RESUMO
Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO2 and VE/VCO2 parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO2 (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO2), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI > 25 kg/m2 and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.
Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Doenças Cardiovasculares/etiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Função Ventricular/fisiologia , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Sistema Cardiovascular/fisiopatologia , Ecocardiografia Doppler em Cores , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Rigidez Vascular/fisiologiaRESUMO
OBJECTIVES: This 52-week, randomised, double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol (CZP) as add-on therapy to non-biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with low to moderate disease activity, and stopping therapy in patients in sustained remission. METHODS: Patients were randomised 1:1 to CZP (400â mg at weeks 0, 2 and 4, then 200â mg every 2â weeks) or placebo (every 2â weeks) plus current non-biologic DMARDs. At week 24, patients who achieved the primary endpoint of Clinical Disease Activity Index (CDAI) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52. RESULTS: Of 194 patients (CZP=96; placebo=98), >90% had moderate disease activity at baseline. Significantly more CZP patients met the primary endpoint than placebo patients (week 20 and 24 CDAI remission rates: 18.8% vs 6.1%; p≤0.05). At week 24, 63.0% vs 29.7% of CZP versus placebo patients (p<0.001) achieved LDA. Disease activity score (ESR) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo (19.8% vs 3.1%; p≤0.01 and 14.6% vs 4.1%; p≤0.05). CZP patients reported improvements in physical function versus placebo (mean Health Assessment Questionnaire-Disability-Index change from baseline: CZP, -0.25 vs placebo, -0.03; p≤0.01). During the period following withdrawal of CZP or placebo, only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52, but CZP reinstitution allowed renewed improvement. Adverse and serious adverse event rates were comparable between CZP and placebo groups. CONCLUSIONS: Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity, allowing low-disease activity or remission to be reached in a majority of the patients. However, the data suggest that CZP cannot be withdrawn in patients achieving remission. TRIAL REGISTRATION NUMBER: NCT00674362.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adolescente , Adulto , Idoso , Certolizumab Pegol , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV). METHODS: Study part I developed a questionnaire for CV to be included in the formal, second part (study part II). Positivity of serum cryoglobulins was defined by experts as an essential condition for CV classification. In study part II, a core set of classification items (questionnaire, clinical and laboratory items, as agreed) was tested in three groups of patients and controls-that is, group A (new patients with the CV), group B (controls with serum cryoglobulins but lacking CV) and group C (controls without serum cryoglobulins but with features which can be observed in CV). RESULTS: In study part I (188 cases, 284 controls), a positive response to at least two of three selected questions showed a sensitivity of 81.9% and a specificity of 83.5% for CV. This questionnaire was employed and validated in study part II, which included 272 patients in group A and 228 controls in group B. The final classification criteria for CV, by pooling data from group A and group B, required the positivity of questionnaire plus clinical, questionnaire plus laboratory, or clinical plus laboratory items, or all the three, providing a sensitivity of 88.5% and a specificity of 93.6% for CV. By comparing data in group A versus group C (425 controls), the same classification criteria showed a sensitivity 88.5% and a specificity 97.0% for CV. CONCLUSION: Classification criteria for CV were developed, and now need validation.
