Claudia Diniz Lopes Marques

A importância dos níveis de vitamina D nas doenças autoimunes

Alem do seu papel na homeostase do calcio, acredita-se que a forma ativa da vitamina D apresenta efeitos imunomoduladores sobre as celulas do sistema imunologico, sobretudo linfocitos T, bem como na producao e na acao de diversas citocinas. A interacao da vitamina D com o sistema imunologico vem sendo alvo de um numero crescente de publicacoes nos ultimos anos. Estudos atuais tem relacionado a deficiencia de vitamina D com varias doencas autoimunes, como diabetes mellitus insulino-dependente (DMID), esclerose multipla (EM), doenca inflamatoria intestinal (DII), lupus eritematoso sistemico (LES) e artrite reumatoide (AR). O artigo faz uma revisao da fisiologia e do papel imunomodulador da vitamina D, enfatizando sua participacao nas doencas reumatologicas, como o lupus e a artrite reumatoide.In addition to its role in calcium homeostasis, it is believed that the active form of vitamin D has immunomodulatory effects on cells of the immune system, particularly T lymphocytes, as well as on the production and action of several cytokines. The interaction of vitamin D with the immune system has been the target of a growing number of publications in recent years. Current studies have linked the deficiency of vitamin D with different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), multiple sclerosis (MS), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). This article reviews the physiology and immunomodulatory role of vitamin D, emphasizing its involvement in rheumatic diseases such as SLE and RA.

Comorbidades em pacientes com osteoartrite: frequência e impacto na dor e na função física

INTRODUCTION: As the prevalence of osteoarthritis (OA) increases with age, the coexistence of other chronic diseases is common. OBJECTIVES: To evaluate the frequency of comorbidities in OA patients and to measure their impact on pain and physical function of those patients. METHODS: Cross-sectional study in OA patients of a public rheumatology clinic. Pain was measured by use of the Visual Analogue Scale (VAS) and physical function by use of the Lequesnes and SACRAH indices. A screening for depression was performed, as were the following measurements: anthropometric data; blood pressure; fasting glycemia; and lipid profile. RESULTS: The study assessed 91 patients (mean age 59.3 years; 91.4% female). The metabolic syndrome frequency was 54.9%. Hypertension occurred in 75.8% of the patients, dyslipidemia in 52.6%, and obesity in 57.1%. The screening for depression was positive in 61.3% of patients. When comparing the metabolic syndrome components individually, patients with hypertension had higher SACRAH scores, with statistically significant differences (P = 0.035). For the other variables, no differences among the Lequesnes, SACRAH and VAS scores were observed. CONCLUSION: This group of OA patients showed a high frequency of depression, metabolic syndrome and its components in isolation, which can impact the pain and physical function of those patients. Such results showed the need for investigating and treating those comorbidities in OA patients.

Níveis séricos de 25-hidroxivitamina D3 e sua associação com parâmetros clínicos e laboratoriais em pacientes com lúpus eritematoso sistêmico

INTRODUCTIONnThe immunoregulatory role of vitamin D has been the object of a growing number of studies in patients with systemic lupus erythematosus (SLE).nnnOBJECTIVESnTo determine the serum levels of 25-hydroxyvitamin D3 [25(OH) D] in patients with SLE, and to assess the association of 25(OH)D insufficiency/deficiency with clinical parameters and laboratory tests.nnnMETHODSnCross-sectional, prospective study performed at the SLE Clinic, Department of Rheumatology, Hospital das Clínicas, Universidade Federal de Pernambuco with convenience sampling, including 78 patients with SLE and 64 volunteers (comparison group), matched by gender and age.nnnRESULTSnInsufficiency/deficiency of 25(OH)D was found in 45 (57.7%) patients with SLE and 25 (39%) individuals in the comparison group. The mean serum levels of 25(OH)D were 29.3 ng/mL (6.1-55.2 ng/mL) in patients with SLE and 33.12 ng/mL (15.9-63.8 ng/mL) in the comparison group, and this difference was statistically significant (P = 0.041). No statistically significant difference was observed between the mean ages of both groups. No statistically significant association was observed between 25(OH)D insufficiency/deficiency and the following: time to diagnosis; disease activity (SLEDAI > 6); fatigue; use of corticosteroids and antimalarials; and anti-DNA.nnnCONCLUSIONSnHigh prevalence of 25(OH)D insufficiency/deficiency was found in patients with SLE (57.7%), with statistically significant difference as compared with the comparison group. No association of vitamin D insufficiency/deficiency was observed with the clinical variables and laboratory tests studied. The authors emphasize the importance of determining 25(OH)D serum levels in all patients with SLE, regardless of where they live and time to disease diagnosis.INTRODUCTION: The immunoregulatory role of vitamin D has been the object of a growing number of studies in patients with systemic lupus erythematosus (SLE). OBJECTIVES: To determine the serum levels of 25-hydroxyvitamin D3 [25(OH) D] in patients with SLE, and to assess the association of 25(OH)D insufficiency/deficiency with clinical parameters and laboratory tests. METHODS: Cross-sectional, prospective study performed at the SLE Clinic, Department of Rheumatology, Hospital das Clinicas, Universidade Federal de Pernambuco with convenience sampling, including 78 patients with SLE and 64 volunteers (comparison group), matched by gender and age. RESULTS: Insufficiency/deficiency of 25(OH)D was found in 45 (57.7%) patients with SLE and 25 (39%) individuals in the comparison group. The mean serum levels of 25(OH)D were 29.3 ng/mL (6.1-55.2 ng/mL) in patients with SLE and 33.12 ng/mL (15.9-63.8 ng/mL) in the comparison group, and this difference was statistically significant (P = 0.041). No statistically significant difference was observed between the mean ages of both groups. No statistically significant association was observed between 25(OH)D insufficiency/deficiency and the following: time to diagnosis; disease activity (SLEDAI > 6); fatigue; use of corticosteroids and antimalarials; and anti-DNA. CONCLUSIONS: High prevalence of 25(OH)D insufficiency/deficiency was found in patients with SLE (57.7%), with statistically significant difference as compared with the comparison group. No association of vitamin D insufficiency/deficiency was observed with the clinical variables and laboratory tests studied. The authors emphasize the importance of determining 25(OH)D serum levels in all patients with SLE, regardless of where they live and time to disease diagnosis

