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Objective To identify concerns and learning interests of patients with arthritis. Methods A questionnaire was developed, pilot tested, and then used to evaluate 197 patients with arthritis, including osteoarthritis (OA) (n = 41), rheumatoid arthritis (RA) (n = 57), back disease (n = 55), systemic lupus erythematosus (n = 27), and systemic sclerosis (SSc) (n = 17). Twenty concerns and 12 learning interests were rated. Questionnaires were also administered to assess physical disability (Health Assessment Questionnaire), psychological disability (Arthritis Impact Measurement Scales 2), and pain (visual analog scale). Participants addressed accessibility of health services, satisfaction with their physician, psychosocial needs, use of self-help groups, and behavioral strategies used to assist coping. Patients with RA, OA, and back disease, at both a community and a hospital center, were tested to assess whether concerns and learning interests differed based on site of treatment. Analytic methods included analysis of variance, factor analysis, and multiple linear regression. Results There were no differences in concerns or learning interests based on treatment site. Between diagnostic groups, patients with SSc were more interested in learning about self-help groups. The most frequently reported concern was worsening of the illness. The majority of respondents were interested in learning more about topics that were illness specific. The physician was chosen as the preferred source of information, and the preferred format was in writing. On factor analysis, the 20 concerns were reduced to 5 factors: psychological, coping, medication, social, and financial. Three factors were identified for learning interests: the illness, traditional health management topics, and nontraditional health management topics. Stepwise multiple linear regression revealed predictors for the 5 concern and 3 learning interest factors. The concerns were best predicted by self-reported disease severity, physical disability, and psychological distress, while learning interests were best predicted by self-reported disease severity, pain, and self-help group membership. Conclusion Concerns and learning interests of persons with arthritis did not differ based on the center of treatment or the diagnosis, but can be predicted by the level of pain and simple measures of disability. Better understanding of the relationship between health status and patient-perceived needs will result in improved patient-centered care.

Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities.Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined.One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren's syndrome-related autoantibodies (β = -43.32; 95% confidence interval [95% CI] -80.89, -5.75), but not with disease severity (β = -2.51; 95% CI -8.75, 3.73). Decreased interincisal distance was related to disease severity (β = -1.02; 95% CI -1.63, -0.42) and the modified Rodnan skin thickness score (β = -0.38; 95% CI -0.53, -0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease.In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren's syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear.

The goal of this study was to determine the sensitivity of the new 2013 classification criteria for systemic sclerosis (SSc; scleroderma) in an independent cohort of SSc subjects and to assess the contribution of individual items of the criteria to the overall sensitivity.SSc subjects from the Canadian Scleroderma Research Group cohort were assessed. Sensitivity was determined in several subgroups of patients. In patients without the criterion of skin thickening proximal to the metacarpophalangeal (MCP) joints, we recalculated sensitivity after removing the individual criterion.A total of 724 SSc patients were included. Most were women (86%), mean age was 55.8 years, mean disease duration was 10.9 years, and 59% had limited cutaneous SSc (lcSSc). Overall, the sensitivity of the 2013 criteria was 98.3% compared to 88.3% for the 1980 criteria. This pattern was consistent among those with lcSSc (98.8% versus 85.6%), anticentromere antibodies (98.9% versus 79.8%), disease duration ≤3 years (98.7% versus 84.7%), and no skin involvement proximal to the MCP joints (97% versus 60%). In the latter subgroup, removing Raynaud's phenomenon and sclerodactyly from the criteria reduced the sensitivity to 77% and 79%, respectively. Removing both sclerodactyly and puffy fingers reduced the sensitivity to 62%.The 2013 SSc classification criteria classify more SSc patients than the 1980 criteria. The improvement in sensitivity is most striking in those with lcSSc, especially those without skin involvement proximal to the MCP joints. The addition of Raynaud's phenomenon and puffy fingers to the 2013 criteria accounts for important gains in sensitivity.

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

In his letter, Jan Damoiseaux advocates testing of anti-RNA polymerase III antibodies (ARA), and also other (novel) systemic sclerosis (SSc)-associated antibodies, only for those patients who are really suspected for SSc.1 Damoiseaux argues that there is a necessity to provide clinical information together with the request for testing for rheumatic systemic autoimmune diseases. We very much agree that testing for SSc-associated antibodies should only be requested for those people who really are suspected to have SSc. We feel that a correct request of testing for these autoantibodies is, first and foremost, a responsibility of the requestor, that is, the rheumatologist. However, immunologists and rheumatologists almost certainly can learn from each other in optimising requests for antibody …

This study was designed to estimate the burden of care that would be placed on rheumatologists to undertake cardiovascular (CV) risk assessment of traditional CV risk factors in their patients. This cross-sectional study was set in a rheumatology ambulatory clinic of a tertiary care, university hospital. Consecutive rheumatoid arthritis (RA) patients were recruited over 6 weeks and matched 1:1 on age and sex to patients with non-inflammatory problems who presented to the same clinic. CV risk was calculated using the Framingham Risk Score. We recruited 68 RA patients and 64 controls. The distribution of CV risk factors in RA patients and controls was similar. Ten-year Framingham CV risk scores based on traditional risk factors were moderate and similar in RA patients and controls (13.7 and 14.3 %, respectively). Nevertheless, the proportion of RA patients with a history of coronary artery disease was more than twice that of controls (13 versus 5 %, respectively). Approximately 20 % of RA patients and controls did not have a primary care physician. In rheumatology practice, the problem of elevated CV risk due to traditional risk factors is not unique to RA patients. The burden for rheumatologists of undertaking CV risk assessment in their clinic could be considerable. Rheumatologists should manage inflammatory disease and health services should be improved to ensure the optimal management of traditional CV risk factors for all rheumatology patients.

Anti-PM/Scl autoantibodies are found in polymyositis, dermatomyositis, systemic sclerosis (SSc), and systemic autoimmune disease overlap syndromes. PM-1α is a major epitope of the PM/Scl complex, and antibodies against PM-1α can be detected using a validated enzyme-linked immunosorbent assay (ELISA). This study was undertaken to determine the prevalence and identify the clinical correlates of anti-PM-1α antibodies in a large cohort of patients with SSc.Serum samples were obtained from 763 patients with SSc enrolled in a multicenter Canadian cohort. The sera were analyzed by ELISA for the presence of antibodies against PM-1α. Associations between the presence of anti-PM-1α antibodies and demographic, clinical, and other serologic manifestations of SSc were investigated.Anti-PM-1α antibodies were present in 55 patients with SSc (7.2%), of whom almost 50% (26 of 55; 3.4% of the overall cohort) had no other SSc-specific antibodies, namely anticentromere, anti-topoisomerase I, and anti-RNA polymerase III. Features positively associated with the presence of anti-PM-1α antibodies included younger age at disease onset, skeletal muscle involvement, calcinosis, inflammatory arthritis, and overlap disease. Interstitial lung disease was less frequent and there were fewer gastrointestinal symptoms present in patients with anti-PM-1α antibodies compared to patients without these antibodies.Anti-PM-1α antibodies are relatively common in SSc and are associated with a distinct clinical phenotype, consistent with that described in association with other anti-PM/Scl autoantibodies. Although anti-PM-1α antibodies are not exclusive of other SSc-specific antibodies, they can be present in the absence thereof. Thus, anti-PM-1α antibodies may have considerable diagnostic and prognostic relevance in SSc.

