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BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA. OBJECTIVE: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA. METHODS: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose. RESULTS: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines. CONCLUSION: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity.
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Artritis Reumatoide , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Masculino , Brasil/epidemiología , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/complicaciones , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , ChAdOx1 nCoV-19/efectos adversos , Estudios Prospectivos , Adulto , SARS-CoV-2/inmunología , Anciano , Cefalea/inducido químicamente , Cefalea/etiología , Mialgia/inducido químicamente , Mialgia/etiología , Artralgia/etiología , Vacunas de Productos InactivadosRESUMEN
Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition.
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Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedades Raras , Inmunoglobulina G/sangreRESUMEN
Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of six patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (Pâ =â 0.031 and Pâ =â 0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (Pâ =â 0.016 and Pâ =â 0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T-cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rhoâ =â -0.610 and rhoâ =â -0.463, respectively) and with Th17 cells (rhoâ =â -0.365 and rhoâ =â -0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet, and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.
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Aorta , Linfocitos T CD4-Positivos , Subgrupos de Linfocitos T , Arteritis de Takayasu , Humanos , Arteritis de Takayasu/inmunología , Arteritis de Takayasu/sangre , Femenino , Adulto , Masculino , Aorta/inmunología , Aorta/patología , Linfocitos T CD4-Positivos/inmunología , Subgrupos de Linfocitos T/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Persona de Mediana Edad , Factor de Transcripción GATA3/metabolismo , Proteínas de Dominio T Box/metabolismo , Células Th17/inmunología , Adulto Joven , Estudios Longitudinales , Células Th2/inmunología , Células TH1/inmunologíaRESUMEN
OBJECTIVES: To evaluate common femoral vein thickness (CFVT) as a diagnostic tool in Brazilian patients with Behçet's disease (BD) and to analyse associations between increased CFVT and disease features. METHODS: A cross-sectional study was performed including 100 BD patients and 100 controls. The CFVT and the diameters of great saphenous vein (GSV), and small saphenous vein (SSV) were measured by Doppler ultrasound. RESULTS: BD patients had higher right CFVT [0.600mm (0.500-0.700) vs. 0.525mm (0.450-0.637); p=0.012] and left CFVT [0.550mm (0.450-0.650) vs. 0.500mm (0.450-0.550); p=0.004] compared to controls. Vascular involvement of BD and previous deep venous thrombosis were associated with increased CFVT (p<0.05). The number of vascular events correlated with right and left CFVT (Rho = 0.475 p=0.030 and Rho = 0.429 p=0.052, respectively). The 0.575mm cut-off point of right and left CFVT had area under the curve (AUC) of 0.602; 95% confidence interval (95% CI): 0.524-0.680 and AUC: 0.615; 95% CI: 0.537-0.693, respectively. The right and left CFVT had a sensitivity for BD diagnosis of 52% and 43%, and a specificity of 64% and 77%, respectively. No significant differences were found between BD patients and controls regarding the GSV and SSV diameters in both legs (p>0.05). CONCLUSIONS: In this study, CFVT measurement was not shown to be a reliable diagnostic test for BD. CFVT was increased in BD patients presenting vascular involvement and correlated with the number of previous events.
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OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.
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Síndrome de Behçet , Úlceras Bucales , Niño , Humanos , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamiento farmacológico , Úlceras Bucales/etiología , Úlceras Bucales/tratamiento farmacológico , Estudios Transversales , Inmunosupresores/uso terapéutico , Árboles de DecisiónRESUMEN
OBJECTIVE: The aim of this study was to analyze HLA alleles in patients with Behçet disease (BD) and their correlation with ophthalmic manifestations (OMs) in a multiethnic Brazilian population. METHODS: This case-control study compared 72 BD patients with or without OM who underwent a thorough ophthalmologic evaluation, including best-corrected visual acuity, bino-ophthalmoscopy, and HLA analysis, with 144 matched healthy controls. Fluorescein angiography was also performed in the patients with BD and OM. HLA class I (A, B, and C) and II (DRB1, DQB1, and DQA1) typing were performed using PCR-SSO. RESULTS: Of 72 patients with BD, 42 (58%) had OM. The HLA-B*51 and -A*26 alleles were more frequent in patients with BD than in controls (23.6% vs 14.6% and 12.5% vs 4.3%, respectively), but could not differentiate OM risk. The HLA alleles of BD patients that differentiated those with and without OM were HLA-B*15 (40.5% vs 20.7%; odds ratio [OR], 2.59; p = 0.0059), HLA-C*02 (33.3% vs 13.4%; OR, 3.20; p = 0.0024), and HLA-DQB1*03 (64.3% vs 45.7%, p = 0.017), whereas HLA-A*03 (0.0% vs 13.3%, p = 0.006) and HLA-DRB1*15 (4.8% vs 19.5%; OR, 0.21; p = 0.0121) were protective against OM. CONCLUSIONS: In this study of a Brazilian multiethnic BD population, alleles were similar between groups of BD patients with and without OM. We described HLA-B*15, -C*02, and -DQB1*03 as risk factors and -A*03 and -DRB1*15 as protective factors for OM in BD, which could function as biomarkers for predicting disease phenotypes.
