[Libman-Sacks endocarditis under apixaban in a patient with a high-risk profile venous antiphospholipid syndrome]. / Une endocardite de Libman-Sacks survenant sous apixaban chez une patiente atteinte de SAPL veineux de profil à haut risque.

INTRODUCTION: Libman-Sacks endocarditis is a rare complication of antiphospholipid syndrome. Anti-vitamin K therapy is the standard treatment, although valvular replacement surgery may be required in some severe cases. In the latest EULAR recommendations, it is advised not to use direct oral anticoagulants in the management of antiphospholipid syndrome, especially of high-risk profile. CASE REPORT: We present a case of a mitral Libman-Sacks endocarditis complicated with multiple strokes occurring in the setting of an antiphospholipid syndrome with triple positive antibody profile in a 63-year-old woman with multiple sclerosis. She was previously treated with apixaban for two years. Tinzaparin followed by prolonged warfarine treatment and two months of hydroxychloroquine resulted in valvular improvement. CONCLUSION: To our knowledge, this is the first case of Libman-Sacks endocarditis occurring during apixaban therapy in a patient with antiphospholipid syndrome. This severe case highlights the inefficiency of direct oral anticoagulants to prevent thrombotic events in the antiphospholipid syndrome.

Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases.

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients. MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017. RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.). CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

[Illnesses unrelated to systemic sclerosis (IUSS) diagnosed throughout the patient's follow-up in a referral center: A cohort of 200 patients]. / Affections non-directement attribuables à la sclérodermie systémique (ANDAS) diagnostiquées au cours du suivi dans un centre de compétence: à propos d'une cohorte de 200 patients.

INTRODUCTION: Our work aimed to investigate the illnesses unrelated to systemic sclerosis (IUSS), diagnosed among patients with systemic sclerosis (SSc) throughout their follow-up in a referral tertiary care center. METHODS: All the patients with SSc followed in the Internal Medicine Department of the University Hospital between October, 2014 and December, 2015, were included. We specifically reviewed the medical records of the patients who exhibited IUSS, defined as an illness that could not be considered as a typical clinical manifestation or as a usual complication of the disease. RESULTS: Two hundred patients were included, and 38 IUSS were diagnosed among 31 SSc patients, over a 4 years median follow-up period. These diagnoses included vascular diseases (26%), heart diseases (21%), neoplasia (8%), infectious diseases (6%), autoimmune diseases (5%), endocrinopathies (5%), and others (24%). The median follow-up time before IUSS diagnosis was two years. Seventeen (45%) of these diagnoses were considered in patients showing suggestive clinical signs. A specific therapy was delivered in 25 cases (66%). Group comparisons revealed that dyslipidemia was more frequent in patients with IUSS (OR = 2.6 [1.1-1.5]; p = 0.014), while no differences were found for the other characteristics. Especially, no association between auto-antibodies specificity and the occurrence of IUSS was found. CONCLUSION: This study focused on IUSS in SSc patients and highlights the need for a polyvalent clinical approach all along the follow up of SSc patients.

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.

Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature.

BACKGROUND: Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis. METHODS: A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors. RESULTS: A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68-6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity < 70%, diffusing capacity of the lungs for carbon monoxide < 70%, pulmonary hypertension (PH), telangiectasia, valvular disease, malignancy, anemia, and CRP > 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03-3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival. CONCLUSIONS: Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Combined pulmonary fibrosis and emphysema in systemic sclerosis: A syndrome associated with heavy morbidity and mortality.

BACKGROUND: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc). METHODS: In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema. RESULTS: Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10-4), experienced more frequent unscheduled hospitalizations (50 % vs 25%, p < 0.01), and had decreased survival (p < 0.02 by Kaplan-Meier survival analysis) as compared to ILD-SSc controls. CONCLUSIONS: The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management.

[Non-infective endocarditis]. / Les endocardites non infectieuses.

