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Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities and differences in vascular disease patterns underlying different rheumatic autoimmune diseases., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Major advances have been made in the pathogenesis of rheumatoid arthritis, spondyloarthritis and connective tissue diseases, leading to new biotherapies. In rheumatoid arthritis, the discovery of anti-citrulline antibodies (ACPA, anti-citrullinatedpeptide antibodies), whose specificity is between 95% and 98% and may be present before symptom onset, allowed early diagnosis and provided new pathological insights. Studies of the role of cytokines, B cells and co-stimulation of T cells revealed novel therapeutic targets. TNF inhibitors are effective in spondyloarthritis. In lupusandSjigren'ssyndrome, genes stimulatedby IFNtypel are hyper-expressed, along with BAFF (or BLyS), a B lymphocyte-activating cytokine.

Natriuretic peptides (NP) are secreted by cardiomyocytes and are reliable markers of cardiac dysfunction and cardiovascular risk by reflecting myocardial stress due to various etiologies. Clinical and occult heart involvement is frequently observed in patients with rheumatic diseases and is associated with increased morbidity and mortality. Cardiac disease in autoimmune disorders encompasses different pathophysiological mechanisms including inflammation and involving either the myocardium or the coronary/pulmonary vessels. Although the major trigger for the synthesis and release of NP is myocardial strain, there is also some support for the concept that inflammation stimulates the neurohormonal system of the heart leading to increased production of NP. Recent studies have focused on the association of NP and inflammation in the context of rheumatic diseases, suggesting that up-regulation of neurohormonal axis in these conditions is linked with inflammation. Additionally the NP have a well-documented role in the diagnostic work-up of patients with connective tissue disease who are at increased risk of developing pulmonary hypertension, as the right ventricular overload results in increased NP synthesis and release. However the precise role of NP in the assessment and the management of cardiovascular risk in patients with rheumatic diseases is yet to be established. In the current article we discuss the pathophysiologic mechanisms involved in enhanced NP expression in patients with rheumatic disorders and their potential clinical implication in daily practice., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Questionnaires to evaluate hand function are variable in the number of items, domains and diseases in which they had been previously used., Objectives: a) To translate to Spanish and validate the m-SACRAH and AUSCAN questionnaires; b) to do a transcultural adaptation of DASHe, previously validated in Spain), and c) to compare them and the Cochin questionnaire (previously validated in México), in rheumatic patients with variable impairment of hand function., Material and Methods: m-SACRAH, AUSCAN and DASH were translated/retro-translated and adapted. The final version was revised to determine content validity and them, plus Cochin were applied to 10 healthy subjects (pilot study) with a variable educational level and in 16 rheumatic patients with variable diagnoses and degrees of hand function impairment; all patients answered 4 questionnaires and were evaluated clinically by blinded investigators., Results: Seventy six percent were women, mean age 45.7±11.4 years. Cronbach́s alpha >0.90; time to answer went from 2.3±0.087 (AUSCAN) to 3.5±0.36 minutes (DASH). There was good correlation among them (r=0.0683 AUSCAN-m-SACRAH to r=0.889 AUSCAN-DASH) and good capability for discrimination between patients with mild VS moderate to severe impairment was also demonstrated; patients with mild impairment needed less time to answer them and there were no significant differences among questionnaire scores. Patients prefered AUSCAN (10/16), Cochin (4/16) and m-SACRAH (2/16)., Conclusion: The 4 questionnaires are useful to evaluate hand function in rheumatic patients and have good discrimination capability. More patients preferred AUSCAN., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Unlabelled: Selecting the appropriate treatment decision is essential for achieving optimal results in the management of algo-dysfunctional syndrome of the temporo-mandibular joint (TMJD). The study aims to decide on the most effective (symptomatic control, preserved motility) kinetic program in patients with TMJ involvement., Material and Methods: prospective observational study on 83 consecutive patients with rheumatic diseases and TMJ dysfunction. Clinical assessment (pain, noises, muscle spasm, range of motion, ROM) was performed at baseline and after 3 months of specific kinetic rehabilitation program. Change in clinical parameters and TM3 index was reported, p<0.05., Results: over 45% TMJ involvement at baseline as defined by TMJ index (mean value of 13.56) and only 36.66% at 3 months (p<0.05). Significant improvement in pain (presence, severity) was demonstrated at 3 moths (p<0.05): 18.05% spontaneous pain, 75.9% provoked pain, with 12.11% respectively 2.41% decreased in nocturnal respectively diurnal pain. Significant decrease (p<0.05) in joint noises at movements: 27.71% when opening and 12.04% when closing the mouth, 8.43 at protrusion and 3.61% at retraction, while 18% at the side movements., Conclusions: Complex accurate kinetic reeducation is mandatory for achieving correct posture (head, neck and trunk), normal mastication, swallowing and respiration, as well as correction of neuromuscular imbalances in patients with TMJD secondary to rheumatic disorders.

