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OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.
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Imunossupressores , Nefrite Lúpica , Sociedades Médicas , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Brasil , Creatinina/sangue , Proteinúria/diagnóstico , Proteinúria/etiologia , Ácido Micofenólico/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Reumatologia/normas , Rituximab/uso terapêutico , Biópsia , Ciclofosfamida/uso terapêutico , Leflunomida/uso terapêutico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico , Azatioprina/uso terapêutico , Indução de Remissão , Ciclosporina/uso terapêutico , Medicina Baseada em Evidências , Consenso , Progressão da Doença , Falência Renal Crônica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Inflammatory T lymphocyte cytokines contribute to tissue damage in SLE patients. Vitamin D (Vit D) has a well-established immunomodulatory action, but few studies have addressed the effect of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) on peripheral blood mononuclear cells (PBMCs) in SLE patients. The aim of this study was to evaluate the immnunomodulatory effect of 1,25 (OH)2D3 on T lymphocyte-related cytokines. Blood from 27 female SLE patients was collected for PBMC isolation and anti-DNA, complement, and serum 25 (OH)D3 level measurements. PBMCs were stimulated with anti-CD3/anti-CD28 in the presence or absence of dexamethasone or various concentrations of 1,25 (OH)2D3 for 48 h. We assessed IL-17A, IL-22, IL-21, IL-9, IFN-γ, IL-4, IL-10, IL-2, IL-6, and TNF by cytometric bead assay (CBA) and enzyme immune assay (ELISA) on culture supernatant. The mean age of patients was 36.2 (± 10.5 years) and the median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 4 (0-6). The addition of 1,25 (OH)2D3 in PBMC culture reduced IL-17 A, IL-22, IL-9, and IFN-γ levels at 100 nM (p ≤ 0.0001). Furthermore, the addition of 1,25 (OH)2D3 at all concentrations increased IL-4 (p ≤ 0.0006), and 0.1 and 1 nM increased IL-10 (p ≤ 0.0004) and 0.1 nM increased IL-2 levels (p ≤ 0.0001). There was no difference regarding IL-21 and TNF levels. The addition of 1,25 (OH)2D3 in PBMC culture presented an inhibitory effect on proinflammatory cytokines and increased immunoregulatory cytokines in SLE patients, suggesting the beneficial effect of this vitamin.
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Citocinas , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Interleucina-10/farmacologia , Leucócitos Mononucleares , Interleucina-2/farmacologia , Interleucina-4/farmacologia , Interleucina-9 , Linfócitos T , Vitamina D/farmacologia , Vitaminas , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
BACKGROUND/OBJECTIVES: Endothelial dysfunction and reduced number of endothelial progenitor cells (EPCs) in peripheral blood are contributing factors to cardiovascular disease in systemic lupus erythematosus (SLE) patients. Endothelial progenitor cell proliferation is regulated by vascular endothelial growth factor (VEGF). Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality in patients with coronary heart disease. METHODS: This was a randomized trial including 37 female SLE patients without cardiovascular risk factors allocated into 2 groups: 19 patients received ramipril 10 mg/d for 12 weeks (IG) and 18 patients maintained without ramipril (CG). Endothelial function was assessed by brachial artery ultrasound measuring flow-mediated dilation, and EPCs were quantified by flow cytometry and cell culture, at baseline and after 12 weeks. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Statistical analysis was intention to treat. p < 0.05 was considered significant. RESULTS: After 12 weeks, higher flow-mediated dilation (6.17% vs. 11.14%, p < 0.001) was observed in IG, without change in CG (5.37% vs. 5.02%, p = 0.630). Higher number of EPC colony-forming units was also observed in IG (21.3 ± 10.4 vs. 31.6 ± 8.5, p < 0.001), without difference in CG ( p = 0.714). No difference was found in EPCs evaluated by flow cytometry. Vascular endothelial growth factor level increased after 12 weeks in IG ( p = 0.048), with no difference in CG ( p = 0.661). CONCLUSION: Ramipril improved endothelial function and increased the numbers of EPCs evaluated by cell culture and VEGF levels in SLE patients without cardiovascular risk factors. These data suggest that angiotensin-converting enzyme inhibitor bring an extra benefit beyond the hypotensive action and should be considered as a preferred antihypertensive drug in SLE patients.
