[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

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.

Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus.

OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France.

BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.

[IgA-mediated auto-immune haemolytic anaemia revealing a hepatitis C virus infection]. / Anémie hémolytique auto-immune à Coombs IgA révélant une infection par le virus de l'hépatite C.

INTRODUCTION: Confirmation of autoimmune hemolytic anaemia usually relies on the detection of erythrocyte membrane-bound autoantibodies using a direct antiglobulin test. In the rare case of IgA autoantibodies-mediated autoimmune hemolytic anemia, the direct antiglobulin test can be negative, because routinely used polyspecific direct antiglobulin test reagents contain only anti-IgG and anticomplement antibodies. EXEGESIS: We report the case of a 41-year-old woman presenting a severe autoimmune hemolytic anaemia caused by the presence of warm autoantibodies of IgA type that revealed a chronic hepatitis C virus infection. CONCLUSION: A negative direct antiglobulin test does not completely rule out the diagnosis of autoimmune hemolytic anaemia especially in the rare case of IgA mediated immune hemolysis. The diagnosis strategy of autoimmune hemolytic anaemia associated with negative direct antiglobulin test and the potential links between autoimmune hemolytic anaemia and HCV are discussed.

Hepatitis C virus-associated B-cell proliferation--the role of serum B lymphocyte stimulator (BLyS/BAFF).

OBJECTIVE: B lymphocyte stimulator (BLyS) is known to support B-cell proliferation (BCP) in B-cell haemopathies and autoimmune diseases. We assume that BLyS may play a role in the initiation and expression of hepatitis C virus (HCV)-associated BCP. We assessed BLyS serum levels in HCV-infected patients and in various forms of HCV-associated BCP [i.e. mixed cryoglobulin (MC), rheumatoid factor (RF) and systemic vasculitis]. METHODS: A total of 76 HCV-infected patients (HCV RNA+) were compared with 13 healthy volunteers. Epidemiological, clinical, immunochemical and virological data were prospectively collected. BLyS serum levels were assessed by an ELISA sandwich method. RESULTS: Of the 76 patients, 38 females, 38 males, mean age 53 +/- 15 yrs; 47 (62%) patients had type II (27 patients) or type III MC (20 patients); 27 (35.5%) patients had HCV-systemic vasculitis. BLyS serum levels tended to be higher in HCV-infected patients than in healthy controls (1.8 +/- 0.9 vs 1.5 +/- 0.2 ng/ml), were higher in patients with MC than without (2.03 +/- 1.02 vs 1.5 +/- 0.5 ng/ml; P = 0.008), and even higher in type II than type III MC (2.3 +/- 1.2 vs 1.7 +/- 0.6 ng/ml; P = 0.03). There was a correlation between BLyS and MC serum levels (R = 0.4; P = 0.004). BLyS serum levels were higher in patients with a positive RF than in those without (2.06 +/- 1.09 vs 1.6 +/- 0.56 ng/ml, P = 0.035), and with systemic vasculitis than in those without (2.24 +/- 1.16 vs 1.6 +/- 0.6 ng/ml; P = 0.006). CONCLUSION: BLyS serum levels are significantly correlated with B-cell proliferation during chronic HCV infection. These results strongly suggest a role for BLyS in the induction and expression of HCV-BCP.

[Update in Hepatitis C virus associated extrahepatic manifestations]. / Actualités des manifestations extrahépatiques associées au virus de l'hépatite C.

INTRODUCTION: Since the discovery of the hepatitis C virus, many manifestations, so called extra-hepatic manifestations (EHM), are largely reported with more or less relationship proofs. ACTUALITIES AND MAIN POINTS: This article proposes a review of the main extra-hepatic manifestations associated with the Hepatis C Virus infection and which remain a topical subject, more than fifteen years after the discovery of this virus. Mixed cryoglobulin and its vasculitic manifestations are still one of the more frequent Hepatis C Virus associated-extra-hepatic manifestations. Its management may be critically changed due to the increasing use of anti-CD20 therapy. Among other HCV-EHM, the following extra-hepatic manifestations are still of interest: the chronic fatigue syndrome, the sicca syndrome, the non-insulin-dependent diabetes mellitus, malignant B cell proliferations, mainly the Hepatis C Virus-related splenic lymphoma with villous lymphocytes and the production of auto-antibodies. PERSPECTIVES AND PROJECTS: The mechanisms underlying these HCV-associated EHM are ill-elucidated and still remain of great interest as proved by current studies. The use of anti-CD20 antibodies in the treatment of cryoglobulinemic vasculitis is also under investigation.

