The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = −0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = −0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex.     

Sonographically guided hydrodissection and corticosteroid injection for scleroderma hand

Scleroderma is associated with intractable hand pain from vasospasm, digital ischemia, tenosynovitis, and nerve entrapment. This study investigated the effect of hydrodissection of the carpal tunnel followed by corticosteroid injection for the painful scleroderma hand. Twenty-six consecutive subjects [12 with painful scleroderma hand and 14 with rheumatoid arthritis and carpal tunnel syndrome (RA/CTS)] underwent sonographically observed carpal tunnel hydrodissection with 3 ml of 1% lidocaine administered with a 25-gauge 1-in. needle on a 3-ml RPD mechanical syringe (reciprocating procedure device). After hydrodissection, a syringe exchange was performed, and 80 mg of triamcinolone acetonide was injected. Baseline pain, procedural pain, pain at outcome, responders, therapeutic duration, and reinjection interval were determined. Hydrodissection and injection with corticosteroid significantly reduced pain scores by 67% in scleroderma (p < 0.001) and by 47% in RA/CT (p < 0.001). Scleroderma and RA/CTS were similar in outcome measures: injection pain (p = 0.47), pain scores at outcome (p = 0.13), responders (scleroderma, 83.3%; RA/CTS, 57.1%, p = 0.15), pain at 6 months (p = 0.15), and therapeutic duration (p = 0.07). Scleroderma patients responded better in time to next injection (scleroderma, 8.5 ± 3.0 months; RA/CTS, 5.2 ± 3.1 months, p = 0.03). Reduced Raynaud’s attacks and healing of digital ulcers occurred in 83% of subjects. There were no complications. Hydrodissection with lidocaine followed by injection of triamcinolone reduces pain and vasomotor changes in the scleroderma hand. The mechanism may be a combination of hydrodissection-mediated mechanical freeing of entrapped arteries, nerves, and tendinous structures and corticosteroid-induced reduction of inflammatory vasospasm.     

Differences between the United States and the United Kingdom in the treatment of rheumatoid arthritis: analyses from a hand arthroplasty trial

Previous studies have found differences in rheumatoid hand surgical practice around the world. The specific aim of this study is to compare baseline characteristics of rheumatoid arthritis (RA) patients in the United States (US) and the United Kingdom (UK) that may be influenced by the two different health-care systems. Patients were recruited from three sites (two in the US and one in England) as part of a National Institutes of Health funded study to examine outcomes of silicone metacarpophalangeal joint (MCPJ) arthroplasty in RA patients. Outcomes measurements included biomechanical assessments (grip strength, pinch strength, and mean ulnar drift and extensor lag at the MCPJs of all four fingers), a health-related quality of life questionnaire (the Michigan Hand Outcomes Questionnaire), and a medication assessment. American patients have a significantly higher income level (p < 0.001) and have completed higher levels of education (p < 0.001) than British patients. There were no significant differences in terms of self-reported disease severity or deformity at the MCPJs. RA patients in the US are more likely to take biologic medications (p < 0.001), steroids (p = 0.02), and Cox-2 inhibitors (p = 0.02). Patients in the UK are significantly more likely (p < 0.001) to take nonsteroidal anti-inflammatory drugs. There are differences in the demographic characteristics and medication use of RA patients with hand deformities in the US and UK. These differences may be influenced by the private versus socialized health-care systems. However, the perception of hand disease severity in participants in this study appears to be comparable between these countries.     

Soluble receptor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid arthritis - relationship with bone mineral density,disease activity and bone turnover

