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.
Heart valve disease (HVD) is frequent in patients with systemic lupus erythematosus (SLE), and the role of antiphospholipid antibodies (aPL) is controversial. Thus, our objective was to estimate the ...risk of HVD, including Libman-Sacks endocarditis, associated with aPL in patients with SLE.
Studies were selected if they investigated the association between aPL and HVD in SLE patients and if aPL-negative patients were included for comparison. Data sources were MEDLINE, Embase, Cochrane Library, hand search, contact with investigators, and reference lists of studies, without language restrictions. Data on study and patient characteristics, risk estimates, and study quality were independently extracted by 2 investigators. Pooled effect estimates were obtained by using the DerSimonian-Laird method. Of 234 identified abstracts, 23 primary studies (15 cross-sectional, 7 cohort, 1 case-control) met inclusion criteria, including 1656 SLE patients and 508 cases of HVD. Compared with SLE patients without aPL (n=988), the overall pooled odds ratios for HVD and Libman-Sacks endocarditis in aPL-positive patients (n=668) were 3.13 (95% confidence interval, 2.31 to 4.24) and 3.51 (95% confidence interval, 1.93 to 6.38), respectively. The risk of HVD depending on aPL subtypes was the highest for lupus anticoagulant at 5.88 (95% confidence interval, 2.92 to 11.84) and IgG anticardiolipin antibodies at 5.63 (95% confidence interval, 3.53 to 8.97).
Overall, the presence of aPL in SLE patients is significantly associated with an increased risk for HVD including Libman-Sacks endocarditis. The risk conferred by IgG anticardiolipin antibodies is as strong as by lupus anticoagulant. Systematic echocardiographic examinations in SLE patients with aPL should be performed.
We report an original case of reversible antiphospholipid syndrome (APS) due to minocycline in a young male patient who experienced recurrent strokes while taking minocycline. He started minocycline ...therapy (50 mg twice daily) at 15 years old for acne. After three years of treatment, the patient experienced a lateral medullary syndrome. He was treated with aspirin while minocycline was continued. Eighteen months later, the patient complained about horizontal binocular diplopia. MRI revealed an infarct of the oculomotor nerve nucleus. Laboratory investigations revealed high titers of anti-beta 2 glycoprotein 1 (antiβ2GP1) antibodies of 470 U/ml (normal range <15 U/ml) and antiphosphatidylethanolamine antibodies of 137.4 U/ml (normal range <18 U/ml). Other laboratory tests were normal. Six weeks after discontinuation of minocycline, anti-β2GP1 antibodies decreased to 335 U/ml and to 36 U/ml at six months and then remained negative for six years. Many drugs have been considered as possibly causing APS but only in a limited number of patients. To our knowledge this is the first case of drug-induced APS with complete disappearance of high titers of anti-β2GP1 antibodies after minocycline withdrawal.
This case also illustrates the need to monitor the levels of antiphospholipid antibodies, even though initial values are high and confirmed after 12 weeks.
Purpose
Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically ...unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6‐negative patients.
Methods
First, family‐based exome sequencing was performed, in one ABCC6‐negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6‐negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients.
Results
6.4% of ABCC6‐negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE.
Conclusion
CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.
The purpose of this study was to describe the epidemiologic characteristics of adult uveitis evaluated at the regional center of excellence specializing in systemic and autoimmune disease in the ...Nancy university medical center. The secondary objectives were to describe the progression over time of the various etiologies and to identify local specificities.
We performed a retrospective epidemiological study of patients diagnosed with uveitis. All patients were referred to the regional center of excellence of the Nancy university medical center between January 1, 2005 and December 31, 2016. Patients under 18 years of age, patients with a first episode of acute anterior uveitis, as well as patients for whom the etiological diagnosis was made by the ophthalmologist with no need of internal medicine referral, were excluded. Age, gender, laterality, site of inflammation, clinical signs, etiology (infectious, non-infectious or idiopathic, as well as diagnosis), and date of first consultation were recorded.