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Síndrome de Behçet , Humanos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/genética , Alelos , Estudios de Casos y Controles , Factores de Riesgo , Brasil/epidemiologíaRESUMEN
BACKGROUND: Giant cell arteritis (GCA) is the most common primary systemic vasculitis in people 50 years of age and over, and it is considered a medical emergency due to the potential risk of permanent visual loss. Color Doppler ultrasound (CDU) of the temporal arteries is a rapid, noninvasive method to diagnose GCA. This study aims to determine the diagnostic accuracy of the halo sign in temporal arteries by CDU in people with suspected GCA. METHODS: The systematic literature review included the search for publications in the following electronic databases: PubMed, Embase, CENTRAL, LILACS, WHO ICTRP, ClinicalTrials.gov, gray literature up to December 2022, and no date or language restrictions were applied. We analyzed studies including patients over 50 years of age with suspected GCA evaluating CDU of temporal arteries as a diagnostic tool against clinical diagnosis as a standard reference. Paper titles and abstracts were selected by two investigators independently for all available records. The quality of the studies was assessed using the Quality of Diagnostic Accuracy Studies tool (QUADAS-2) and the R software (version 4.2.1) was used for data analysis. The protocol of this review is registered with PROSPERO (CRD42016033079). RESULTS: Twenty-two studies including 2893 participants with suspected GCA who underwent temporal artery CDU were evaluated. The primary analysis results showed a sensitivity of 0.76 [95% confidence interval (95 CI) 0.69-0.81] and specificity of 0.93 (95 CI 0.89-0.95) when the halo sign was compared to clinical diagnosis. The sensitivity value of 0.84 (95 CI 0.72-0.92) and specificity of 0.95 (95 CI 0.88-0.98) were found in five studies involving 1037 participants that analyzed the halo sign and temporal artery compression sign. A sensitivity of 0.86 (95 CI 0.78-0.91) and specificity of 0.95 (95 CI 0.89-0.98) were found in four studies with 603 participants where the halo sign was evaluated CDU on temporal and axillary arteries. CONCLUSION: The detection of the halo sign by CDU of temporal arteries has good accuracy for the diagnosis of cranial GCA. The compression sign in temporal arteries and the addition of axillary arteries assessment improves the diagnostic performance of CDU for GCA. TRIAL REGISTRATION: PROSPERO CRD42016046860.
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Arteritis de Células Gigantes , Humanos , Persona de Mediana Edad , Arteritis de Células Gigantes/diagnóstico por imagen , Sensibilidad y Especificidad , Arterias Temporales/diagnóstico por imagen , Ultrasonografía/métodos , Ultrasonografía Doppler en Color/métodosRESUMEN
BACKGROUND: Modifiable cardiovascular risk factors (MCRFs), such as those related to aerobic capacity, muscle strength, physical activity, and body composition, have been poorly studied in Takayasu arteritis (TAK). Therefore, the aim of the study was to investigate MCRFs and their relationships with disease status and comorbidities among patients with TAK. METHODS: A multicenter cross-sectional study was conducted between 2019 and 2020, in which 20 adult women with TAK were compared with 16 healthy controls matched by gender, age, and body mass index. The following parameters were analyzed: aerobic capacity by cardiopulmonary test; muscle function by timed-stands test, timed up-and-go test, and handgrip test; muscle strength by one-repetition maximum test and handgrip test; body composition by densitometry; physical activity and metabolic equivalent by IPAQ, quality of life by HAQ and SF-36; disease activity by ITAS2010 and NIH score; and presence of comorbidities. RESULTS: Patients with TAK had a mean age of 41.5 (38.0-46.3) years, disease duration of 16.0 (9.5-20.0) years, and a mean BMI of 27.7±4.5 kg/m2. Three out of the 20 patients with TAK had active disease. Regarding comorbidities, 16 patients had systemic arterial hypertension, 11 had dyslipidemia, and two had type 2 diabetes mellitus, while the control group had no comorbidities. TAK had a significant reduction in aerobic capacity (absolute and relative VO2 peak), muscle strength in the lower limbs, increased visceral adipose tissue, waist-to-hip ratio, reduced walking capacity, decreased weekly metabolic equivalent, and quality of life (P< 0.05) as compared to controls. However, there were no correlations between these MCRFs parameters and disease activity. CONCLUSIONS: TAK show impairment in MCRFs; therefore, strategies able to improve MCRF should be considered in this disease.
