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BackgroundCerebral venous thrombosis (CVT), which includes cerebral vein and dural sinus thrombosis, is a rare disorder that can lead to significant morbidity and mortality. Its occurrence in SLE in the absence of APS has been rarely reported. In this study we aimed to describe a cohort of SLE patients suffering from CVT without APS.MethodsWe collected retrospectively clinical and biological data of patients with confirmed CVT in the Pitié-Salpêtrière cohort of SLE (n=1352 patients). Patients fulfilled ACR SLE criteria. The diagnosis of CVT was confirmed by brain imaging studies. Exclusion criteria were patient with a lupus anticoagulant or IgG/IgM anticardiolipin antibodies or anti-β2 glycoprotein-1 abs. We searched on PUBMED database for case report of this association published in English until 31 August 2017. Lupus flares were defined according the SELENA Flare instrument.ResultsWe included 10 patients (8 women and 2 men). The median (range) age at diagnosis of CVT was 28 years.9–53 The CVT occurred with a median delay of 4 years (0–11) after the diagnosis of SLE. At the time of the CVT diagnosis: no patients had a past medical history of thrombotic event or miscarriage or foetal loss; 7 patients had a lupus flare (5 lupus nephritis [1 class I, 1 class V, 2 class IV and 1 class III+V], 4 immune thrombocytopenia, 2 autoimmune hemolytic anaemia, 3 cutaneous lupus, 1 serositis and 1 arthritis); 7 patients were treated with corticosteroids, 4 with hydroxychloroquine and 4 with immunosuppressive drugs. Other potential precipiting factors of CVT were: 2 nephrotic syndromes, 2 anaemia and 1 hyperhomocysteinemia. CVT was symptomatic for 9 patients: 8 headaches, 3 epilepsia and 1 sensitivo-motor deficit. The diagnosis of CVT was confirmed by magnetic resonance imaging (MRI) for 9 patients and cerebral angiography for 1 patient. The median delay between the onset of clinical symptoms and the diagnosis of thrombosis was 10 days.3–37 Nine patients presented a single localisation of CVT (superior longitudinal or lateral or cavernous sinus, or cortical cerebral vein). Only 1 patient had thrombosis of both lateral and sigmoid sinus. Cerebral infarction or haemorrhage was seen for 2 patients. Corticosteroids and immunosuppressant treatment were increased or introduced because of a concomitant lupus flare for 2 patients. All patients were treated with heparin followed by vitamin K antagonists for 7 patients or apixaban for 2 patients. One patient received long-term heparin. After a median survey of 19.5 (1–120) months: anti-coagulant drugs were stopped for 6 patients; recanalisations were complete in 7 of the 7 patients assessed on brain MRI; no patient had a residual neurological damage; only 1 patient had a new vascular event in the form of a brain haemorrhage. In addition to these 10 cases we found 17 cases from a literature review.ConclusionsCVT is a rare event in SLE in absence of APS. In our cohort SLE was often active at the time of the CVT occurrence. Most of the CVT were limited in extension and severity. The outcome on anticoagulant treatment was favourable without residual neurological damage. The occurrence of CVT in SLE is not an indication by itself to increase or to introduce corticosteroids or immunosuppressive drug.Disclosure of InterestNone declared

