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1.
RMD Open ; 7(1)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33863842

RESUMO

OBJECTIVE: To determine the non-inferiority of nurse-led care (NLC) in patients with anticitrullinated protein antibody (ACPA)-positive and/or rheumatoid factor (RF)-positive rheumatoid arthritis (RA) with active disease who are starting disease-modifying antirheumatic drug therapy, following treat-to-target (T2T) recommendations. METHODS: A multicentre, pragmatic randomised controlled trial was conducted to assess clinical effectiveness, anxiety, depression and patient satisfaction following a non-inferiority design. The participants were 224 adults with ACPA/RF-positive RA who were randomly assigned to either NLC or rheumatologist-led care (RLC). The primary outcome was the Disease Activity Score in 28 Joints measured with C reactive protein (DAS28-CRP) assessed at baseline and after 3, 6, 9 and 12 months. A DAS28-CRP difference of 0.6 was set as the non-inferiority margin. Mean differences between the groups were assessed following per-protocol and intention-to-treat strategies. RESULTS: Demographic data and baseline characteristics of patients in the NLC group (n=111) were comparable to those of patients in the RLC group (n=113). The improvement in disease activity (change in DAS28-CRP, primary outcome) over the course of 12 months was significant in both groups (p<0.001). No significant differences were observed between the NLC and RLC groups (p=0.317). Non-inferiority of NLC was shown for the primary outcome and all secondary outcomes. CONCLUSION: This study supported the non-inferiority of NLC in managing T2T and follow-up care of patients with RA with moderate to high disease activity and poor prognostic factors in addition to RLC. TRIAL REGISTRATION NUMBER: DRKS00013055.

2.
J Rheumatol ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722943

RESUMO

We have read with great interest the letter of Verhoeven, et al,1 referring to our recent publication on the diagnostic value of optical spectral transmission (OST) in rheumatoid arthritis (RA).2 In our work we had described for the first time, to our knowledge, that OST values could be influenced not only by disease-associated factors (i.e., inflammatory activity) but also by patient-associated characteristics, such as sex, BMI, and age.2.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33770421

RESUMO

OBJECTIVES: To develop and validate a composite RA disease activity index using optical spectral transmission (OST)-scores obtained with the HandScan replacing tender and swollen joint counts. METHODS: RA patients from a single centre routinely undergoing HandScan measurements and at least one concurrent OST-score and DAS28 were included. Data was extracted from medical records. Linear regression analyses with DAS28 as outcome were performed to create a disease activity index (DAS-OST). OST-score, ESR and patient global assessment (PGA-)VAS, gender, age, disease duration and RF-status were evaluated as independent variables. Final models were derived, based on statistical significance of coefficients and model fit. Of the data, 2/3 was used for development and 1/3 for validation; external validation was performed in a cohort from another centre. Agreement between DAS-OST and DAS28 was assessed using the Bland-Altman plot method and intra-class correlation coefficient (ICC). Diagnostic value of DAS-OST was determined for established definitions of remission, and low (L), and high (H) disease activity (DA). RESULTS: Data of 3358 observations from 1505 unique RA patients were extracted. DAS-OST was defined as: -0.44 + OST*0.03 + male*-0.11 + LN(ESR)*0.77 + PGA-VAS*0.03. The ICC between DAS-OST and DAS28 were 0.88 (95%CI 0.87-0.90) and 0.82 (95%CI 0.75-0.86) and measurement errors 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA and HDA were 79%, 91%, 43%, and specificity 92%, 80%, 96% in external validation. CONCLUSION: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PGA-VAS and gender into a disease activity index (DAS-OST).

4.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669022

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. METHODS: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6-/- MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. RESULTS: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. CONCLUSION: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.


Assuntos
Endotélio Vascular/metabolismo , Interleucina-6/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Linfócitos T/imunologia , Acetilcolina/farmacologia , Animais , Aorta/imunologia , Aorta/patologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/genética , Rim/metabolismo , Rim/patologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
6.
Rheumatol Ther ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544369