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Factores de Riesgo de Enfermedad Cardiaca , Arteritis de Takayasu/fisiopatología , Adulto , Factores de Edad , Índice de Masa Corporal , Capacidad Cardiovascular/fisiología , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Dislipidemias/epidemiología , Femenino , Fuerza de la Mano/fisiología , Humanos , Hipertensión/epidemiología , Persona de Mediana Edad , Actividad Motora/fisiología , Fuerza Muscular , Consumo de Oxígeno , Calidad de Vida , Factores de Riesgo , Factores Sexuales , Arteritis de Takayasu/epidemiologíaRESUMEN
Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X-linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease-specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost-effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.
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Exoma , Enfermedades Raras , Niño , Estudios de Cohortes , Consanguinidad , Exoma/genética , Femenino , Humanos , Embarazo , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Secuenciación del ExomaRESUMEN
BACKGROUND/OBJECTIVE: The epidemiology of vasculitis is variable in different geographic areas, and this issue has not been approached in Brazil yet. The objective of this study was to assess the frequency of vasculitis in specialized centers in Brazil. METHODS: This cross-sectional study was performed in 9 vasculitis outpatient clinics from 6 different states mainly from the Southeast and the Northeast regions of Brazil between 2015 and 2017. Diagnosis and/or classification criteria for Behçet disease (BD), Takayasu arteritis (TA), giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and cryoglobulinemic vasculitis (CryoVas) were used to include patients with at least 6 months of follow-up in this hospital-based survey. RESULTS: A total of 1233 patients with systemic vasculitis were included from the Southeast region. Behçet disease was the most frequent vasculitis (35.0%) followed by TA (26.4%), GPA (16.2%), PAN (5.8%), GCA (5.8%), EGPA (4.3%), MPA (3.4%), and CryoVas (3.0%). Up to 7.8% of vasculitis patients had a juvenile onset, and the frequency of vasculitides found in children and adolescents was as follows: TA (52.6%), BD (24.7%), GPA (12.4%), and PAN (10.3%). No cases of EGPA, MPA, and CryoVas were diagnosed before the age of 18 years. As a comparator, 103 vasculitis patients were included in the Northeast of Brazil where TA was found in 36.9% and BD in 31.1% of vasculitis cases. No GCA cases were found in the Northeast part of Brazil. CONCLUSIONS: Similar to the epidemiology of vasculitis in Asia, BD and TA are the most frequent vasculitis in Southeastern Brazilian referral centers.
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Síndrome de Churg-Strauss , Granulomatosis con Poliangitis , Adolescente , Brasil/epidemiología , Niño , Estudios Transversales , Hospitales , HumanosRESUMEN
BACKGROUND: Endothelial progenitor cells (EPCs) are responsible for endothelial damage repair. Takayasu's arteritis (TA) is a chronic inflammatory disease that affects large vessels. The aim of the study was to evaluate the number of EPCs and the levels of vascular endothelial growth factor (VEGF) and the relationship of these variables in patients with TA. METHODS: Thirty women with TA and 30 healthy controls were included. EPCs were assessed by flow cytometry and cell culture and VEGF quantification was performed by commercial ELISA kits. RESULTS: Ages of patients and controls were similar. The number of EPCs in patients and controls (median (interquartile range) were 0.0073% (0.0081%) vs. 0.0062% (0.0089%), p = 0.779 by flow cytometry and 27.0 (42.3) colony forming units (CFUs) vs. 27.0 (20.5) CFUs, p = 0.473 by cells culture, respectively. VEGF levels in patients and controls was 274.5 (395.5) pg/ml vs. 243.5 (255.3) pg/ml, p = 0.460. There was no difference in the number of EPCs and VEGF level between patients with active and inactive disease. There was a tendency of the number of angioblast-like EPCs in patients taking anti-TNFs to be higher; and in patients using methotrexate to be lower. CONCLUSION: No significant difference was found in the quantification of EPCs and VEGF levels in TA patients compared to controls, and no difference was observed between patients with active and inactive disease.
