2), 29 patients were classified as TNFi responders. Baseline level of MMP-3 was independently associated with responder status (OR 1.067 for each 1-unit increase, p = 0.045). A reduction in MMP-3 levels with therapy increased the odds of achieving response (OR 1.213 for each 1-unit change, p = 0.030), whereas a reduction in COMP decreased the odds (OR 0.587, for each 100-unit increase, p = 0.039). None of the other biomarkers was associated with response. CONCLUSION: Baseline as well as reduction in serum MMP-3 and increase in serum COMP are independently associated with response to TNFi therapy in patients with PsA.

79 Article The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C. 2013

Pollock, R A / Chandran, V / Pellett, F J / Thavaneswaran, A / Eder, L / Barrett, J / Rahman, P / Farewell, V / Gladman, D D. ·University of Toronto Psoriatic Arthritis Program, Toronto Western Research Institute, Toronto, Ontario, Canada. ·Tissue Antigens · Pubmed #23611695.

ABSTRACT: A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.

80 Article Physician scores vs patient self-report of joint and skin manifestations in psoriatic arthritis. 2013

Chaudhry, Salman R / Thavaneswaran, Arane / Chandran, Vinod / Gladman, Dafna D. ·Internal Medicine Department, McMaster University, Hamilton, Ontario, Canada. ·Rheumatology (Oxford) · Pubmed #23267168.

ABSTRACT: OBJECTIVE: We aimed to determine the degree of agreement between patient self-report and physician assessment of joint disease activity and damage and degree of skin disease. METHODS: Patients were followed up in the PsA clinic for homunculus for tender joints, swollen joints, deformed joints and problematic joints, as well as the severity of their psoriasis. A rheumatologist documented tender joints, swollen joints and damaged joints as well as psoriasis area and severity index score. The scores were compared using the concordance correlation coefficient and Bland-Altman plots were constructed. RESULTS: One hundred and forty outpatients participated in the study (60 females and 80 males) with a mean age of 52.8 years. Their mean age at onset of psoriasis was 27.4 years and at PsA onset was 36.9 years. The average duration of psoriasis at the time of the study was 25.3 years and of PsA was 16.2 years. The correlation between patient and physician scores was poor for tender and swollen joints, although it was better for deformed joints and psoriasis area and severity index score but still did not reach a level of good agreement. CONCLUSION: PsA patient's self-report has a poor correlation with physician assessment. Thus patient self-reported data are insufficient to accurately monitor PsA disease activity when compared with a physician's joint examination and skin score. Expert physical examination should remain the gold standard for the assessment of actively inflamed joint and skin disease in patients with PsA in both clinical trials and observational cohort studies.

81 Article Serum adipokines in patients with psoriatic arthritis and psoriasis alone and their correlation with disease activity. 2013

Eder, Lihi / Jayakar, Jai / Pollock, Remy / Pellett, Fawnda / Thavaneswaran, Arane / Chandran, Vinod / Rosen, Cheryl F / Gladman, Dafna D. ·Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, , Toronto, Ontario, Canada. ·Ann Rheum Dis · Pubmed #23243196.

ABSTRACT: OBJECTIVE: To compare the prevalence of metabolic syndrome (MetS) and the levels of related biomarkers in patients with psoriatic arthritis (PsA) and psoriasis without arthritis (PsC). METHODS: This study compared patients with PsA and patients with PsC. The presence of MetS was determined. Serum levels of insulin, adiponectin and leptin were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. HOMA-IR, adiponectin and leptin were log-transformed. Continuous variables were compared using the t test and the χ(2) test was used for discrete variables. Multivariate regression models were used to investigate the association of MetS and adiponectin with PsA compared to PsC after adjusting for potential confounding variables. RESULTS: 203 PsA and 155 PsC patients were analysed. The prevalence of MetS was higher in PsA patients compared to those with PsC. However, this did not reach statistical significance (36.5% vs 27.1%, p=0.056). The levels of adipokines were significantly higher in PsA compared to PsC: adiponectin (8.8±5.2 vs 7.4±4.5 log (µg/ml), p=0.009) and leptin in women (3.1±0.8 vs 2.8±0.8, log (ng/ml), p=0.04). HOMA-IR was also higher in PsA (0.97±0.63 vs 0.68±0.81, p<0.001). No difference was observed in leptin levels in men. In multivariate regression analysis, PsA (p=0.04) and the psoriasis area and severity index score (p=0.02) were associated with MetS. Adiponectin was significantly associated with PsA (p=0.005), the use of anti-tumour necrosis factor α therapy (p=0.03) and active joint count (p=0.001). CONCLUSIONS: MetS and related adipokines correlated with an increased burden of skin and joint inflammation.

