RESUMO
OBJECTIVE: This pragmatic, multicenter, open-label, randomized controlled trial (RCT) aimed to compare the effectiveness, safety, and cost-utility of a custom-made knee brace versus usual care over 1 year in medial knee osteoarthritis (OA). DESIGN: 120 patients with medial knee OA (VAS pain at rest >40/100), classified as Kellgren-Lawrence grade II-IV, were randomized into two groups: ODRA plus usual care (ODRA group) and usual care alone (UCA group). The primary effectiveness outcome was the change in VAS pain between M0 and M12. Secondary outcomes included changes over 1 year in KOOS (function) and OAKHQOL (quality of life) scores. Drug consumption, compliance, safety of the knee brace, and cost-utility over 1 year were also assessed. RESULTS: The ODRA group was associated with a higher improvement in: VAS pain (adjusted mean difference of -11.8; 95% CI: -21.1 to -2.5); all KOOS subscales (pain: +8.8; 95% CI: 1.4-16.2); other symptoms (+10.4; 95% CI: 2.7-18); function in activities of daily living (+9.2; 95% CI: 1.1-17.2); function in sports and leisure (+12.3; 95% CI: 4.3-20.3); quality of life (+9.9; 95% CI: 0.9-15.9), OAKHQOL subscales (pain: +14.8; 95% CI: 5.0-24.6); and physical activities (+8.2; 95% CI: 0.6-15.8), and with a significant decrease in analgesics consumption at M12 compared with the UCA group. Despite localized side-effects, observance was good at M12 (median: 5.3 h/day). The ODRA group had a more than 85% chance of being cost-effective for a willingness-to-pay threshold of 45 000 per QALY. CONCLUSIONS: The ERGONOMIE RCT demonstrated significant clinical benefits of an unloader custom-made knee brace in terms of improvements in pain, function, and some aspects of quality of life over 1 year in medial knee OA, as well as its potential cost-utility from a societal perspective.
Assuntos
Osteoartrite do Joelho/reabilitação , Idoso , Braquetes , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Resultado do TratamentoRESUMO
To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions ( O2-°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O2-° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O2-° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1ß and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation.
Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Acetilcolina/farmacologia , Animais , Aorta/fisiopatologia , Arginase/farmacologia , Artrite , Artrite Reumatoide/fisiopatologia , Fatores Biológicos/metabolismo , Glicemia/análise , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Colesterol/sangue , Ciclo-Oxigenase 2/farmacologia , Citocinas/sangue , Frequência Cardíaca , Masculino , Distribuição Aleatória , Ratos , Superóxidos/metabolismo , Triglicerídeos/sangueRESUMO
AIM: To test the efficiency of tumour necrosis factor blockers (adalimumab) in patients with painful refractory (non-responders to analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)) hand osteoarthritis (OA). METHODS: We performed a randomised, double-blind, placebo-controlled, parallel group, multicentre study. Patients were randomised to: 1/1 adalimumab 40â mg for two subcutaneous injections at a 15-day interval or placebo and monitored for 6â months. The primary outcome was the percentage of patients with an improvement of more than 50% in global pain (Visual Analogue Scale) between week 0 (W0) and week 6 (W6). Secondary outcomes included the number of painful joints, swollen joints, morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, and consumption of analgesics. Analysis on the mean primary outcome measure was done on patients who received at least one injection. RESULTS: 99 patients were recruited and 85 patients were randomised. Among them, 37 patients in the placebo group and 41 in the adalimumab group received at least one injection and were evaluated at W6 (n=78) on the main efficacy outcome. Mean age was 62â years, 85% were women, and mean level of pain was 62â mm at W0. At W6, 35.1% in the adalimumab group versus 27.3% in the placebo group had a pain reduction ≥50% (RR 1.12 (95% CI 0.82 to 1.54; p=0.48). There were no statistical differences for all secondary end points. The rate of adverse events was similar in the two groups. CONCLUSIONS: Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs. TRIALS REGISTRATION NUMBER: NCT00597623.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Articulação da Mão , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Adalimumab , Idoso , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/complicações , Dor/etiologia , Medição da Dor , Falha de Tratamento , Resultado do TratamentoRESUMO
The classification criteria recently developed by the Assessment of Spondyloarthritis International Society (ASAS) highlighted a specific entity: non radiographic axial spondyloarthritis (nr-axSpA). Although more and more widely used in the literature as well as clinical trials, limits and profile of this entity is still under known or debated. Some studies have already compared those forms to classical AS, even in recent forms. They showed that, apart from the difference in the ossification process, and the greater degree and frequency of systemic and MRI inflammation in AS, those 2 forms of SpA share the same genetic background, clinical patterns, and burden of disease. TNF antagonists seemed as effective in controlling symptoms in patients with nr-axSpA. Concerning the long-term outcome of nr-ax-SpA, only long-term ongoing cohorts of patients with recent nr-axSpA will be able to determine what proportion of patients have persistent non-radiographic disease and what proportion do progress to AS.