BackgroundOutcome of juvenile-onset SLE (j-SLE) during adulthood is poorly described.ObjectivesTo report adult outcome of j-SLE and compare SLE course during childhood and adulthood.Methodsj-SLE was defined as a SLE fulfilling ACR criteria and diagnosed before the age of 16 years. Mac Nemar test for paired nominal data and Wilcoxon signed rank test for paired data were used.ResultsOne hundred and six patients j-SLE (88 women and 18 men, female to male ratio: 4.9), mean age at diagnosis: 12.3 years were followed during a mean duration of 13.8 years, from childhood (mean: 4 years) to adulthood (mean: 10.3 years). 97.2% patients received corticosteroids (with intravenous pulses for 50.9%) and 77.3% immunosuppressant drugs. 105 (99%) patients received antimalarial drugs.Clinical manifestations of the first flare were: arthritis (67.9%), cutaneous (57.5%), nephritis (23.6%), fever (17.9%), hematologic: ITP, AIHA (15%). Neuropsychiatric manifestations were found in 6.6%. Digestive involvement was only present in 6% of cases. According to the revised SELENA FLARE INDEX (SFI), the first flare was severe for half of the patients (n=55).Disease course during adulthood had two patterns: 82 patients (77.3%) had at least one SLE flare and 24 (22.6%) a sustained remission. Mean follow up was however significantly higher in the relapsing group (15 years vs 9.8 years, p=0.0014). No difference was found between these 2 groups for first flare severity and clinical manifestations during childhood.Significantly more cutaneous (61.3 vs 42.4%, p=0.003), musculoskeletal (75.5 vs 59.4%, p=0.007), neuropsychiatric (10.4 vs 3.8%, p=0.035), or hematologic manifestations like AIHA (9.4 vs 2.8%, p=0.039) or ITP (26.4 vs 10.4%, p=0.001), and fever (32.1 vs 3.7%, p<0,001) were observed during childhood than during adulthood. Nephritis occurred at similar frequencies in childhood and adulthood (34.9% and 30.2% respectively). Half of adulthood nephritis were relapses of j-SLE nephritis.At the end of the survey mean global SLICC damage index (SDI) was 0.64. Mean childhood SDI was lower than mean adulthood SDI (0.21 vs 0.45, p=0.016). However mean adult follow up was significantly longer. Mean SDI increase per year was similar during childhood and adulthood (0.053 vs 0.049 respectively, p=0.563).13 patients (12.3%), had musculoskeletal damage occurring more frequently during adulthood than childhood (11 vs 2, p=0.022), specially avascular necrosis (8 vs 0, p=0.008). 5 (4.7%) patients had a renal damage that occurred mostly during adulthood (n=4). Ocular damage was present for 9 (8.5%) patients. Premature gonadal failure occurred for 5 women (5.7%). Among the 88 women 19 had 32 pregnancies, leading to 22 births.ConclusionsDamage accrual seems to increase at the same pace during childhood and adulthood. SDI was low at the end of the survey. This could reflect a protective role for HCQ, more immunosuppressant use with lower dose of steroids. Juvenile SLE nephritis are at high risk of relapsing during adulthood raising the issue of duration of immunosuppressive treatment.Disclosure of InterestNone declared

BackgroundPoor adherence to medication regimens is a major cause of relapse during systemic lupus erythematosus (SLE). Hydroxychloroquine (HCQ), the main therapy of SLE, has a long half-life. Thus, undetectable blood HCQ concentrations can be used to identify patients who do not take their treatmentObjectivesTo identify the determinants of poor therapeutic adhesion in patients with SLE.MethodsCase-control, retrospective, monocentric study. The cases were enrolled in our centre from 02/11/2011 to 13/01/2015 according to the following criteria: SLE defined according to ACR classification criteria and blood concentration of HCQ <100 ng/ml after a minimum of 2 months on therapy. For each case, the matched control was a lupus patient, enlisted from our centre the same week, with an HCQ dose greater than or equal to 800 ng/ml. Case and control characteristics were compared using standard tests and a uni-multivariate logistic regression.ResultsOne hundred and fifty patients were included, 75 cases (68 women) and 75 controls (72 women), with an average age of 35.7 years (±11.3 years) vs 35.6 years (±10.6 years). Most patients had inactive lupus (3 patients had SLEDAI ≥4), 27% of them had benefited from therapeutic education sessions. The average dosage of HCQ was 1110 ng/ml within the control group. In our univariate analysis, nonadherent patients lived significantly further away from the centre than adherent patients (median distance [interquartile range]: 2211–52 vs 14 km [5.9–35], respectively, p=0.03) and were more likely to be unemployed, (23 vs 8%, respectively, p=0.006). Nonadherent patients had less often benefited from the patient‘s therapeutic education program (18 vs 35%, respectively, p=0.018), were taking less treatment (3 vs 4, respectively, p=0.008), had a significantly lower level of education (61% compared to 89% of patients with at least a bachelor’s degree, p<0.001). In our multivariate analysis, a level of education below the A levels was the strongest factor explaining poor therapeutic adherence, OR (IC 95): 4.09 (1.5–10.8).ConclusionsThe main drivers of therapeutic adherence during SLE are socio-economic factors. The least educated and most disadvantaged patients are most likely to display poor therapeutic adherence. Targeted preventive actions and enhanced therapeutic education should be provided to them.Disclosure of InterestNone declared