Non-infective endocarditis, also referred to as non-bacterial thrombotic endocarditis, represent a wide range of rare pathologies, often severe. This review gathered the data available in the literature, to decipher the major information collected on the pathophysiology, the diagnosis and the treatment of these heterogeneous diseases, often misdiagnosed. Characteristics of non-infective endocarditis are similar to infective endocarditis in terms of valvular lesions (mostly left-sided, with regurgitations and vegetations), and their complications (embolism). The diagnosis of non-infective endocarditis is usually considered in patients with blood culture-negative endocarditis. Beyond the usual suspects - marastic endocarditis and systemic lupus erythematosus - which represent more than 75% of the cases, Behçet disease and hypereosinophilic syndrome are the main causes of non-infective endocarditis. More seldomly, rheumatoid arthritis, adult-onset Still disease, allergy to pork in patients with valvular procine bioprosthesis, systemic scleroderma, Cogan or Sneddon syndrome should be suspected. Diagnostic approach is based on history and physical examination, with a special focus on extra-cardiac manifestations, as well as echocardiography, and computed tomography. Treatment relies on intensive management of the underlying disease. Curative anticoagulation is often necessary. Although indications for cardiac surgery are poorly defined, as compared to infective endocarditis, data currently available suggest that an optimal control of the underlying disease before cardiac surgery is of utmost importance, as it dramatically reduces the risk of postoperative complications.

[Intra-cardiac manifestation during adult-onset Still's disease's, a tricuspid vegetation as a rare expression of systemic disease]. / Végétation tricuspidienne au cours d'une maladie de Still, une manifestation non infectieuse rare de lésion intracardiaque.

INTRODUCTION: Adult-onset Still's Disease is a rare multisystemic inflammatory disease characterized by fever, maculo-papular erythematous rash and arthralgia. Adult-onset Still's disease is a diagnosis of exclusion. CASE REPORT: We report the case of a 33 years old man, hospitalized for fever, arthralgia and throat manifestations, leading to Adult-onset Stills's Disease diagnosis. Cardiac ultrasound revealed tricuspid vegetation. Once infectious causes were ruled out, the vegetation was related to Adult-onset Still's Disease according to Fautrel and Yamaguchi criteria. The patient was treated with systemic high doses corticosteroid and cardiac surgery. Histological examination excluded infection and neoplasia, and showed cruoric and fibrinous vegetation. CONCLUSION: Non-infectious endocarditis, with a vegetation made of cruoric and fibrinous material, is a rare complication of Adult-onset Still's disease.

[Screening for pulmonary arterial hypertension in patients with systemic sclerosis: Comparison of DETECT algorithm to decisions of a multidisciplinary team, in a competence centre]. / Dépistage de l'hypertension artérielle pulmonaire au cours de la sclérodermie systémique : comparaison de l'algorithme DETECT à une discussion pluridisciplinaire en centre de compétence.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis and detecting PAH efficiently remains challenging. The DETECT study has offered in 2013 a composite screening tool for PAH. The objective of our study was to compare the indication of right heart catheterisation (RHC) as suggested by the DETECT algorithm with the decisions of a multidisciplinary team. METHODS: This prospective monocentric non-interventional study consecutively included systemic sclerosis patients when data required to apply DETECT algorithm were available. We evaluate the number of RHC as requested by this algorithm and confronted it with the indications of RHC suggested by a multidisciplinary group blinded for the result of DETECT algorithm. RESULTS: In total, 117 systemic sclerosis patients were included. When DETECT algorithm was applied to all patients, RHC was suggested by this algorithm for 70 patients, whereas only 15 indications were required by the multidisciplinary group; among those patients only 7 had PAH. When DETECT algorithm was applied only to the 42 patients with DLCO<60% and disease duration of more than 3 years, RHC was suggested for 31 patients whereas only 13 were indicated by the multidisciplinary group; among those patients only 7 had PAH. CONCLUSION: The DETECT algorithm is able to efficiently detect all PAH patients finally diagnosed by our multidisciplinary team. However, it increases by 3 the number of RHC that should be performed.

[Hereditary thrombophilia testing and its therapeutic impact on venous thromboembolism disease: Results from a retrospective single-center study of 162 patients]. / La recherche de thrombophilie héréditaire et son impact thérapeutique dans la maladie thromboembolique veineuse : résultats d'une étude monocentrique rétrospective sur 162 patients.