Evaluation of an interferon gamma assay in the diagnosis of latent tuberculosis infection in patients with rheumatoid arthritis.

The tuberculin skin test is not an ideal screening test for the patients with rheumatoid arthritis to identify cases of latent tuberculosis infection (LTBI) prior to the start of treatment with anti-TNFs, as it responds inadequately to late hypersensitivity, which is fundamental for producing a response to the inoculated antigen. Assays based on detection of the production of IFNγ in vitro by mononuclear peripheral cells stimulated by specific antigens are more specific than PPD in detecting LTBI. The aim of this study was to evaluate the performance of T-SPOT.TB in diagnosis of LTBI in patients with rheumatoid arthritis, comparing with the PPD. The specificity of the T-SPOT.TB varied from 87 to 90% and the negative-predictive value (NPV) from 94.4 to 100%. It can be concluded that the T-SPOT.TB showed high specificity and NPV, proving the capability of identifying false-negative cases of PPD, raising the level of safety for the use of anti-TNFs.

The Role of PPAR Gamma in Systemic Sclerosis

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.

Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon?

The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618u2009pg/mL) and in SLE patients (12,26 ± 25,235u2009pg/mL) than in healthy individuals (1,22 ± 0,706u2009pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = −0,1948; u2009p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target.

Resposta atenuada ao PPD no diagnóstico de infecção tuberculosa latente em pacientes com artrite reumatoide

INTRODUCTION: With the introduction of Tumor Necrosis Factor Inhibitors (anti-TNFs) into rheumatological practice, it has become obligatory to identify cases of latent tuberculosis infection (LTBI) prior to the start of treatment, using PPD, chest radiography and clinical history of tuberculosis contact. Patients with Rheumatoid Arthritis (RA) have an abnormality of the cellular immune function, characterized by decreasing responsiveness of peripheral mononuclear cells (T Reg lymphocytes), leading to a loss in delayed hypersensitivity, which is fundamental for the recognition of antigens, such as PPD. OBJECTIVES: The purpose of our study was to evaluate the response to PPD in patients with RA, compared with healthy people, in an area where tuberculosis is endemic, as is the state of Pernambuco. METHODOLOGY: We studied 96 patients, 48 with RA and 48 healthy subjects, most of them females. All patients were given an interdermic injection of 0.1 mL PPD RT-23. The reading of the PPD result was carried out 72 hours after application, by way of palpation of maximum transverse diameter of induration, and the result was expressed in millimeters. RESULTS:In the RA group, the average time of diagnosis was 10.2 years, the average dosage of methotrexate was 15.5 mg / week, the average dosage of prednisone 12.7 mg / day and the average activity of the disease, measured using CDAI, was 30.4. In the healthy subjects group there was a greater number of positive PPD results (33.3%) when compared with the results for the RA group (14.6%), with a statistically significant difference (p = 0.034). CONCLUSION:The performance of PPB in LTBI diagnosis is poor in patients with RA. These results suggest that more careful screening needs to be undertaken before treatment with an anti-TNF drug.

Peroxisome proliferator-activated receptor agonists (PPARs): a promising prospect in the treatment of psoriasis and psoriatic arthritis

Psoriasis is a polygenic, inflammatory and progressive disease, characterized by an abnormal differentiation and hyperproliferation of keratinocytes, associated with impaired immunologic activation and systemic disorders, while psoriatic arthritis is a chronic inflammatory articular disease. Pathophysiology of psoriasis comprises a dysfunction of the immune system cells with an interactive network between cells and cytokines supporting the initiation and perpetuation of disease and leading to inflammation of skin, enthesis and joints. Recent studies have shown an important role of systemic inflammation in the development of atherosclerosis. Corroborating these findings, patients with severe Psoriasis have marked incidence of psoriatic arthritis, cardiovascular diseases, hypertension, dyslipidemia, obesity and diabetes mellitus, showing an increased risk for acute myocardial infarction, which suggests that the condition is not restricted to the skin. Nuclear receptors are ligand-dependent transcription factors, whose activation affects genes that control vital processes. Among them the peroxisome proliferator-activated receptor is responsible for establishing the relationship between lipids, metabolic diseases and innate immunity. In the skin, peroxisome proliferator-activated receptors have an important effect in keratinocyte homeostasis, suggesting a role in diseases such as psoriasis. The peroxisome proliferator-activated receptors agonists represent a relevant source of research in the treatment of skin conditions, however more clinical studies are needed to define the potential response of these drugs in patients with psoriasis and psoriatic arthritis.

Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement

The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08u2009±u20090.76xa0pg/ml) than in healthy individuals (1.89u2009±u20090.69xa0pg/ml; pu2009<u20090.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75u2009±u20091.36 and 3.08u2009±u20090.70xa0pg/ml, respectively, pu2009=u20090.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc.

Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 - Treatment

Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment.