João Carlos Tavares Brenol

Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis.

OBJECTIVE To study the association of the presence of fibromyalgia (FM) with the Disease Activity Score in 28 joints (DAS28), the Health Assessment Questionnaire (HAQ), and the Medical Outcomes Study Short Form 36 (SF-36) health survey in patients with rheumatoid arthritis (RA). METHODS A total of 270 outpatients with RA were enrolled in a prospective cross-sectional study. The patients underwent clinical evaluation and application of the HAQ and SF-36 questionnaires. Disease activity was evaluated using the DAS28 score. FM and RA diagnoses were made according to American College of Rheumatology criteria. RESULTS The overall prevalence of FM was 13.4%. This group of patients had a higher prevalence of female sex, older mean age, higher functional class, and longer morning stiffness than patients with only RA. Mean +/- SD DAS28 scores were significantly higher in patients with RA and FM (5.36 +/- 0.99) than in patients with RA only (4.03 +/- 1.39; P < 0.001). In a multivariable linear regression analysis, FM was an important predictor of the DAS28 score, even after adjusting for the erythrocyte sedimentation rate, number of swollen joints, functional class, number of disease-modifying antirheumatic drugs currently in use, current dose of steroids, and articular erosions. HAQ and SF-36 scores were also worse in patients with RA and associated FM. CONCLUSION FM is related to worse scores on the DAS28, HAQ, and SF-36 in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 score because it is related to higher scores independently of objective evidence of RA activity.

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

OBJECTIVE To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

The role of mannose-binding lectin in systemic lupus erythematosus

Susceptibility to systemic lupus erythematosus (SLE) is associated with genetic, hormonal, immunological, and environmental factors. Many genes have been related with the appearance of SLE, including several loci that code different complement components and their receptors. Some genetic deficiencies of complement molecules are strongly associated with SLE, probably because these deficiencies could cause decreased clearance of apoptotic cell material. As a consequence of the apoptotic material accumulation, high levels of autoantigens can be presented inappropriately to the immune system in an inflammatory context, resulting in an imbalance on the mechanisms of immunological tolerance, immune system activation, and autoantibody production. Recent studies proposed a role to the mannose-binding lectin (MBL) in the SLE physiopathogenesis. This protein activates the complement system, and the presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at the plasma levels of MBL. Some of these polymorphisms have been associated with SLE susceptibility, as well as with clinical and laboratory typical features of this disease, cardiovascular events, and infections. Besides, it has been described that the presence of anti-MBL autoantibodies in sera of SLE patients can influence MBL plasma levels and its functional activity.

Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile idiopathic arthritis and rheumatoid arthritis

We tested the possible association of the 14-bp polymorphism of the HLA-G gene in the course of two inflammatory diseases, rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Patients and controls were genotyped for the 14-bp polymorphism by polymerase chain reaction with specific primers for the exon 8 of the human leukocyte antigen (HLA)-G gene and the amplified fragment was visualized in a 6% polyacrylamide gel. A total of 106 JIA patients, 265 RA patients, 356 healthy adults and 85 healthy children were genotyped for the 14-bp polymorphism. Female JIA patients presented a higher frequency of the -14 bp allele when compared with female healthy children (0.743 and 0.500, corrected P=0.003), which reflected in the JIA group as a whole. This increased frequency of the -14-bp allele was observed in all JIA subtypes. In RA patients, no differences in allelic and genotypic frequencies were observed between patients and controls. No correlations were observed among genotype and disease severity or clinical manifestations. Our data suggest that the HLA-G -14 bp allele is probably a risk factor for JIA, mainly in females. Considering the differences observed in relation to gender, we suggest that hormonal differences can interfere with the development of JIA. Considering the RA patients, our data agree with results from the literature and highlight the differences in the etiology of RA and JIA.

Consenso de lúpus eritematoso sistêmico

DESCRICAO DO METODO DE COLETA DE EVIDENCIAS Dez reumatologistas que trabalham em servicos que atendem grande numero de pacientes com lupus eritematoso sistemico, alguns dos quais tem pesquisa e publicacoes cientificas nesta area, foram convidados a participar do grupo de trabalho. Todos se reuniram para discutir o tratamento das diferentes manifestacoes da doenca, subdivididos em grupos de trabalho, cada qual ficando responsavel por buscar a melhor evidencia para o tratamento de um ou mais comprometimentos da doenca. A ultima edicao de Dubois’s Lupus Erythematosus, editado por Wallace D e Hahn B, em 2007 (Lippincott Williams & Wilkins), foi utilizada como base da discussao. Trabalhos publicados nos ultimos cinco anos foram pesquisados no MedLine. Em virtude da frequencia e da heterogeneidade de manifestacoes da doenca, a maioria dos trabalhos terapeuticos nao contempla grande casuistica, nem sao randomicos e controlados. Como as manifestacoes e a gravidade da doenca variam em diferentes grupos populacionais, devem ser avaliados com cuidado os estudos realizados em grupos populacionais distintos.

