RESUMO
OBJECTIVE: Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and relapse prevention and may be at risk for severe coronavirus disease 2019 (COVID-19). The study objective was to analyse risk factors and outcomes of COVID-19 in well-characterized AAV patients. METHOD: Data were retrieved from March 2020 to May 2021 from medical records of AAV cohorts in Stockholm and Uppsala, Sweden. COVID-19 was confirmed by positive PCR test or by ELISA. Severe COVID-19 was defined as need for non-invasive ventilation, intensive care unit care, and/or death. Age, gender, ANCA antibody type, ongoing immunosuppressive medication, and estimated glomerular filtration rate were recorded. RESULTS: The cohort comprised 310 AAV patients, of whom 29 (9%) were diagnosed with COVID-19. Four deaths were attributed to COVID-19. Fifteen patients (52%) were on prednisolone in the COVID-19 group and 130 (46%) in the non-COVID group, with significantly higher doses in COVID-19 patients (p < 0.01). Ongoing induction therapy was more prevalent in the COVID-19 group (p < 0.01). Severe COVID-19 was diagnosed in 9/29 (31%). Significant risk factors for severe COVID-19 were impaired kidney function (p = 0.01) and more intense immunosuppressive therapy (p = 0.02), with a trend for age (p = 0.07). Maintenance therapy with rituximab was not associated with severe COVID-19. CONCLUSIONS: Our findings highlight risks and suggest that more attention should be given to optimal AAV treatment in a pandemic situation. They also emphasize the need for continued shielding, mitigation strategies, and effective vaccination of AAV patients.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , COVID-19 , Humanos , Imunossupressores/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos , Rituximab/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnósticoRESUMO
OBJECTIVE: The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. METHOD: Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. RESULTS: Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (ρ = 0.45, p < 0.001, and ρ = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. CONCLUSION: Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Proteína C-Reativa , Humanos , Proteína C-Reativa/metabolismo , Albuminúria , Biomarcadores , Anticorpos Anticitoplasma de NeutrófilosRESUMO
Arthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non-erosive, as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n = 17) were analyzed with cytokine bead array for T helper-associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) could also be captured and were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE-derived SFMC were further stimulated in vitro to measure their capacity for producing interferon (IFN)-γ and interleukin (IL)-17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of co-morbidities such as osteoarthritis or overlap with RA. IL-17A and IL-6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4+ T cells expressed CCR6+ , a marker associated with T helper type 17 (Th17) cells. IL-17A-production was validated among CD4+ CCR6+ T cells following in-vitro stimulation. Furthermore, a strong IFN-γ production was observed in both CD4+ and CD8+ cells. Our study shows high IL-17A and IL-6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway has been implicated in several aspects of SLE disease pathogenesis and our data also point to Th17 involvement for lupus arthritis.
Assuntos
Artrite/imunologia , Interleucina-17/imunologia , Interleucina-6/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Líquido Sinovial/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Feminino , Humanos , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Células Th17/imunologiaRESUMO
To investigate presence of circulating myeloperoxidase-positive microparticles (MPO+MPs) in relation to disease activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Forty-six patients with AAV and 23 age- and sex-matched healthy controls were included. Vasculitis disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). MPs were analyzed in citrate plasma by flow cytometry and phenotyped based on MPO expression and co-expression of pentraxin-3 (PTX3), high mobility group box 1 protein (HMGB1), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). Serum levels of PTX3, sTWEAK, and HMGB1 were also determined. Twenty-three patients had active vasculitis (BVAS ≥ 1). Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls (p < 0.001, p < 0.01, p < 0.001, respectively), while concentrations of PTX3+ and HMGB1+MPO+MPs were significantly higher in active AAV compared to patients in remission. MPO+MPs expressing either PTX3 or HMGB1 were associated with BVAS (r = 0.5, p < 0.001; r = 0.3, p = 0.04, respectively). Significantly higher serum PTX3 levels were found in active- than in inactive AAV (p < 0.001), correlating strongly with BVAS (r = 0.7, p < 0.001). Serum levels of sTWEAK and HMGB1 did not differ between patients and controls. Concentration of MPO+MPs is increased in plasma from AAV patients compared to healthy individuals. PTX3 in serum as well as PTX3 and HMGB1 expressed on MPO+MPs were associated with disease activity in the investigated patients. KEY MESSAGES: Myeloperoxidase-positive microparticles (MPO+MPs) are increased in plasma from patients with ANCA-associated vasculitis. Concentrations of MPO+MPs expressing PTX3, HMGB1, and TWEAK were significantly higher in patients compared to healthy controls. MPO+MPs expressing PTX3 and HMGB1 are associated with disease activity in ANCA-associated vasculitis.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/metabolismo , Biomarcadores , Micropartículas Derivadas de Células/metabolismo , Peroxidase/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Estudos Transversais , Suscetibilidade a Doenças , Feminino , Citometria de Fluxo , Humanos , Masculino , Peroxidase/metabolismo , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti-ß2 glycoprotein I (anti-ß2GPI) in healthy pregnant and non-pregnant women of different ethnicities. METHODS: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-ß2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-ß2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti-cyclic citrullinated peptide 2 (anti-CCP2) and anti-thyroid peroxidase (anti-TPO) were investigated in Sudanese females. RESULTS: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-ß2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-ß2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-ß2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-ß2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased. CONCLUSIONS: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.
Assuntos
Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/imunologia , Imunoglobulina A/sangue , beta 2-Glicoproteína I/imunologia , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Feminino , Humanos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/imunologia , Fator Reumatoide , Sudão , Suécia , Adulto JovemRESUMO
Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-ß2 -glycoprotein-I (anti-ß2 GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-ß2 GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n = 100), primary Sjögren's syndrome (n = 50) and blood donors (n = 507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-ß2 GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and ≥ 1 aCL/anti-ß2 GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-ß2 GPI, 34 (6%) being seronegative regarding IgG/IgM anti-ß2 GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-ß2 GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-ß2 GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR) = 0·21, 95% confidence interval (CI) = 0·06-0·72) and photosensitivity (OR = 0·19, 95% CI = 0·05-0·72). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.
Assuntos
Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Artrite Reumatoide/sangue , Estudos Transversais , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Nefrite/imunologia , Nefrite/patologia , Síndrome de Sjogren/sangue , Suécia , Adulto JovemRESUMO
Objective Rituximab-mediated late-onset neutropenia (LON) has been described in various diseases. We investigated its occurrence, consequences and contributing factors in patients with systemic lupus erythematosus (SLE). Methods Rituximab-treated patients from the Karolinska University Hospital ( n = 107) were surveyed. LON was defined as an absolute neutrophil count <1500 cells/µl, occurring four weeks to two years following rituximab treatment, or later during sustained B-cell depletion. Serum levels of B-cell-related cytokines and growth factors of the myeloid lineage were determined using enzyme-linked immunosorbent assay. Results Thirty-two patients (29.9%) developed LON after a median time of 201.5 days. Thirteen patients were admitted to the hospital; 10 due to fever. Three patients developed critical conditions. BAFF levels increased from baseline (median: 0.62 ng/ml) to the post-treatment evaluation (median: 1.16 ng/ml; p < 0.001); post-treatment levels were higher in the LON group ( p = 0.021). APRIL levels were higher in the LON group both at baseline (median: 1.54 versus 1.15 ng/ml; p = 0.027) and post-treatment (median: 2.39 versus 1.11 ng/ml; p = 0.011). IL-6 and GM-CSF levels decreased in the non-LON group ( p < 0.001), but not in LON patients. High baseline disease activity predicted LON development (OR: 4.1; 95% CI: 1.1-15.2 for SLEDAI-2K > 8). No association with neutropenia prior to rituximab treatment was documented. Conclusion Post-rituximab LON was a common complication. Although the phenomenon was predominantly self-limiting, several patients developed severe conditions. Distinct roles of BAFF and APRIL are implicated: BAFF may contribute to LON development, whereas high APRIL levels may be predictive. Rituximab-treated SLE patients should be monitored for neutrophil counts, fever and infections.
