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1.
Medicine (Baltimore) ; 100(5): e24553, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592909

RESUMO

ABSTRACT: Studies on predicting factors for adverse pregnancy outcomes (APOs) in Thai patients with systemic lupus erythematosus (SLE) are limited. This retrospective observation study determined APOs and their predictors in Thai patients with SLE.Medical records of pregnant SLE patients in a lupus cohort, seen from January 1993 to June 2017, were reviewed.Ninety pregnancies (1 twin pregnancy) from 77 patients were identified. The mean age at conception was 26.94 ±â€Š4.80 years. At conception, 33 patients (36.67%) had active disease, 23 (25.56%) hypertension, 20 (22.22%) renal involvement, and 6 of 43 (13.95%) positive anti-cardiolipin antibodies or lupus anti-coagulants, and 37 (41.11%) received hydroxychloroquine. Nineteen patients (21.11%) had pregnancy loss. Of 71 successful pregnancies, 28 (31.11%) infants were full-term, 42 (46.67%) pre-term and 1 (11.11%) post-term; 19 (26.39%) were small for gestational age (SGA), and 38 (52.58%) had low birth weight (LBW). Maternal complications occurred in 21 (23.33%) pregnancies [10 (11.11%) premature rupture of membrane (PROM), 8 (8.89%) pregnancy induced hypertension (PIH), 4 (4.44%) oligohydramnios, 2 (2.22%) post-partum hemorrhage, and 1 (1.11%) eclampsia]. Patients aged ≥ 25 years at pregnancy and those ever having renal involvement had predicted pregnancy loss with adjusted odds ratio (AOR) [95% CI] of 4.15 [1.10-15.72], P = .036 and 9.21 [1.03-82.51], P = .047, respectively. Renal involvement predicted prematurity (6.02 [1.77-20.52, P = .004), SGA (4.46 [1.44-13.78], P = .009), and LBW in infants (10.01 [3.07-32.62], P < .001). Prednisolone (>10 mg/day) and immunosuppressive drugs used at conception protected against prematurity (0.11 [0.02-0.85], P = .034). Flares and hematologic involvement predicted PROM (8.45 [1.58-45.30], P = .013) and PIH (9.24 [1.70-50.24], P = .010), respectively. Cutaneous vasculitis (33.87 [1.05-1,094.65], P = .047), and renal (31.89 [6.66-152.69], P < .001), mucocutaneous (9.17 [1.83-45.90], P = .007) and hematologic involvement (128.00 [4.60-3,564.46], P = .004) during pregnancy predicted flare; while prednisolone (>10 mg/day) and immunosuppressive drug use at conception reduced that risk (0.08 [0.01-0.68, P = .021).APOs remain a problem in Thai pregnant SLE patients. Renal involvement and SLE flares were associated with the risk of APOs.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Fatores Etários , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia , Insuficiência Renal/epidemiologia , Estudos Retrospectivos , Tailândia/epidemiologia , Adulto Jovem
2.
JAMA Netw Open ; 3(12): e2029917, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315114

RESUMO

Importance: Patients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown. Objective: To determine the association between autoimmune disease and lung cancer survival. Design, Setting, and Participants: Retrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020. Exposure: Presence of autoimmune disease. Main Outcomes and Measures: Overall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group. Results: Of the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease. Conclusions and Relevance: Compared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.


Assuntos
Neoplasias Pulmonares , Pulmão/patologia , Idoso , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Autoimunidade , Biópsia/métodos , Biópsia/estatística & dados numéricos , Comorbidade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Pesquisa Interdisciplinar , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Estadiamento de Neoplasias , Noroeste dos Estados Unidos/epidemiologia , Prognóstico , Estudos Retrospectivos , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Padrão de Cuidado/organização & administração , Padrão de Cuidado/estatística & dados numéricos , Análise de Sobrevida
3.
BMJ Case Rep ; 13(12)2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33376090

RESUMO

Autoimmune hepatitis (AIH) is an autoimmune liver disease characterised by the presence of autoantibodies including antinuclear antibodies, anti-smooth muscle antibody and hypergammaglobulinaemia. Systemic lupus erythematosus (SLE) is a systemic disease that can affect multiple organs. Coexistence of AIH and SLE as an overlap syndrome occurs in about 1%-2.6% of the AIH cases. Since both conditions share common autoimmune features, their coexistence can pose a diagnostic dilemma which can result in a delay in treatment. We present here a challenging case of a middle-aged woman with AIH in remission who later developed new-onset fatigue, pleural effusion and splenomegaly.


