RESUMEN
Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.
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Enfermedades Autoinmunes , Trasplante de Células Madre Hematopoyéticas , Esclerodermia Sistémica , Humanos , Acondicionamiento Pretrasplante/métodos , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Trasplante Autólogo , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/terapiaRESUMEN
Autologous haematopoietic stem cell transplantation for systemic scleroderma, developed over more than 25 years, has shown in three randomised controlled clinical trials a significant impact not only in event-free survival, overall survival, cutaneous and pulmonary involvement, but also in the quality of life of patients living with recent severe diffuse cutaneous systemic scleroderma, compared with IV cyclophosphamid despite a transplant-related mortality between 2.4 and 10%. No immunosuppressants or biologics have shown such an impact on mortality in this disease. The risk of relapse is estimated between 9 and 24%, two years after transplant. On the basis of these results, French and international guidelines now position autologous haematopoietic stem cell transplantation as a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma.
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Trasplante de Células Madre Hematopoyéticas , Esclerodermia Sistémica , Humanos , Calidad de Vida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante Autólogo , Esclerodermia Sistémica/tratamiento farmacológicoRESUMEN
BACKGROUND/OBJECTIVES: Idiopathic inflammatory myopathies (IIM) diagnosis and sub-classification can be improved by detection of myositis specific antibodies (MSA) as a first step in diagnosis. However, when using semi-quantitative immunodots for MSA detection, clinical assay performance needs to be improved. METHODS: A retrospective study was done for the "myositis" and "synthetase" immunodots (SRP, NXP2, TIF1gamma, SAE1/2, Mi2, MDA5, Jo1, PL7, PL12, EJ, OJ, KS, ZO and HA) from D-Tek used for 270 patients who had tested positive for MSA in a tertiary laboratory hospital. RESULTS: Results from this analysis revealed: (i) none of the 60 healthy controls presented MSA; (ii) a low assay specificity among patients who tested positive for MSA, 128/270 (47%) were labeled IIM based on the manufacturer's recommended threshold; (iii) in non-IIM patients (53%), the MSA spectrum overlaps predominantly with other autoimmune diseases or idiopathic interstitial lung disease; and (iv) use of a clinical cut-off improves assay specificity for anti-SRP, anti-NXP2, anti-MDA5, anti-Jo1 and anti-PL7 Abs. CONCLUSION: Determining the clinical threshold of the semi-quantitative immunodot assay for MSA is effective for improving its capacity to discriminate IIM from non-IIM and, when IIM diagnosis is excluded, another autoimmune disease or an idiopathic interstitial lung disease should be considered in front of a positive MSA.
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Enfermedades Autoinmunes , Miositis , Autoanticuerpos , Humanos , Miositis/diagnóstico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). METHODS: We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. RESULTS: Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. CONCLUSION: This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.
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Productos Biológicos , Granulomatosis con Poliangitis , Productos Biológicos/uso terapéutico , Granulomatosis con Poliangitis/tratamiento farmacológico , Humanos , Uso Fuera de lo Indicado , Estudios Retrospectivos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis TumoralRESUMEN
INTRODUCTION: TAFRO syndrome is a systemic inflammatory syndrome in the spectrum of Castleman's disease, associating thrombocytopenia, anasarca, fever, renal failure and/or reticulin myelofibrosis and organomegaly. Its association with necrotizing cutaneous vasculitis has not yet been reported. CASE REPORT: A 69-year-old woman presented with weight loss, fever, anasarca, organomegaly, lymphadenopathy, anuria and extensive necrotic livedo occurring after acute diarrhea. Biology showed anemia, thrombocytopenia, renal failure, hypergammaglobulinemia, a circulating B-lymphocyte clone, hypoparathyroidism and autoimmune hypothyroidism. The skin biopsy showed small vessel vasculitis with fibrinoid necrosis. Methylprednisolone infusions associated with tocilizumab were ineffective and the patient became anuric. Rituximab and plasma exchanges associated to corticosteroids allowed remission for 2 months. Combination of rituximab, cyclophosphamide and dexamethasone resulted in a prolonged remission. CONCLUSION: We report here the first case of severe cutaneous necrotizing vasculitis in a patient suffering from TAFRO syndrome. The possible resistance to tocilizumab should be known.
