Outcome and prognosis of isolated carotid vasculitis.

OBJECTIVE: To assess the prognosis and outcome of patients with isolated carotid vasculitis. METHODS: We performed a retrospective multicenter study of 36 patients (median age at diagnosis was 37 [IQR 27-45] years and 11 [31 %] patients were men) with initial presentation as isolated carotid vasculitis. Study endpoints included vascular complications, relapses, and progression to large vessel vasculitis (i.e. Giant cell arteritis or Takayasu). RESULTS: The most frequent involvement was the left internal carotid artery (39 %), and 81 % had stenosis. After a median follow-up of 32 months [IQR 12-96], 21 (58 %) patients had a vascular event, including 31 % of new onset vascular lesions and 25 % of stroke/transient ischemic attack. Patients with stroke had less carotidynia at diagnosis (33 % vs 74 %, p = 0.046), higher significant carotid stenosis (i.e. > 50 %) (89 % vs. 30 %, p = 0.026) and higher severe carotid stenosis (i.e. >70 %) (67 % vs 19 %, p = 0.012), compared to those without stroke. Twenty (52 %) patients experienced relapses. High CRP at diagnosis was associated with relapses (p = 0.022). At the end of follow-up, 21 (58 %) patients were classified as having Takayasu arteritis, 13 (36 %) as isolated carotid vasculitis, and two (6 %) as giant cell arteritis. CONCLUSION: Carotid vasculitis may occur as a topographically limited lesion and is associated with significant rate of vascular complications.

Behçet's disease uveitis.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis.

French recommendations for the management of non-infectious chronic uveitis.

This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.

[Neurological involvement of sarcoidosis: current diagnostic and therapeutic strategies]. / Atteinte neurologique de la Sarcoïdose : stratégies diagnostiques et thérapeutiques actuelles.

Neurosarcoidosis (NS) is a rare but severe form of sarcoidosis. NS is associated with significant morbidity and mortality. Mortality is about 10% at 10 years with more than 30% of patients who have a significant disability. The most frequent features are cranial neuropathy (the facial and optic nerve most commonly affected), cranial parenchymal lesions, meningitis, spinal corn abnormalities (20-30%) and more rarely peripheral neuropathy (approximately 10-15%). The challenge of diagnosis is to eliminate other diagnoses. Atypical presentations should make to discuss the need for cerebral biopsy in order to highlight the presence of granulomatous lesions while eliminating alternative diagnosis. Therapeutic management is based on corticosteroid therapy and immunomodulators. There are no comparative prospective study to allow us to define the first-line immunosuppressive treatment and the therapeutic strategy in refractory patients. Conventional immunosuppressants such as methotrexate, mycophenolate mofetil and cyclophosphamide are commonly used. Data on the efficacy of anti-TNFα (including infliximab) in refractory and/or severe forms are increasing during the last ten years. Additional data is necessary to assess their interest in first line in patients with severe involvement and a significant risk of relapse.

[Thoracic manifestations of Behcet's disease]. / Atteintes thoraciques de la maladie de Behçet.

Behcet's disease (BD) is a multisystemic vasculitis involving arteries and veins of all sizes. While joint and dermatological manifestations are the most common features of BD and are associated with a good prognosis; vascular involvement, remains the principal cause of death. Arterial manifestations occur in 5-10% of cases and manifest as occlusion/thrombosis or aneurysms. Arterial aneurysms are likely multiple and the most common sites are pulmonary arteries, aorta and arteries of lower limbs. Parenchymal involvement is less frequent and may manifest as consolidation or nodules, which may evolve to excavation. Aneurysms may occur at the sites of arterial puncture; then, non-traumatic techniques are favored. Patients with arterial manifestations may present with fever and increased inflammatory markers. Artery damage is rare, serious, and may result in massive hemoptysis. The prognosis of pulmonary artery aneurysms is severe (mortality estimated up to 26%) but has been improved by earlier diagnosis and the introduction of immunosuppressants. Treatment of severe arterial manifestations is based on high-dose corticosteroids along with cyclophosphamide or anti-TNF antagonists. Anticoagulation could be added to immunosuppressants in case of venous thrombosis if a coexisting pulmonary aneurysm is ruled out. Endovascular treatment should be performed in case of severe symptomatic pulmonary aneurysms, along with an adequate medical management. Long-term maintenance therapy of these severe forms is of paramount importance because of relapse risk (40% at five years).

[Cardiac sarcoidosis: Diagnosis, prognosis and therapeutics]. / Sarcoïdose cardiaque : stratégies diagnostiques et thérapeutiques actuelles.

Sarcoidosis is a systemic granulomatous disease characterized by pulmonary involvement in most patients and more rarely by extrapulmonary involvement such as ocular, skin, salivary, lymph nodes and joints damages. Neurological and cardiac involvements are uncommon but are associated with increased morbidity and mortality. Cardiac sarcoidosis affects 5 to 20% of patients depending on the studies and autopsy studies even report cardiac involvement in 25% of sarcoidosis patients. This review aims to summarise main data on the diagnostic value of the different imaging techniques in cardiac sarcoidosis and to also detail the management of these patients who require a multidisciplinary approach.