Assuntos
Autoanticorpos/sangue , Hepatite Autoimune , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico , Derrame Pleural , Esplenomegalia , Biópsia/métodos , Comorbidade , Diagnóstico Diferencial , Progressão da Doença , Feminino , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/imunologia , Hepatite Autoimune/terapia , Humanos , Fígado/patologia , Testes de Função Hepática/métodos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Linfadenopatia/diagnóstico , Linfadenopatia/etiologia , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
4.
Molecules ; 25(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202656

RESUMO

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Betacoronavirus/patogenicidade , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/fisiopatologia , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Esquema de Medicação , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/virologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia , Zika virus/patogenicidade , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologia
5.
Am J Physiol Regul Integr Comp Physiol ; 319(4): R448-R454, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32813539

RESUMO

Hypertension and kidney involvement are common in patients with autoimmune disease. Sodium intake is linked to hypertension in both human and animal studies. Evidence suggests that dietary salt may be an important environmental factor that promotes autoimmune activity. Therefore, we hypothesized that a long-term high-salt diet would accelerate the progression of autoimmunity, hypertension, and albuminuria during systemic lupus erythematosus (SLE), an autoimmune disease that predominantly affects young women and has a high prevalence of hypertension and renal disease. To test this hypothesis, an established experimental model of SLE (female NZBWF1 mice) that develops hypertension and renal disease was used. SLE mice were fed a high-salt (4% NaCl) or normal (0.4% NaCl) diet for 24 wk beginning at 10 wk of age and ending at 34 wk of age, a time by which female NZBWF1 mice typically have hypertension and exhibit signs of renal disease. Plasma anti-dsDNA autoantibodies were measured as an indicator of active SLE disease, and urinary albumin was monitored longitudinally as a marker of renal disease. Arterial pressure was measured in conscious, freely moving mice at 34 wk of age. Urinary endothelin-1 (ET-1) excretion, renal endothelin A and B receptor protein expression, and renal mRNA expression of NOS1, NOS2, NOX2, MCP-1, TNF-α, serum- and glucocorticoid-regulated kinase 1, and interleukin-2 (IL-2) were assessed to determine the impact on gene products commonly altered by a high-salt diet. SLE mice fed a high-salt diet had increased circulating autoantibodies, but the high-salt diet did not significantly affect albuminuria or arterial pressure. Urinary ET-1 excretion was increased, whereas renal endothelin A receptor and IL-2 expression were decreased in response to a high-salt diet. These data suggest that a chronic high-salt diet may not accelerate cardiovascular and renal consequences commonly associated with SLE.


Assuntos
Albuminúria/fisiopatologia , Pressão Sanguínea/fisiologia , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Sódio na Dieta , Albuminúria/imunologia , Animais , Autoanticorpos , DNA/imunologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Hipertensão/imunologia , Hipertensão/fisiopatologia , Rim/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Camundongos
6.
Clin Rheumatol ; 39(11): 3195-3204, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32852623

RESUMO

INTRODUCTION: Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic. METHOD: This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test. RESULTS: A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to "Italian general population" (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various "connective tissue diseases" compared to "inflammatory arthritis group" (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011). CONCLUSIONS: The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases. Key Points • Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients' increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement. • The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing. • Patients with "connective tissue diseases" show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to "inflammatory arthritis group". • Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.


Assuntos
Doenças Autoimunes/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/fisiopatologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/fisiopatologia , Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/epidemiologia , Dermatomiosite/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/fisiopatologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/fisiopatologia , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/fisiopatologia , Doenças do Tecido Conjuntivo Indiferenciado/tratamento farmacológico , Doenças do Tecido Conjuntivo Indiferenciado/epidemiologia , Doenças do Tecido Conjuntivo Indiferenciado/fisiopatologia
7.
Reumatol. clín. (Barc.) ; 16(4): 255-261, jul.-ago. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-194951

RESUMO

OBJECTIVES: To investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients. PATIENTS AND METHODS: This study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection. RESULTS: The NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9. CONCLUSION: NLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging


OBJETIVOS: Investigar el papel de la proporción de neutrófilos a linfocitos (NLR), y la relación de plaquetas a linfocitos (PLR) como marcadores de actividad en el lupus eritematoso sistémico (LES) sin nefritis, y pacientes con nefritis lúpica (NL). PACIENTES Y MÉTODOS: Este estudio incluyó a 60 pacientes con LES con NL, 60 pacientes con LES sin afectación renal y 30 controles sanos. Analizamos las correlaciones entre NLR y PLR con la actividad de la enfermedad y la afección renal. RESULTADOS: La NLR de los pacientes con LES fue mucho más alta que los de los controles. Ambas razones mostraron valores significativamente mayores en pacientes con LES con enfermedad activa. La NLR y la PLR se correlacionaron positivamente con SLEDAI, ESR y CRP y se correlacionaron negativamente con C4. Los pacientes con LES con LN tenían niveles más altos de NLR que aquellos sin nefritis. La NLR mostró correlaciones positivas con BUN, urea sérica, creatinina sérica y proteína urinaria de 24h. Encontramos que la NLR está relacionada con el nivel de anti-dsDNA y las clases de biopsia renal. Mientras que la PLR estaba relacionada solo con anti-dsDNA. La mejor NLR para predecir la enfermedad activa del SLE fue de 2,2 y el mejor valor de corte de la PLR fue 132,9. CONCLUSIÓN: La NLR y la PLR son marcadores inflamatorios útiles para evaluar la actividad de la enfermedad en pacientes con LES. Además, la NLR podría reflejar la afectación renal en pacientes con LES y se asocia con las diferentes clases de su estadificación histológica


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Lúpus Eritematoso Sistêmico/sangue , Plaquetas/imunologia , Neutrófilos , Linfócitos , Lúpus Eritematoso Sistêmico/fisiopatologia , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Estudos Transversais , Biomarcadores , Curva ROC
9.
Autoimmun Rev ; 19(9): 102612, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32668290

RESUMO

"Rhupus" or "rhupus syndrome" is a poorly described and underdiagnosed disease in which features of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) appear in the same patient, most often sequentially. The SLE-related involvement is usually mild, dominated by hematological abnormalities and skin, serosal and renal involvement. The natural history of rhupus arthritis follows an RA-like pattern and can progress towards typical inflammatory erosions, deformations and disability. Despite the lack of consensus on the definition of rhupus and on its place in the spectrum of autoimmunity, a growing number of studies are pointing towards a true overlap between RA and SLE. However, the inclusion criteria employed in the literature during the last 4 decades are heterogeneous, making the already rare cohorts and case reports difficult to analyze. Because of this heterogeneity and due to the rarity of the disease, the prevalence, pathophysiology and natural history as well as the radiological and immunological profiles of rhupus are poorly described. Moreover, since there is no validated therapeutic strategy, treatment is based on clinicians' experience and on the results of a few studies. We herein present a systematic literature review to analyze the clinical and laboratory data of all reported rhupus patients and to provide up-to-date information about recent advances in the understanding of the pathophysiological mechanisms, diagnostic tools and treatment options.


Assuntos
Artrite Reumatoide/complicações , Lúpus Eritematoso Sistêmico/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Prevalência , Síndrome
10.
Isr Med Assoc J ; 22(6): 348-351, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32558439

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is more frequent in patients with systemic lupus erythematosus (SLE) compared with age- and sex-matched healthy subjects. SLE is an autoimmune disease that is more prevalent in women (9:1). Women tend to develop CVD in post-menopausal years; however, women with SLE may develop endothelial dysfunction and CVD at a younger age in the pre-menopausal years. OBJECTIVES: To study the endothelial function of adult-onset SLE patients from the north of Israel (the Galilee region) and to determine whether modern management (including biological treatments) changes the risk of developing CVD. METHODS: Thirteen females with adult-onset SLE without renal involvement were recruited to this prospective study. Clinical parameters (age, height, body mass index [BMI]), laboratory parameters (C-reactive protein [CRP] and hemoglobin level), and vascular responsiveness (flow mediated diameter percent change [FMD%]) were evaluated and compared to 11 age-matched healthy females. Student's t-test was used to find differences between the two groups. RESULTS: No difference was observed in adult-onset SLE female patients and their age- and sex-matched controls with regard to age (42.1 ± 11.8 years vs. 36.6 ± 10.8 years, P = NS), BMI (25 ± 1.8 kg/m2 vs. 25 ± 2.5 kg/m2, P = NS), and hemoglobin level (11.9 ± 0.9 gr% vs. 12.7 ± 1.2 gr%, P = NS). However, a significant difference was found in CRP (2.57 ± 2.2 mg vs. 0.60 ± 0.37 mg, P = 0.001), vascular responsiveness (0.94 ± 6.6 FMD% vs. 9.2 ± 8.1 FMD%, P = 0.012), and height (165.7 ± 4.5 cm vs. 171.6 ± 5.8 cm, P = 0.009). CONCLUSIONS: Adult-onset SLE females had impaired endothelial function even though they were treated by modern protocols.