INTRODUCTION: Venous thromboembolic disease is a multifactorial, frequently recurrent pathology, whose treatment is based on anticoagulation. As part of the etiological investigation, screening for an inherited thrombophilia is framed by French guidelines published in 2009. The aim of the study is to assess the contribution of inherited thrombophilias testing in common practice. METHOD: This is a retrospective single-center observational study. Over a period of a year, all records of patients who were screened for a hereditary thrombophilia were analyzed. The conformity of the indication of hereditary thrombophilia workup in balance with the guidelines, its completeness and therapeutic impact were studied. RESULTS: Of the 494 records analyzed, 225 were related to venous thromboembolism. Among them, there were 162 pulmonary embolisms or deep vein thrombosis of the lower limbs. In this subgroup, 57 % of records complied with guidelines and 69 % were complete. Thirty-four thrombophilias were highlighted: 4 protein S deficiencies, 1 protein C deficiency, 4 combined deficiencies, 17 factor V Leiden mutations and 8 factor II G20210A mutations. For one patient, hereditary thrombophilia diagnosis had profoundly changed the curative therapeutic approach. CONCLUSION: Adherence to French guidelines remains limited. In clinical practice, diagnosis of hereditary thrombophilia has little impact on the curative therapeutic approach in venous thromboembolic disease.

Use of bosentan for digital ulcers related to systemic sclerosis: a real-life retrospective French study of 89 patients treated since specific approval.

OBJECTIVES: Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France. METHOD: An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination. RESULTS: The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes. CONCLUSIONS: Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.

Using rituximab plus fludarabine and cyclophosphamide as a treatment for refractory mixed cryoglobulinemia associated with lymphoma.

OBJECTIVE: Treatment of refractory mixed cryoglobulinemia (MC) with severe organ involvement remains challenging. Fludarabine, cyclophosphamide, and rituximab (FCR) treatment is highly effective for patients with chronic lymphocytic leukemia and marginal-zone lymphoma. We first report the safety and efficacy of FCR treatment in severe and refractory MC vasculitis associated with lymphoma. METHODS: We report the safety and efficacy of fludarabine (40 mg/m(2) orally on days 2-4), cyclophosphamide (250 mg/m(2) orally on days 2-4), and rituximab (375 mg/m(2) on day 1), every 4 weeks, for 3 to 6 cycles in 7 consecutive patients with severe and refractory MC. RESULTS: Clinical features of MC included purpura (n = 7), polyneuropathy (n = 6), and kidney (n = 4) and cardiac involvement (n = 2). Previous treatment included rituximab (n = 5), corticosteroids (n = 5), antiviral therapy (n = 5), cyclophosphamide (n = 3), and plasmapheresis (n = 2). All patients achieved clinical response, with 3 patients (42.9%) achieving a complete remission and 4 patients (57.1%) a partial remission. Cryoglobulin decreased from 0.94 to 0.41 gm/liter (P = 0.015). After a followup of 27 months, 2 patients experienced a relapse of MC. Five patients (71.4%) experienced side effects, including cytopenia (n = 5), pneumopathy (n = 2), and serum sickness (n = 1). CONCLUSION: The FCR regimen represents an effective treatment in severe and refractory MC.

[The yellow nail syndrome: a series of five cases]. / Le syndrome des ongles jaunes: présentation de cinq cas.

INTRODUCTION: The yellow nail syndrome is a rare disorder described for the first time in 1964. The pathophysiology remains unclear. Its definition is based on a clinical triad of yellow nails, lymphoedema and chronic respiratory disorders including pleural effusions and bronchiectasis. CASES REPORTS: We describe a retrospective series of five patients diagnosed with the yellow nail syndrome. All the patients were male, aged from 52 to 71 years (median=56). Three patients were diagnosed with the classic triad, whereas the other two had only yellow nails and bronchiectasis. Yellow nails and chronic sinusitis were present in all five patients. We also report atypical manifestations such as a transudative pleural effusion and facial oedema. The yellow nail syndrome was associated with cancer in two cases. CONCLUSION: More common alternative diagnoses must be excluded. The association with cancer should be explored. The treatment is only symptomatic.

[Diagnosis of solid malignancies in an internal medicine unit: a series of 114 consecutive cases]. / Le diagnostic des cancers solides dans un service de médecine interne: étude descriptive de 114 cas consécutifs.