Assuntos
Espondilartrite/classificação , Terminologia como Assunto , Anti-Inflamatórios/uso terapêutico , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , Radiografia , Espondilartrite/diagnóstico por imagem , Espondilartrite/imunologia , Espondilartrite/terapia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: To explore cardiac structural and functional parameters and myocardial sensitivity to ischemia in a rat model of chronic arthritis, pristane-induced arthritis (PIA), and to investigate the effects of a running exercise protocol on cardiac disorders related to rheumatoid arthritis (RA). MAIN METHODS: 3 groups of male Dark Agouti rats were formed: Controls, PIA and PIA-Exercise. The PIA-Exercise group was subjected to an individualized treadmill running protocol during the remission phase. At acute and chronic phases of PIA, cardiac structure was analyzed by histology. Cardiac function was explored in isolated hearts to measure left ventricular developed pressure (LVDP), cardiac compliance and infarct size before and after ischemia/reperfusion. Cardiac inflammation was evaluated through VCAM-1 mRNA expression by RT-qPCR. Plasma irisin levels were measured by ELISA. KEY FINDINGS: PIA rats exhibited myocardial hypertrophy fibrosis and inflammation at the 2 inflammatory phases of the model. At chronic phase only, LVDP and cardiac compliance were lower in PIA compared to controls. As compared to sedentary PIA, exercise did not change cardiac function but reduced fibrosis, inflammation, infarct size, and arthritis severity and increased irisin levels. Cardiac inflammation positively correlated with fibrosis, while irisin levels negatively correlated with cardiac inflammation and fibrosis. SIGNIFICANCE: In the PIA model that recapitulated most cardiac disorders of RA, a daily program of treadmill running alleviated cardiac fibrosis and inflammation and improved resistance to ischemia. These data provide arguments to promote the practice of exercise in RA patients for cardiac diseases prevention.
Assuntos
Artrite Experimental , Artrite Reumatoide , Cardiopatias , Terpenos , Humanos , Ratos , Masculino , Animais , Artrite Experimental/metabolismo , Fibronectinas/efeitos adversos , Inflamação , Artrite Reumatoide/metabolismo , Isquemia , Infarto , FibroseRESUMO
BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. RESULTS: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.
Assuntos
Anti-Inflamatórios/efeitos adversos , Antirreumáticos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Métodos Epidemiológicos , Etanercepte , Feminino , França/epidemiologia , Humanos , Imunoglobulina G/efeitos adversos , Infliximab , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Receptores do Fator de Necrose TumoralRESUMO
This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.