BackgroundPatients with systemic lupus erythematosus (SLE) are at higher risk than the general population of developing lymphoma. Relatively little is known about the risk factors, the treatment and the outcome of lymphoma in SLE.ObjectivesWe aimed to describe a cohort of patients suffering from lymphoma in the setting of SLE and to study the risk factors of developing this complication.MethodsWe collected clinical data of SLE patients with confirmed lymphoma in a multicentric and retrospective study. SLE patients were eligible for the study if they fulfilled at least 4 of the 1997 ACR criteria for SLE. Exclusion criteria were HIV or C hepatitis infection.ResultsWe included 38 patients (34 women and 4 men) coming from 10 different French University Hospitals. The lymphoma occurred after the diagnosis of SLE for 35 patients, with a median (range) time of 8.8 years (0–39). In their past or present medical history, 11 (29%) had a haematological involvement (5 immune thrombocytopenias, 4 autoimmune hemolytic anemias and 2 patients with both). Nine patients (24%) had associated Sjögren syndrome. 22 patients (58%) had a polyclonal hypergammaglobulinemia. Before the occurrence of the lymphoma, 18 patients (47%) had received an immunosuppressant during a median (range) period of 67 months.6–195 17 patients had an indolent B cell lymphoma (IBCL), 14 a high-grade B cell lymphoma (11 diffuse large B cell lymphoma [DLBCL]; 2 a primary DLBCL of the central nervous system; and 1 an iatrogenic immunodeficiency-associated lymphoproliferative disorder), 5 a Hodgkin’s disease (HD), and 2 a T cell lymphoma. The EBER in situ hybridization stain was positive in 7 of the 13 patients assessed (3/3 HD, 3/7 DLBCL and 1/2 IL) and was not associated with the immunosuppressant prescription. The median (range) of the survey after the lymphoma was 28.5 month (0–235.1). The 14 DLBCL patients except 1 were treated with chemotherapy: 4 died, 9 were in complete remission and 1 was in progression. Regarding the 17 IBCL, 9 patients were treated with chemotherapy, 2 patients with surgery, 1 patient with radiotherapy and 5 patients were not treated: 3 patients had to short follow-up or were lost, 1 died, 2 developed a DLBCL, 4 were stable and 7 were in complete remission. The 5 HL were treated with chemotherapy and all were in complete remission.ConclusionsIBCL and DLBCL were the most common type of lymphomas in SLE patients. Data suggest a role for EBV but not for exposition to immunosuppressant in the pathogenesis of SLE-associated lymphoma. The outcome of lymphoma in the setting of SLE seems not different from the outcome of lymphoma in the general population. A case-control study is ongoing to study the risk factors associated with the occurrence of lymphoma in SLEDisclosure of InterestNone declared

To compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease. A monocentric, 12-month, superiority, open-label, randomised (1:1) controlled trial was conducted with 61 patients continuing 5 mg/day prednisone and 63 stopping it. Eligibility criteria were SLE patients who, during the year preceding the inclusion, had a clinically inactive disease and a stable SLE treatment including 5 mg/day prednisone. The primary endpoint was the proportion of patient experiencing a flare defined with the SELENA-SLEDAI flare index (SFI) at 52 weeks. Secondary endpoints included time to flare, flare severity according to SFI and British Isles Lupus Assessment Group (BILAG) index and increase in the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI). Proportion of patients experiencing a flare was significantly lower in the maintenance group as compared with the withdrawal group (4 patients vs 17; RR 0.2 (95% CI 0.1 to 0.7), p=0.003). Maintenance of 5 mg prednisone was superior with respect to time to first flare (HR 0.2; 95% CI 0.1 to 0.6, p=0.002), occurrence of mild/moderate flares using the SFI (3 patients vs 12; RR 0.2 (95% CI 0.1 to 0.8), p=0.012) and occurrence of moderate/severe flares using the BILAG index (1 patient vs 8; RR 0.1 (95% CI 0.1 to 0.9), p=0.013). SDI increase and adverse events were similar in the two treatment groups. Subgroup analyses of the primary endpoint by predefined baseline characteristics did not show evidence of a different clinical response. Maintenance of long term 5 mg prednisone in SLE patients with inactive disease prevents relapse. NCT02558517; Results.

