RESUMO
OBJECTIVE: In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. METHOD: Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28-C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. RESULTS: Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0-6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. CONCLUSIONS: Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.
Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Etanercepte/uso terapêutico , Resultado do Tratamento , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Proteína C-Reativa , Indução de RemissãoRESUMO
Objectives: Anti-carbamylated protein antibodies (anti-CarP) are reported to be associated with increased disease activity and with more severe joint damage in rheumatoid arthritis (RA) patients. The present study investigated the presence of anti-CarP in various rheumatic diseases, and their specific clinical significance in RA, in Belgian rheumatology patients.Method: We tested sera from 254 RA patients, 56 healthy controls, and 153 patients with different rheumatic conditions: juvenile idiopathic arthritis (JIA), axial spondyloarthritis, systemic sclerosis, and Sjögren's syndrome (SS). An in-house enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies against carbamylated foetal calf serum.Results: Anti-CarP were detected in 88 RA patients (34.6%), of whom 82% were also positive for anti-citrullinated protein antibodies (ACPAs) and 81% were also rheumatoid factor (RF) positive. Of note, 11 anti-CarP single-positive patients were detected (4.3%). The previously reported association with joint erosions was not detected. However, in ACPA- and RF-negative RA patients, the presence of anti-CarP was associated with higher disease activity and disability. Fifteen per cent of JIA patients and 30% of SS patients also tested positive for anti-CarP and their antibody levels did not differ significantly from those of anti-CarP-positive RA patients. Anti-CarP levels were, however, significantly higher in ACPA- or RF-positive patients.Conclusion: Anti-CarP antibodies were detected in the sera of a cohort of Belgian RA patients. Moreover, they were also detected in primary SS patients and in JIA patients. In the seronegative subset of RA patients, anti-CarP antibodies showed prognostic value.
Assuntos
Artrite Juvenil/imunologia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Escleroderma Sistêmico/imunologia , Síndrome de Sjogren/imunologia , Espondilartrite/imunologia , Adulto , Artrite Juvenil/sangue , Artrite Reumatoide/sangue , Autoanticorpos/sangue , Bélgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/sangue , Estudos Soroepidemiológicos , Síndrome de Sjogren/sangue , Espondilartrite/sangueRESUMO
Since the field around morphea and systemic sclerosis (SSc) is evolving rapidly, this review approaches conventional as well as more recent clinical developments from a dermatological point of view. Skin manifestations are critical in sub-classifying these diseases ensuring a correct prognosis for these patients. They can be discretely present, and therefore, diagnosis can be challenging sometimes, implicating a thorough dermatological examination is mandatory. Furthermore, a growing amount of dermatologists perform nailfold videocapillaroscopy (NVC), a more recent reliable non-invasive imaging technique used for in vivo assessment of the microcirculation at the nailfold. After all, specific NVC-changes are present in a majority of patients with SSc. This way, dermatologists not only take part in the diagnosis process through clinical investigation but also through the use of a modern state of the art imaging technique that is becoming the golden standard in SSc multidisciplinary workup. In this review, current understandings for NVC in morphea and SSc are revised. So far, the role of NVC in the diagnosis/prognosis/classification of morphea patients has not been thoroughly investigated to make proper conclusions. As for SSc, it is well known that NVC contributes to the diagnosis and can make a fundamental difference especially when obvious clinical SSc signs are absent. This review emphasizes the (somewhat underestimated) role of dermatologists in the process of diagnosis and follow-up, and thus, the difference we can make for our patients and fellow colleagues in the multidisciplinary workup of SSc and morphea.
Assuntos
Esclerodermia Localizada , Escleroderma Sistêmico , Capilares , Humanos , Microcirculação , Angioscopia Microscópica , Unhas , Esclerodermia Localizada/diagnóstico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnósticoRESUMO
Rheumatoid arthritis is the most common chronic inflammatory rheumatic disorder, and is characterized by inflammation of the joint, which can lead to irreversible bone damage, joint deformity and disability, if not diagnosed timely or treated adequately. New classification criteria were developed in 2010 in order to identify patients at risk of developing persistent or erosive arthritis, and requiring early therapy. In order to detect early arthritis or bone erosions before their appearance on X-rays, ultrasound and magnetic resonance imaging are now routinely used by clinicians, and also seem to deliver prognostic information about the disease. Synovial biopsies are potentially interesting in case of early arthritis to identify markers of diagnosis, prognosis or therapeutic response. Genetic or environmental risk factors were described to play a role in the development or maintenance of the disease; they could also help to screen early RA. A rapid diagnosis is eventually based on the right information and a tight collaboration between the primary care physician and the rheumatology care specialist.
