RESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.
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Progressão da Doença , Lúpus Eritematoso Sistêmico/etnologia , Feminino , Humanos , América Latina/etnologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Espanha/epidemiologia , População Branca/estatística & dados numéricosRESUMO
OBJECTIVE: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. METHODS: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. RESULTS: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). CONCLUSION: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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Antirreumáticos/uso terapêutico , Rituximab/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Idoso , Feminino , Fibrose , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/etiologia , Sistema de Registros , Testes de Função Respiratória , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Pele/patologia , Resultado do Tratamento , Capacidade VitalRESUMO
Objective The objective of this study was to describe the demographic, clinical, and immunological manifestations of systemic lupus erythematosus (SLE) in male patients. Methods A cross-sectional, multicenter study was carried out of 3651 patients (353 men, 9.7%, and 3298 women, 90.2%) diagnosed with SLE, included in the Spanish Rheumatology Society SLE Registry (RELESSER). Results Mean ages (18-92 years) of symptom onset were 37 (SD 17) years (men) and 32 (SD 14) years (women). Male/female ratio was 1/9. Age of onset of symptoms and age at diagnosis were higher in men than in women ( p < 0.001). Males were diagnosed earlier than females (p = 0.04) and had more cardiovascular comorbidities ( p < 0.001). Two hundred and thirty-six males (68%) with SLE required hospitalization in comparison with 1713 females (53%) ( p < 0.001). During follow-up, 208 patients died: 30 men (9.3%) and 178 women (5.9%) ( p = 0.02). As regards clinical manifestations, loss of weight ( p = 0.01), lymphadenopathies ( p = 0.02), and splenomegaly ( p = 0.02) were more common in male patients. Female patients were more likely to have inflammatory rash, alopecia, and arthritis ( p < 0.05). As for lung involvement, men with SLE had more pleural fibrosis ( p < 0.001) and pulmonary embolism ( p = 0.01). However, Raynaud's phenomenon was more common in women (35%) than in men (23.7%) ( p < 0.001); lupus nephritis was more common in men, being present in 155 (44.8%) of males versus 933 (29%) of females ( p < 0.001). Multivariate analysis showed that SLE patients with a high Charlson index (more than 3 points) and age > 50 years had a higher mortality (odds ratios 3.6 and 2.1, respectively). Furthermore, SLE patients who developed pulmonary hemorrhage, pulmonary hypertension, psychiatric involvement, complement deficiency, and hemophagocytic syndrome also had higher mortality, regardless of gender. Conclusion Patients with SLE over the age of 50 years have an increased risk of mortality. In Caucasians, age at diagnosis and symptom onset is higher in men than in women. The diagnostic delay is shorter in men. Male SLE patients present more cardiovascular comorbidities, and also more serositis, adenopathies, splenomegaly, renal involvement, convulsion, thrombosis, and lupus anticoagulant positivity than women.
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Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/epidemiologia , Doença de Raynaud/epidemiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Espanha , Adulto JovemRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a very rare syndrome with a mortality up to 95% of cases if not treated. It is characterised by an excessive activation of the immune system that leads to a disproportionate and destructive inflammatory response. The high mortality rates are in part due to a delay in the diagnosis, and therefore clinicians must maintain a high index of suspicion. When the treatment is started early, the survival rate reaches around 55% of cases. HLH usually presents with persistent fever, pancytopenia, and organomegaly and is associated with very high levels of serum ferritin. In this manuscript, we present the case of a patient with primary Sjögren's syndrome who developed HLH after an acute infection by Cytomegalovirus. We will describe and discuss the pathogenesis, differential diagnosis and a pragmatic approach to the treatment for this critically important and, when diagnosed early, potentially curable syndrome.
Assuntos
Infecções por Citomegalovirus/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Síndrome de Sjogren/complicações , Idoso , Feminino , HumanosRESUMO
OBJECTIVES: The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. RESULTS: A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. CONCLUSIONS: A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.
