Abstract  It is well established that there are people with higher risk of developing acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Mediterranean fever (MEFV) gene mutations might be one of the genetic predisposition factors in the development of ARF/RHD since defect in familial Mediterranean fever (FMF) patients is proposed to be heightened inflammatory response to certain stimuli. Previous clinical observations suggested a relationship between FMF and ARF/RHD. The aim of this study was to investigate the role of the MEFV gene mutations in the susceptibility to RHD in Turkish patients. A total of 100 patients with RHD and 100 healthy controls were included in the study. Diagnosis of RHD was based on echocardiographic findings in which a predominant mitral stenosis was used as an inclusion criterion. Genetic analysis was carried out by sequence analysis investigating two hot spots (exons 2 and 10) for MEFV mutations. Mutation analysis showed that 22 RHD patients (22%) and 24 healthy controls (24%) carried at least one mutated allele. MEFV mutations were identified in 22 of 200 (11%) chromosomes in RHD patients while 26 of the 200 (13%) chromosomes of healthy controls were found to carry a mutated allele. No difference was found in allele frequencies and their distribution between the patients and healthy controls (p?=?0.54). MEFV mutations are not associated with a predisposition to develop RHD in adult Turkish patients.

Abstract  In rheumatic patients candidate to anti-TNF-? treatment, there is an increased risk of developing tuberculosis (TB). The tuberculin skin test (TST), the standard diagnostic test for latent tuberculosis infection (LTBI), suffers low specificity and sensitivity. Here, we compared the performance characteristics of an in-house ELISPOT-IFN-? assay (using a restricted pool of Mycobacterium tuberculosis-specific peptides or MTP) to TST for the diagnosis of LTBI in 69 rheumatic patients candidate to anti-TNF-? treatment and in 60 healthy LTBI individuals. Among the 69 patients enrolled, 17 (25%) had a positive TST response and 15 (22%) a positive ELISPOT-MTP response. Among the patients with a positive TST result, eight had a positive and nine a negative ELISPOT-MTP response, whereas among the 49 patients with a negative TST result, 42 were ELISPOT-MTP negative, but seven (14%) were ELISPOT-MTP positive, with three indeterminate results. The agreement between the two tests was poor (k?=?0.341, 95% CI?=?0.060 to 0.622) and the test of symmetry was not significant (P?=?0.8). Considering the ELISPOT assay, rheumatic patients had a reduced number of spot-forming cells after stimulation of lymphocytes with PHA or PPD when compared with healthy LTBI individuals. Thus, the ELISPOT-IFN-? assay performs better than the TST in recognizing patients with LTBI, on one hand reducing the number of patients submitted to isoniazid prophylaxis, and on the other hand, since the assay is less biased by immunosuppressive regimens than TST, recognizing LTBI patients among those with a negative TST response.

Abstract  The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated with tumor necrosis factor-alpha (TNF?) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n?=?32, and psoriatic arthritis, n?=?17) initiating TNF? inhibitor therapy (infliximab, n?=?38; etanercept, n?=?8; and adalimumab, n?=?3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6?12 weeks for up to 3 years. Patients with co-morbidities (n?=?4), missing baseline samples (n?=?3), and adverse events (n?=?5) were excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98?64) vs. 1.3 (0.33?26)), VEGF (105 ng/l (22?752) vs. 45 (12?351)), YKL-40 (74 ?g/l (14?572) vs. 43 (20?184)), and MMP-3 (43 ?g/l (9.1?401) vs. 16 (2.5?47), p???0.001), whereas total aggrecan was lower (662 ?g/l (223?2,219) vs. 816 (399?2,190),p???0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p???0.03) in clinical responders (n?=?24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p???0.02) in non-responders (n?=?13). The study demonstrated changes of plasma IL-6, VEGF, YKL-40, MMP-3, and total aggrecan and a potential value for monitoring disease activity and treatment response in SpA patients. Larger prospective studies are required to clarify clinical utility of these biomarkers.

