Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels.

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.

Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases.

OBJECTIVES: Pericardial involvement is a frequent manifestation of systemic lupus erythematosus (SLE). Growing evidence suggests that colchicine may be useful for acute or recurrent pericarditis. We report for the first time a series of 10 consecutive cases of SLE with pericarditis treated with colchicine. METHODS: Inclusion criteria in this retrospective study were diagnosis of SLE, pericarditis and receiving colchicine. RESULTS: We included 10 consecutive cases of SLE with pericarditis treated with colchicine (nine women, mean age at the index pericarditis 35 ± 12 years). Pericarditis was the initial manifestation of SLE for two patients, whereas eight patients had SLE lasting for a median of 2.5 years (15 days to 13 years) and had received prednisone (n = 7, 2-30 mg/d), hydroxychloroquine (n = 7), azathioprine (n = 3), methotrexate (n = 2), and mycophenolate mofetil (n = 1). For six patients, pericarditis was associated with other SLE manifestations. Altogether, colchicine avoided the use (n = 2) or increase in dosage (n = 5) of steroids in seven cases; the increase in steroids dosage was minimal for two patients. Colchicine 1 mg was given for a median of 39 days (10 days to 54 months). Symptoms completely resolved after a median of 2.5 days (1-30 days) after initiation of colchicine. Colchicine was maintained or resumed in six patients to prevent recurrence, with no further relapse. CONCLUSIONS: Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up.

Immunosuppressants reduce venous thrombosis relapse in Behçet's disease.

OBJECTIVE: To investigate and describe the long-term outcome of venous thrombosis in patients with Behçet's disease (BD). METHODS: In a retrospective cohort of 807 BD patients, a reported 296 patients (36.7%) (73.3% male, median age 30 years [interquartile range 24-36 years]) met the international classification criteria for BD and had venous thrombosis. We assessed factors associated with thrombosis relapse and mortality. RESULTS: There were a total of 586 venous thrombosis events, including 560 cases of deep thrombosis and 26 cases of superficial thrombosis. Deep venous thrombosis events included 323 cases of limb thrombosis (55.1%), 77 cases of cerebral venous thrombosis (13.1%), 57 cases of pulmonary embolism (9.7%), 63 cases of vena cava lesions (10.7%), 14 cases of Budd-Chiari syndrome (2.4%), and 13 cases of cervical vein thrombosis (2.2%). One hundred of 296 patients (33.8%) experienced at least 1 venous thrombosis relapse. The mortality rate was 6.4% (19 of 296 patients) after a median followup of 4.75 years (interquartile range 2-7 years). In univariate analysis, death was associated with cardiac involvement (P = 0.026) and Budd-Chiari syndrome (P = 0.004). In multivariate analysis, the use of immunosuppressive agents was found to prevent relapse of venous thrombosis (hazard ratio 0.27 [95% confidence interval 0.14-0.52], P = 0.00021), and there was a trend toward prevention of relapse with the use of glucocorticoids (hazard ratio 0.62 [95% confidence interval 0.40-0.97], P = 0.058). CONCLUSION: Immunosuppressive agents significantly reduce venous thrombosis relapse in BD.

Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.

Tangier disease (TD) was first discovered nearly 40 years ago in two siblings living on Tangier Island. This autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy and frequently premature coronary artery disease (CAD). In heterozygotes, HDL-C levels are about one-half those of normal individuals. Impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary heart disease in some TD families. We report here refining of our previous linkage of the TD gene to a 1-cM region between markers D9S271 and D9S1866 on chromosome 9q31, in which we found the gene encoding human ATP cassette-binding transporter 1 (ABC1). We also found a change in ABC1 expression level on cholesterol loading of phorbol ester-treated THP1 macrophages, substantiating the role of ABC1 in cholesterol efflux. We cloned the full-length cDNA and sequenced the gene in two unrelated families with four TD homozygotes. In the first pedigree, a 1-bp deletion in exon 13, resulting in truncation of the predicted protein to approximately one-fourth of its normal size, co-segregated with the disease phenotype. An in-frame insertion-deletion in exon 12 was found in the second family. Our findings indicate that defects in ABC1, encoding a member of the ABC transporter superfamily, are the cause of TD.

Factors influencing the efficacy of two injections of a pandemic 2009 influenza A (H1N1) nonadjuvanted vaccine in systemic lupus erythematosus.