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Células Progenitoras Endoteliales/citología , Arteritis de Takayasu/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Antiinflamatorios/administración & dosificación , Brasil , Estudios de Casos y Controles , Recuento de Células , Estudios Transversales , Células del Cúmulo , Células Progenitoras Endoteliales/clasificación , Femenino , Citometría de Flujo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Leflunamida/uso terapéutico , Persona de Mediana Edad , Monocitos/clasificación , Monocitos/citología , Prednisona/administración & dosificación , Células Madre , Arteritis de Takayasu/dietoterapia , Arteritis de Takayasu/patología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
BACKGROUND: Studies have suggested that soluble factors in plasma from patients with active (aBD) and inactive (iBD) Behçet's disease (BD) stimulate neutrophil function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation in BD. Its expression and effect on neutrophil oxidative burst and neutrophil extracellular trap (NET) release have not been characterized. In this study, we sought to investigate the role of plasma and the CD40L pathway on NET release and the oxidative burst profile in patients with aBD and iBD. METHODS: Neutrophils and peripheral blood mononuclear cells (PBMCs) were obtained from patients with aBD (n = 30), patients with iBD (n = 31), and healthy control subjects (HCs; n = 30). sCD40L plasma concentration was determined in individual samples. A pool of plasma for each group was created. In some experiments, plasma pools were treated with recombinant CD40 (rhCD40-muIg) for sCD40L blockade. NET release and H2O2/O2- production were determined after stimulation with phorbol 12-myristate 13-acetate, sCD40L, or plasma pool. Flow cytometric analysis was performed to evaluate the expression of (1) CD40, Mac-1, and phosphorylated NF-κB p65 on neutrophils and monocytes and (2) CD40L on activated T cells and platelets. CD40L gene expression in PBMCs was determined by qRT-PCR. RESULTS: sCD40L plasma levels were significantly higher in patients with iBD (median 17,234, range 2346-19,279 pg/ml) and patients with aBD (median 18,289, range 413-19,883 pg/ml) than in HCs (median 47.5, range 33.7-26.7 pg/ml; p < 0.001). NET release was constitutively increased in BD compared with HC. NET release and H2O2/O2- were higher after stimulation with sCD40L or BD plasma and decreased after sCD40L blockade. Mac-1 expression was constitutively increased in neutrophils of patients with aBD (88.7 ± 13.2% of cells) and patients with iBD (89.2 ± 20.1% of cells) compared with HC (27.1 ± 18.8% of cells; p < 0.01). CD40 expression on phagocytes and CD40L expression on platelets were similar in the three groups. PBMCs as well as nonactivated and activated CD4+ T cells from patients with BD showed higher CD40L expression. CONCLUSIONS: Plasma from patients with aBD exerts a stimulus on NET release and oxidative burst, probably induced by sCD40L.