Assuntos
Crioglobulinemia/classificação , Vasculite/classificação , Adulto , Idoso , Crioglobulinemia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Inquéritos e Questionários , Síndrome , Vasculite/etiologiaRESUMO
Platelet activation and aggregation are key elements of the pathogenesis of acute coronary syndromes, of endothelial damage in chronic inflammatory and connective tissue disease (i.e. systemic sclerosis-SSc). Patients affected by chronic inflammatory diseases as well as by connective tissue diseases such as systemic sclerosis, often have the need to take anti-platelet therapy (e.g. ASA or clopidogrel). Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. Although each single PPI has similar efficacy in many cases, differences between them should be considered when choosing a treatment regimen. Many studies show PPI and clopidogrel drug interaction, with clopidogrel non-responsiveness in about 25% of the population. Only pantoprazole, which does not inhibit CYP P450 2C19, doesn't seem to have interaction with clopidogrel or other drugs. Patients affected by systemic sclerosis have high frequency of oesophageal mucosal abnormalities and should take long-term PPI therapy. When addressing long-term therapy safety data are clearly needed. Two recent studies have reported increased hip fracture rates with long-term PPI use, raising concerns about adverse effects of this class of drugs on mineral metabolism. The use of PPIs is also associated with an increase in the risk of development of Clostridium difficile infection (CDI) and the use of PPIs during CDI treatment is associated with an increased risk of recurrence. In order to achieve the desired results and, as with all medications, PPIs should always be used appropriately taking care never to exceed correct dosage and duration. When necessary use of pantoprazole arises as one of the best possible choices.
Assuntos
Fraturas Espontâneas/prevenção & controle , Inibidores da Bomba de Prótons/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Hidrocarboneto de Aril Hidroxilases/deficiência , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/farmacocinética , Cálcio da Dieta/farmacocinética , Clopidogrel , Clostridioides difficile , Comorbidade , Citocromo P-450 CYP2C19 , Suscetibilidade a Doenças , Interações Medicamentosas , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/etiologia , Fraturas Espontâneas/epidemiologia , Fraturas Espontâneas/etiologia , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Hiperparatireoidismo Secundário/complicações , Infecções/epidemiologia , Osteoporose/complicações , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacocinética , Doenças Reumáticas/complicações , Doenças Reumáticas/metabolismo , Risco , Trombofilia/complicações , Trombofilia/tratamento farmacológico , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Ticlopidina/farmacocinéticaRESUMO
INTRODUCTION: Several studies demonstrated the benefits of rehabilitation in uraemic patients. This study evaluates physical and psychosocial effects of exercise on renal transplant recipients (RTRs). PATIENTS AND METHODS: Eight RTRs were evaluated before and after an exercise training consisting of thirty 40-minute sessions, three times a week, performed with the interval training technique. RESULTS: Hospital Anxiety and Depression Scale (HADS) significantly decreased (p<0.04 and <0.008, respectively). Quality of life mean scores (SF-36 test) significantly increased (p<0.000). No differences were recorded for muscle and fat mass, maximal explosive power of the lower limbs, alkaline and acid phosphatase, parathormone (PTH), myoglobin, lipoprotein-A, glomerular filtration rate (GFR), at rest heart rate, and cardiac troponin. IL-6 decreased from 2.8±0.6 to 1.7±0.5 pg/mL (p<0.01). Resting MAP fell from 112±4 to 99±3 mmHg (p<0.02). The metabolic threshold rose from 33±4 to 43±5% (p<0.033). The blood lactate level at peak exercise increased from 5.2±0.9 to 6.2±0.7 mmol/L (p<0.012). The maximum oxygen uptake increased from 1200±210 to 1359±202 mL/min (p<0.05), iso-load oxygen uptake decreased from 1110±190 to 1007±187 mL/min (p<0.034). The maximum working capacity increased from 90±14 to 115±15 watts (p<0.000). CONCLUSION: This study suggests that an appropriate dose of physical training is a useful, safe and non-pharmacologic contribution to RTR treatment.
Assuntos
Terapia por Exercício , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/psicologia , Transplante de Rim , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Mycophenolic acid (MPA) is an immunosuppressive agent, more and more extensively used in transplantation, rheumatology and nephrology. In this review, we will analyze the molecular mechanisms of its action, including the newest insights, in particular the inhibition of lymphocytes and the induction of tolerogenic dendritic cells (DCs) and its direct effects on non-immune cells (fibroblasts and myofibroblasts, mesangial cells, vascular smooth muscle cells [VSMC], endothelial cells). The latters suggest new therapeutic indications, specifically fibrosis (i.e. glomerulosclerosis and interstitial lung diseases), vascular damage and pulmonary hypertension, which represent key pathogenic features in connective tissue diseases. Given the differences in sensitivity to MPA among the various cell types and the great inter-individual variability in MPA pharmacokinetics, adequate daily doses and therapeutic drug monitoring may be decisive to ensure those MPA concentrations needed to switch off inflammation and restore peripheral tolerance in autoimmune disease (AID) patients. A warning on the severe adverse events strictly linked to immune suppression (i.e. progressive multifocal leukoencephalopathy [PML]) will be stressed.