Anti-C1q antibodies in hepatitis C virus infection.

Autoantibodies against C1q have been described in many immune-complex diseases including hypocomplementaemic urticarial vasculitis and systemic lupus erythematosus (SLE). No study has focused on the role of anti-C1q antibodies in hepatitis C virus (HCV) infection. The aim of this study was (i) to evaluate the prevalence of anti-C1q antibodies in HCV infection; and (ii) to analyse the association of anti-C1q antibodies with clinical and biological features of HCV-mixed cryoglobulinaemia (MC) vasculitis. We searched for anti-C1q antibodies using an enzyme-linked immunosorbent assay (ELISA) test in 111 HCV patients (75 had cryoglobulin and 23 systemic vasculitis), 60 SLE patients and 109 blood donors. Anti-C1q antibodies were detected in 26% of HCV patients compared to 10% of healthy donors (P < 0.01), and 38% in patients with SLE. Although there was a higher prevalence of anti-C1q antibodies among HCV patients with type III cryoglobulin (50%, P < 0.01), the overall prevalence of anti-C1q antibodies was similar in HCV patients being cryoglobulin-positive or cryoglobulin-negative (26%versus 25%, P = 0.98). A significant association was found between anti-C1q antibodies and low C4 fraction of complement (P < 0.05). No association was found between anti-C1q antibodies and HCV genotype, severity of liver disease or with specific clinical signs of HCV-MC vasculitis. This study shows an increased prevalence of anti-C1q antibodies in HCV-infected patients. Anti-C1q antibodies were associated with low C4 levels. No association was found between anti-C1q antibodies and HCV-MC vasculitis, nor between anti-C1q antibodies and cryoglobulinaemia.

[Central serous chorioretinopathy and systemic diseases report of 2 cases associated with corticotherapy]. / Choriorétinopathie séreuse centrale et maladies systémiques: deux cas observés sous corticothérapie.

INTRODUCTION: Central serous chorioretinopathy is an uncommon retinal disease, whose pathogenesis is largely unknown. It is characterized by an accumulation of subretinal fluid at the posterior pole of the fundus, creating a circumscribed area of serous retinal detachment. It manifests generally as a visual loss or an abnormal colour vision. It is often idiopathic but may also be associated with numerous pathological situations, with frequent exposure to corticosteroids. EXEGESIS: We report on two patients with central serous chorioretinopathy. The first female patient had been treated with steroids for a systemic lupus erythematosus for fifteen years, and the second male patient had been treated with steroids for an idiopathic hypereosinophilic syndrome for a few months. Visual loss led to a diagnosis of central serous chorioretinopathy. Lowering of steroids doses was followed by a clinical improvement in both cases. CONCLUSION: Similarly to cataract or glaucoma, central serous chorioretinopathy belongs to the potential ocular side-effect of steroid treatment, and thus deserves to be known by internists.

Anti-cyclic citrullinated peptide antibodies in hepatitis C virus associated rheumatological manifestations and Sjogren's syndrome.

OBJECTIVE: To investigate the diagnostic reliability of anti-CCP antibodies (anti-CCP Ab) in distinguishing hepatitis C virus (HCV) associated rheumatological manifestations and Sjögren's syndrome from rheumatoid arthritis. METHODS: 147 HCV infected patients (HCV RNA positive) were compared with 64 patients with definite rheumatoid arthritis in a retrospective study. Anti-CCP Ab were detected using the Immunoscan ELISA kit (second generation) and rheumatoid factor (RF) by the FIDIStrade mark Rheuma kit. RESULTS: Among the 147 HCV infected patients (77 women; mean (SD) age 58 (16) years), 77 (52%) had a mixed cryoglobulin (MC), 38 (26%) an MC associated systemic vasculitis, 35 (24%) arthralgia/arthritis, and seven (5%) definite Sjögren's syndrome. HCV infected patients with arthralgia were more often RF positive than those without arthralgia (54% v 27%; p = 0.003), but less often than patients with rheumatoid arthritis (54% v 81%; p = 0.009). Anti-CCP Ab were detected in only two HCV infected patients with arthralgia (5.7%), in none without arthralgia or with Sjögren's syndrome, and in 78% of patients with rheumatoid arthritis. With a specificity of 93.5% and a positive predictive value of 96% for rheumatoid arthritis, anti-CCP Ab were the most specific biological marker. CONCLUSIONS: Anti-CCP antibodies are very rarely found in HCV infected patients with rheumatological manifestations or Sjögren's syndrome. They are reliable serological markers to distinguish these from patients with rheumatoid arthritis.

