RESUMO
Neuropsychiatric manifestations in lupus (NPSLE) affect â¼20-40% of patients. In the central nervous system, lipocalin-2 (LCN2) can promote injury through mechanisms directly linked to NPSLE, including brain barrier disruption, neurotoxicity, and glial activation. Since LCN2 is elevated in lupus and has been implicated in neuroinflammation, we investigated whether LCN2 is required for the pathogenesis of NPSLE. Here, we investigated the effects of LCN2 deficiency on the development of neurobehavioral deficits in the B6.Sle1.Sle3 (Sle1,3) mouse lupus model. Sle1,3 mice exhibited depression-like behavior and impaired spatial and recognition memory, and these deficits were attenuated in Sle1,3-LCN2KO mice. Whole-brain flow cytometry showed a significant increase in brain infiltrating leukocytes in Sle1,3 mice that was not reduced by LCN2 deficiency. RNA sequencing on sorted microglia revealed that several genes differentially expressed between B6 and Sle1,3 mice were regulated by LCN2, and that these genes are key mediators of the neuroinflammatory cascade. Importantly, LCN2 is upregulated in the cerebrospinal fluid of NPSLE patients across 2 different ethnicities. Our findings establish the Sle1,3 strain as an NPSLE model, demonstrate that LCN2 is a major regulator of the detrimental neuroimmune response in NPSLE, and identify CSF LCN2 as a novel biomarker for NPSLE.
Assuntos
Biomarcadores/metabolismo , Leucócitos/imunologia , Lipocalina-2/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/metabolismo , Inflamação Neurogênica/metabolismo , Animais , Barreira Hematoencefálica , Modelos Animais de Doenças , Feminino , Humanos , Lipocalina-2/antagonistas & inibidores , Lipocalina-2/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Inflamação Neurogênica/diagnóstico , Regulação para CimaRESUMO
Objectives The aim of this study was to study the relationship between immunosuppressive drug treatment and survival in patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled four or more American College of Rheumatology criteria for SLE were followed longitudinally. Clinical characteristics, use of immunosuppressive agents and mortality were reviewed. Cox regression was used to study the relationship between immunosuppressive treatment and survival, adjusted for age, sex, vascular risk factors, organ damage, the anti-phospholipid antibodies and a propensity score for the indication of individual immunosuppressive agent derived from separate regression models. Results A total of 803 SLE patients were studied (92% women; age of SLE onset 33.2±14 years; follow-up time 10.8±7.7 years). The frequencies of ever use of immunosuppressive agents were: high-dose prednisolone (≥0.6 mg/kg/day for ≥4 weeks) (85%), azathioprine (63%), cyclophosphamide (25%), mycophenolate mofetil (27%), the calcineurin inhibitors (23%) and hydroxychloroquine (69%). Ninety-seven patients (12%) died and 56 (7%) patients were lost to follow-up. The causes of death were infection (44%), cerebrovascular events (12%), cardiovascular events (10%) and malignancy (8.2%). Cox regression revealed that the ever use of high-dose prednisolone, mycophenolate mofetil, calcineurin inhibitors or cyclophosphamide was not significantly associated with improved survival. However, the ever use of hydroxychloroquine (hazard ratio 0.59 (0.37-0.93); P=0.02) and azathioprine (hazard ratio 0.46 (0.28-0.75); P=0.002) was significantly associated with reduced mortality (41% and 54%, respectively) after adjustment for the propensity score and other confounding factors. A similar beneficial effect of hydroxychloroquine and azathioprine on survival was also observed in patients with lupus nephritis. Conclusions In this longitudinal cohort of Chinese SLE patients, the ever use of hydroxychloroquine and azathioprine was significantly associated with a probability of better survival. Treatment with high-dose prednisolone, cyclophosphamide, mycophenolate mofetil or the calcineurin inhibitors was not associated with long-term survival benefit.
Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Humanos , Imunossupressores/efeitos adversos , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lupus erythematosus (SLE) and LupusPRO were compared, stratified by (a) presence of LN (ACR classification criteria (ACR-LN)) at any time and, (b) active LN (on SLEDAI) at study visit. Damage was assessed by SLICC/ACR-SDI. Multivariate regression analyses for QOL against ACR-LN (active LN) after adjusting for age, gender, ethnicity and country of recruitment were performed. Results Mean (SD) age was 41.7 (13.5) yrs, 93% were women. Five hundred and thirty-nine of 1259 SLE patients had ACR-LN. ACR-LN group was younger, were more often on immunosuppressive medications, had worse QOL on lupus medications and procreation than non-ACR-LN patients. HRQOL and non-HRQOL scores were similar in both groups. One hundred and twenty-nine of 539 ACR-LN patients had active LN. Active LN group was younger, had greater disease activity and had worse HRQOL and non-HRQOL compared to patients without active LN. Specific domains adversely affected were lupus symptoms, lupus medications, procreation, emotional health, body image and desires-goals domains. Patients with ACR-LN and active LN fared significantly worse in lupus medications and procreation HRQOL domains, even after adjusting for age, ethnicity, gender and country of recruitment. Conclusions Lupus nephritis patients have poor QOL. Patients with active LN have worse HRQOL and non-HRQOL. Most domains affected are not included in the generic QOL tools used in SLE. LN patients must receive discussion on lupus medications and procreation issues. Patients with active LN need comprehensive assessments and addressal of QOL, along with treatment for active LN.
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Lúpus Eritematoso Sistêmico/psicologia , Nefrite Lúpica/classificação , Nefrite Lúpica/psicologia , Qualidade de Vida/psicologia , Adulto , Imagem Corporal/psicologia , Estudos Transversais , Emoções/fisiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/etnologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de DoençaRESUMO
Systemic lupus erythematosus (SLE) is a complex multi-systemic autoimmune disease with considerable clinical and immunological heterogeneity. Family physicians should be familiar with the protean manifestations of SLE to aid early diagnosis and monitoring of disease progression. The role of family physicians in SLE includes education, counselling, psychological support, management of mild disease, and recognition of the need for referral to other specialists for more serious disease and complications. Surveillance of cardiovascular risk factors and osteoporosis and advice about vaccination and reproductive issues can be performed in the primary care setting under close collaboration with rheumatologists and other specialists. This review provides family physicians with the latest classification criteria for SLE, recommendations on SLE-related health issues, and pharmacological therapies for SLE.
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Lúpus Eritematoso Sistêmico/diagnóstico , Médicos de Família , Padrões de Prática Médica , Humanos , Lúpus Eritematoso Sistêmico/terapia , Atenção Primária à Saúde , Encaminhamento e ConsultaRESUMO
OBJECTIVES: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA). METHOD: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. RESULTS: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 ± 10.9 years; disease duration 4.4 ± 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms. CONCLUSIONS: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment.
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Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Vértebra Cervical Áxis , Difosfonatos/uso terapêutico , Imageamento por Ressonância Magnética , Espondilartrite/tratamento farmacológico , Espondilartrite/patologia , Adulto , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Difosfonatos/administração & dosagem , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Pamidronato , Índice de Gravidade de Doença , Espondilartrite/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: To study the level of anti-müllerian hormone (AMH) and its relationship to age and previous exposure to cyclophosphamide (CYC) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive female patients ages 18-52 years who had menses at least once during the preceding 12 months and fulfilled ≥4 American College of Rheumatology criteria for SLE were recruited. AMH was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum AMH levels were compared in patients with and without previous use of immunosuppressive agents. The relationship of the AMH level to the patient's age and CYC exposure was studied by linear regression and receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 216 patients were studied (mean±SD age 35.1±10.1 years, mean±SD SLE duration 7.6±5.9 years). The mean±SD AMH level was significantly lower in patients previously exposed to CYC therapy than in those who had not been exposed after adjustment for age (1.58±2.92 versus 1.73±2.11 ng/ml; P=0.04). The median time interval between the AMH assay and the last dose of CYC administered was 6.7 years (interquartile range 3.4-8.5). AMH levels in users versus nonusers of other immunosuppressive agents, including mycophenolate mofetil, azathioprine, and the calcineurin inhibitors, were not statistically different. Linear regression revealed increasing age (beta -0.32, P=0.02) and each 5 gm of CYC exposure (beta -0.28, P=0.047) were independently associated with a lower AMH level. In patients ages 30 years and younger, a cumulative CYC dose cutoff of 5.9 gm yielded a sensitivity of 0.75 and a specificity of 0.80 for the prediction of undetectable AMH level on ROC curve analysis. CONCLUSION: AMH is a sensitive marker for ovarian damage due to previous CYC exposure in women with SLE.
Assuntos
Hormônio Antimülleriano/sangue , Ciclofosfamida/efeitos adversos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/sangue , Ovário/fisiopatologia , Insuficiência Ovariana Primária/induzido quimicamente , Adolescente , Adulto , Fatores Etários , Ciclofosfamida/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pessoa de Meia-Idade , Ovário/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To study the effect of renal disease on the standardized mortality ratio (SMR) and life expectancy of patients with systemic lupus erythematosus (SLE). METHODS: Patients whose diagnosis met ≥4 American College of Rheumatology criteria for SLE were longitudinally followed up from 1995 to 2011. The cumulative survival rate, SMR, and life expectancy were calculated, and the effect of renal involvement, histologic class of lupus nephritis, renal damage, and end-stage renal disease (ESRD) on these parameters was evaluated. RESULTS: Of the 694 SLE patients studied, 368 (53%) had renal disease, and the distribution of histologic classes (among 285 patients) was class I (1%), class II (6%), class III (19%), class IV (47%), class III/IV + class V (10%), and class V (16%). Renal damage was present in 79 patients (11%), and 24 (3%) developed ESRD. The age- and sex-adjusted hazard ratios (HRs) of mortality in SLE patients with renal disease, those with renal damage, and those with ESRD, as compared to those without, were 2.23 (95% confidence interval [95% CI] 1.29-3.85), 3.59 (95% CI 2.20-5.87), and 9.20 (95% CI 4.92-17.2), respectively. Proliferative lupus nephritis (adjusted HR 2.28, 95% CI 1.22-4.24), but not the pure membranous type (adjusted HR 1.09, 95% CI 0.38-3.14), was associated with a significant increase in mortality. The age- and sex-adjusted SMRs of SLE patients without renal involvement, those with lupus nephritis, those with proliferative nephritis, those with pure membranous nephritis, those with renal damage, and those with ESRD were 4.8 (95% CI 2.8-7.5), 9.0 (95% CI 6.7-11.9), 9.8 (95% CI 6.5-14.1), 6.1 (95% CI 2.0-14.1), 14.0 (95% CI 9.1-20.5), and 63.1 (95% CI 33.6-108.0), respectively. The life expectancy of SLE patients with renal disease and those with renal damage was reduced by 15.1 years and 23.7 years, respectively, compared to the general population. CONCLUSION: The presence of renal disease, in particular proliferative nephritis causing renal insufficiency, significantly reduces the survival and life expectancy of SLE patients.
Assuntos
Expectativa de Vida , Nefrite Lúpica/mortalidade , Mortalidade , Adolescente , Adulto , Idoso , Criança , Feminino , Hong Kong/epidemiologia , Humanos , Rim/patologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Estudos Longitudinais , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Taxa de Sobrevida , Adulto JovemAssuntos
Lúpus Eritematoso Sistêmico/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies. METHODS: In the present study, isobaric tags for relative and absolute quantitation-based mass spectrometry was used to screen the sera of patients with SLE to uncover potential disease biomarkers. RESULTS: 85 common proteins were identified, with 16 being elevated (≥1.3) and 23 being decreased (≤0.7) in SLE. Of the 16 elevated proteins, serum alpha-1-microglobulin/bikunin precursor (AMBP), zinc alpha-2 glycoprotein (AZGP) and retinol-binding protein 4 (RBP4) were validated in independent cross-sectional cohorts (Cohort I, N=52; Cohort II, N=117) using an orthogonal platform, ELISA. Serum AMBP, AZGP and RBP4 were validated to be significantly elevated in both patients with inactive SLE and patients with active SLE compared with healthy controls (HCs) (p<0.05, fold change >2.5) in Cohort I. All three proteins exhibited good discriminatory power for distinguishing active SLE and inactive SLE (area under the curve=0.82-0.96), from HCs. Serum AMBP exhibited the largest fold change in active SLE (5.96) compared with HCs and correlated with renal disease activity. The elevation in serum AMBP was validated in a second cohort of patients with SLE of different ethnic origins, correlating with serum creatinine (r=0.60, p<0.001). CONCLUSION: Since serum AMBP is validated to be elevated in SLE and correlated with renal disease, the clinical utility of this novel biomarker warrants further analysis in longitudinal cohorts of patients with lupus and lupus nephritis.
