[Gastrointestinal tract involvement in systemic sclerosis]. / Atteinte digestive de la sclérodermie systémique.

Gastrointestinal tract involvement in systemic sclerosis concerns more than 90% of patients but is of heterogeneous clinical expression. It can involve the entire intestinal tract and be responsible for multifactorial malnutrition, which is frequent in this disease. It is a major source of deterioration in the quality of life and can even be life-threatening. Management is complex and multidisciplinary, ranging from simple hygienic and dietary measures, to specialized endoscopic or surgical interventional procedures, also including medical treatments, particularly proton pump inhibitors and prokinetics, with potential side effects. Ongoing research for new diagnostic and therapeutic tools promises to improve the management and prognosis of these patients.

[Monocentric study on pharmaceuticals taken by patients to treat systemic sclerosis]. / Étude monocentrique sur les médicaments pris par les patients pour le traitement de la sclérodermie systémique.

INTRODUCTION: Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients. METHODS: This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance. RESULTS: The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009). CONCLUSION: This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient.

[An hereditary hemorrhagic telangiectasia of late revealed by a cerebral venous thrombosis: A case report]. / Une télangiectasie hémorragique héréditaire révélée tardivement par une thrombose veineuse cérébrale : à propos d'un cas.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the triad of nose bleeding, telangiectasia and familial heredity. CASE REPORT: We report the case of a patient who had idiopathic venous cerebral thrombosis complicated by a cerebral infarction treated with warfarin. In the context of a psoas hematoma by warfarine overdose and immobilization, the patient had deep vein thrombosis of the left lower limb with pulmonary embolism revealing a pulmonary arteriovenous malformation. After a reexamination, the patient clinical phenotype of HHT was confirmed genetically. The patient was treated with rivaroxaban allowing clinical improvement and partial recanalization of all thrombosis after six months. Thrombotic overisk has already been studied in HHT patients but the use of anticoagulants is at higher risk in these patients. However this patient experienced no adverse event with rivaroxaban. CONCLUSION: This is the first case described of cerebral venous thrombosis treated with rivaroxaban revealing an HHT.

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.

Concomitant association of giant cell arteritis and malignancy: a multicenter retrospective case-control study.

INTRODUCTION: Some studies suggest that there is an increased risk of malignancies in giant cell arteritis (GCA). We aimed to describe the clinical characteristics and outcomes of GCA patients with concomitant malignancy and compare them to a GCA control group. METHOD: Patients with a diagnosis of GCA and malignancy and with a maximal delay of 12 months between both diagnoses were retrospectively included in this study and compared to a control group of age-matched (3:1) patients from a multicenter cohort of GCA patients. RESULTS: Forty-nine observations were collected (median age 76 years). Malignancies comprised 33 (67%) solid neoplasms and 16 (33%) clonal hematologic disorders. No over-representation of a particular type of malignancy was observed. Diagnosis of GCA and malignancy was synchronous in 7 (14%) patients, while malignancy succeeded GCA in 29 (59%) patients. Malignancy was fortuitously diagnosed based on abnormalities observed in laboratory tests in 26 patients, based on imaging in 14 patients, and based on symptoms or clinical examination in the nine remaining patients. Two patients had a concomitant relapse of both conditions. When compared to the control group, patients with concomitant GCA and malignancy were more frequently male (p < 0.001), with an altered general state (p < 0.001), and polymyalgia rheumatica (p < 0.01). CONCLUSIONS: This study does not indicate an over-representation of any particular type of malignancy in GCA patients. Initial follow-up dictated by vasculitis may have led to an early identification of malignancy. Nevertheless, GCA male patients with an altered general state and polymyalgia rheumatica might more frequently show concomitant malignancies.

[Upper-extremity venous thrombosis: A retrospective study about 160 cases]. / Épidémiologie des thromboses veineuses des membres supérieurs : étude rétrospective de 160 thromboses aiguës.

AIM: To describe the clinical features and etiologies of upper limb venous thrombosis (ULVT). METHODS: All patients with a clinically suspected ULVT, were included retrospectively from January to December 2016. Diagnosis of ULVT was based on doppler-ultrasonography. Clinical features, topography and symptomatic pulmonary embolism (PE) were analyzed. The sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative value (NPV) of clinical symptoms leading to ULVT suspicion were estimated by comparing patients with and without ULVT. RESULTS: Among 488 patients with a suspected ULVT, 160 were diagnosed with ULVT, including, 80 with deep venous thrombosis (DVT) and 80 with superficial venous thrombosis (SVT). Symptomatic PE was found in 2.5 % of cases (n=4). None of the clinical symptoms of ULVT had a sensitivity greater than 40 %. For DVT, presence of superior vena cava syndrome had a 100 % PPV, 71.6 % NPV and 100 % Sp. For SVT, the presence of an cord-like induration had a 85.7 % PPV, 75.3 % NPV and 98.4 % Sp. An endovenous device was present in 87.5 % of DVT and 97.5 % of SVT cases. Malignant hemopathy was found in 43.8 % and 31.3 % of cases of DVT and SVT, respectively. Sepsis and solid neoplasia were present in 25 % and 15 % of cases of ULVT, respectively. Peripherally inserted central catheter or implantable sites were present in 40 % and 17.5 % of DVT patients. No solid neoplasia, hematological malignancy or thrombophilia were diagnosed in patients with ULVT. CONCLUSION: An endovenous device was involved in 92.5 % of cases of ULVT. The prevalence of symptomatic PE was low. Hematological malignancies, sepsis and neoplasia were the most common conditions present in patients with ULVT.

