Giant cell arteritis-related aortitis with positive or negative temporal artery biopsy: a French multicentre study.

Objective: To compare the clinical presentation and outcome of giant cell arteritis (GCA)-related aortitis according to the results of temporal artery biopsy (TAB).Method: Patients with GCA-related aortitis diagnosed between 2000 and 2017, who underwent TAB, were retrospectively included from a French multicentre database. They all met at least three American College of Rheumatology criteria for the diagnosis of GCA. Aortitis was defined by aortic wall thickening > 2 mm on computed tomography scan and/or an aortic aneurysm, associated with an inflammatory syndrome. Patients were divided into two groups [positive and negative TAB (TAB+, TAB-)], which were compared regarding aortic imaging characteristics and aortic events, at aortitis diagnosis and during follow-up.Results: We included 56 patients with TAB+ (70%) and 24 with TAB- (30%). At aortitis diagnosis, patients with TAB- were significantly younger than those with TAB+ (67.7 ± 9 vs 72.3 ± 7 years, p = 0.022). Initial clinical signs of GCA, inflammatory parameters, and glucocorticoid therapy were similar in both groups. Coronary artery disease and/or lower limb peripheral arterial disease was more frequent in TAB- patients (25% vs 5.3%, p = 0.018). Aortic wall thickness and type of aortic involvement were not significantly different between groups. Diffuse arterial involvement from the aortic arch was more frequent in TAB- patients (29.1 vs 8.9%, p = 0.03). There were no differences between the groups regarding overall, aneurism-free, relapse-free, and aortic event-free survival.Conclusion: Among patients with GCA-related aortitis, those with TAB- are characterized by younger age and increased frequency of diffuse arterial involvement from the aortic arch compared to those with TAB+, without significant differences in terms of prognosis.

Outcome of essential cryofibrinogenaemia in a series of 61 patients.

OBJECTIVES: The present study assessed the outcome of several cases of cryofibrinogenaemia detected in our hospitals during a 10-yr period (December 1996-April 2007), and also attempted to evaluate the clinical manifestations and associated diseases. METHODS: We performed a retrospective study in a series of 61 consecutive cryofibrinogenemia patients detected in our hospitals. RESULTS: In the 61 cryofibrinogenaemia patients, 18 had essential cryofibrinogenaemia and 43 secondary cryofibrinogaemia. Five out of the 18 patients with primary cryofibrinogaemia (27%) developed lymphoma after a 5-yr follow-up period. The main manifestations were cutaneous, and there were no differences in clinical presentation and disease severity in both types of cryofibrinogenaemia. A small number of patients (six) had cryofibrinogenaemia associated with cryoglobulinaemia, and in two cases, hepatitis C virus infection was detected; but no differences were observed between these two groups of patients. CONCLUSION: Cryofibrinogenaemia was found in our study with a high prevalence, suggesting that this pathology is rather underestimated. Our data further suggests that these patients should have a regular follow-up because of the high risk of symptom recurrence. We also hypothesize that in some cases essential cryofibrinogenaemia might be a prerequisite for a secondary disease.

[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.

[Tuberculosis peritonitis: an always present disease. About 4 new cases]. / La tuberculose péritonéale: une entité toujours présente. A propos de quatre observations.

INTRODUCTION: Tuberculous peritonitis, a major problem in developing country, occurs preferentially in immigrant population and in patients with acquired immune deficiency syndrome (AIDS). Although rare in France, it did not disappear and epidemiological, clinical and therapeutic approach deserve to be reminded. EXEGESIS: We reported 4 patients (immigrants in two cases), occurred in caucasian and African persons (one with AIDS). Disease was characterized by fever, abdominal pain, anorexia, weight loss and ascites. Biological and radiological were unconclusive. Cell count analysis from ascitic fluid show a lymphocytic predominance with negative direct smear for Ziehl-Neelsen strain. Tuberculous peritonitis was established with combined visual and histological diagnosic laparoscopic examination. CONCLUSION: These observations have the interest to underline that tuberculous peritonitis must be evoked in case of lymphocytic ascitis. We believe an aggressive diagnostic approach, particulary with peritoneal biopsy, is warranted for the diagnosis of tuberculous peritonitis. Validity of PCR amplification is ascitic fluid still needs to be established.

[Spontaneous splenic hematoma: trauma injury or drug reaction or both?]. / Hématome spontané de la rate: traumatisme et/ou médicament?