OBJECTIVE: To assess the factors influencing the efficacy of 2 injections of a pandemic 2009 influenza A (H1N1) vaccine in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a single-center, observational prospective study of 111 patients who were vaccinated with a monovalent, inactivated, nonadjuvanted, split-virus vaccine during December 2009 and January 2010 and received a second dose of vaccine 3 weeks later. The antibody response was evaluated using the hemagglutination inhibition assay according to the guidelines recommended for the pandemic vaccine, consisting of 3 immunogenicity criteria (i.e., a seroprotection rate of 70%, a seroconversion rate of 40%, and a geometric mean ratio [GMR] of 2.5). RESULTS: The 3 immunogenicity criteria were met on day 42 (seroprotection rate 80.0% [95% confidence interval (95% CI) 72.5-87.5%], seroconversion rate 71.8% [95% CI 63.4-80.2%], and GMR 10.3 [95% CI 2.9-14.2]), while only 2 criteria were met on day 21 (seroprotection rate 66.7% [95% CI 57.9-75.4%], seroconversion rate 60.4% [95% CI 51.3-69.5%], and GMR 8.5 [95% CI 3.2-12.0]). The vaccine was well tolerated. Disease activity, assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, the British Isles Lupus Assessment Group score, and the Systemic Lupus Activity Questionnaire, did not increase. In the multivariate analysis, vaccination failure was significantly associated with immunosuppressive treatment or a lymphocyte count of ≤ 1.0 × 109/liter. The second injection significantly increased the immunogenicity in these subgroups, but not high enough to fulfill the seroprotection criterion in patients receiving immunosuppressive treatment. CONCLUSION: Our findings indicate that the efficacy of the vaccine was impaired in patients who were receiving immunosuppressive drugs or who had lymphopenia. A second injection increased vaccine immunogenicity without reaching all efficacy criteria for a pandemic vaccine in patients receiving an immunosuppressive agent. These results open possibilities for improving anti-influenza vaccination in SLE.

[Heart involvement in systemic lupus erythematosus and antiphospholipid syndrome]. / Cœur et médecine interne : lupus systémique et syndrome des antiphospholipides.

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.

EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs.

OBJECTIVES: To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. METHODS: The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design. RESULTS: Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence > 5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1-5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD. CONCLUSIONS: Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

Serum cartilage oligomeric matrix protein (COMP) level is a marker of disease activity in relapsing polychondritis.

OBJECTIVES: Relapsing polychondritis (RP) is a rare and severe disease which may lead to destruction of elastic cartilages. Until now, no reliable biomarker of disease activity in RP has been available. This study was designed to measure serum levels of cartilage biomarkers during both active and inactive phases of the disease. METHODS: Serum levels of cartilage oligomeric matrix protein (COMP), chondroitin sulfate 846 epitope (CS846) of proteoglycan aggrecan and collagen type II collagenase cleavage neoepitope (C2C) were measured retrospectively in 21 subjects with RP. The Wilcoxon matched-pairs signed-rank test was used for statistical comparisons of biomarker levels in active and inactive phases of RP. RESULTS: Only the serum level of COMP was significantly increased during disease flares. Steroids did not alter the serum cartilage-related biomarker levels. However, during the active phase, C2C levels were significantly higher in steroid treated patients compared with non-steroid treated patients. CONCLUSIONS: This study suggests that serum COMP level may be useful for monitoring disease activity of RP. Further prospective studies are required to confirm this result.

Antimyeloperoxidase antibodies are a useful marker of disease activity in antineutrophil cytoplasmic antibody-associated vasculitides.

OBJECTIVE: To evaluate the relevance of monitoring antimyeloperoxidase antibody levels in the management of antimyeloperoxidase-associated vasculitides. METHODS: Thirty-eight patients with antimyeloperoxidase-associated vasculitides were included: microscopic polyangiitis (n = 18), Wegener's granulomatosis (n = 15) and Churg-Strauss syndrome (n = 5). Baseline characteristics and outcomes were recorded. Serial measurements of antimyeloperoxidase antibody levels were performed (ELISA, positive > or = 20 IU/ml). RESULTS: All patients achieved vasculitis remission after a mean time of 2.0 months (SD 0.9), with a significant decrease in the mean antimyeloperoxidase antibody level at remission (478 vs 41 IU/ml (SD 598 vs 100); p<0.001). Twenty-eight (74%) patients became antimyeloperoxidase antibody negative. After a mean follow-up of 54 months (SD 38), 12 cases of clinical relapse occurred in 11/38 (29%) patients. Relapses were associated with an increase in antimyeloperoxidase antibody levels in 10/11 (91%) patients (34 vs 199 IU/ml (88 vs 314); p = 0.002). The reappearance of antimyeloperoxidase antibodies after achieving negative levels was significantly associated with relapse (odds ratio 117; 95% CI 9.4 to 1450; p<0.001). Antimyeloperoxidase antibodies showed a positive predictive value of 90% and a negative predictive value of 94% for relapse of vasculitis. Up to 60% of cases of relapse occurred less than 12 months after the reappearance of antimyeloperoxidase antibodies. Relapse-free survival was significantly worse for patients who exhibited a reappearance of antimyeloperoxidase antibodies than in those with persistent negative antimyeloperoxidase antibodies (p<0.001). The antimyeloperoxidase antibodies serum level was strongly correlated with the Birmingham vasculitis activity score and the disease extent index (r = +0.49; p = 0.002). CONCLUSION: Through monitoring, antimyeloperoxidase antibodies are a useful marker of disease activity and a good predictor of relapse in antimyeloperoxidase-associated vasculitides.