82 Article Serum kallikrein-8 correlates with skin activity, but not psoriatic arthritis, in patients with psoriatic disease. 2013

Eissa, Azza / Cretu, Daniela / Soosaipillai, Antoninus / Thavaneswaran, Arane / Pellett, Fawnda / Diamandis, Anastasia / Cevikbas, Ferda / Steinhoff, Martin / Diamandis, Eleftherios P / Gladman, Dafna / Chandran, Vinod. ·Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. ·Clin Chem Lab Med · Pubmed #23096109.

ABSTRACT: BACKGROUND: About 30% of cutaneous psoriasis (PsC) patients develop psoriatic arthritis (PsA) in the joint, which is under-recognized by dermatologists. Biomarkers for PsA are needed so that early referral to a rheumatologist is made. Kallikreins (KLKs) are secreted serine proteases implicated in skin desquamation and inflammation. This study examined KLK potential as serum biomarkers of PsA in cutaneous psoriasis patients. METHODS: KLKs were measured by ELISAs in synovial fluids of three PsA patients and three control early osteoarthritis (OA) patients, as well as in a cohort of 152 serum samples collected from age- and sex-matched PsC patients, with (n=76) or without PsA (n=76). KLK expression in psoriatic plaques was examined by immunohistochemistry. Univariate and multivariate logistic regression analyses were conducted to analyze the association between serum KLK levels and disease class (PsC, PsA). Serum KLKs that associated with PsA were correlated with clinical parameters of skin and joint activity. RESULTS: Among the seven KLKs tested, KLK6 and KLK8 were elevated in both PsA synovial fluids and psoriatic plaques, but only serum KLK8 levels were associated with psoriatic disease (odds ratio=2.56, p=0.03). Although significantly elevated in PsC and PsA sera compared to healthy controls, KLK8 did not discriminate PsA from PsC patients. KLK8 correlated positively with the psoriasis area and severity index (PASI) (r=0.43, p=0.001) independent of age, sex and psoriasis duration ( β=1.153, p=0.0003) and exhibited no correlations with tender or swollen joint counts. CONCLUSIONS: Increased KLK8 serum level in PsA patients reflects disease activity in the skin but not in the joints. Serum KLK levels are not useful for screening psoriasis patients for PsA.

83 Article The burden of carotid artery plaques is higher in patients with psoriatic arthritis compared with those with psoriasis alone. 2013

Eder, Lihi / Jayakar, Jai / Shanmugarajah, Sutha / Thavaneswaran, Arane / Pereira, Daniel / Chandran, Vinod / Rosen, Cheryl F / Gladman, Dafna D. ·Department of Rheumatology, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto Psoriatic Arthritis Program, Toronto, Ontario, Canada. ·Ann Rheum Dis · Pubmed #22736087.

ABSTRACT: AIM: To compare the extent of atherosclerosis in patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis without arthritis (PsC). METHODS: In this cross-sectional study the authors compared patients with PsA with PsC patients. Psoriasis patients underwent a rheumatological assessment to exclude inflammatory arthritis. Ultrasonographic measurements of carotid total plaque area (TPA) and carotid intima-media thickness (cIMT) were performed. t Test was used to compare the imaging findings between the two groups. Multivariate linear regression analysis was used to assess the association between disease status and imaging findings after adjusting for potential confounders. RESULTS: Overall, 125 PsA and 114 PsC patients were compared. There were no significant differences in age, gender or cardiovascular risk factors between the two groups. Patients with PsA exhibited greater TPA than did PsC patients (TPA (square root of area in mm(2)) 3.33±3.34 vs 2.43±2.72, p=0.03). This difference remained statistically significant in the multivariate regression analysis after adjusting for potential confounders (p=0.03). The difference in cIMT between the groups did not achieve statistical significance (p=0.09). The following disease-related variables were associated with increase in TPA in multivariate regression analysis among PsA patients: duration of PsA (p=0.04), highest Psoriasis Area and Severity Index recorded in the first 3 years of follow-up (p=0.02) and erythrocyte sedimentation rate (p=0.005). CONCLUSIONS: PsA patients suffer from more severe subclinical atherosclerosis compared with patients with PsC. This difference is independent of traditional cardiovascular risk factors and correlates with PsA disease duration, more severe skin disease and increased inflammatory markers.

84 Article Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis. 2013

Eder, Lihi / Thavaneswaran, Arane / Chandran, Vinod / Gladman, Dafna D. ·Correspondence to Dafna D Gladman, University of Toronto, Toronto Western Research Institute, Psoriatic Arthritis Clinic, Centre for Prognostic Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto 97914, Canada. ·Ann Rheum Dis · Pubmed #22589379.