INTRODUCTION: Spontaneous splenic hematomas are uncommon and frequently associated with infectious, hematologic, or neoplastic diseases. Presentation is typically acute but progressive forms have been described. CASE: We report the case of a 45-year-old man consulting for abdominal pain that was found to be due to a spontaneous splenic hematoma. No recent injuries, infections, or hematologic, neoplastic or gastrointestinal diseases were found, but the patient had had a minor injury 9 months earlier and had been treated with selective serotonin reuptake inhibitors (venlafaxine) for the past year. This history suggested that the drug might play a role. DISCUSSION: Although the likely cause of this splenic hematoma appears to be a minor injury 9 months before the onset of pain, we cannot rule out the possibility that selective serotonin reuptake inhibitor treatment was a predisposing factor.

[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.

Specificity, pathogenecity, and clinical value of antiendothelial cell antibodies.

OBJECTIVE: To characterize the putative target antigens for antiendothelial cell antibodies (AECA), the possible pathophysiological role of AECA, and the clinical value of these antibodies as markers of disease activity. METHODS: A structured literature search was done using Medline in combination with a manual search. Two physicians reviewed all articles of special interest. RESULTS: AECA are a heterogenous group of antibodies directed against a variety of antigen determinants on endothelial cells (EC). The EC antigens can be constitutively expressed, constitutively expressed and modulated by cytokines, or cryptic. In addition, antigen determinants for AECA may also be molecules that adhere to EC ("planted" antigens). However, many AECA antigens are currently not well characterized. AECA are detected in a wide variety of inflammatory disorders. Although probably of limited value in disease diagnosis, the detection of these antibodies may be valuable in following disease activity. In several diseases such as systemic lupus erythematosus and systemic vasculitis, high AECA titers are found during active disease whereas lower titers or disappearence of AECA have been reported during remission. The correlation between changes in AECA titers and disease activity suggests an important role for AECA in processes in which vessel wall damage occurs, although it does not exclude the possibility that AECA are an epiphenomenon of vascular injury. Several recent in vitro studies support a role of AECA in the pathophysiology of these inflammatory disorders. AECA may play a role in the pathophysiology by inducing activation of EC resulting in upregulation in the expression of endothelial adhesion molecules and/or secretion of chemoattractants and cytokines. An alternative mechanism by which AECA could be a trigger in the pathogenesis of some diseases is complement dependent cytotoxicity (CDC) and/or antibody dependent cellular cytotoxicity (ADCC). In experimental animal models, antibodies to antigenic determinants expressed on EC were capable of inducing vascular injury. CONCLUSION: AECA represent a heterogenous group of antibodies directed against a variety of antigenic determinants on EC. They are present in a variety of inflammatory disorders. The detection of these antibodies may be valuable in following disease activity. Further characterization of putative antigens is needed to better understand their pathophysiological role.

[Venous tromboembolic treatment in patients with cancer]. / Traitement de la maladie thromboembolique veineuse chez les patients souffrant de cancers.

PURPOSE: Venous tromboembolic treatment in patients with cancer can be a clinical dilemma. Comorbid conditions, significant risk of recurrence of bleeding associated with warfarin, difficult venous access, are some of the factors that often complicate anticoagulants therapy in patients with cancer. EXEGESIS: Low molecular weight heparin has replaced unfractionated heparin as the first line treatment in the majority of patients with venous thromboembolism and cancer, in hospital or safely at home. Recent trial demonstrated that long-term low molecular weight heparin administrated over a 6-month period reduced the rate of recurrence venous thromboembolism with non increase in bleeding compared with oral anticoagulant therapy. Placement of an inferior vena caval filter should be reserved for patients with active or very high risk of bleeding, but oncologist should consider these sobering results in such patients. Whether anticoagulants might also improve cancer survival rates independent of their effect on thromboembolism deserves further investigation. PERSPECTIVE: In future, new antithrombotic agents such as oral direct thrombin or long-acting synthetic factor Xa inhibitor may be useful in these patients.

Compliance with recommendations of clinical practice in the management of venous thromboembolism in cancer: the CARMEN study.

UNLABELLED: Cancer is associated with venous thromboembolism in 20% of patients. In such patients, thrombosis is difficult to treat, associated with bleeding, recurrence, and death. Specific treatments for venous thromboembolism in cancer are recommended. Guidelines have been implemented in many countries and international guidelines have been recently developed. We evaluated the adhesion to national French guidelines via a survey of cancer patients treated for venous thromboembolism. METHODS: A national cross-sectional observational study evaluated the adhesion to guidelines in hospitalized patients. Good clinical practice was defined as initial 10-day treatment with injectable molecules followed by long-term treatment with low molecular weight heparin for at least 3 months. Demographic data, cancer type, stage, treatment, risk factors and type of thrombosis, were recorded. RESULTS: Five patients were included in 47 centers. Overall adhesion to guidelines was present in 59% (55-63%) of patients (295/500). During initial treatment, adhesion was high (487/496; 98%) but dropped (296/486; 62%) during the long-term maintenance. In patients with renal insufficiency, only a fourth of them received the adequate treatment. A majority of patients had metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). Lung and hematological malignancies were significantly associated with the highest and lowest rates of adhesion. CONCLUSION: Adhesion to national guidelines for treatment of venous thromboembolism in cancer is not optimal. Good compliance is observed during initial treatment, but drops after 10 days, underlying the need for further education to achieve a better implementation on a national level.

