Ariel Masetto

High prevalence of occult left heart disease in scleroderma-pulmonary hypertension

Our study aimed to determine the prevalence of occult left-heart disease in patients with scleroderma and pulmonary hypertension. In patients with pulmonary hypertension (mean pulmonary artery pressure (mean PAP) ≥25 mmHg), differentiation between pre- and post-capillary pulmonary hypertension has been made according to pulmonary artery wedge pressure (PAWP) less than or more than 15 mmHg, respectively. We performed a retrospective chart review of 107 scleroderma patients. All patients with suspected pulmonary hypertension had routine right or left heart catheterisation with left ventricular end-diastolic pressure (LVEDP) measurement pre-/post-fluid challenge. We extracted demographic, haemodynamic and echocardiographic data. Patients were classified into one of four groups: haemodynamically normal (mean PAP<25 mmHg); pulmonary venous hypertension (PVH) (mean PAP≥25 mmHg, PAWP>15 mmHg); occult PVH (mean PAP≥25 mmHg, PAWP≤15 mmHg, LVEDP>15 mmHg before or after fluid challenge); and pulmonary arterial hypertension (PAH) (mean PAP≥25 mmHg, PAWP≤15 mmHg and LVEDP≤15 mmHg before or after fluid challenge). 53 out of 107 patients had pulmonary hypertension. Based on the PAWP-based definition, 29 out of 53 had PAH and 24 out of 53 had PVH. After considering the resting and post-fluid-challenge LVEDP, 11 PAH patients were reclassified as occult PVH. The occult PVH group was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group. PVH had high prevalence in our scleroderma-pulmonary hypertension population. Distinguishing PAH from PVH with only PAWP may result in some PVH patients being misclassified as having PAH. Left heart catheterisation with saline infusion helps in the diagnosis of suspected PH in scleroderma http://ow.ly/mxuXE

2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Systemic Sclerosis Outperform the 1980 Criteria: Data From the Canadian Scleroderma Research Group

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.

Reports of abnormal cervical cancer screening tests in systemic sclerosis

OBJECTIVE To assess the prevalence of abnormal cervical cancer screening (Pap tests) reported by women with SSc onset before the age of 50 yrs. METHODS Female members of a Canadian multi-centre SSc cohort completed standardized assessments and were questioned regarding a history of an abnormal Pap test. Potential correlates examined included demographics, reproductive history, smoking, diffuse vs limited SSc type, immunosuppressant exposure and SSc duration. RESULTS In the 320 women with SSc onset before the age of 50 yrs, the life-time prevalence of an abnormal Pap test (according to self-report) was 25.4% (95% CI CI 20.9, 30.4%). By comparison, self-reported prevalence of abnormal Pap tests among general population Canadian females was recently reported at 13.8% (95% CI 11.6, 16.4%). Women with diffuse SSc (n = 142), tended to have a higher prevalence of self-reported cervical dysplasia (31.7%) compared with those with limited disease (20.7%), but the CIs overlapped. A multivariate logistic regression found a significant positive association between self-reported abnormal Pap test and diffuse disease [odds ratio (OR) 1.87; 95% CI 1.01, 3.47]. An independent association of an abnormal Pap test with smoking (OR 2.43; 95% CI 1.23, 4.78) and with younger age at disease onset was also noted. CONCLUSIONS We noted a high prevalence of abnormal Pap tests self-reported in our sample. Increased risk was seen among those with diffuse SSc, and also among smokers and those with a younger age at disease onset. Thus, it seems prudent to ensure that adequate attention is paid to cervical cancer screening for women with SSc.

Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis

Objective. The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts. Methods. Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis. Results. We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa− in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa− were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase. Conclusion. In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.

Relationship Between Disease Characteristics and Orofacial Manifestations in Systemic Sclerosis: Canadian Systemic Sclerosis Oral Health Study III

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.

Progressive Multifocal Leukoencephalopathy Associated with Belimumab in a Patient with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) and its treatment have been associated with progressive multifocal leukoencephalopathy (PML)1. We report a case of PML in a 58-year-old woman with SLE treated with belimumab, a biological therapy approved in 2011 for refractory SLE2. To the best of our knowledge, to date, 1 other such case has been described in the literature3. There was no …

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

IntroductionWe hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity.MethodsSerum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables.ResultsIn both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort.ConclusionUsing both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production.

