The influence of lean mass in trabecular and cortical bone in juvenile onset systemic lupus erythematosus

The aim of this study was to evaluate risk factors for low bone mineral density (BMD) and vertebral fractures, in juvenile systemic lupus (JSLE). Thirty-one consecutive patients with JSLE were compared with 31 gender- and age-matched healthy controls. BNID and body composition from all participants were measured using dual-energy X-ray absorptiometry. Vertebral fractures were defined as a reduction of >= 20% of the vertebral height for all patients. Lumbar spine and total femur BMD was significantly decreased in patients compared with controls (P = 0.021 and P = 0.023, respectively). A high frequency of vertebral fractures (22.58%) was found in patients with JSLE. Analysis of body composition revealed lower lean mass (P = 0.033) and higher fat mass percentage (P = 0.003) in patients than in controls. Interestingly, multiple linear regression using BMD as a dependent variable showed a significant association with lean mass in lumbar spine (R(2) = 0.262; P = 0.004) and total femur (R(2) = 0.419, P = 0.0001), whereas no association was observed with menarche age, SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology, and glucocorticoid. This study indicates that low BMD and vertebral fractures are common in JSLE, and the former is associated with low lean mass, suggesting that muscle rehabilitation may be an additional target for bone therapeutic approach.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behcet`s disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjogren`s syndrome, Takayasu`s arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener`s) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p < 0.0001), seroconversion rates (63.4% vs 76.9%, p < 0.001) and the factor increase in GMT (8.9 vs 13.2 p < 0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p < 0.0001), RA (p < 0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p < 0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

Juvenile onset systemic sclerosis (JoSSc) is a rare disease, and there are no studies focusing in bone mineral density and biochemical bone parameters. Ten consecutive patients with JoSSc and 10 controls gender, age, menarche age, and physical activity matched were selected. Clinical data were obtained at the medical visit and chart review. Laboratorial analysis included autoantibodies, 25-hydroxyvitamin D (25OHD), intact parathyroid hormone, calcium, phosphorus, alkaline phosphatase and albumin sera levels. Bone mineral density was analyzed by dual-energy X-ray absorptiometry, and bone mineral apparent density (BMAD) was calculated. A lower BMAD in femoral neck (0.294 +/- A 0.060 vs. 0.395 +/- A 0.048 g/cm(3), P = 0.001) and total femur (0.134 +/- A 0.021 vs. 0.171 +/- A 0.022 g/cm(3), P = 0.002) was observed in JoSSc compared to controls. Likewise, a trend to lower BMAD in lumbar spine (0.117 +/- A 0.013 vs. 0.119 +/- A 0.012 g/cm(3), P = 0.06) was also found in these patients. Serum levels of 25OHD were significantly lower in JoSSc compared to controls (18.1 +/- A 6.4 vs. 25.1 +/- A 6.6 ng/mL, P = 0.04), and all patients had vitamin D insufficiency (< 20 ng/mL) compared to 40% of controls (P = 0.01). All other biochemical parameters were within normal range and alike in both groups. BMAD in femoral neck and total femur was correlated with 25OHD levels in JoSSc (r = 0.82, P = 0.004; r = 0.707, P = 0.02; respectively). We have identified a remarkable high prevalence of 25OHD insufficiency in JoSSc. Its correlation with hip BMAD suggests a causal effect and reinforces the need to incorporate this hormone evaluation in this disease management.

A single dose of zoledronic acid reverses the deleterious effects of glucocorticoids on titanium implant osseointegration

This study evaluates the effect of zoledronic acid (ZOL) on the osseointegration of titanium implants in rabbits with glucocorticoid (GC)-induced bone loss, and our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of GCs on the osseointegration of titanium implants. The purpose of this study is to evaluate the effect of ZOL on the osseointegration of titanium implants in rabbits with GC-induced bone loss. Three groups of six NZW rabbits were treated for 18 weeks with saline (SALINE), GC (methylprednisolone, 0.35 mg/kg three times a week), or GC + ZOL (methylprednisolone + single dose of ZOL, 0.1 mg/kg). The animals received a titanium implant in the left tibia after 6 weeks and were killed at the 18th week. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at baseline, eighth week (W8), and 18th week (W18) after treatment to determine the change upon treatment (a dagger BMD). Histomorphometric and serum bone alkaline phosphatase analysis (BAP) were also performed. At W8, GC group had a significant reduction in lumbar spine and tibia BMD compared with SALINE (p = 0.003 and p = 0.000), as also observed for GC + ZOL group (p = 0.014 and p = 0.003) just 2 weeks after ZOL treatment. In contrast, at W18, the GC + ZOL had an evident BMD rescue with similar lumbar spine and tibia a dagger BMD compared with SALINE (0.043 +/- 0.006 vs. 0.055 +/- 0.009 g/cm(2), p = 0.457 and 0.027 +/- 0.003 vs. 0.041 +/- 0.011 g/cm(2), p = 0.232) and a significantly higher a dagger BMD compared with the GC (p = 0.024 and p = 0.001). Histomorphometry revealed that osseointegration was significantly reduced in GC (tibia cortical thickness and diameter, bone-implant contact, total and peri-implant bone area) whereas GC + ZOL had these parameters similar to SALINE (p > 0.05). Likewise, ZOL reversed the BAP alteration induced by GC. Our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of glucocorticoids on the osseointegration of titanium implants, suggesting that ZOL therapy may improve the outcome of bone implants in patients with glucocorticoid-induced osteoporosis.