We describe a patient with advanced shoulder osteoarthritis who developed a spontaneous hemarthrosis due to a bleeding pseudoaneurysm. This rare cause of intra-articular hemorrhage is important to establish because specific treatment may offer relief and prevent further bleeding.

Contains fulltext : 118230.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Increasingly, medical research involves patients who complete outcomes in different languages. This occurs in countries with more than one common language, such as Canada (French/English) or the United States (Spanish/English), as well as in international multi-centre collaborations, which are utilized frequently in rare diseases such as systemic sclerosis (SSc). In order to pool or compare outcomes, instruments should be measurement equivalent (invariant) across cultural or linguistic groups. This study provides an example of how to assess cross-language measurement equivalence by comparing the Center for Epidemiologic Studies Depression (CES-D) scale between English-speaking Canadian and Dutch SSc patients. METHODS: The CES-D was completed by 922 English-speaking Canadian and 213 Dutch SSc patients. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess the amount of differential item functioning (DIF). RESULTS: A two-factor model (positive and negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 items on the CES-D. The English-speaking Canadian sample endorsed more feeling-related symptoms, whereas the Dutch sample endorsed more somatic/retarded activity symptoms. The overall estimate in depression scores between English and Dutch was not influenced substantively by DIF. CONCLUSIONS: CES-D scores from English-speaking Canadian and Dutch SSc patients can be compared and pooled without concern that measurement differences may substantively influence results. The importance of assessing cross-language measurement equivalence in rheumatology studies prior to pooling outcomes obtained in different languages should be emphasized. 8 p.

Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusion The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease. Copyright © 2013 by the American College of Rheumatology.

Introduction: Psychosocial and rehabilitation interventions are increasingly used to attenuate disability and improve health-related quality of life (HRQL) in chronic diseases, but are typically not available for patients with rare diseases. Conducting rigorous, adequately powered trials of these interventions for patients with rare diseases is difficult. The Scleroderma Patient-centered Intervention Network (SPIN) is an international collaboration of patient organisations, clinicians and researchers. The aim of SPIN is to develop a research infrastructure to test accessible, low-cost self-guided online interventions to reduce disability and improve HRQL for people living with the rare disease systemic sclerosis (SSc or scleroderma). Once tested, effective interventions will be made accessible through patient organisations partnering with SPIN. Methods and analysis: SPIN will employ the cohort multiple randomised controlled trial (cmRCT) design, in which patients consent to participate in a cohort for ongoing data collection. The aim is to recruit 1500– 2000 patients from centres across the world within a period of 5 years (2013–2018). Eligible participants are persons ≥18 years of age with a diagnosis of SSc. In addition to baseline medical data, participants will complete patient-reported outcome measures every 3 months. Upon enrolment in the cohort, patients will consent to be contacted in the future to participate in intervention research and to allow their data to be used for comparison purposes for interventions tested with other cohort participants. Once nterventions are developed, patients from the cohort will be randomly selected and offered interventions as part of pragmatic RCTs. Outcomes from patients offered interventions will be compared with outcomes from trial-eligible patients who are not offered the interventions. Ethics and dissemination: The use of the cmRCT design, the development of self-guided online interventions and partnerships with patient organisations will allow SPIN to develop, rigourously test and effectively disseminate psychosocial and rehabilitation interventions for people with SSc., (undefined)

The objective of this study was to investigate the frequency of autoantibodies to hydroxymethylglutaryl coenzyme A reductase (HMGCR) in systemic sclerosis (SSc) and associations with inflammatory myositis and statin exposure. This was a cross-sectional, multicenter study of 306 subjects from the Canadian Scleroderma Research Group cohort who had complete data on statin exposure and serology for anti-HMGCR antibodies assayed by an addressable laser bead immunoassay (ALBIA). Descriptive statistics were used to summarize the baseline characteristics of the patients and to compare subjects with and without anti-HMGCR antibodies. Four (1.3%) subjects had anti-HMGCR antibodies. None of the subjects with anti-HMGCR antibodies titers had a history of an inflammatory myositis or overlap with polymyositis/dermatomyositis, compared to 8.6% and 2.0% of those without anti-HMGCR antibodies, respectively. In addition, none of the subjects with anti-HMGCR antibodies had past or current exposure to statins compared to 12% of those with negative titers. Anti-HMGCR antibodies are rare in SSc and are not associated with inflammatory myopathy or statin exposure. Larger studies will be required to confirm these preliminary observations. Nevertheless, we conclude that anti-HMGCR antibodies are unlikely to play a major role in inflammatory myopathy in SSc and anti-HMGCR antibodies can be present in subjects without exposure to statins.

Supplemental Digital Content is available in the text, Autoantibodies directed against the Ku autoantigen are present in systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of single-specificity anti-Ku in SSc. An international (Canada, Australia, USA, Mexico) cohort of 2140 SSc subjects was formed, demographic and clinical variables were harmonized, and sera were tested for anti-Ku using a line immunoassay. Associations between single-specificity anti-Ku antibodies (i.e., in isolation of other SSc-specific antibodies) and outcomes of interest, including myositis, ILD, and survival, were investigated. Twenty-four (1.1%) subjects had antibodies against Ku, and 13 (0.6%) had single-specificity anti-Ku antibodies. Subjects with single-specificity anti-Ku antibodies were more likely to have ILD (58% vs 34%), and to have increased creatine kinase levels (>3× normal) at baseline (11% vs 1%) and during follow-up (10% vs 2%). No difference in survival was noted in subjects with and without single-specificity anti-Ku antibodies. This is the largest cohort to date focusing on the prevalence and disease characteristics of single-specificity anti-Ku antibodies in subjects with SSc. These results need to be interpreted with caution in light of the small sample. International collaboration is key to understanding the clinical correlates of uncommon serological profiles in SSc.