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Células Progenitoras Endoteliais , Lúpus Eritematoso Sistêmico , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos , Endotélio Vascular/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ramipril/metabolismo , Ramipril/farmacologia , Ramipril/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Little is known about the epidemiology of systemic vasculitis in South American countries. The aim of this study is to compare the prevalence of systemic vasculitides in two vasculitis referral centers from Brazil and Peru. A cross-sectional study was performed and all patients above 18 years of age, with at least 6 months of follow-up and who met classification or diagnosis criteria for the most common forms of vasculitis, were included. A total of 562 patients with systemic vasculitis were analyzed, 345 (61.4%) from Brazil and 217 (38.6%) from Peru. The frequency of Behçet's disease (37.9% vs. 1.8%; p < 0.0001), Takayasu arteritis (TAK) (25.2% vs. 6.9%; p < 0.0001), and giant cell arteritis (9.8% vs. 0.9%; p < 0.0001) was higher in the Brazilian center than the Peruvian one. On the other hand, the frequency of microscopic polyangiitis (MPA) (67.3% vs. 2.8%; p < 0.0001) and renal-limited vasculitis (2.8% vs. 0.0%; p = 0.009) was higher in the Peruvian center. No differences were found concerning other forms of vasculitis. At diagnosis, Brazilian patients with TAK, granulomatosis with polyangiitis, and MPA were younger than Peruvian patients. Epidemiologic differences in the frequency of systemic vasculitis are observed between a vasculitis referral center from Brazil and another from Peru. Key Points ⢠Significant differences are observed regarding the epidemiologic profile of systemic vasculitis between Brazil and Peru. ⢠MPA is the predominant form of vasculitis in Peru while BD and TAK are the most frequent forms of vasculitis in Brazil. ⢠The age at diagnosis of TAK, MPA, and GPA was lower in Brazilian patients than in Peruvian patients.
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Poliangiite Microscópica , Vasculite Sistêmica , Brasil/epidemiologia , Estudos Transversais , Humanos , Lactente , Poliangiite Microscópica/epidemiologia , Peru/epidemiologia , Encaminhamento e Consulta , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/epidemiologiaRESUMO
BACKGROUND: Acute transverse myelitis (ATM) is an infrequent but severe complication of systemic lupus erythematosus (SLE). The purpose of study was to describe clinical features and prognostic factors of patients with SLE-related ATM. METHODS: In this medical records review study, data were collected from 60 patients from 16 centers seen between 1996 and 2017 who met diagnostic criteria for SLE and myelitis as defined by the American College of Rheumatology/Systemic International Collaborating Clinics and the Working Group of the Transverse Myelitis Consortium, respectively. Objective neurological impairment was measured with American Spinal Injury Association Impairment Scale (AIS) and European Database for Multiple Sclerosis Grade Scale (EGS). RESULTS: Among patients included, 95% (n = 57) were female, and the average age was 31.6 ± 9.6 years. Myelitis developed after diagnosis of SLE in 60% (n = 36). Symmetrical paraparesis with hypoesthesia, flaccidity, sphincter dysfunction, AIS = A/B, and EGS ≥ 8 was the most common presentation. Intravenous methylprednisolone was used in 95% (n = 57), and 78.3% (n = 47) received intravenous cyclophosphamide. Sensory/motor recovery at 6 months was observed in 75% (42 of 56), but only in 16.1% (9 of 56) was complete. Hypoglycorrhachia and EGS ≥ 7 in the nadir were associated with an unfavorable neurological outcome at 6 months (p < 0.05). A relapse rate during follow-up was observed in 30.4% (17 of 56). Hypoglycorrhachia and hypocomplementemia seem to be protective factors for relapse. Intravenous cyclophosphamide was associated with time delay to relapse. CONCLUSIONS: Systemic lupus erythematosus-related ATM may occur at any time of SLE course, leading to significant disability despite treatment. Relapses are infrequent and intravenous cyclophosphamide seems to delay it. Hypoglycorrhachia, hypocomplementemia, and EGS at nadir are the most important prognostic factors.
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Lúpus Eritematoso Sistêmico , Mielite Transversa , Adulto , Feminino , Humanos , América Latina , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Mielite Transversa/diagnóstico , Mielite Transversa/tratamento farmacológico , Mielite Transversa/epidemiologia , Recidiva Local de Neoplasia , Prognóstico , Adulto JovemRESUMO
Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).
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Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.(AU)
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Humanos , Cloroquina/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Cloroquina/farmacologia , Hidroxicloroquina/farmacologiaRESUMO
Abstract Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease which impairs the quality of life. The objective of study was to evaluate the effectiveness of Brief Group Psychoanalytic Psychotherapy to improve quality of life, depression, anxiety and coping strategies in SLE patients. Methods: In a randomized clinical trial, 80 female SLE patients were allocated into two groups: therapy group (n = 37) and control group (n =43). Therapy group (TG) attended weekly psychotherapy sessions for 20 weeks; control group (CG) remained on a waiting list. Both groups received standard medical care. Questionnaires and scales were applied by blinded evaluators at baseline (T1) and after 20 weeks (T2): Socioeconomic Status, SLE International Collaborating Clinic/American College of Rheumatology-Damage Index, SLE International Disease Activity, SLE Specific Symptom Checklist, SLE Quality of life, Hospital Anxiety Depression Scale, Coping Strategies Inventory. Intent to treat intra- and inter-group analysis was performed for all variables in T1 and T2 using Qui-square, t-Student, Mann-Whitney and Wilcoxon tests. Analysis of Variance was used to compare categorical variables overtime. P < 0.05 was considered significant. Results: The mean age of patients was 42 years; 54% were white, with mean disease duration of years 12. At baseline, both groups were homogeneous in all variables, including medications. After 20 weeks of psychotherapy TG was significantly different from CG, with lower frequency of symptoms (p = 0.001), lower level of anxiety (p = 0.019) and depression (p = 0.022), better index in five of six domains of quality of life scale (p ≤ 0.005), including total SLEQOL (p < 0.001) and with higher positive planful problem solving strategy (p = 0.017). No change in disease activity score was observed in both groups. Conclusions: Psychoanalytic psychotherapy was effective to improve many domains of quality of life and one positive coping skill and to reduce SLE symptoms, anxiety and depression levels. Brief group psychotherapy can be a useful tool to complement medical care in SLE patients. Trial registration: Number NCT01840709.
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Adulto , Feminino , Humanos , Ansiedade/terapia , Terapia Psicanalítica/métodos , Qualidade de Vida , Adaptação Psicológica , Depressão/terapia , Lúpus Eritematoso Sistêmico/psicologia , Psicoterapia Breve , Psicoterapia de Grupo , Fatores Socioeconômicos , Seleção de PacientesRESUMO
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 Endoteliais/citologia , Arterite de Takayasu/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Anti-Inflamatórios/administração & dosagem , Brasil , Estudos de Casos e Controles , Contagem de Células , Estudos Transversais , Células do Cúmulo , Células Progenitoras Endoteliais/classificação , Feminino , Citometria de Fluxo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Leflunomida/uso terapêutico , Pessoa de Meia-Idade , Monócitos/classificação , Monócitos/citologia , Prednisona/administração & dosagem , Células-Tronco , Arterite de Takayasu/dietoterapia , Arterite de Takayasu/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
OBJECTIVES: The aim of this study was to evaluate the efficacy of atorvastatin to reduce the plasma levels of TNF system molecules (TNF-α, sTNFR1 and sTNFR2) and to assess their association with risk factors for accelerate atherosclerosis and clinical disease activity scores in SLE patients. METHODS: In a previous study, 64 female SLE patients received 20 mg/day of atorvastatin and 24 SLE patients (non-treated group) were followed for 8 weeks. Plasma levels of TNF-α, sTNFR 1 and sTNFR 2 were measured by ELISA, at baseline and at the end of the study. RESULTS: The plasma levels of sTNFR1 and sTNFR 2 showed a positive correlation with SLEDAI score. We also found a positive correlation between TNF-α and sTNFR 1 levels and SLICC score. Patients with current nephritis and patients with anti-ds-DNA antibodies presented higher sTNFR1 and sTNFR2 levels. Patients with abdominal obesity and arterial hypertension also had higher plasma levels of soluble receptors. At the end of 8 weeks, we observed a significant decrease in sTNFR1 plasma levels in patients receiving atorvastatin [median (percentile), 876.5 (717-1284 pg/ml) vs. 748 (629.6-917.3 pg/ml), p=0.03], without difference regarding TNF-α and sTNFR2 plasma levels. The SLEDAI and SLICC scores were independent determinants of the plasma levels of sRTNF1. CONCLUSIONS: Atorvastatin reduced soluble receptors of TNF-α. The plasma levels of TNF-α, sTNFR1 and sTNFR2 may play a role in SLE activity and atherosclerosis, and might be evaluated as targets for new therapies.
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Anti-Inflamatórios/uso terapêutico , Aterosclerose/prevenção & controle , Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/imunologia , Biomarcadores/sangue , Brasil , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
INTRODUCTION: Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV. METHODS: Twenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. RESULTS: In GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 ± 4.19 ng/ml vs. 4.17 ± 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45-2.10) ng/ml vs. 1.46 (0.89-3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63-2.16) ng/ml vs. 0.75 (0.39-2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29-1.46) ng/ml vs. 1.93 (0.88-3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status. CONCLUSIONS: Patients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV.
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Biomarcadores/sangue , Arterite de Células Gigantes/sangue , Proteína HMGB1/sangue , Arterite de Takayasu/sangue , Fatores Etários , Idoso , Área Sob a Curva , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e EspecificidadeRESUMO
ABSTRACT Permanent visual loss can be caused by improper use of immunosuppressive therapy in cases of uveitis without differential diagnosis of syphilitic uveitis. We present four cases of syphilitic uveitis that were incorrectly diagnosed as being secondary to rheumatic diseases and were subsequently treated with immunosuppressive therapy, leading to permanent visual loss. These cases highlight the importance of ruling out syphilis in the differential diagnosis of inflammatory ocular diseases before starting use of immunosuppressive therapy.
RESUMO Elucidar os efeitos adversos do uso de medicações imunossupressoras em pacientes com uveíte não diagnosticada por sífilis. Avaliação de quatro pacientes com uveíte por sífilis submetidos a tratamento com drogas imunossupressoras por suspeita de uveíte secundária a doenças reumáticas, que desenvolveram perda visual permanente. Sífilis deve ser sempre um diagnóstico diferencial nas doenças inflamatórias oculares, principalmente antes do início de terapia imunossupressora.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Sífilis/tratamento farmacológico , Uveíte/tratamento farmacológico , Transtornos da Visão/etiologia , Diagnóstico Diferencial , Teste de Absorção do Anticorpo Treponêmico Fluorescente , Imunossupressores/uso terapêutico , Sífilis/complicações , Uveíte/etiologia , Acuidade Visual/efeitos dos fármacosRESUMO
Objetivo Elaborar recomendações para o diagnóstico, manejo e tratamento da nefrite lúpica no Brasil. Método Revisão extensa da literatura com seleção dos artigos com base na força de evidência científica e opinião dos membros da Comissão de Lúpus Eritematoso Sistêmico da Sociedade Brasileira de Reumatologia. Resultados e conclusões 1) A biópsia renal deve ser feita sempre que possível e houver indicação e quando não for possível, o tratamento deve ser orientado com base na inferência da clase histológica. 2) Devem ser implementados medidas e cuidados idealmente antes do início do tratamento, com ênfase na atenção ao risco de infecção. 3) Devem-se compartilhar riscos e benefícios do tratamento com pacientes e familiares. 4) O uso da hidroxicloroquina (preferencialmente) ou difosfato de cloroquina é recomendado para todos os pacientes (exceto contraindicação) durante as fases de indução e manutenção. 5) A avaliação da eficácia do tratamento deve ser feita com critérios objetivos de resposta (remissão completa/remissão parcial/refratariedade). 6) Os IECA e/ou BRA são recomendados como antiproteinúricos para todos os pacientes (exceto contraindicação). 7) A identificação de sinais clínicos e/ou laboratoriais sugestivos de GN laboratoriais sugestivos de glomerulonefrite proliferativa ou membranosa deve indicar início imediato de terapia específica incluindo corticosteroides e agente imunossupressor, mesmo que não seja possível comprovação histológica. 8) O tempo de uso dos imunossupressores deve ser no mínimo de 36 meses, mas eles podem ser mantidos por períodos mais longos. A sua suspensão só deve ser feita quando o paciente atingir e mantiver remissão completa sustentada. 9) Deve-se considerar nefrite lúpica refratária quando a remissão completa ou parcial não for alcançada após 12 meses de tratamento adequado, quando uma nova biópsia renal deve ser considerada para auxiliar na identificação da causa da refratariedade e decisão terapêutica. .
