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Objectives To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. Methods Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. Results A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (β = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (β = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P Conclusions Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

ObjectiveTo investigate sex-based sonographic differences in patients with psoriatic arthritis (PsA).MethodsThe study population included consecutive prospectively recruited patients with PsA, as determined by the CASPAR (Classification for Psoriatic Arthritis) criteria, who underwent clinical and physical examinations, followed by a detailed ultrasound (US) evaluation (greyscale and Doppler). US evaluation included 52 joints, 40 tendons, and 14 points of entheses (Modified Madrid Sonographic Enthesis Index [MASEI] plus lateral epicondyles) performed by an experienced sonographer blinded to the clinical data. The US score was based on the summation of a semiquantitative score for synovitis, tenosynovitis, and enthesitis. The US enthesitis score was categorized into inflammatory lesions (ie, hypoechogenicity, thickening, bursitis, and Doppler) and structural lesions (ie, enthesophytes/calcifications and erosions).ResultsThe study population of 158 patients included 70 males and 88 females. The males had higher rates of employment (P= 0.01), Psoriasis Area and Severity Index scores (P= 0.04), and mean swollen joint counts (P= 0.04). The total US score and its subcategory scores—the synovitis and tenosynovitis scores—were similar for both sexes, whereas the total enthesitis score and its subcategory score—the inflammatory enthesitis score—were significantly higher for the males compared to the females (P= 0.01 andP= 0.005, respectively). Hypoechogenicity, thickening, and enthesophytes were more prevalent in males compared to females (P< 0.05). Multivariate ordinal logistic regression models showed that male sex was associated with a higher US inflammatory enthesitis score compared to female sex (odds ratio 1.96,P= 0.02).ConclusionSonographic enthesitis was more prevalent in males compared to females with PsA. These differences were not reflected by enthesitis disease activity scores derived from clinical assessment.

As members of a gender minority, transgender individuals face many challenges. Many experience distress, depression, anxiety and suicidal ideation related to gender non-conformity and transphobia. Stress and trauma may contribute to the development of fibromyalgia (FM) syndrome, characterised by widespread pain and fatigue. The prevalence of FM among transgenders is not known.Transgender participants were recruited at a specialised clinic. Questionnaires included the Widespread Pain Index (WPI), the Symptom Severity Score (SSS) and the SF-36. Data concerning hormonal treatment protocols was retrieved from charts. The current prevalence of FM was determined, as well as the prevalence before and after testosterone treatment among TM. Pearson correlations were calculated between all measures.115 participants were recruited, 62.6% transgender men (TM), 37.4% transgender women (TW). 17 individuals (14.8%) fulfilled the 2011 modified ACR FM criteria, for a rate of 19.4% among TM and 6.98% among TW. Among TM, FM was associated with younger age, smoking and SF-36 sub-scales related to physical functioning, role limitation due to physical pain, fatigue, pain and general health. Among TW, FM was associated with social status, employment, depression, existing medical treatment and substance abuse, as well as SF-36 subscales related to role limitations affected due to pain.Fibromyalgia symptoms are highly prevalent among Israeli transgender individuals and may be related to psychological distress and gender dysphoria. Healthcare professionals treating transgenders should remain vigilant for the occurrence of chronic pain, fatigue and other FM-related symptoms and be prepared to treat and/or refer such patients accordingly.

The coping mechanisms utilised by patients with the fibromyalgia syndrome (FM) pose a crucial focus of treatment. Previous research points to the positive effects of religiosity and spirituality (R/S) as tools for coping with illness. The role of these factors in coping with chronic pain in FM has not previously been studied. The aim of this study was to evaluate the link between R/S and FM outcomes.Fifty-five FM patients (ACR criteria) attending a tertiary rheumatology clinic completed a packet of questionnaires assessing demographic data, levels of religiosity and spirituality (SpREUK) and locus of control (LOC). These variables were then individually assessed for influence on FM outcome measures, using the Fibromyalgia Impact Questionnaire (FIQ), the SF-36, and the Beck Depression Index (BDI).A high score on SpREUK I (search for meaningful support) was negatively correlated with the Role-Physical (p=0.032) and Role-Emotional (p0.005) scales on SF-36. Secular patients scored higher on SF-36 domains of "Role limitation due to emotional health" and "General health" (p0.05). Employment demonstrated a positive correlation with the FIQ (p0.01), the BDI (p0.001), and the SF-36 (p0.05). Physical activity correlated positively with BDI scores (p=0.012) and better scores on SF-36: energy/fatigue (p=0.024), social-functioning (p=0.014) and physical-functioning (p0.01). No significant correlation was found between LOC (internal versus external) and FM outcomes. No significant correlation was found between SpREUK domains and the BDI.FM patients do not appear to benefit from high levels of R/S. Physicians should be aware of the impact of R/S on well-being in this population.