Anti-inflammatory effect of bee venom on antigen-induced arthritis in rabbits: Influence of endogenous glucocorticoids

Aim of the study: This study assessed the involvement of endogenous glucocorticoids (GCs) in the anti-arthritic properties of bee venom (BV) on antigen-induced arthritis (AIA) in rabbits. Materials and methods: BV (1.5-6 mu g/kg/day) was injected for 7 days before AIA induction, whereas the control group received sterile saline. The total and differential leukocyte count. PGE(2) levels in synovial fluid and synovial membrane cell infiltrate were evaluated. The contribution of GCs to BV action was assessed in rabbits treated with BV plus metyrapone, an inhibitor of GC synthesis, or RU-38 486, a steroid antagonist. Results: Treatment with BV (1.5 mu g/kg/day) reduced the leukocyte count and PGE2 level (18571 +/- 1909 cells/mm(3) and 0.49 +/- 0.05 ng/mL, respectively) as well as the cellular infiltrate compared with the control group (40968 +/- 5248 cells/mm(3) and 2.92 +/- 0.68 ng/mL, p < 0.05). The addition of metyrapone to BV treatment completely reversed the inhibition of AIA, whereas RU-38 486 was ineffective. Conclusion: Our data show that bee venom treatment prevents the development of antigen-induced arthritis in rabbits through the action of GCs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Low-Level Laser Therapy in Chronic Autoimmune Thyroiditis: A Pilot Study

Background and Objectives: Chronic autoimmune thyroiditis (CAT) remains the most common cause of acquired hypothyroidism There is currently no therapy that is capable of regenerating CAT-damaged thyroid tissue The objective of this study was to gauge the value of applying low-level laser therapy (LLLT) in CAT patients based on both ultrasound studies (USs) and evaluations of thyroid function and thyroid autoantibodies. Study Design/Materials and Methods: Fifteen patients who had hypothyroidism caused by CAT and were undergoing levothyroxine (LT4) treatment were selected to participate in the study Patients received 10 applications of LLLT (830 nm, output power 50 mW) in continuous mode, twice a week, using either the punctual technique (8 patients) or the sweep technique (7 patients), with fluence in the range of 38-108 J/cm(2) USs were performed prior to and 30 days after LLLT USs included a quantitative analysis of echogenicity through a gray-scale computerized histogram index (El). Following the second ultrasound (30 days after LLLT), LT4 was discontinued in all patients and, if required, reintroduced Truodothyronine, thyroxine (T4), free T4, thyrotropin, thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies levels were assessed before LLLT and then 1, 2, 3, 6, and 9 months after LT4 withdrawal. Results: We noted all patients` reduced LT4 dosage needs, including 7 (47%) who did not require any LT4 through the 9-month follow-up The LT4 dosage used pre-LLLT (96 +/- 22 mu g/day) decreased in the 9th month of follow-up (38 23 mu g/day; P<0.0001) TPOAb levels also decreased (pre-LLLT = 982 +/- 530 U/ml, post-LLLT = 579 454 U/ml, P = 0 016) TgAb levels were not reduced, though we did observe a post-LLLT increase in the EI (pre-LLLT = 0 99 +/- 0.09, post-LLLT= 1.21 +/- 0.19, P=0.001) Conclusion: The preliminary results indicate that LLLT promotes the improvement of thyroid function, as patients experienced a decreased need for LT4, a reduction in TPOAb levels, and an increase in parenchymal echogenicity Lasers Surg. Med. 42:589-596, 2010. (C) 2010 Wiley-Liss, Inc

Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area

Tuberculosis has emerged as a major concern in patients with immuno-mediated diseases, including psoriasis, undergoing treatment with biologicals. However, it is not known whether the chronically activated immune system of psoriasis patients interferes with their Mycobacterium tuberculosis (Mtb)-specific immunity, especially in tuberculosis-endemic areas like Brazil. We evaluated T-cell responses to a Mtb lysate and to the recombinant Mtb proteins ESAT-6 and Ag85B of tuberculin skin test (TST) positive and TST negative patients with severe or mild/moderate, untreated psoriasis in three different assays: lymphocyte proliferation, enzyme immunoassay for interferon (IFN)-gamma and interleukin (IL)-10 production by peripheral blood mononuclear cells and overnight enzyme immunospot (ELISpot) for enumerating IFN-gamma-secreting cells. In our cohort, a low proportion (29%) of the severe psoriasis patients tested were TST-positive. IFN-gamma and IL-10 secretion and T-cell proliferation to Mtb antigens were reduced in TST-negative but not in TST-positive patients with severe psoriasis when compared to healthy controls with the same TST status. Similarly, severe psoriasis patients had decreased cytokine secretion and proliferative response to phytohemagglutinin. However, most psoriasis patients and healthy controls showed detectable numbers of IFN-gamma-secreting effector-memory T-cells in response to Mtb antigens by ELISpot. TST-negative, mild/moderate psoriasis patients had responses that were mostly intermediary between TST-negative controls and severe psoriasis patients. Thus, patients with severe psoriasis possess decreased anti-Mtb central memory T-cell responses, which may lead to false-negative results in the diagnosis of TB infection, but retain T-cell memory-effector activity against Mtb antigens. We hypothesize that the latter may confer some protection against tuberculosis reactivation.

Physical function interfering with pain and symptoms in fibromyalgia patients

Objectives. The aim of this study was to assess the relationship between variables of physical assessment - muscular strength, flexibility and dynamic balance - with pain, pain threshold, and fibromyalgia symptoms (FM). Methods. Our sample consists of 55 women, with age ranging from 30 to 55 years (mean of 46.5, (standard deviation, SD=6.6)), mean body mass index (BMI) of 28.7(3.8) and diagnosed for FM according to the American College of Rheumatology criteria. Pain intensity was measured using a visual analogue scale (VAS) and pain threshold (PT) using Fisher`s dolorimeter. FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ); flexibility by the third finger to floor test (3FF); the muscular strength index (MSI) by the maximum volunteer isometric contraction at flexion and extension of right knee and elbow using a force transducer, dynamic balance by the time to get up and go (TUG) test and the functional reach test (FRT). Data were analysed using Pearson`s correlation, as well as simple and multivariate regression tests, with significance level of 5%. Results. PT and FIQ were weakly but significantly correlated with the TUG, MSI and 3FF as well as VAS with the TUG and MSI (p<0.05). VAS, PT and FIQ was not correlated with FRT. Simple regression suggests that, alone, TUG, FR, MSI and 3FF are low predictors of VAS, PT and FIQ. For the VAS, the best predictive model includes TUG and MSI, explaining 12.6% of pain. variability. For TP and total symptoms, as obtained by the FIQ, most predictive model includes 3FF and MSI, which respectively respond by 30% and 21% of the variability. Conclusion. Muscular strength, flexibility and balance are associated with pain, pain threshold, and symptoms in FM patients.

Therapeutic potential of interleukin-6 antagonism in bipolar disorder

Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder. Its underlying neurobiology remains largely unclear. A significant body of evidence indicates that inflammatory activation expressed by increased cytokines is relevant in its pathophysiology. IL-6 is one of the most important cytokines involved in the pathogenesis of immune and inflammatory disorders. Several studies recently showed increased levels of IL-6 in manic and depressive episodes and also during euthymia in subjects with BD. Tocilizumab is an IL-6 receptor antagonist being marketed for the treatment of rheumatoid arthritis and Castleman`s disease. In this article we discuss the possibility that tocilizumab may have a therapeutic role in treatment of BD through its anti-inflammatory action. (C) 2010 Elsevier Ltd. All rights reserved.

Chronic polyarthritis as the first manifestation of juvenile systemic lupus erythematosus patients