[Late-onset systemic sclerosis: A retrospective study of 27 patients diagnosed after the age of 70]. / Sclérodermie systémique de révélation tardive : étude rétrospective de 27 patients diagnostiqués après l'âge de 70 ans.

BACKGROUND: The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70. PATIENTS AND METHODS: This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years. RESULTS: Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively. CONCLUSION: Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor.

Use of a thrombopoietin receptor agonist in von Willebrand disease type 2B (p.V1316M) with severe thrombocytopenia and intracranial hemorrhage.

We present here a 63-year old woman with a long history of immune thrombocytopenia. She was hospitalized for a traumatic intracranial hemorrhage with thrombocytopenia. Following inefficient treatment of four platelet transfusions, immunoglobulins, and corticosteroids, we initiated treatment with a thrombopoietin (TPO) receptor agonist (eltrombopag 25 mg/d) with a good efficacy. Her mother and sister also had chronic thrombocytopenia. Clinical history, hemostasis results, and gene analysis revealed von Willebrand disease (VWD) type 2B with the mutation (c.3946G>A; p.V1316M), which combines a von Willebrand factor defect with severe thrombocytopenia, as well as a thrombocytopathy. The efficacy of TPO receptor agonists appears to counterbalance, at least to some extent, the thrombocytopathy associated with this mutation. As such, the use of TPO receptor agonists could represent an alternative therapeutic approach in cases of VWD type 2B with severe thrombocytopenia.

[Place of azathioprine in the treatment of giant cell arteritis]. / Utilisation de l'azathioprine dans le traitement de l'artérite à cellules géantes.

OBJECTIVE: The aim of this bicentric retrospective study was to describe the use of azathioprine in giant cell arteritis, and to appreciate its corticosteroid-sparing effect in glucocorticoid-dependent patients or with severe glucocorticoid related side effects. METHODS: We retrospectively reviewed the medical records of patients diagnosed with giant cell arteritis between 2000 and 2011 in two departments of internal medicine. Only the patients treated with azathioprine were included in this study. Sociodemographic, clinical, biological, radiological and therapeutic data were collected by a standardized questionnaire. A comparative analysis of daily prednisone dose at the initiation and 1 year after the prescription of azathioprine was made. RESULTS: Of the 28 patients included, 21 responded to azathioprine. At 1 year of follow-up after the initiation of azathioprine, 18 patients (64%) were still in sustained response, asymptomatic, without increase in acute phase response laboratory markers, and with a daily dose of prednisone<10 mg. Three patients (11%) experienced a relapse during azathioprine treatment. Mean daily dose of prednisone were 25.4 mg at the time of initiation of azathioprine, and 4.7 mg at 1 year of treatment, suggesting a corticosteroid-sparing effect (P<0.001). Ten patients experienced azathioprine serious side effects, leading to discontinuation of treatment in seven cases. CONCLUSION: Azathioprine may be an alternative treatment for patients with giant cell arteritis requiring prolonged high dose glucocorticoid therapy or developing severe glucocorticoid related side effects. However, given the potential adverse effects of azathioprine, a close monitoring is necessary.

Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).

PURPOSE: Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. METHODS: Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d'étude français des artérites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed. RESULTS: The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. CONCLUSIONS: The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.

[Three cases of Jaccoud's arthropathy during systemic sclerosis]. / Trois observations de rhumatisme de Jaccoud au cours de la sclérodermie systémique.

INTRODUCTION: Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis. CASE REPORTS: We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained. CONCLUSION: We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish.

[Qualitative and quantitative evaluation of an internal medicine assistance line dedicated to the diagnosis and treatment of diseases for general practice]. / Évaluation qualitative et quantitative d'un service d'assistance téléphonique de médecine interne dédié à l'aide diagnostique et thérapeutique de pathologies relevant du champ de la médecine générale.