In a previous study, we showed that the subjective item assessing cognitive impairment (SSS-Cog) for fibromyalgia (FM) did not correlate with the objective cognitive measures. In the current study, we describe two modifications designed to enhance this correlation: extending the SSS-cog scale from 0-3 to 1-5, and administration of a new questionnaire that specifically targets the cognitive impairments associated with FM.Sixty-two FM patients underwent a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ); the Widespread Pain Index (WPI); the Symptom Severity Scale (SSS), the new SSS-Cog scale ranging from 1 to 5, the Beck Depression Inventory (BDI) and the new cognitive questionnaire developed by the authors.Significant correlations were found between the new SSS-Cog, the global cognitive score and all indices [Global Score r=-0.532, p=0.00; Indices: Memory r=-0.305, p=.01; Executive function r=-0.514, p=0.00; Attention r=-0.471, p=0.00; Processing Speed r=-0.468, p=0.00; Motor Skills r=-0.495, p=.00]. Significant correlations were found between the new questionnaire and the global cognitive score and all indices except the memory index [Global Score r=-0.522, p=0.00; Indices: Memory r=-0.163, p=0.212; Executive function r=-0.477, p=0.00; Attention r=-0.439, p=0.00; Processing Speed r=-0.496, p=0.00; Motor Skills r=-0.532, p=0.00].Given the simplicity involved in extending the scale, we suggest incorporating this modification into the FM diagnostic criteria of the American College of Rheumatology (ACR).

Cognitive dysfunction is one of the criteria for the diagnosis of fibromyalgia (FM) and is typically based on self-report questionnaires such as the Symptom Severity Scale. However, recent studies have shown that there is no correlation between these subjective measures of cognitive dysfunction and more lengthy objective measures of cognitive functioning. This points to the need for a briefer valid evaluation tool for cognitive dysfunction in FM. The aim of this study is to examine whether the Montreal Cognitive Assessment (MoCA) test is a valid measure of cognitive assessment in FM patients, by comparing it to a comprehensive computerised cognitive assessment battery.Sixty-two FM patients (55 women, 7 men, mean age = 46.17 years, sd=12.56) were administered the MoCA and a computerised cognitive assessment battery. FM symptoms were assessed on the Fibromyalgia Impact Questionnaire (FIQ), the Widespread Pain Index (WPI), the Symptom Severity Scale (SSS), and the Beck Depression Inventory (BDI-2). Patient effort was controlled on the TOMM (Test of Memory Malingering).Moderate positive correlations were found between the MoCA and the computerised cognitive scores as follows: Global Cognitive Score (r=0.493**, p=0.00), Memory Index Score (r= 0.384**, p=0.002), Executive Function Index Score (r=0.461**, p=0.00), Attention Index Score (r=0.310*, p=0.016), Information Processing Speed Index Score (r=0.435**, p=0.001), and Motor Skills (r=0.406**, p=0.002).The MoCA is an acceptable cognitive screening test for the cognitive evaluation of FM patients.

Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors.An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment.Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p0.01), lower levels of pain (p0.05) and less sleep disturbances (p0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p0.01).Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.

Objectives To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA. Methods All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK). Results The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P Conclusion There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain, sleep disturbances, fatigue, and cognitive impairment, associated in some cases with anxiety and depression. FM affects quality of life in many aspects and remains a therapeutic challenge. Comprehensive treatment of this condition aims not only to alleviate pain but rather needs a holistic approach to address both physical and psychological symptoms: to treat pain and functional consequences of pain. In this regard, nonpharmacological interventions have been shown to be effective, most of them with low cost and high tolerability.

Objective Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. Methods This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. Results sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′lateral and E/e′septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. Conclusions Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.