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Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Anticorpos Antinucleares/análise , Antimaláricos/administração & dosagem , Estudos de Coortes , Estudos Transversais , Feminino , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Modelos Logísticos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
OBJECTIVES: The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients. METHODS: In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2 and <5.1 were used to determine whether detectable IFX levels were any predictor of clinical disease activity. Logistic regression analysis was run to check other possible factors associated with RA clinical outcomes such as MTX concomitant use, CRP and ESR. RESULTS: Sixteen (27%) out of the 60 patients tested negative; 28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX levels were higher in patients either in remission or showing low disease activity than in those with moderate and high disease activity (p=0.014). Significant association was found between IFX levels and clinical disease activity (p=0.001). Detectable levels of IFX shows better sensitivity and specificity to identify patients with DAS28<3.2 than to identify patients with DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E 0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did not interfere with this association. Seven out of the 8 patients with anti-IFX antibodies presented DAS28>3.2 (p=0.005). CONCLUSIONS: DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.
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Artrite Reumatoide , Infliximab , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Anticorpos/sangue , Antirreumáticos/imunologia , Antirreumáticos/farmacocinética , Área Sob a Curva , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Disponibilidade Biológica , Sedimentação Sanguínea , Estudos Transversais , Feminino , Humanos , Infliximab/imunologia , Infliximab/farmacocinética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença , Espanha , Estatística como Assunto , Resultado do TratamentoRESUMO
OBJECTIVES: This paper aims to identify clinical and serological differences, damage accrual and mortality, in juvenile, adult and late-onset SLE. METHODS: We conducted our study with patients fulfilling SLE classification criteria taken from the Hospital Gregorio Marañon Autoimmune Systemic Rheumatic Diseases' Registry (1986 to 2012). Clinical characteristics, laboratory data and therapies used during the course of the disease were analysed with patients divided into 3 groups: juvenile-onset (≤ 18 years), adult-onset (19-50) and late onset (>50 years). RESULTS: Four hundred and forty-five patients were included. Renal disease and cutaneous manifestations were more frequent in the juvenile-onset group at disease onset. During follow-up, juvenile-onset group presented a higher incidence of renal disease, malar rash, Raynaud's phenomenon, cutaneous vasculitis, and neuropsychiatric manifestations than the other two groups. Arthritis and lymphopoenia were more frequent in the adult-onset group. Arterial hypertension and neoplasm were more frequent in the late-onset group. Low serum complement, anti-dsDNA, anti-U1RNP and anti-Sm antibodies were more common in the juvenile-onset group. Patients with late-onset SLE had more damage accrual. Thirty-seven patients (8.3%) died during the study. All-cause mortality was significantly higher in the late-onset group. Age at disease onset >50 years was an independent risk factor for damage accrual (OR, 2.2; 95%CI, 1.1-4.6; p=0.029) and mortality (OR, 2.6; 95%CI, 1.1-6.3; p=0.03). CONCLUSIONS: We found significant differences in clinical and serological profiles between juvenile, adult and late-onset SLE. The most significant of which was a higher prevalence of neuropsychiatric and renal complications as well as different autoantibody signatures for the juvenile-onset group.
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Autoanticorpos , Hipertensão , Lúpus Eritematoso Sistêmico , Neoplasias , Adulto , Distribuição por Idade , Idade de Início , Idoso , Autoanticorpos/sangue , Autoanticorpos/classificação , Criança , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Monitorização Imunológica/métodos , Neoplasias/epidemiologia , Neoplasias/etiologia , Prevalência , Fatores de Risco , Espanha/epidemiologia , Análise de SobrevidaRESUMO
Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.
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Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Doenças Cardiovasculares/genética , Loci Gênicos/genética , Predisposição Genética para Doença , Adulto , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Artérias Carótidas/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , EspanhaRESUMO
Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.
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Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Cromossomos Humanos Par 11/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/genética , Demografia , Feminino , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.
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Anticorpos Monoclonais Murinos/uso terapêutico , Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Depleção Linfocítica , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Estudos Longitudinais , Depleção Linfocítica/efeitos adversos , Depleção Linfocítica/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Resultado do TratamentoRESUMO
OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.
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Fibrose Pulmonar , Escleroderma Sistêmico , Humanos , Estados Unidos , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/complicações , Pontuação de Propensão , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
We report a patient who developed pericarditis and pericardial tamponade coinciding with polymyalgia rheumatica onset. Our patient did not show any clinical sign of vasculitis; temporal artery biopsies were negative for giant cell arteritis. Pericardial biopsy in our case shows inflammatory perivascular lymphocytary infiltrates thus we believe pericardial effusion has an inflammatory-immunologic origin. Cardiac manifestations are exceptional in polymyalgia rheumatica, though it should be considered in the differential diagnosis in patients with pericarditis over 50 years. The recognition of this uncommon manifestation is very important due to the good response to corticosteroid treatment.