Abstract  Osteoporosis is a generalized disease of bone that increases fracture risk. Multiple factors influence this risk, besides low bone mass. To decrease osteoporotic fractures, those patients who require preventive management should be readily identified. This paper aims to review current information on the use of the fracture risk assessment tool (FRAX?) in Latin America. Bone mineral density measurement is currently the method of reference for evaluating the fracture risk and opting for treatment; but, it misses a notable proportion of individuals who have clinical risk factors for osteoporosis and fractures. FRAX? was designed to predict the 10-year absolute risk of sustaining a major osteoporotic fracture or a hip fracture. Although data is available for several countries, from Latin America, only Argentina appears in the current version of the tool. Its present use in other Latin American countries is possible with some adaptations based in similarities of epidemiological information of each country with some of the existing databases. The cutoff value beyond which treatment should be initiated needs to be determined, based not only on clinical criteria, but also on economic considerations.

Abstract  We aimed to investigate the effect of regular supervised exercise program on functinal status, disease activity, and total antioxidant status (TAS) level in patients with ankylosing spondylitis (AS). Thirty-two patients (mean age: 44 years) with AS were included in the study and divided into two groups. Group 1, the exercise group (n?=?16), attended a supervised exercise program that consisted of aerobic, strengthening, and stretching exercises for 1 h a day, five times a week for 3 weeks. Group 2, the control group, received a home exercise program (n:16). Bath AS Activity Index (BASDAI) and Bath AS Functional Index (BASFI) were calculated and serum TAS levels were measured for each patient at 0 and 3 weeks. There was no significant difference in patients' baseline characteristics (age, disease duration, BASFI, and BASDAI scores) between exercise and control groups. In the exercise group, there were significant improvements between pre-exercise and post-exercise assessments in BASFI (2.8?±?1,8; 1.7?±?1,40, p?=?0.004) and BASDAI scores (2.1?±?1.7; 1.2?±?1.3, p?=?0.01). Mean TAS levels were significantly decreased after supervised exercise program (1.48?±?0.16 mmol/L; 1.36?±?0.20 mmol/L, p?=?0.03). In the control group, BASFI score (2.4?±?1.7; 2.9?±?2.1, p?=?0.19), BASDAI score (2.6?±?2.2; 3.1?±?2.6, p?=?0.33), and mean TAS levels (1.38?±?0.23 mmol/L; 1.39?±?0.20 mmol/L, p?=?0.66) did not differ significantly between 0 and 3 weeks. Short-term, supervised exercise program improved functional status and decreased disease activity. However, the mechanism of this beneficial clinical effect does not seem to be through antioxidant activity.

The role of IL-23/IL-17 axis in the etiopathogenesis of Behçet's disease

Abstract  Churg?Strauss syndrome (CSS) is a rare, systemic, necrotizing, small- and middle-sized vessel vasculitis which is accompanied by blood eosinophilia, eosinophil infiltration of various tissues, and bronchial asthma. The lungs are the organs most often involved in CSS. The aim of this study was a retrospective evaluation of the pulmonary findings in chest X-rays and high resolution computed tomography (HRCT) in CSS patients at the time of initial diagnosis and to determine their frequency, character, and location. Seventeen CSS patients were studied (12 women; 5 men; aged 29?56 years). In all patients at the time of initial diagnosis, chest X-rays were performed, and in 15 patients, HRCT was performed additionally. The radiological images were evaluated independently by two radiologists who reached a decision by consensus. Out of 17 patients studied, chest X-rays revealed parenchymal abnormalities in 11, pleural effusion in three, and bronchial wall thickening in one. In five patients, no abnormalities in chest X-rays were found. In HRCT, abnormalities were found in all patients (15 patients, 100%). Predominant HRCT findings consisted of: ground-glass opacities and consolidations found in 13 patients (86.7%). Additionally, in four patients, pulmonary micronodules were described; in ten, interlobular septal thickening; in three, linear opacities; in ten, bronchial wall thickening and/or bronchial dilatation; and in three, pleural effusions. Ground-glass opacities and consolidation abnormalities distribution pattern were peripheral in seven and random in six patients. In patients with CSS, the most common pulmonary radiological findings are parenchymal opacities, which may be peripheral or random in distribution. Pathologic changes were found in 70.6% of patient in chest X-rays, and in 100%, when HRCT was performed. These changes are nonspecific; however, they should be not overlooked, as they may help in establishing the diagnosis and suggest the prognosis.