Serum-free light chain assessment in hepatitis C virus-related lymphoproliferative disorders.

OBJECTIVE: To evaluate the relevance of serum-free light chain (FLC) assessment in hepatitis C virus (HCV)-related lymphoproliferative disorders, including mixed cryoglobulinemia (MC) and B cell non-Hodgkin lymphoma (B-NHL). PATIENTS AND METHODS: A total of 59 patients infected with HCV were prospectively followed, including patients without MC (n = 17), with asymptomatic MC (n = 7) and with MC vasculitis (n = 35, 9 of whom had B-NHL). Clinical and biological data were recorded at the time of the initial evaluation and at the end of follow-up. Serum FLC quantitation was carried out using a serum FLC assay. RESULTS: The mean (SD) serum kappa FLC level was higher in patients with asymptomatic MC (27.9 (8.6) mg/litre), MC vasculitis (36.7 (46.2) mg/litre) and B-NHL (51.3 (78.3) mg/litre) than without MC (21.7 (17.6) mg/litre) (p = 0.047, 0.025 and 0.045, respectively). The mean serum FLC ratio was higher in patients with MC vasculitis (2.08 (2.33)) and B-NHL (3.14 (3.49)) than in patients without MC (1.03 (0.26)) (p = 0.008). The rate of abnormal serum FLC ratio (>1.65) correlated with the severity of HCV-related B cell disorder: 0/17 (0%) without MC, 0/7 (0%) asymptomatic MC, 6/26 (23%) MC vasculitis without B-NHL and 4/9 (44%) B-NHL (p = 0.002). Serum kappa FLC levels and the serum FLC ratio correlated with the cryoglobulin level (r = 0.32, p<0.001 and r = 0.25, p = 0.002, respectively) and the severity of the B cell disorder (r = 0.26, p = 0.045 and r = 0.41, p = 0.001, respectively). Among patients with an abnormal serum FLC ratio at baseline, the FLC ratio correlated with the virological response to HCV treatment. CONCLUSIONS: In patients infected with HCV, an abnormal serum FLC ratio appears to be a very interesting marker, as it is consistently associated with the presence of MC vasculitis and/or B-NHL. After antiviral therapy, the serum FLC ratio could be used as a surrogate marker of the control of the HCV-related lymphoproliferation.

Pathological features of temporal arteries in patients with giant cell arteritis presenting with permanent visual loss.

BACKGROUND: Permanent visual loss (PVL) is the most feared complication of giant cell arteritis (GCA), and its risk factors are still unclear. OBJECTIVES: The aim of our study was to assess the pathological features predictive of PVL on temporal artery biopsy (TAB) specimens in patients with GCA. METHODS: The slides of 391 TAB specimens from patients with GCA were reviewed by two pathologists without clinical information. RESULTS: A total of 29 patients (26 females and 3 males, mean age 78.3 years) presented with unilateral PVL at the onset of the disease, and 362 patients (258 females, 104 males, mean age 74.7 years), did not. The pathological features strongly predictive for PVL were the presence (p = 0.003), number (p = 0.001) and aggregates of giant cells (p = 0.001), presence of plasmocytes (p = 0.002), thickened intima (p = 0.007), neoangiogenesis (p = 0.001) and degree of arterial occlusion (p = 0.006). Presence of neutrophils, eosinophils, parietal necrosis, calcification in the arterial wall and disruption of the internal elastic membrane were similar in both groups. Total obstruction of the arterial lumen by a thrombus, intensity of the inflammatory cells infiltration and inflammation of small vessels, nerves and veins surrounding the temporal artery were not associated with blindness. In multivariate analysis, only giant cells remained significantly associated with PVL. CONCLUSION: Giant cells are strongly associated with PVL, with a significant gradient between great risk and large number of giant cells. However, PVL was neither associated with the intensity of the inflammatory infiltrate, nor with the presence of arterial thrombosis.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. DESIGN: ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. RESULTS: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. CONCLUSIONS: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints.