Assuntos
Tamponamento Cardíaco/complicações , Pericardite/complicações , Polimialgia Reumática/complicações , Idoso , Anti-Inflamatórios/uso terapêutico , Biópsia , Tamponamento Cardíaco/tratamento farmacológico , Tamponamento Cardíaco/patologia , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Pericardite/tratamento farmacológico , Pericardite/patologia , Polimialgia Reumática/tratamento farmacológico , Polimialgia Reumática/patologia , Prednisona/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. RESULTS: Mean age (years)⯱â¯S.D. at diagnosis was 14.2⯱â¯2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI⯱â¯S.D. was 1.27⯱â¯1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, Pâ¯<â¯0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (Pâ¯<â¯0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (Pâ¯<â¯0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (Pâ¯<â¯0.017 for both comparisons). CONCLUSIONS: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.
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Lúpus Eritematoso Sistêmico/mortalidade , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Sistema de Registros , Espanha , Taxa de SobrevidaRESUMO
Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.
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Antituberculosos/uso terapêutico , Terapia Biológica/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Tuberculose/prevenção & controle , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antituberculosos/administração & dosagem , Monitoramento de Medicamentos , Hidradenite Supurativa/tratamento farmacológico , Humanos , Imunidade Celular , Tuberculose Latente/diagnóstico , Seleção de Pacientes , Psoríase/tratamento farmacológico , Risco , Subpopulações de Linfócitos T/imunologia , Tuberculose/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The objective of this study was to determine the prevalence of antibodies against alpha-fodrin (alpha-fodrin) of the immunoglobulin G (IgG) isotype in Sjögren's syndrome (SS), as defined by European Community Study Group (ESG) and ESG-modified criteria. We arrived at the prevalence and mean concentrations of IgG anti-alpha-fodrin antibodies using enzyme-linked immunosorbent assay (ELISA) in 507 patients with SS, primary SS (pSS), and secondary SS (sSS), classified according to either the ESG or the ESG-modified criteria. IgG anti-alpha-fodrin antibodies were detected in 6/507 (1.2%) and 4/228 (1.7%) of the SS group, according to the ESG or ESG-modified criteria, respectively. Similar prevalence was found for patients with pSS or sSS. Anti-Ro/SSA antibodies were present in 151/409 (36.9%) vs. 149/213 (70.0%) of the SS group, 85/195 (43.6%) vs. 83/101 (82.2%) of the pSS group, and 66/214 (30.8%) vs. 66/112 (58.9%) of the sSS group. Anti-La/SSB antibodies were detected in 77/403 (19.1%) vs. 73/212 (34.4%) of the SS group, 47/194 (24.2%) vs. 45/101 (44.5%) of the pSS group, and 30/209 (14.3%) vs. 28/111 (25.2%) of the sSS group. No clinical associations were found. Only two IgG anti-alpha-fodrin-positive sera were anti-Ro/SSA-negative. We conclude that IgG antibodies against alpha-fodrin are present in a small percentage of people with SS, pSS, and sSS. The lower prevalence in patients classified according to the ESG criteria reflects the lower specificity of these criteria. IgG anti-alpha-fodrin antibodies can be detected in some SS patients whose sera do not contain anti-Ro/SSA antibodies.
Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Proteínas de Transporte/análise , Imunoglobulina G/análise , Proteínas dos Microfilamentos/análise , Prevalência , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/imunologia , Anticorpos Antinucleares/análise , Ensaio de Imunoadsorção Enzimática , Humanos , Síndrome de Sjogren/classificação , Síndrome de Sjogren/fisiopatologia , Espanha/epidemiologiaRESUMO
OBJECTIVES: Clinical and immunological features of patients with clinical manifestations of the antiphospholipid syndrome (APS) with anti-beta2-glycoprotein-I antibodies (anti-beta2-GP-I) but without anticardiolipin antibodies (aCL) or any other autoimmune condition are not well documented. We sought to determine the clinical significance of positive anti-beta2-GP-I with negative aCL. METHODS: From July 2002 through July 2003, 1,179 serum samples obtained in our hospital from the Community of Madrid were tested for anti-beta2-GP-I and aCL by enzyme-linked immunosorbent assay. Clinical records of patients with discordant anti-beta2-GP-I and aCL were retrospectively analysed. RESULTS: A total of 56 patients with discordant anti-beta2-GP-I and aCL were identified. By logistic regression analysis, after adjusting for age, sex and risk factors of thrombosis, the risk for developing APS criteria associated with anti-beta2-GP-I was significant [odds ratio 3.88; 95% confidence interval (CI): 1.05-14.27; p = 0.04). 15 out of 56 patients (26.8%) had positive anti-beta2-GP-I and negative aCL. 5 out of 15 anti-beta2-GP-I-positive patients had clinical APS without serological nor clinical evidence of any autoimmune disease. CONCLUSION: Determination of anti-beta2-GP-I should be considered in individual cases with clinical manifestations of primary APS and repeated negative results on conventional antiphospholipid antibody test.
Assuntos
Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Glicoproteínas/sangue , Idoso , Anticorpos Anticardiolipina/imunologia , Síndrome Antifosfolipídica/epidemiologia , Pré-Escolar , Feminino , Glicoproteínas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , beta 2-Glicoproteína IRESUMO
Nine cases of primary septic arthritis in heroin addicts are reported. Fibrous and cartilaginous joint localizations are prominent (four sternoarticular, three sacroiliac, one sacroccocygeal, and one knee). In all patients but one, conventional roentgenographic studies were negative. In six cases the causative agent was Staphylococcus aureus and in two cases, Candida albicans. In one case, it could not be determined. Our clinical observations, correlating the radioisotopic studies, suggest that in the first week of evolution the diagnostic procedure of choice is the [67Ga]citrate scintigram. Indeed, during this period the [99Tc]MDP bone scan is usually negative. The early demonstration and localization of the disease, together with the rapid bacteriologic diagnosis, allows for an early and more appropriate antibiotic treatment and better results.
Assuntos
Artrite Infecciosa/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Candidíase/diagnóstico por imagem , Radioisótopos de Gálio , Dependência de Heroína/complicações , Articulações/diagnóstico por imagem , Articulação Sacroilíaca/diagnóstico por imagem , Infecções Estafilocócicas/diagnóstico por imagem , Articulações Esternocostais/diagnóstico por imagem , Medronato de Tecnécio Tc 99m , Adolescente , Adulto , Artrite Infecciosa/etiologia , Candidíase/etiologia , Feminino , Humanos , Masculino , Cintilografia , Infecções Estafilocócicas/etiologia , Fatores de TempoRESUMO
A number of clinical and laboratory features of HIV infection are found in systemic lupus erythematosus (SLE). The objective of this study was to analyze the presence of circulating antibodies to small nuclear ribonucleoproteins (snRNP) in both diseases. Sera from 44 HIV-infected children, from 22 patients with childhood-onset SLE, and from 50 healthy children were studied. Anti-snRNP antibodies were detected by ELISA using recombinant and affinity-purified nuclear antigens, by counterimmunoelectrophoresis (CIE), and by immunoblotting using extractable nuclear antigens. Results included the detection of anti-snRNP antibodies by ELISA in 30 HIV-infected patients (68.1%) and 19 SLE patients (86.3%). These antibodies were directed against U1-RNP (61.3% and 77.2%, respectively), Sm (29.5% and 54.5%, respectively), 60 kDa Ro/SS-A (47.7% and 50%, respectively), and La/SS-B proteins (18.1% and 9%, respectively). None of the HIV-infected children and 11 SLE patients (50%) showed anti-snRNP antibodies by CIE. None of the HIV-infected patients showed anti-70 kDa U1-RNP or anti-D-Sm antibodies by immunoblotting. No differences between the two groups were noted on the presence of nonprecipitating anti-snRNP antibodies. No such reactivities were observed among the normal sera tested. The authors concluded that nonprecipitating anti-snRNP antibodies in HIV-infected children are as frequent as in childhood-onset SLE. The significance of these antibodies is not clear at present. Although polyreactive and low-affinity antibodies and a mechanism of molecular mimicry may explain these results, a specific stimulation of B cells by nuclear antigens could not be excluded.