Assuntos
Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Diagnóstico por Imagem , Diagnóstico Precoce , HumanosRESUMO
" Spondyloarthritis" consists of a group of several diseases sharing clinical, radiological and genetic similarities. Ankylosing spondylitis is the main representative of this group and is characterized by a predominant axial involvement. The presence of radiographic sacroiliitis is essential for the diagnosis of ankylosing spondylitis according to the modified New York criteria. Because the occurence of radiographic sacroiliitis takes 8 to 11 years, the diagnosis of spondyloarthritis is often delayed. Magnetic resonance imaging can depict sacroiliac joint inflammation before the appearance of radiographic damage thereby defining the concept of " non-radiographic axial spondylo-arthritis". This entity was defined by the axial spondyloarthritis classification criteria published by the Assessment of SpondyloArthritis international Society (ASAS). Some factors, such as elevated levels of C-reactive protein at baseline, have been identified as predictors of radiographic sacroiliitis progression, leading to a definite diagnosis of ankylosing spondylitis. These two entities show similar clinical expression (clinical features and activity levels), suggesting continuity between the two diseases. Non-radiographic forms most often affect women and patients with recent symptoms, and are therefore considered as a pre-radiographic status. If the use of magnetic resonance imaging is necessary for the identification of non-radiographic axial spondyloarthritis according to the ASAS criteria, the presumptive diagnosis is mainly based on complaints of inflammatory back pain. The presence of other typical clinical features, such as HLA B27 positivity and/or radiographic sacroiliitis increases the diagnostic probability and indicates the need for referral to a specialist.
Assuntos
Espondilartrite/classificação , Espondilartrite/diagnóstico , Diagnóstico por Imagem , HumanosRESUMO
Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.
Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Esclerodermia Difusa , Escleroderma Sistêmico , Humanos , Doenças Raras/complicações , Doenças Raras/epidemiologia , Doenças Raras/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Doenças Pulmonares Intersticiais/complicaçõesRESUMO
OBJECTIVES: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific markers of rheumatoid arthritis (RA). Considering the heterogeneity of the target antigens involved, and the test platforms and conjugates proposed in commercial anti-CCP assays, we assessed the diagnostic performances of four fully automated anti-CCP assays in a cohort of patients with RA compared to patients with other autoimmune and inflammatory disorders. We also evaluated the agreement between the qualitative results of these immunoassays. METHOD: We evaluated three anti-CCP2 assays [Eurodiagnostica enzyme-linked immunosorbent assay (ELISA), Elecsys electrochemiluminescence immunoassay (ECLIA) on the Modular E170 Analyzer, and Zenit chemiluminescence immunoassay (CLIA) on the Zenit RA Analyzer] and one anti-CCP3 assay (Inova ELISA). ELISAs were performed on an automated workstation. Samples from 112 patients with RA and a disease control group of 136 patients (53 with autoimmune diseases, 65 non-autoimmune disorders, and 18 infectious diseases) were studied (included 161 samples submitted consecutively to the laboratory). RESULTS: At a fixed specificity of 92%, the anti-CCP3 assay presented the highest sensitivity (75%) compared to the anti-CCP2 assays evaluated (63-72%). The Zenit anti-CCP2 assay gave the most false-positive results (especially in patients with viral infections and connective tissue diseases). The agreement between assays ranged from 86.3% to 95.2% and Kappa coefficients ranged from 0.724 to 0.899. CONCLUSIONS: Recently released automated workstations provide a valuable alternative to ELISA to diagnose RA. However, differences in diagnostic performances are highlighted in our experience, especially for the Zenit assay. In our cohort, the anti-CCP3 assay gave slightly better performances than the anti-CCP2 assays (with the exception of the Zenit assay).