Objective Osteoarthritis (OA) is a widespread degenerative joint disease leading to progressive loss of function and pain. Available treatments do not provide long-term relief or improvement. This study aimed to assess the safety and efficacy of a novel intra articular supplement, made of high molecular-weight hyaluronic acid (HA) uniquely conjugated to either purified (RegenoGel) or autologous plasma-derived fibrinogen (RegenoGel-OSP), as a long-term treatment for knee OA. Methods Sixty-seven consecutive participants (mean age 67.26 ± 7 years) with symptomatic OA were randomly assigned to receive intraarticular injections of either RegenoGel, RegenoGel-OSP or saline solution (placebo). The active treatment groups received a second, repeat injection of the corresponding treatment at the 3-month evaluation, at which time, the placebo group was divided into two subgroups, one receiving RegenoGel and the other receiving RegenoGel-OSP. The OA symptoms were assessed by VAS, WOMAC, and IKDC questionnaires at baseline and at 1, 3, 4, and 6 months following the first injection. OA-related quality of life was evaluated by the SF-12 survey. Results Our preliminary data suggests that both fibrin-HA formulations have positive effects on OA symptoms for all assessed parameters with the most prominent trend for reduction in OA-associated pain. Pooled data analysis of RegenoGel and RegenoGel-OSP shows significantly improved VAS scores compared to placebo at three months after the first injection, and sustained for another three months after the second injection. Both RegenoGel, RegenoGel-OSP had an excellent safety profile. Conclusions Interim analysis results indicate that RegenoGel and RegenoGel-OSP are safe and are potentially effective for at least six months in alleviating pain and symptoms of knee OA., Health sciences; Rehabilitation; Knee osteoarthritis, Hyaluronic acid, Viscosupplement, Hydrogel, Plasma fibrinogen, Intraarticular injection, Regenerative medicine.

Rheumatoid arthritis (RA) and fibromyalgia syndrome (FM) are common diagnoses encountered in rheumatology practice, but do not enjoy the same status. We aimed to examine physician's illness perceptions regarding these two rheumatologic disorders and to evaluate how they correlate with their relationship with these patients.Forty-five rheumatologists were enrolled in the study. Demographic data were registered. Measures collected included the Brief Illness Perception Questionnaire (BIPQ) and the Difficult Doctor- Patient Relation Questionnaire (DDPRQ-10). Both were recorded twice, related to FM and RA. Empathy and burnout were also assessed.Of 45 physicians included in the study, only 53% were willing to accept FM patients. FM was considered a more severe disease than RA (FM-BIPQ mean score 54, SD 5.5 versus RA-BIPQ mean 45.6 SD 6.5, p0.00) in terms of treatment control, understanding and emotional response generated by the disease. Doctor-patient relationship was perceived more difficult with FM patients compared to RA patients (FM-DDPRQ mean score 35.1, SD 9.2 versus RA-DDPRQ mean 19.6, SD 7.1, p0.00), and was significantly correlated to the patient's concern about the illness (p0.034) and patient's emotional response (p0.036). Resistance to accept FM patients was largely influenced by difficult doctor-patient relationship. Higher levels of empathy were found in physicians experiencing less difficulty with FM patients.FM patients were perceived as more difficult than RA patients, with a high level of concern and emotional response. A high proportion of physicians were reluctant to accept them because they feel emotional/psychological difficulties meeting and coping with these patients.

Objective To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. Methods Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA–B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. Results Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. Conclusion Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

Chronic pain is an issue of increasing health concern, with a negative impact on suffering patients, their families, and society since it is contributing to high health care costs and loss of productivity. Fibromyalgia is one of the most common causes of chronic pain, especially in women, and is associated with several comorbidities, leading to both increased levels of distress as well as decreased function. Obesity is another chronic disease, with increasing prevalence around the world, associated with increasing morbidity and mortality. In their study published in the present issue of Harefuah, Blokh Kerpel et al found a strong link between these two epidemics - fibromyalgia and obesity. This association contributes to our understanding regarding the epidemiology and pathogenesis of fibromyalgia. Obesity also negatively affects the course of fibromyalgia. Obese patients with fibromyalgia experience more pain, are more depressive, have reduced mobility and function and use more medications. Moreover, feasibility and efficacy of treatment interventions is challenging, especially in terms of physical activity - the mainstream of fibromyalgia treatment - which is severely reduced in obese patients. Optimal treatment for obese patients with fibromyalgia must address these issues.

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. Methods. 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. Results. The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), p=0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. Conclusion. Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS.

The presence of serological markers associated with inflammatory bowel disease (IBD) has been studied in spondyloarthritis with conflicting results. The anti-glycan antibodies: anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies (ALCA, ACCA, and AMCA) are serological markers previously associated with IBD. We aim to investigate the prevalence of these antibodies in spondyloarthritis in comparison with rheumatoid arthritis (RA) patients.Serum samples were obtained from consecutive patients with spondyloarthritis and were compared to RA and healthy controls. Anti-glycan antibodies - ALCA, ACCA and AMCA - were assessed using ELISA (Glycominds Ltd, Israel). Demographic characteristics, family history, disease pattern, skin evaluation (for PsA), disease activity and a questionnaire for gastrointestinal symptoms were recorded.Seventy patients were recruited: 36 ankylosing spondylitis (AS) and 28 psoriatic arthritis (PsA). No difference in ALCA or AMCA levels was observed between all the study groups. Significantly higher levels of ACCA were observed in RA patients, compared to healthy controls (p=0.002). One or more of the anti-glycan antibodies was found in 16.7%, and 3.6% of patients with AS and PsA, respectively, compared to 7.3% in healthy controls and 27% in RA (p=0.09). No correlation was found between the presence of anti-glycan antibodies and gastrointestinal symptoms.Our data fail to show an increased prevalence of anti-glycan antibodies in AS or PsA patients. ACCA were found to be significantly higher in RA patients than in controls, and may serve as an inflammatory biomarker. The present results do not support a role for antiglycan antibodies as biomarkers for spondyloarthritis.

To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging.Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA-B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index.Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment.Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

Objectives. To evaluate the effect of presurgical symptoms characteristic of fibromyalgia on the postsurgical outcome of patients undergoing spinal surgery. Methods. In this observational cohort study, participants were patients scheduled for spinal surgery, including cervical or lumbar laminectomy and foraminectomy. Presurgical evaluation included physical examination and manual dolorimetry. Questionnaires included the widespread pain index (WPI), symptom severity scale (SSS), and SF-36. Postsurgical evaluation performed at 10–12 weeks included questionnaires, physical examination, and dolorimetry. Results. Forty patients (21 male, 19 female) were recruited. Four patients (10%) fulfilled American College of Rheumatology (ACR) 1990 fibromyalgia; nine patients fulfilled 2010 criteria (22.5%). Overall, a significant 34% reduction in WPI was observed postsurgically ( P

BACKGROUND: Leptin, an adipocyte-produced cytokine, interacts with various hormones, including those of the hypothalamic-pituitary-adrenal axis. Fibromyalgia is a syndrome characterized by widespread pain accompanied by tenderness. The pathogenesis involves a disturbance in pain processing and transmission by the central nervous system, leading to a general increase in pain perception.OBJECTIVES: To analyze potential changes in leptin levels among female fibromyalgia patients compared with healthy controls, and to evaluate the changes in leptin levels during treatment.METHODS: Sixteen female fibromyalgia patients were recruited. Patients underwent clinical evaluation, physical examination, including manual dolorimetry, and were evaluated regarding quality of life, pain, fatigue, anxiety and depression. Plasma leptin levels were determined by ELISA. Patients were offered standard treatment for fibromyalgia. Clinical evaluation and leptin determination were repeated after three months.RESULTS: No significant difference was observed between leptin levels among fibromyalgia patients and controls; no significant correlation was observed between leptin levels and clinical parameters reflecting fibromyalgia severity; and no significant change was observed in leptin levels over three months of treatment. These results did not change after adjustment of leptin levels for body mass index values.CONCLUSIONS: The results of the present study do not support the existence of a significant relationship between leptin and fibromyalgia pathogenesis. Increasing the sample size or examining the interaction between leptin and additional hormones/mediators of metabolism and body weight control may yet uncover significant information in this field.