Objective: To evaluate the prevalence of chronic polyarthritis in juvenile systemic lupus erythematosus (JSLE) and to describe the manifestations, treatments, and outcomes in these patients. Methods: From January 1983 to July 2010, 5419 patients were followed up at the Pediatric Rheumatology Unit of the University Hospital and 271 (5%) of them had JSLE (American College of Rheumatology [ACR] criteria). `Rhupus` was classified as the overlap of juvenile idiopathic arthritis (International League of Associations for Rheumatology [ILAR] criteria) and JSLE. We evaluated demographic data, polyarthritis and other clinical manifestations, disease activity and damage, laboratory exams, radiographic findings, treatments, and outcomes. Results: The prevalence of chronic polyarthritis in this JSLE population was 2.6% (7/271). This articular involvement was the initial manifestation in all seven JSLE patients. The median duration of chronic polyarthritis was 11 months (range 2-15 months). Interestingly, rhupus with chronic polyarthritis and limitation of movement, presence of rheumatoid factor, autoantibodies, and/or radiographic abnormalities (juxtaarticular osteopenia, joint-space narrowing, or erosions) was evidenced in three patients. No patient had deformities of hands and feet associated with Jaccoud`s arthropathy or osteonecrosis. All patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs, naproxen 10-15 mg/kg/day) when polyarthritis diagnosis was established. Prednisone and antimalarials were administered at JSLE diagnosis. The three non-responsive rhupus patients were treated in conjunction with immunosuppressive drugs (methotrexate, azathioprine, and/or cyclosporine). Conclusions: Chronic polyarthritis was a rare lupus manifestation in active pediatric patients. The interesting overlap between chronic arthritis and lupus, called rhupus suggests a new entity with a different clinical profile and a poor response to treatment with NSAIDs alone. In addition, the occurrence of this association in JSLE patients could be classified as a clinical sub-group of JSLE with possible specific genetic determinants. Lupus (2011) 20, 960-964.

Pathogenic role of anti-endothelial cell antibodies in autoimmune rheumatic diseases

Anti-endothelial cells antibodies have been detected in numerous autoimmune and inflammatory diseases, including systemic lupus erythematous, rheumatoid arthritis, vasculitis and sarcoidosis. Anti-endothelial cells antibodies bind to endothelial cell antigens and induce endothelial damage. Their effects on the endothelial cell have been considered responsible, at least in part, by the vascular injury which occurs in these pathological conditions. Lupus (2009) 18, 1233-1238.

Anti-Ro antibody and cutaneous vasculitis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with various clinical and serological manifestations. Previous studies have shown the association of SLE and anti-Ro antibody with a series of clinical manifestations. We investigated this association in Brazilian patients with SLE. Five hundred and nine consecutive patients who fulfilled the revised American College of Rheumatology criteria for the SLE were enrolled in the study from June to December 2007. All patients were from our Service of Rheumatology, School of Medicine, University of Sao Paulo, Brazil. Frequencies of a series of laboratorial and clinical manifestations were calculated. Anti-Ro antibody was associated to anti-La antibody, female, and cutaneous vasculitis. In multivariate analysis, patients with anti-Ro antibody has 1.63 (95% CI 1.07-2.50) more risk to develop cutaneous vasculitis than patients without this antibody. Our data have demonstrated that anti-Ro antibody is an independent useful serologic marker for cutaneous vasculitis.

Mannose binding lectin gene (MBL2) functional polymorphisms are associated with systemic lupus erythematosus in southern Brazilians

Susceptibility to systemic lupus erythematosus (SLE) has been associated with immunologic, environmental, and genetic factors. To uncover a possible association between MBL2 gene polymorphisms and SLE, we analyzed functional polymorphisms in the promoter and first exon of the MBL2 gene in 134 Brazilian SLE patients and 101 healthy controls. Genotype and allele frequencies of MBL2 A/O polymorphism were significantly different between patients and controls, and the 0 allele was associated with an increased risk of SLE. An association between low mannose binding lectin (MBL) producer combined genotypes and increased risk for SLE was also reported. Furthermore, when stratifying SLE patients according to clinical and laboratory data, an association between the A/O genotype and nephritic disorders and between the X/Y genotype and antiphospholipid syndrome was evident. Combined genotypes responsible for low MBL production were more frequently observed in SLE patients with nephritis. Our results indicate MBL2 polymorphisms as possible risk factors for SLE development and disease-related clinical manifestations. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Frequency of HLA-B27 alleles in Brazilian patients with psoriatic arthritis

This prospective study analyzed the frequency of HLA-B27 and its alleles in 102 Brazilian patients with psoriatic arthritis (PsA). The association of the HLA-B27 alleles with these variants was compared to a control healthy HLA-B27 positive group of 111 individuals. There was a predominance of male gender (59.8%), Caucasian race (89.2%), and negative HLA-B27 (79.4%) patients. Asymmetric oligoarthritis (62.7%) was the most frequently observed clinical PsA subgroup, followed by spondylitis (16.7%), and polyarthritis (15.7%). Male gender and the spondylitis subgroup were statistically associated to the positive HLA-B27, and the oligoarthritis subgroup was associated to the negative HLA-B27. Among the 21 HLA-B27-positive PsA patients, there was a significant prevalence of the HLA-B*2705 allele (90.5%), similar to that observed in the control group (80.2%); HLA-B*2703 and HLA-B*2707 were statistically associated to the control group.