OBJECTIVE: To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. METHODS: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. RESULTS: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. CONCLUSION: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients.

OBJECTIVES: To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance. METHODS: The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed. RESULTS: 200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected. CONCLUSION: Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

[Antiphospholipid antibodies, antiphospholipid syndrome and viral infections]. / Anticorps antiphospholipide, syndrome des anticorps antiphospholipides et infections virales.

Since the association between antiphospholipid antibodies and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce antiphospholipid antibodies, notably anticardiolipin antibodies. These aPL are usually associated neither with anti-beta2 glycoprotein I antibodies (anti-beta2-GPI) nor with thrombotic events, even if cases of arterial and deep venous thrombosis have been reported in such circumstances. A literature review shows that anticardiolipin antibodies occur frequently in viral infections, particularly in HIV (49.8%), HBV (24%) and HCV (20%). The prevalence of anti-beta2 glycoprotein I antibodies (anti-beta2GPI) is lower (HCV: 1.7%, HIV: 5.6%, HBV: 3.3%) and there is no demonstrated association with a risk of thrombotic events or hematological manifestations defining antiphospholipid syndrome (APS). Regarding other viral infections, including viral hepatitis A, herpes virus (CMV, EBV, VZV), parvovirus B19 and HTLV-1 infections, only a few studies are available but data confirm the high prevalence of antiphospholipid antibodies at the acute phase. Finally, antiphospholipid antibodies, mainly anticardiolipin, are frequently associated with viral infections. Their presence may probably reflect an intense or chronic antigenic stimulation of the immune system. However, their evolution under antiviral therapy and correlation with the quality of the virological control and/or the immune restoration remain to be determined.

[Pathogenesis of primary large vessel arteritis]. / Immunopathologie des artérites primitives des gros vaisseaux.

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are the two primary large-vessel arteritides. Recent advances in cellular immunology have allowed better understanding of pathogenesis of these diseases. In GCA and TA, resident adventitial dendritic cells are activated by unidentified stimuli. This activation induces chemokine synthesis which enhances recruitment of inflammatory cells. T-cells infiltrate the vascular wall and specifically recognize one or a few antigens presented by shared epitopes associated with specific HLA molecules on dendritic cells. Activated T-cells produce IFNgamma stimulating two distinct populations of macrophages. Macrophages located in the intima produce pro-inflammatory cytokines (IL-1, IL-6). Macrophages located in the media differentiate into giant cells and/or produce reactive oxygen species, nitric oxide and matrix metallo-proteinases. Macrophages of the media also produce VEGF, which leads to neovascularization and PDGF, which induces intimal hyperplasia and vascular occlusion. In TA, cytotoxic T cells infiltrate the vascular wall and induce apoptosis of the vascular cells. Better understanding of the pathogenesis of large-vessel arteritis may lead to development of immunosuppressive drugs specifically targeting the immunological mechanisms implicated in GCA and TA.

[Necrotizing folliculitis in Behçet's disease]. / Folliculite nécrosante atypique et maladie de Behçet.

We report a 24-year-old man with a known Behcet's disease who was lost to follow-up for a year. The patient was admitted for the association of scrotal ulceration and inguinal folliculitis, suggesting a Behcet's disease flare-up. Necrotizing course of the folliculitis led to the diagnosis of skin infection caused by a community-acquired methicillin-resistant Staphylococcus aureus strain, carrying Panton-Valentine leukocidin genes. Bacteriological analysis should be mandatory in the absence of specific criteria for the diagnosis of Behcet's disease.

[Liver disease and pregnancy]. / Pathologies hépatiques et grossesse.

Liver dysfunction during pregnancy can be related or not to pregnancy itself. The purpose of this review is to summarize the possible causes of liver dysfunction during pregnancy and their management. Liver dysfunction during pregnancy can be chronic or acute, independent or specific to pregnancy. Management of liver disease can be different during pregnancy. The knowledge of liver dysfunction during pregnancy is of help for a better management of the mother in order to avoid maternal and fetal mortality and morbidity.

EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. RESULTS: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. CONCLUSION: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.