The Canadian Systemic Sclerosis Oral Health Study II: the relationship between oral and global health-related quality of life in systemic sclerosis

OBJECTIVE Both oral and global health-related quality of life (HRQoL) are markedly impaired in SSc. In this study we aimed to determine the degree of association between oral HRQoL and global HRQoL in SSc. METHODS Subjects were recruited from the Canadian Scleroderma Research Group registry. Global HRQoL was measured using the Medical Outcomes Trust 36-item Short Form Health Survey (SF-36) and oral HRQoL with the Oral Health Impact Profile (OHIP). The Medsger Disease Severity Score was used to determine organ involvement. Multivariate regression models determined the independent association of the OHIP with the SF-36 after adjusting for confounders. RESULTS This study included 156 SSc subjects. The majority (90%) were women, with a mean age of 56 years, mean disease duration 13.8 years (s.d. 8.5) and 29% of the subjects had dcSSc. Mean total OHIP score was 40.8 (s.d. 32.4). Mean SF-36 mental component summary (MCS) score was 49.7 (s.d. 11.1) and physical component summary (PCS) score was 37.0 (s.d. 10.7). In adjusted analyses, the total OHIP score was significantly associated with the SF-36 MCS and PCS, accounting for 9.7% and 5.6% of their respective variances. Measures of disease severity were not related to OHIP score. CONCLUSION Oral HRQoL in SSc is independently associated with global HRQoL. Oral HRQoL, however, is not related to physician-assessed disease severity. This suggests that physicians may be disregarding issues related to oral health. HRQoL is an additional dimension of HRQoL not captured by generic instruments such as the SF-36.

Clinical correlates of faecal incontinence in systemic sclerosis: identifying therapeutic avenues

Objectives. The aim was to establish the prevalence and severity of faecal incontinence (FI) in SSc, its association with other intestinal manifestations and potential predictors of FI, and its impact on quality of life. Methods. A multicentre, cross‐sectional study of 298 SSc subjects followed in the Canadian Scleroderma Research Group cohort was performed using validated questionnaires: Jorge‐Wexner score (an FI severity scale), Bristol stool scale (a visual scale of stool consistency) and FI Quality‐of‐Life scale. Constipation was defined by the Rome III criteria. Associations between the Jorge‐Wexner score and other clinical variables were determined using multivariate regression analyses. Results. Eighty‐one (27.2%) subjects had FI, which was mild in 37 (12.4%) and moderate to severe in 44 (14.8%). Most patients had well‐formed stools, 111 (38.8%) reported constipation and 38 (13.4%) had been previously treated for small intestinal bacterial overgrowth (SIBO). Variables independently associated with FI were: loose vs well‐formed stools [odds ratio (OR) = 7.01, 95% CI: 2.09, 23.51)], constipation (OR = 3.64, 95% CI: 1.61, 8.27, P = 0.002), history of SIBO (OR = 2.97, 95% CI: 1.06, 8.27) and urinary incontinence (OR = 2.45, 95% CI: 1.14, 5.27). Quality of life measured with the FI Quality‐of‐Life scale was inversely correlated with FI severity (correlation coefficients between −0.602 and −0.702, P < 0.001). Conclusion. FI was common and often severe in SSc. Loose stools, SIBO, constipation and urinary incontinence were strongly associated with FI. Other than targeting anorectal dysfunction, concomitant treatment of clinical correlates could lead to improvement in FI and quality of life in SSc.

Depressive symptoms predict future simple disease activity index scores and simple disease activity index remission in a prospective cohort of patients with early inflammatory polyarthritis

OBJECTIVE To determine whether depressive symptoms assessed in treated patients with early inflammatory polyarthritis (EPA) influence disease activity during follow-up. METHODS Consecutively recruited EPA patients were actively treated to remission. Simple disease activity index (SDAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores were calculated at inclusion and up to 42 months into disease. SDAI scores were log-transformed to compute univariate and multivariate linear regressions. Parametric interval-censored Kaplan-Meier and survival regressions using Weibull distribution were used to assess time to and predictors of SDAI remission. RESULTS A total of 275 EPA patients were recruited at a median of 4 months into disease. In multivariate linear regression models, accounting for baseline demographic, clinical, serological and functional variables and 12-month inflammation markers, CES-D scores at 12 months into disease were correlated (r(2) = 0.14) with subsequent SDAI scores. Patients with 12-month high CES-D (≥19; suggestive of depression) had a lower proportion of SDAI remission (31.3% vs 84.3%; P < 0.001) and reached SDAI remission less rapidly [hazard ratio = 0.25 (95% CI 0.12, 0.53); P < 0.001]. CONCLUSION Each follow-up SDAI correlated significantly with 12-month depressive symptoms, a median of 7 months after initiation of treatment. CES-D scores suggestive of depression at 12 months were strongly correlated with delay and failure to reach remission later on. Depressive symptoms in treated EPA patients represent important clinical issues with long-term association with disease activity. Interventions to alleviate persistent depressive symptoms in treated EPA warrant careful evaluation of their potential to improve disease remission rates.