Assuntos
Antirreumáticos/efeitos adversos , Nefrite Lúpica/tratamento farmacológico , Neutropenia/induzido quimicamente , Rituximab/efeitos adversos , Adulto , Fator Ativador de Células B/sangue , Feminino , Humanos , Nefrite Lúpica/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangueRESUMO
Essentials ß2 glycoprotein-I (ß2 GPI) is a scavenger molecule that binds to microparticles (MPs). ß2 GPI expression on MPs was measured in systemic lupus erythematosus (SLE) patients and controls. ß2 GPI positive MPs is depressed among SLE patients positive for antiphospholipid antibodies. Complex formation between ß2 GPI on MPs and patients own anti-ß2 GPI may disturb MP clearance. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini SUMMARY: Background Antiphospholipid antibodies (aPLs) together with thrombosis and/or pregnancy morbidities characterize the antiphospholipid syndrome. ß2 -Glycoprotein I (ß2 GPI), the most important antigen for aPLs, is a scavenger molecule that specifically binds to phosphatidylserine (PS) expressed on microparticles (MPs). Objectives To evaluate ß2 GPI-expressing MPs in patients with systemic lupus erythematosus (SLE) stratified for aPL status, and in healthy controls. Patients/Methods We investigated 18 aPL/anti-ß2 GPI-positive and 22 aPL-negative patients from a large SLE cohort and 19 healthy controls. ß2 GPI-positive MPs and IgG-positive MPs were detected by flow cytometry. We measured plasma levels of ß2 GPI, and performed in vitro experiments to investigate the binding properties of ß2 GPI on MPs. Results SLE patients had more MPs and IgG-positive MPs than controls. We observed fewer ß2 GPI-positive MPs in aPL/anti-ß2 GPI-positive patients than in aPL/anti-ß2 GPI-negative patients and controls (approximately two-fold). ß2 GPI levels in plasma did not differ with aPL/anti-ß2 GPI status in patients; however, controls had slightly higher levels of ß2 GPI than aPL/anti-ß2 GPI-positive patients. In vitro experiments revealed that ß2 GPI preferentially binds to PS-positive MPs. Conclusions Despite abundant total MPs and MPs in immune complexes, ß2 GPI-positive MPs were depleted in SLE patients, and the levels were especially low in aPL/anti-ß2 GPI-positive patients. We suggest that anti-ß2 GPI antibodies bind to ß2 GPI-PS complexes expressed on MPs. Consequent loss of ß2 GPI-PS expression on MPs may impair scavenging and contribute to the accumulation of circulating PS-negative MPs, a possible source of autoantigens. Autoantibodies delaying MP clearance may thus constitute an important mechanism underlying autoimmunity.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Micropartículas Derivadas de Células/metabolismo , Lúpus Eritematoso Sistêmico/sangue , beta 2-Glicoproteína I/sangue , Adulto , Idoso , Autoimunidade , Biomarcadores/sangue , Estudos de Casos e Controles , Micropartículas Derivadas de Células/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , beta 2-Glicoproteína I/imunologiaRESUMO
OBJECTIVES: We compared patients' assessments of systemic lupus erythematosus (SLE) disease activity by a Swedish version of the Systemic Lupus Activity Questionnaire (SLAQ) with physicians' assessments by the Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). We also explored the performance of the SLAQ in patients with short (< 1 year) versus long (≥ 1 year) disease duration. METHOD: Patients filled out the SLAQ before physicians' assessments. Correlations between SLAQ total, subscales (Symptom score, Flares, Patients global) and SLAM and SLEDAI-2K, as well as between the corresponding items in SLAQ and SLAM, were evaluated using Spearman's ρ. Comparisons between patients with different disease durations were performed with Mann-Whitney U or chi-squared tests. RESULTS: We included 203 patients (79% women), with a median age of 45 years [interquartile range (IQR) 33-57 years] and disease duration of 5 years (IQR 0-14 years). Correlations between physicians' SLAM without laboratory items (SLAM-nolab) and patients' assessments were: SLAQ total, ρ = 0.685, Symptom score, ρ = 0.651, Flares, ρ = 0.547, and Patients global, ρ = 0.600. Of the symptom items, fatigue (ρ = 0.640), seizures (ρ = 0.635), and headache (ρ = 0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (ρ < 0.24). Patients' and physicians' assessments were notably more discordant for patients with short disease durations. CONCLUSION: We confirm that the SLAQ can be used to monitor disease activity. However, the discrepancy between patients' and physicians' assessments was greater for patients with short versus long disease duration. We encourage further use of the SLAQ, but would like to develop a shorter version which would be valuable in modern, partly web-based, clinical care.
