Background Antiphospholipid syndrome is defined by the combination of thrombotic events and/or obstetric morbidity in patients who have tested positive persistently for antiphospholipid antibodies. ...With good treatment, approximately 70% of pregnant women with antiphospholipid syndrome will deliver a viable live infant. However, current management does not prevent all maternal, fetal, and neonatal complications of antiphospholipid syndrome. Objectives This observational, retrospective, single-center cohort study aimed to assess pregnancy outcome in women with antiphospholipid antibodies who were treated with hydroxychloroquine in addition to conventional treatment during pregnancy. Study Design One-hundred seventy pregnancies in 96 women with persistent antiphospholipid antibodies were analyzed: (1) 51 pregnancies that occurred in 31 women were treated with hydroxychloroquine for at least 6 months before pregnancy, and the therapy continued throughout gestation (group A); (2) 119 pregnancies that occurred in 65 women with antiphospholipid antibodies that were not treated with hydroxychloroquine were included as controls (group B). Results Hydroxychloroquine-treatment was associated with a higher rate of live births (67% group A vs 57% group B; P = .05) and a lower prevalence of antiphospholipid antibodies–related pregnancy morbidity (47% group A vs 63% B; P = .004). The association of hydroxychloroquine with a lower rate of any complication in pregnancy was confirmed after multivariate analysis (odds ratio, 2.2; 95% confidence interval, 1.2–136; P = .04). Fetal losses at >10 weeks of gestation (2% vs 11%; P = .05) and placenta-mediated complications (2% vs 11%; P = .05) were less frequent in group A than group B. Pregnancy duration was longer in group A than group B (27.6 6-40 vs 21.5 6-40 weeks; P = .03). There was a higher rate of spontaneous vaginal labor in hydroxychloroquine-treated women compared with group B (37.3% vs 14.3%; P = .01). Conclusions Despite the heterogeneity in the 2 groups in terms of systemic lupus erythematosus prevalence and previous pregnancy history, our results support the concept that women with antiphospholipid antibodies may benefit from treatment with hydroxychloroquine during pregnancy to improve pregnancy outcome. The addition of hydroxychloroquine to conventional treatment is worthy of further assessment in a proper designed randomized controlled trial.
Objective
People affected by chronic rheumatic conditions, such as systemic lupus erythematosus (SLE), frequently rely on the Internet and search engines to look for terms related to their disease ...and its possible causes, symptoms and treatments. ‘Infodemiology’ and ‘infoveillance’ are two recent terms created to describe a new developing approach for public health, based on Big Data monitoring and data mining. In this study, we aim to investigate trends of Internet research linked to SLE and symptoms associated with the disease, applying a Big Data monitoring approach.
Methods
We analysed the large amount of data generated by Google Trends, considering ‘lupus’, ‘relapse’ and ‘fatigue’ in a 10-year web-based research. Google Trends automatically normalized data for the overall number of searches, and presented them as relative search volumes, in order to compare variations of different search terms across regions and periods. The Menn–Kendall test was used to evaluate the overall seasonal trend of each search term and possible correlation between search terms.
Results
We observed a seasonality for Google search volumes for lupus-related terms. In the Northern hemisphere, relative search volumes for ‘lupus’ were correlated with ‘relapse’ (τ = 0.85; p = 0.019) and with fatigue (τ = 0.82; p = 0.003), whereas in the Southern hemisphere we observed a significant correlation between ‘fatigue’ and ‘relapse’ (τ = 0.85; p = 0.018). Similarly, a significant correlation between ‘fatigue’ and ‘relapse’ (τ = 0.70; p < 0.001) was seen also in the Northern hemisphere.
Conclusion
Despite the intrinsic limitations of this approach, Internet-acquired data might represent a real-time surveillance tool and an alert for healthcare systems in order to plan the most appropriate resources in specific moments with higher disease burden.
To develop and validate a risk score global APS score (GAPSS) derived from the combination of independent risk for thrombosis and pregnancy loss (PL), taking into account the aPL profile, ...conventional cardiovascular risk factors and the autoimmune antibody profile.
This cross-sectional study included 211 consecutive SLE patients. Data on clinical manifestations, conventional cardiovascular risk factors, aPL profile, ANAs, ENA and anti-dsDNA were collected. Long-term low-dose aspirin, oral anticoagulant and HCQ treatment were also included in the analysis. Patients were randomly divided into two sets by a computer-generated randomized list. We developed GAPSS in the first set of patients (n = 106), assigning the risk factors identified by multivariate analysis weighted points proportional to the β-regression coefficient values. GAPSS was validated in the second set of patients (n = 105). The relationship between GAPPS and thrombosis and/or PL was analysed.
In the first set, higher values of GAPSS were seen in patients who experienced thrombosis and/or PL compared with those without clinical events GAPSS 9.3 (4.8) (range 1-19) and 5.3 (4) (range 0-16), P < 0.001. Also taken separately, patients who experienced thrombosis or PL showed higher GAPSS compared with those without clinical events GAPSS 9.6 (4.8) (range 1-19) vs 4.9 (5) (range 0-14), P = 0.027 for thrombosis; 7.3 (5) vs 3.9 (5.1) (range 0-16), P = 0.024 for PL, respectively. In the second set, the results were similar, with statistically higher values of GAPSS in patients with a clinical history of thrombosis and/or PL compared with those without events GAPSS 9.5 (5.6) (range 0-20) and 3.9 (4.1) (range 0-17), P < 0.001). Higher values were also seen when subclassifying the patients according to the clinical manifestation, thrombosis or PL GAPSS 9.5 (5.6) (range 0-20) vs 4.8 (5.4) (range 0-17), P = 0.036 for thrombosis; 7.9 (3.3) vs 3.8 (5.4) (range 0-16), P = 0.037 for PL, respectively).
