The contribution of nailfold video capillaroscopy (NVC) in identifying patients with Raynaud's phenomenon (RP) at risk for systemic sclerosis (SSc) is well established. Herein we comparatively assess ...the performance of different capillaroscopic parameters in diagnosing SSc among patients with RP and evaluate the prognostic capacity of NVC in SSc.
At baseline we clinically and capillaroscopically evaluated 242 consecutive patients referred to our department for NVC (138 with SSc); 175 were reevaluated after 3.38±1.47 years. Sixty-two healthy volunteers served as controls. Capillaroscopy pattern (normal/early/active/late) was qualitatively defined. Capillary loss, dilated, giant or ramified capillaries and micro-haemorrhages were scored semi-quantitatively.
Capillary loss score had the highest diagnostic accuracy at discriminating patients with an SSc-spectrum disorder from patients with RP of different etiology and controls, as defined by ROC curve analysis AUC (95% CI)=0.905 (0.869-0.942), followed by dilatation score 0.863 (0.818-0.907) and giant score 0.835 (0.787-0.884). By contrast, micro-haemorrhages 0.720 (0.662-0.779) and ramifications scores 0.604 (0.539-0.670) performed worse. Multivariate analysis in 94 SSc patients indicated that active (OR=3.305, p=0.043) and late (OR=6.900, p=0.023) baseline capillaroscopy pattern predicted occurrence of a combined adverse disease outcome forced vital capacity (FVC) deterioration>10% and/or DLCO deterioration>15% and/or mRSS deterioration>3.5 and/or first occurrence of digital ulcers and/or death) at 3 year follow-up.
Dilatation score performs best of all semi-quantitative NVC parameters in diagnosing SSc. In addition, our study confirms earlier reports that worse capillaroscopy pattern at baseline correlates with higher likelihood for adverse prognosis.
Background:
Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and ...treatment patterns in RA.
Methods:
This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD) and glucocorticoid (GC) use were also recorded.
Results:
The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR<3.2) while 43% did not (34%: moderate disease activity: DAS28ESR ⩾3.2 to <5.1, 9%: high disease activity, DAS28ESR ⩾5.1). By multivariate analysis, male sex was positively associated with LDA odds ratio (OR) = 2.29 p < 0.001 whereas advanced age (OR = 0.98, p = 0.005), high Health Assessment Questionnaire (HAQ) score (OR = 0.57, p < 0.001), use of GCs (OR = 0.75, p = 0.037) or ⩾2 bDMARDs (OR = 0.61, p = 0.002), high co-morbidity index (OR = 0.86, p = 0.011) and obesity (OR = 0.62, p = 0.002) were negative predictors of LDA. During follow-up, among active patients (DAS28ESR >3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs.
Conclusion:
In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors.
We have observed several cases of patients with systemic lupus erythematosus (SLE) who developed antiphospholipid antibodies (aPL) or full blown antiphospholipid syndrome (APS) after being ...successfully treated with cyclophosphamide (CYC). To further evaluate the significance of this phenomenon we undertook a retrospective study of our patient population with SLE.
The charts of 320 patients with SLE, either CYC treated (n = 117) or non-treated (n = 203), were reviewed. The disease activity over time was evaluated using the European Consensus Lupus Activity Measurement (ECLAM) scoring system, as well as initial and cumulative anti-dsDNA antibody titers and C3, C4 complement levels. aPL titers (IgG and IgM) were documented for all patients. Seroconversion was defined as the de novo appearance of aPL antibodies at a titer higher than the 99th percentile of 100 normal sera, tested on 2 occasions 12 weeks apart.
Seroconversion occurred in 22 out of 117 patients treated with CYC as compared with 2 out of 203 non-CYC treated patients odds ratio (OR) = 23.27, 95% confidence interval (CI) 5.36-101.01. Six patients from the seroconverted CYC treated group were diagnosed with APS compared to none in the non-CYC treated group. The association between seroconversion and CYC remained significant after adjustment for ECLAM score after treatment, prednisone dose and disease duration (OR = 13.4, 95% CI 2.67-67.50). Seroconversion occurred despite successful disease remission as judged by significant decrease of: anti-dsDNA antibody titers (p < 0.01), ECLAM scores (p < 0.01), and C3 (p < 0.01) and C4 levels (p < 0.01).
Our data suggest that CYC therapy might be associated with upregulation of aPL and development of antiphospholipid syndrome despite suppression of SLE activity.
Objective
To determine the ability of initial forced vital capacity (FVC) of patients with scleroderma to predict subsequent pulmonary function deterioration.