Six hundred and ninetypatients were included, with 59 % women and a mean age of 49 years. The uveitis was unilateral in 53 % of cases. Panuveitis was the most common form (52 %, N=358), followed by recurrent anterior uveitis (30 %, N=205), posterior uveitis (16 %, N=107), and intermediate uveitis (3 %, N=20). Non-infectious etiologies accounted for 35 % of all uveitis (the most common being HLA-B27 uveitis, sarcoidosis, ankylosing spondylitis and Behçet's disease) and infectious etiologies for 13 % (tuberculosis, toxoplasmosis and Lyme disease were the most frequent). The uveitis was idiopathic in 52 %. A trend toward improvement in diagnostic yield was observed : 53 % of uveitides were considered idiopathic prior to 2011 compared to 50 % after 2011 (P<0,01).
We identified a majority of panuveitis, which is explained by our inclusion criteria. Fifty-two percent of our series remained idiopathic, with an improvement in the diagnostic yield over time. This could be related to both repeated etiological assessments and better diagnostic performance. The study of this large cohort of patients improved our knowledge of the characteristics of uveitis in our center.
Our objective was to study acquired Activated Protein C (APC) resistance in patients with antiphospholipid antibodies (aPL) using a thrombin generation based assay. We compared patients with and ...without lupus (systemic lupus erythematosus, SLE). A parameter summarizing APC inhibition of thrombin generation with increasing APC concentrations (IC50-APC) was increased in all patient groups compared to controls: median values were 15.3 (interquartile range, IQR, 9.7 to 34.0) in patients with primary antiphospholipid syndrome (APS), 27.3 (IQR 23.5 to 43.5) in patients with SLE without APS, 64.1 (IQR 25.9 to 65.0) in patients with SLE/APS compared to 10.4 IQR 8.5 to 15.8 in controls, respectively p = 0.003, p = 0.0001 and p = 0.0001.
In conclusion, patients with SLE and primary APS displayed a hypercoagulable state characterized by APC resistance.
Simulation-based education (SBE) has demonstrated its acceptability and effectiveness in improving ultrasound training. Because of the high cost of its implementation (investment in equipment and ...supervision), a pragmatic assessment of the transfer of skills learned in SBE to clinical practice and the identification of its optimal scheduling conditions have been requested to optimize its input.
To quantify the long-term impact of simulation-based education (SBE) on the adequate performance of ultrasound fetal biometry measurements (I). The secondary objective was to identify the temporal patterns that enhanced SBE input in learning (II).
Trainees were arbitrarily assigned to a 6-month course in obstetric ultrasound with or without an SBE workshop. In the SBE group, the workshop was implemented 'before' or at an 'early' or a 'late-stage' of the course. Those who did not receive SBE were the control group. The ultrasound skills of all trainees were prospectively collected, evaluated by calculating the delta between OSAUS (Objective Structured Assessment of Ultrasound Skills) scores before and after the course (I). Concomitantly, the accuracy of trainees' measurements was assessed throughout the course by verifying their correlation with the corresponding measurements by their supervisors. The percentage of trainees able to perform five consecutive sets of correct measurements in the control group and in each SBE subgroup were compared (II).
The study included 61 trainees (39 SBE and 22 controls). Comparisons between groups showed no significant difference in the quantitative assessment of skill enhancement (difference in the pre- and post-internship OSAUS score: 1.09 ± 0.87 in the SBE group and 0.72 ± 0.98 in the control group) (I). Conversely, the predefined acceptable skill level was reached by a significantly higher proportion of trainees in the 'early' SBE subgroup (74%, compared with 30% in the control group, P<0.01)(II).
The quantitative assessment does not support the existence of long-term benefits from SBE training, although the qualitative assessment confirmed SBE helped to raise the minimal level within a group when embedded in an 'early' stage of a practical course.
Objectives
Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and ...assessed the impact of thromboembolic history.
Methods
HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified.
Results
A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3).
Conclusion
Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient’s perspective and to provide patients with the support they need.
PDF