These data propose a substantial improvement in risk prediction of thrombosis or PL in SLE based on assessment of the GAPSS, a quantitative scoring system.
Objectives: To evaluate the clinical accuracy of antiphospholipid antibody (aPL) specificities both individually and/or in combination, in a wide cohort of systemic lupus erythematosus (SLE) patients ...in an attempt to identify a panel of tests that may provide the best accuracy for diagnosing antiphospholipid syndrome (APS). Patients and Methods: This study included 230 patients (218 women, mean age 42.7 ± 11.9 years, mean disease duration 12.2 ± 8.7 years), all fulfilling the 1982 criteria for SLE. All patients were tested for lupus anticoagulant (LA), anti‐cardiolipin (aCL), anti‐β2glycoprotein I (anti‐β2GPI), solid phase anti‐prothrombin (aPT), anti‐phosphatidylserine/prothrombin (aPS/PT), and anti‐phosphatidylethanolamine (aPE) antibodies. Sensitivity, specificity and predictive values were calculated. The diagnostic accuracy for each combination of tests was assessed by ROC and their area under the curve analysis as well as by the Youden’s index (YI). Results: Testing for six aPL derived 23 possible combinations of results. Among them, LA + anti‐β2GPI + aPS/PT had the best diagnostic accuracy for APS as a whole and individually for both thrombosis and pregnancy loss (AUC 0.712, OR 3.73 95% CI 1.82–5.38, P = 0.0001, YI = 0.32 and AUC 0.709, OR 3.75 95% CI 2.13–6.62, P = 0.0001, YI = 0.37 and AUC 0.677, OR 4.82 95% CI 2.17–10.72, P = 0.0007, YI = 0.38, respectively) and the best specificity when compared with all the other obtainable combination of tests. Triple positivity for LA + anti‐β2GPI + aPS/PT was more strongly associated with clinical events (thrombosis and/or PL) when compared with double or single positivity (OR 23.2 95% CI 2.57–46.2 vs. OR 7.3 95% CI 2.21–25.97, OR 5.7 95% CI 2.12–17.01 or OR 3.11 95% CI 1.56–7.8 for single positivity for LA, aPS/PT and anti‐β2GPI, respectively). Conclusions: Combining LA, anti‐β2GPI and aPS/PT improves the diagnostic power and helps in stratifying the risk for each patient, according to their aPL profile.
Objective
The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other ...systemic autoimmune diseases.
Methods
Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years.
Results
We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States.
Conclusion
Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking.
Background and purpose
The most common neurological manifestation of antiphospholipid syndrome (APS) is ischaemic stroke. Identifying patients with APS at high risk for developing any thrombotic ...event remains a major challenge. In this study, the aim was to identify predictive factors of ischaemic stroke in a cohort of primary APS (PAPS) patients who presented with new onset symptoms suggestive of acute stroke.
Methods
This prospective multicentre study included 36 consecutive PAPS patients who presented with new onset symptoms suggestive of an acute stroke. Patients were prospectively followed up for 12 months.
Results
In 10 (28%) out of 36 PAPS patients mean age 41 years (SD 13.4), 70% female, the suspicion of an acute stroke was confirmed by brain magnetic resonance imaging. Sixty per cent of these patients were <50 years old. Eight of the 10 patients had a history of previous venous thrombosis and were receiving vitamin K antagonist (VKA), with international normalized ratio target 2–3; one patient had a history of a previous arterial event receiving treatment with VKA target international normalized ratio 2–3 plus low dose aspirin; and one patient had a history of previous pregnancy morbidity receiving only low dose aspirin. Time in the therapeutic range for patients receiving VKA was 77.7% (SD 6.6%). Hypercholesterolaemia was significantly higher in patients with confirmed stroke compared to those without (P < 0.05). Similarly, a significantly higher rate of anti‐β2 glycoprotein‐I (β2GPI) antibodies (immunoglobulin G/immunoglobulin M; P < 0.05) and higher adjusted global APS score (aGAPSS) values were found in patients with a confirmed stroke mean aGAPSS 8.9 (SD 4.7) vs. mean aGAPSS 6.4 (SD 2.5); P < 0.05.
Conclusions
Patients with PAPS, including young patients, have a high risk of recurrent thrombosis despite anticoagulation treatment. A careful risk assessment is mandatory to identify patients at risk for recurrence.
Antibodies to prothrombin can be detected by ELISA using prothrombin coated onto irradiated plates (aPT) or the phosphatidylserine/prothrombin complex as antigen (aPS/PT) and they have been both ...related with the clinical manifestation of APS. Current evidence supports the concept that they belong to distinct populations of autoantibodies. Nevertheless, they can both be detected simultaneously in one patient.
This mini-review will focus on data available on aPS/PT antibodies and their clinical utility in the diagnosis of APS.
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