PURPOSE: A deterioration of the general condition, a prolonged fever or an unexplained inflammatory syndrome are frequent reasons for hospitalization in a internal medicine unit. In these situations, it is not rare to make a diagnosis of cancer. PATIENTS AND METHODS: A descriptive study was carried out over a three years period (1st October 1999 to 30th September 2002) in an internal medicine unit. Every week, all patients in whom a cancer was diagnosed were enrolled in the study. RESULTS: During this period, 165 patients were identified (3.8% of the in-patients). A histological proof was obtained in 114 patients. Digestive and bronchopulmonary cancers were the most frequent. The first signs were very varied but digestive disorders and ferriprive anaemia were the most frequent. The number of investigations necessary to diagnosis were weak (1.56 procedures) when a sign was identified but were high (5.12 procedures) when no information was provided by interview, clinical examination or usual biological tests. CONCLUSION: Diagnosis of cancer is an usual situation in an internal medicine unit. Interview and clinical examination are essential in the diagnostic step. It could decrease the number of procedures. Internal unit services are fully concerned by the announcement of cancer.

[Thoracic infectious aortitis: microbiology, pathophysiology and treatment]. / Aortites thoraciques infectieuses: implications microbiologiques, physiopathologiques et thérapeutiques.

BACKGROUND: Thoracic infectious aortitis are currently rare. They are always lethal without any treatment. The microorganisms involved are numerous with particular pathophysiological characteristics for each bacterium. Treatment is difficult and must associate medical and surgical care. RECENT FINDINGS: Bacterial epidemiology of infectious aortitis has been profoundly modified with the large use of antibiotics. Syphilitic aortitis were frequent in the beginning of the twentieth century but its incidence has dramatically fallen. It still exists and its clinical presentation must be known to begin an adequate treatment. Other bacterial aetiologies of these aortitis are more classical with high frequencies of Staphylococcus aureus and Streptococcus, which are often associated with infective endocarditis. Among Gram-negative bacteria, Salmonella spp are the most frequently met microorganisms. Atherosclerosis represents the principal risk factor of these infectious aortitis. It provokes arterial parietal damage useful for bacterial attach. A saccular aneurysm of infective origin can then appear. Treatment must consist on antibiotics before surgery; Tuberculous aortitis are also possible but are much more rare. CONCLUSION: Thoracic infectious aortitis are very rare but must be known because of their poor prognosis. Treatment is difficult and prevention of atherosclerosis which is the most important risk factor of these diseases is therefore of greatest importance.

Regulation of salmon gonadotrophin-releasing hormone gene expression by sex steroids in rainbow trout brain.

Salmon gonadotrophin-releasing hormone (sGnRH) is the major form of gonadotrophin-releasing hormone in the brain of Salmonids and is encoded by two different genes: sGnRH1 and sGnRH2. In the present study, we examined the expression patterns of these two genes during development and throughout the reproductive cycle of the female rainbow trout (Oncorhynchus mykiss), and also investigated the feedback action of sex steroids on brain mRNA levels. Both genes are expressed as early as 14 days postfertilisation and show a similar expression pattern during early life stages. In the adult female, sGnRH1 and sGnRH2 mRNAs are both present in neurones located in the ventral forebrain. This gene expression in the brain appears to be low during early vitellogenesis, and increases during oocyte maturation to reach a maximum after ovulation. The expression of sGnRH1 was not modified by in vivo steroid treatments in any experiment; however, testosterone and 5alpha-dihydrotestosterone down-regulate brain sGnRH2 gene in immature and adult ovariectomised females. Oestradiol treatment decreases sGnRH2 mRNA levels in the brain of adult ovariectomised females only. In the triploid fish brain, none of the steroids affect brain sGnRH mRNA levels. Our results suggest that, unlike sGnRH1, the sGnRH2 gene is under a strongly androgenic inhibitory control in the immature and adult female rainbow trout.

[Cryptococcal infections in non-HIV infected patients. Study of four cases and review of literature]. / Infections à cryptocoque chez des patients non VIH. A propos de quatre cas et revue de la littérature.

BACKGROUND: Cryptococcal infections are frequent in HIV-infected patients and are regularly looked after. This infection may occur in others immunosuppressives situations and, in those cases, diagnosis is often delayed. METHODS: We report four cases of cryptococcal infections in patients whose immunosuppression isn't related with HIV infection but due to chronic lymphocytic leukemia, giant cell temporal arteritis, gastric neoplasm and lupus. Diagnosis, prognostic and treatment are detailed. RESULTS: Four patients aged from 25 to 76 presented a cryptococcal infection (three meningitis). A woman died at the admission. Another died seven years later. The two others are still alive under treatment. When infected, all patients were immunodeficiency. CONCLUSION: Cryptococcal infection may occur in patients non-HIV-infected patients. Early detection is needed to improve prognostic.