Endothelial progenitor cells (EPCs) are a population of bone marrow derived cells which have been attributed with the ability to migrate into areas of tissue ischemia and to posses reparative qualities. EPCs have been shown to be decreased in level and function in various inflammatory disorders. Psoriasis and psoriatic arthritis are associated with an increase in cardiovascular morbidity. The aim of the study was to investigate the number of EPCs among patients suffering from psoriasis and psoriatic arthritis. Patients suffering from active psoriasis and psoriatic arthritis were recruited as well as healthy controls. Disease activity was assessed with the DAS-28, BASDAI and PASI scores. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using the CD34/133 and CD34/KDR. No significant difference was found between numbers of EPCs between healthy controls, patients with psoriasis and psoriatic arthritis. A significant correlation was found between levels of VGEF and the BASDAI score. The results of the current study do not support a significant role for EPCs in the pathogenesis of psoriasis and psoriatic arthritis.

Background Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, its pathogenesis is unknown. In a previous functional magnetic resonance imaging (fMRI) study we demonstrated altered brain activity dynamics and less brain deactivation in patients with SLE as compared with healthy controls, when performing a learning and memory task. Our findings localized this impairment to the default mode network (DMN), and particularly to its anterior medial prefrontal cortex node. In addition, altered networking of the hippocampal subsystem of the DMN was seen in patients with SLE when performing this task, as well as atrophy of the left hippocampus. The present study aimed to search for a structural substrate for the altered recruitment pattern observed in fMRI studies using diffusion tensor imaging (DTI). Patients and methods Using DTI, we characterized brain diffusivity in 10 patients with SLE and nine healthy controls. Two tracts associated with the DMN were reconstructed: the corpus callosum (CC) and the cingulum bundle. The CC was segmented according to the Witelson segmentation scheme and the cingulum was segmented into superior and descending bundles. Results A significant increase in mean diffusivity (MD) was seen in patients with SLE without neuropsychiatric SLE (NPSLE) as compared with healthy controls in all five segments of the CC (segment 1: p = 0.043; segment 2: p = 0.005; segment 3: p = 0.003; segment 4: p = 0.012; segment 5: p = 0.023) as well as in the descending portion of the left cingulum bundle ( p = 0.026). Conclusions Increased MD values in the CC and the left cingulum may indicate impaired organization/reduced integrity of these tracts, which may underlie the abnormal pattern of brain activity recruitment of the DMN observed during a verbal learning and memory task. Taking into account the central role of the left hippocampus in verbal memory, the abnormal integrity of the left cingulum may contribute to the reduced performance of patients with SLE on verbal memory tasks.

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis.To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder.Active seropositive RA patients (N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance.A significant 33.4% increase (p0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, (p0.002) while a 37.6% increase was observed in mean EPC adhesion (p0.001). These changes were associated with a 17.5% decrease in the DAS-28 (p0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs.A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.

Objectives To report 4 cases of propythiouracil (PTU)-induced lupus or vasculitis and to review the literature on that subject. Methods We describe the clinical presentation, course, and outcome of 4 patients and review the medical literature registered in the Medline PubMed database from 1966 to 2004 by using the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis, arthritis, rash, ANA, and ANCA. Cases were classified into drug-induced lupus (DIL) or vasculitis using accepted definitions and evaluated with emphasis on gender, age, origin, duration of treatment, delay in diagnosis, clinical and serological features, and outcome. Results We described our 4 patients and analyzed 42 well-documented cases of DIL- and PTU-induced vasculitis (30 had vasculitis and 12 fulfilled the classification criteria of DIL). Patients with vasculitis were significantly older (mean 43 versus 22 years) and had a longer duration of treatment in comparison with DIL (35 versus 24 weeks). Musculoskeletal symptoms were prominent in DIL, while renal and pulmonary involvement was found in a significantly higher proportion of PTU-induced vasculitis. ANA, anti-DNA, and anti-histone were predominantly found in DIL, while p-ANCA was found in a similar proportion of patients in both groups. c-ANCA was detected only in patients with vasculitis. All patients with DIL completely recovered (most after stopping PTU), while about 50% of PTU-induced vasculitis needed steroids or immunosuppressive drugs, including cyclophosphamide and plasmapheresis. Conclusions Most of the cases of PTU-induced autoimmune phenomena are due to vasculitis. Despite the common presence of p-ANCA in both DIL- and PTU-induced vasculitis, substantial differences in demographic, clinical, and outcome features of these entities allow an accurate diagnosis and consequent management.

Over the past years, considerable progress has been made in understanding the pathogenesis of the fibromyatgia syndrome and the evidence based approach to the diagnosis and management has been significantty extended. The purpose of the current project is to develop practicat and evidence based guidetine recommendations for the Israeli health care system. A panet of physicians with clinical and research experience in the fibromyalgia field was convened under the auspices of the Israeli Rheumatology Association. A systematic review was performed on the current literature regarding the diagnosis and treatment of fibromyalgia. Using an interactive discussion procedure, recommendations were reached and expert opinion was introduced where evidence was considered incomplete. The panel recommendations underline the importance of concomitant and integrated medical therapy, such as serotonin and noradrenaline reuptake inhibitor (SNRI) anti-depressants or gamma-aminobutyric acid (GABA) related anti-epileptics, with regular aerobic physical exercise.

Fibromyalgia represents the tip of the iceberg of chronic pain in the general population. We have attempted to estimate the prevalence of fibromyalgia in the Israeli population, using the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ), an instrument previously utilised in several European countries.The LFESSQ-4 screens for widespread pain, and the LFESSQ-6 for widespread pain and chronic fatigue. The LFESSQ was administered via telephone to a sample of 1019 individuals. To estimate the positive predictive value (PPV) of LFESSQ-4 and LFESSQ-6, this questionnaire was submitted to a sample of rheumatology outpatients (n=76), who were examined to confirm or exclude fibromyalgia according to the 1990 criteria. The prevalence of fibromyalgia in the general population was estimated by applying the PPV to community subjects.In the community survey, 5.1% and 3.9% of individuals screened positive for the LFESSQ-4 and LFESSQ-6, respectively. The point prevalence of FMS in the Israeli general population was 2.6% (95%CI 1.7-3.4) when using LFESSQ-4 and 2.0% (95%CI 1.3-2.7) when using the LFESSQ-6 criteria.The prevalence of the fibromyalgia syndrome in the Israeli population is considerable and constitutes a significant health care issue. The prevalence is similar to that observed in other western populations. Based on this tool, over 25% of fibromyalgia cases appear to be among males, a proportion higher than generally appreciated.

Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells present in the peripheral circulation, which possess the ability to migrate into areas where angioneogenesis is required and differentiate upon adhesion into mature endothelial cells. EPCs have reparative properties, are able to combat ischemia and have previously been shown to be decreased in level and function in inflammatory conditions. Systemic lupus erythematosus (SLE) is a multi-organ autoimmune inflammatory disorder associated with significantly increased cardiovascular morbidity and mortality. To investigate the numbers and functional properties of EPCs among patients suffering from SLE, thirty-one patients suffering from active SLE (American College of Rheumatology criteria) as well as 54 healthy controls were recruited. Disease activity was assessed using the SLEDAI score. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Functional properties were evaluated by EPC adherence to fibronectin. No significant difference was found between numbers of circulating EPC colony-forming units (CFUs) among patients with SLE and healthy individuals. A significant increase in adhesive capacity of EPCs to immobilized fibronectin was evident in patients with SLE compared to controls. An increase in adhesive capacity of circulating EPCs was observed in patients with SLE which may be related to altered endothelial function.

