Mechanisms and Mediators of Pain in Chronic Inflammatory Arthritis

Abstract Purpose of the review Pain in chronic inflammatory joint diseases is a common symptom reported by patients. Pain becomes of absolute clinical relevance especially when it becomes chronic, i.e., when it persists beyond normal healing times. As an operational definition, pain is defined chronic when it lasts for more than 3 months. This article aims to provide a review of the main mechanisms underlying pain in patients with chronic inflammatory joint diseases, discussing in particular their overlap. Recent findings While it may be intuitive how synovial inflammation or enthesitis are responsible for nociceptive pain, in clinical practice, it is common to find patients who continue to complain of symptoms despite optimal control of inflammation. In this kind of patients at the genesis of pain, there may be neuropathic or nociplastic mechanisms. Summary In the context of chronic inflammatory joint diseases, multiple mechanisms generally coexist behind chronic pain. It is the rheumatologist's task to identify the mechanisms of pain that go beyond the nociceptive mechanisms, to adopt appropriate therapeutic strategies, including avoiding overtreatment of patients with immunosuppressive drugs. In this sense, future research will have to be oriented to search for biomarkers of non-inflammatory pain in patients with chronic inflammatory joint diseases

Doppler ultrasound imaging techniques for assessment of synovial inflammation

We investigated the effect of ego depletion on risk taking. Specifically, we conducted three studies (total n= 1,716) to test the prediction that ego depletion results in decisions that are more strongly in line with prospect theory, i.e., that ego depletion reduces risk taking for gains, increases risk taking for losses, and increases loss aversion. Ego depletion was induced using two of the most common manipulations from previous literature: the letter e task (Studies 1 and 3) and the Stroop task (Study 2). Risk taking was measured using a series of standard, incentivized economic decision-making tasks assessing risk preferences in the gain domain, risk preferences in the loss domain, and loss aversion. None of the studies revealed a significant effect of ego depletion on risk taking. Our findings cast further doubts about the ability of ego-depletion manipulations to affect actual behavior in experimental settings.Funding Agencies|Swedish Research Council [2019-00849]; Marianne and Marcus Wallenberg Foundation [2014.0187]</p

Utility of a simplified ultrasound assessment to assess interstitial pulmonary fibrosis in connective tissue disorders - preliminary results

Interstitial pulmonary fibrosis (IPF) is a frequent manifestation in patients with connective tissue disorders (CTD). Recently the ultrasound (US) criterion validity for its assessment has been proposed; however, the US scoring systems adopted include the study of several lung intercostal spaces (LIS), which could be time-consuming in daily clinical practice. The aim of this study was to investigate the utility of a simplified US B-lines scoring system compared with both the US comprehensive assessment and the high-resolution computed tomography (HRCT) findings of IPF in CTD patients. METHODS:Thirty-six patients with a diagnosis of CTD were enrolled. Each patient underwent chest HRCT and lung US by an experienced radiologist and rheumatologist, respectively. Both comprehensive and simplified US B-lines assessments were scanned. The comprehensive US assessment was performed at 50 LIS level, whereas the simplified US assessment included bilaterally 14 LIS; for the anterior chest: the second LIS along the para-sternal lines, the fourth LIS along the mid-clavear, anterior axillary and mid-axillary lines; for the posterior chest: the eighth LIS along the paravertebral, sub-scapular and posterior axillary lines. For criterion validity, HRCT was considered the gold standard. Feasibility, inter and intra-observer reliability was also investigated. RESULTS: A highly significant correlation between comprehensive and simplified US assessment was found (P = 0.0001). A significant correlation was also found between the simplified US assessment and HRCT findings (P = 0.0006). Kappa values for the inter-observer simplified US assessment were in a range from 0.769 to 0.885, whereas the concordance correlation coefficient values for the intra-observer were from 0.856 to 0.955. There was a relevant difference in time spent on comprehensive (mean 23.3 ± SD 4.5 minutes) with respect to the simplified US assessment (mean 8.6 ± SD 1.4) (P < 0.00001). CONCLUSIONS:Our results provide a new working hypothesis in favor of the utility of a simplified US B-lines assessment as an adjunct method to assess IPF in patients with CTD