Assuntos
Endotélio Vascular/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Idade de Início , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Clinics (Sao Paulo) ; 75: e1515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321114

RESUMO

This study aimed to systematically review neuropsychiatric lupus erythematosus (NPSLE) and establish a simplified diagnostic criterion for NPSLE. Publications from 1994 to 2018 in the database (Wanfang data (http://www.wanfangdata.com.cn/index.html) and China National Knowledge Internet (http://www.cnki.net)) were included. In total, 284 original case reports and 24 unpublished cases were collected, and clinical parameters were analyzed. An attempt was made to develop a set of simplified diagnostic criteria for NPSLE based on cases described in the survey and literature; moreover, and pathophysiology and management guidelines were studied. The incidence rate of NPSLE was estimated to be 12.4% of SLE patients in China. A total of 408 NPSLE patients had 652 NP events, of which 91.2% affected the central nervous system and 8.8% affected the peripheral nervous system. Five signs (manifestations, disease activity, antibodies, thrombosis, and skin lesions) showed that negative and positive predictive values were more than 70%, included in the diagnostic criteria. The specificity, accuracy, and positive predictive value (PPV) of the revised diagnostic criteria were significantly higher than those of the American College of Rheumatology (ACR) criteria (χ2=13.642, 15.591, 65.010, p<0.001). The area under the curve (AUC) for revised diagnostic criteria was 0.962 (standard error=0.015, 95% confidence intervals [CI] =0.933-0.990), while the AUC for the ACR criteria was 0.900 (standard error=0.024, 95% CI=0.853-0.946). The AUC for the revised diagnostic criteria was different from that for the ACR criteria (Z=2.19, p<0.05). Understanding the pathophysiologic mechanisms leading to NPSLE is essential for the evaluation and design of effective interventions. The set of diagnostic criteria proposed here represents a simplified, reliable, and cost-effective approach used to diagnose NPSLE. The revised diagnostic criteria may improve the accuracy rate for diagnosing NPSLE compared to the ACR criteria.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , China , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Reumatologia , Inquéritos e Questionários
12.
J Hum Genet ; 65(8): 675-681, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32313195

RESUMO

Previous studies are inconclusive on the relationships between BLK gene polymorphisms and clinical features of systemic lupus erythematosus (SLE). The present study aimed to estimate association between BLK loci and SLE clinical features in Chinese population. Associations between BLK single-nucleotide polymorphisms (SNPs) and susceptibility to SLE in this study were estimated using data of 1205 health controls previously reported in the same population. And a total of 814 SLE patients recruited from two different sources according with ACR criteria were analyzed for genotype-phenotype associations. A meta-analysis was conducted of the associations between BLK loci and renal disorder in SLE. The expression quantitative trait locus (eQTL) data were also extracted from the public databases for the selected SNPs. Significant associations were observed between these SNPs and susceptibility to SLE. In addition, the data showed that rs2618479 and rs7812879 were associated with renal disorder [OR = 1.51 (95% CI: 1.15, 1.99) and 1.61 (95% CI: 1.21, 2.14), Pcorr = 0.033 and 0.011, respectively] and proteinuria [OR = 1.47 (95% CI: 1.12, 1.95) and 1.52 (95% CI: 1.14, 2.03), Pcorr = 0.048 and 0.040, respectively]. The consistent associations were observed in two independent centers as well as new cases group. The result of meta-analysis for rs2618479 was also significant [OR = 1.35 (95% CI: 1.12, 1.62)]. In addition, bioinformatics analysis demonstrated that the two SNPs were significantly associated with the expression of BLK in whole blood and several immune cells. Our data support that variant loci of BLK are associated with presence of renal disorder in patients with SLE.