Objective To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. Method Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. Results and conclusions (1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. (2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. (3) Risks and benefits of treatment should be shared with the patient and his/her family. (4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. (5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). (6) Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers are recommended as antiproteinuric agents for all patients (unless contraindicated). (7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including corticosteroids and an immunosuppressive agent, even though histological confirmation is not possible. (8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient could achieve and maintain a sustained and complete remission. (9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when ...
Assuntos
Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Biópsia , Brasil , Progressão da Doença , Indução de RemissãoRESUMO
OBJECTIVE: To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. METHOD: Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.
Assuntos
Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Biópsia , Brasil , Progressão da Doença , Humanos , Indução de RemissãoRESUMO
OBJETIVO: Avaliar a associação entre a presença de anticorpos antinucleossomo (anti-NCS) e a síndrome antifosfolipídica primária (SAFP) e o posterior desenvolvimento de lúpus eritematoso sistêmico (LES). MATERIAIS E MÉTODOS: Trinta e seis mulheres com o diagnóstico de SAFP foram avaliadas prospectivamente para manifestações de doenças reumáticas autoimunes e para a presença de anticorpos antifosfolípides, anticorpos antinucleares e anti-NCS/cromatina. RESULTADOS: Após um período médio de seguimento de 45,7 meses, anticorpos anti-NCS/cromatina foram detectados em apenas uma paciente (2,8%), que desenvolveu manifestações de LES tais como poliartrite, linfopenia, neurite óptica, lesões compatíveis com esclerose múltipla em substância branca cerebral e perfil de autoanticorpos altamente sugestivo de LES. CONCLUSÃO: A frequência de anticorpos anti-NCS/cromatina é baixa em pacientes com SAFP, e sua presença pode associar-se ao desenvolvimento de manifestações de LES.
OBJECTIVE: To study the association of anti-nucleosome (anti-NCS) antibodies in primary antiphospholipid syndrome (APS) and the development of systemic lupus erythematosus (SLE) during follow-up. MATERIALS AND METHODS: Thirty-six women with primary APS were evaluated prospectively for clinical features of systemic autoimmune diseases and for the presence of antiphospholipid antibodies, antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in only one patient (2.8%), who developed features of SLE including polyarthritis, lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin antibodies in primary APS patients is very low, and they may be associated with the development of SLE manifestations.
Assuntos
Adulto , Feminino , Humanos , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Autoanticorpos/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Nucleossomos/imunologia , Estudos ProspectivosRESUMO
Los pacientes con enfermedades autoinmunitarias sistémicas (EAIS) presentan un riesgo incrementado de desarrollar aterosclerosis (AE). Esto responde a la presencia de factores deriesgo cardiovascular (FRCV) tradicionales ûdislipemia, hipertensión arterial, diabetes, tabaquismo, obesidad, sedentarismoû y no tradicionales ûactividad de la enfermedad,hiperhomocisteinemia, corticoterapiaû que por diferentes caminos están incrementados. Los scores de riesgo cardiovascular absoluto no se mostraron útiles para predecir enfermedadcardiovascular en esta población, ya que al considerar solo los FRCV tradicionalessubestiman el riesgo de futuros eventos. Las manifestaciones clínicas tienen características diferenciales que deben ser consideradas para no desestimarlas en la práctica clínica. El screening sistemático de los FRCV y la búsqueda de aterosclerosis subclínica deben estardentro de la rutina de seguimiento de esta población. En ausencia de guías específicas y bajo el postulado que las EAIS imprimen un riesgo cardiovascular (CV) similar a la diabetes mellitus, los objetivos terapéuticos se asimilan a los propuestos para esta enfermedad. Elcontrol agresivo de los FRCV con medidas farmacológicas y no farmacológicas es el único camino capaz de reducir una de las principales causas de muerte en portadores de EAIS.
Patients with systemic autoimmune diseases have an increased risk to develop atherosclerosis. This is due to the presence of traditional cardiovascular risk factors - dyslipidemia, high blood pressure, diabetes, smoking, obesity,sedentary lifestyleû and non-traditional ones ûthe disease itself, hyperhomocisteinemia, corticotherapyû , which rise in a number of ways. Absolute cardiovascular risk scores were not useful to predict cardiovascular disease in this population since by considering just the traditionalcardiovascular risk factors futures events are being underestimated.Systematic screening of cardiovascular risk factors and looking for subclinical atherosclerosis must be a part of the follow-up routine for this population. Upon absence of specific guidelines and understanding systematicautoimmuune diseases is a cardiovascular risk factor similar to diabetes mellitus, therapeutic objectivesadopted are similar to those used for the latter. Aggressive pharmacological and non-pharmacological control ofcardiovascular risk factors is the only way to reduce and is one of the leading causes of death in carriers of systemicautoimmune diseases.