Objective: Chronic conditions can lead to considerable deterioration in functioning. Several condition-specific Core Sets, selections of categories from the International Classification of Functioning, Disability and Health (ICF), have been developed to facilitate the rehabilitation process. Considering the increase in patients with more than one specific condition, we evaluated the impact of multimorbidity on functioning and the implications for the Core Set approach., Design: Internet survey., Subjects: A total of 127 people with a rheumatic disease and 707 people with rheumatic disease and multimorbidity were included., Methods: Self-report information on chronic conditions and perceived functioning using the IMPACT-S (ICF Measure of Participitation and Activities Screener) questionnaire, measuring the ICF component activities and participation (32 items)., Results: The mean number of reported serious limitations/restrictions was 5.6 (standard deviation (SD) 5.7) for respondents with rheumatic disease and 6.7 (SD 6.8) for respondents with rheumatic disease and multimorbidity (p < 0.05). Seventeen items were relevant (more than 20% of the respondents reported serious limitations/restrictions) for individuals with rheumatic disease and multimorbidity, and 12 items were relevant for individuals with rheumatic disease only., Conclusion: Multimorbidity seriously aggravates the already existing functioning problems of people with rheumatic disease. We recommend that in the ICF Core Set approach more emphasis is given to systematic empirical analysis of the impact of multimorbidity on functioning.

In rheumatic and other chronic inflammatory diseases, high amounts of energy for the activated immune system have to be provided and allocated by energy metabolism. In recent time many new insights have been gained into the control of the immune response through metabolic signals. Activation of immune cells as well as reduced nutrient supply and hypoxia in inflamed tissues cause stimulation of glycolysis and other cellular metabolic pathways. However, persistent cellular metabolic signals can promote ongoing chronic inflammation and loss of immune tolerance. On the organism level, the neuroendocrine immune response of the hypothalamic-pituitary adrenal axis and sympathetic nervous system, which is meant to overcome a transient inflammatory episode, can lead to metabolic disease sequelae if chronically activated. We conclude that, on cellular and organism levels, a prolonged energy appeal reaction is an important factor of chronic inflammatory disease etiology.

Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.

We introduce a method for extracting hidden patterns seen in rheumatic diseases by using articles from the widely used biomedical database MEDLINE. Rheumatic diseases affect hundreds of millions of people worldwide and lead to substantial loss of functioning and mobility. Diagnosing rheumatic diseases can be difficult because some symptoms are common to many of them. We use Facta system as a biomedical text mining tool for finding symptoms and then create a dataset with the frequencies of symptoms for each disease and apply hierarchical clustering analysis to find similarities between diseases. Clustering analysis yields four distinct types or groups of rheumatic diseases. Although our results cannot remove all the uncertainty for the diagnosis of rheumatic diseases, we believe they can contribute to the diagnosis of rheumatic diseases to a certain extent. We hope that some similarities exposed can provide additional information at the stage of decision-making.

Introduction: Empowerment is a central concept in both rheumatology and diabetes care. A Swedish empowerment instrument for patients with rheumatic diseases has not been created before now. The aim of the present study was to determine the psychometric properties of the Swedish Rheumatic Disease Empowerment Scale, SWE-RES-23, such as construct validity, internal consistency reliability, inter-item correlations and discriminant validity., Methods: The already existing instrument, the Swedish Diabetes Empowerment Scale (SWE-DES-23), was adapted for use in patients with rheumatic diseases. The adapted instrument was called the SWE-RES-23. In 2009, 260 patients with rheumatic diseases from a rheumatology unit in Sweden completed the instrument. Construct validity was tested by using exploratory factor analysis. Internal consistency reliability was tested by the use of Cronbach's α-coefficient. In order to determine unidimensionality of the empowerment subscales, inter-item correlations were calculated. To establish discriminant validity, an item about self-perceived health from the Short Form (SF) 36 was used in addition to the SWE-RES-23., Results: The exploratory factor analysis resulted in five factors (empowerment subscales) with eigenvalues >1, explaining 64.1% of the total variance: Goal achievement and overcoming barriers to goal achievement; Self-knowledge; Managing stress; Assessing dissatisfaction and readiness to change; and Support for caring. Cronbach's α values ranged from 0.59 to 0.91, and the value for the total score was 0.92., Conclusion: The results support the possibility of adapting the SWE-DES-23 for use in patients with rheumatic diseases. The SWE-RES-23 shows acceptable psychometric properties, in terms of construct validity and internal consistency reliability. To validate the SWE-RES-23 fully, further studies are needed, with a focus on test-retest correlations., (Copyright © 2012 John Wiley & Sons, Ltd.)