PURPOSE: Clinical reasoning and treatment challenges within the scope of general practice led to the development of an internal medicine assistance line provided by Nantes University Hospital. The primary outcome of this study was to describe callers' profile, their requests and answers provided. METHODS: A prospective, cross-sectional, observational, descriptive study was undertaken. For each call were identified the calling physician, her/his specialty and work setting, the call's object and adequacy, the answer provided, the time needed to connect with the assistance line, the time devoted by the internal medicine physician to provide an answer to the request, and whether the assistance line prevented a visit to the emergency room. Each calling physician was then called back to obtain demographic and professional characteristics, and data relating to the call and to the assistance line. RESULTS: Sixty-three days were analyzed and 276 calls identified. The 237 identified calling physicians were mainly females (54%, n=93), with a mean age of 46 years, graduated from Nantes University (65%, n=86), practicing ambulatory general medicine (69%, n=164) in Loire-Atlantique department area (82%, n=176) for a mean duration of 15 years. Calls were mostly associated with diagnostic challenges (61%, n=166) concerning clinical issues (57%, n=155). A sole telephone advice was the main type of answer provided (56%, n=147) and a visit to the emergency room was prevented for 17% of calls. CONCLUSION: The assistance line activity is adequate with its missions and seems to facilitate patients' healthcare delivery advocating for the development of similar structures in other units. Improvements relating to the information, availability and physicians' training should be considered.

[Thrombin generation test]. / Le test de génération de thrombine.

Thrombin is a key enzyme of the coagulation cascade, having both pro- and anticoagulant functions. Global haemostasis assay, the so-called thrombin generation test is appropriate for its assessment. Estimation of an individual's potential to generate thrombin may correlate more closely with a hyper- or hypo-coagulable phenotype, compared to traditional coagulation tests. In patients at risk of venous thrombosis, thrombin generation analysis may be utilized to detect underlying thrombophilia. In patients with documented venous thromboembolism, increased thrombin generation values are seen in those patients at greatest risk for recurrence. In patients with arterial vascular disease, the data are limited. In case of haemophilia thrombin generation assays reflect bleeding severity. It is applicable for monitoring of both conventional haemophilia treatment and inhibitor-bypassing therapy, which is needed when inhibitors develop in patients. Standardization of thrombin generation methods and determination of cut off-values are required before its application in clinical practice.

[Antisynthetase syndrome with pulmonary hypertension: 4 original observations]. / Syndrome des antisynthétases compliqué d'une hypertension pulmonaire : 4 observations originales.

INTRODUCTION: Pulmonary hypertension (PH) may occur in patients with antisynthetase syndrome (ASS) but this association is poorly studied. In this article, we report 4 new cases of PH associated with ASS, and we discuss PH mechanisms in this specific disease. CASES: Four patients (3 females, 1 male) with confirmed ASS associated with anti-Jo1 (n=3), anti-PL7 (n=1), and anti-Ro52 (n=3) antibodies were analyzed. They presented with subacute dyspnea in average ten years after they were first diagnosed as ASS. Diagnosis of pre-capillary PH was made (mean of mPAP: 34mmHg): PAH (n=1), group 3 PH (n=2) and PH associated to hyperthyroidism (n=1). Among three patients who received specific PAH therapy, two had significant improvement in both clinical and hemodynamic parameters. CONCLUSION: During ASS, PH may occur in 5 to 10 % of cases, caused by various mechanisms. Unexplained dyspnea may be due to PH among ASS patients.

[Aortitis in giant cell arteritis and its complications]. / Aortite et complications aortiques de l'artérite à cellules géantes (maladie de Horton).

Aortitis is a serious complication of giant cell arteritis (GCA), because of the risk of aortic aneurism, rupture, or dissection. Aortitis is present either at presentation or, more frequently, occurs as a delayed complication, typically as an aortic aneurism of the ascending part of the aorta. An aortic aneurism may occur in up to 10% of patients. Aortitis is sometimes associated to arteritis of the supra-aortic vessels. Risk factors for aortitis remain unknown. Recent clinical studies indicate that prevalence of aortitis was initially under-estimated. Imaging studies show signs of infra-clinical aortitis in 20 to 65% of cases at diagnosis. Using ultrasonography, thickening of the vascular wall with an hypoechoic halo around the abdominal aorta is suggestive of abdominal aortitis. Positron emission tomography shows a metabolic hypersignal of the aorta in about 50% of patients with giant cell arteritis. Aortic computed tomographic (CT) scan visualizes aneurysmal dilatations, ectasia or focal or concentric parietal thickenings. When present at the time of diagnosis of GCA, these findings seem to be associated with frequent relapses and perhaps with a higher long-term vascular mortality rate. Therefore, we recommend the screening of aortitis lesions at GCA diagnosis by an aortic CT-scan and follow-up. Therapeutic trials should be conducted to try to improve the treatment of aortitis in GCA.

[Superior vena cava syndrome induced by pacemaker probes, 12 years after introduction]. / Un syndrome cave supérieur 12ans après l'implantation d'un pacemaker.

Superior vena cava syndrome is a rare disease, most often found to result from a malignant process, which causes extrinsic compression of the superior vena cava. In recent years, there has been an increase of superior vena cava syndrome related to medical devices (implantable site, pacemaker [PM], central venous line for parenteral nutrition...). We report the case of a 37-year-old patient who developed a superior vena cava syndrome 12 years after implantation of a PM. The diagnosis was established on venography after two negative venous-CT focused on the superior vena cava. The superior vena cava syndrome improved immediately after angioplasty and stenting covering the PM probes at the superior vena cava/brachiocephalic venous trunk junction.