RESUMO

INTRODUCTION: We evaluated incidence, prevalence, costs, and healthcare utilization associated with systemic lupus erythematosus (SLE) in patients in Germany. METHODS: Adult patients with SLE were identified from the German Betriebskrankenkassen (BKK) health insurance fund database between 2009 and 2014. SLE incidence and prevalence were calculated for each year and extrapolated (age and sex adjusted) to the German population. The 2009 SLE population was followed through 2014. Healthcare utilization and costs for patients with SLE were calculated and compared with controls matched by age, sex, and baseline Charlson Comorbidity Index scores. RESULTS: This analysis included 1160 patients with SLE. Estimated SLE incidence between 2009 and 2014 ranged from 4.59 to 6.89 per 100,000 persons and prevalence ranged from 37.32 to 47.36 per 100,000. SLE incidence in Germany in 2014 was 8.82 per 100,000 persons; prevalence was 55.80 (corrected for right-censored data). At baseline, 12.8, 41.7, and 45.5% of patients were categorized as having mild, moderate, and severe SLE, respectively. Patients with SLE had greater mean (standard deviation [SD]) annual medical costs compared with matched controls 1 year after index diagnosis (€6895 [14,424] vs. €3692 [3994]; P < 0.0001) and in subsequent years. Patients with moderate or severe SLE had significantly more hospitalizations, outpatient visits, and prescription medication use compared with matched controls. Mean annual costs for 5 years ranged from €1890 to 3010, €4867 to 5876, and €8396 to 10,001 for patients with mild, moderate, and severe SLE, respectively. CONCLUSIONS: SLE incidence in Germany increased 1.4-fold over 5 years. Patients with SLE have higher healthcare costs, and costs increase with baseline severity. Early and effective treatments may delay progression and reduce the burden of SLE.

7.
RMD Open ; 7(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33408124

RESUMO

OBJECTIVE: Here, we assess the usage of high throughput sequencing (HTS) in rheumatic research and the availability of public HTS data of rheumatic samples. METHODS: We performed a semiautomated literature review on PubMed, consisting of an R-script and manual curation as well as a manual search on the Sequence Read Archive for public available HTS data. RESULTS: Of the 699 identified articles, rheumatoid arthritis (n=182 publications, 26%), systemic lupus erythematous (n=161, 23%) and osteoarthritis (n=152, 22%) are among the rheumatic diseases with the most reported use of HTS assays. The most represented assay is RNA-Seq (n=457, 65%) for the identification of biomarkers in blood or synovial tissue. We also find, that the quality of accompanying clinical characterisation of the sequenced patients differs dramatically and we propose a minimal set of clinical data necessary to accompany rheumatological-relevant HTS data. CONCLUSION: HTS allows the analysis of a broad spectrum of molecular features in many samples at the same time. It offers enormous potential in novel personalised diagnosis and treatment strategies for patients with rheumatic diseases. Being established in cancer research and in the field of Mendelian diseases, rheumatic diseases are about to become the third disease domain for HTS, especially the RNA-Seq assay. However, we need to start a discussion about reporting of clinical characterisation accompany rheumatological-relevant HTS data to make clinical meaningful use of this data.

8.
Transplant Proc ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478746

RESUMO

A 53-year-old female patient with acute myeloid leukemia developed severe chronic graft vs host disease (cGVHD) of the oral mucosa after allogeneic hematopoietic stem cell transplantation with leukoplakia and relapsing oral squamous cell carcinoma (SCC) of the tongue. cGVHD needed long-lasting immunosuppressive therapy; SCC was treated with radiation and surgery. Acute myeloid leukemia remained in complete remission. The patient developed a myositis with pain of all muscles as well as paraparesis with elevated creatine kinase and C-reactive protein and detection of antiskeletal muscle autoantibodies 3500 days after hematopoietic stem cell transplantation. No other clinical features of chronic GVHD were apparent at this time. Symptoms disappeared after treatment with corticosteroids but relapsed while tapering. Weekly therapy with the B-cell-depleting antibody rituximab was started and administered for 6 weeks. Symptoms disappeared again but partly returned after some weeks, so therapy with azathioprine was started. During therapy with azathioprine slow tapering of corticosteroids was possible and clinical symptoms remained absent. Here we present a case report and review of the literature on alloimmune myositis as paraneoplastic complication of an oral SCC of the tongue after severe chronic GVHD or as late manifestation of chronic GVHD itself.

9.
Autoimmun Rev ; 20(2): 102736, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33333233

RESUMO

The B cell activating factor (BAFF), or B lymphocyte stimulator (BLyS), is a B cell survival factor which supports autoreactive B cells and prevents their deletion. BAFF expression is closely linked with autoimmunity and is enhanced by genetic alterations and viral infections. Furthermore, BAFF seems to be involved in adipogenesis, atherosclerosis, neuro-inflammatory processes and ischemia reperfusion (I/R) injury. BAFF is commonly overexpressed in Systemic Lupus Erythematosus (SLE) and strongly involved in the pathogenesis of the disease. The relationship between BAFF levels, disease activity and damage accrual in SLE is controversial, but growing evidence is emerging on its role in renal involvement. Belimumab, a biologic BAFF inhibitor, has been the first biologic agent licensed for SLE therapy so far. As Rituximab (RTX) has been shown to increase BAFF levels following B cell depletion, the combination therapy of RTX plus belimumab (being evaluated in two RCT) seems to be a valuable option for several clinical scenarios. In this review we will highlight the growing body of evidence of immune and non-immune related BAFF expression in experimental and clinical settings.