ABSTRACT: OBJECTIVE: The authors aimed to assess gender-related differences in severity of psoriatic arthritis (PsA) as reflected by measures of disease activity, joint damage, quality of life and disability. METHODS: A cross-sectional analysis was performed among patients who have been followed in a large PsA clinic. Demographic, clinical and radiographic data as well as information about quality of life and function were retrieved from the clinic database. Radiographic damage was assessed according to modified Steinbrocker score (mSS). The association between gender and the following outcome variables, radiographic joint damage, axial involvement and measures of quality of life and function, was assessed by multivariate regression analysis after adjustment for potential confounders. RESULTS: Three hundred and forty-five men and 245 women were included in the study. Axial involvement was more frequent in men (42.9% vs 31%, p=0.003). In multivariate analysis, adjusting for potential confounders, men were more likely to develop axial involvement (OR 1.8, p=0.003). Men were also more likely to develop more severe radiographic damage in the peripheral joints as evident by mSS. Men were more likely to be in a higher mSS damage category compared with women after adjusting for potential confounders in multivariate analysis (OR 1.6, p=0.007). Women suffered from more severe limitations in function and worse quality of life compared with men based on several patients' reported outcomes. CONCLUSIONS: Men with PsA are more likely to develop axial involvement and radiographic joint damage, while women are more likely to report about limitation in function and impaired quality of life.

85 Article Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. 2012

Tsoi, Lam C / Spain, Sarah L / Knight, Jo / Ellinghaus, Eva / Stuart, Philip E / Capon, Francesca / Ding, Jun / Li, Yanming / Tejasvi, Trilokraj / Gudjonsson, Johann E / Kang, Hyun M / Allen, Michael H / McManus, Ross / Novelli, Giuseppe / Samuelsson, Lena / Schalkwijk, Joost / Ståhle, Mona / Burden, A David / Smith, Catherine H / Cork, Michael J / Estivill, Xavier / Bowcock, Anne M / Krueger, Gerald G / Weger, Wolfgang / Worthington, Jane / Tazi-Ahnini, Rachid / Nestle, Frank O / Hayday, Adrian / Hoffmann, Per / Winkelmann, Juliane / Wijmenga, Cisca / Langford, Cordelia / Edkins, Sarah / Andrews, Robert / Blackburn, Hannah / Strange, Amy / Band, Gavin / Pearson, Richard D / Vukcevic, Damjan / Spencer, Chris C A / Deloukas, Panos / Mrowietz, Ulrich / Schreiber, Stefan / Weidinger, Stephan / Koks, Sulev / Kingo, Külli / Esko, Tonu / Metspalu, Andres / Lim, Henry W / Voorhees, John J / Weichenthal, Michael / Wichmann, H Erich / Chandran, Vinod / Rosen, Cheryl F / Rahman, Proton / Gladman, Dafna D / Griffiths, Christopher E M / Reis, Andre / Kere, Juha / Anonymous6390741 / Anonymous6400741 / Anonymous6410741 / Anonymous6420741 / Nair, Rajan P / Franke, Andre / Barker, Jonathan N W N / Abecasis, Goncalo R / Elder, James T / Trembath, Richard C. ·Department of Biostatistics, Center for Statistical Genetics, University of Michigan Ann Arbor, MI, USA. ·Nat Genet · Pubmed #23143594.

ABSTRACT: To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

86 Article Psoriasis and psoriatic arthritis in Peruvian aborigines: a report from the GRAPPA 2011 annual meeting. 2012

Toloza, Sergio M A / Vega-Hinojosa, Oscar / Chandran, Vinod / Valle Onate, Rafael / Espinoza, Luis R. ·Department of Medicine, Hospital San Juan Bautista, Catamarca, Argentina; Hospital III, Juliaca, Peru. ·J Rheumatol · Pubmed #23118292.

ABSTRACT: OBJECTIVE: To determine the presence of psoriasis and psoriatic arthritis (PsA) in aboriginal people living in the Andean Mountains of Peru. METHODS: Consecutive patients with psoriasis and PsA attending an arthritis clinic in Juliaca, Puno, Peru, located 3824 m above sea level were examined. The CASPAR (ClASsification of Psoriatic ARthritis) criteria were used for classification of PsA. Diagnosis of psoriasis was confirmed by a dermatologist. RESULTS: Seventeen patients [11 (65%) men and 6 (35%) women] fulfilled classification criteria for PsA; one patient was of European ancestry and is not included in this report. Of the 16 aboriginal patients in this report, 5 were natives of Quechua ancestry and one was native Aymara. At the time of their first clinic visit, no native patient with PsA had a family history of psoriasis or PsA, and all patients exhibited an established disease of long duration and severity. Methotrexate was the drug of choice for all patients; 2 patients are currently receiving biological therapy. CONCLUSION: Contrary to what has been reported in the literature, both psoriasis and PsA are present in aboriginal people from the Andean Mountains of Peru. More studies are needed to further define the phenotype of these disorders, as well as the pathogenetic role of genetic and environmental factors.