Chronic Chlamydia pneumoniae infection in patients with symptomatic atherothrombosis.

OBJECTIVES: The aim of the present study was to search for an association between chronic Chlamydia pneumoniae infection, indicated by elevated antibody titers against the pathogen, atherothrombosis and the occurrence of arterial ischemic events. METHODS: We studied 52 patients presenting at baseline with at least one symptomatic episode of atherothrombosis. A screening for fasting blood glucose and a lipid profile was performed on all patients who had no known history of diabetes or hypercholesterolemia. RESULTS: The prevalence of IgG and IgA anti-C. pneumoniae antibodies at baseline was 90% (95% CI: 79-97) and 81% (67-90), respectively. Forty-two of the 52 patients (81%) experienced a new arterial ischemic event after a mean follow-up of 9 years [heart: 19 (37%); brain: 12 (23%); lower limbs: 8 (15%); and other: 13 (25%)]. Occurrence of a new arterial ischemic event was related to age (p=0.003), sex (p=0.009), and tobacco smoking (p=0.06). Prevalences of IgA and IgG anti-C. pneumoniae were significantly higher in patients with atherothrombosis at baseline than that in controls. CONCLUSION: Our study confirmed the links between C. pneumoniae and atherothrombosis. However, neither IgA nor IgG antibodies for C. pneumoniae was a significant predictive factor for new ischemic arterial events in patients with atherothrombosis.

[Interest of performing systematically the protein profile in an internal medicine department. National survey and prospective study on 229 admissions]. / Intérêt de la réalisation systématique du profil protéique d'orientation dans un service de médecine interne. Enquête nationale des pratiques et étude prospective sur 229 admissions.

INTRODUCTION: Despite a wide national use, the usefulness of the protein profile has only been evaluated in a small number of studies, essentially in patients with unknown diagnoses. METHODS: We conducted a survey on 339 french internal medicine departments to evaluate how the protein profile was used in these services. Concomitantly we achieved a prospective study on 229 patients in our department, with a mean follow up of 9 months, to evaluate how did the protein profile influence the diagnosis process. RESULTS: We received 183 responses to our national survey: the protein profile was available in 110/183 (60%) departments with 94/110 (85%) using it during hospitalisation and 20/94 (21.3%) using it systematically. Among the 229 protein profile analysed in our department, 44 (19.2%) were considered useful with 20 (8.7%) of them allowing the diagnosis of a new pathology. If the profile had not been done systematically, the physicians of our department would have performed the profile in 102/229 (44.5%) cases, whereas seven (3%) useful profiles would not have been done. CONCLUSION: We think that the profile has a consistent interest in hospitalized patients with a known or unknown pathology but performing systematically such a test appears to be of limited benefit.

Management of chronic hepatitis C in French departments of internal medicine and infectious diseases.

This prospective, multicentre study was conducted during 2-30 April 2001 in the internal medicine/infectious diseases services in France and included data from 1858 hepatitis C virus (HCV)-infected patients, half of whom were HIV co-infected. The aims were to outline the type of pre-therapeutic evaluation of HCV infection performed (HCV RNA, genotype, liver biopsy); determine the proportion and characteristics of patients receiving antiviral treatment; and determine if any changes in these parameters had occurred between 1995 and 2001. Patients whom had a complete pre-therapeutic evaluation (39%, 709/1834) and received antiviral treatment (38%, 690/1830) were more likely to have abnormal liver biochemistry, cirrhosis and cryoglobulinaemia (P < 0.001). Injecting drug users and HIV-co-infected patients were less likely to have a complete pre-therapeutic evaluation or receive antiviral treatment (P < 0.001). A complete pre-therapeutic evaluation was more often performed in 2001 than in 1995 (39% vs. 6%, P < 0.001), including qualitative HCV RNA testing (91% vs. 68%, P < 0.001), genotyping (59% vs. 7%, P < 0.001) and a liver biopsy (60% vs. 29%, P < 0.001). The frequency of anti-HCV treatment approximately doubled between 1995 and 2001 (20% vs. 38%, P < 0001). Although adherence to consensus recommendations regarding pre-therapeutic evaluation is not ideal, a substantial improvement has occurred since 1995. Nevertheless, means of increasing the availability of antiviral therapies, particularly for patients with HIV co-infection or injecting drug use, require further study.