Because of its substantial personal social and economic costs, workforce participation among individuals with rheumatic diseases has received considerable research attention. This chapter reviews non-pharmacological employment interventions for people with rheumatic diseases, focussing on the comprehensiveness of interventions, whether they have been targeted to those groups identified as most at risk, and intervention outcomes and effectiveness. Findings highlight that early diagnosis and treatment of rheumatic diseases may not be enough to keep individuals employed and that comprehensive work interventions may have positive psychological effects, as well as result in increased work participation. However, we lack data addressing the optimum time to intervene and subgroup analyses to determine whether some groups are at increased risk for poor work outcomes. Consistent inclusion of behavioural and psychological outcomes to evaluate interventions and compare studies is also needed, along with cost-benefit studies, to determine the long-term feasibility of work interventions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To investigate the lag structure effects from exposure to atmospheric pollution in acute outbursts in hospital admissions of paediatric rheumatic diseases (PRDs)., Methods: Morbidity data were obtained from the Brazilian Hospital Information System in seven consecutive years, including admissions due to seven PRDs (juvenile idiopathic arthritis, systemic lupus erythematosus, dermatomyositis, Henoch-Schönlein purpura, polyarteritis nodosa, systemic sclerosis and ankylosing spondylitis). Cases with secondary diagnosis of respiratory diseases were excluded. Daily concentrations of inhaled particulate matter (PM(10)), sulphur dioxide (SO(2)) nitrogen dioxide (NO(2)), ozone (O(3)) and carbon monoxide (CO) were evaluated. Generalized linear Poisson regression models controlling for short-term trend, seasonality, holidays, temperature and humidity were used. Lag structures and magnitude of air pollutants' effects were adopted to estimate restricted polynomial distributed lag models., Results: The total number of admissions due to acute outbursts PRD was 1,821. The SO(2) interquartile range (7.79 µg/m(3)) was associated with an increase of 1.98% (confidence interval 0.25-3.69) in the number of hospital admissions due to outcome studied after 14 days of exposure. This effect was maintained until day 17. Of note, the other pollutants, with the exception of O(3), showed an increase in the number of hospital admissions from the second week., Conclusion: This study is the first to demonstrate a delayed association between SO(2) and PRD outburst, suggesting that oxidative stress reaction could trigger the inflammation of these diseases.

TNFα is a cytokine that is central to the pathogenesis of several autoimmune diseases. More specifically, the deleterious effects of TNFα in rheumatoid arthritis (RA) are well established. The proinflammatory influence of TNFα in RA is related both to direct effects mediated by the induction of other proinflammatory cytokines, metalloproteinases, and free radicals; and to modulation of the regulatory T cells (Tregs). Furthermore, the TNFα antagonists used to treat RA can induce the emergence of a distinctive Treg subpopulation. Nevertheless, a recent body of data suggests that TNFα may also exert anti-inflammatory effects, which may be mediated in part via Tregs. TNFα binds to the TNF receptor 2 expressed preferentially at the Treg surface, thereby activating and promoting the development of Tregs. Data from patients with RA and more recent evidence obtained in the absence of disease are consistent with a paradoxical effect of TNFα on Tregs. TNFα may have different effects on naturally occurring Tregs and induced Tregs., (Copyright © 2011. Published by Elsevier SAS.)

In this study, we evaluated the relationship between enthesitis and clinical, laboratory and quality-of-life parameters in ankylosing spondylitis (AS) in Moroccan patients. Seventy-six patients were included in this cross-sectional study according to the modified New York criteria for AS. All patients had enthesitis involvement. Clinical and biological parameters were evaluated. Enthesitis were assessed by two indices: Mander Enthesis Index (MEI) and Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). Disease activity was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional impact was assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). The quality of life was measured by the Short form-36 (SF-36). Severity of enthesitis was significantly correlated with disease activity, functional disability and degradation of quality of life. There was no relation between enthesitis indices and disease duration or laboratory parameters. The clinical assessment of enthesitis in AS is an important outcome measure, and enthesitis indices could be used to evaluate disease activity in patients with AS.

Objective: To examine the factor structure and convergent validity of the Illness Intrusiveness Scale--Parent Version in mother and fathers of children and adolescents ages 7 to 18 (M = 13.56 years, SD = 2.67) diagnosed with a juvenile rheumatic disease., Design: Parents of 122 children and adolescents (82 girls, 40 boys) completed the Illness Intrusiveness Scale-Parent Version, and both parents and children and adolescents completed measures of functional disability, general distress, and illness uncertainty. An exploratory factor analysis was conducted on the Illness Intrusiveness Scale--Parent Version to identify the factor structure. The factors were then compared with parent- and child-report measures of functional disability, general distress, and uncertainty. Finally, analyses were conducted to determine whether the magnitude of the correlations was significantly different between factors for parents and children and adolescents., Results: The Illness Intrusiveness Scale--Parent Version was found to have a two-factor structure. The Relationships/Personal Development factor contained items related to self-fulfillment and interactions with others, and the Instrumental factor contained items related to health and work. These factors were found to have good internal consistency and were significantly correlated with measures of parent-reported functional disability and parent- and youth-reported distress and uncertainty. The magnitude of these correlations was also found to differ depending on informant and outcome measure., Conclusion: The Illness Intrusiveness Scale--Parent Version appears to be a valid measure for use in parents of children with juvenile rheumatic disease.

The management of rheumatoid arthritis (RA) depends more on the patient history than most other chronic diseases. A patient questionnaire provides a uniform, quantitative, protocolized, "scientific" patient history, with documented prognostic significance for work disability and mortality in RA greater than radiographs and laboratory tests and capacity to distinguish active from control treatment in clinical trials and to monitor clinical care with equivalent or greater significance than joint counts or laboratory tests. Therefore, a "scientific" approach to care of a person with a rheumatic disease involves review of patient function, pain, global status, fatigue, RAPID3, review of systems, self-report joint count, and recent medical history on an MDHAQ before conversation with the patient. This practice may be viewed as analogous to a doctor reviewing blood pressure, hemoglobin A1c, viral load, or radiograph before meeting with a patient who has hypertension, diabetes, HIV, or a healing fracture to provide a roadmap or agenda for the visit. Some sites have implemented RAPID3 without the remainder of MDHAQ, a practice that is discouraged. The MDHAQ requires only 5 to 10 minutes of the patient's time and involves a single sheet of paper, which is needed for a simple RAPID3, or even a patient global estimate of status to score a DAS28 or CDAI. Completion of MDHAQ/RAPID3 by each patient at each visit in the infrastructure of care with review by the doctor helps prepare the patient for the visit, improves doctor-patient communication, saves time for the doctor, and provides a roadmap or agenda for the visit.