87 Article Psoriatic arthritis in Canadian clinical practice: the PsA assessment in rheumatology. 2012

Gladman, Dafna D / Chandran, Vinod / Thavaneswaran, Arane / Zummer, Michel. ·University of Toronto, Toronto Western Research Institute, Psoriatic Arthritis Program, University Health Network, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, 1E-410B, Toronto, Ontario M5T 2S8, Canada. dafna.gladman@utoronto.ca ·J Rheumatol · Pubmed #22859361.

ABSTRACT: OBJECTIVE: We aimed to determine disease severity and treatment of patients with psoriatic arthritis (PsA) in rheumatology practices in Canada through the PsA Assessment in Rheumatology (PAIR) study. METHODS: Rheumatologists who were members of the Canadian Rheumatology Association were asked to complete a form for each patient addressing demographic questions, history, clinical examination, and patient-reported outcomes. Results were compared with a cohort seen in a PsA clinic during the same period. RESULTS: From across Canada, 22 rheumatologists from 5 provinces submitted information about 233 consecutive patients with PsA [145 men (62.2%), 88 women (37.8%), mean age 53.2 yrs (±12.7), 88.4% disease duration>2 yrs]. A majority (80.7%) fulfilled ClASsification for Psoriatic ARthritis (CASPAR) criteria, and 30% had taken no disease-modifying antirheumatic drugs. Clinical joint damage was documented in 60% of the patients, active skin disease in 70%, and nail lesions in 32%. Only 22% were rated as having moderate to high disease activity, while 52% were rated as low disease activity and 26% were deemed in remission. The decision was based on joint counts, patient global assessment, physician global assessment, and acute-phase reactants. Twenty-seven percent of the patients were to have their medications changed based on the current visit, the majority for inadequate response to medications. Patients in the PAIR cohort had more inflamed joints but similar damage to those in the PsA clinic. CONCLUSION: Patients with PsA seen in regular rheumatology practice fulfill CASPAR criteria, have active disease, and more than half have joint damage. The majority have low activity or are in remission.

88 Article Soluble biomarkers may differentiate psoriasis from psoriatic arthritis. 2012

Chandran, Vinod. ·Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Toronto, Ontario M5T 2S8, Canada. vchandra@uhnresearch.ca ·J Rheumatol Suppl · Pubmed #22751596.

ABSTRACT: Patients with psoriatic arthritis (PsA) have a higher inflammatory burden and poorer quality of life compared to patients with psoriasis without PsA. Early identification of PsA may prevent joint damage progression and improve quality of life. Soluble biomarkers have the potential to be useful for screening patients with psoriasis for underlying PsA so that appropriate referral to a rheumatologist is made. Pilot studies have shown that C-reactive protein, interleukin 6, cartilage oligomeric matrix protein (COMP), Dickkopf-1, and macrophage-colony stimulating factor may differentiate PsA from psoriasis without PsA. Compared with controls, increased serum levels of receptor activator of nuclear factor-κB ligand, tumor necrosis factor superfamily member 14, matrix metalloproteinase-3 (MMP-3), and COMP are independently associated with psoriatic disease. Increased levels of high-sensitivity CRP (hsCRP), osteoprotegerin (OPG), MMP-3, and the ratio of C-propeptide of type II collagen (CPII) to collagen fragment neoepitopes Col2-3/4 C(long mono) (C2C) are independently associated with PsA. A combination of hsCRP, OPG, MMP-3, and the ratio CPII of C2C was able to distinguish patients with PsA from those with psoriasis alone in a receiver-operating characteristic curve analysis, with area under the curve 0.904. Therefore, a combination of the above biomarkers may at least have a role in screening patients with psoriasis for PsA. These findings need to be validated in prospective studies.

89 Article Differential human leucocyte allele association between psoriasis and psoriatic arthritis: a family-based association study. 2012

Eder, Lihi / Chandran, Vinod / Pellett, Fawnda / Shanmugarajah, Sutha / Rosen, Cheryl F / Bull, Shelley B / Gladman, Dafna D. ·Center for Prognosis Studies in the Rheumatic Diseases,Toronto Western Hospital, University of Toronto Psoriatic Arthritis Clinic, Toronto, Canada. ·Ann Rheum Dis · Pubmed #22586163.