Assuntos
Fadiga/fisiopatologia , Cefaleia/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Convulsões/fisiopatologia , Adulto , Progressão da Doença , Fadiga/etiologia , Feminino , Cefaleia/etiologia , Humanos , Lúpus Eritematoso Cutâneo/etiologia , Lúpus Eritematoso Cutâneo/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Linfadenopatia/etiologia , Linfadenopatia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Convulsões/etiologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Inquéritos e Questionários , SuéciaRESUMO
Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C16:0- and C24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.
Assuntos
Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/sangue , Esfingolipídeos/sangue , Adulto , Estudos de Casos e Controles , Cromatografia Líquida/métodos , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espectrometria de Massas em Tandem/métodosRESUMO
OBJECTIVES: We investigated the performance of soluble tumour necrosis factor receptor-2 (sTNFR2) as a biomarker of renal activity, damage, treatment response, and long-term outcome in lupus nephritis (LN). METHOD: Serum sTNFR2 levels were assessed in 64 LN patients (52 proliferative, 12 membranous) before and after induction treatment, and in 314 non-lupus controls. In LN patients, renal biopsies were performed at baseline and post-treatment. Patients with ≥ 50% reduced proteinuria, normal or improved estimated glomerular filtration rate (eGFR) by ≥ 25%, and inactive urinary sediment were considered clinical responders (CRs). Patients with ≥ 50% improved renal activity index were considered histopathological responders (HRs). Long-term renal outcome was determined using the chronic kidney disease (CKD) stage after a median follow-up of 11.3 years. RESULTS: sTNFR2 levels were elevated in LN patients versus controls both at baseline (p < 0.001) and post-treatment (p < 0.001), and decreased following treatment (p < 0.001). Baseline sTNFR2 correlated with Chronicity Index scores in both baseline (r = 0.34, p = 0.006) and post-treatment (r = 0.43, p < 0.001) biopsies. In membranous LN, baseline sTNFR2 levels were higher in CRs (p = 0.048) and HRs (p = 0.03) than in non-responders, and decreased only in CRs (p = 0.03). Both baseline (p = 0.02) and post-treatment (p = 0.03) sTNFR2 levels were associated with decreasing eGFR throughout long-term follow-up, and post-treatment levels were higher in patients with long-term follow-up CKD stage ≥ 3 versus 1-2 (p = 0.008). CONCLUSIONS: Our data suggest serum sTNFR2 as a marker of kidney tissue damage and a predictor of long-term prognosis in LN, and merit further evaluation of sTNFR2 as a predictor of clinical and histopathological treatment outcomes in membranous LN.
Assuntos
Nefrite Lúpica/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Insuficiência Renal Crônica/sangue , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/uso terapêutico , Biomarcadores/sangue , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/metabolismo , Rituximab/uso terapêutico , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines. METHODS: The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. RESULTS: A total of seven ARDS interventions were assessed. We suggest fluid restriction in patients with ARDS (weak recommendation, moderate quality evidence). Also, we suggest early use of neuromuscular blocking agents (NMBAs) in patients with severe ARDS (weak recommendation, moderate quality evidence). We recommend against the routine use of other drugs, including corticosteroids, beta2 agonists, statins, and inhaled nitric oxide (iNO) or prostanoids in adults with ARDS (strong recommendations: low- to high-quality evidence). These recommendations do not preclude the use of any drug or combination of drugs targeting underlying or co-existing disorders. CONCLUSION: This guideline emphasizes the paucity of evidence of benefit - and potential for harm - of common interventions in adults with ARDS and highlights the need for prudence when considering use of non-licensed interventions in this patient population.
