Search

Objective There are no identified clinical markers that reliably predict long-term progression of interstitial lung disease (ILD) in systemic sclerosis (SSc; scleroderma). Elevated C-reactive protein (CRP) levels have been reported in SSc patients. We examined the predictive significance of CRP level for long-term ILD progression in a large early SSc cohort.

Objective To investigate the association of cigarette smoking with susceptibility to systemic sclerosis (SSc) in a large, well-defined patient population. Methods We conducted a review of 1,379 patients with SSc enrolled in the Scleroderma Family Registry and DNA Repository and/or the Genetics versus Environment in Scleroderma Outcome Study cohort. Smoking history was obtained from chart review or via telephone interview. Patients with SSc were subsequently categorized as never smokers or ever smokers. Patients with SSc for whom smoking data were available were matched 2:1 by age, sex, ethnicity, and state of residence to control subjects, using the Behavioral Risk Factor Surveillance System. Results The majority of patients were white (74.2%), with Hispanics and blacks representing 11.3% and 9.7%, respectively. Most patients had limited cutaneous involvement (54%). For our comparative analyses, 621 patients were matched with control subjects. There was no significant difference in age, sex, ethnicity, and SSc subtype between matched versus unmatched patients. The majority of patients had never smoked (57%), while 43% of patients were classified as ever smokers. The patients with SSc did not differ from control subjects in terms of their smoking behavior (odds ratio [OR] 1.020, 95% confidence interval [95% CI] 0.839–1.240, P = 0.842). Anti–topoisomerase I antibody–positive patients were more likely to be never smokers (OR 0.648, 95% CI 0.421–0.998, P = 0.049), whereas no such association was observed with anticentromere and anti–RNA polymerase III antibodies. Conclusion Unlike its role in rheumatoid arthritis, smoking does not confer a risk for development of SSc, although it may impact disease severity.

Antiphospholipid syndrome is a systemic autoimmune disease associated with thrombosis and recurrent fetal loss in the setting of detectable antiphospholipid (aPL) antibodies. The major antigenic target has been identified as β2-glycoprotein I (β2GPI), which mediates binding of aPL antibodies to target cells including endothelial cells, monocytes, platelets and trophoblasts, leading to prothrombotic and proinflammatory changes that ultimately result in thrombosis and fetal loss. This article summarizes recent insights into the role of β2GPI in normal hemostasis, interactions between aPL antibodies, β2GPI and cell-surface molecules, molecular prothrombotic and proinflammatory changes induced by aPL antibodies and pathogenic changes leading to fetal loss in antiphospholipid syndrome. New directions in therapy using these insights are examined.

The fifth author, Brock E. Harper, was incorrectly indicated as having contributed equally to the paper with the first and second authors.

Objective Illness behaviors (cognitive, affective, and behavioral reactions) among individuals with systemic sclerosis (SSc; scleroderma) are of clinical concern due to relationships between these behaviors and physical and mental quality of life, such as pain and symptoms of depression. Self-report measures with good psychometric properties can aid in the accurate assessment of illness behavior. The Illness Behavior Questionnaire (IBQ) was designed to measure abnormal illness behaviors; however, despite its longstanding use, there is disagreement regarding its subscales. The goal of the present study was to evaluate the validity of the IBQ in a cohort of patients with SSc. Methods Patients with SSc (n = 278) completed the IBQ at enrollment into the Genetics Versus Environment in Scleroderma Outcome Study. Structural validity of previously derived factor solutions was investigated using confirmatory factor analysis. Exploratory factor analysis was utilized to derive SSc-specific subscales. Results None of the previously derived structural models were supported for SSc patients. Exploratory factor analysis supported an SSc-specific factor structure with 5 subscales. Validity analyses suggested that the subscales were generally independent of disease severity, but were correlated with other health outcomes (i.e., fatigue, pain, disability, social support, and mental health). Conclusion The proposed subscales are recommended for use in SSc, and can be utilized to capture illness behavior that may be of clinical concern.

Historically, aPL antibodies were classified based on the clinical laboratory test in which they were detected, i.e. LA and aCL antibodies. It is now widely accepted that aPL antibodies are a heterogenous group of antibodies that react with a myriad of phospholipids (PLs), PL-protein complexes and PL binding proteins. The main antigenic target of these antibodies is recognized to be 2glycoprotein I (2GPI), which along with prothrombin accounts for more than 90% of the antibody binding activity in APS patients. Other potentially significant antigenic targets include tissue plasminogen activator (tPA), phosphatidylserine (PS), plasmin, annexin 2, activated protein C (APC), thrombin, antithrombin (AT) and annexin A5 [2,3].