Background Endpoints in systemic sclerosis (SSc), such as modified Rodnan skin score (mRSS) and pulmonary function tests represent only parts of a multisystem disease. The European Scleroderma Study Group (EScSG) developed an SSc activity index, which captures involvement of multiple organs. The predictive validity of the SSc activity index is unclear. Objectives To estimate the effect of disease activity as measured by EScSG activity index, on the risk of subsequent organ damage in the Canadian Scleroderma Research Group (CSRG) cohort. Methods Of 421 SSc patients from the CSRG database with disease duration of ≤3 years, 197 who had no evidence of endstage organ damage initially and 3-year follow-up were included. Disease activity was assessed by EScSG activity index with two variability measures: 1. adjusted mean (am) EScSG activity score (the area under the curve of EScSG activity index over observation period), and 2. persistently active disease (PAD)/flare (EScSG score of ≥3 at follow-up visit). Internal organ involvement assessed over follow-up was based on Medsger severity scale and included accrual of a new severity score overall and by specific organ systems. Adjusted odds ratios (OR) for association between disease activity, severity and progression were calculated using regression analysis. Results After adjustment for covariates, amEScSG activity score was the most consistent predictor of risk at 3 year follow-up: disease progression as accrual of a new severity grade (Δ≥1) in any of the major internal organs (OR 1.42, 95%CI 1.14–2.25, p=0.007), lung disease (OR 1.86, 95%CI 1.31–2.64, p Conclusions The mean adjusted EScSG reliably captured disease activity over time in individual patients and predicted the risk of deterioration in health status, disease progression and development of severe internal organ involvement in diffuse SSc, after adjustment for key covariates. Disclosure of Interest None declared

Objectives. Patients with SSc experience a range of problems affecting their quality of life, but only one small study has assessed the prevalence of major depressive disorder (MDD) in SSc. The objectives of this study were: (i) to assess the prevalence of current (30-day), 12-month and lifetime MDD in a large sample of Canadian SSc patients; and (ii) to investigate socio-demographic and disease factors associated with 12-month MDD. Methods. SSc patients were recruited from seven Canadian Scleroderma Research Group Registry sites (April 2009 to May 2012). MDD and history of a prior depression episode (major or minor) were assessed with the Composite International Diagnostic Interview. Results. Among 345 patients, prevalence of 30-day, 12-month and lifetime MDD was 3.8% (95% CI 2.2%, 6.3%; n = 13), 10.7% (95% CI 7.9%, 14.4%; n = 37) and 22.9% (95% CI 18.8%, 27.6%; n = 79), respectively. Patients with 12-month MDD had more severe gastrointestinal track involvement than patients without 12-month MDD, but there were no other significant differences on socio-demographic or disease variables. Among patients with 12-month MDD, 81.1% (95% CI 65.8%, 90.3%) reported a prior depression episode compared with 3.9% (95% CI 2.2%, 6.7%) among patients without 12-month MDD (P < 0.01). Conclusion. The prevalence of 30-day, 12-month and lifetime MDD among Canadian SSc patients is approximately twice that of the Canadian general population and somewhat higher than in arthritis. SSc patients face a range of psychosocial problems and may benefit from a broad supportive care approach.

Pruritus is a common complaint in systemic sclerosis (SSc) and impairs patients' quality of life. Little is known about the pathogenesis of itch in SSc, but complex and multi-factorial mechanisms of itch are appreciated in many chronic diseases. This review discusses the putative mechanisms of the pathogenesis of itch to better understand the mechanisms that may be relevant to pruritus in SSc. It discusses possible therapeutics in the context of this complex pathogenesis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) should be seen by a rheumatologist promptly; however, there are no recommendations for patients with osteoarthritis (OA). Our goal was to describe wait times from referral by the primary care provider to rheumatology consultation and to explore whether wait times are associated with type of arthritis diagnosis, geographic area, or type of rheumatology office. METHODS: Appointments were requested by telephone using case scenarios that were created by a group of experts and included (1) presumed RA, (2) possible RA, and (3) presumed OA. Wait times were evaluated as the time between the initial request and the appointment date provided. We used descriptive statistics, bivariate analysis, and logistic regression in the analysis. RESULTS: For all scenarios combined, 34% were given an appointment with a rheumatologist within 3 months of referral, 32% waited longer than 3 months, and 34% were told that the rheumatologist was not accepting new referrals at the time the request was made. Patients with presumed RA were much more likely to be seen within 3 months of referral compared with those with presumed OA (odds ratio, 13; 95% confidence interval, 1.70-99.38). CONCLUSIONS: Rheumatoid arthritis is prioritized over OA for rheumatology appointments. However, most patients with RA are still not receiving an appointment to a rheumatologist in a timely manner. Effective triage tools to decrease these delays should be instituted.

Objective. Fatigue is a common and important problem in SSc. No studies, however, have compared the properties of fatigue measures in SSc. The objective of this study was to compare the performances of the Short Form-36 (SF-36) Vitality subscale and Functional Assessment of Chronic Illness TherapyFatigue (FACIT) in SSc. Methods. Cross-sectional, multi-centre study of Canadian Scleroderma Research Group Registry patients. The associations of the two instruments with other patient-reported outcome measures, as well as physician- and patient-rated disease variables were compared. Item response theory models were used to compare the degree to which items and the total scores of each measure effectively covered the full spectrum of fatigue levels. Results. There were 348 patients (297 women, 85%) in the study. The instruments correlated at r = 0.65 with each other. The FACIT tended to correlate slightly higher than the SF-36 Vitality subscale with physician- and patient-rated disease variables and patient-reported physical function and disability, whereas the SF-36 Vitality subscale correlated minimally higher with mental health measures. The FACIT had markedly better discrimination across the range of fatigue, particularly at average to high fatigue levels, whereas the SF-36 Vitality subscale discriminated well only among patients in the low to average range. Conclusion. The FACIT discriminates better than the SF-36 Vitality subscale at average to high ranges of fatigue, which is common in SSc, suggesting that it is preferred for measuring fatigue in SSc.