Assuntos
Cuidados Críticos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Hidratação , Humanos , Bloqueadores Neuromusculares/uso terapêuticoRESUMO
BACKGROUND: Rituximab (RTX) is being used increasingly in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV). Late-onset neutropenia (LON) and risks of infections have been observed following RTX therapy in rheumatological diseases including granulomatosis with polyangiitis (GPA) but data on microscopic polyangiitis (MPA) are lacking. METHOD: We studied the occurrence of LON in 59 AAV (47 GPA/12 MPA) patients treated with RTX. Patient charts were retrospectively reviewed for the occurrence of LON and clinical data were extracted and included in the analysis. RESULTS: Seven of the total 59 patients (11.9%) developed LON after a median time of 86 days (range 56-168 days) since their latest RTX treatment. Of these seven LON patients, 5/47 (10.6%) had a diagnosis of GPA and 2/12 (16.7%) of MPA. Three of the patients developed LON after the first RTX treatment and four had received repeated courses. Five LON patients developed infectious symptoms. Six of the patients were hospitalized. Retreatment with RTX was given in three cases without further LON episodes. CONCLUSIONS: LON is a potentially severe side-effect of RTX occurring in both GPA and MPA and may develop after both single and repeated treatment courses. As infections are commonly seen, the condition requires an increased awareness. No predisposing factors for LON were identified.
Assuntos
Antirreumáticos/efeitos adversos , Granulomatose com Poliangiite/tratamento farmacológico , Poliangiite Microscópica/tratamento farmacológico , Neutropenia/induzido quimicamente , Rituximab/efeitos adversos , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials. METHODS: This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process. RESULTS: We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS. Also, we suggest positive end-expiratory pressure (PEEP) > 5 cm H2O in moderate to severe ARDS and prone ventilation 16/24 h for the first week in moderate to severe ARDS (weak recommendation, low quality evidence). Volume controlled ventilation or pressure control may be equally beneficial or harmful and partial modes of ventilatory support may be used if clinically feasible (weak recommendation, very low quality evidence). We suggest utilising recruitment manoeuvres as a rescue measure in catastrophic hypoxaemia only (weak recommendation, low quality evidence). Based on high-quality evidence, we strongly recommend not to use high-frequency oscillatory ventilation. We could find no relevant data from randomised trials to guide decisions on choice of FiO2 or utilisation of non-invasive ventilation. CONCLUSION: We strongly recommend pressure- and volume limitation and suggest using higher PEEP and prone ventilation in patients with severe respiratory failure.(AU)
Assuntos
Humanos , Adulto , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/reabilitação , Ventilação de Alta Frequência/efeitos adversosRESUMO
OBJECTIVE: The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression. METHODS: Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale. RESULTS: Three clusters, denominated "High," "Intermediate" and "Low" fatigue clusters, were identified. The "High" contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The "Intermediate" (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the "Low" regarding sleep/rest whereas social status and smoking were closer to the "High." The"Low" contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥ 3 times/week. CONCLUSION: Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored.
Assuntos
Fadiga/psicologia , Hábitos , Estilo de Vida , Lúpus Eritematoso Sistêmico/psicologia , Adulto , Ansiedade/etiologia , Ansiedade/fisiopatologia , Ansiedade/psicologia , Estudos de Casos e Controles , Análise por Conglomerados , Depressão/etiologia , Depressão/fisiopatologia , Depressão/psicologia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials. METHODS: This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process. RESULTS: We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS. Also, we suggest positive end-expiratory pressure (PEEP) > 5 cm H2O in moderate to severe ARDS and prone ventilation 16/24 h for the first week in moderate to severe ARDS (weak recommendation, low quality evidence). Volume controlled ventilation or pressure control may be equally beneficial or harmful and partial modes of ventilatory support may be used if clinically feasible (weak recommendation, very low quality evidence). We suggest utilising recruitment manoeuvres as a rescue measure in catastrophic hypoxaemia only (weak recommendation, low quality evidence). Based on high-quality evidence, we strongly recommend not to use high-frequency oscillatory ventilation. We could find no relevant data from randomised trials to guide decisions on choice of FiO2 or utilisation of non-invasive ventilation. CONCLUSION: We strongly recommend pressure- and volume limitation and suggest using higher PEEP and prone ventilation in patients with severe respiratory failure.