Assuntos
Lúpus Eritematoso Sistêmico , Viroses , Autoimunidade , Fator Ativador de Células B , Linfócitos B , Humanos , Lúpus Eritematoso Sistêmico/terapia
10.
Front Immunol ; 11: 597863, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381119

RESUMO

Introduction: Anti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients. Objective: The main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group. Methodology: This retrospective study was performed on SLE patients' sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml). Results: The cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found "ambivalent" (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies. Conclusion: Anti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33175957

RESUMO

OBJECTIVE: The prevalence of fatigue is high in patients with systemic lupus erythematosus (SLE). In this study, we used latent class analysis to reveal patterns of fatigue, anxiety, depression and organ involvement in a large international cohort of SLE patients. METHODS: We used the Lupus BioBank of the upper Rhein to analyse patterns of fatigue using latent class analysis (LCA). After determining the optimal number of latent classes, patients were assigned according to model generated probabilities, and characteristics of classes were compared. RESULTS: A total of 502 patients were included. Significant fatigue, anxiety and depression were reported by 341 (67.9%), 159 (31.7%) and 52 (10.4%) patients, respectively. LCA revealed a first cluster (67.5% of patients) with low disease activity [median (25th-75th percentile interquartile range) Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI: 2 (0-4)], significant fatigue (55.5%, P < 0.0001), low anxiety (11.8%, P < 0.0001) and depression (0.9%, P < 0.0001). Cluster 2 (25.3%) also comprised patients with low disease activity [SELENA-SLEDAI: 2 (0-6)], but those patients had a very high prevalence of fatigue (100%, P < 0.0001), anxiety (89%, P < 0.0001) and depression (38.6%, P < 0.0001). Cluster 3 (7.2%) comprised patients with high disease activity [SELENA-SLEDAI: 12 (8-17), P < 0.0001] and high fatigue (72.2%, P < 0.0001) with low levels of anxiety (16.7%, P < 0.0001) and no depression (0%, P < 0.0001). CONCLUSION: LCA revealed three patterns of fatigue with important practical implications. Based on these, it is crucial to distinguish patients with active disease (in whom remission will be achieved) from those with no or mild activity but high levels of fatigue, depression and anxiety, for whom psychological counselling should be prioritized.

12.
Rheumatol Ther ; 7(4): 949-965, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33206344

RESUMO

INTRODUCTION: The real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE. METHODS: OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation). Endpoints (month 6 vs. index) included physician-assessed overall clinical response to belimumab in the overall population (primary) and high disease activity subgroups (secondary; patients with a SLEDAI-2K/SELENA-SLEDAI score ≥ 10 or patients with high anti-dsDNA or low complement at index); other secondary endpoints included changes in glucocorticosteroid (GCS) use and changes in disease activity. Factors associated with physician-assessed overall clinical response were also evaluated. RESULTS: In total, 830 patients were included in the overall population (mean [standard deviation (SD)] age: 41.9 [12.57] years; female: 89.3%; 60.4% from the USA). Nearly half (48.1%) of belimumab-treated patients experienced a ≥ 50% physician-assessed improvement in their overall manifestations, and 13% achieved a near normalization of their condition (equal to ≥ 80% improvement). Initiating belimumab while on high-dose (> 7.5 mg/day) GCS use was associated with ≥ 50% clinical improvement at month 6 (OR: 1.9, p = 0.003). Most (78.1%; n = 518/663) patients were able to reduce or discontinue their oral GCS dose after 6 months of belimumab, with a mean (SD) change of - 8.5 (10.74) mg/day prednisone-equivalent. The mean (SD) change from belimumab initiation in disease activity score (SLEDAI-2K/SELENA-SLEDAI) was - 5.7 (4.5; n = 344). CONCLUSIONS: Belimumab improves clinical manifestations of SLE and is associated with GCS dose reductions in a real-world clinical setting, supporting the real-world effectiveness of belimumab for SLE.