Objective Reports of low sexual activity rates and high impairment rates among women with chronic diseases have not included comparisons to general population data. The objective of this study was to compare sexual activity and impairment rates of women with systemic sclerosis (SSc) to general population data and to identify domains of sexual function driving impairment in SSc. Methods Canadian women with SSc were compared to women from a UK population sample. Sexual activity and, among sexually active women, sexual impairment were evaluated with a 9-item version of the Female Sexual Function Index (FSFI). Results Among women with SSc (mean age = 57.0 years), 296 of 730 (41%) were sexually active, 181 (61%) of whom were sexually impaired, resulting in 115 of 730 (16%) who were sexually active without impairment. In the UK population sample (mean age = 55.4 years), 956 of 1,498 women (64%) were sexually active, 420 (44%) of whom were impaired, with 536 of 1,498 (36%) sexually active without impairment. Adjusting for age and marital status, women with SSc were significantly less likely to be sexually active (OR = 0.34, 95%CI = 0.28–0.42) and, among sexually active women, significantly more likely to be sexually impaired (OR = 1.88, 95%CI = 1.42–2.49) than general population women. Controlling for total FSFI scores, women with SSc had significantly worse lubrication and pain scores than general population women. Conclusions Sexual functioning is a problem for many women with scleroderma and is associated with pain and poor lubrication. Evidence-based interventions to support sexual activity and function in women with SSc are needed.

Since the 1980 ACR classification criteria for systemic sclerosis (SSc) do not identify 20% with SSc, revised criteria are necessary.Suggested new criteria from the literature were sent in random order to 96 SSc experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis reduced items. The Canadian Scleroderma Research Group (CSRG) database was used to determine the prevalence of each item.Seventy-one of 96 (71%) completed all 3 rounds; 47 items were expanded to 76 in round 2. Thirty items had at least 50% consensus and 18 had75% agreement to include (a priori cut point). Clustering occurred for 4 categories: proximal to MCP skin involvement, vascular abnormalities, autoantibodies and tissue damage. Proximal to MCPs skin involvement identified 80% of patients. Adding one item from each of the other 3 categories or 1 or more items from 2 of 3 remaining categories increased the proportion of patients classified to 94% in CSRG patients. Categories included (1) Vascular (dilated capillaries, telangiectasia, Raynaud's phenomenon [RP]), (2) Autoantibodies (anticentromere [ACA] or antitopoisomeraseI [Topo1]) and (3) Fibrosis/damage (esophogeal dysmotility dysphagia, sclerodactyly, digital ulcers). In the CSRG, 98% were identified if using proximal skin involvement; or sclerodactyly plus one of: RP, ACA or Topo1.This is a first step toward developing new SSc classification criteria. A Delphi exercise alone cannot suffice for item reduction. Also, validation prospectively in SSc patients and diseases that mimic SSc is needed in order to calculate sensitivity and specificity of future criteria.

Systemic sclerosis (SSc) is a chronic inflammatory disorder characterized by a disturbance in fibroblast function culminating in the telltale skin thickening and fibrosis of visceral organs. Interstitial lung disease (ILD) is common (Steele et al. 2011) and is the leading cause of death in this disease (Steen and Medsger 2007). The immunohistopathogenesis of SSc-ILD is characterized by immune dysfunction and inflammation. Thus, immunosuppression has been hypothesized as a useful treatment for SSc-ILD. However, randomized clinical trials (RCTs) have thus far only revealed a modest effect of immunosuppression (Hoyles et al. 2006; Tashkin et al. 2006). We believe that these small observed effects are due, at least in part, to the actual design of the RCTs, in particular subject selection, which did not properly identify patients likely to respond to treatment.

Background Medical research increasingly utilizes patient-reported outcome measures administered and scored in different languages. In order to pool or compare outcomes from different language versions, instruments should be measurement equivalent across linguistic groups. The objective of this study was to examine the cross-language measurement equivalence of the Patient Health Questionnaire-9 (PHQ-9) between English- and French-speaking Canadian patients with systemic sclerosis (SSc). Methods The sample consisted of 739 English- and 221 French-speaking SSc patients. Multiple-Indicator Multiple-Cause (MIMIC) modeling was used to identify items displaying possible differential item functioning (DIF). Results A one-factor model for the PHQ-9 fit the data well in both English- and French-speaking samples. Statistically significant DIF was found for 3 of 9 items on the PHQ-9. However, the overall estimate in depression latent scores between English- and French-speaking respondents was not influenced substantively by DIF. Conclusions Although there were several PHQ-9 items with evidence of minor DIF, there was no evidence that these differences influenced overall scores meaningfully. The PHQ-9 can reasonably be used without adjustment in Canadian English- and French-speaking samples. Analyses assessing measurement equivalence should be routinely conducted prior to pooling data from English and French versions of patient-reported outcome measures.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9), which inquires about both passive thoughts of death and active ideas of self-harm, has been used to assess suicide risk in arthritis. The objectives of this study were 1) to determine the proportion of systemic sclerosis (SSc; scleroderma) patients who responded "yes" to item 9 who endorsed active suicidal ideation in response to more direct questions during a structured clinical interview, and 2) to report whether the PHQ-8, which does not include item 9 from the PHQ-9, performs similarly to the PHQ-9.Patients were recruited from the Canadian Scleroderma Research Group Registry. The PHQ-9 and Composite International Diagnostic Interview (CIDI) depression module were administered during a phone interview. Scores on the PHQ-8 were calculated by removing item 9 from the PHQ-9. Item 9 responses were compared to suicidal ideation and intent in the last year based on the CIDI. Scores on the PHQ-8 and PHQ-9 were compared using Pearson's correlations.There were 345 patients interviewed, of whom 31 (9.0%) endorsed item 9 of the PHQ-9. Of those, based on the CIDI, 14 (45.2%) had passive thoughts of suicide or death. Only 1 patient (3.2%) had thoughts about suicide in some detail at any point in the last 12 months. The correlation between PHQ-9 and PHQ-8 scores was 0.998.Item 9 appears to identify many patients who do not report active suicidal ideation. The PHQ-8 may be a better option for assessment of depressive symptoms than the PHQ-9 in patients with SSc.