Abstract  Compare the medium-term effectiveness and tolerance between joint lavage (JL) in combination with triamcinolone hexacetonide (TH) intra-articular injection (IAI) and IAI with TH alone for treatment of primary osteoarthritis (OA) of the knee. A randomized, double-blind, controlled study was carried out on 60 patients with primary OA of the knee, randomized into two intervention groups: JL/TH group, joint lavage in combination with TH intra-articular injection and TH group, TH intra-articular injection. Patients were followed for 12 weeks by a blind observer using the following outcome measurements: visual analogue scale for pain at rest and in movement, goniometry, WOMAC, Lequesne?s index, timed 50-ft walk, perception of improvement, Likert scale for improvement assessment, use of nonsteroidal anti-inflammatory drugs and analgesics, and local side effects. There were no statistical differences in the inter-group analysis for any of the variables studied over the 12-week period. Although both groups demonstrated statistical improvement in the intra-group evaluation (except for Likert scale according to patient and the use of anti-inflammatory drugs). In the Kellgren?Lawrence scale (KL) 2 and 3 sub-analysis, there was a statistical difference regarding joint flexion among patients classified as KL 2, favoring the TH group (p?=?0.03). For the KL 3 patients, there were statistical differences favoring the JL/TH group regarding Lequesne (p?=?0.021), WOMAC pain score (p?=?0.01), and Likert scale according to the patient (p?=?0.028) and the physician (p?=?0.034). The combination of joint lavage and IAI with TH was not more effective than IAI with TH alone in the treatment of primary OA of the knee. However, KL 3 patients may receive a major benefit from this combination.

Abstract  Adequate knowledge and clinical competency are essential for sound rheumatology practice. The aim of this study was the assessment of the adequacy of rheumatology education at the primary care level. Two hundred and ninety-seven primary care physicians participated in this cross-sectional survey. Participants were asked to complete a question survey and to take a previously validated rheumatology examination. The participants rated rheumatology education as important but rated the time spent on rheumatology education as poor. More than 80% of the participants reported a low level of confidence in performing a musculoskeletal physical examination. Of the participants, 75% scored 65% or less in the validated rheumatology examination. The findings of the present study indicate that medical education in rheumatology is inadequate at both the basic and clinical levels. The competence level of graduating physicians in musculoskeletal problem solving is inadequate. Furthermore, the time devoted to rheumatology education and training is disproportionately low compared to the frequency of musculoskeletal complaints encountered in general practice.

Abstract  Takayasu?s arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. The clinical features of TA vary in different ethnic populations. The objective of this study is to characterize the clinical features, angiographic findings, and response to treatment of patients with TA in Changhai Hospital, Shanghai, China. The hospital records of 125 patients diagnosed with TA were retrospectively evaluated. Eighty patients were followed for a median duration of 36 months. Females (86.4%) were most frequently affected. The mean age at onset was 26.9 years. Constitutional symptoms were present in only 38.4% of patients. The most common clinical finding was pulse deficit. Histological findings from 12 clinically inactive patients showed active lesions in 58.3%. Angiographic classification showed that type I was the most common, followed by type V and IV. Type I was more common in adult patients than in pediatric patients. Although immunosuppressive treatment induced remission in most patients, over 90% of those who achieved later remission relapsed. Both bypass procedures and angioplasty showed high rates of initial success, but restenosis occurred in 34.7% of bypass procedures and 77.3% of angioplasty procedures. Eight patients died during the follow-up period with the main cause of death being congestive heart failure. Constitutional symptoms were not frequent in our study. Correlation between the clinical assessment of disease activity and histologic findings is often poor in TA. Angiographic findings showed that type I was the most common in our study. Over the longer term, the outcomes of revascularization were superior to angioplasty.