Methods
Data on 78 patients with ...scleroderma were retrospectively collected and analyzed. FVC (percent predicted), diffusing capacity for carbon monoxide (percent predicted), and various clinical and laboratory parameters were recorded. Pulmonary function decline (outcome) was defined as at least a 15‐point sustained decrease in FVC (percent predicted). Kaplan‐Meier analyses were performed separately for 60 patients initially assessed within the first 3 years from disease onset (group A) and 16 patients whose FVC values in the fourth or fifth year from disease onset were ascribed as baseline measurements (group B).
Results
Based on baseline FVC, patients in each group were categorized into those with normal FVC (≥80% predicted) and those with decreased FVC (<80% predicted). In group A, the percent‐predicted FVC of 89% of patients with normal initial FVC and of 75% of patients with reduced baseline FVC did not decrease by ≥15 points at 5 years (log rank P = 0.04). Four patients with decreased baseline FVC developed respiratory failure (FVC <50% predicted) versus none with normal initial FVC. Analysis of group B showed no difference between patients with normal baseline FVC and those with decreased FVC in the ability to further predict pulmonary function decline (log rank P = 0.13). Clinical and laboratory parameters (age, male sex, baseline diffusion capacity, anti–topoisomerase I, or duration of Raynaud's phenomenon preceding skin manifestations) were not associated with pulmonary function decline.
Conclusion
Measured within the first 3 years from disease onset, baseline FVC (percent predicted) may predict deterioration of pulmonary function in patients with scleroderma. Patients with normal pulmonary function at initial assessment are at low risk to develop considerable impairment of pulmonary function.
Hyponatremia is a commonly encountered clinical problem with potentially severe complications. Among the underlying implicated etiologies are medications such as oxcarbazepine, which has been well ...documented and attributed to the syndrome of inappropriate antidiuretic hormones (SIADH). We report the case of a 28-year-old woman with a diagnosis of secondary antiphospholipid syndrome who presented with asymptomatic hyponatremia secondary to excessive water intake after oxcarbazepine ingestion, suggesting a new mechanism for oxcarbazepine-induced hyponatremia.
The International Congress on Antiphospholipid Antibodies is held every three years to discuss the recent advances and future directions in Antiphospholipid Syndrome (APS). This volume collects the ...scientific highlights and new findings about APS that were generated from the most recent 13th Congress, held in Galveston, Texas in 2010. Chapters were written by an internationally-distinguished group of scientists from the point-of-view of multiple specialty areas. Each chapter was written in a uniform and systematic basis to present the latest evidence-based research, including the basic science of APS, task force reports from the Congress on controversial aspects of APS, and future directions of APS research. This book will appeal to all clinicians involved in the treatment and management of APS patients, to residents in a variety of medical subspecialties, and to research scientists interested in a better understanding of this complex and evolving disease.
Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by arterial/venous thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies that mainly ...recognize beta2 glycoprotein I (beta2GPI). To investigate potential platelet ligands of beta2GPI, platelet membrane proteins from healthy persons and patients with APS were passed through a beta2GPI-affinity column. By using mass spectrometry, platelet factor 4 (PF4) appeared as the dominant beta2GPI binding protein. PF4 could bind in vitro, with high-affinity, recombinant beta2GPI, and the binding was abrogated by soluble beta2GPI. Coprecipitation experiments further confirmed this interaction. In silico molecular docking showed that PF4 tetramers can bind 2 beta2GPI molecules simultaneously. Size exclusion chromatography confirmed that anti-beta2GPI antibodies selectively interact with complexes composed of (beta2GPI)(2)-(PF4)(4). In addition, as shown by the beta2GPI antigenicity evaluation, the reactivity of APS sera was higher against PF4-beta2GPI complex than against beta2GPI alone. On complex formation, anti-beta2GPI-beta2GPI-PF4 significantly induced platelet p38MAPK phosphorylation and TXB2 production, mainly through F(ab')(2) fragments of antibodies. In summary, this study makes evident that beta2GPI forms stable complexes with PF4, leading to the stabilization of beta2GPI dimeric structure that facilitates the antibody recognition. This interaction can probably be involved in the procoagulant tendency of APS.
From viruses to multicellular organisms, life is inseparable from the genetic instructions aimed at regulating its maintenance, division, multiplication, differentiation and death (apoptosis). Over ...the past 15 years, structural studies have begun to resolve the complex reactions involved in these fundamental processes in biology. The three-dimensional representations of the complexes formed with peptides and/or proteins have allowed interpretation of the biochemical data and formulation of novel hypotheses about the control and execution of these processes. Moreover, they have opened the way to rational approaches for designing compounds able to interfere with these crucial events in normal or pathological conditions. Various results obtained in our laboratory in these fields are briefly summarized in this review.
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