RESUMO
Objectives: Insulin resistance (IR) constitutes a major underlying abnormality driving cardiovascular disease in the general population and has been linked to inflammatory diseases. In this study, we aimed to determine the prevalence of IR in patients with spondyloarthritis (SpA) and whether IR can be explained by disease-related features in such cases. Method: The study included 577 subjects: 306 patients diagnosed with SpA according to Assessment of SpondyloArthritis international Society criteria and 271 controls. Insulin and C-peptide serum levels, IR and ß-cell function (%B) indices by homoeostatic model assessment (HOMA2), and lipid profiles were assessed in patients and controls. A multivariable regression analysis was performed to evaluate the differences in IR indices between patients and controls and to determine how IR is associated with disease-related characteristics in SpA patients. Results: HOMA2-%B and HOMA2-IR scores, both calculated with insulin or C-peptide, had significantly higher values in SpA patients compared to controls in multivariable analysis adjusted for age, gender, traditional IR-related factors, and glucocorticoid intake. Disease activity, functional status, and metrological SpA indices were positively related to IR, but only in univariable analysis. Disease duration and positivity for human leucocyte antigen-B27 were independently associated with a higher HOMA2-%B after multivariable analysis. Conclusion: Patients with SpA have an increased IR compared to controls. SpA disease-related data are independently associated with ß-cell dysfunction.
Assuntos
Glicemia/metabolismo , Resistência à Insulina/fisiologia , Insulina/sangue , Espondilartrite/metabolismo , Adulto , Idoso , Peptídeo C/sangue , Estudos Transversais , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: In 2006 the European League Against Rheumatism (EULAR) proposed new classification criteria for Henoch-Schönlein purpura (HSP). We aimed to establish the applicability of these criteria in patients with primary cutaneous vasculitis (CV). We also compared these criteria with previously established classification criteria for HSP. METHODS: A series of 766 (346 women/420 men; mean age 34 years) consecutive unselected patients with CV was assessed. One hundred and twenty-four of them with secondary CV or with CV associated with other well defined entities were excluded from the analysis. The 2006 EULAR criteria for HSP were tested in the remaining 642 patients with primary CV. Two sets of criteria for HSP were used for comparisons: a) the 1990 American College of Rheumatology (ACR-1990), and b) the ACR modified criteria proposed by Michel et al. in 1992 (Michel-1992). RESULTS: 451 (70.2%) of 642 patients were classified as having HSP according to the EULAR-2006 criteria, 405 (63.1%) using the ACR-1990 criteria, and 392 (61.1%) by the Michel-1992 criteria. However, only 336 patients (52.3%) met at the same time the EULAR-2006 and the ACR-1990 criteria, and only 229 patients (35.7%) fulfilled both the EULAR-2006 and Michel-1992 criteria. It is noteworthy that only 276 (43%) patients met the three set of criteria. Children fulfilled all the sets of criteria more commonly than adults (215 [66.6%] of 323 vs. 61 [19%] of 319, respectively; p<0.0001). CONCLUSIONS: According to our results, the EULAR-2006 criteria show low concordance with previous sets of classification criteria used for HSP.
Assuntos
Vasculite por IgA/diagnóstico , Vasculite Leucocitoclástica Cutânea/diagnóstico , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos , Dermatopatias Vasculares/diagnóstico , Vasculite/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: To assess the clinical spectrum of severe bacterial infections presenting as cutaneous vasculitis (CV) in a defined population. METHODS: Unselected series of 766 patients with CV diagnosed at a single university referral center. RESULTS: An underlying severe bacterial infection was diagnosed in 27 (22 men/5 women; mean age ± standard deviation [SD]: 53 ± 18 years) of 766 cases presenting with CV (3.5%). These infections were: pneumonia (n=8), endocarditis (n=6), meningitis (n=4), intra-abdominal infections (n=3), septic arthritis (n=2), septicaemia (n=2), septic bursitis (n=1), and urinary tract infection (n=1). All the patients were admitted for suspected CV. The median delay from admission to the diagnosis of infection was 4 days. A typical palpable purpura without relevant visceral vasculitic involvement was the main clinical manifestation. Patients with severe bacterial infections were older, with male predominance, had more frequently fever, constitutional symptoms, focal infectious features, and leukocytosis with left shift and anaemia than the remaining patients with CV. Although antibiotics were prescribed in all the patients, seven also required the use of low-dose corticosteroids to achieve complete resolution of the cutaneous lesions. Most patients experienced full recovery but two of them underwent prosthetic cardiac valve replacement, and another two died due to infection-related complications. CONCLUSIONS: CV may be the presenting manifestation of a severe underlying bacterial infection. Physicians should keep in mind this fact to make an early diagnosis of infection and, consequently, prevent life-threatening complications.