13.
JMIR Res Protoc ; 9(11): e18291, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141101

RESUMO

BACKGROUND: Systemic lupus erythematosus is a systemic autoimmune disease, which is associated with high cardiovascular risk, a predisposition to metabolic disorders, muscle wasting, and fatigue. Exercise therapy has become an important part of the long-term treatment of comorbidities in systemic lupus erythematosus. Exercise can lead to various benefits in patients with systemic lupus erythematosus such as increased aerobic capacity and exercise tolerance, resulting in an increased quality of life, decreased depression, and decreased fatigue. At the moment, no evidence-based treatment guidelines that recommend exercise for patients with systemic lupus erythematosus exist. Also, the efficacy of different training programs requires further investigation. OBJECTIVE: This study focuses on the feasibility, efficacy, and safety of an internet-based exercise program in patients with systemic lupus erythematosus. Furthermore, we investigate the feasibility and efficiency of anaerobic training compared to aerobic training. METHODS: Overall, patients with systemic lupus erythematosus from the Division of Nephrology, Rheumatology, and Immunology outpatient clinic of the University Medical Center Mainz who are clinically stable status are included and randomized in an aerobic exercise group (n=10), anaerobic exercise group (n=10), or treatment as usual group (n=10). After completing initial clinical testing and physical fitness tests, patients undergo supervised 12-week online exercise programs, receiving weekly individualized training plans adapted to their physical performance. The primary outcome is change in physical fitness (VO2 peak) after 12 weeks compared to baseline. Secondary outcomes are disease activity measured via laboratory results (complement, autoantibodies) and questionnaires, as well as changes in muscle mass (anaerobic exercise group), results of the Chair-Stand test, and measurements of circulating cell-free DNA and extracellular vesicles. RESULTS: The study was registered in May 2019. Enrollment began in May 2019. Of 40 patients who were initially screened, 30 patients fulfilled the inclusion criteria and were included in the study; 1 participant withdrew prior to the start of the exercise program. Among the 25 patients who completed the study, no serious adverse events have been reported; 3 participants withdrew during the program (due to frequent colds, n=1; Crohn relapse, n=1; physical strain, n=1), and 1 participant has not yet completed the program. Data analysis is ongoing, and results are expected to be submitted for publication in January 2021. CONCLUSIONS: We expect the online exercise intervention to be a feasible and efficient tool to provide regular individualized exercise for patients with systemic lupus erythematosus. TRIAL REGISTRATION: ClinicalTrials.gov NCT03942718; http://clinicaltrials.gov/ct2/show/NCT03942718. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18291.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32940712

RESUMO

OBJECTIVES: To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. METHODS: SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices]. RESULTS: We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P<0.001 and r = 0.664; P<0.001, respectively). Moreover, cfPWV correlated with BMI (Padj=0.001) and diabetes (Padj=0.043). CCA-RI and CCA-PI showed significant associations with creatine phosphokinase (r = 0.629; P=0.012 and r = 0.574; P=0.032, respectively) and ICA-RI and ICA-PI were higher in patients with lung involvement (both; P=0.039). CONCLUSION: ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.

15.
J Med Case Rep ; 14(1): 135, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859260

RESUMO

BACKGROUND: Rituximab is a well-established component of treatment regimens for B-cell non-Hodgkin lymphoma. Rituximab binds the CD20 antigen on the surface of B lymphocytes, causing an enhanced clearance of malignant and benign B cells. Thus, rituximab leads to depletion of normal B lymphocytes as well, which can cause substantial immunodeficiency. Ibrutinib inhibits the Bruton tyrosine kinase and thereby B-cell activity. It is used for the treatment of different B-lymphocyte malignancies, such as mantle cell lymphoma. Recently, the combination of both drugs has been tested in various clinical scenarios. CASE PRESENTATION: We present a case of disseminated enterovirus infection resulting from combined rituximab and ibrutinib maintenance treatment in a 57-year-old Caucasian patient. with mantle cell lymphoma. Initially presenting with myositis symptoms, further diagnostic investigation revealed myocarditis, enteritis, myeloencephalitis, and hepatitis. These organ manifestations led to potentially life-threatening complications such as rhabdomyolysis, delirium, and heart rhythm disturbances. After treatment with high-dose intravenous immunoglobulins, virus clearance was achieved and organ functions could be restored. CONCLUSIONS: This case emphasizes the risk of combined therapy with rituximab/ibrutinib for severe immune-related side effects with the necessity of continuous patient monitoring. High-dose intravenous therapy should be considered as treatment for severe enterovirus infection. In severe enterovirus infections, we recommend subtyping for the development of efficient preventive and therapeutic strategies.

16.
Lupus Sci Med ; 7(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32616563

RESUMO

OBJECTIVE: Systemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%-40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined. METHODS: 998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×106/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia. RESULTS: 208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57-10.3)), lymphopaenia (OR 4.41 (2.51-11.5)) and low C3 (OR 1.91 (1.03-4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers. CONCLUSION: This study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren's disease.