Assuntos
Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Adulto , Humanos , Países Escandinavos e Nórdicos , Sociedades MédicasRESUMO
OBJECTIVES: A renal biopsy is generally recommended for diagnosis and is necessary for classification of lupus nephritis (LN), but second biopsies after immunosuppressive therapy are seldom a routine procedure. We investigated how repeat biopsies contribute to the evaluation of treatment response and long-term outcome in LN. METHODS: Sixty-seven patients with active LN were included. Renal biopsies were performed at diagnosis and after standard induction immunosuppressive therapy in all patients (median 8â months), regardless of clinical outcome. Biopsies were evaluated according to the International Society of Nephrology/Renal Pathology Society classification. Clinical response was defined as complete (CR), partial (PR) or non-response (NR) according to recent definitions. Histological response (HR) was defined as Class I, II or III/IV-C on repeat biopsies. Long-term renal outcome was determined in 55 patients after a median of 10â years. RESULTS: CR was demonstrated in 25%, PR in 27% and NR in 48% of patients. HR was shown in 42% and histopathological non-response (HNR) in 58% of patients. Twenty-nine per cent of CR and 61% of patients with PR had active lesions on repeat biopsies, that is, were HNR. Poor long-term renal outcome was associated with high chronicity index at repeated biopsies, but not with clinical or histological response. CONCLUSIONS: Despite apparent clinical response to immunosuppressive therapy, repeated biopsies revealed persisting active nephritis in almost half of the patients, thus providing additional information to clinical response criteria. Repeated renal biopsies may be a tool to improve the evaluation of treatment response in LN.
RESUMO
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with multiple organ involvement. B-lymphocyte activity plays a pivotal role in the development and course of the disease. A newly developed agent called belimumab has recently been approved to treat active, autoantibody positive SLE as an add-on to standard therapy. Specifically binding to soluble B-lymphocyte stimulator protein, it reduces the formation of immunoglobulins and autoantibodies. Its effects have been studied in one phase II and two phase III clinical trials, showing sustained improvement across various clinical indicators and no evidence of increased risk of serious adverse events. Further post-hoc analyses indicate that treatment with belimumab lowers levels of autoimmune antibodies, normalizes low complement and improves SLE activity predominantly in musculoskeletal and mucocutaneous organ domains. Further studies are needed to determine the efficacy of belimumab for patients with severe lupus nephritis and with active involvement of the central nervous system. The introduction of belimumab as the first biological drug approved for the management of SLE likely heralds a surge in the development and use of selectively addressed agents for this heterogeneous and complex disease.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Autoanticorpos/imunologia , Fator Ativador de Células B/antagonistas & inibidores , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Desenho de Fármacos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/imunologiaRESUMO
Renal involvement in systemic lupus erythematosus (SLE) is a severe disease manifestation in which novel therapeutic strategies are needed, especially in non-responding patients or patients who relapse after conventional treatment. Rituximab has been used as off-label treatment for lupus nephritis (LN) during the last decade, and to date reports on the clinical effects on more than 400 patients, including the randomized controlled LUNAR study population, have been published. Despite promising results obtained from observational studies and registries, with complete or partial renal response after 6-12 months in 67-77% of patients, the LUNAR trial failed to attain the primary endpoint and rituximab is today unlikely to be approved as treatment for LN. Rituximab has mainly been used as induction therapy in combination with standard of care but the optimal treatment protocol is still to be determined. From observational studies, rituximab has been shown to be efficient in both proliferative and membranous LN, and histopathological studies have demonstrated improvement in renal activity. Adverse events mainly include infusion reactions and infections. Although not approved for the treatment of LN, the currently available data support that rituximab may be used in severe, refractory cases of LN.