Assuntos
Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Doenças Reumáticas/tratamento farmacológico , Vasos Sanguíneos/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Monitoramento de Medicamentos , Fibrose/tratamento farmacológico , Humanos , Imunossupressores/farmacologia , Leucoencefalopatias/induzido quimicamente , Linfócitos/efeitos dos fármacos , Ácido Micofenólico/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Doenças Reumáticas/imunologiaRESUMO
OBJECTIVE: To develop a set of national evidence-based recommendations for the use of Methotrexate (MTX) in daily clinical practice. METHODS: A panel of 37 Italian Rheumatologists reviewed 10 international recommendations formulated during the "3E (Evidence, Expertise, Exchange) initiative" for the year 2007-8, following a systematic literature search in Medline, Embase, Cochrane Library, and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts and the revision of selected papers and the appraisal of Oxford levels of evidence. Moreover, the same panel by the same methodology formulated further 5 recommendations on topics previously selected by Italian representatives to 3E initiative. The agreement about the set of proposed recommendations was stated by a consensus process and the potential impact on clinical practice was assessed. RESULTS: International Recommendations were analysed and changed when appropriate. In addition, 5 national recommendations were developed by identifying 6371 references, selecting and evaluating the 29 ones satisfying Evidence Based Medicine principles. CONCLUSIONS: A set of 15 national recommendations for the use of MTX in daily clinical practice was developed. These recommendations are evidence-based and integrate the expertise of a large panel of Italian rheumatologists.
Assuntos
Antirreumáticos , Artrite Reumatoide , Consenso , Metotrexato , Doenças Reumáticas , Humanos , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ensaios Clínicos Controlados como Assunto , Técnica Delphi , Itália , Metanálise como Assunto , Metotrexato/uso terapêutico , Doenças Reumáticas/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate the role of the HS1,2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome. METHODS: Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 with longstanding RA (LSRA)) and from 248 gender-matched controls from the same geographical area. Clinical and immunological characteristics were recorded for all the patients. RESULTS: The percentage of the 2/2 genotype was higher in patients with ERA (27.0%), and in patients with LSRA (34.2%), than in controls (14.9%) (ERA: OR = 2.11 (95% CI 1.20 to 3.70) vs controls; LSRA: OR = 2.96 (95% CI 1.76 to 5.00) vs controls). A lower representation of allele *3 was present in patients with ERA (2.0%) than in controls (6.0%; OR = 0.32 (95% CI 0.11 to 0.91)). No significant associations were found between polymorphisms and autoantibodies positivity. CONCLUSION: The HS1,2A allele *2 associates with early and longstanding RA.
Assuntos
Alelos , Artrite Reumatoide/genética , Cadeias Pesadas de Imunoglobulinas/genética , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Estudos de Coortes , Elementos Facilitadores Genéticos , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Sequências Reguladoras de Ácido Nucleico , Fator Reumatoide/sangue , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Spondyloarthritis (SpA) is a well recognized extraintestinal manifestation of Inflammatory Bowel Diseases (IBDs), either Crohn's Disease(CD) or Ulcerative Colitis (UC). A much larger percentage of SpA patients have subclinical gut inflammation manifested either by endoscopic findings or by histology. The aim of the present article is to review clinical and experimental evidences regarding the immunological and genetic links between gut and joint inflammation in IBDs and SpA. EVIDENCE AND INFORMATION SOURCES: A systematic review using PubMed database entering IBD and SpA as key words was performed. STATE OF THE ART: The association with HLA-B27 is less strong in IBD-associated SpA than in Idiopathic Ankylosing Spondylitis (AS) and there is some evidence for an association between gut inflammation in SpA and CD related CARD15 mutations. A common inflammatory pathogenic pathway has been suggested in gut and joint inflammation in IBD. Treatment of SpA associated with IBD has gained major advances in recent years with the advent of anti-TNF-alpha therapy. PERSPECTIVES: The adaptive immune response in IBD is thought to be strictly differentiated between Th1 and Th2 in CD and UC respectively. Recent findings, however, suggest that novel effector pathways could drive tissue damage. The most important pathway now emerging is the IL-23/IL-17 axis. CONCLUSIONS: Present and future advancements of knowledge on mechanisms of inflammation will likely lead to new therapeutic targets.