Assuntos
Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Medições Luminescentes/métodos , Peptídeos Cíclicos/imunologia , Adulto , Idoso , Artrite Reumatoide/imunologia , Bioensaio/métodos , Estudos de Casos e Controles , Estudos de Coortes , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
We previously demonstrated that baseline synovial overexpression of the interleukin-7 receptor α-chain (IL-7R) is associated with poor response to tumour necrosis factor (TNF) blockade in rheumatoid arthritis (RA). We found that IL-7R gene expression is induced in fibroblast-like synovial cells (FLS) by the addition of TNF-α, IL-1ß and combinations of TNF-α+ IL-1ß or TNF-α+ IL-17, thereby suggesting that these cytokines play a role in the resistance to TNF blockade in RA. Because FLS and CD4 T cells also produce a soluble form of IL-7R (sIL-7R), resulting from an alternative splicing of the full-length transcript, we wondered whether expression of sIL-7R is similarly regulated by pro-inflammatory cytokines. We also investigated whether sIL-7R is detectable in the serum of RA patients and associated with response to TNF blockade. RA FLS were cultured in the presence of pro-inflammatory cytokines and sIL-7R concentrations were measured in culture supernatants. Similarly, sIL-7R titres were measured in sera obtained from healthy individuals, early untreated RA patients with active disease and disease-modifying anti-rheumatic drug (DMARD)-resistant RA patients prior to initiation of TNF-blockade. Baseline serum sIL-7R titres were correlated with validated clinical measurements of disease activity. We found that exposure of RA FLS to pro-inflammatory cytokines (TNF-α, IL-1ß and combinations of TNF-α and IL-1ß or TNF-α and IL-17) induces sIL-7R secretion. Activated CD4 T cells also produce sIL-7R. sIL-7R serum levels are higher in RA patients as compared to controls. In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade. In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA.
Assuntos
Artrite Reumatoide/imunologia , Citocinas/farmacologia , Receptores de Interleucina-7/biossíntese , Membrana Sinovial/citologia , Adulto , Idoso , Processamento Alternativo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Biomarcadores , Linfócitos T CD4-Positivos/metabolismo , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Fibroblastos/imunologia , Fibroblastos/metabolismo , Humanos , Interleucina-17/metabolismo , Interleucina-17/farmacologia , Interleucina-1beta/farmacologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-7/sangue , Receptores de Interleucina-7/genética , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. It typically occurs in young women receiving oral contraceptive therapy or during the peripartum period. In the case presented here, spontaneous complete healing at angiography and the favorable outcome may support the role of conservative treatment in such patients.
Assuntos
Aneurisma Coronário/diagnóstico por imagem , Angiografia Coronária , Adulto , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Aneurisma Coronário/complicações , Eletrocardiografia , Feminino , Seguimentos , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologiaRESUMO
Reversible dementia and polyneuropathy in an elderly woman: a case of late onset systemic lupus erythematosus. We report the case of a 76-year-old woman with undiagnosed systemic lupus erythematosus. She presented with severe dementia. She was given prednisolone 20 mg daily with dramatic improvement occurring within one month. Electrophysiological study showed evidence of axonal neuropathy.
Assuntos
Demência/etiologia , Lúpus Eritematoso Sistêmico/complicações , Polineuropatias/etiologia , Idoso , Demência/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisolona/uso terapêuticoRESUMO
Atrial fibrillation (AF) and other cardiac arrhythmias may occur after stroke in absence of cardiac disease. We report a case of pontine ischemic stroke with paroxysmal atrial fibrillation of spontaneous resolution. Cardiac investigations were normal. We propose that the AF was the consequence of the stroke.
Assuntos
Fibrilação Atrial/etiologia , Isquemia Encefálica/complicações , Ponte/irrigação sanguínea , Idoso , Fibrilação Atrial/diagnóstico , Isquemia Encefálica/diagnóstico , Eletrocardiografia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
OBJECTIVES: Evaluation of disease activity in systemic lupus erythematosus (SLE) nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a previous cross-sectional study, we reported that serum soluble form of the interleukin-7 receptor (sIL7R) levels is strongly associated with nephritis in SLE patients. In the present study, we wanted to confirm the association between changes in serum sIL7R concentrations and renal disease activity in a large longitudinal cohort of SLE nephritis patients. METHODS: Sera were harvested longitudinally in 105 SLE nephritis patients. Serum sIL7R cut-off value for the detection of SLE nephritis activity was determined as the mean sIL7R concentration in non-nephritis SLE patients + 2â SDs using data collected in our previous study. Patients with glomerular filtration rate (GFR) <60â mL/min/1.73â m(2) (n=17) were excluded from the study due to persistently elevated serum sIL7R values. RESULTS: Serum sIL7R concentrations above the renal cut-off value were observed in 25 (out of 88) patients with a normal GFR. These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio. Strikingly, 12 of them developed a renal British Isles Lupus Assessment Group index (BILAG) A within the next 3â months, while this was only the case in four out of the 63 other patients (p<0.0001). The test had 75.0% sensitivity and 81.9% specificity for the detection of a renal BILAG A. Combination of serum sIL7R with any of the classical tests (anti-dsDNA Ab titres, UPC ratio, serum C3) resulted in an increased specificity for the detection of a renal flare. Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations. CONCLUSIONS: Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are associated with or predict the occurrence of an SLE nephritis flare.