Objective This study was performed to determine the prevalence of elevated C-reactive protein (CRP) levels and the significance of CRP in clinical parameters in systemic sclerosis (SSc; scleroderma) patients. Methods Canadian Scleroderma Research Group data were used. Statistical comparisons were made for CRP levels ≤8 mg/liter versus >8 mg/liter, early (≤3 years from first non–Raynaud's phenomenon symptom) versus late SSc, and diffuse cutaneous SSc (dcSSc) versus limited cutaneous SSc (lcSSc). A survival analysis was analyzed between patients with normal versus elevated CRP levels. Results A total of 1,043 patients (mean ± SD age 55.4 ± 12.1 years, mean ± SD disease duration of 11.0 ± 9.5 years) were analyzed; elevation of CRP level and erythrocyte sedimentation rate (ESR; >20 mm/hour) occurred in 25.7% and 38.2%, respectively. Mean ± SD baseline CRP level in dcSSc (11.98 ± 25.41 mg/liter) was higher than in lcSSc (8.15 ± 16.09 mg/liter; P = 0.016). SSc patients with an early disease duration had a higher mean ± SD CRP level (12.89 ± 28.13 mg/liter) than those with a late disease duration (8.60 ± 17.06 mg/liter; P = 0.041). Although not consistent in all subsets, CRP was significantly associated (P < 0.01) with ESR, modified Rodnan skin score (MRSS), worse pulmonary function parameters, disease activity, damage, and Health Assessment Questionnaire. CRP level seemed to normalize in many SSc patients over time. Total lung capacity

The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on sauto-antibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti-cyclic citrullinated peptides (CCPs), and anti-HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking-induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti-HSP70 auto-antibodies were identified in CS-exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti-HSP70 IgM, smoke exposure promoted the switch to anti-HSP70 IgG autoantibodies. Elevated anti-CCP autoantibodies were not detected in CS-exposed mice or smokers. AKR/J splenocytes stimulated in vitro by immune complexes (ICs) of HSP70/anti-HSP70 antibodies produced RFs. The CD91 scavenger pathway was required as anti-CD91 blocked the HSP70-IC-induced RF response. Blocking Toll-like receptors did not influence the HSP70-IC-induced RFs. These studies identify both anti-HSP70 and RFs as serological markers of smoke-related LD in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS, in a number of different disease settings.

Objective.To study the clinical phenotypes of centromeric proteins (CENP)-A- and CENP-B-positive patients with systemic sclerosis (SSc) and to compare them to anticentromere antibody (ACA)-positive and negative SSc patients.Methods.Sera samples were collected from 802 patients with SSc enrolled in a multicenter cohort study. Antibodies to CENP-A and B were detected by ELISA, and ACA by indirect immunofluorescence. Associations with clinical and other serological manifestations of SSc were investigated.Results.CENP-A antibodies were detected in 276 (34%), CENP-B in 286 (36%), and ACA in 279 (35%) patients. Patients having ACA, CENP-A, and/or CENP-B resembled each other and differed from the remainder of the cohort in the following respects: older chronologically and at disease onset; more commonly women; more likely to have limited disease and lower skin scores; less likely to have finger ulcers, digital tuft resorption, or finger contractures; more likely to have pulmonary hypertension; less likely to have interstitial lung disease, scleroderma renal crisis, inflammatory arthritis, and inflammatory myositis; and having lower overall disease severity. CENP-A and/or B status was predictive of the extent of skin involvement over time. Patients with limited disease who were CENP-A-negative at baseline were more likely to progress to diffuse disease compared to CENP-A-positive patients (OR 2.55, 95% CI 1.37, 4.85, p = 0.004).Conclusion.Clinical immunology laboratories are increasingly using high-throughput ELISA tests for CENP antibodies, with or without ACA detected by indirect immunofluorescence. The phenotype of CENP-A and/or B-positive patients is generally similar to that associated with ACA.

Depression symptom measures that include somatic symptoms may inflate severity estimates among medically ill patients, including patients with systemic sclerosis (SSc; scleroderma). The 9-item Patient Health Questionnaire (PHQ-9) is increasingly used to assess depressive symptoms in medical settings, but it is not known whether PHQ-9 scores are influenced by somatic symptoms common in medical illness. The objective was to assess whether SSc patients had higher somatic symptom scores on the PHQ-9 than non-medically ill respondents from the general population matched on cognitive/affective scores.SSc patients from the Canadian Scleroderma Research Group Registry were matched with respondents from a random population survey of Alberta, Canada residents who were without chronic disease on total PHQ-9 cognitive/affective scores (5 items), sex, and, as close as possible, age. PHQ-9 somatic scores (4 items) were compared between SSc patients and healthy Alberta survey respondents using t-tests for unadjusted analyses and analysis of covariance to adjust for age differences that remained after matching.Somatic symptoms accounted for 64% of the total PHQ-9 scores for 762 matched SSc patients (n = 837 total) compared to 56% for 762 matched Alberta population survey respondents (n = 3,304 total), a mean difference of 1.0 point, or 19% of the total scores for the SSc patients (Hedges's g = 0.38). After adjusting for age, the mean difference increased to 1.4 points, reflecting 25% of the SSc patients' total scores (Hedges's g = 0.55).PHQ-9 scores among patients with SSc may include a small to moderate amount of variance from somatic symptoms that are not necessarily related to depression.

Objective.We determined congruence with published guidelines from the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trials and Research group, for systemic sclerosis (SSc) investigations and treatment practices within the Canadian Scleroderma Research Group (CSRG).Methods.Investigations and medication use for SSc complications were obtained from records of patients with SSc in the CSRG to determine adherence to guidelines for patients enrolled before and after the guidelines were published.Results.The CSRG database of 1253 patients had 992 patients with SSc enrolled before publication of the guidelines and 261 after. For pulmonary arterial hypertension (PAH) treatment, there were no differences in use before and after the guidelines, yet annual echocardiograms for PAH screening were done in 95% of patients enrolled before the guidelines and in only 86% of those enrolled after (p 80% with gastroesophageal reflux disease before and after the guidelines. One-quarter with gastrointestinal symptoms were taking prokinetic drugs. For those with past SSc renal crisis, use of angiotensin-converting enzyme inhibitors was not different before and after the guidelines. For early diffuse SSc < 2 years, ever-use of methotrexate was similar (one-quarter of each group); and for symptomatic interstitial lung disease, 19% had ever used cyclophosphamide before the guidelines and 9% after (p = nonsignificant). CSRG practices were generally comparable to recently published guidelines; however, use of iloprost and bosentan was low for digital ulcers because these drugs are not approved for use in Canada.Conclusion.There did not seem to be an increase in adherence to recommendations once the guidelines were published. For many guidelines, 25% to 40% of patients who would qualify received the recommended treatment.