Assuntos
Biomarcadores , Lúpus Eritematoso Sistêmico , Proteínas Plasmáticas de Ligação ao Retinol , Humanos , Lúpus Eritematoso Sistêmico/sangue , Biomarcadores/sangue , Feminino , Masculino , Adulto , Estudos Transversais , Proteínas Plasmáticas de Ligação ao Retinol/análise , Pessoa de Meia-Idade , Espectrometria de Massas/métodos , Ensaio de Imunoadsorção Enzimática/métodos , alfa-Globulinas/análise , Estudos de Coortes , Glicoproteínas/sangue , Estudos de Casos e Controles , Adulto Jovem , Glicoproteína Zn-alfa-2RESUMO
Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age. The infrequency of SLE in men and disease onset in prepubertal or postmenopausal women suggests a role of estrogen in the predisposition to the disease. Patients with hypergonadotrophic hypogonadism are prone to the development of SLE, and the use of exogenous estrogens in women increases the relative risk of SLE onset and disease flares. These observations provide indirect evidence for an opposite role of estrogens and androgens in the pathogenesis of SLE. We report on a male-to-female transsexual who developed SLE 20 years after sex-reassignment surgery and prolonged estrogen therapy. The role of sex hormones in SLE is revisited.
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Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/efeitos adversos , Estrogênios/efeitos adversos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Cirurgia de Readequação Sexual/efeitos adversos , Testosterona/metabolismo , Pessoas Transgênero , Transexualidade/cirurgia , Adulto , Antipsicóticos/uso terapêutico , Autoanticorpos/sangue , Autoimunidade/efeitos dos fármacos , Biomarcadores/sangue , Estrogênios/administração & dosagem , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Imunossupressores/uso terapêutico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Masculino , Fatores de Risco , Transexualidade/sangueRESUMO
OBJECTIVE: The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy. METHODS: Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥ 2 immunosuppressive regimens. While prednisolone (≤ 10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months. RESULTS: Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V+III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal. CONCLUSIONS: Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.
Assuntos
Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Tacrolimo/administração & dosagem , Adulto , Creatinina/urina , Quimioterapia Combinada , Feminino , Humanos , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Albumina Sérica/análise , Linfócitos T/imunologia , Tacrolimo/efeitos adversosRESUMO
OBJECTIVES: The purpose of this study was to identify the effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus (SLE). METHODS: Subgroup data were analyzed for postmenopausal female SLE patients who participated in a randomized controlled trial of raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a stable daily dose of prednisolone (≤10 mg) for ≥6 months were assigned to receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D. Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians' global assessment (PGA) every three months. Lupus flares were assessed by the SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C-reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured. RESULTS: A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 ± 6.7 years; SLE duration 9.3 ± 7.6 years; menopause duration 7.2 ± 6.6 years). The SLEDAI at entry was 1.8 ± 2.3 (SLEDAI ≥ 6 in 8%). After 12 months, a significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p = 0.02), and reduction in bone resorption and formation markers was observed in the raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA scores area under the curve over 12 months were not significantly different between the two groups. There were three episodes of mild/moderate lupus flares (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological) in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol level increased significantly in the placebo but not raloxifene treated patients. No significant changes in homocysteine, hsCRP and sTM levels were observed in either group of patients. CONCLUSIONS: Raloxifene significantly improves lumbar spine BMD in SLE patients but does not cause an increase in lupus activity or flares.