Objective: To analyze the attainment of inactive disease following initiation of tumor necrosis factor-α (TNF-α) inhibitors in a heterogeneous cohort of children with juvenile idiopathic arthritis (JIA)., Methods: We performed retrospective chart review of all children with JIA at 1 academic center who had started TNF-α inhibitor therapy. We retrospectively determined inactive disease status according to the 2004 criteria of Wallace, et al. We evaluated inactive disease status at 1 year after initiation of TNF-α inhibitor and attainment of inactive disease at any point during the study period. Predictors of inactive disease were determined using univariate analyses and multivariable logistic regression models., Results: A total of 125 patients started TNF-α inhibitors, and 88 patients had data available for the 1-year followup visit. Many patients (49%) started TNF-α inhibitors within 6 months of the diagnosis of JIA. Diverse JIA phenotypes were represented: at baseline, 29% of all patients had active enthesitis and only 23% had active polyarthritis. At the 1-year followup, 36 of 88 (41%) patients had inactive disease. Overall, 67 of 125 (54%) patients ever attained inactive disease status during the study period. In multivariable models, enthesitis-related arthritis (ERA) and higher Childhood Health Assessment Questionnaire (CHAQ) scores at baseline were independently associated with failure to later attain inactive disease status., Conclusion: Treatment with TNF-α inhibitors appears to be less effective for attaining inactive disease status in patients with ERA or higher baseline CHAQ scores. Further studies are needed regarding the clinical effectiveness of TNF-α inhibitor therapy and the optimal treatment of ERA.

Objective: To determine the current practice of UK rheumatologists regarding driving advice and intra-articular injection. A secondary objective was to clarify legal advice on driving after intra-articular injection., Methods: A link to an online questionnaire was sent out via the British Society of Rheumatology (BSR) monthly e-newsletter to all BSR members in January 2010. In addition, we contacted the Medical Defence union (MDU), Medical Protection Society (MPS), Driving and Vehicle Licensing Agency (DVLA) and insurance companies for statements regarding legal advice., Results: A total of 134 responses were obtained. These were collected on a web-based database. The majority of forms returned were from consultant rheumatologists. Fifty-six per cent of respondents said that they routinely asked patients about driving prior to joint injection. Seventy-six respondents (57%) considered driving to be an issue when injecting joints. If a patient had driven to clinic, 30% of respondents said that they would inject as normal, 28% opting to inject but ask the patient to wait following injection. Only 12% (16 respondents) said that they would not undertake an injection if the patient was driving. Sixty-one (46%) respondents did not run an injection clinic. Of those who did (71 respondents) 55% pre-warned patients not to drive., Conclusion: There is no clear consensus among rheumatologists as to practice regarding driving following an intra-articular injection. Medico-legally, there is no absolute bar to driving following an intra-articular injection, and guidance points to clinicians' own judgement as to the safety of driving., (Copyright © 2011 John Wiley & Sons, Ltd.)

Philip S. Hench, MD, the first Mayo Clinic rheumatologist, came to Mayo Clinic in 1921. Because of his efforts in patient care, education, and research, and those of his colleagues, Mayo Clinic has been considered the first academic rheumatology center established in the United States. An early, popular lecture he gave to the internal medicine residents was an important and unique part of the rheumatology education program and was entitled "Axiomatic Generalizations Useful in the Diagnosis of Rheumatic Diseases." We review the axioms in light of the status of rheumatology in the 1920s and 1930s when they were written, and assess their relevance today, 70 to 80 years later.

Objectives: To describe the clinical manifestations of rheumatic disorders with isolated head and neck (H&N) affection and to introduce a novel diagnostic pathway., Methods: From 2004 to 2010, 90 patients presented with isolated H&N symptoms of a rheumatic disorder were included in the study. Rheumatic disorders were classified according to the ACR criteria. In 2008, we introduced a novel diagnostic pathway to reduce under-diagnosis of primary rheumatic disorders in the H&N. Disease-related data were assessed retrospectively and set into clinical context., Results: The majority of patients suffered from SS (n = 42), granulomatosis with polyangiitis (Wegener's) (n = 13) and sarcoidosis (n = 18) with predominance for female patients (n = 65). Enlargement of the major salivary glands (n = 47), sicca symptoms (n = 41) and cervical lymphadenopathy (n = 25) represented the most frequent symptoms. Interestingly, 3% of all enlargements of salivary glands and 4% of all cervical lymphadenopathy could be contributed to rheumatic disorders. The mean time to diagnosis was 20.71 months for SS, 8.4 months for granulomatosis with polyangiitis and 57.5 months for sarcoidosis. After implementation of the newly developed diagnostic pathway in 2008, the annually diagnosed rheumatic disorders increased 5-fold., Conclusions: The majority of rheumatic diseases of the H&N can be related to SS, granulomatosis with polyangiitis and sarcoidosis. However, the lack of specific symptoms and the clinical variability of H&N manifestation may contribute to a prolonged time to diagnosis. Our retrospective study points out the variability of symptoms and suggests a diagnostic pathway to reduce the cases of undetected H&N affection in rheumatic disorders.