Abstract  To clarify the optimal management of rehabilitative intervention for limited glenohumeral joint mobility (LGHM) arising from adhesive capsulitis, particularly focusing on the frequency of sessions for joint mobilization and the self-exercise compliance, the functional results of 120 patients with LGHM were prospectively investigated as follows: Differences in improved angle of the shoulder joint (IA) and the time required to reach the range of motion plateau point (T) were compared by (1) age, (2) gender, (3) handedness, (4) duration before rehabilitative intervention, (5) frequency of sessions for joint mobilization by physical therapists in the hospital setting, and (6) self-exercise compliance in the home setting. The lengths of therapy and follow-up were 4.6 and 5.9 months, respectively. IA significantly decreased in the 71-year-old and above group. There were no significant differences in IA between male and female. IA of the dominant-handed group was significantly higher than that of the non-dominant-handed group. There were no significant differences in T in each item. IA of the group that had experienced more than 7 months of the condition was significantly low. Although the frequency of joint mobilization by physical therapists in the hospital setting showed no relationship with IA or T, IA was significantly higher and T was significantly shorter in the group that performed self-exercise every day than in the groups that performed less. In conclusion, early intervention and self-exercise in the home setting are more important factors than session frequency of joint mobilization in the hospital setting for the successful management of rehabilitation for LGHM.

Abstract  Circulating autoantibodies against neutrophils (ANCA) are a distinctive finding in patients with Wegener?s granulomatosis (WG). B-lymphocyte activating factor (BAFF) promotes autoantibody production by increasing B cell survival and proliferation. We investigated serum BAFF levels (s-BAFF) in a WG patient cohort in relation to ANCA titers and disease activity. Baseline data were obtained in twenty-two WG patients (55% female, age 44 years, disease duration 1 year). S-BAFF was determined by capture ELISA and associations between s-BAFF, clinical (Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI) and Disease Extent Index (DEI)) and biochemical (C-reactive protein (CRP), IgG and ANCA) disease measures were analysed in a cross sectional as well as longitudinal analysis. S-BAFF was increased in WG patients compared to healthy controls (1.8 vs. 0.55 ng/ml, p?<?0.01). S-BAFF was higher in ANCA negative than ANCA-positive WG sera (2.16 vs. 1.29 ng/ml, p?<?0.01), correlated independently and inversely with ANCA levels (Rs ?0.48, p?<?0.01) but did not correlate with CRP, BVAS, DEI or VDI scores. Individual s-BAFF profiles were stable over time in 68% of patients. The finding of a negative correlation between ANCA levels and s-BAFF that is independent of steroid treatment indicates that BAFF does not directly drive ANCA production in WG.

Abstract  A 68-year-old woman developed tenosynovitis of the right second digit without a history of injury or animal bites. Apart from high titer anti-nuclear antibodies, serological studies were unremarkable. Tuberculin test and interferon gamma release assay were both negative. Several immunosuppressive therapies led only to partial relief of symptoms. Of note, clinical symptoms worsened significantly after introduction of adalimumab therapy. Tenosynovectomy was performed revealing a granulomatous inflammatory process. Seven weeks later, Mycobacterium malmoense could be cultured from the surgical specimen. A four drug antibiotic regimen was started and immunosuppressive therapy discontinued resulting in complete clinical remission. Our case highlights non-tuberculous mycobacterial (NTM) tenosynovitis as an important differential diagnosis of atypical arthritis. A negative tuberculin skin test as well as negative Ziehl?Neelsen stain does not argue against NTM infection. In fact, mycobacterial culture for extended periods remains the gold standard for diagnosis.

Abstract  QUALEFFO-31 is a recently developed disease-specific instrument derived from QUALEFFO-41 and intended to have improved efficacy and response rates. We aimed to validate QUALEFFO-31 in Chinese and examine the use of QUALEFFO-31 in clinical practice. This questionnaire was translated into Chinese and applied to 118 case?control pairs aged between 50 and 85 years with prevalent osteoporotic vertebral fractures to evaluate its validity, repeatability, and discriminatory ability. It was also used to evaluate the quality of life (QOL) of 69 case?control trios with prevalent clinical and morphometric fractures. The QOL of all subjects was concurrently assessed using SF-36 for comparison. QUALEFFO-31 had good internal consistency with adequate convergent and discriminatory validity. The median test?retest repeatability ranged from 0.65?0.85. In general, there were good correlations between QUALEFFO-31 and SF-36. ROC curve analysis revealed that QUALEFFO-31 had significant ability to discriminate between clinical fracture subjects versus morphometric fracture subjects and controls. QUALEFFO-31 also demonstrated higher discriminatory capacity for pain. Subjects with clinical vertebral fractures (CVFs) had a significant reduction in QOL compared with other subjects. The QUALEFFO-31 is a useful tool for assessing QOL in Chinese. It was well accepted and significantly predictive of subjects with CVFs.