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Enfermedad de Castleman , Vasculitis , Anciano , Enfermedad de Castleman/complicaciones , Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/tratamiento farmacológico , Edema , Femenino , Humanos , Reticulina , Vasculitis/complicaciones , Vasculitis/diagnósticoRESUMEN
BACKGROUND: The objective of the study was to evaluate the indication, efficacy and safety of tocilizumab, a humanized anti-interleukin-6 receptor antibody, in patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated diseases (MOGAD) encountered in current neurological practice. MATERIAL AND METHODS: We conducted a retrospective analysis of an exhaustive cohort of patients with inflammatory CNS disorders at Toulouse University Hospital, France, from 2014 to 2020. Efficacy was evaluated with clinical outcome by the Annual Relapse Rate, and radiological outcome with MRI data. The other outcomes were adverse events and effectiveness according to the form of injection (intravenous or subcutaneous). RESULTS: Seven patients were treated with tocilizumab: four patients had NMOSD with AQP4+ antibodies (57%) and three had MOGAD (43%). Tocilizumab was administered in the presence of persistent clinical activity and/or severe side effects with other immunosuppressant medications. The median follow-up on tocilizumab was 23 months (4-50 months). All patients started with monthly intravenous injection, then three switched to a subcutaneous form. All patients were relapse-free throughout the duration of treatment with tocilizumab, and one presented with a new cervical lesion on MRI. Four patients had no adverse effect, two had a significant increase in infection rate, and one had dyslipidemia. CONCLUSION: tocilizumab appears to be an effective therapy for patients with refractory NMOSD or MOGAD. Subcutaneous and intravenous injections appear to be equally effective.
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Neuromielitis Óptica , Anticuerpos Monoclonales Humanizados , Acuaporina 4 , Autoanticuerpos , Francia , Humanos , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/tratamiento farmacológico , Uso Fuera de lo Indicado , Estudios RetrospectivosRESUMEN
INTRODUCTION: Extramedullary hematopoiesis is a complication of myeloproliferative neoplasms or of chronic hemolysis. The more frequent localizations are splenic, ganglionic or paraspinal. Rarely, extramedullary hematopoiesis is associated with solid cancer. CASE REPORT: We report an original case of sarcoma located in an extramedullary hematopoiesis mass in a 72-year-old woman suffering from hereditary spherocytosis. An asymptomatic right paravertebral mass was found in 2004; the biopsy confirmed extramedullary hematopoiesis. In 2016, the patient was hospitalized due to paravertebral pain. Computed tomography showed the extension of the right paraspinal mass to pleura and mediastinum as well as vertebral bone lysis. Positron emission tomography showed an intense hypermetabolism. The biopsy showed undifferentiated sarcoma. CONCLUSION: This case report illustrates the risk of neoplastic transformation of extramedullary hematopoiesis, and the need for a biopsy when confronted to atypical aspect.
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Hematopoyesis Extramedular/fisiología , Sarcoma/diagnóstico , Esferocitosis Hereditaria/complicaciones , Neoplasias Torácicas/diagnóstico , Anciano , Resultado Fatal , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiología , Sarcoma/etiología , Esferocitosis Hereditaria/diagnóstico , Neoplasias Torácicas/etiologíaRESUMEN
PURPOSE: To evaluate the rate of seasonal influenza vaccination coverage (IVC) in incident giant cell arteritis (GCA) patients compared with controls. METHODS: The vaccination rate was estimated from vaccine dispensation. IVC was compared between GCA and their controls using longitudinal multivariate Poisson regression. RESULTS: During the influenza campaigns from 2005-2006 to 2010-2011, the IVC rates in the GCA group and the control group ranged from 60.8 to 74.7% vs. 56.6 to 70.4%, respectively. Incident GCA influenza vaccination rate was 20% higher than controls (RR=1.20 ; IC 1.09 to 1.32, P<0.001). CONCLUSION: Although suboptimal, IVC in incident GCA was statistically better than controls.
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Arteritis de Células Gigantes/epidemiología , Gripe Humana/prevención & control , Cobertura de Vacunación/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Francia/epidemiología , Humanos , Incidencia , Gripe Humana/epidemiología , Masculino , Estudios Retrospectivos , Factores de Riesgo , Vacunación/normas , Cobertura de Vacunación/normasRESUMEN
INTRODUCTION: Propionibacterium acnes endocarditis is rare and difficult to diagnose. We report a case of Propioniacterium acnes endocarditis revealed by a lower limb fasciitis. CASE REPORT: A 54-year-old patient presented with recurrent febrile myalgia of the lower limbs, that appeared three years after an aortic surgery (aortic valve sparing reimplentation and ascending aortic prosthesis implantation). Computer tomography showed fasciitis of both legs. Positron emission tomography showed 18Fluorodeoxyglucose intake of the aortic prosthesis and in muscles of the lower limbs. Ten days after blood sample drawing, cultures showed the presence of Propionibacterium acnes. The aortic prosthesis was surgically removed, whose culture confirmed infection by Propionibacterium acnes. The diagnosis of infective endocarditis revealed by lower limb emboli was made. Evolution was favorable. CONCLUSION: In patients with vascular prostheses, Propionibacterium acnes infection must be evoked face to an atypical inflammatory process. Very prolonged blood culture incubation is needed to identify the pathogen.
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Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/microbiología , Infecciones por Bacterias Grampositivas/diagnóstico , Propionibacterium acnes , Endocarditis Bacteriana/complicaciones , Fiebre/etiología , Infecciones por Bacterias Grampositivas/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Mialgia/etiologíaAsunto(s)
Codificación Clínica/estadística & datos numéricos , Bases de Datos Factuales/estadística & datos numéricos , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Hospitales , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. RESULTS: 125 patients, 99â¯GPA (79,2%) and 26â¯MPA (20,8%), were followed 88.4⯱â¯78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.