Assuntos
Infecções Bacterianas/complicações , Dermatopatias Vasculares/etiologia , Vasculite/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Infecciosa/complicações , Bursite/complicações , Estudos de Coortes , Endocardite Bacteriana/complicações , Feminino , Humanos , Infecções Intra-Abdominais/complicações , Masculino , Meningites Bacterianas/complicações , Pessoa de Meia-Idade , Pneumonia Bacteriana/complicações , Estudos Retrospectivos , Sepse/complicações , Infecções Urinárias/complicaçõesRESUMO
OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.
Assuntos
Anticorpos Monoclonais , Gelsolina/metabolismo , Espondilite Anquilosante , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adipocinas/metabolismo , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Humanos , Inflamação/tratamento farmacológico , Infliximab , Infusões Intravenosas , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Gravidade do Paciente , Fatores Sexuais , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismo , Espondilite Anquilosante/fisiopatologia , Estatística como Assunto , Resultado do TratamentoRESUMO
Neurologic manifestations are found in 5-15 % of patients with sarcoidosis. This granulomatous disease may affect any part of the peripheral or the central nervous system, being potentially severe and difficult to treat. Corticosteroids are the cornerstone of therapy in sarcoidosis. However, some patients become resistant or experience side effects to corticosteroids. In these patients, second line therapies including immunosuppressive drugs such as methotrexate, azathioprine, mycophenolate, cyclophosphamide and leflunomide have been used. Anti-TNF-α drugs have been proposed as a therapeutic option for those who are refractory to immunosuppressive drugs or initially in cases of severe sarcoidosis. We report on 5 patients with neurosarcoidosis treated with anti-TNF-α drugs in our center. A literature review of patients with neurosarcoidosis treated with anti-TNF-α drugs was conducted. In our series successful response to anti-TNF-α therapy was achieved. However, the high frequency of relapses following anti-TNF-α discontinuation makes necessary a close follow-up of these patients when the biologic agent is stopped.
Assuntos
Doenças do Sistema Nervoso Central , Imunossupressores , Sarcoidose , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Idoso , Biópsia , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/fisiopatologia , Resistência a Medicamentos , Feminino , Granuloma/imunologia , Granuloma/patologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/classificação , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose/imunologia , Sarcoidose/fisiopatologia , Prevenção Secundária , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.
Assuntos
Angiopoietina-2/sangue , Anticorpos Monoclonais , Aterosclerose , Osteopontina/sangue , Espondilite Anquilosante , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Infliximab , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Fatores de Risco , Espanha , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismo , Estatística como Assunto , Resultado do TratamentoRESUMO
Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.
Assuntos
Receptor gp130 de Citocina/genética , Predisposição Genética para Doença , Vasculite por IgA/genética , Receptores de Interleucina-6/genética , Adulto , Criança , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Vasculite por IgA/imunologia , Masculino , Polimorfismo Genético , EspanhaRESUMO
Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Cromossomos Humanos Par 11/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/genética , Demografia , Feminino , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVES: Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are related syndromes. In the present study we aimed to compare the clinical characteristics and outcome of a large and unselected series of patients diagnosed as having HSPN and IgAN. METHODS: Comparative study of a wide and unselected population of HSPN (142 patient) and IgAN (61 patients) from a teaching hospital of Northern Spain. RESULTS: All of the following comparisons were expressed between HSPN vs. IgAN, respectively. HSPN patients were younger (30.6±26.4 vs. 37.1±16.5 years, p<0.001). Precipitating events, usually an upper respiratory tract infection and/or drug intake, were more frequently observed in HSPN (38% vs. 23%, p=0.03). Extra-renal manifestations were also more common in HSPN than in IgAN; skin lesions (100% vs. 1.8%; p<0.001), gastrointestinal (62% vs. 7.4%; p<0.001), and joint involvement (61.3% vs. 3.6%; p<0.001). However, nephritis was less severe in HSPN, renal insufficiency (25% in HSPN vs. 63.4% in IgAN; p<0.001), nephrotic syndrome (12.5%, vs. 43.7%; p<0.001), and nephritic syndrome (6.8% vs. 10.7%; NS). Leukocytosis was more frequent in HSPN (22.5% vs. 8.2%; p=0.015) and anaemia in IgAN (12.7% in HSPN vs. 36% in IgAN, p<0.001). The frequency of corticosteroid (79.6% vs. 69%; NS) and cytotoxic drug (19% vs. 16.5%, NS) use was similar. The frequency of relapses was similar (38.6% in HSPN vs. 36.3% in IgAN). After a median follow-up of 120.8 (IQR; 110-132) months in HSPN and 138.6 (IQR; 117-156) in IgAN, requirement for dialysis (2.9% vs. 43.5%; p<0.001), renal transplant (0% vs. 36%, p<0.001) and residual chronic renal insufficiency (4.9% vs. 63.8%; p<0.001) was more frequently observed in patients with in IgAN. CONCLUSIONS: HSPN and IgAN represent different syndromes. IgAN has more severe renal involvement while HSPN is associated with more extra-renal manifestations.