The aim of our study was to investigate determinants of bone mineral density (BMD) measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN) in patients with rheumatoid arthritis (RA) with special respect to bone resorbing proinflammatory cytokines and their physiological antagonists. In 142 RA patients the following parameters were measured in parallel with BMD: serum levels of soluble receptor activator of nuclear factor kappa-B-ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-6, soluble glycoprotein 130 (sgp130), 25-hydroxyvitamin D3 (25OHD₃), 1,25-dihydroxyvitamin D3 (1,25[OH]₂D₃), intact parathyroid hormone, osteocalcin, ionized calcium, renal excretion of pyridinolin and deoxypyridinolin, C-reactive protein, and erythrocyte sedimentation rate (ESR). No significant differences of sRANKL, OPG, IL-6, and spg130 were found between patients with osteoporosis (47.9% of patients), osteopenia (36.6%), and normal BMD (15.5%). However, total sRANKL was significantly higher in postmenopausal women with osteoporosis at FN than in those without (p < 0.05) and showed a negative correlation with BMD-LS in patients older than 60 years (p = 0.01). BMD-LS and BMD-FN (p < 0.001) and total sRANKL (p < 0.01) were negatively related with the age of the patients. Only IL-6 (positive correlation, p < 0.001) and 1,25(OH)₂D₃ (negative correlation, p < 0.001) but not sRANKL, OPG, and sgp130 were related to disease activity. Using multiple linear regression analysis, menopause was identified as the crucial negative determinant of BMD-LS (R ² = 0.94, p = 0.001), whereas cumulative glucocorticoid dose (β = −0.80, p = 0.001) and ESR (β = −0.44, p = 0.016) were the negative determinants of BMD-FN (R ² = 0.86, p = 0.001). The results indicate that influences of age and gender must be considered in investigations on the relationship between BMD and sRANKL in RA and that high serum levels of sRANKL seems to be associated with osteoporosis only in subgroups of RA patients.     

Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis

We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis clinic. At the time of recruitment, all had clinical evidence of synovitis. Patients were assessed at baseline and at 1-year follow-up. Periarticular and axial bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay. A total 38 patients were included in the study. Twenty had rheumatoid arthritis (RA) and 18 had a seronegative spondylarthropathy (SpA). At baseline, periarticular hand BMD measurements were similar in RA and SpA. At 1 year, the mean periarticular hand BMD was significantly lower in RA (p < 0.05). Significant inverse correlations between both the Ritchie articular index and C-reactive protein levels and the change in periarticular hand BMD at 1 year were observed in RA (r = −0.792, p < 0.001 and r = −0.478, p = 0.045, respectively). Baseline TIMP-1 levels correlated with the change in periarticular hand BMD at 1 year in RA (r = 0.519, p = 0.02). At 1 year, radiographic measures of joint damage were highest in RA. Inverse correlations between the change in periarticular hand BMD and the changes in erosion score (r = −0.90, p = 0.04) were observed in patients demonstrating significant periarticular bone loss. Persistent disease activity was associated with increased periarticular bone loss in the hands in patients with RA, consistent with synovitis-mediated periarticular bone loss. The correlation between baseline TIMP-1 levels and periarticular bone loss over 1 year suggests that TIMP-1 may have utility as a biomarker of periarticular bone loss in early RA.     

Effects of an educational–behavioral joint protection program on people with moderate to severe rheumatoid arthritis: a randomized controlled trial

The aim of this study was to asses the effects on pain, disability, and health status of an educational–behavioral joint protection program in a group of moderate–severe rheumatoid arthritis (RA) patients. Eighty-five subjects with RA in treatment with anti-tumor necrosis factor alpha (TNFα) drugs (infliximab) were enrolled into the study and randomized into either an experimental group (46, EG) or a control group (39, CG). We organized four EG meetings, which included information on pathophysiology and evolution of RA, joint protection during normal activities of daily living, suggestions on how to adapt the surrounding environment, and self-learning exercises to perform at home. Sociodemographic characteristics and degree of knowledge of the disease, measured by the Health Service Interview (HSI), were recorded at baseline. The outcome measures included the Visual Analogue Scale (VAS), the Arthritis Impact Measurement Scale 2 (AIMS2), and the Health Assessment Questionnaire (HAQ), which were administered at the beginning and end of the trial. Thirty-six patients from the EG (7 men and 29 women; mean age 54.2 years) and 34 from the CG (6 men and 28 women; mean age 52.2 years) completed the trial. No statistical differences in baseline evaluations were found between the two groups. According to the answers given on the HSI, the majority of our patients had poor knowledge of RA and its consequences. After a mean time of 8 months, the patients receiving educational training displayed a significant decrease, compared to the CG, in the VAS (p = 0.001), HAQ (p = 0.000), and physical (p =0.000), symptoms (p = 0.049), and social interaction (p = 0.045) scores on the AIMS2, but not in other items. Our study showed that 8 months after attending an educational–behavioral joint protection program, subjects with moderate–severe RA presented less pain and disability and thus an enhanced health status. This approach may efficiently complement drug therapy in these patients.     