Assuntos
Guias de Prática Clínica como Assunto , Espondilite Anquilosante/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Humanos , Cooperação Internacional , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: The aim of this study was to assess the anti-inflammatory effects of local cryotherapy in human non-septic knee arthritis. METHODS: In the phase I of the study, patients were randomized to receive either ice (30 min; N = 16) or cold CO2 (2 min; N = 16) applied twice during 1 day at an 8-h interval on the arthritic knee. In phase II, 16 other ice-treated arthritic knees according to the same protocol were compared to the contralateral non-treated arthritic knees (N = 16). The synovial fluid was analyzed just before the first cold application, then 24 h later. IL-6, IL-1ß, TNF-α, IL-17A, VEGF, NF-kB-p65 protein, and PG-E2 levels were measured in the synovial fluid and compared before/after the two cold applications. RESULTS: Forty-seven patients were included (17 gouts, 11 calcium pyrophosphate deposition diseases, 13 rheumatoid arthritides, 6 spondyloarthritides). Local ice cryotherapy significantly reduced the IL-6, IL-1ß, VEGF, NF-kB-p65, and PG-E2 synovial levels, especially in the microcrystal-induced arthritis subgroup, while only phosphorylated NF-kB-p65 significantly decreased in rheumatoid arthritis and spondyloarthritis patients. Cold CO2 only reduced the synovial VEGF levels. In the phase II of the study, the synovial PG-E2 was significantly reduced in ice-treated knees, while it significantly increased in the corresponding contralateral non-treated arthritic knees, with a significant inter-class effect size (mean difference - 1329 [- 2232; - 426] pg/mL; N = 12). CONCLUSIONS: These results suggest that local ice cryotherapy reduces IL-6, IL-1ß, and VEGF synovial protein levels, mainly in microcrystal-induced arthritis, and potentially through NF-kB and PG-E2-dependent mechanisms. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03850392-registered February 20, 2019-retrospectively registered.
Assuntos
Crioterapia/métodos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Osteoartrite do Joelho/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/metabolismo , Líquido Sinovial/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation. METHODS: We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids. RESULTS: BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range. CONCLUSIONS: In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.
Assuntos
Anticorpos Monoclonais/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/fisiopatologia , Remodelação Óssea/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Absorciometria de Fóton , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/fisiopatologia , Reabsorção Óssea/prevenção & controle , Cartilagem Articular/fisiopatologia , Feminino , Articulação do Quadril/efeitos dos fármacos , Articulação do Quadril/fisiopatologia , Humanos , Infliximab , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Anti-TNF-alpha agents have been tried in cases of refractory sarcoidosis, giving favourable results. Thus, the occurrence of a granulomatous disease in a patient receiving such drug seems paradoxical. We describe 2 patients with inflammatory rheumatic disease, the first with ankylosing spondylitis, the second with rheumatoid arthritis, under anti-TNF-alpha treatment (infliximab and etanercept respectively) who developed non-caseating granulomas of the lungs and lymph nodes consistent with the diagnosis of sarcoidosis. Limited and various similar cases have been reported. It is generally considered that these granulomatous diseases are related to the anti-TNF-alpha agent.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Imunoglobulina G/efeitos adversos , Doenças Reumáticas/tratamento farmacológico , Sarcoidose/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Etanercepte , Feminino , Granuloma/induzido quimicamente , Granuloma/patologia , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Pneumopatias/induzido quimicamente , Pneumopatias/patologia , Doenças Linfáticas/induzido quimicamente , Doenças Linfáticas/patologia , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Sarcoidose/diagnóstico , Sarcoidose/patologiaRESUMO
INTRODUCTION: Anti TNF-alpha agents may represent a possibility of treatment in cases of refractory polymyositis. CASE REPORT: We report a case of polymyositis refractory to corticosteroids and immunosuppressive agents in whom adjunction of infliximab led to a mild and transient improvement, and a secondary improvement after discontinuation of the treatment. DISCUSSION: In the reported cases of polymyositis treated with infliximab or etanercept a short-term response was seen in 9 out of 11 cases. Adverse events of the treatment are mentioned, and should be taken into account in the decision of treatment.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Polimiosite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Resistência a Medicamentos , Feminino , Humanos , InfliximabRESUMO
INTRODUCTION: Multiple myeloma and primary hyperparathyroidism are two causes of hypercalcemia. This association has already been described to be not casual, despite their link is still unknown. OBSERVATION: We describe a 68 years old woman, without notable background, was admitted for low back pain. Biology showed an IgG Kappa multiple myeloma (stade 3) and an hypercalcemia without renal failure. Hypercalcemia was difficult to control with bisphosphonate and calcitonin. At first, there was also an hypophosphoremia and a high parathormone level (287 pg/ml). Imaging showed spread myeloma impairment and a right paramediastinal tissular mass. Biopsy diagnosed an ectopic parathyroidal adenoma. DISCUSSION: Multiple myeloma and primary hyperparathyroidism can be associated. They are often revealed by an hypercalcemia difficult to control or refractory to the treatment. Hypophosphoremia can suggest the diagnosis of hyperparathyroidism. Both this observation and litterature (about twenty case reports) suggest that this double diagnosis should be systematicly evoked and explored by an assay of parathormone and a seric proteins electrophoresis in all hypercalcemia. CONCLUSION: Multiple myeloma and parathyroidal adenoma should be both explored in all hypercalcemia, because they can be associated.
Assuntos
Adenoma/diagnóstico , Hipercalcemia/etiologia , Mieloma Múltiplo/diagnóstico , Neoplasias das Paratireoides/diagnóstico , Adenoma/complicações , Idoso , Dor nas Costas/etiologia , Coristoma/diagnóstico , Feminino , Humanos , Hiperparatireoidismo/etiologia , Mieloma Múltiplo/complicações , Neoplasias das Paratireoides/complicaçõesRESUMO
BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with axial involvement but its physiopathology remains unexplained. This latter combines genetic and environmental factors as well as an abnormal immune response. CURRENT TOPICS AND IMPORTANT RESULT: This review addresses the different aspects of AS immunogenetic. A genetic background in AS is suggested by familial cases, concordance rate in twins and transmission of the disease in siblings. Ankylosing spondylitis is strongly associated with the expression of the HLA Class I antigen, B27, but also with other genes not yet identified since currently, only chromosomic area have been linked to AS. Studies of candidate genes or genome screening allow to determine these chromosomic regions. HLA-B27 is directly associated with the disease physiopathology as suggested by animal models of rats transgenic for human HLA-B27 and beta2 microglobulin. This HLA molecule have original biological properties, in particular a slow heavy chain folding and the formation of heavy chain homodimers without light chain. However, HLA B27 is a functional molecule and assumes its property of presenting peptide of 9 amino acids to CD8+ T cells. Interaction modelling studies between HLA B27 and peptides have identified peptide and peptide groove amino acid sequences, with the identification of critical positions on the HLA B27 molecule for the peptide interaction. Original biochemical properties of HLA-B27 include diminished bacterial antigen response and CD4+ T lymphocyte stimulation. Innate immunity is also of interest in AS, as suggested by the presence of macrophage and polymorphonuclear neutrophils in AS synovitis, as well as the contribution of Toll-like receptors. FUTURE PROSPECTS AND PROJECTS: Thus in AS, the inflammatory process and then the clinical consequences may be explained by the involvement of HLA-B27, a bacterial antigen presentation, an abnormal immune response and the contribution of innate immunity, T CD4+ but also T CD8+ cells. The original molecular structures of HLA-B27 are certainly involved in this complex physiopathology, but their direct influence on the disease remains to be precised.
Assuntos
Antígeno HLA-B27/imunologia , Espondilite Anquilosante/genética , Espondilite Anquilosante/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Antígeno HLA-B27/genética , Humanos , Linhagem , Peptídeos/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVE: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). METHODS: A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. RESULTS: One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. CONCLUSION: In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.
Assuntos
Complemento C4/imunologia , Crioglobulinemia/epidemiologia , Neoplasias Pulmonares/epidemiologia , Linfoma/epidemiologia , Linfopenia/epidemiologia , Fator Reumatoide/imunologia , Neoplasias das Glândulas Salivares/epidemiologia , Síndrome de Sjogren/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , França/epidemiologia , Doença de Hodgkin/epidemiologia , Humanos , Leucemia Linfocítica Crônica de Células B/epidemiologia , Linfoma de Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Micose Fungoide/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome de Sjogren/imunologia , Reino Unido/epidemiologiaAssuntos
Toxidermias/etiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Granuloma Anular/induzido quimicamente , Humanos , Psoríase/induzido quimicamente , Nódulo Reumatoide/induzido quimicamente , Sarcoidose/induzido quimicamente , Vasculite Leucocitoclástica Cutânea/induzido quimicamenteRESUMO
In this study, the polymorphisms of the HLA DMA and DMB genes in patients with rheumatoid arthritis (RA) were examined.DMA and DMB typing was performed in 120 white RA patients from eastern France and 100 healthy controls, using PCR-SSO (sequence specific oligonucleotide probes) method for DMA determination and PCR-RFLP (restriction fragment length polymorphism) method for DMB typing. All patients and controls had been HLA DRB1* genotyped.DMA*0103 was found significantly increased in RA patients (RA vs. controls: 18.3% vs. 4%) (p(corr) = 0.004; OR: 5.39; CI: 1.67-19.23). A decreased frequency of DMA*0102 was also observed in the RA group (RA vs. controls: 18.3% vs. 31%), but not significantly. There were no differences in the prevalence of DMB alleles between RA and controls. The patients and the controls were then stratified according to the expression of the HLA DRB1* RA-linked alleles (DRB1*01 and *04) and this allowed us to find no linkage disequilibrium between DMA*0103 and DRB1*01 or *04 alleles. Finally, most DMA*0103 patients were positive for rheumatoid factors and had extraarticular involvement such as subcutaneous nodules. Thus, our results suggest that DMA*0103 could be an additional genetic factor for RA susceptibility in French whites.