Prognosis of vasculitis associated myelodysplasia.

Systemic and immune manifestations have been reported in patients with MDS. The correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients remains controversial. Most of the authors agree that the median survival in myelodysplastic syndrome is not related to the presence of systemic and immune manifestations, but only with the existence of a systemic vasculitis.

A 5-year prospective follow-up study in essential cryofibrinogenemia patients.

INTRODUCTION: Cryofibrinogenemia may be essential, or secondary to diseases such as neoplasia, infection, thrombosis, and collagen vascular diseases. In a previous study, we reported the occurrence of neoplasia in some essential cryofibrinogenemia patients after a short period of follow-up. PURPOSE: We performed a prospective multi-center 5-year follow-up study in essential cryofibrinogenemia patients (2005-2009). RESULTS: 23 patients with essential cryofibrinogenemia were included, mean age 59 years (range: 33-79), 14 males. After a mean follow-up period of 24 months, 11/23 (47%) of cases that were initially diagnosed as essential cryofibrinogenemia were found to have an underlying lymphoma (6 T lymphoma and 5 B lymphoma). CONCLUSION: This prospective study suggests that some cases of cryofibrinogenemia that are initially considered as essential, may have underlying lymphoma. Thus, we further suggest that regular follow-up should be performed in patients with essential cryofibrinogenemia.

Systemic and immune manifestations in myelodysplasia: a multicenter retrospective study.

OBJECTIVE: The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002-2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations. METHODS: Forty-six patients with myelodysplasia presenting with systemic and/or immune manifestations were compared in terms of survival with 189 patients with myelodysplasia lacking these features. RESULTS: The clinical picture in these cases consisted of fever (13%), arthralgia or arthritis (13%), and cutaneous manifestations (67%). Four cases of systemic vasculitis have been reported in our series, and they have a worse prognosis. Immune anomalies were recorded in 29% of the cases, and the presence of cryoglobulins was also associated with a worse prognosis. CONCLUSION: A difference in survival between patients with myelodysplastic syndrome with systemic manifestations and patients lacking these manifestations has been observed in the presence of systemic vasculitis and/or cryoglobulins.

Anti-Ku antibodies: Clinical, genetic and diagnostic insights.

Anti-Ku antibodies are reported in various connective tissue diseases and the Ku complex can be responsible for a very strong autoimmune answer in autoimmune disease. Nowadays, anti-Ku antibodies are detected by ELISA, counterimmunoelectrophoresis (CIE), immunoblot (IB) and new highly performant techniques. Although the prevalence of anti-Ku antibodies is not homogenous, depending on several features such as disease type, genetic and geographical clustering, and also method of detection, they could be found in 55% overlap PM/systemic sclerosis patients. Moreover, anti-Ku antibodies are not associated with a particular clinical outcome, and especially with cancer related to myositis.

Antiphospholipid antibodies induce vascular functional changes in mice: a mechanism of vascular lesions in antiphospholipid syndrome?

A premature atherosclerosis has been presumed in patients with antiphospholipid syndrome. The potential role of antiphospholipid antibodies in the development of atheroma is rather controversial. In this study, we tested the hypothesis that antiphospholipid antibodies could induce atherosclerosis via vascular functional changes. CD1 mice received one single injection of antiphospholipid monoclonal antibodies derived from male (BXSB x NZW) F1 mice with a lupus-like disease associated with an antiphospholipid syndrome and coronary artery disease. One week later, first-order mesenteric arteries (diameter 220-260 microm) were isolated and mounted on a small-vessel myograph for the measurement of the relaxation responses to acetylcholine or the NO donor nitroprusside after precontraction by phenylephrine. Five out of eight antiphospholipid monoclonal antibodies reduced the response to acetylcholine compared with control mice, and this effect was especially marked with one of them. No change in the response to nitroprusside was observed. The impairment was maintained after 3 weeks of treatment and appeared related to a moderate decrease in NO-mediated responses and a marked decrease in prostanoid-mediated relaxations. These vascular functional changes could be prevented by chronic treatment with statins or aspirin. These data could constitute additional elements supporting a direct pathogenic role of antiphospholipid antibodies. We suggest that a sub-population of these autoantibodies could be responsible for the endothelial dysfunction observed in antiphospholipid syndrome.