Anti-agalactosyl IgG antibody in ankylosing spondylitis and psoriatic arthritis

Anti-agalactosyl IgG antibody (anti-Gal(0) IgG) has been regarded as a useful serological marker for rheumatoid arthritis (RA). It is unknown whether it is also elevated in serum and implicated in the pathogenesis of joint inflammation in seronegative spondyloarthropathy (SpA) such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Sera were collected from 43 patients with AS or PsA with axial joint involvement, 22 patients with RA, and 25 healthy normal individuals for the detection of anti-Gal(0) IgG with a cup-type lectin enzyme immunoassay (Eitest CA^.RF). The disease activity of the AS/PsA was evaluated by Bath Ankylosing Spondylitis Disease Activity Score (BASDAI), the serum C-reactive protein (CRP) and IgA were measured by nephelometry, and erythrocyte sedimentation rate (ESR) was measured by Westergren’s method. The median titers of anti-Gal(0) IgG were significantly elevated in patients with RA (167.85, 15.73∼797.58 AU/mL) and AS/PsA (186.15, 34.71∼651.19 AU/mL), compared to those of the normal controls (13.04, 12.00∼202.43 AU/mL). The titers of the anti-Gal(0) IgG in patients with AS/PsA were correlated to the BASDAI scores (r ² = 0.422, SEE = 1.443, p < 0.001) and serum CRP (r ² = 0.345, SEE = 2.434, p < 0.001) but not to IgA (r ² = 0.0259, SEE = 126.30, p < 0.001) or ESR (r ² = 0.171, SEE = 31.053, p = 0.0059). Collectively, the anti-Gal(0) IgG is elevated and vaguely correlated with the disease activity of AS/PsA although its titers in these patients were erratic. The result of the present investigation has suggested that anti-Gal(0) IgG may be more ubiquitously present in inflammatory arthritides including RA or SpA.     

The predictors of foot ulceration in patients with rheumatoid arthritis: a preliminary investigation

We explored the predictors of foot ulceration in patients with rheumatoid arthritis (RA). The cases were 15 patients with RA reporting foot ulceration in response to a postal survey of patients sampled from a diagnostic register in secondary care (n = 1,130). The controls were 66 patients with RA randomly sampled from the survey respondents (n = 883) after matching for age, sex and disease duration. Patients with co-existent diabetes were excluded. Clinical examination included the assessment of known risk factors for foot ulceration in diabetes including: neuropathy (insensitivity to 10 g monofilament), peripheral vascular disease (ankle brachial pressure index [ABPI]), foot deformity (Platto indices) and raised plantar pressure (PressureStat™ readings). A 44 swollen-joint count, the presence of pre-ulcerative lesions and current steroid therapy were identified through univariate analysis as additional potential predictors in patients with RA. Forward step-wise logistic regression analysis showed that the following variables were significant predictors of ulceration: steroid therapy (OR = 9.70, 95%CI = 2.09–45.11, p = 0.004), abnormal ABPI (OR = 13.45, 95%CI = 1.19–151.43, p = 0.035), the presence of pre-ulcerative lesions (OR = 7.40, 95%CI = 1.51–36.30, p = 0.014) and swollen-joint count (OR = 1.25, 95%CI = 1.02–1.53, p = 0.034). Abnormal sensation, foot deformity and raised plantar pressures were not significant predictors of ulceration. The wide confidence intervals for ABPI were due to sparse data with very few abnormal values, and the results of exact logistic regression (more accurate where data is sparse and case matching employed) found that ABPI was no longer a significant predictor (p = 0.054). The significance of the other predictors did not differ substantially. In this preliminary study, abnormal sensation, foot deformity and raised plantar pressures were not significantly associated with foot ulceration but active disease and current steroid therapy were. The contribution of peripheral vascular disease to risk is unclear and further investigation is needed in a larger cohort.     

Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes

Aims/hypothesis Intramyocellular lipids, including ceramide, a second messenger in the sphingomyelin signalling pathway, might contribute to the development of insulin resistance. The aim of our study was to assess parameters of the skeletal muscle sphingomyelin signalling pathway in men at risk of developing type 2 diabetes. Methods We studied 12 lean (BMI < 25 kg/m²) men without a family history of diabetes (control group), 12 lean male offspring of type 2 diabetic patients, and 21 men with overweight or obesity comprising 12 with NGT (obese-NGT) and nine with IGT (obese-IGT). A euglycaemic-hyperinsulinaemic clamp and a biopsy of vastus lateralis muscle were performed. Ceramide, sphingomyelin, sphinganine and sphingosine levels and sphingomyelinase and ceramidase activities were measured in muscle. Muscle diacylglycerol and triacylglycerol levels were estimated in a subgroup of 27 men (comprising men from all the above groups). Results Compared with the control group, the lean offspring of diabetic patients and the men with overweight or obesity showed lower insulin sensitivity (all p < 0.005) and a greater muscle ceramide level (all p < 0.01). The obese-IGT group had lower insulin sensitivity (p = 0.0018) and higher muscle ceramide (p = 0.0022) than the obese-NGT group. There was lower muscle sphingosine level and alkaline ceramidase activity in offspring of diabetic patients (p = 0.038 and p = 0.031, respectively) and higher sphinganine level in the obese-NGT (p = 0.049) and obese-IGT (p = 0.002) groups than in the control group. Muscle sphingomyelin was lower (p = 0.0028) and neutral sphingomyelinase activity was higher (p = 0.00079) in the obese-IGT than in the obese-NGT group. Muscle ceramide was related to insulin sensitivity independently of other muscle lipid fractions. Conclusions/interpretations Ceramide accumulates in muscle of men at risk of developing type 2 diabetes.     

Juvenile Chronic Arthritis in Adult Life: A Study of Long-term Outcome in Patients with Juvenile Chronic Arthritis or Adult Rheumatoid Arthritis

We compared the prognostic factors and outcome of 30 patients with juvenile chronic arthritis (JCA) extending into adult life with those of 30 patients with adult rheumatoid arthritis (RA) at a university adult rheumatology clinic; pairs were matched for sex and duration of disease (mean 8 years). One-third of JCA patients had seronegative polyarticular disease and another third had oligoarticular disease. In a third of the JCA patients, the clinical presentation changed during the follow-up. Over half of the RA patients had seropositive polyarticular and a one-third had seronegative polyarticular disease. Fewer seropositive patients were recorded in the JCA group than in the RA group both at the beginning (16.7% versus 56.7%; p = 0.003) and at the end of the follow-up (14.3% versus 59.3%; p = 0.001). JCA patients developed less radiographic changes than RA patients (46.7% versus 76.7%; p = 0.034); oligoarthritis in the JCA group had the best prognosis whereas seropositive polyarthritis in the RA group had the worst prognosis. Significantly more patients with JCA than RA (60% versus 23%; p = 0.009) were in remission at the end of the follow-up. In conclusion, when studied in adult life, the long-term prognosis is better in patients with JCA than in those with RA. Received: 23 March 1998 / Accepted: 3 November 1998     

Assessment of cervical pain and function in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, which can lead to deformities and functional disability. Unlike the dorsal and lumbar spine, the cervical spine is often affected by RA. The objective of this paper is to assess cervical pain and function in patients with RA and correlate these variables with overall function, quality of life, and radiographic findings on the cervical spine. One hundred individuals aged 18 to 65 years were divided into study group (50 patients with rheumatoid arthritis) and control group (50 healthy individuals, paired for gender and age). Patients with prior surgery, prior trauma or other symptomatic cervical spine condition were excluded. The visual analogue pain scale (VAS), Neck Pain and Disability Scale (NPDS), SF-36, HAQ and X-rays were used for evaluation purposes. Mean disease duration was 11.1 years. The cervical VAS was 2.4 cm and 1.3 cm for the study and control groups, respectively (p = 0.074). Statistical differences were found in NPDS scores, mean = 26.7 and 6.9, and HAQ scores, mean = 1.1 and 0.1, for the study and control groups, respectively (p < 0.001). SF-36 scores were statistically worse in the study group, except for the vitality, social aspects and mental health subscales. There was a positive correlation between the NPDS and VAS (r = 0.54) and between the NPDS and HAQ (r = 0.67). There was a negative correlation between the NPDS and SF-36 functional capacity domain (r = −0.53) and physical limitation domain (r = −0.58). The radiographic findings revealed more prevalent anterior atlanto-axial subluxation (p = 0.030), listhesis in neutral posture (p = 0.037), listhesis in extension (p = 0.007), degenerative alteration of C4–C5 segment (p = 0.023), size of C2 spinal canal (p = 0.002) and C3 spinal canal (p = 0.029) in the study group. Patients with RA have poorer cervical function than healthy individuals, although there is no difference in cervical pain.     

Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. TNF-α is a critical mediator of inflammation and metabolic response in patients with RA. Increased insulin resistance and dyslipidemia were known risk factors in patients with active RA, however, the regulation of these metabolic parameters by TNF-α is poorly understood. Neutralization of TNF-α with infliximab offers a unique opportunity to study TNF-α-mediated regulation of these metabolic parameters in RA. The aim of the study was to assess the in vivo TNF-α-mediated regulation of insulin resistance and lipids levels in RA. Nineteen patients with active RA treated with infliximab were prospectively followed for 14 weeks. Plasma lipids levels and insulin resistance were measured at baseline, 6 and 14 weeks after infliximab treatment. At week 14, the disease activity (DAS-28 score) improved significantly (p < 0.000), with a significant reduction in both C-reactive protein (p = 0.007) and erythrocyte sedimentation rate (p = 0.006) levels. The body weight did not change during the study period. After infliximab treatment, insulin resistance improved as reflected by the significant reduction in the Homeostasis Model Assessment Index. Total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoprotein B (apoB) levels all increased significantly from baseline. Nonetheless, the atherogenic index, LDL-cholesterol/HDL-cholesterol ratio, and the LDL/apoB ratio remained unchanged. Infliximab improves insulin sensitivity and alters lipid profile in patients with active RA.     

Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA

The aim of this study was to evaluate serum and synovial levels of IL-17A by ELISA in rheumatoid arthritis (RA) and find out the correlations between IL-17A levels and various clinical, laboratory parameters and RA disease activity and severity indices. Group I consists of 30 adult active RA patients fulfilling the ARA 1987 revised criteria, with knee effusion and receiving basic therapy, and with a mean age of 41.47 ± 11.49 years and mean disease duration of 9.5 ± 4.16 years. Group II consisted of 13 healthy volunteers, age- and sex-matched, with a mean age of 39.08 ± 14.19 years. RA patients showed significantly higher mean serum IL-17A levels than controls (11.25 ± 9.67 vs. 0.6 ± 1.4 pg/mL, respectively, p = 0.0002). Synovial IL-17A levels showed a significant positive correlation with serum IL-17A levels (r = 0.5 and p = 0.005). RA patients with negative rheumatoid factor (RF) had non-significantly higher mean serum IL-17A levels (12 ± 9.86 pg/mL) compared to those with positive RF (10.82 ± 9.81 pg/mL); however, the mean synovial IL-17A levels were nearly the same. Significant positive correlations were found between both serum and synovial IL-17A levels and DAS-28 scores (r = 0.556, 0.392 and p = 0.001, 0.032, respectively). RA patients with class III functional status showed significantly higher mean serum IL-17A levels (17.53 ± 13.43 pg/mL) than classes I and II (8.97 ± 6.97 pg/mL, p = 0.009). These led us to conclude that the elevated serum and synovial IL-17A levels in RA patients parallel the degree of disease activity and severity. This may highlight the usefulness of IL-17 (especially serum level) as a possible marker for more aggressive joint involvement and damage.     

Augmentation index in patients with rheumatoid arthritis and ankylosing spondylitis treated with infliximab

Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p < 0.001). The AIx for all patients increased from 22.0 ± 14.0% to 24.6 ± 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 ± 23.7% to 141.2 ± 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.     

CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis—results and the review of the literature

Autoimmune thyroid diseases frequently overlaps with rheumatoid arthritis (RA). Among genetic factors, the role of the HLA antigens and CTLA4 gene polymorphisms in the overlapping has been suggested. The aim of this study was to investigate the alleles and genotypes frequency of the CTLA4 exon1 A49G polymorphism in Slovak patients with RA, Hashimoto thyroiditis (HT), both (RA + HT) and in healthy controls. Fifty-seven unrelated adults with RA, 57 patients with HT, 34 patients with both (RA + HT), and 51 normal subjects were studied. All were ethnic Slovaks living in the same geographical area. The CTLA4 exon1 A49G polymorphism was genotyped by using small amplicon melting analysis after real-time PCR. The CTLA4 49GG genotype and G allele frequency in the group with RA was not significantly higher in comparison with controls (10.53% vs. 9.8%, p = 0.62, OR 1.39, 95% CI 0.35–5.74 and 39.47% vs. 34.31%, p = 0.43, OR 1.25, 95% CI 0.72–2.18). The frequency of GG genotype was slightly but not significantly higher in patients with HT as compared with control group (19.3% vs. 9.8%, p = 0.17, OR 2.27, 95% CI 0.67–8.45). However, the frequency of GG genotype and G allele in patients with both RA and HT was significantly higher than that in controls (29.41% vs. 9.8%, p = 0.02, OR 4.49, 95% CI 1.20–18.54 and 51.47% vs. 34.31%, p = 0.03, OR 2.02, 95% CI 1.08–3.81). The frequency of GG genotype of CTLA4 A49G gene polymorphism in Slovak patients with RA is not significantly higher in comparison to control group. However, carriers of GG genotype with RA may be susceptible to develop HT.     

Underweight and obese states both associate with worse disease activity and physical function in patients with established rheumatoid arthritis

Obesity is characterised by low-grade inflammation and could potentially affect disease activity and severity in patients with rheumatoid arthritis (RA). Body mass index (BMI), body fat (BF), erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, physical function (health assessment questionnaire) and presence of erosions and joint surgery were assessed in 294 (female = 219) volunteers with established RA [age 63.3 (56.2–69.6); disease duration 13 (7–20) years]. Smoking status, rheumatoid factor and anti-cyclic citrullinated peptide positivity were also assessed. BMI and BF independently associated with disease characteristics. Compared to normal-weight patients, underweight and obese had higher C-reactive protein (p = 0.046) and physical dysfunction (p = 0.034). BMI or BF did not associate with presence of erosions or joint surgery. In patients with established RA, both very low and very high BMI and BF associate independently with increased disease activity and physical dysfunction; however, this does not seem to associate with presence of erosions or joint surgery. Further longitudinal studies are required to address this apparent dissociation.     

Distressed personality is associated with lower psychological well-being and life satisfaction,but not disability or disease activity in rheumatoid arthritis patients

The distressed personality type (“type D personality”) has been shown to be associated with low quality of life and higher morbidity and mortality in various patient groups. Because the role of type D personality is unknown in patients with rheumatoid arthritis (RA), the aim of the present study was to investigate the association of type D personality with aspects of quality of life and disease activity in RA patients. In addition, a potential buffering effect by accepting mindfulness was examined. Participants were 147 patients between 22 and 87 years of age. Patients completed relevant questionnaires at home and the disease activity score was determined. After controlling for potentially confounding variables, multivariate analyses of covariance showed an association of type D personality with a lower satisfaction with life (p < 0.001) and a lower psychological well-being (p < 0.001), but not disease activity in RA patients. Although mindfulness was associated with a higher satisfaction with life (p = 0.02) and positive mood (p = 0.01), it did not diminish the unfavourable associations between type D and well-being. In conclusion, although type D personality is related with lower well-being, it does not seem to be associated with disability or disease activity in RA patients.     

Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)