Specific Follicular Helper T Cell Signature in Takayasu Arteritis.

OBJECTIVE: Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS: Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS: Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/ß TCR repertoire. CONCLUSION: We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

[Observational study of QuantiFERON® management for ocular tuberculosis diagnosis: Analysis of 244 consecutive tests]. / Étude observationnelle de l'usage du QuantiFERON® pour le diagnostic de tuberculose oculaire, basée sur 244 tests consécutifs.

INTRODUCTION: Ocular tuberculosis (TB) diagnosisremains difficult and quantiferon (QFT) contribution needs still yet to be specified, despite its generalization in France. The purpose of this observational study is to assess in which ocular inflammation (OI) presentation QFT is prescribed and to evaluate the added value of new QuantiFERON®-TB Gold Plus (QFT-Plus) test for diagnosis ocular TB diagnosis. PATIENTS AND METHODS: Monocentric, observational study, carried out in an ophthalmology department over a period of 5 months. Inclusion criteria were defined as an existence of an OI for which a QFT-Plus test was part of the etiological investigations. Of the 316 consecutive files, 72 were excluded (indeterminate test, prescription before anti-TNFα or immunosuppressant initiation, missing data, wrong indication) and 244 were selected and divided into two groups: group one (anterior uveitis/episcleritis, n=129) and group two (intermediate/posterior uveitis/optic neuritis/ocular myositis, n=115). All positive QFT patients underwent an etiological investigation including thoracic imaging. RESULTS: Forty-five patients, aged 52±12 years, had positive QFT (18.5%), including 18 patients for group 1 and 27 for group 2. Living in TB-endemic area, TB exposure and chest imaging abnormalities were identified in 70%, 27% and 22% of cases, respectively. OI was chronic in 36% of cases (group one, 4/18; group two, 12/27). None of the 18 patients, in group 1, received anti-tuberculosis treatment (ATT) or experienced a relapse during one-year follow-up. Four QFT+ patients, from group 2 (15%) had another associated disease explaining their uveitis. Among the 23 other patients without identified etiology, 13 had at least one relevant ophthalmological signs predictive of TB uveitis (posterior synechiae, retinal vasculitis and/or choroidal granuloma) (59%). Eleven patients received a 6-month ATT trial. Radiological abnormalities and granulomas at angiography were significantly more frequent among treated patients (p=0.03 and 0.001, respectively). A full OI recovery was observed for 8 patients (73%), considered ex-post as ocular TB. Nine patients in group 2 received rifampicin/isoniazid dual therapy for 3 months, but no conclusion could be drawn as to the benefit of such prescription on OI. QFT rate comparison, according to CD4 stimulation by ESAT-6/CFP-10 peptides or by CD4/CD8 co-stimulation, was comparable and found only 4 cases of discrepancy (1.6%). None of these 4 cases had ocular TB diagnosis. CONCLUSION: Positive QFT frequency among patients consulting for posterior OI remains high. In this study, radiological abnormalities and granulomas at angiography seemed to be more closely related to clinician decision for starting ATT trial in QFT+ patients, which was effective in 73% of cases. QFT-Plus does not seem more relevant than QFT-TB in exploring an OI. Prospective studies are necessary to codify QFT management in the etiological assessment of OI and clearly define ATT trial indications as well as their modalities.

La fibrose rétropéritonéale idiopathique.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibro-inflammatory tissue around the aorta entrapping the adjacent structures. RPF can be idiopathic or secondary to many disorders. The physiopathology is unknown but can be part of the spectrum of IgG4 related diseases. Imaging studies and inflammatory markers are essential for initial evaluation and follow-up. Biopsy is usually not recommended. The first line of treatment is corticosteroids associated or not with immunosuppressive drugs. In case of ureteral obstruction with renal failure, ureteral stent placement or nephrostomies are recommended. Initial response to treatment is usually good but relapses are frequent.

[Review on anti-glomerular basement membrane disease or Goodpasture's syndrome]. / Mise au point sur la maladie des anticorps anti-membrane basale glomérulaire ou syndrome de Goodpasture.

Anti-glomerular basement membrane (anti-GBM) disease or Goodpasture's syndrome is a small vessel vasculitis affecting the capillary beds of kidneys and lungs. It is an autoimmune disease mediated by autoantibodies targeting the glomerular and alveolar basement membranes, leading to pneumorenal syndrome. It is a rare, monophasic and severe disease, associating rapidly progressive glomerulonephritis and alveolar hemorrhage. The presence of antineutrophil cytoplasmic antibodies (ANCA) is reported in 20 to 60% of cases. Management should be prompt and combine plasma exchange with systemic corticosteroids and immunosuppressive therapy by cyclophosphamide. The objective of this review is: 1) to describe the pathogenesis, clinical and histological features of the disease; 2) to characterize double-positive anti-GBM/ANCA patients; 3) to highlight the prognostic factors of renal and global survival, and 4) to focus on the treatment of anti-GBM disease.