Objective To develop a clinical decision rule to predict the presence of interstitial lung disease (ILD) in systemic sclerosis (SSc; scleroderma) and to estimate the prevalence of SSc-ILD. Methods Patient data were extracted from the Canadian Scleroderma Research Group registry. Three algorithms for the clinical decision rule were considered based on lung auscultation, chest radiography (CXR), and % predicted forced vital capacity (FVC). High-resolution computed tomography (HRCT) scans were used as the gold standard to determine the diagnostic properties of the 3 algorithms. Multiple imputation was used to impute HRCT data when missing, thereby avoiding bias due to differential referral for HRCT. Results This study included 1,168 patients. Of the patients with HRCT scans, 65% had evidence of ILD, compared to 26% by physical examination and 22% by CXR. The FVC of those who did not have HRCT was 8.8% greater than those who did (95% confidence interval [95% CI] 6.0–11.6%). Algorithm A, which identified the presence of ILD based on crackles on lung auscultation and/or findings on CXR, had a likelihood ratio of 3.9, compared to 3.2 for Algorithm B (which included patients with FVC

Systemic sclerosis (SSc) is a heterogeneous disease or possibly a family of closely related diseases characterized by vasculopathy, immune activation, and fibrosis. Its clinical manifestations vary across individuals, resulting in differences in organ system involvement, treatment regimens, and prognosis. In the absence of a diagnostic test for SSc, several sets of classification criteria have been developed and used to identify patients with similar features for recruitment into clinical studies.(1–4) The use of classification criteria as inclusion criteria for study participation has facilitated comparison of results across studies. Existing classification criteria for SSc should be updated.(5–10) With improved understanding of the disease, the items regarded to be important for SSc have increased.(5, 11, 12) Goetz and Berne were among the first to describe gastrointestinal involvement in SSc, yet they did not incorporate this domain into their criteria.(13) It has also been recognized that use of the 1980 American Rheumatism Association (ARA) preliminary criteria(1–3) for recruitment into clinical trials results in the exclusion of up to 20% of patients with either early SSc or the limited cutaneous subtype of SSc.(8, 9, 14) The exclusion of the limited cutaneous SSc patients is likely due to the fact that a disproportionate number of diffuse cutaneous SSc patients were entered into the ARA prospective study. Thus the statistical analysis resulted in criteria that identified 100% of diffuse cutaneous SSc patients, but only 80% of limited cutaneous SSc patients. It has been demonstrated recently that the addition of nailfold capillary abnormalities and telangiectasias to the ARA SSc criteria improve their sensitivity.(6, 8) Few criteria sets were developed for wide-scale application in classifying patients for clinical research studies.(15, 16) Most criteria sets were developed for use in the clinic or a study at hand, limiting their generalizability.(17, 18) Standards for devising classification criteria have evolved since the original criteria sets were proposed.(19) The methodologies used to develop previous criteria do not meet current standards.(20, 21) For example, one previous SSc criteria proposal utilized healthy subjects and rheumatoid arthritis patients as the comparator groups.(2) It has been argued that these patients are so different that they can nearly always be differentiated from SSc patients.(7) In keeping with the differential diagnosis faced by clinicians in practice, it has been suggested that criteria should be tested against control populations selected because they have SSc-like features.(7) Examples include other connective tissue diseases: mixed connective tissue disease (MCTD), Sjogren’s syndrome, systemic lupus erythematosus (SLE), dermatomyositis/polymyositis, undifferentiated CTD, other fibrosing syndromes (eosinophilic fasciitis, linear scleroderma, generalized morphea, scleromyxedema, nephrogenic systemic fibrosis), and Raynaud’s disease. The Committee on Classification and Response Criteria, a subcommittee of the ACR Quality Measures Committee, has published recommendations for the development and validation of new criteria sets based on the current standards of measurement science,(19–21) which are complemented by recommendations from the European League Against Rheumatism (EULAR) Standing Committees of Clinical Epidemiology, and for International Studies Including Clinical Trials, respectively.(22, 23) Recommendations for modern criteria development include 1) collaboration between clinical experts and clinical epidemiologists in criteria development; 2) evaluation of the psychometric properties of each candidate criterion; and 3) description of the derivation sample (origin of the patients and control subjects), and gold standard.(21–23) Ideally, phases of criteria development should have a balance between expert opinion and data-driven methods.(21) Yet there should be avoidance of circularity of reasoning (a bias which can occur when the same experts developing the criteria are the ones contributing cases and comparison patients).(19) A joint international, collaborative initiative supported by EULAR and ACR is underway to develop revised classification criteria for SSc where the methodology has considered these issues. During Phase 1 of the development process, potential items for revised SSc classification criteria were generated through two independent international consensus exercises performed by the Scleroderma Clinical Trials Consortium (SCTC) and the EULAR Scleroderma Trials and Research group (EUSTAR), resulting in a list of 168 potential items.(24) A Delphi exercise of 105 international SSc experts reduced the list of potential items to 102 items. The item list was again rated and subjected to a consensus meeting using nominal group technique by a separate group of European and North American SSc experts, further reducing the list to 23 items.(24) As recommended, the next phase of SSc criteria development requires evaluation of the psychometric properties of each candidate criterion.(21, 23) An important psychometric property of criteria is their validity – the degree to which their application corresponds to the truth. In this study we aimed to evaluate the validity of candidate items for revised SSc criteria. In particular, the objectives of this study were to evaluate the face, discriminant and construct validity of the candidate items. This knowledge will inform the subsequent phases of SSc criteria development.

Objective Depression symptom measures that include somatic symptoms may inflate severity estimates among medically ill patients, including patients with systemic sclerosis (SSc; scleroderma). The 9-item Patient Health Questionnaire (PHQ-9) is increasingly used to assess depressive symptoms in medical settings, but it is not known whether PHQ-9 scores are influenced by somatic symptoms common in medical illness. The objective was to assess whether SSc patients had higher somatic symptom scores on the PHQ-9 than non–medically ill respondents from the general population matched on cognitive/affective scores. Methods SSc patients from the Canadian Scleroderma Research Group Registry were matched with respondents from a random population survey of Alberta, Canada residents who were without chronic disease on total PHQ-9 cognitive/affective scores (5 items), sex, and, as close as possible, age. PHQ-9 somatic scores (4 items) were compared between SSc patients and healthy Alberta survey respondents using t-tests for unadjusted analyses and analysis of covariance to adjust for age differences that remained after matching. Results Somatic symptoms accounted for 64% of the total PHQ-9 scores for 762 matched SSc patients (n = 837 total) compared to 56% for 762 matched Alberta population survey respondents (n = 3,304 total), a mean difference of 1.0 point, or 19% of the total scores for the SSc patients (Hedges's g = 0.38). After adjusting for age, the mean difference increased to 1.4 points, reflecting 25% of the SSc patients' total scores (Hedges's g = 0.55). Conclusion PHQ-9 scores among patients with SSc may include a small to moderate amount of variance from somatic symptoms that are not necessarily related to depression.

Interstitial lung disease commonly develops in patients with Systemic sclerosis (SSc). High resolution computed tomography (HRCT) has become the gold standard for detection and evaluation of lung involvement in SSc. Several HRCT scoring methods have been described and used to characterize and quantify the disease. This article reviews the different scoring systems and how they have been validated clinically and applied to prognosticate patients, assess disease progression and evaluate response to treatment.