ABSTRACT: OBJECTIVE: A recent population-based study identified several HLA alleles as conferring a risk for psoriatic arthritis (PsA) among patients with psoriasis. The authors aimed to confirm these results using a family-based association study. METHODS: PsA probands, psoriasis probands and their first-degree family members were included. All participants were evaluated for the presence of psoriasis and inflammatory arthritis. HLA-B and -C genotyping was performed. The family-based association test was used to test for differences between PsA and psoriasis patients in transmission of candidate alleles from parents to offspring. RESULTS: A total of 178 PsA and 30 psoriasis probands and 561 first degree family members were analysed. The following HLA alleles were over-transmitted to PsA compared with psoriasis: HLA-C*12 (p=0.005), HLA-B*38 (p=0.04), HLA-B*39 (p=0.03), HLA-B*27 (p=0.002). CONCLUSIONS: HLA-B*27, HLA-B*38, HLA-B*39 and HLA-C*12 alleles are potential PsA-specific genetic markers among patients with psoriasis.

90 Article How can psoriatic arthritis be diagnosed early? 2012

Haddad, Amir / Chandran, Vinod. ·Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Canada. ·Curr Rheumatol Rep · Pubmed #22576859.

ABSTRACT: Psoriatic arthritis (PsA) is an inflammatory arthritis that usually develops after the onset of cutaneous psoriasis. Early diagnosis of PsA may lead to less joint damage and better long-term outcomes. Identifying inflammatory arthritis in individuals with psoriasis is the key to early diagnosis of PsA. Screening strategies targeted at individuals with psoriasis, as well as family members of patients with PsA will result in early identification of PsA. This article describes the various strategies that could be employed to identify inflammatory arthritis in patients with psoriasis so that appropriate referral to a rheumatologist for early diagnosis of PsA may be made.

91 Article Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. 2012

Jordan, Catherine T / Cao, Li / Roberson, Elisha D O / Duan, Shenghui / Helms, Cynthia A / Nair, Rajan P / Duffin, Kristina Callis / Stuart, Philip E / Goldgar, David / Hayashi, Genki / Olfson, Emily H / Feng, Bing-Jian / Pullinger, Clive R / Kane, John P / Wise, Carol A / Goldbach-Mansky, Raphaela / Lowes, Michelle A / Peddle, Lynette / Chandran, Vinod / Liao, Wilson / Rahman, Proton / Krueger, Gerald G / Gladman, Dafna / Elder, James T / Menter, Alan / Bowcock, Anne M. ·Division of Human Genetics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA. ·Am J Hum Genet · Pubmed #22521419.

ABSTRACT: Psoriasis is a common inflammatory disorder of the skin and other organs. We have determined that mutations in CARD14, encoding a nuclear factor of kappa light chain enhancer in B cells (NF-kB) activator within skin epidermis, account for PSORS2. Here, we describe fifteen additional rare missense variants in CARD14, their distribution in seven psoriasis cohorts (>6,000 cases and >4,000 controls), and their effects on NF-kB activation and the transcriptome of keratinocytes. There were more CARD14 rare variants in cases than in controls (burden test p value = 0.0015). Some variants were only seen in a single case, and these included putative pathogenic mutations (c.424G>A [p.Glu142Lys] and c.425A>G [p.Glu142Gly]) and the generalized-pustular-psoriasis mutation, c.413A>C (p.Glu138Ala); these three mutations lie within the coiled-coil domain of CARD14. The c.349G>A (p.Gly117Ser) familial-psoriasis mutation was present at a frequency of 0.0005 in cases of European ancestry. CARD14 variants led to a range of NF-kB activities; in particular, putative pathogenic variants led to levels >2.5× higher than did wild-type CARD14. Two variants (c.511C>A [p.His171Asn] and c.536G>A [p.Arg179His]) required stimulation with tumor necrosis factor alpha (TNF-α) to achieve significant increases in NF-kB levels. Transcriptome profiling of wild-type and variant CARD14 transfectants in keratinocytes differentiated probably pathogenic mutations from neutral variants such as polymorphisms. Over 20 CARD14 polymorphisms were also genotyped, and meta-analysis revealed an association between psoriasis and rs11652075 (c.2458C>T [p.Arg820Trp]; p value = 2.1 × 10(-6)). In the two largest psoriasis cohorts, evidence for association increased when rs11652075 was conditioned on HLA-Cw*0602 (PSORS1). These studies contribute to our understanding of the genetic basis of psoriasis and illustrate the challenges faced in identifying pathogenic variants in common disease.