Assuntos
Nefropatias/genética , Lúpus Eritematoso Sistêmico/genética , Quinases da Família src/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Estudos de Associação Genética , Humanos , Nefropatias/complicações , Nefropatias/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Quinases da Família src/sangue , Quinases da Família src/metabolismo
13.
Sci Rep ; 10(1): 6400, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286471

RESUMO

Systemic lupus erythematosus (SLE) gastrointestinal (GI) complication is characterized by multi-segment and multi-compartment involvement. The aim of this study is to develop a computed tomography (CT) image-based system for disease evaluation. SLE patients with GI involvement from two independent cohorts were retrospectively included. Baseline abdominal CT scan with intravenous and oral contrast was obtained from each individual. A CT scoring system incorporating the extent of GI tract involvement and intestinal wall thickness, along with extra-GI compartment involvement, was developed and validated. The outcome measurement was the time to GI functional recovery, defined as the time to tolerable per os (PO) intake ≥50% of ideal calories (PO50). A total of 54 and 37 patients with SLE GI involvement were enrolled in the derivation and validation cohorts, respectively. The CT scores for SLE GI involvement were positively correlated with patients' time to PO50 (r = 0.57, p < 0.0001, derivation cohort; r = 0.42, p = 0.0093, validation cohort). Patients with a CT score ≤ 3 had a shorter time to PO50 (median time of 0 day) in pooled cohort, whereas those with a CT score > 3 incurred a significantly prolonged recovery with a median time to PO50 of 13 days (p < 0.0001). The CT-based scoring system may facilitate more accurate assessment and individualized management of SLE patients with GI involvement.


Assuntos
Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/patologia , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologia , Tomografia Computadorizada por Raios X , Adulto , Feminino , Trato Gastrointestinal/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Resultado do Tratamento
14.
Arch Oral Biol ; 113: 104708, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32203722

RESUMO

OBJECTIVE: The important role of intestinal microbiota in systemic lupus erythematosus (SLE) has been recognized. Oral-gut microbiome axis is a crucial link in human health and disease, but few researches indicated the relationship between oral microorganisms and SLE. This study mainly explored the composition and changes of oral microorganisms in SLE patients with different stages, clinical manifestations and biomarkers. DESIGN: Oral microbiota was detected by 16S ribosomal RNA gene sequencing from 20 SLE patients and 19 healthy controls (HCs). The evenness, diversity and composition of oral microbiota were analyzed. Moreover, receiver-operating characteristic analysis was conducted. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to investigate microbiota functions. RESULTS: The oral microbiota of SLE patients was imbalanced and the diversity was decreased, but no difference was found between new-onset and treated SLE patients. Families Lactobacillaceae, Veillonellaceae and Moraxellaceae were enriched in SLE patients. Families like Corynebacteriaceae, Micrococcaceae, Defluviitaleaceae, Caulobacteraceae, Phyllobacteriaceae, Methylobacteriaceae, Hyphomicrobiaceae, Sphingomonadaceae, Halomonadaceae, Pseudomonadaceae, Xanthomonadaceae, etc. were decreased in SLE patients. After multiple testing adjustment, families Sphingomonadaceae, Halomonadaceae, and Xanthomonadaceae were significantly decreased in SLE patients. And area under the curve was 0.953 (95% confidence intervals 0.890-1.000) to distinguish SLE patients from HCs. There were differences in metabolic pathways between SLE and HCs (P = 0.025). CONCLUSIONS: These findings collectively support that oral microbiota dysbiosis and aberrant metabolic pathways were observed in patients with SLE. Our findings may provide suggestive evidences for the diagnosis and treatment of SLE.


Assuntos
Disbiose , Microbioma Gastrointestinal , Lúpus Eritematoso Sistêmico/microbiologia , Boca/microbiologia , Estudos de Casos e Controles , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Filogenia , RNA Ribossômico 16S
15.
Arch Osteoporos ; 15(1): 54, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221755

RESUMO

PURPOSE: Recently, trabecular bone score (TBS) has emerged as an important supplementary assessment tool in osteoporosis diagnosis and management. The high incidence of fragility fracture within the non-osteoporotic range of bone mineral density (BMD), among systemic lupus erythematosus (SLE) patients, highlights the crucial role of bone microarchitecture in osteoporosis. This study aimed to evaluate whether TBS identified existing vertebral fractures (VF) more accurately than BMD in SLE patients. METHODS: This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively. RESULT: The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605). CONCLUSION: Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.