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Síndrome de Behçet/sangre , Síndrome de Behçet/inmunología , Ligando de CD40/sangre , Activación Neutrófila/fisiología , Estallido Respiratorio/fisiología , Adulto , Trampas Extracelulares/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Takayasu arteritis (TA) is a rare systemic vasculitis that affects large vessels often resistant to treatment and associated with high morbidity and mortality. Treatment is defied by the relapsing nature of the disease and frequent adverse effects of corticosteroids and immunosuppressors, rendering failure of treatment in a significant portion of patients. Considering the low quantity and quality of published studies focusing on treatment of TA, synthesis and critical assessment of the available evidence is fundamental to establish recommendations for clinical practice. OBJECTIVE: To evaluate the effectiveness and safety of clinical interventions for TA. METHODS: Systematic review conducted in accordance to recommendations stated in the Cochrane Handbook, with inclusion of all comparative studies focusing on any type of clinical intervention for TA. RESULTS: Five comparative studies were included (one randomised clinical trial, two non-randomised clinical trials, and two historical cohorts) totalling 342 patients, aiming at the assessment of effectiveness of corticosteroids, immunosuppressors, biologics and other types of pharmacological treatment for distinct clinical presentations of TA. The quality of studies, assessed by the use of instruments developed specifically for each study design, was considered low. Data scarcity and clinical heterogeneity prevented quantitative synthesis (meta-analysis). CONCLUSION: Despite an extensive literature search, few comparative studies with small sample sizes were retrieved. The quality of these studies was considered low, preventing recommendations on effectiveness and safety of the studied interventions for clinical practice. Until new comparative studies with more robust sample sizes are conducted, treatment of TA should be guided individually taking into account the severity of disease and the availability of treatment options.
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Corticoesteroides/uso terapéutico , Inmunosupresores/uso terapéutico , Arteritis de Takayasu/tratamiento farmacológico , Productos Biológicos/uso terapéutico , HumanosRESUMEN
There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.
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Biomarcadores/sangre , Quimiocinas/inmunología , Citocinas/inmunología , Arteritis de Takayasu/inmunología , HumanosRESUMEN
BACKGROUND: Macrophages may present two distinct phenotypes indicated as M1 and M2 under different stimuli. M1 and M2 macrophages have divergent functions that range from enhancement of inflammation for M1 to tissue repair and remodeling for M2 macrophages. The objective of this study was to evaluate the distribution of M1 and M2 macrophage phenotypes in biopsies from the airways of patients with active granulomatosis with polyangiitis (GPA) and to analyze their associations with T and B cells in those biopsies, and with nasal carriage of Staphylococcus aureus, disease parameters and therapy. METHODS: Consecutive GPA patients (n = 35) with active airway disease, who underwent respiratory tract biopsy were included. Immunohistochemical evaluation was performed to assess the distribution of macrophages and T and B cells using the markers CD68, CD3 and CD20, respectively. CD86 was used as the M1 marker and CD163 as the M2 marker while Tbet and GATA-3 were used as Th1 and Th2 markers, respectively. At the time of the biopsy patients were assessed for nasal carriage of Staphylococcus aureus and treatment. RESULTS: Percentages of macrophages and T cells were significantly higher than those of B cells in lesional tissue from the respiratory tract in GPA. M2 macrophages and Th2 cells were more frequent than M1 macrophages (p = 0.0007) and Th1 cells (p < 0.0001), respectively. Percentages of T cells were higher in nose biopsies than in biopsies from other sites (p = 0.021); macrophages and CD163+ macrophages were more predominant in biopsy sites other than the nose (p = 0.039 and p = 0.012, respectively). Carriage of Staphylococcus aureus was associated with higher T cell scores (p = 0.014). The frequency of macrophages, especially M2 macrophages, was higher in GPA patients treated with immunosuppressive agents (p = 0.010); daily prednisolone dose was positively correlated with all macrophage markers. However, in multivariate analysis no independent associations were found between disease parameters and therapy with macrophage markers or T cells. CONCLUSION: In GPA, M2 is the predominant macrophage phenotype in the respiratory tract. Although some associations were observed between macrophages and T cells with therapy and nasal carriage of Staphylococcus aureus, they were not independently significant in multivariate analysis.
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Granulomatosis con Poliangitis/patología , Macrófagos/patología , Fenotipo , Sistema Respiratorio/patología , Adulto , Femenino , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/inmunología , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/inmunologíaRESUMEN
Primary central nervous system vasculitis (PCNSV) is a challenging diagnosis due to broad clinical manifestations and variable specificity and sensitivity of laboratory and imaging diagnostic tools. Differential diagnosis includes reversible cerebral vasoconstriction syndrome (RCVS), secondary vasculitis of the CNS and other noninflammatory vasculopathies. Brain biopsy is essential for definitive diagnosis and to exclude mimickers. Recent data show that data large-vessel PCNSV present worse prognosis when compared to small-vessel PCNSV. Herein we review diagnosis and management of PCNSV, secondary vasculitis of CNS and RCVS.
