Central nervous system vasculitis in VEXAS syndrome: A rare involvemen.

INTRODUCTION: VEXAS (Vacuoles, E1 Enzyme, X-linked, autoinflammatory, Somatic) syndrome is a recently described severe adult-onset autoinflammatory disorder mediated by X-linked gene UBA1 somatic mutations, responsible of recurrent fever, skin involvement, chondritis, macrocytic anemia and inflammatory syndrome. Neurological manifestations are rarely described, and predominantly involve peripheral nervous system (PNS) impairment. RESULTS: We report the first central nervous system (CNS) vasculitis in VEXAS syndrome, characterized by headache, cognitive dysfunction and focal signs (cerebellar ataxia). Magnetic resonance imaging (MRI) revealed multifocal white-matter lesions corresponding to recent ischemic strokes, combined with cortical hemorrhagic lesions and gadolinium enhancement of the distal wall vessels. Treatment with methylprednisone, ruxolitinib and tocilizumab led to clinical improvement and a decrease of the inflammatory syndrome. The patient died few months after due to infectious complications. CONCLUSION: CNS vasculitis, occurring as a manifestation of the systemic auto-inflammatory state of VEXAS syndrome, might be a rare but severe complication. We suggest that it be added to the list of inflammatory vasculopathies. More prospective studies are needed to optimize the treatment.

[Venous thrombo-embolism during immune-mediated thrombotic thrombocytopenic purpura is prevalent in patients with a prolonged treatment with therapeutic plasma exchange]. / La maladie thrombo-embolique veineuse au cours du purpura thrombotique thrombocytopénique autoimmun est associée à un traitement prolongé par échanges plasmatiques.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a devastating disease characterized by disseminated microvascular thrombosis. Despite pro-thrombotic predisposing conditions, the prevalence of macrovascular venous thrombosis event (VTE) in immune-mediated TTP (iTTP) has rarely been assessed. METHODS: We reviewed data of all iTTP patients of the French reference Center for thrombotic microangiopathies registry prospectively enrolled through a 10-year period, between 2008 and 2018. Venous thrombosis included either thrombosis of central venous catheter, symptomatic deep venous thrombosis of the limbs or pulmonary embolism. RESULTS: Forty-eight (12.7%) VTE were diagnosed. VTE was diagnosed after a median time of 7 [IQR, 3-16] days following the first therapeutic plasma exchange (TPE) and consisted mainly in catheter-related thrombosis (73%), and to a lesser extend symptomatic deep venous thrombosis (16%), proximal pulmonary embolism (8%) and splanchnic vein thrombosis (2%). Cases with VTE (VTE+ cases), required more TPE to achieve remission (P < 0.01), and the total volume of plasma required to achieve remission was larger (P < 0.01) than for VTE- cases. There was also a trend for more rituximab use in the VTE+ cases as compared to the VTE- cases (47% vs 33%; respectively; P = 0.07). Curative anticoagulation was started in 38 cases (79%), while 6 VTE cases did not receive any antithrombotic agents, and catheter was systematically removed when catheter-related thrombosis was diagnosed. VTE+ cases had a higher number of inserted central venous catheters than VTE- cases (P < 0.05). CONCLUSION: VTE is a frequent condition occurring during iTTP management and is observed when patients require a prolonged treatment with daily TPE and multiple catheter insertions. Therapeutic strategies aimed at reducing the duration of TPE treatment in iTTP should substantially reduce this complication.

Granulomatosis with polyangiitis and pregnancy: A case report and review of the literature.

The association of granulomatosis with polyangiitis and pregnancy is rare and therapeutic options are limited by the risk of teratogenicity and fetotoxicity. There is a paucity of published literature to guide clinical decision-making in these cases. We report the case of a 26-year-old woman with no medical history who presented at 21 weeks of gestation with a bilateral sudden loss of hearing and erosive rhinitis. The diagnosis of granulomatosis with polyangiitis was confirmed radiologically and biologically. Corticosteroids were not enough to stabilize the disease and she received intravenous immunoglobulins with remission. A successful delivery of a healthy male newborn was done at 36 weeks. A review of all published literature on granulomatosis with polyangiitis in pregnancy between 1970 and 2017 is presented. Trial registration: Not applicable.