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Antagonistas de Estrogênios/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pós-Menopausa , Cloridrato de Raloxifeno/uso terapêutico , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Homocisteína/metabolismo , Humanos , Vértebras Lombares , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Cloridrato de Raloxifeno/farmacologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Community treatment orders (CTOs) enable patients to actively engage in mental health services while being supervised in the community outside the hospital setting. However, the efficacy of CTOs remains controversial in terms of mental health services usage or service contacts, emergency visits, and violence. METHODS: The databases PsychINFO, Embase, and Medline were searched on 11 March 2022 by 2 independent reviewers through the Covidence website (www.covidence.org). Randomised or non-randomised case-control studies and pre-post studies were included if they examine the effect of CTOs on service contacts, emergency visits, and violence in individuals with mental illnesses by comparing with control groups or pre-CTO conditions. Conflicts were resolved by consultation of the third independent reviewer. RESULTS: Sixteen studies provided sufficient data in the target outcome measures and were included in analysis. Variability in the risk of bias was high among studies. Meta-analyses were conducted separately for case-control studies and pre-post studies. For service contacts, a total of 11 studies with 66,192 patients reported changes in the number of service contacts under CTOs. In 6 case-control studies, a small non-significant increase in service contacts was observed in those under CTOs (Hedge's g = 0.241, z = 1.535, p = 0.13). In 5 pre-post studies, a large and significant increase in service contacts was noted after CTOs (Hedge's g = 0.830, z = 5.056, p < 0.001). For emergency visits, a total of 6 studies with 930 patients reported changes in the number of emergency visits under CTOs. In 2 case-control studies, a small non-significant increase in emergency visits was noted in those under CTOs (Hedge's g = -0.196, z = -1.567, p = 0.117). In 4 pre-post studies, a small significant decrease in emergency visits was noted after CTOs (Hedge's g = 0.553, z = 3.101, p = 0.002). For violence, a total of 2 pre-post studies reported a moderate significant reduction in violence after CTOs (Hedge's g = 0.482, z = 5.173, p < 0.001). CONCLUSION: Case-control studies showed inconclusive evidence, but pre-post studies showed significant effects of CTOs in promoting service contacts and reducing emergency visits and violence. Future studies on cost-effectiveness analysis and qualitative analysis for specific populations with various cultures and backgrounds are warranted.
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Serviços Comunitários de Saúde Mental , Transtornos Mentais , Serviços de Saúde Mental , Humanos , Transtornos Mentais/terapia , Violência/prevenção & controle , Serviço Hospitalar de EmergênciaRESUMO
OBJECTIVES: To study the sensitivity and specificity of vitamin D deficiency for predicting disease activity and damage of systemic lupus erythematosus (SLE) in comparison with anti-dsDNA and anti-C1q. METHODS: Consecutive patients who fulfilled four or more ACR criteria for SLE were studied. Levels of 25-hydroxyvitamin D3, anti-C1q, anti-dsDNA and complement levels were measured. Relationship among these markers, concurrent disease activity and damage scores of SLE was studied by Spearman's rank correlation method. RESULTS: In total, 290 SLE patients were studied (95% women; mean age 38.9 ± 13.1 years; SLE duration 7.7 ± 6.7 years). Clinical or serological lupus activity (SLEDAI ≥ 1) was present in 225 (78%) patients. Vitamin D deficiency (< 15 ng/ml) was detected in 78 (27%) patients. Levels of 25-hydroxyvitamin D3 correlated inversely with the clinical SLE disease activity score (Rho = -0.26; p < 0.001). A negative correlation was also observed between 25-hydroxyvitamin D3 and anti-dsDNA levels (Rho = -0.13; p = 0.02), or anti-C1q (Rho = -0.14; p = 0.02). However, there was no significant relationship between levels of 25-hydroxyvitamin D3 and complement C3 (Rho = 0.09; p = 0.12) or C4 (Rho = 0.09; p = 0.13). Both 25-hydroxyvitamin D3 deficiency and anti-C1q were more specific but less sensitive than anti-dsDNA for concurrent clinical renal and non-renal SLE activity. Levels of 25-hydroxyvitamin D3, anti-dsDNA or anti-C1q did not correlate significantly with the SLE damage scores. CONCLUSIONS: 25-hydroxyvitamin D3 correlated inversely and significantly with clinical SLE activity, anti-C1q and anti-dsDNA titers, but not with complement levels or damage scores. Deficiency of 25-hydroxyvitamin D3 was as specific as anti-C1q, but less sensitive than anti-dsDNA, for detecting concurrent renal and non-renal clinical activity of SLE.