92 Article Does the change in season affect disease activity in patients with psoriatic arthritis? 2012

Touma, Zahi / Thavaneswaran, Arane / Chandran, Vinod / Gladman, Dafna D. ·Psoriatic Arthritis Clinic, Centre for Prognostic Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto, Toronto Western Research Institute, Toronto, Canada. ·Ann Rheum Dis · Pubmed #22504562.

ABSTRACT: OBJECTIVES: To determine whether there is seasonal variation in disease activity of patients with psoriatic arthritis (PsA). METHODS: The authors identified the first available set of consecutive summer and winter visits for every patient from the prospective cohort of PsA. Comparison between summer and winter visits, and comparison of the repeated summer/winter visits, from 1978 until 2011 for the same identified patients was conducted for demographics, disease activity outcomes, laboratory results and treatment. The authors categorised disease activity into high, moderate and low states, and improvement versus flare/worsening. Descriptive statistics were computed and multivariate analyses using logistic regression and generalised estimating equations were conducted. RESULTS: The first available summer and winter visit were identified for 253 patients, and 1789 observations were analysed. There was no statistically significant difference in patients' demographics, disease activity outcomes, laboratory results and treatment between summer and winter visits. Bath Ankylosing Spondylitis Disease Activity Index scores were greater for summer visits and patients graded their disease as being worse in winter as compared with summer in the univariate analysis, but this difference did not hold in the multivariate analysis. CONCLUSIONS: The change in season does not affect PsA patients' characteristics and disease activity outcomes as determined by the physicians and patients.

93 Article Patients with psoriatic arthritis have worse quality of life than those with psoriasis alone. 2012

Rosen, Cheryl F / Mussani, Farheen / Chandran, Vinod / Eder, Lihi / Thavaneswaran, Arane / Gladman, Dafna D. ·Toronto Western Hospital,Toronto, ON M5T 2S8, Canada. ·Rheumatology (Oxford) · Pubmed #22157469.

ABSTRACT: OBJECTIVE: PsA is an inflammatory arthritis present in ∼30% of people with psoriasis (PsC). Both conditions have a significant impact on quality of life (QoL). Our objective was to test the hypothesis that people with PsA have poorer QoL than patients with PsC because of the added burden of arthritis, age and comorbidities. METHODS: Consecutive patients with PsA (CASPAR criteria) and PsC were approached to participate in this study. Patients with PsC were examined by a rheumatologist using a standardized protocol to exclude PsA. Patients completed the HAQ, Medical Outcome Study 36-item Short Form Health Survey, Dermatology Life Quality Index (DLQI), EuroQoL 5 domains (EQ-5D) and Fatigue Severity Scale (FSS). Mean scores were compared and multivariate analyses were conducted to compare the QoL measures between the two patient groups. RESULTS: Two hundred and one patients with PsC and 201 patients with PsA were studied. A significant decrease in QoL for patients with PsA compared with those with PsC was identified by all questionnaires except for the DLQI. This skin-specific questionnaire revealed a lower QoL in patients with PsC. Multivariate analyses for each QoL measure confirmed the results of these analyses. After adjusting for age, sex, duration of PsC, comorbidities, DMARDs and biologic therapy, HAQ and DLQI were independently associated with PsA in a logistic regression. CONCLUSION: Patients with PsA have a poorer QoL compared with those with PsC as measured by all questionnaires except the DLQI.

94 Article TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. 2012

Tejasvi, Trilokraj / Stuart, Philip E / Chandran, Vinod / Voorhees, John J / Gladman, Dafna D / Rahman, Proton / Elder, James T / Nair, Rajan P. ·Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5675, USA. ·J Invest Dermatol · Pubmed #22113471.

ABSTRACT: The tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene has been associated with psoriasis, rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus, and celiac disease. TNFAIP3 encodes A20, a tumor necrosis factor (TNF)-α-inducible zinc finger protein thought to limit NF-κB-mediated immune responses. In this study, we report association of response of psoriasis to TNF blockers with two TNFAIP3 single-nucleotide polymorphisms (rs2230926 in exon 7 and rs610604 in intron 3) and their haplotypes. Treatment response was self-evaluated using a 0-5 visual analog scale in 433 psoriasis patients who received TNF blockers. Confirmation was sought in 199 psoriasis and psoriatic arthritis patients from Toronto who were followed up prospectively. Response variables were dichotomized separately in the two cohorts, yielding similar proportions of good responses. Whereas significant associations were observed only for the Michigan cohort, fixed-effects meta-analysis retained significant association between dosage of the G allele of rs610604 and good combined response to all TNF blockers (odds ratio (OR) = 1.50, P(corr) = 0.050) and etanercept (OR = 1.64, P(corr) = 0.016). The rs2230926 T-rs610604 G haplotype was similarly associated. By demonstrating an association with therapeutic response, these results provide a clinically relevant functional correlate to the recently described genetic association between psoriasis and TNFAIP3.