Assuntos
Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Espondiloartropatias/genética , Espondiloartropatias/imunologia , Predisposição Genética para Doença , Antígeno HLA-B27/metabolismo , Humanos , Imunidade Inata , Imunidade nas Mucosas , Doenças Inflamatórias Intestinais/complicações , Modelos Biológicos , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único , Espondiloartropatias/complicaçõesRESUMO
It is thought that in genetically predisposed individuals, autoimmune diseases can be promoted and/or exacerbated by viruses, bacteria, or parasitic infectious agents. Pathogens can activate innate immune response interacting with Toll-like receptors that recognize pathogen-associated molecules. As a consequence of infections, a prolonged inflammatory response may occur leading to chronic inflammation with activation of adaptive immune response. In addition, the defective clearance of apoptotic infected cells, which progress- es to secondary necrosis, can foster the autoimmune reactions. Although numerous data from humans and/or animal models support the hypothesis of a direct contribution of pathogens to the induction of the disease, some infectious agents are able to prevent autoimmune disorders. In this review, data on the innate and adaptive immune response induced by pathogens are summarized, focusing on the possible protective or non-protective role of infections in the development of autoimmune diseases.
Assuntos
Doenças Autoimunes/microbiologia , Doenças Autoimunes/virologia , Infecções/complicações , Infecções/imunologia , Doenças Reumáticas , Animais , Humanos , Doenças Reumáticas/imunologia , Doenças Reumáticas/microbiologia , Doenças Reumáticas/virologiaRESUMO
Retroperitoneal fibrosis (RPF) is a rare disease characterized by an inflammatory proliferative fibrosing process occurring in the retroperitoneum, often causing urinary tract obstruction. Medical therapy is not well-defined, but glucocorticoids have been the mainstay of therapy. Recently, positive response to tamoxifen, an antiestrogen drug, has been reported among patients with RPF. We report the case of a 65-year-old male with a renal cell carcinoma in the upper pole of the right kidney showing acute renal failure due to a biopsy-confirmed RPF determining bilateral hydronephrosis. After polar resection of the right kidney, a high-dose oral steroid therapy did not modify the hydronephrosis. At 6 months, therapy with tamoxifen determined the retroperitoneal fibrotic mass regression and resolved the ureteral obstruction, that persists at the 13th month of follow-up. Tamoxifen can be considered as an effective alternative to corticosteroids and immunosuppressors in treating RPF.
Assuntos
Antagonistas de Estrogênios/uso terapêutico , Fibrose Retroperitoneal/tratamento farmacológico , Tamoxifeno/uso terapêutico , Corticosteroides/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fibrose Retroperitoneal/patologiaRESUMO
Rheumatoid arthritis is the most common autoimmune arthritis in adult population. This disease is characterized by joint damage and systemic involvement that lead to general physical and mental impairment with consequent worsening of quality of life. Rheumatoid arthritis is also associated with a large economic burden to healthcare systems. The evidence from the literature indicates that, despite available treatments, several unmet needs still interfere with rheumatoid arthritis management. Based on this evidence, some of the unmet medical needs currently present in the management of the rheumatoid arthritis were identified and a Delphi questionnaire was submitted to 60 Italian Rheumatologists. The aim of this Delphi was to achieve a broad consensus on the most relevant unmet needs identified, in order to present the Italian reality in view of the availability of new molecules that could provide an effective therapeutic option in the treatment of patients with rheumatoid arthritis.