Objective. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine. Methods, Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo. Results. After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2—9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response. Conclusion. Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined.

Objective To assess 1) the rates of sexual activity and impairment, 2) clinical correlates of sexual activity/impairment, and 3) common sources of pain during and after sex in a large sample of female patients with systemic sclerosis (SSc; scleroderma). Methods We performed a cross-sectional multicenter study of female SSc patients from the Canadian Scleroderma Research Group Registry. Patients underwent medical examinations and clinical histories and were asked whether they had engaged in sexual activities with their partner in the past 4 weeks. Sexually active patients completed a 9-item version of the Female Sexual Function Index (FSFI) and items related to problems that may be linked to sexual dysfunction in SSc. Multivariate logistic regressions assessed independent predictors of activity/inactivity and sexual dysfunction. Results A total of 226 (41%) of 547 patients, including 215 (54%) of the 401 patients currently in relationships, reported having engaged in sexual activities with a partner in the past 4 weeks. Among 165 sexually active patients with complete data for all variables, 102 (62%) had FSFI total scores ≤22.5, indicating impaired function. Seventeen percent of the patients were sexually active and not impaired. Independent predictors (P < 0.05) of sexual activity were younger age, fewer gastrointestinal symptoms, and less severe Raynaud's phenomenon symptoms. Sexual impairment was independently associated with older age, higher skin scores, and more severe breathing problems. Vaginal pain was 8 times more likely among women with impairment. Conclusion Research is needed to compare the extent of activity and impairment in SSc compared to women without SSc and to develop interventions to address impaired sexual function in women with SSc.

Contractures and deformities of the hand are major factors in disability and reduced health-related quality of life in systemic sclerosis (SSc). Physical (PT) and occupational therapy (OT) have been emphasised to address impaired hand function, but little is known about the extent they are employed. The objective of this study was to determine the proportion of Canadian SSc patients with hand involvement who are referred to and use PT or OT services and factors associated with referral.Participants were respondents to the Canadian Scleroderma Patient Survey of Health Concerns and Research Priorities who rated ≥1 of 5 hand problems (hand stiffness, difficulty making fist, difficulty holding objects, difficulty opening hand, difficulty with faucet) as occurring at least sometimes with moderate or higher impact. Patients indicated if their physicians recommended PT or OT and if they used these services. Multivariate logistic regression assessed independent predictors of PT or OT referral.Of 317 patients with hand involvement, 90 (28%) reported PT or OT referral, but only 39 (12%) reported using these services. PT or OT referral was associated with more hand problems (odds ratio [OR]=1.24, 95% confidence interval [CI] 1.02-1.51, p=0.031) younger age (OR=0.96, 95% CI 0.94-0.99, p=0.004) and not being employed (OR=0.50, 95% CI 0.26-0.97, p=.0041).Few SSc patients with hand involvement are referred to PT or OT, and even fewer use these services. High-quality randomised controlled trials of PT and OT interventions to improve hand function in SSc are needed.

Objective.The University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium GI Tract Instrument (UCLA SCTC GITI) was recently developed to measure gastrointestinal tract disease in systemic sclerosis (SSc). Our study assesses the internal consistency and validity of the instrument in a different population than was used in the original study.Methods.A sample of 113 consecutive patients with SSc from the Canadian Scleroderma Research Group (CSRG) Registry completed the UCLA SCTC GITI, a self-administered questionnaire with 7 scales and an overall score. Reliability was evaluated using Cronbach’s alpha coefficient and validity was determined by testing multiple constructs.Results.Our subjects were slightly older than the original cohort, and had less formal education and less diffuse cutaneous disease. The overall score of the instrument correlated well with the GI scale of the Health Assessment Questionnaire for the Spondyloarthropathies (GI-S-HAQ; r = 0.58, p < 0.001) and the total number of GI symptoms (r = 0.77, p < 0.001). Each subscale correlated well with the GI-S-HAQ. The individual scales and the overall score were able to differentiate between categorical groupings of the GI-S-HAQ. The scale scores differentiated well those patients with clinical involvement of the corresponding GI problem. Multiple linear regression adjusting for age, disease duration, sex, and ethnicity showed that the UCLA SCTC GITI had a significant association with both the physical component summary and the mental component summary of the Medical Outcomes Study Short-Form 36 questionnaire.Conclusion.Our study confirms that the UCLA SCTC GITI version 2.0 will be a useful tool for assessing the role of GI involvement in SSc, even in a population with substantially different characteristics than the subjects originally tested.

Objective.Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc.Methods.Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival.Results.Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493).Conclusion.Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival.

There is currently no consensus on best practice in systemic sclerosis (SSc). To determine if variability in treatment and investigations exists, practices among Canadian Sclerodermia Research Group (CSRG) centres were compared.Prospective clinical and demographic data from adult SSc patients are collected annually from 15 CSRG treatment centres. Laboratory parameters, self-reported socio-demographic questionnaires, current and past medications and disease outcome measures are recorded. For centres with50 patients enrolled, treatment practices were analysed to determine practice variability.Data from 640 of 938 patients within the CSRG database met inclusion criteria, where 87.3% were female, the mean ± SEM age was 55.3±0.5, 48.9% had limited SSc and 47.8% had diffuse SSc (and 3.3% uncharacterised). Some investigation and treatment practices were inconsistent among 6 centres including proportion receiving: PDE5 (phosphodiesterase type 5) inhibitors for Raynaud's phenomenon (p=0.036); cyclophosphamide (p=0.037) and azathioprine (p=0.037) for treatment of ILD; and current use of D-penicillamine, although uncommon, varied among sites. Annual echocardiograms and PFTs were frequently done and did not vary among sites but the rate of pulmonary arterial hypertension (PAH) was directly related to site size and this was not the case for other organ involvement.Despite routine tests within a database, site variation in SSc with respect to investigations and management among CSRG centres exists suggesting a need for a standardised approach to the investigation and treatment of SSc. One can speculate that larger centres are more export in detecting PAH.

Significant weight loss in systemic sclerosis (SSc) is an ominous sign. Low body mass index (BMI) is one of the few variables able to predict mortality in SSc. Weight loss usually implies severe underlying intestinal disease. Gastrointestinal (GI) tract involvement is frequent in SSc and can be the presenting symptom. It is possibly the second most common site of organ damage after the skin and is a major cause of morbidity. Severe GI disease is found in 8% of patients and carries a high mortality rate. The pathophysiology of intestinal involvement includes vascular and neurologic abnormalities with subsequent smooth muscle atrophy and fibrosis resulting in dilatation of the intestine and altered peristaltic activity. Subsequent problems include pseudo-obstruction, pneumatosis cystoides intestinalis, small intestine bacterial overgrowth (SIBO), malabsorption, and ultimately malnutrition. The panel of diagnostic tools for small bowel disease includes standard and barium radiographic studies, breath tests for small intestinal bacterial overgrowth, and various tests for malabsorption. Unfortunately, there is no cure and treatment is symptom driven. Therapy may, however, improve the patient’s symptoms and quality of life. Team work between rheumatologist, nutritionist, and gastroenterologist is essential for this very complicated problem.