[Agranulocytosis related to fluindione: A case report]. / Agranulocytose à la fluindione: à propos d'un cas.

INTRODUCTION: While in most countries warfarin is the preferred anti-vitamin K, fluindione, a molecule with a prolonged half-life remains largely prescribed in France. Some of its side effects, including immuno-allergic complications, remain poorly understood. CASE REPORT: A 77-year-old woman presented with a febrile severe neutropenia of immunoallergic mechanism with a favourable outcome associated with fluindione, introduced 25 days earlier for the treatment of atrial fibrillation. CONCLUSION: This rare side effect is a reminder of the importance of biological monitoring in the first weeks following the introduction of fluindione and key diagnostic elements and therapeutic aspects of iatrogenic agranulocytosis.

[Which place for direct oral anticoagulants in routine hospital medical practice?]. / Quelle place pour les anticoagulants oraux directs en pratique hospitalière quotidienne?

PURPOSE: More than one million patients received an oral anticoagulant treatment in France. This medication is the first aetiology of iatrogenic events. Recently, direct oral anticoagulant (DOA) provided efficacy and safety in the treatment of atrial fibrillation and venous thromboembolic events. Given the growing increase in the prescription of these molecules, with many advantages but also disadvantages, it seemed interesting to assess in routine hospital medical practice, the proportion of patients for which the initiation of AOD could be safe. METHODS: This prospective, observational study was conducted in the department of internal medicine from October 2012 and September 2013. All inpatients receiving oral anticoagulant treatment have been included. Demographic data, indication of anticoagulant treatment, contraindications and interactions have been reported. From these information, we have established the percentage of patients who could benefit from DOA safely and securely. RESULTS: Two hundred and ninety inpatients were included with a mean age of 76.3±15.2 years old. Atrial fibrillation and thromboembolic venous disease were the most prevalent indications of anticoagulant treatments (67.2% and 22.4% of cases respectively). Among all patients, 260 had an indication of DOA (89.7%), authorized by the French National health agency. Eighty percent had both indication and no contraindication for DOA. However, only 53.1% of patients neither had drug-drug interaction. Main contraindications were severe renal failure (clearance<30mL/min) in 10.7% of cases, and recent history of gastric ulcer in 15.3% of cases. The most frequent interactions with DOA were antiplatelet agent (14.5%) and amiodarone (11.6%). Almost two thirds of inpatients (65.1%) had at least one drug-drug interaction with VKA. CONCLUSION: These results, coming from "real life", provide that only 53.1% of inpatients under anticoagulants could receive DOA safely. Caution is warranted, and VKA still have a preponderant role among anticoagulant drugs.

[Recurrent facial palsy revealing Human T-lymphotropic virus type 1 (HTLV-1) infection]. / Paralysie faciale à bascule révélatrice d'une infection à Human T-lymphotropic virus type 1 (HTLV-1).

INTRODUCTION: Neurological involvement of Human T-lymphotropic virus type 1 (HTLV-1) mainly results in myelopathy (tropical spastic paraparesis). However, cranial nerve impairment, including facial nerve damage, is rare in patients with HTLV-1 infection. OBSERVATION: We report the case of a patient, originally from Caribbean islands, who developed recurrent bilateral facial palsy (six recurrences during the 7-year follow-up). Both blood and cerebrospinal fluid serologies were positive for HTLV-1. The diagnosis of recurring bilateral facial palsy revealing HTLV-1 infection was made. CONCLUSION: Our case report underscores that HTLV-1 infection should be considered in patients, coming from endemic areas (Caribbean islands, South America, Japan and Africa), who exhibit recurrent bilateral facial palsy. Our data therefore indicate that HTLV-1 serology should be routinely performed in these patients.

[The revolution of monoclonal antibodies in the treatment of thrombotic microangiopathy]. / La révolution des anticorps monoclonaux dans la prise en charge des microangiopathies thrombotiques.