Assuntos
Absorciometria de Fóton/estatística & dados numéricos , Osso Esponjoso/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Adulto , Idoso , Ásia Sudeste/epidemiologia , Densidade Óssea , Osso Esponjoso/fisiopatologia , Feminino , Humanos , Incidência , Modelos Logísticos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
16.
Am J Physiol Renal Physiol ; 318(5): F1074-F1085, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32150445

RESUMO

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by circulating autoantibodies, prevalent hypertension, renal injury, and cardiovascular disease. Onset of the disease often occurs in young women of childbearing age. Although kidney involvement is common to patients with SLE, little is known about temporal changes in renal hemodynamic function and its relationship to the pathogenesis of hypertension during autoimmune diseases. We hypothesized that the loss of immunological tolerance and subsequent production of autoantibodies in SLE leads to impaired renal hemodynamic function that precedes the development hypertension. Female NZBWF1 (SLE) mice and female NZW/LacJ (control) mice were instrumented with carotid artery and jugular vein catheters to determine mean arterial pressure (MAP) and glomerular filtration rate, respectively, at ages of 15, 20, 24, 28, 31, and 34 wk. In addition, urinary albumin excretion, blood urea nitrogen, circulating autoantibodies, and glomerulosclerosis were assessed at each age. Levels of circulating autoantibodies are increased between 24 and 28 wk of age in NZBWF1 mice and were significantly greater than in control mice. Glomerular filtration rate was significantly increased at 28 wk of age in NZBWF1 mice followed by a sharp decline at 34 wk of age. NZBWF1 mice had an increase in MAP that occurred by 34 wk of age. These data show that changes in circulating autoantibodies, renal hemodynamic function, and glomerular injury occur in NZBWF1 mice before changes in MAP, suggesting an important mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.


Assuntos
Pressão Arterial , Hipertensão/fisiopatologia , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Albuminúria/imunologia , Albuminúria/fisiopatologia , Animais , Autoanticorpos/sangue , Autoimunidade , Nitrogênio da Ureia Sanguínea , Modelos Animais de Doenças , Feminino , Taxa de Filtração Glomerular , Hipertensão/sangue , Hipertensão/imunologia , Rim/patologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Camundongos Endogâmicos NZB , Fatores de Tempo
17.
Int J Mol Sci ; 21(4)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079137

RESUMO

Autonomic neuropathy has been reported in autoimmune rheumatic diseases (ARD) including Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathophysiological mechanism underlying autonomic dysfunction remains unknown to researchers. On the other hand, autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder, which causes dysautonomia that is mediated by autoantibodies against ganglionic acetylcholine receptors (gAChRs). The purpose of this review was to describe the characteristics of autonomic disturbance through previous case reports and the functional tests used in these studies and address the importance of anti-gAChR antibodies. We have established luciferase immunoprecipitation systems to detect antibodies against gAChR in the past and determined the prevalence of gAChR antibodies in various autoimmune diseases including AAG and rheumatic diseases. Autonomic dysfunction, which affects lower parasympathetic and higher sympathetic activity, is usually observed in ARD. The anti-gAChR antibodies may play a crucial role in autonomic dysfunction observed in ARD. Further studies are necessary to determine whether anti-gAChR antibody levels are correlated with the severity of autonomic dysfunction in ARD.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Gânglios Autônomos/fisiopatologia , Receptores Colinérgicos/imunologia , Doenças Reumáticas/fisiopatologia , Animais , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Sistema Nervoso Autônomo/imunologia , Sistema Nervoso Autônomo/fisiopatologia , Gânglios Autônomos/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Doenças Reumáticas/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/fisiopatologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia
18.
Int J Med Sci ; 17(2): 153-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32038098