We systematically study the optimal linear convergence rates for several relaxed alternating projection methods and the generalized Douglas-Rachford splitting methods for finding the projection on the intersection of two subspaces. Our analysis is based on a study on the linear convergence rates of the powers of matrices. We show that the optimal linear convergence rate of powers of matrices is attained if and only if all subdominant eigenvalues of the matrix are semisimple. For the convenience of computation, a nonlinear approach to the partially relaxed alternating projection method with at least the same optimal convergence rate is also provided. Numerical experiments validate our convergence analysis

ObjectivesLupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN.MethodsWIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2–3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events.ResultsBetween 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI −1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups.ConclusionsNon-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares.Trial registration number NCT01284725.

Compared to secondary antiphospholipid syndrome (APS), little is known on intima-media thickness (IMT) in primary APS. Previous reports suggest that intima-media thickness may be associated with anti-cardiolipin antibodies, anti-β2-glycoprotein-1 antibodies, and with stroke in APS1. To assess clinical significance of intima-media thickness in primary APS. We have included 29 patients with primary APS (defined according to international consensus criteria) seen, at least once, in our tertiary center for a cardiovascular risk assessment from April 2014 to November 2018. 29 patients were included (females 83%). Mean (SD) age at evaluation was 48 years (16.1). Mean APS duration before assessment was 9.1 years (6.2). 27 patients had thrombotic APS (93%), among which 13 (45%) had a history of arterial thrombosis (12 strokes and 1 myocardial infarction) and 16 (55%) of venous thrombosis. Obstetrical APS was present in 7 patients (24%). Positive APL antibodies were: anti-cardiolipin antibodies (aCL) n = 15 (54%), anti-β2-glycoprotein I (anti-β2GP1) n = 10 (36%), lupus-anticoagulant (LAC) n = 11 (39%) and anti-phospholipid antibodies (aPL) n = 19 (68%). Mean IgG levels (GPL) were 52.4 (80.3) UGPL, 52.2 (124) UI, 39.2 (40.5) UGPL for aCL anti-βG2P1, and aPL, respectively. 6 patients (21%) were simple positive, 3 (11%) were double positive, and 10 (36%) were triple positive. Cardiovascular risk factors were: smoking n = 6 patients (21%), overweight n = 11 (39%), hypercholesterolemia n = 12 (43%), arterial hypertension n = 11 (38%), chronic kidney disease (defined by estimated glomerular filtration rate < 60 mL/mn) n = 5 (17%). No patient had diabetes mellitus. Median risk SCORE was 0.65 (0-2.4). Male sex, obesity, chronic kidney disease and risk SCORE were significantly more frequent in patients with arterial APS compared to patients with venous and/or obstetrical APS (38% vs 0%, P=0.01; 33% vs 0%, P=0.02; 38% vs 0%, P=0.01; 2.3 vs 0.7, P=0.03). 22 patients (76%) underwent an IMT measurement. Mean IMT was 0.57 (0.14) millimeters (mm). Median IMT was significantly higher in APS patient with stroke than in those without (0.63 IQR (0.55-0.77) mm versus 0.51 (0.44-0.55) mm, P=0.02) (Figure 1A). IMT was neither correlated with duration of APS nor with antibody titers. Variables associated with IMT were studied on uni- and multivariate analysis (Table 1). On univariate analysis, age, aCL positivity and stroke were significantly associated with IMT and were included in the multivariate analysis. On multivariate analysis, there was a positive, independent and significant association between IMT and stroke (P=0.047) and between IMT and age (P=0.024). aCL positivity was not associated with IMT on multivariate analysis (Figure 1B). Intima-media thickness is independently associated with stroke in primary antiphospholipid antibody syndrome. [1]Medina G. Increased carotid artery intima-media thickness may be associated with stroke in primary antiphospholipid syndrome. Ann Rheum Dis. 2003;62(7):607-610. doi:10.1136/ard.62.7.607 Characters from table content including title and footnotes. None declared [Display omitted] Table 1Predictors of intima-media thickness on uni- and multivariate analysis.Univariate analysisMultivariate analysis*βP-valueβP-valueAge (years)0.006<0.0010.0040.024Female sex-0.1020.18APS duration (years)0.00040.31Smoker-0.050.61Overweight0.0660.39Arterial hypertension0.0470.48Hypercholesterolemia0.054290.412Anti-cardiolipin antibodies0.120.050.0840.076Anti-phospholipid antibodies0.0540.44Anti-β2GP10.0940.15Lupus-anticoagulant0.0440.49Anticoagulation-0.070.31Stroke0.1390.020.0990.047β Linear regression coefficientsAPS Antiphospholipid antibody syndrome* Variables with a P-value <0.1 on univariate analysis were included