17.
Rheumatol Ther ; 7(3): 433-446, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32488652

RESUMO

Despite recent improvements in the treatment of systemic lupus erythematosus (SLE), disease activity, comorbidities and drug toxicity significantly contribute to the risk of progressive irreversible damage accrual and increased mortality in patients with this chronic disease. Moreover, even lupus patients in remission often report residual symptoms, such as fatigue, which have a considerable impact on their health-related quality of life. In recent decades, SLE treatment has moved from the use of hydroxychloroquine, systemic glucocorticosteroids and conventional immunosuppressive drugs to biologic agents, of which belimumab is the first and only biologic agent approved for the treatment for SLE to date. Novel therapies targeting interferons, cytokines and their receptors, intracellular signals, plasma cells, T lymphocytes and co-stimulatory molecules are being evaluated. In the context of a holistic approach, growing evidence is emerging of the importance of correct lifestyle habits in the management of lupus manifestations and comorbidities. The aim of this paper is to provide an overview of current pharmacological and non-pharmacological treatment options and emerging therapies in SLE.

18.
J Rheumatol ; 47(9): 1314-1322, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238511

RESUMO

OBJECTIVE: To examine the value of optical spectral transmission (OST) in detecting joint inflammation in patients with rheumatoid arthritis (RA) and to evaluate whether OST correlates with certain patient characteristics. METHODS: OST measurements were performed in the metacarpophalangeal, proximal intraphalangeal, and wrist joints of 168 patients with RA and 114 controls. OST difference between the 2 groups was statistically examined and subsequently controlled for the effect of possible confounding factors. Diagnostic OST performance was tested by receiver-operating characteristics. Moreover, associations of OST with clinical and serological activity markers (patient group), joint ultrasound (US; patient subgroup) and various anthropometric and epidemiologic parameters (patient and control group) were evaluated by Spearman correlation coefficient and a generalized linear statistical adjustment model. RESULTS: OST was significantly higher in the RA group than in the control group, even after adjustment for confounding factors (1.89; 95% CI 0.709-3.070, padj = 0.002). Taking US as a reference, area under the curve for all 1251 joints simultaneously was 0.67 (95% CI 0.631-0.709). In the patient group, correlation and adjustment analyses showed associations of OST with various disease activity markers [28-joint count Disease Activity Score (rho 0.313), swollen joint counts (rho 0.361), C-reactive protein (rho 0.389); all, padj = 0.001], age (rho 0.276, p < 0.001), and osteoarthritis (p = 0.022). Moreover, OST associated with a power Doppler US score (rho 0.442; p = 0.001) and a greyscale US score (rho 0.591; p < 0.001). In both groups males had significantly higher OST values than females and OST associated moderately weakly with body mass index (rho patients 0.316, rho controls 0.24; all, p < 0.001). CONCLUSION: Patients with RA showed higher OST values in comparison to controls. Moreover, OST associated with clinical, US, and laboratory disease activity markers.

20.
Clin Exp Rheumatol ; 38(1): 74-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30943131

RESUMO

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are under increased risk for cardiovascular events (CVE) and mortality. Aortic stiffness, as measured by carotid-femoral pulse wave velocity (cfPWV), has been shown to predict CVE and mortality in the general population. The aim of the present study was to examine the factors associated with cfPWV in patients with SLE and to determine differences of SLE patients in comparison to healthy controls. METHODS: 125 patients with SLE and 104 controls were included. Demographic, medication and cardiovascular risk factor data were collected from all participants. Furthermore, clinical and laboratory SLE associated parameters were documented in the patients' group. All subjects underwent measurements of blood pressure and cfPWV. RESULTS: Interestingly, only age (ß=0.55; p<0.001), mean arterial pressure (MAP) (ß=0.29; p<0.001) and estimated glomerular filtration rate (eGFR) (ß=-0.20; p=0.033) were associated independently with cfPWV in patients with SLE. Moreover, there was no difference of cfPWV between patients with SLE and controls before (p=0.301) and after adjustment for disparities between the groups (p=0.671). CONCLUSIONS: Vascular stiffness in patients with SLE seems to be independent from SLE-related factors and from most traditional CVRF and is mainly associated with age, MAP and renal function defined as eGFR. There is an independent correlation between eGFR and cfPWV in a SLE population with a widely normally ranged eGFR. There is no difference of cfPWV between patients with SLE and controls.


Assuntos
Lúpus Eritematoso Sistêmico , Rigidez Vascular , Pressão Sanguínea , Estudos de Casos e Controles , Taxa de Filtração Glomerular , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Análise de Onda de Pulso , Fatores de Risco
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