Assuntos
Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Biomarcadores/metabolismo , Complemento C1q/imunologia , DNA/imunologia , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Deficiência de Vitamina D/metabolismo , Adulto , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.
Assuntos
Povo Asiático/genética , Complexo CD3/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Adulto , China , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Hong Kong , Humanos , Desequilíbrio de Ligação , Razão de Chances , Polimorfismo de Nucleotídeo Único , TailândiaRESUMO
OBJECTIVES: To study the effect of concurrent psychiatric disorders on health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA). METHODS: Consecutive Chinese patients who fulfilled the American College of Rheumatology (ACR) criteria for RA were recruited and interviewed by a psychiatrist for psychiatric disorders using the Chinese Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders, Patient version (CB-SCID-I/P). HRQOL was assessed by the validated Chinese version of the 36-item Short Form Health Survey (SF-36). Sociodemographic and clinical data were also collected. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). RESULTS: Two hundred patients with RA were studied (79% women, mean age 51.4 ± 10.5 years; median RA duration 4.0 years). Forty-seven (23.5%) patients were diagnosed with a psychiatric disorder: depressive disorders in 29 patients and anxiety disorders in 26 patients. Patients with either condition had significantly higher fatigue scores (26 ± 8.8 vs. 16 ± 6.9, p < 0.001) and were more likely to be unemployed (p = 0.02) and dependent on government subsidy for living (p < 0.001) than those without. The scores of the eight domains and the physical and mental components of the SF-36 were significantly lower in RA patients with psychiatric disorders (p < 0.001 in all). In a linear regression model, the presence of either depressive or anxiety disorders (ß = -0.23, p < 0.001), older age (ß = -0.16, p = 0.006), self-perceived pain (ß = -0.25, p < 0.001) and fatigue (ß = -0.42, p < 0.001) were independently and inversely associated with the total SF-36 score after adjustment for disease activity and other sociodemographic variables. CONCLUSIONS: Concomitant depressive or anxiety disorders in RA patients are associated with significantly poorer HRQOL. Early identification and treatment of psychiatric disorders in RA patients are warranted.
Assuntos
Transtornos de Ansiedade/complicações , Artrite Reumatoide/complicações , Transtorno Depressivo/complicações , Qualidade de Vida/psicologia , Adulto , Idoso , Antirreumáticos/uso terapêutico , Transtornos de Ansiedade/psicologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/psicologia , Transtorno Depressivo/psicologia , Fadiga/complicações , Fadiga/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To examine the life expectancy, standardized mortality ratios (SMRs), and causes of death in 6 groups of patients from Hong Kong with different rheumatic diseases. METHODS: Patients with a diagnosis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic vasculitis (SV), or systemic sclerosis (SSc) registered in 37 public hospitals between 1999 and 2008 were identified in the hospital registry. SMRs were calculated by comparing the mortality rate in patients with each disease with that in the general population. Life expectancy was calculated by abridged life-table analysis, and the causes of death were compared. RESULTS: In 2008, data on 8,367 RA, 5,243 SLE, 2,154 AS, 1,636 SV, 778 PsA, and 449 SSc patients were available in our registry. The age- and sex-adjusted SMRs were highest for SLE (5.25 [95% confidence interval 4.79-5.70]), SSc (3.94 [95% confidence interval 3.20-4.68]), and SV (2.64 [95% confidence interval 2.36-2.93]). In female patients, the loss in life expectancy was greatest for SSc (34.1 years), SV (19.3 years), and SLE (19.7 years). In male patients, the loss in life expectancy was highest for SV (28.3 years), SLE (27 years), and SSc (16 years). There were 2,486 deaths during the study period (1999-2008), and the principal causes were infections (28%), cardiovascular complications (18%), cancer (16%), and disease activity (7%). Infection was the leading cause of death in SLE, RA, AS, and PsA, whereas deaths from disease-related activity and cardiovascular complications were most frequent in SSc. Cancer was the most common cause of death in SV. CONCLUSION: Our findings indicate that patients with SLE, RA, AS, PsA, SV, and SSc have increased mortality rates and reduced life expectancy. SLE has the highest adjusted SMR, and female SSc patients have the greatest loss in life expectancy. Infection is the leading cause of death, followed by cardiovascular complications and malignancies.