The purpose of this study was to investigate the relationship of ossification of posterior longitudinal ligament (OPLL) with enthesis, the site where the posterior longitudinal ligament (PLL) attaches to the vertebral body, by multi-detector CT reconstruction images. Twenty-nine patients with OPLL were studied. According to the plaques' continuity to the vertebral body, OPLL plaques were classified into two categories: "free" and "contiguous". A "broken sign" was defined as a crack between two plaques. The sites where each "contiguous" plaque attached to the vertebral body were then analysed. There were 78 ossified plaques in total, and six were "free". There were eight cases with a "broken sign", including six "free" ones. The site where all 72 "contiguous" plaques attached to the vertebral body included the zone where the PLL enthesis was situated, while other zones were included in only part of the plaques. Our conclusion was that there might be no real "free type" ossified plaques, and OPLL could start from enthesis, which indicated OPLL could be a kind of enthesopathy.

It is well known that infection is one of the major causes of morbidity and mortality in rheumatic disease patients treated with high-dose glucocorticoids, especially in the early phase after achievement of disease remission. The aim of this study was to identify the risk factors for infection, with a focus on the dose of glucocorticoids administered, following the achievement of disease remission in rheumatic diseases patients. We retrospectively analyzed the medical records of rheumatic disease patients who had been treated with glucocorticoids. The primary endpoint was the incidence rate of infection during a period from 1 to 2 months after the commencement of treatment. From April 2006 to March 2010, 19 of 92 patients suffered from infection during the observation period. Age ≧ 65 yrs, presence of interstitial pneumonia, diagnosis of systemic vasculitis and serum creatinine level ≧ 2.0 mg/dl were found to be univariate predictors for infection. However, only the presence of interstitial pneumonia was an independent risk factor for infection (HR＝4.50, 95%CI＝1.65 to 14.44) by the Cox proportional hazard model. Even after achievement of clinical remission, careful observation is needed for patients with interstitial pneumonia, more so than for those receiving high-dose glucocorticoids.

Objective: To provide information regarding the (1) responsiveness and reliability of different outcome measures used with persons who have impairments in upper extremity function and (2) their content validity based on the International Classification of Functioning, Disability, and Health (ICF)., Data Sources: MEDLINE, CINAHL, PsycINFO, and EMBASE databases were systematically searched for studies on outcome measures used to evaluate upper extremity function; only studies written in English and published between July 1997 and July 2010 were considered., Study Selection: One investigator reviewed titles and abstracts of the identified studies to determine whether the studies met predefined eligibility criteria (eg, study design, age <18 years). Another investigator did the same for 70% of the studies., Data Extraction: All types of outcome measures in the included studies were extracted, and the information retrieved from these outcome measures was linked to the ICF by 2 independent investigators who used standardized linking rules. In addition, studies reporting the clinical responsiveness, interrater reliability, and test-retest reliability of the outcome measures were identified., Data Synthesis: From among the 894 studies that were included in this review, 17 most frequently used outcome measures in the different study populations were identified. Five were patient-reported outcome measures and 12 were clinical outcome measures. The outcome measures show large variability with regard to the areas of functioning and disability addressed. Reliability and responsiveness data are missing for a few outcome measures or for certain populations for which they have been used., Conclusion: This systematic review provides an overview of the outcome measures used to address functioning and disability as they are related to the upper extremity. The results of this study may help clinicians and researchers select the most appropriate outcome measure for their clinical population or research question according to ICF-based content validity, and additional information on the reliability and responsiveness of the measures is provided. Our findings also can provide directions for further research., (Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

The glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, mediates most of the known biologic effects of glucocorticoids. The human GR gene consists of 9 exons and expresses 2 alternative splicing isoforms, the GRα and GRβ. GRα is the classic receptor that binds to glucocorticoids and mediates most of the known actions of glucocorticoids, while GRβ does not bind to these hormones and exerts a dominant negative effect upon the GRα-induced transcriptional activity. Each of the two GR splice isoforms has 8 translational variants with specific transcriptional activity and tissue distribution. GRα consists of three subdomains, translocates from the cytoplasm into the nucleus upon binding to glucocorticoids, and regulates the transcriptional activity of numerous glucocorticoid-responsive genes either by binding to its cognate DNA sequences or by interacting with other transcription factors. In addition to these genomic actions, the GR also exerts rapid, non-genomic effects, which are possibly mediated by membrane-localised receptors or by translocation into the mitochondria. All these actions of the GR appear to play an important role in the regulation of the immune system. Specifically, the splicing variant GRβ may be involved in the pathogenesis of rheumatic diseases, while the circadian regulation of the GR activity via acetylation by the Clock transcription factor may have therapeutic implications for the preferential timing of glucocorticoid administration in autoimmune inflammatory disorders.