95 Article The association between smoking and the development of psoriatic arthritis among psoriasis patients. 2012

Eder, Lihi / Shanmugarajah, Sutha / Thavaneswaran, Arane / Chandran, Vinod / Rosen, Cheryl F / Cook, Richard J / Gladman, Dafna D. ·Psoriatic Arthritis Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto, ON, Canada. ·Ann Rheum Dis · Pubmed #21953342.

ABSTRACT: AIM: To investigate the association between smoking and psoriatic arthritis (PsA) among patients with psoriasis and its interaction with the HLA-C*06 allele. METHODS: 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. RESULTS: 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). CONCLUSION: Smoking may be inversely associated with PsA among psoriasis patients. This association is not present among HLA-C*06-positive individuals.

96 Article Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis. 2012

Eder, Lihi / Chandran, Vinod / Pellet, Fawnda / Shanmugarajah, Sutha / Rosen, Cheryl F / Bull, Shelley B / Gladman, Dafna D. ·Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada. ·Ann Rheum Dis · Pubmed #21900282.

ABSTRACT: METHODS: 712 adult patients with PsA, 335 adult patients with PsC and 713 healthy controls were genotyped for HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ alleles. Differences in allelic distributions for each of the HLA loci were compared using a likelihood ratio test. Logistic regression analysis of multiple loci was performed to account for linkage disequilibrium. Haplotype information was inferred using the expectation-maximisation algorithm (given HLA-C and HLA-B genotypes) and analysed similarly. RESULTS: The following HLA alleles were found to be significantly associated with patients with PsA compared to patients with PsC in multivariate regression analysis: B*08 (OR 1.61, p=0.009), B*27 (OR 5.17, p<0.0001), B*38 (OR 1.65, p=0.026) and C*06 (OR 0.58, p=0.0002). HLA-B*27, HLA-B*38 and HLA-C*06 frequencies were also significantly higher in patients with PsA than in healthy controls (B*27: OR 3.05, p<0.0001; B*38: OR 5.9, p<0.0001; HLA-C*06: OR 1.71, p<0.0001). The following haplotypes were independently associated with PsA compared to PsC: HLA-B*18-C*07 (OR 10.1, p=0.004), HLA-B*27-C*01 (OR 41.1, p<0.0001), HLA-B*27-C*02 (OR 19.9, p<0.0001), HLA-B*38-C*12 (OR 2.9, p=0.01), HLA-B*08-C*07 (OR 2.6, p=0.004) and HLA-B*57-C*06 (OR 0.5, p=0.03). CONCLUSIONS: Certain HLA-B and HLA-C alleles confer susceptibility to PsA among patients with psoriasis and may be used to identify patients with PsC who may develop PsA.

97 Article Seasonal variation in vitamin D levels in psoriatic arthritis patients from different latitudes and its association with clinical outcomes. 2011

Touma, Zahi / Eder, Lihi / Zisman, Devy / Feld, Joy / Chandran, Vinod / Rosen, Cheryl F / Shen, Hua / Cook, Richard J / Gladman, Dafna D. ·Centre for Prognosis Studiesin the Rheumatic Diseases, Toronto, Ontario, Canada. ·Arthritis Care Res (Hoboken) · Pubmed #22121512.

ABSTRACT: Objective. Vitamin D insufficiency appears to be a pandemic problem and is more common in inhabitants of high latitude compared to low latitude areas. We aimed to determine the prevalence of vitamin D deficiency/insufficiency in patients with psoriatic arthritis (PsA), its seasonal and geographic variation, and the possible association with demographics and disease activity.Methods. This study was conducted in a northern geographic area and in a subtropical region from March 2009 to August 2009. Most subjects were assessed in both winter and summer. Demographics, clinical data, skin photo type, and serum 25-hydroxyvitamin D (25[OH]D) levels were determined. Multivariate linear and logistic mixed models were used to assess the relationship with serum 25(OH)D levels.Results. In total, 302 PsA patients were enrolled. Two hundred fifty-eight patients were evaluated during the winter,while 214 patients were evaluated during the summer. 25(OH)D levels in winter and summer were adequate (north: 41.3%winter and 41.4% summer, south: 42.1% winter and 35.1% summer), insufficient (north: 55.7% winter and 58.6% summer,south: 50.9% winter and 62.2% summer), and deficient (north: 3% winter and 0% summer, south: 7% winter and 2.7%summer) among patients. There was no association between 25(OH)D levels, geographic and seasonal interaction, race,employment status, and skin photo type or disease activity in both seasons. No association between disease activity in summer and vitamin D levels in winter could be found.Conclusion. A high prevalence of vitamin D insufficiency among PsA patients was found. There was no seasonal variation in 25(OH)D levels among PsA patients in the southern and northern sites. No association could be established between disease activity and vitamin D level.