RESUMO

Aims: Systemic Lupus Erythematosus (SLE) is a connective tissue disease characterized by a wide range of pleomorphic pictures, including mucocutaneous, renal, musculoskeletal and neurological symptoms. It involves oral tissues, with hyposalivation, tooth decay, gingivitis, angular cheilitis, ulcers and glossitis. Temporomandibular disorders represent a heterogeneous group of inflammatory or degenerative diseases of the stomatognatic system, with algic and/or dysfunctional clinical features involving temporomandibular joint (TMJ) and related masticatory muscles. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD) in SLE patients (Lp) compared with a control group. Methods: Fifty-five patients (9 men and 46 women) with diagnosed Lupus were recruited in the study group. A randomly selected group of 55 patients, matched by sex and age, served as control group. The examination for TMD symptoms and signs was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) through a questionnaire and clinical examination. Results: Lupus patients complained more frequently (95.8%) of oral and TMJ symptoms (dysgeusia, stomatodynia, masticatory muscle pain during function, neck and shoulder muscles pain and presence of tinnitus) but only xerostomia (χ2=4,1548 p=0,0415), temple headache (χ2=4,4542 p=0,035) and the sensation of a stuck jaw (Mid-p-test p=0,043) were significant. About signs, cheilitis (p=0,0284) oral ulcers (χ2=4,0104 p=0,045) and fissured tongue are significantly more frequent in study group. The salivary flow was significantly decreased in the study group respect to the control one (p<0.0001). As regard to the oral kinematics, restricted movements (RM) in protrusion and left lateral movement were significantly different between study group and controls. In particular, 85,2% of Lp showed limited protrusion versus 56,4% of controls (χ2= 10,91 p<0,001); 59,3% of Lp had also a limitation during left lateral movement versus 47,3% of controls (T=2,225 p=0,0282). About bruxism, only the indentations on the lateral edges of the tongue were found in Lp group (72,7%), with a significant difference respect to controls (χ2=7,37 p=0,007). Conclusions: While masticatory muscles have an overlapping behavior in both groups, the findings collected show a more severe TMJ kinematic impairment in Lp than in controls, with protrusion and left lateral movements significantly different. In addition, a remarkable reduction of salivary flow has been detected in Lp compared to controls. In conclusion, this autoimmune disease seems to play a role in oral manifestations and TMJ disorders, causing an increase in orofacial pain and an altered chewing function.


Assuntos
Bruxismo/fisiopatologia , Dor Facial/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adulto , Bruxismo/complicações , Bruxismo/diagnóstico , Dor Facial/complicações , Dor Facial/diagnóstico , Feminino , Cefaleia/complicações , Cefaleia/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Mastigação , Músculos da Mastigação/fisiopatologia , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Inquéritos e Questionários , Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/diagnóstico , Doenças Dentárias/complicações , Doenças Dentárias/diagnóstico , Doenças Dentárias/fisiopatologia , Xerostomia/complicações , Xerostomia/diagnóstico , Xerostomia/fisiopatologia
20.
Arthritis Rheumatol ; 72(7): 1134-1142, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32017464

RESUMO

OBJECTIVE: To identify potential clusters of systemic lupus erythematosus (SLE) organ-specific flares and their relationship to fine particulate matter pollution (PM2.5), temperature, ozone concentration, resultant wind, relative humidity, and barometric pressure in the Hopkins Lupus Cohort, using spatiotemporal cluster analysis. METHODS: A total of 1,628 patients who fulfilled the Systemic Lupus International Collaborating Clinics classification criteria for SLE and who had a home address recorded were included in the analysis. Disease activity was assessed using the Lupus Activity Index. Assessment of rash, joint involvement, serositis, and neurologic, pulmonary, renal, and hematologic activity was quantified on a 0-3 visual analog scale (VAS). An organ-specific flare was defined as an increase in VAS of ≥1 point compared to the previous visit. Spatiotemporal clusters were detected using SaTScan software. Regression models were used for cluster adjustment and included individual, county-level, and environmental variables. RESULTS: Significant clusters unadjusted for environmental variables were identified for joint flares (P < 0.05; n = 3), rash flares (P < 0.05; n = 4), hematologic flares (P < 0.05; n = 3), neurologic flares (P < 0.05; n = 2), renal flares (P < 0.001; n = 4), serositis (P < 0.001; n = 2), and pulmonary flares (P < 0.001; n = 2). The majority of the clusters identified changed in significance, temporal extent, or spatial extent after adjustment for environmental variables. CONCLUSION: We describe the first spatiotemporal clusters of lupus organ-specific flares. Seasonal, as well as multi-year, cluster patterns were identified, differing in extent and location for the various organ-specific flare types. Further studies focusing on each individual organ-specific flare are needed to better understand the driving forces behind these observed changes.


Assuntos
Poluição do Ar/estatística & dados numéricos , Pressão Atmosférica , Lúpus Eritematoso Sistêmico/fisiopatologia , Material Particulado , Exacerbação dos Sintomas , Tempo (Meteorologia) , Adulto , Artrite/fisiopatologia , Estudos de Coortes , Exantema/fisiopatologia , Feminino , Doenças Hematológicas/fisiopatologia , Humanos , Umidade , Pneumopatias/fisiopatologia , Nefrite Lúpica/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Ozônio , Serosite/fisiopatologia , Análise Espaço-Temporal , Temperatura , Vento
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