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Enfermedad de la Arteria Coronaria/epidemiología , Granulomatosis con Poliangitis/epidemiología , Isquemia/epidemiología , Poliangitis Microscópica/epidemiología , Accidente Cerebrovascular/epidemiología , Enfermedad Aguda , Anciano , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Granulomatosis con Poliangitis/mortalidad , Humanos , Isquemia/mortalidad , Masculino , Poliangitis Microscópica/mortalidad , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Accidente Cerebrovascular/mortalidad , Análisis de SupervivenciaAsunto(s)
Linfadenitis Necrotizante Histiocítica/diagnóstico , Ganglios Linfáticos/patología , Adolescente , Diagnóstico Diferencial , Edema/etiología , Párpados , Femenino , Fiebre/etiología , Glucocorticoides/uso terapéutico , Linfadenitis Necrotizante Histiocítica/tratamiento farmacológico , Humanos , LabioRESUMEN
Postural tachycardia syndrome (PoTS) is a multifactorial syndrome defined by an increase in heart rate ≥30bpm, within 10minutes of standing (or during a head up tilt test to at least 60°), in absence of orthostatic hypotension. It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve in supine position. Patients have an intense fatigue with a high incidence on quality of life. This syndrome can be explained by many pathophysiological mechanisms. It can be associated with Ehlers-Danlos disease and some autoimmune disorders. The treatment is based on nonpharmacological measures and treatment with propranolol, fludrocortisone or midodrine.
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Síndrome de Taquicardia Postural Ortostática , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/fisiopatología , Síndrome de Ehlers-Danlos/complicaciones , Síndrome de Ehlers-Danlos/epidemiología , Síndrome de Ehlers-Danlos/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Síndrome de Taquicardia Postural Ortostática/epidemiología , Síndrome de Taquicardia Postural Ortostática/etiología , Síndrome de Taquicardia Postural Ortostática/fisiopatología , Postura/fisiología , Calidad de VidaAsunto(s)
Antirreumáticos/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Miocarditis/etiología , Enfermedad de Still del Adulto/tratamiento farmacológico , Adulto , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Miocarditis/tratamiento farmacológico , Enfermedad de Still del Adulto/complicacionesAsunto(s)
Dolor Abdominal/etiología , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Riñón/diagnóstico por imagen , Postura/fisiología , Dolor Abdominal/patología , Adulto , Femenino , Humanos , Riñón/patología , Enfermedades Renales/patología , Prolapso , Urografía/métodosAsunto(s)
Azatioprina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dedos , Poliarteritis Nudosa , Prednisona/administración & dosificación , Arteria Radial/diagnóstico por imagen , Arteria Cubital/diagnóstico por imagen , Anciano , Angiografía/métodos , Femenino , Dedos/irrigación sanguínea , Dedos/patología , Humanos , Inmunosupresores/administración & dosificación , Masculino , Microaneurisma/diagnóstico por imagen , Microaneurisma/etiología , Persona de Mediana Edad , Necrosis , Poliarteritis Nudosa/complicaciones , Poliarteritis Nudosa/diagnóstico , Poliarteritis Nudosa/tratamiento farmacológico , Poliarteritis Nudosa/fisiopatología , Inducción de Remisión , Ultrasonografía Doppler/métodosRESUMEN
Objective The objective of this study was to assess the safety and efficacy of abatacept in patients with SLE refractory to conventional treatment in routine clinical practice. Methods This retrospective study included 11 SLE patients treated with abatacept for an active and refractory disease. The primary endpoint was the change in SLE Disease Activity Index (SLEDAI) score at six months. Response was defined as a decrease of SLEDAI ≥4 in a patient continuing abatacept. Results Indications of abatacept treatment were articular ( n=8), renal ( n=1) and cutaneous ( n=1) involvement and autoimmune thrombocytopenia ( n=1). Abatacept was discontinued before six months in two patients, because of adverse event ( n=1) and/or lupus flare ( n=2). The median SLEDAI decreased from 6 (2-20) to 4 (0-20) ( p=0.031). Decrease of SLEDAI ≥4 was observed in 6/11 patients (55%) and response to treatment according to the physician's judgement in 8/11 (73%) patients. Improvement of articular involvement was observed in 7/8 (87.5%) patients. Four adverse events were observed in three patients, but no severe infection occurred. Conclusion This study suggests some efficacy of abatacept in patients with refractory disease in routine clinical practice, particularly in the case of articular manifestations, with an acceptable safety profile. These data support conducting new controlled trials of abatacept in SLE patients.
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Abatacept/administración & dosificación , Inmunosupresores/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Abatacept/uso terapéutico , Adulto , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
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.