Inflammatory rheumatic disorders are related to different pathophysiological mechanisms and, hence, their therapeutic management varies according to the underlying disease. Crystal-induced arthritis is characterized by its almost specific responsiveness to colchicine. Regarding ankylosing spondylitis, non steroidal anti-inflammatory drugs (NSAIDs) and TNF blockers are the cornerstones of pharmacological intervention whereas oral corticosteroids at conventional doses are of little value, if any. Conversely, corticosteroids are the drug of choice to treat polymyalgia rheumatica. Furthermore, low-dose corticosteroids were shown to be more effective than NSAIDs in patients with rheumatoid arthritis (RA). However, the main goal being to achieve remission, disease-modifying antirheumatic drugs, either synthetic, especially methotrexate, and/or biologic, such as TNF inhibitors, have a major role in the management of RA. Finally, enhanced understanding of molecular pathogenesis of inflammatory disorders may help to find out how to best target available drugs to right individuals in the future., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

Since pediatric rheumatology diseases are rare, multicenter and even international collaboration is necessary to perform meaningful research. Multicenter research can enable rapid enrollment of sufficient numbers of patients for studies of epidemiology, diagnostic and classification criteria, genetic disease predisposition, pathogenesis, outcome and treatment protocols. In the last 20 years the vision of few has become a reality of collaboration of several hundred centers around the world in pediatric rheumatology research. In this paper we will describe the evolution of this international collaboration and important research findings that resulted from key international studies on the major pediatric rheumatology diseases.

Important advances in our understanding of the relationships between adipokines, inflammation and the immune response have been achieved in the past 10 years. White adipose tissue has emerged as a highly dynamic organ that releases a plethora of immune and inflammatory mediators that are involved in numerous diseases, including not only rheumatic diseases such as rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus, but also cardiovascular and metabolic complications that are frequently observed in rheumatic diseases. Our rapidly growing knowledge of adipokine biology is revealing the complexity of these amazing proteins, thereby redefining white adipose tissue as a key element of the inflammatory and immune response in rheumatic diseases. Adipokines exert potent modulatory actions on target tissues and cells involved in rheumatic disease, including cartilage, synovium, bone and various immune cells. In this Review, we describe the most recent advances in adipokine research in the context of rheumatic diseases, focusing primarily on leptin, adiponectin, visfatin and resistin, and also the potential role of newly identified adipokines such as chemerin, lipocalin 2 and serum amyloid A3.

Rheumatologic and autoimmune diseases are among foremost diseases for which patients seek complementary and integrative medicine options. Therefore, physicians should be informed on the advances in research of these therapies, in order to be able to discuss possible indications and contraindications for these treatment modalities with their patients. This review summarizes several therapeutic modalities of complementary medicine that may be involved in the cholinergic anti-inflammatory pathway. The analysis of systematic reviews of acupuncture for rheumatic conditions has concluded that the evidence is sufficiently sound to warrant positive recommendations of this therapy for osteoarthritis, low back pain and lateral elbow pain. There is relatively strong evidence to support the use of hypnosis in pain treatment, such as in cases of fibromyalgia. A recent controlled study that evaLuated tai-chi in fibromyalgia has reported reductions in pain, improvements in mood, quality of Life, self efficacy and exercise capacity. There is also cumulative evidence that acupuncture, hypnosis and tai-chi may decrease the high frequency of heart rate variability, suggesting enhancement of vagus nerve activity. Hence, it has been hypothesized that these modalities might impact the cholinergic anti-inflammatory pathway to modulate inflammation. Further clinical and basic research to confirm this hypothesis should be performed in order to validate integration of these therapies in comprehensive treatment for some inflammatory and autoimmune diseases.

Rheumatic diseases comprise a heterogeneous group of highly prevalent, usually chronic and progressively disabling disorders associated with poor patient quality of life and high healthcare resource utilization. The pain associated with these degenerative or inflammatory conditions represent some of the most important and complex problems of modern medicine, demanding an increasingly attentive, multidisciplinary, and continuous therapeutic approach. Extra-articular syndromes, notably fibromyalgia, can be a lifelong rheumatic condition characterized by widespread musculoskeletal pain and functional impairment, without any known structural or inflammatory cause. Irritable bowel syndrome (IBS) occurs in around half of patients with fibromyalgia raising the possibility of a possible overlapping or underlying pathophysiology. The dysfunction of bidirectional neural pathways and viscerovisceral cross-interactions within the central nervous system has been proposed as a possible central hypersensitization disorder responsible for the extraintestinal manifestations of IBS. Common inflammatory and molecular pathways may also be present in which a dysregulation of the immune system leads to a chronic inflammatory response. Given that the treatment of degenerative chronic pain remains suboptimal, these findings may suggest new treatment strategies.

Objective: To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables., Methods: A total of 81 IBD patients [55 Crohn's disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls., Results: Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability)., Conclusions: US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

Pulmonary involvement is a common complication of vasculitides, especially small vessel vasculitides. This review provides an overview of vasculitic manifestations of the lung as well as of other organs involved in vasculitides. Furthermore, it provides the diagnostic procedures required to asses a patient with vasculitic lung involvement and gives an overview of current treatment strategies.

Circadian rhythms play an important role in the function of the body. Among others, the activity of the immune system is subject to daily variability which explains the different intensity of rheumatic symptoms during the day (e.g. morning stiffness). Circadian rhythms are subject to continuous adaptation via external time signals (zeitgebers), such as light-dark periods, time of food intake, as well as daily activity and resting periods. Following an acute phase shift of these external zeitgebers, e.g. via transmeridian travel (east-west or west-east), the body has to adjust all circadian systems to these new circumstances during an adjustment response, which lasts for several days. The classical symptoms of jet lag, such as tiredness during the day, mood swings and cognitive malfunction occur during this adjustment period. The impact of acute phase shifts as a result of transmeridian travel in subjects with rheumatic disorders, as well as strategies to prevent jet lag will be discussed in the following article.

Approximately 40 million Germans travel abroad every year. Air travel is the most frequently used mean of transportation followed by the automobile. During airplane flights rheumatic patients are subjected to numerous physical, biological and climatic factors which can cause stress and adverse effects on general health. Therefore, preventive strategies are helpful to protect against health damage, provided that there is general fitness for air travel. The present article focuses on physical and biological stress as well as psychological aspects during air travel and reviews prophylactic measures.

The objectives of this study are to assess: (a) the prevalence of vitamin D deficiency among new patients attending rheumatology outpatient departments, (b) the age profile of these low vitamin D patients and (c) whether any diagnostic category had a particularly high number of vitamin D-deficient patients. All new patients seen consecutively in general rheumatology clinics between January to June 2007 inclusive were eligible to partake in this study, and 231 out of 264 consented to do so. Parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium, phosphate, albumin and alkaline phosphatase levels were measured. We defined vitamin D deficiency as ≤53 nmol/l and severe deficiency as ≤25 nmol/l. Overall, 70% of 231 patients had vitamin D deficiency, and 26% had severe deficiency. Sixty-five percent of patients aged ≥65 and 78% of patients aged ≤30 years had low vitamin D levels. Vitamin D deficiency in each diagnostic category was as follows: (a) inflammatory joint diseases/connective tissue diseases (IJD/CTD), 69%; (b) soft tissue rheumatism, 77%; (c) osteoarthritis, 62%; (d) non-specific musculoskeletal back pain, 75% and (e) osteoporosis, 71%. Seasonal variation of vitamin D levels was noted in all diagnostic groups apart from IJD/CTD group, where the degree of vitamin D deficiency persisted from late winter to peak summer. Very high prevalence of vitamin D deficiency was noted in all diagnostic categories (p = 0.006), and it was independent of age (p = 0.297). The results suggest vitamin D deficiency as a possible modifiable risk factor in different rheumatologic conditions, and its role in IJD/CTD warrants further attention.

Purpose of Review: Whereas antimalarials have been in use to treat rheumatic disease for over 50 years, their exact mechanism of action remains unclear. Over the past decade, new theories have been proposed in this regard both for rheumatic disease, as well as related conditions., Recent Findings: Whereas the classical explanation was an impairment of phago/lysosomal function, antimalarials also appear to have an impact through inhibition of intracellular toll-like receptors (TLRs), particularly TLR9. This may mediate its effect on lupus, rheumatoid arthritis, as well as ancillary conditions including diabetes and hyperlipidemia. The potential role for antimalarials in antiphospholipid syndrome also appears clearer, with an effect proposed through Annexin5 binding., Summary: Despite their established clinical utility, the mode of action for antimalarials remains uncertain despite recent advances and still requires further investigation. By better understanding how antimalarials function, their optimal use in the clinical setting can be ensured.

Measurement of serum C-reactive protein (CRP) level is in widespread clinical use as a sensitive marker of inflammation. CRP has a role in the clearance of bacteria and of dying and altered cells, and might also have more complex immunomodulatory functions. Impaired clearance of apoptotic cells is important in the pathogenesis of systemic lupus erythematosus (SLE), raising the possibility that CRP dysregulation plays a part in this process. We review the available functional and genetic evidence supporting a role for CRP in the pathogenesis of SLE, but recognize that inconsistencies in the existing data mean that conclusions have to be interpreted with caution. More consistent is the evidence that the genetic variants influencing basal CRP level also influence the magnitude of the acute-phase rise in CRP level in active inflammation. Initial reports suggest that these genetic effects might be large enough to directly influence clinical decision-making processes that are based on an interpretation of CRP thresholds. This concept is explored further in this article, particularly in relation to the use of the CRP-based disease activity score in the evaluation of rheumatoid arthritis, where a systematic under-scoring or over-scoring of disease activity could result from a failure to consider the genetic influences on CRP level.

This review focuses on several basic mechanisms of allergy and when a rheumatologist should consider an external agent as being responsible for seemingly 'rheumatic' manifestations. Typical allergic diseases are discussed in order to help the physician to recognise them. In addition, allergic aspects and adverse drug reactions of antirheumatic drugs and biopharmaceutical agent therapies will be discussed.

Objective: To explore how intimate relationships and sexuality are influenced by rheumatic diseases and to describe self-management strategies used to manage disease consequences., Methods: To ensure that data were grounded in patients' language and experiences, individual and focus group interviews were conducted. Purposeful sampling was used to ensure variation in age, sex, disease duration, diagnosis, and marital status among the informants. Participants were men and women ages 18 years or older, were diagnosed with inflammatory rheumatic disease by a rheumatologist, and had a disease duration of ≥2 years., Results: The mean age of the 23 participants was 44 years, the mean disease duration was 13.6 years, and the mean ± SD modified Health Assessment Questionnaire score was 1.58 ± 0.46. Four key themes summarized the main issues described by the informants: between disease and normality, relational aspects, disease-related sexual challenges, and self-management strategies. The results reveal that the disease constituted a disruption in life, requiring a new orientation of sexual identity and relationship. Participants' experiences of sexuality went beyond specific sexual activity, including aspects such as body image and relational issues, illustrating a multidimensional perception of sexuality. A large inter- and intrapersonal variety of impact and a wide range of management strategies were reported., Conclusion: This study shows that sexuality is a vital area of life for people living with arthritis. It is a source of physical pleasure and intimacy with their partner, but may cause anxiety and distress when affected by rheumatic disease. However, various self-management strategies are applied to enhance intimate relationships and sexual activity. Knowledge and openness concerning sexual issues need to be emphasized as part of the competence of health professionals and researchers., (Copyright © 2011 by the American College of Rheumatology.)