Assuntos
Artrite Reumatoide/genética , Genes MHC da Classe II , Antígenos HLA-D/genética , Antígenos de Histocompatibilidade Classe II , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Artrite Reumatoide/imunologia , Feminino , Frequência do Gene , Ligação Genética , Predisposição Genética para Doença , Genótipo , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness and discomfort. Several drugs are currently available in the management of AS, and may be divided into 3 groups. The first includes nonsteroidal anti-inflammatory drugs (NSAIDs), which are the main drug group used in AS because they reduce pain and stiffness in most patients. Several NSAIDs are available but phenylbutazone is considered the NSAID of choice in AS. However, other NSAIDs give similar beneficial results and the medication of preference in specific to each patient. All NSAIDs share common gastrointestinal toxicity, and they should be administered during periods of flare-up of the disease. The second drug group that has been used in the treatment of patients with AS comprises analgesics, muscle relaxants and low dose corticosteroids. They can be considered as adjuvant therapy. These drugs are helpful when NSAIDs are poorly tolerated or ineffective. Second-line treatments or disease modifying antirheumatic drugs (DMARDs) are included in the third group. These drugs are required in cases of longstanding severe or refractory AS. Sulfasalazine has proven to be effective in such cases, leading to improvement in clinical and laboratory indices of disease activity. Beneficial results are mainly evident in patients with AS who have peripheral disease involvement. Other medications (such as methotrexate or gold salts, for instance) require properly designed controlled studies to evaluate their effectiveness in the treatment of this disorder, while immunosuppressive agents have little to offer in the management of patients with AS and require further studies. Some specific clinical features are observed in AS: enthesopathy may be treated with local injection of corticosteroids; sacroiliac joint pain may be managed by corticosteroid injection performed under fluoroscopic control or guided by computed tomography. The management of patients with AS includes some other procedures such as patient education, rest, a programme of physical exercise and physiotherapy. In parallel with pharmacotherapy, these procedures are of great importance in reducing stiffness and spinal ankylosis, and thus improve the patient's quality of life.
Assuntos
Espondilite Anquilosante/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Penicilamina/uso terapêutico , Sulfassalazina/uso terapêuticoRESUMO
Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease involving spinal and sacroiliac joints. This condition is responsible for back pain, stiffness, but also loss of functional capacity with socio-economic consequences. The management of AS includes patient education, rest, a programme of regular physical exercise, together with the use of NSAIDs. Second-line treatments are required in cases of severe or refractory AS, however only sulfasalazine has proven to benefit AS patients with peripheral arthritis. In spite of this management, the disease may not be adequately controlled, mainly for patients with refractory axial disease, enthesopathy or extra-articular features. Thus, new innovative treatments are needed for AS. It is likely that the new NSAIDs or COX-2 specific inhibitors will certainly take the place of the conventional NSAIDs, with regard to their superior tolerability. Methotrexate is a therapeutic option for AS treatment, but its usefulness in this disease remains to be established in adequate controlled studies. Finally, the TNF-alpha targeting drugs, namely thalidomide and the anti-TNF-alpha mAb, infliximab, have given promising results in the treatment of severe and/or refractory AS patients, however further controlled studies are required. In addition, the long-term use (efficacy and tolerability) of these two agents deserves attention.