OBJECTIVE: Problems with sleep are common in patients with SSc and impact daily function. Little research, however, has examined factors associated with sleep disruption in SSc. Therefore, the objective of this study was to investigate socio-demographic and medical factors associated with sleep disruption in SSc. METHODS: Cross-sectional study of 70 patients from one Canadian Scleroderma Research Group site who were assessed with a 100-mm sleep disruption visual analogue scale (VAS). Patients also completed measures of pain and depressive symptoms and underwent clinical histories and medical examinations. Pearson's correlations were used to assess bivariate association of socio-demographic and medical variables with sleep VAS scores. Multivariable associations of socio-demographic (Step 1) and medical (Step 2) variables with sleep VAS scores were assessed using hierarchical multiple linear regression. RESULTS: The mean (s.d.) sleep disruption VAS score was 38.5 (29.9). In bivariate analyses, sleep disruption was associated with marital status (r = -0.24, P = 0.042), smoking (r = 0.27, P = 0.025), gastrointestinal symptoms (r = 0.27, P = 0.023), breathing problems (r = 0.31, P = 0.009), pain (r = 0.53, P

Objective.To assess disability in systemic sclerosis (SSc) longitudinally and to identify disease-specific determinants, after accounting for informative patient dropout.Methods.We performed a multicenter, longitudinal study of 745 patients with SSc followed in the Canadian Scleroderma Research Group registry. Disability was assessed using the Health Assessment Questionnaire (HAQ). Longitudinal changes in disability were modeled using statistical approaches accounting for various levels of patient dropout.Results.In all the models, disability in SSc worsened over time. The magnitude of the worsening was small when patient dropout was assumed to be completely at random (increase in the HAQ of 0.022, 95% CI 0.002–0.042, per year). After accounting for different levels of informative patient dropout, the increase in the HAQ ranged from 0.039 (95% CI 0.018–0.061) per year to 0.071 (95% CI 0.048–0.094) per year. Thus, using the most conservative of these estimates, this was equivalent to an increase in the HAQ of 0.12 over 3 years. The disease correlates found to be most closely associated with disability were diffuse disease and breathing problems.Conclusion.Our study provides strong evidence that SSc causes increased disability over time, with breathing problems and disease type being the strongest predictors of disability. Statistical modeling accounting for informative patient dropout is necessary to properly assess the outcomes of patients followed longitudinally.

Objective.To describe the magnitude and correlates of discordance between patient and physician assessments of disease severity in patients with systemic sclerosis (SSc).Methods.Subjects were patients enrolled in the Canadian Scleroderma Research Group Registry. The outcomes of interest were patient and physician global assessments of disease severity (scales ranging from 0–10). Predictors of disease severity represented the spectrum of disease in SSc (skin involvement, severity of Raynaud’s phenomenon, shortness of breath, gastrointestinal symptoms and pain, number of fingertip ulcers, tender and swollen joints, creatinine, and fatigue). The results of the analysis were validated in an independent sample of patients with SSc from the United States.Results.Patients perceived greater disease severity than physicians (mean difference 0.78 ± 2.65). The agreement between patient and physician assessments of disease severity was, at best, modest (intraclass correlation 0.3774; weighted κ 0.3771). Although both patients and physicians were influenced by skin scores, breathlessness, and pain, the relative importance of these predictors differed. Patients were also influenced by other subjective symptoms, while physicians were also influenced by disease duration and creatinine. The predictors explained 56% of the deviance in the patient global assessments and 29% in the physician assessments. These findings were confirmed in the US dataset.Conclusion.Patients and physicians rate SSc disease severity differently in magnitude and are influenced by different factors. Patient-assessed and physician-assessed measures of severity should be considered as complementary and used together in future studies of SSc.

Objective.Oxidative stress has been implicated in the pathogenesis of systemic sclerosis (SSc). Our objective was to determine whether SSc is associated with altered redox homeostasis in human saliva.Methods.Study participants were 70 women with SSc and 120 female controls. 8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-epi-prostaglandin F 2α (8-epi-PGF2α), and total protein carbonyls were assayed by ELISA to quantify oxidative damage to nucleic acids, lipids, and proteins, respectively, in whole nonstimulated saliva.Results.We observed a significantly positive association between salivary log protein carbonyls and SSc in a crude statistic (OR 9.06, p < 0.0001), and multivariable model adjusted for log 8-OHdG, log 8-epi-PGF2α, and antioxidant exposure (OR 9.26, p < 0.0001). No significant association was noted between SSc and salivary log 8-epi-PGF2α or log 8-OHdG.Conclusion.Salivary redox homeostasis is perturbed in patients with SSc and may inform on the pathophysiology and presence of the disease (biomarkers) and efficacy of therapeutic interventions.

We designed the current study to describe the spectrum of disease expression in systemic sclerosis (SSc) in a large cohort and to develop diagnostic criteria for SSc. We assessed patients in the Canadian Scleroderma Research Group Registry by standardized history, physical examination, and laboratory testing. We performed regression tree analysis to determine the sensitivity of various clinical and serologic features for diagnosing SSc. Over 1000 (n = 1048) patients were included: mean age 55 (+/- 12) years, 87% female, 90% white, mean disease duration 11 (+/- 10) years, and 38% with diffuse skin involvement. Common clinical features were Raynaud phenomenon (98%), sclerodactyly (92%), clinically visible mat-like telangiectasias (78%), skin involvement above the fingers (58%), lung fibrosis (35%), pulmonary hypertension (15%), and gastrointestinal tract involvement (mean number of self-reported symptoms, 4 (+/- 3) out of a possible 14). Almost 90% of patients had at least 1 SSc-related autoantibody, including 34% with anti-centromere and 16% with anti-topoisomerase I. The sensitivity of Raynaud and proximal finger skin thickening for the diagnosis of SSc was only 57%. Addition of clinically visible mat-like telangiectasias and SSc-related antibodies improved the sensitivity to 97%. We conclude that important diagnostic clues in patients with SSc include Raynaud phenomenon, skin involvement, clinically visible mat-like telangiectasias, and SSc-related autoantibodies.