Objective To measure interferon (IFN)–inducible chemokines in the plasma of patients with systemic sclerosis (SSc) and investigate whether the chemokine levels are correlated with disease severity. Methods Plasma levels of the IFN-inducible chemokines IFNγ-inducible protein 10 (IP-10/CXCL10), IFN-inducible T cell α chemoattractant (I-TAC/CXCL11), and monocyte chemoattractant protein 1 (CCL2) were measured in SSc patients and examined for correlation with the IFN gene expression signature. A composite IFN-inducible chemokine score was generated for chemokines showing a correlation with the IFN gene signature (IP-10 and I-TAC), and this score was compared between 266 patients with SSc enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort and 97 matched control subjects. Subsequently, the correlation between the IFN-inducible chemokine score at baseline and markers of disease severity was assessed. In addition, the course of the IFN-inducible chemokine score over time was examined. Results The plasma IFN-inducible chemokine score correlated with the IFN gene expression signature, and this score was higher in SSc patients compared to controls. The IFN-inducible chemokine score was also associated with the absence of anti–RNA polymerase III antibodies and presence of anti–U1 RNP antibodies, but not with disease duration, disease type, or other autoantibodies. The chemokine score correlated with concomitantly obtained scores on the Medsger Severity Index for muscle, skin, and lung involvement in SSc, as well as the forced vital capacity, diffusing capacity for carbon monoxide, and creatine kinase levels. The association of the chemokine score with disease severity was independent of the presence of anti–U1 RNP or other potential confounders (age, sex, ethnicity, disease duration, and treatment with immunosuppressive agents). Finally, there was not a significant change in the IFN-inducible chemokine score over time. Conclusion The IFN-inducible chemokine score is a stable serologic marker of a more severe form of SSc and may be useful for risk stratification of patients, regardless of disease type (limited or diffuse) or duration of disease.

To investigate the association of cigarette smoking with susceptibility to systemic sclerosis (SSc) in a large, well-defined patient population.We conducted a review of 1,379 patients with SSc enrolled in the Scleroderma Family Registry and DNA Repository and/or the Genetics versus Environment in Scleroderma Outcome Study cohort. Smoking history was obtained from chart review or via telephone interview. Patients with SSc were subsequently categorized as never smokers or ever smokers. Patients with SSc for whom smoking data were available were matched 2:1 by age, sex, ethnicity, and state of residence to control subjects, using the Behavioral Risk Factor Surveillance System.The majority of patients were white (74.2%), with Hispanics and blacks representing 11.3% and 9.7%, respectively. Most patients had limited cutaneous involvement (54%). For our comparative analyses, 621 patients were matched with control subjects. There was no significant difference in age, sex, ethnicity, and SSc subtype between matched versus unmatched patients. The majority of patients had never smoked (57%), while 43% of patients were classified as ever smokers. The patients with SSc did not differ from control subjects in terms of their smoking behavior (odds ratio [OR] 1.020, 95% confidence interval [95% CI] 0.839-1.240, P=0.842). Anti-topoisomerase I antibody-positive patients were more likely to be never smokers (OR 0.648, 95% CI 0.421-0.998, P=0.049), whereas no such association was observed with anticentromere and anti-RNA polymerase III antibodies.Unlike its role in rheumatoid arthritis, smoking does not confer a risk for development of SSc, although it may impact disease severity.

Spondyloarthritis (SpA), a family of inflammatory back diseases including ankylosing spondylitis, is an important and under-recognized cause of chronic back pain in younger patients who are likely to participate in sports and athletic activities. These diseases are characterized by the presence of inflammatory back pain--lumbar or buttock/hip pain lasting longer than 3 months associated with improvement with activity, worsening with rest, relief with non-steroidal anti-inflammatory drugs (NSAIDs), and morning stiffness lasting longer than 30 min. There are also characteristic radiographic findings involving the sacroiliac joints, vertebrae, and in certain diseases, the peripheral joints. Exercise has long been recognized as a key component of the therapy of SpA, yielding benefits in mobility, pain, stiffness, functionality, and depression. Sports also pose a risk to patients with SpA as these patients are at high risk of spinal fracture and spinal cord injury.

Objective To evaluate the prognostic significance of baseline electrocardiogram (ECG) abnormalities in a multiethnic cohort of patients with early systemic sclerosis (SSc) and to determine the serological, clinical, and echocardiogram correlates of ECG findings. Methods SSc patients with disease duration of≤5 years were enrolled in the GENISOS (Genetics versus Environment in Scleroderma Outcome Study) cohort. At the first visit, a standard 12 lead ECG was obtained along with demographic information, clinical data, and autoantibodies. The results of echocardiograms were also recorded. All ECGs were interpreted by a cardiologist unaware of the patients' clinical data. Results Of 265 SSc patients with average disease duration at enrollment of 2.5 years, 140 (52.8%) had abnormal ECG findings. These findings were not associated with SSc disease type or autoantibody profile but were associated with more severe heart and lung involvement. A total of 75 patients (28.3%) died over a follow up time of 9.9 years. Complete right bundle branch block (± left anterior hemiblock) on ECG, present in 7 (2.6%) patients, predicted a higher risk of mortality (HR: 5.3; 95% CI: 2.1 to 13.4; p