Assuntos
Expectativa de Vida , Doenças Reumáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Distribuição de Qui-Quadrado , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10â»8, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10â»9, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.
Assuntos
Povo Asiático/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Lúpus Eritematoso Sistêmico/genética , Mutação de Sentido Incorreto/genética , Alelos , Sequência de Aminoácidos , Frequência do Gene , Ordem dos Genes , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Hong Kong , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único/genética , Ubiquitina-Proteína LigasesRESUMO
Systemic lupus erythematosus (SLE) is a fairly common rheumatic disease in Hong Kong, China. The prevalence and annual incidence of SLE are estimated to be 0.1% and 6.7/100,000 population, respectively. The 10-year cumulative survival of SLE patients in Hong Kong is 83% and the age and gender-adjusted standardized mortality ratio was 5.25 (1.64-10.4) from 1999 to 2008. The commonest cause of death is infections (60%), followed by cardiovascular complications (16%). Life expectancy analysis reveals a loss of 20 years in women and 27 years in men when SLE develops at birth. The loss in life years is greatest in the younger age groups. Renal damage is the most frequent disease-related damage, whereas musculoskeletal damage is the commonest treatment-related complication. The quality of life of our SLE patients is impaired and declines over time, which is contributed by new organ damage. One-third of our patients lose their ability to work within 5 years of disease onset, which is mainly attributed to musculoskeletal pain, fatigue, anxiety and depression symptoms, and memory deterioration. With the availability of novel therapeutics and an increased awareness of complication prevention in SLE, it is expected that our patients will live longer with a better quality of life in the next decade.
Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Qualidade de Vida , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Hong Kong/epidemiologia , Humanos , Lactente , Expectativa de Vida , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Sobrevida , Análise de Sobrevida , Fatores de Tempo , Avaliação da Capacidade de Trabalho , Adulto JovemRESUMO
OBJECTIVES: To summarize the clinical presentation, histological features, treatment, and outcome of minimal change nephropathy (MCN) in patients with systemic lupus erythematosus (SLE). METHODS: We performed a systematic review of cases of MCN in SLE patients reported in the English literature from January 1985 to May 2009 by a Medline search. RESULTS: The estimated prevalence of MCN in biopsy-proven lupus nephritis is 2.3% in childhood and 1.1% in adults. There are 13 individual cases (12 women, one man) of SLE-related MCN reported in the literature. The mean age of nephritis onset was 32.7 years. In six (46%) patients, MCN was the initial manifestation of SLE. All patients presented with nephrotic syndrome and two (15%) had active urinary sediments. Renal function was impaired in eight (62%) patients and six (46%) patients had active lupus serology. All patients responded promptly to high-dose glucocorticoids but four (31%) had relapse of proteinuria during their course of SLE. None of the patients developed thromboembolic or infective complications. CONCLUSIONS: MCN is an uncommon histological class of lupus nephritis. Typically, patients present with heavy proteinuria, and transient renal dysfunction is common. The prognosis of MCN in SLE appears to be good because of its rapid response to glucocorticoids. Relapses of proteinuria may be reduced by the use of maintenance immunosuppression. Alkylating agents, calcineurin inhibitors, mycophenolate mofetil, and rituximab can be considered in glucocorticoid-dependent or refractory cases of SLE-related MCN.