Aims/hypothesis  The aim of the study was to determine the loss of muscle volume in the lower leg and foot in long-term diabetic patients in relation to the presence of neuropathy. Methods  We re-examined 26 type 1 diabetic patients who had participated in magnetic resonance imaging (MRI) studies on muscle volume in the lower leg and foot 9 to 12 years earlier. Re-examination involved MRI, isokinetic dynamometry, clinical examination, electrophysiological studies and quantitative sensory examinations. Results  Annual loss of muscle volume of ankle dorsal and plantar flexors was 4.5 (5.5–3.9)% (median [range]) and 5.0 (7.0–4.2)% in neuropathic patients, 1.9 (3.2–1.0)% and 1.8 (2.6–1.3)% in non-neuropathic patients, and 1.7 (2.8–0.8)% and 1.8 (2.4–0.8)% in controls, respectively (p < 0.01). Annual change of volume and strength correlated for ankle dorsal flexors (r _s = 0.73, p < 0.01) and for ankle plantar flexors (r _s = 0.63, p < 0.05) in diabetic patients. In addition, annual change of muscle volume for dorsal and plantar flexors was related to the combined score of all measures of neuropathy (r _s = −0.68, p < 0.02 and r _s = −0.73, p < 0.01, respectively). Foot muscle volume declined annually by 3.0 (3.4–1.0)% in neuropathic patients and by 1.1 (4.0–0.2)% in non-neuropathic patients, both values being significantly different from controls (0.2 [−2.5 to 2.4]%). Loss of foot muscle volume was related to severity of neuropathy assessed at clinical evaluation (r _s = −0.6, p < 0.05). Conclusions/interpretation  Muscular atrophy in long-term diabetic neuropathy occurs early in the feet, progresses steadily in the lower legs, relates to severity of neuropathy and leads to weakness at the ankle. An erratum to this article can be found at     

Increased frequencies of hysterectomy and early menopause in fibromyalgia patients: a comparative study

The objective was to determine the relationship between symptoms of fibromyalgia (FM) and early menopause and hysterectomy. We included 115 postmenopausal patients with FM (mean age 54.6 ± 7.6) and 67 rheumatoid arthritis (RA) patients (mean age 55.5 ± 9) into our study. All patients were questioned about the severity of their symptoms of FM, anxiety, and depression by using a visual analog scale and FM impact questionnaire. Patients’ history of menopause and hysterectomy were recorded. Menopause (≤45 years) was accepted to be early. The frequencies of early menopause (38.3% vs. 13.4%, p = 0.001) and hysterectomy (16.5% vs. 6%, p = 0.039) in FM patients were significantly higher than in RA patients. While chronic widespread pain and other FM-related symptoms started after menopause in 58.3% of FM patients, the disease started after menopause in 64.2% of RA patients (p > 0.05). FM-related symptoms started in 30 patients (26.1%) with FM with menopause or within the first postmenopausal year. When the clinical features of FM patients whose symptoms started within the first menopausal year were compared to other FM patients; it was observed that the frequency of early menopause was higher in the former group (p = 0.048). Duke anxiety and depression score was higher in patients with hysterectomy whose FM symptoms started within the first year of post-hysterectomy than other FM patients (9.1 ± 2.7 vs. 6.7 ± 2.7, p = 0.022). Early menopause and hysterectomy may be one of the factors contributing to the development of FM.     

What is the ability of anti-cyclic citrullinated peptide antibodies determination in synovial fluid in discriminating rheumatoid arthritis from non-rheumatoid arthritis patients? A Tunisian cross-sectional study

Anti-cyclic citrullinated peptide antibodies (ACPA) seem to be produced locally at the site of joints inflammation in the first stage of rheumatoid arthritis (RA). A strong correlation between serum ACPA and ACPA in the synovial fluid (SF-ACPA) is now suggested. A case-control study was conducted to evaluate the usefulness of ACPA determination in SF of patients with RA. A total of 53 patients with a knee-joint effusion (26 RA, 18 peripheral spondyloarthropathies (SPA), and 9 osteoarthritis (OA)) were included in our study. SF samples were obtained by performing therapeutic arthrosynthesis. IgG serum ACPA and SF-ACPA levels were determined by the enzyme-linked immunosorbent assay (ELISA). We have also determined IgG levels in serum and SF by nephelometry. Higher levels of IgG ACPA antibodies in SF (p = 0.045) and serum (p = 0.045) were found in patients with RA with respect to SPA and OA patients. The Spearman correlation analysis showed a significant and positive correlation between ACPA in serum and SF (rho = 0.516; p = 0.007) not only in the RA group but also in patients with SPA. Serum ACPA discriminated RA from non-RA at a cut-off value of 2.7 U/ml (sensitivity, 69%; specificity, 78%; and area under the curve (AUC), 0.72), whereas SF-ACPA discriminated RA from non-RA at a higher cut-off value of 4.95 U/ml (sensitivity, 73%; specificity, 61%; and AUC, 0.71). Our study suggests that the determination of SF-ACPA give complement information to serum ACPA in patients with RA.