Asunto(s)
Vasculitis del Sistema Nervioso Central/diagnóstico , Adulto , Diagnóstico Diferencial , HumanosRESUMEN
OBJECTIVE: To evaluate the extended follow-up data on efficacy and toxicity of leflunomide therapy in Takayasu arteritis (TA) patients previously enrolled in the original open-label study of short-term effects of leflunomide in TA. METHODS: An open-label long-term longitudinal study was performed in TA patients who fulfilled the 1990 American College of Rheumatology criteria for TA and had participated in a previous study that evaluated short-term efficacy of leflunomide in TA. Complete follow-up information could be retrieved from 12 out of 15 patients enrolled in the original study. Disease activity was evaluated by Kerr's criteria and by the Indian Takayasu Activity Score 2010 (ITAS2010). RESULTS: The mean follow up time was 43.0±7.6 months and 5 (41.6%) TA patients remained on leflunomide therapy while 7 (58.3%) TA patients had to change to another therapy due to failure to prevent relapses in 6 patients and toxicity in one patient. No significant differences were found between patients who remained on leflunomide therapy and those who changed to another agent regarding age at study entry, time since diagnosis, prednisone daily dose at study entry, baseline ITAS2010, mean or maximum ESR and CRP, and cumulative prednisone dose at study end. Among TA patients who had changed leflunomide to another agent, two had an additional clinical relapse and needed to change therapy. CONCLUSION: Leflunomide led to sustained remission in approximately half of patients at a mean time of 12 months and was well tolerated by TA patients.
Asunto(s)
Isoxazoles/uso terapéutico , Arteritis de Takayasu/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Leflunamida , Estudios Longitudinales , Prednisona , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the extended follow-up data on efficacy and toxicity of leflunomide therapy in Takayasu arteritis (TA) patients previously enrolled in the original open-label study of short-term effects of leflunomide in TA. METHODS: An open-label long-term longitudinal study was performed in TA patients who fulfilled the 1990 American College of Rheumatology criteria for TA and had participated in a previous study that evaluated short-term efficacy of leflunomide in TA. Complete follow-up information could be retrieved from 12 out of 15 patients enrolled in the original study. Disease activity was evaluated by Kerr's criteria and by the Indian Takayasu Activity Score 2010 (ITAS2010). RESULTS: The mean follow up time was 43.0±7.6 months and 5 (41.6%) TA patients remained on leflunomide therapy while 7 (58.3%) TA patients had to change to another therapy due to failure to prevent relapses in 6 patients and toxicity in one patient. No significant differences were found between patients who remained on leflunomide therapy and those who changed to another agent regarding age at study entry, time since diagnosis, prednisone daily dose at study entry, baseline ITAS2010, mean or maximum ESR and CRP, and cumulative prednisone dose at study end. Among two TA patients who had changed laflunomide to another agent, two had a clinical relapse and needed to change therapy. CONCLUSION: Leflunomide led to sustained remission in approximately half of patients at a mean time of 12 months and was well tolerated by TA patients.
RESUMEN
Takayasu arteritis (TA) is a chronic large vessel vasculitis that affects aorta, its main branches and pulmonary arteries. The inflammatory process results in stenosis, occlusion, dilation or aneurysm formation in the arterial wall. TA has been described in different parts of the world and affects predominantly young individuals (<50 years of age). Patients with TA may present constitutional symptoms, vascular pain (e.g. carotidynia) and typical features such as limb claudication, decreased or absent peripheral pulses, vascular bruits, hypertension, and reduction or discrepancies in blood pressure between arms. A proper diagnosis of TA is an important issue since delays may result in significant morbidity. The definition of TA was included in the 1994 and 2012 Chapel Hill Consensus Conference and TA was categorized as a large vessel vasculitis. The first diagnostic criteria for TA were developed by Ishikawa in 1988 and modified by Sharma et al., in 1995. Two sets of classification criteria were developed for TA to include patients in epidemiologic studies and clinical trials: the 1990 ACR Classification Criteria for TA and the Classification Criteria for childhood TA proposed by the European League Against Rheumatism (EULAR), the Pediatric Rheumatology European Society (PRES) and by the Pediatric Rheumatology International Trials Organization (PRINTO) to be used for patients younger than 18 years. The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) is an international effort that is under way to develop a single classification system and a validated set of diagnostic criteria for systemic vasculitides using data-driven methods.