Objectives: To look for correlations among clinical, radiographic, and sonographic scores for enthesitis in patients with ankylosing spondylitis (AS)., Methods: Prospective study of 60 patients meeting modified New York criteria for AS. The clinical evaluation relied on the BASDAI, BASFI, and ASQoL and on a visual analog scale (VAS) for entheseal pain, as well as on two specific enthesitis indices, the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Radiographs and ultrasound scans were taken of five entheses on both sides (patellar insertion of the quadriceps tendon, proximal and distal insertions of the patellar tendon, and calcaneal insertions of the Achilles tendon and superficial plantar fascia). Ultrasound scans were obtained using a Philips HD 11™ machine with a high-frequency linear probe., Results: We studied 48 men and 12 women with a mean age of 36±11 years. The radiographic score correlated with the VAS pain score, BASDAI, and BASFI. The sonographic score for acute enthesitis correlated only with the MASES, and the sonographic score for chronic enthesitis correlated with none of the clinical scores. The Doppler score correlated with the VAS pain score, BASDAI, BASFI, and ASQoL. The overall sonographic score correlated with the MASES and SPARCC., Conclusion: Good correlations were found between the clinical and sonographic scores for enthesitis. The radiographic score seemed correlated with the general AS parameters rather than with the clinical scores. Larger studies are needed to better define the role for radiographs and sonography of the entheses in the diagnosis of AS and follow-up of treated AS patients., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

This review introduces/refreshes some basic histopathologic methods and findings of skeletal muscle biopsies with emphasis on those diseases commonly encountered in a rheumatologist's practice. The 3 general areas of myopathology discussed are metabolic myopathies, toxic myopathies, and inflammatory myopathies. The authors, neuropathologists, hope to provide in this article what they think are some commonalities and disease-specific methods in their pathologic workup as well as a practical approach to the collaboration that pathologists undertake with their rheumatology colleagues to come to a working diagnosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-β2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic effects. The official EULAR recommendations on the assessment and management of cardiovascular disease in arthritides have just been published, and similar recommendations in connective tissue diseases are to be developed soon., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Aim: To explore the relationship between muscle strength and bone density in patients with different rheumatic diseases and to examine whether inflammatory arthritis was more harmful for muscle strength and bone loss than degenerative joint diseases., Methods: The study included 361 men and women with a mean±standard deviation age of 60.5±11.4 years and different rheumatic conditions: regional syndromes, osteoarthritis of the hands, shoulders, knees, and hips, and inflammatory arthritis. Maximum voluntary back strength was measured by isometric dynamometry. Bone mineral density (BMD; g/cm2) of the lumbar spine, femoral neck, and distal radius was measured by dual-energy x-ray absorptiometry. Anthropometry and lifestyle characteristics were also assessed., Results: Back strength was lowest in patients with hand and shoulder osteoarthritis (20.0±17.9 kg), followed by patients with inflammatory arthritis (24.8±19.2 kg). Patients with inflammatory arthritis had the lowest BMD at the mid-radius (0.650±0.115 g/cm2) and femoral neck (0.873±0.137 g/cm2), while patients with hand and shoulder osteoarthritis had the lowest BMD at the mid-radius (0.660±0.101). In both sexes, muscle strength was significantly lower in patients who had lower BMD (T score<-1.0). Multiple regression analysis identified significant predictors of back strength to be spine BMD (P=0.024) and body mass index (P=0.004) in men and femoral neck BMD in women (P=0.004)., Conclusion: Muscle strength decline may be connected to bone loss in patients with rheumatic conditions, especially those with inflammatory joint diseases.

Persistent and disabling pain is the hallmark of osteoarthritis, rheumatoid arthritis, fibromyalgia, and various other rheumatologic conditions. However, disease severity (as measured by 'objective' indices such as those that employ radiography or serology) is only marginally related to patients' reports of pain severity, and pain-related presentation can differ widely between individuals with ostensibly similar conditions (for example, grade 4 osteoarthritis of the knee). Increasing evidence in support of the biopsychosocial model of pain suggests that cognitive and emotional processes are crucial contributors to inter-individual differences in the perception and impact of pain. This Review describes the growing body of literature relating depression and catastrophizing to the experience of pain and pain-related sequelae across a number of rheumatic diseases. Depression and catastrophizing are consistently associated with the reported severity of pain, sensitivity to pain, physical disability, poor treatment outcomes, and inflammatory disease activity, and potentially with early mortality. A variety of pathways, from cognitive to behavioral to neurophysiological, seem to mediate these deleterious effects. Collectively, depression and catastrophizing are critically important variables in understanding the experience of pain in patients with rheumatologic disorders. Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of a range of such conditions.

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.