Thrombotic microangiopathies (TMA) define a syndrome characterized by the association of microangiopathic haemolytic anaemia with schistocytes, peripheral thrombocytopenia, and organ injury of variable severity. Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (HUS) are the main forms of TMA. Recent advances in the pathophysiology of those two diseases, which include in HUS the identification of a deregulation of the alternative complement pathway, and in TTP a severe deficiency in ADAMTS-13, allowed to develop specific, pathophysiology-based therapies. Therefore, rituximab and eculizumab tends to be increasingly used, and there is an urgent need to define consensual modes of administration at the international level, as well as common definitions of response evaluation and follow-up explorations.

[Facial diplegia as the presenting feature of Lyme disease]. / Diplégie faciale révélatrice d'une maladie de Lyme.

INTRODUCTION: Diagnosis of neuroborreliosis may be difficult. Neuroborreliosis mainly results in lymphocytic meningitis and in meningoradiculitis (67-83% of cases). CASE REPORT: We report the case of a patient who developed a sudden facial diplegia, revealing neuroborreliosis proved by positive blood and cerebrospinal fluid serology. The patient had no previous history of tick bite and migrans erythema. The patient was given ceftriaxone therapy (2 g/day for 21 days), leading to resolution of all clinical symptoms. CONCLUSION: Our report underscores that neuroborreliosis should be considered in patients exhibiting facial diplegia. Thus, Lyme serology should be performed systematically in these patients. Altogether, early management is crucial, before the onset of neurological manifestations at late stage, leading to disabling sequelae despite antibiotic therapy.

[Azathioprine-associated severe myelosuppression: indication of routine determination of thiopurine S-methyltransferase variant?]. / Aplasie médullaire induite par l'azathioprine: intérêt de la recherche systématique d'une mutation du gène de la thiopurine S-méthyltransférase ?

INTRODUCTION: Myelotoxicity is a well-known adverse effect of azathioprine, leading mainly to leukopenia. Other azathioprine associated hematological adverse effects are uncommon. CASE REPORT: We report a 49-year-old woman with rheumatoid arthritis and acquired hemophilia, who presented a severe myelosuppression occurring 3 weeks after an increase of her azathioprine regimen (at a daily dose of 150 mg). The patient had a heterozygous mutation of the thiopurine S-methyltransferase gene (TPMT*3A). Azathioprine therapy was discontinued and she recovered at 3 weeks. The patient had no relapse of pancytopenia after a 1 year follow-up. CONCLUSION: Routine measurement of TPMT activity or determination of TPMT variant allele may be useful tests, in order to identify the subgroup of patients who are at risk to develop azathioprine induced severe myelosuppression.

[Usefulness of magnetic resonance imaging in Churg-Strauss syndrome related cardiac involvement. A case series of three patients and literature review]. / Intérêt de l'imagerie par résonance magnétique nucléaire au cours de l'atteinte cardiaque du syndrome de Churg-Strauss. Trois observations et revue de la littérature.

PURPOSE: The reported prevalence of cardiac complications is variable in patients with Churg-Strauss syndrome (15-92%) and depends on diagnostic tools. Diagnosis at early stage of heart involvement is crucial, resulting in appropriate management. METHODS: We report three patients who developed cardiac manifestations, revealing Churg-Strauss syndrome. The diagnosis of cardiac involvement was obtained using cardiac magnetic resonance imaging (MRI). RESULTS: Two patients were males and the remaining one was a female. Presenting clinical manifestations were: cardiac failure (n=1) and retrosternal pain (n=2). Laboratory findings disclosed: high blood count of eosinophils (range: 6000-11,000/mm(3)); antineutrophil cytoplasmic antibodies were positive in a single patient. Cardiac MRI demonstrated: (1) late gadolinium enhancement (n=3), involving mainly the apical and mid-cavity left ventricular segments; (2) impaired left ventricular function (n=2), mean left ventricular ejection fraction being: 51%; and (3) pericardial effusion (n=3). Outcome was favourable after institution of combined therapy with prednisone and cyclophosphamide (n=2); one patient also underwent plasma exchanges. CONCLUSION: Our case series underlines that MRI is a helpful tool in the diagnosis of Churg-Strauss syndrome-related cardiac complications. We further suggest that clinical assessment of patients with Churg-Strauss syndrome should include cardiac MRI, in order to detect cardiac involvement at an early stage; indeed, because cardiac manifestations are predictive factors of poor prognosis, diagnosis at early stages of cardiac involvement may result in improvement of patients management.