98 Article Patient-reported outcome in psoriatic arthritis: a comparison of Web-based versus paper-completed questionnaires. 2011

MacKenzie, Heather / Thavaneswaran, Arane / Chandran, Vinod / Gladman, Dafna D. ·Psoriatic Arthritis Program, University Health Network, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. ·J Rheumatol · Pubmed #22045844.

ABSTRACT: OBJECTIVE: Patients followed in observational cohorts often complete patient-reported outcomes on paper questionnaires. With advances in technology, Web-based (WB) formats have been developed. The aims of our study were to determine whether WB and paper-based questionnaires (PB) completed by patients followed in the psoriatic arthritis (PsA) clinic are comparable; whether there is a patient preference for one method or the other; and whether any preference is related to patient characteristics. METHODS: Consecutive patients followed at the PsA clinic completed the Health Assessment Questionnaire, Medical Outcomes Study Short Form-36, fatigue scale, Dermatology Life Quality Index, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life Instrument, and EQ-5D both on paper (PB) and on computer by Internet (WB). Patients were also asked to complete questionnaires regarding their preference for one method or the other. Descriptive statistics and interclass correlation coefficients (ICC) were calculated. RESULTS: Of 110 patients who agreed to participate, 67 (57.3%) successfully completed both PB and WB questionnaires. These patients did not differ from those who did not complete the questionnaires. WB and PB questionnaires took the same length of time to complete, with 20% of the patients complaining of more pain following completion of the questionnaires, more so with the PB. There was excellent agreement between the PB and WB (ICC 0.89-0.97) for all questionnaires. CONCLUSION: The PB and WB versions of 10 standardized self-administered questionnaires in patients with PsA were comparable. The WB format was well accepted by PsA outpatients. Patients may thus be offered a choice of format as well as the choice to complete the questionnaires either in the clinic or remotely by Internet.

99 Article Do patients with psoriatic arthritis who present early fare better than those presenting later in the disease? 2011

Gladman, Dafna D / Thavaneswaran, Arane / Chandran, Vinod / Cook, Richard J. ·Department of Medicine, University of Toronto, Ontario, Canada. dafna.gladman@utoronto.ca ·Ann Rheum Dis · Pubmed #21914627.

ABSTRACT: BACKGROUND: This investigation aimed to determine whether patients presenting to a psoriatic arthritis (PsA) clinic early in the course of the disease had less severe disease at presentation, and whether disease duration at presentation predicts progression of joint damage. METHODS: Patients followed prospectively in a specialised clinic were divided into those first seen within 2 years of diagnosis (group 1) and those seen with more than 2 years of disease (group 2). The groups were compared with regard to demographics and disease characteristics at presentation. A multivariate analysis using a negative binomial model was conducted to determine whether patients with early disease had less progression of joint damage. RESULTS: 436 patients were identified in group 1 and 641 patients in group 2. Patients in group 2 were older, had longer duration of psoriasis and PsA, more joint damage and were less likely to be treated with disease-modifying antirheumatic drugs, but had similar level of education and degree of psoriasis severity. After adjusting for age, sex, education level, clinical joint damage at first visit and treatment, group 2 had significantly greater rate of clinical damage progression compared with group 1. CONCLUSIONS: Disease progression is more marked in patients presenting with established disease of more than 2 years' duration. These results suggest that patients with PsA should be treated earlier in the course of their disease.

100 Article Cardiovascular and other comorbidities in patients with psoriatic arthritis: a comparison with patients with psoriasis. 2011

Husted, Janice A / Thavaneswaran, Arane / Chandran, Vinod / Eder, Lihi / Rosen, Cheryl F / Cook, Richard J / Gladman, Dafna D. ·University of Waterloo, Waterloo, Ontario, Canada. ·Arthritis Care Res (Hoboken) · Pubmed #21905258.

ABSTRACT: OBJECTIVE: To determine whether the presence of psoriatic arthritis (PsA) is associated with greater comorbidity, in particular cardiovascular morbidity, compared to psoriasis without arthritis. METHODS: 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. RESULTS: 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. CONCLUSION: The results suggest that inflammatory joint disease may play a role in both cardiovascular and noncardiovascular morbidity in PsA.

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