Os pacientes com enfermidades auto-imunes sistêmicas (EAIS) têm um risco maior de apresentar aterosclerose (AE). Isto se deve a presença de fatores de risco cardiovascular (FRCV) tradicionais ûdislipemia, hipertensão arterial, diabete, tabagismo, obesidade, sedentarismoû e não tradicionais ûatividade da doença, hiperhomocisteinemia, corticoterapiaû que por diferentes causas estão aumentados. Os indicadores de risco cardiovascular absoluto não foram úteis para fazer a predição de doença cardiovascular nesta população, pois considerando somente os FRCVtradicionais subestimam o risco de futuros eventos. As manifestações clínicas têm características diferenciadasque devem ser consideradas para não serem subestimadas na prática clínica. A triagem sistemática dos FRCV e a busca de ateroscleroses sub-clínica devem ser parte da rotina de seguimento desta população. Considerando a falta de pautas específicas e considerando que as EAIS apresentam um risco cardiovascular (CV) similar à diabetesmellitus, os objetivos terapêuticos são semelhantes aos propostos para esta patologia. O controle agressivo dos FRCV com medidas farmacológicas y não farmacológicas é o único caminho capaz de reduzir uma das principais causas de morte em portadores de EAIS.
Assuntos
Aterosclerose , Doenças Autoimunes/complicações , Fatores de RiscoRESUMO
Pacientes com lúpus eritematoso sistêmico, doença com início aos50 anos ou mais, perfazem um subgrupo com algumas característicasdemográfi cas, clínicas e laboratoriais próprias. Neste artigo,apresentamos uma revisão, buscando no PubMed as palavras-chaveconstantes do título acima, com pesquisa incluindo publicações dosúltimos dez anos, além de bibliografi a mais antiga, constantes em livrostextos. Desde a década de 1960 havia o conceito que o lúpuseritematoso sistêmico, após os 50 anos, teria um curso benigno ecom menor diferença na prevalência entre os sexos. Publicações maisrecentes continuam confi rmando o menor predomínio no sexo femininoem relação ao masculino, em comparação à doença em pacientesmais jovens. Mas, atualmente, diversos estudos realizados em populaçõesetnicamente diferentes, mostram que pacientes com lúpuseritematoso sistêmico tardio têm menor sobrevida, em decorrênciade comorbidades freqüentes nessa faixa etária e que infl uenciam oestado de saúde já comprometido. A causa mais freqüente de mortalidadeé a infecção, seguida de doenças pulmonares e doença arterialcoronariana. A menor freqüência de hipocomplementemia no lúpuseritematoso sistêmico tardio continua sendo encontrada em diversosestudos, porém, o envolvimento renal é considerado semelhante ao depacientes adultos jovens. Há concordância de que o lúpus eritematososistêmico tardio acomete menos a pele, especialmente considerandoo eritema malar e a fotossensibilidade, mas parece não ter um cursotão benigno quanto havia sido demonstrado em estudos realizadosem décadas passadas. Diferenças nos métodos de avaliação podemjustifi car em parte os resultados discrepantes.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idade de Início , Lúpus Eritematoso Sistêmico , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Distribuição por SexoRESUMO
A arterite de Takayasu (AT) é uma vasculite granulomatosa crônica que envolve a aorta e seu principais ramos.A monitoração da atividade da doença e o melhor esquema terapêutico ainda têm sido um desafio para todos os que tratam estes pacientes. Costicorteróides e imunossupressores vêm sendo utilizados na prática clínica diária com resultados nem sempre animadores. Apesar de não haver estudos controlados que abordem o tratamento da AT, diferentes estudos observacionais descrevem a resposta de pacientes com AT ao uso de corticosteróides, metotrexato (MTX), azatioprina e ciclofosfamida. Após a introdução da terapia biológica, novas perspectivas têm surgido para os pacientes com AT refratários aos esquemas terapêuticos tradicionais.