Background Fibromyalgia Syndrome (FMS), considered the result of increased processing of pain by the central nervous system, is a non-inflammatory condition characterized by chronic, widespread musculoskeletal pain and tenderness.Axial spondyloarthritis (SpA) is a group of inflammatory joint disease primarily involving the sacroiliac joints and axial spine. Although FMS and axial SpA differ vastly in their pathogenesis, a considerable clinical overlap may exist between these conditions. Chronic nocturnal back pain and disturbed sleep may accompany either condition. The Assessment of Spondylo-Arthritis international Society (ASAS) has published updated classification criteria for axial SpA with an imaging and clinical arms. We have previously described an increased prevalence of secondary FMS among female SpA patients. Objectives To evaluate the prevalence of axial SpA among FMS patients, utilizing the 2010 ASAS criteria (1). Methods Patients suffering from FMS (ACR 1990 classification criteria) were recruited consecutively from a specialized FMS clinic. Patients were interviewed regarding the presence of SpA features, as defined by the ASAS group (IBP, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn9s/colitis, good response to NSAIDS, family history of SpA) and underwent HLA-B27 testing and CRP measurement. MRI examinations of the sacroiliac joints were performed on a 1.5 T MRI unit using semicoronal T1 weighted, STIR and FSPGR pre- and post-contrast injection sequences. FMS severity was assessed by the FIQ and SF-36 questionnaires and physical examination of the tender points using a dolorimeter. SpA symptom severity was assessed by the BASDAI questionnaire Results 99 unselected patients were recruited and MRI results were available for 74. Sacroiliitis, based on ASAS definition (2), was found among 7 patients, 7 of which fulfilled ASAS SpA classification criteria. 6 patients fulfilled the criteria based on sacroiliitis on imaging and SpA features, one additional patient fulfilled SpA criteria based on HLA-B27 positivity and additional SpA features. Conclusions Imaging findings suggestive of inflammatory SpA were not uncommon among patients presenting with a clinical diagnosis of FMS. Definite sacroiliitis and ASAS criteria SpA positivity were diagnosed among 9.5% of patients and additional changes typical of SpA were frequent. These findings suggest that FMS may mask an underlying SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such co-morbidities. References Sieper J et al. Ann Rheum Dis 2009;68:8(Suppl II):ii1–ii44 Rudwaleit M et al. Ann Rheum Dis 2009; 68(10):1520 Disclosure of Interest J. Ablin Speakers bureau: Pfizer Inc., I. Eshed: None declared, M. Berman: None declared, V. Aloush: None declared, I. Wigler: None declared, D. Caspi: None declared, M. Likhter: None declared, A. Sharabi: None declared, A. Rom-Broyde: None declared, S. Borok: None declared, D. Levartovsky: None declared, Y. Wolman: None declared, D. Paran: None declared, M. Anouk: None declared, O. Elkayam: None declared

Fibromyalgia (FM), pre-dominantly found in women, may accompany other pre-existing rheumatic diseases. The association between FM and ankylosing spondylitis (AS) is uncertain. We evaluated FM in women with AS. Eighteen women with AS were compared with 18 men with AS (controls) for age, duration of symptoms, time to diagnosis, degree of sacroiliac involvement, history of peripheral arthritis, patient global assessment, Health Assessment Questionnaire, Fibromyalgia Impact Questionnaire, level of diffuse pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). Physical examination included the number of tender points and enthesitis sites, Schober test, distance between occiput and wall, chest expansion, lateral spinal flexion, and intermalleolar distance. Inflammatory activity was measured by the erythrocyte sedimentation rate (ESR). Of all tested parameters, the ones with significant differences between the groups were time between symptom onset and AS diagnosis (longer for women), FM incidence and the number of tender points and enthesitis sites (higher for women), BASDAI (higher in women and correlated with FM and the number of tender points but not with ESR), and BASFI and BASDAI scores (increased in FM patients). FM was present in 50% of women with AS and associated with higher disease activity indices (BASDAI and BASFI) and not related to severity of physical findings or ESR. The reliability of well-accepted assessment tools of AS, such as BASDAI and BASFI, in evaluating AS activity in women may be called into question due to a confounding effect of FM.

Pseudomonas aeruginosa , a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR P. aeruginosa and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR P. aeruginosa , and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR P. aeruginosa . Having a malignant disease was a protective factor (odds ratio [OR] = 0.2; P = 0.03). MDR P. aeruginosa was associated with severe outcomes compared to controls, including increased mortality (OR = 4.4; P = 0.04), hospital stay (hazard ratio, 2; P = 0.001), and requirement for procedures (OR = 5.4; P = 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR P. aeruginosa is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR P. aeruginosa infections are associated with severe adverse clinical outcomes.

The fibromyalgia syndrome (FMS) is considered to result from the exposure of a genetically susceptible individual to various triggers, such as physical trauma, stress, viral infections etc. A possible role of vaccination in FMS etiology has been suspected. Our objective was to evaluate the efficacy and safety of influenza vaccination in FMS patients. Nineteen FMS patients underwent physical and dolorimetric examinations and answered the fibromyalgia impact questionnaire (FIQ), the widespread pain index (WPI) checklist and the symptoms severity scale (SSS), which are part of the 2010 diagnostic criteria. Thirty-eight healthy subjects were recruited as controls. All participants were vaccinated with the inactivated split virion influenza vaccine. Serum was collected for antibody titration. Six weeks after vaccination, sera were tested by hemagglutination (HI) against A/California (H1N1), A/Perth (H3N2) and B/Brisbane. Humoral response was defined as either a fourfold or greater increase in titer, or an increase from a non-protective baseline level of

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.