The Expanded Risk Score in Rheumatoid Arthritis: performance of a disease-specific calculator in comparison with the traditional prediction scores in the assessment of the 10-year risk of cardiovascular disease in patients with rheumatoid arthritis

The increased risk of cardiovascular disease has emerged as a major issue in patients with rheumatoid arthritis – it has been estimated that the cardiovascular disease burden in rheumatoid arthritis is comparable to that of diabetes mellitus

Personal non-commercial use only. The Journal of Rheumatology 1552

ABSTRACT. Objective. Vertebral fractures are a common complication of osteoporosis and may have a negative effect on health-related quality of life (HRQOL). We investigated the effect of prevalent vertebral fractures on HRQOL in patients with osteoporosis. Methods. A cross-sectional multicenter study was carried out among postmenopausal women with primary osteoporosis attending primary care centers and hospital outpatient clinics: 234 women with vertebral fractures and 244 asymptomatic women. Women with secondary osteoporosis or taking medications that affect bone metabolism were excluded. All patients were questioned using the miniOsteoporosis Quality of Life Questionnaire (mini-OQLQ), Medical Outcomes Study Short , and the EuroQuol-5D, after assessment of all clinical variables and anthropometric data. To assess comorbidity we used the Self-Administered Comorbidity Questionnaire (SCQ). Diagnosis of osteoporosis was confirmed in all patients by bone mineral density using dual energy x-ray absorptiometry. Radiographic evaluation was performed by a musculoskeletal radiologist. A total of 483 postmenopausal women, randomly matched for age out of 1579 healthy controls, were chosen to compare the SF-36 scores with respect to patients with and without vertebral fractures due to osteoporosis. A multivariable regression analysis was conducted to identify the strongest determinant for low HRQOL, adjusted for potential confounding variables such as comorbid conditions, education level, and psychosocial status. Results. The vertebral fracture group had significantly lower scores than patients without fractures and controls in all domains of the generic and specific questionnaires. Women with only 1 prevalent fracture had statistically significantly lower HRQOL scores than those without fractures on SF-36 measures of bodily pain, physical functioning, and role function physical (all p &lt; 0.01). HRQOL scores were lower in women with lumbar fractures compared with women with thoracic fractures only when the physical functioning and bodily pain dimensions approached statistical significance. Based on the multivariate analysis, the strongest determinant for low HRQOL was physical functioning (explained by number of vertebral fractures) followed by comorbidity score and age. Adjusted R 2 in the final model was 35.9%. Using the SF-36 summary scales, comorbid conditions predominantly affected either mental or physical health (p &lt; 0.0001). A significant correlation (p &lt; 0.0001) was found between total score on the mini-OQLQ and the mean SCQ comorbidity score. Conclusion MATERIALS AND METHODS Recruitment of patients. In this cross-sectional multicenter study we investigated 478 postmenopausal women (mean age 68.5 yrs, range 48-89 yrs) with primary clinically stable osteoporosis (no change in treatment and no new clinical deformities in the last 12 mo) attending primary care centers and hospital outpatient clinics. The patient group included 234 women (mean age 69 yrs, range 48-89) who had vertebral fractures due to osteoporosis, and a group of 244 asymptomatic osteoporotic women matched for age with the patients with vertebral fractures. The women were screened in 5 rheumatology centers in Northern and Central Italy. A simple algorithm, the OPERA 23 , based on age, weight, history of previous low impact fracture, early menopause, and corticosteroid therapy, was used as a prescreening tool to help clinicians identify which women are at increased risk for osteoporosis. Diagnosis of osteoporosis was confirmed by bone mineral density (BMD) using dual-energy x-ray absorptiometry (DEXA). Osteoporosis was defined as a T score lower than -2.5 (the difference between the measured BMD and the mean value of young adults, expressed in standard deviations), according to the World Health Organization Study Group definition 24 . All measurements at the left femoral neck and lumbar spine (L1-L4), in the anteroposterior position, were obtained using the Hologic scanner (Hologic QDR 4500; Hologic, Bedford, MA, USA). One of the inevitable limitations of the study was the use of different densitometry machines, yielding noncomparable BMD data. Thus, machines at each participating center were cross-calibrated at the beginning of the study using the same spine phantom (supplied by the manufacturer). Each phantom was scanned 10 times at each study center. Quality control procedures were followed according to the manufacturer&apos;s recommendations. T scores were based on a large European and US reference database for BMD 25 . Radiographic evaluation was performed centrally (at the Department of Radiology of the Università Politecnica delle Marche) by an experienced musculoskeletal radiologist. Total spine radiographs in lateral standing views in neutral/flexion/extension and in the lateral decubitus position in flexion/extension were taken with a film-tube distance of 1.8 m. The anterior, central, and posterior heights of each of the vertebral bodies from T4 to L5 in a neutral standing radiograph were measured using calipers. Vertebral fracture was considered present if at least one of 3 height measurements (anterior, middle, posterior) of one vertebra had decreased by more than 20% compared with the height of the nearest uncompressed vertebral body Further, 483 postmenopausal women (mean age 69.1 yrs, range 50-87) randomly matched for age out of 1579 healthy controls were chosen for comparison of SF-36 scores of patients with and without vertebral fractures due to osteoporosis. Subjects with fibromyalgia, chronic back pain, and vertebral or other fractures were excluded. As acquisition of radiographs in the control group study was considered unethical in the context of the study, inclusion in this group depended on oral confirmation that the individual had never 1552 The received a clinical diagnosis of vertebral or other fracture. This sample was selected from a previous cross-sectional population-based study, the MAP-PING (MArche Pain Prevalence INvestigation Group) study Background and illness-related variables. Demographic and socioeconomic information was assessed from patient interviews. Education level was separated into 3 categories based on the Italian school system: 1 = primary school, 2 = secondary school, and 3 = high school or university. The body mass index (BMI, body weight/height 2 ) was used to assess overweight. In all patients the presence of comorbidities was also assessed through patient self-reports using the Self-Administered Comorbidity Questionnaire (SCQ) 28 , a modification of the widely used Charlson Index 29 . The SCQ uses patient interview or questionnaire responses rather than chart abstraction for assessment of comorbidity and is in excellent agreement with the chart-based Charlson Index 28 . We evaluated the rate of endorsement of each of 12 specific conditions as well as the number of conditions endorsed. We also calculated a score with 1 point if the condition was endorsed and additional points if the subject reported currently receiving treatment for it, or if it limited activities. Each condition could, therefore, contribute 0 to 3 points for a maximum of 36 points