Serum S100B Levels in Patients with Lupus Erythematosus: Preliminary Observation

ABSTRACT S100B is an astrocytic calcium-binding protein which has been proposed as a biochemical marker of brain damage or dysfunction in acute and chronic diseases. We investigated whether serum S100B levels could be related to systemic lupus erythematosus (SLE) activity. Patients were grouped as having inactive SLE (ISLE), active SLE without central nervous system (CNS) involvement (ASLE), or active SLE with unequivocal neurologic or psychiatric manifestation (NPSLE). The control group consisted of age- and sex-matched healthy blood donors. S100B levels were determined using a luminescence immunoassay. All SLE groups had higher levels of serum S100B than the control group. Among the SLE groups, significantly higher levels of serum S100B protein were found in the NPSLE group than in the ISLE and ASLE groups, and there was no significant difference in S100B levels between the ISLE and ASLE groups. These preliminary results point to a putative relevance of serum S100B protein levels in SLE patients, specifically concerning CNS involvement present in this disease.

Consenso da Sociedade Brasileira de Reumatologia para o diagnóstico, manejo e tratamento da nefrite lúpica

OBJECTIVE To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. METHOD Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision.

Artrite reumatóide e aterosclerose

Rheumatoid arthritis is a systemic inflammatory autoimmune disease characterized by symmetric, erosive and chronic synovitis, especially of minor joints. It is associated with increased prevalence of cardiovascular disease and with high mortality. This occurs because of an accelerated atherogenic process, explained by traditional cardiovascular risk factors such as smoking, hypercholesterolemia, age, diabetes mellitus and systemic arterial hypertension. High levels of hemosedimentation velocity and C-reactive protein are directly correlated with increased cardiovascular events. Pro-inflammatory cytokines contribute with endothelial dysfunction, insulin resistance, dyslipidemia, prothrombotic effects and oxidative stress that are at the basis of the atherogenic process. Recent information about atherosclerosis in rheumatoid arthritis allows for identification of the risk factors involved in atherosclerosis that can be best controlled. This could result in a reduced manifestation of the process and its cutback, with consequent decrease of mortality and morbidity related to rheumatoid arthritis.

The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort

Purpose To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. Methods SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. Results 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate). Conclusions The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.

Differential CCR5Δ32 allelic frequencies in juvenile idiopathic arthritis subtypes: evidence for different regulatory roles of CCR5 in rheumatological diseases

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and is characterized by persistent arthritis for at least 6 weeks. Its aetiopathogenesis is unknown but there is strong evidence that there is a substantial genetic component. Chemokine receptors genes are among the candidate genes for association with arthritis and other inflammatory diseases. The CC chemokine receptor 5 (CCR5)Δ32 polymorphism has been associated with rheumatoid arthritis (RA), conferring a protective effect. Objective: To determine whether the CCR5Δ32 polymorphism is associated with JIA and RA in Brazilian patients. Methods: We investigated 203 RA patients, 101 JIA patients, and 104 healthy individuals by amplification of the CCR5Δ32 deletion. We compared the allelic frequencies among these groups, as well as among different JIA subtypes. Results: The frequency of the Δ32 allele was higher in JIA patients (9.4%) as compared to control subjects (3.8%) and RA patients (3.2%). Grouping the patients according to JIA subtypes, we observed a higher CCR5Δ32 allelic frequency in the subtypes with a greater inflammatory component: 4.1% in oligoarticular (n = 49), 11.2% in polyarticular (n = 40) [9.5% in rheumatoid factor negative (RF−) and 33.3% in RF positive (+)], and 25% in systemic JIA (n = 12). Conclusions: This study suggests that in JIA, unlike in RA, CCR5Δ32 does not have a protective effect, but instead it could be a factor associated with more inflammatory forms of the disease. These observations give rise to new questions about the mechanism and the cellular types involved in JIA as well as about the aetiology of JIA.