Assuntos
Artrite Reumatoide/terapia , Técnica Delphi , Adulto , Artrite Reumatoide/complicações , Doenças Autoimunes , Consenso , Humanos , Itália , Avaliação das Necessidades , Qualidade de VidaRESUMO
TNF-alpha is thought to play a pivotal role in the initiation and perpetuation of the chronic inflammatory process in rheumatoid arthritis. TNF-alpha blockers such as infliximab and etanercept are currently used in the treatment of active rheumatoid arthritis (RA) when traditional DMARDs have failed and are effective in a significant proportion of patients. However, about one third are non-responders to anti-TNF-alpha. The aim of this study was to verify whether rheumatoid patients, after failing infliximab, can benefit from etanercept. We analysed 18 patients with active RA with no response to at least 3 DMARDs and where infliximab therapy had failed. The patients had received infliximab associated with methotrexate: eleven of them did not show any significant response, while seven patients, after a good response, relapsed. Etanercept was then started. EULAR criteria of response were used with calculation of activity index DAS28 at baseline, after 2 weeks, 3 months and every third month until last follow-up. A moderate or good response was achieved with etanercept in 13 out of 18 patients. From our experience, etanercept can be considered as a good alternative choice when infliximab has failed.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Resistência a Medicamentos , Etanercepte , Feminino , Humanos , Imunoglobulina G/farmacologia , Fatores Imunológicos/farmacologia , Infliximab , Masculino , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach.
Assuntos
Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Fator Ativador de Células B/fisiologia , Doenças Reumáticas/patologia , Doenças Reumáticas/terapia , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Doenças Autoimunes/genética , Fator Ativador de Células B/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Doenças Reumáticas/genética , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Síndrome de Sjogren/terapiaRESUMO
Autoimmune chronic inflammatory diseases (ACIDs) represent a growing part of chronic diseases and their cellular and molecular pathways have been deeply investigated in recent years in order to disclose some clue aspects that could be optimal targets of specific therapies. Among the autoimmune rheumatic diseases a major molecular driver was discovered (TNFalpha) which represents along with IL1beta, a key driver of the ongoing chronic inflammation. The same molecule arose as a major player in the pathological mechanism of Crohn's disease. The biomolecular pathways of Ulcerative Colitis appear more complex and not yet defined, although targeting specific integrins (alpha4beta7) has shown some promises, pending the severe side effects related to treatment.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Terapia Biológica , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Espondiloartropatias/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doença Crônica , Tratamento Farmacológico , Humanos , Imunidade nas Mucosas , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Reumáticas/genética , Doenças Reumáticas/imunologia , Espondiloartropatias/genética , Espondiloartropatias/imunologiaRESUMO
T cells exert a fundamental role in different autoimmune chronic inflammatory diseases. The low-affinity autoreactive T cell clones provide the first amplification loop after the antigen (AgX) presentation, and if not counterregulated by the T regulatory cells (Treg), they maintain the inflammation and predispose to organ damage. Interrupting the T cell amplification loop through calcineurin antagonists leads to maintenance of the whole process under the autoimmune threshold.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Linfócitos T/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Doenças Autoimunes/imunologia , Antígenos CD28/fisiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Ciclosporina/uso terapêutico , Citocinas/fisiologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Humanos , Tolerância Imunológica , Inflamação/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologiaRESUMO
OBJECTIVE: To assess the relationship between tumor necrosis factor receptor II (TNF-RII) gene polymorphisms and sTNFRII plasma levels in healthy blood donors (HBDs) and in rheumatoid arthritis (RA) patients. 113 HBDs and 49 RA patients were genotyped for the T/G polymorphism in exon 6 of the TNF-RII gene. In the same cases, sTNF-RII plasma levels were determined by an enzyme-linked immunosorbent assay (ELISA) procedure. sTNF-RII levels were higher in RA patients than in HBDs (p < 0.0001). No difference in sTNF-RII levels arose between RA patients on low oral doses of glucocorticoids versus those not taking glucocorticoids. In healthy controls, we observed lower levels of the sTNF-RII in carriers of the TT genotype compared to TG/GG genotype (p = 0.04). In RA there was the same behaviour between TT and TG/GG carriers, even though the difference was not statistically significant. When analyzing the correlation between sTNF-RII plasma levels and disease activity parameters, significant correlations were seen with disease activity score (r = 0.40, p = 0.01), swollen joint count (r = 0.38, p = 0.01), and tender joint count (r = 0.42, p = 0.01), but not with erythrocyte sedimentation rate (r = 0.22, p = ns) nor with C-reactive protein (r = 0.14, p = NS). The correlation remained significant only in the RA subgroup carrying the TT genotype. Healthy donors carrying the TT genotype showed lower sTNF-RII plasma levels than carriers of the TG/GG genotypes, while in RA patients we observed only a trend.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/genética , Adolescente , Adulto , Idoso , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , SolubilidadeRESUMO
The effects of cyclosporin on the activity of rheumatoid arthritis have mainly been investigated in patients with active, refractory, long-standing disease. The data obtained in these trials suggest that cyclosporin is not only a symptomatic treatment for rheumatoid arthritis but can also be considered a disease-modifying antirheumatic drug (DMARD), since it seems to be capable of slowing the progression of cartilage and bone damage due to rheumatoid arthritis. The trials conducted so far have led to a better understanding of cyclosporin toxicity and, therefore, to better monitoring of patients in order to avoid it. The reasons for studying the role of cyclosporin in patients with early, active and potentially severe rheumatoid arthritis are the poor prognosis of the disease despite the use of the presently available DMARDs, and the hypothesis that the drug is more efficacious and better tolerated in early rheumatoid arthritis. A new classification of antirheumatic drugs proposes that disease-controlling antirheumatic therapies decrease inflammatory synovitis and prevent structural joint damage or significantly reduce its rate of progression. However, few existing drugs meet these criteria. The 12-month results of a disease-controlling antirheumatic therapy clinical trial with a blinded radiological end-point, named GRISAR (Gruppo Reumatologi Italiani Studio Artrite Reumatoide) comparing cyclosporin with conventional DMARDs in patients with early rheumatoid arthritis provide strong evidence that cyclosporin offers better control of ongoing joint damage than do conventional DMARDs.
RESUMO
Ankylosing spondylitis (A.Sp.) and diffuse idiopatic skeletal hyperostosis (DISH), represent the most common inflammatory and degenerative enthesopathies, respectively. Despite their rather frequent occurrence in the rheumatic disease care setting, few case reports of their simultaneous presence in the same patient have appeared in the literature. We describe here a further observation and review the rheumatologic literature.
Assuntos
Hiperostose Esquelética Difusa Idiopática/complicações , Espondilite Anquilosante/complicações , Idoso , Artrite/complicações , Artrite/diagnóstico por imagem , Humanos , Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Masculino , Radiografia , Articulação Sacroilíaca , Espondilite Anquilosante/diagnóstico por imagemRESUMO
Combination therapy has emerged as a crucial therapeutic tool to control aggressive rheumatoid arthritis (RA). Cyclosporine (CsA) when combined with methotrexate (MTX) has shown substantial benefit in clinical practice. The primary benefit is its positive effect in the control of joint-bone erosions. The most feared adverse effect is the development of nephrotoxicity, which may be in part hemodynamic and in part structural, i.e. fibrotic. Careful monitoring of concomitant drugs, hypertension and through blood levels should allow the patient to maintain normal renal function. The successful employment of CsA in lupus nephritis clearly supports this statement.