Validation of the Italian version of the educational needs assessment tool in rheumatoid arthritis patients and factors associated with educational needs

The educational needs assessment tool (ENAT) is a seven-domain questionnaire assessing the educational needs (EN) of patients with rheumatoid arthritis (RA). The aim of this study was to validate the Italian version of the ENAT and to identify factors associated with EN in people with RA. The original English ENAT version was translated into Italian according to Beaton's method and subjected to Rasch analysis for validity testing. Socio-demographic and clinical variables were tested for associations with the ENAT domain scores using a multivariable linear regression model. The ENAT translated well into Italian and retained its construct validity. Some adjustments were needed when pooling the Italian and English datasets. The overall score of the ENAT had a high median: 82.8 (interquartile range (IQR): 57.5 to 100) i.e., 72.4% of the maximum score. The highest score was observed in the domain "Arthritis process" and the lowest was in "Support systems". Only gender was independently associated with EN (females having higher EN than males). The Italian ENAT is feasible for the use in the clinical setting and may help the health care practitioners to tailor educational interventions for RA patients. The characteristics of the patients, particularly female gender, may be associated with higher EN

Axial Spondyloarthritis: Reshape the Future—From the “2022 GISEA International Symposium”

The term &ldquo;axial spondyloarthritis&rdquo; (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium

Diffuse idiopathic skeletal hyperostosis: a review

Coined in 1975 by Resnick et al., diffuse idiopathic skeletal hyperostosis describes a systemic condition that is mainly characterized by flowing ossification of the spine and, less frequently, peripheral entheses. Its overall incidence is 6-12%, but it is more frequently observed in males than in females and subjects aged >50 years, and its increased prevalence in people aged >70 years suggests that the course of the disease begins between the third and fifth decade of life but its clinical manifestations do not appear until later. Its pathogenesis and etiology remain unknown, but it has been reported to be associated with a number of genetic, metabolic, and constitutional factors. The aim of this review is to describe the main features of the disease and stimulate research into its pathogenesis, prevention, and treatment