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

The Bias toward the Right Side of Others Is Stronger for Hands than for Feet

As shown by a series of previous studies, ambiguous human bodies performing unimanual or unipedal actions tend to be perceived more frequently as right-handed or right-footed rather than left-handed or left-footed, which indicates a perceptual and attentional bias toward the right side of others' body. However, none of such studies assessed whether the relative strength of such a bias differs between the upper and lower limbs. Indeed, given that the prevalence of right-handedness is slightly larger than that of right-footedness, and given that hands provide more information than feet as regards both communicative and aggressive acts, it is plausible that the bias toward the right side of human bodies should be stronger for the hand than for the foot. We performed three experiments in each of which participants had to indicate the rotating direction (revealing the perceived handedness/footedness) of ambiguous human figures with either one limb (arm or leg) or two limbs (one arm and the contralateral leg) extended. The hypothesized advantage of the right hand over the right foot was found in both the second and the third experiment

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study

Muscle echogenicity; Musculoskeletal ultrasound; Rheumatic diseasesEcogenicidad muscular; Ecografía musculoesquelética; Enfermedades reumáticasEcogenicitat muscular; Ecografia musculoesquelètica; Malalties reumàtiquesObjectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.RH and JH were supported by Ministry of Health, Czech Republic – conceptual development of research organization, Motol University Hospital, Prague, Czech Republic (00064203)

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study

ObjectivesTo investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases.MethodsForty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients.ResultsThe semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively).ConclusionThe results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases

The Bias toward the Right Side of Others Is Stronger for Hands than for Feet

As shown by a series of previous studies, ambiguous human bodies performing unimanual or unipedal actions tend to be perceived more frequently as right-handed or right-footed rather than left-handed or left-footed, which indicates a perceptual and attentional bias toward the right side of others’ body. However, none of such studies assessed whether the relative strength of such a bias differs between the upper and lower limbs. Indeed, given that the prevalence of right-handedness is slightly larger than that of right-footedness, and given that hands provide more information than feet as regards both communicative and aggressive acts, it is plausible that the bias toward the right side of human bodies should be stronger for the hand than for the foot. We performed three experiments in each of which participants had to indicate the rotating direction (revealing the perceived handedness/footedness) of ambiguous human figures with either one limb (arm or leg) or two limbs (one arm and the contralateral leg) extended. The hypothesized advantage of the right hand over the right foot was found in both the second and the third experiment

A deep learning approach to median nerve evaluation in ultrasound images of carpal tunnel inlet

Ultrasound (US) imaging is recognized as a useful support for Carpal Tunnel Syndrome (CTS) assessment through the evaluation of median nerve morphology. However, US is still far to be systematically adopted to evaluate this common entrapment neuropathy, due to US intrinsic challenges, such as its operator dependency and the lack of standard protocols. To support sonographers, the present study proposes a fully-automatic deep learning approach to median nerve segmentation from US images. We collected and annotated a dataset of 246 images acquired in clinical practice involving 103 rheumatic patients, regardless of anatomical variants (bifid nerve, closed vessels). We developed a Mask R-CNN with two additional transposed layers at segmentation head to accurately segment the median nerve directly on transverse US images. We calculated the cross-sectional area (CSA) of the predicted median nerve. Proposed model achieved good performances both in median nerve detection and segmentation: Precision (Prec), Recall (Rec), Mean Average Precision (mAP) and Dice Similarity Coefficient (DSC) values are 0.916 ± 0.245, 0.938 ± 0.233, 0.936 ± 0.235 and 0.868 ± 0.201, respectively. The CSA values measured on true positive predictions were comparable with the sonographer manual measurements with a mean absolute error (MAE) of 0.918 mm2. Experimental results showed the potential of proposed model, which identified and segmented the median nerve section in normal anatomy images, while still struggling when dealing with infrequent anatomical variants. Future research will expand the dataset including a wider spectrum of normal anatomy and pathology to support sonographers in daily practice

Ultrasound assessment of carpal tunnel in rheumatoid arthritis and idiopathic carpal tunnel syndrome

Objectives: To comparatively assess the sonographic spectrum of carpal tunnel syndrome (CTS) in patients with rheumatoid arthritis (RA) and in patients with idiopathic CTS. Methods: Fifty-seven RA patients and 25 idiopathic CTS patients were consecutively enrolled. The diagnosis of CTS in RA patients was made according to clinical history and examination. The following sonographic findings were assessed at carpal tunnel level: median nerve cross-sectional area (CSA) at the carpal tunnel proximal inlet, finger flexor tendons tenosynovitis, radio-carpal synovitis and intraneural power Doppler (PD) signal. Results: CTS was diagnosed in 15/57 RA patients (26.3%). Twenty-three RA wrists with CTS, 84 RA wrists without CTS and 34 idiopathic CTS wrists were evaluated. The average CSA of the median nerve was higher in idiopathic CTS than in RA wrists with CTS (17.7 mm2 vs 10.6 mm2, p < 0.01). A higher rate of inflammation of synovial structures (flexor tendons sheath and/or radio-carpal joint) was found in RA wrists with CTS compared with those without CTS (p = 0.04) and idiopathic CTS (p = 0.02). Intraneural PD signal was more common in CTS (in both RA and idiopathic CTS) wrists compared with wrists without CTS (p < 0.01). Conclusion: The sonographic spectrum of CTS in RA patients is characterized by an inflammatory pattern, defined by the presence of finger flexor tendons tenosynovitis and/or radio-carpal joint synovitis. Conversely, a marked median nerve swelling is the dominant feature in idiopathic CTS. Intraneural PD signal is a frequent finding in both conditions. Key Points • Carpal tunnel syndrome (CTS) associated with rheumatoid arthritis (RA) and idiopathic CTS have distinct ultrasound patterns. • The most characteristic sonographic features of CTS in RA patients are those indicative of synovial tissue inflammation at carpal tunnel level. Conversely, marked median nerve swelling is the dominant finding in idiopathic CTS. • Intraneural power Doppler signal is a frequent finding in both conditions. • In patients with CTS, differently from electrophysiology, US can provide clues prompting a rheumatology referral in case of prominent inflammatory findings at carpal tunnel level

Imaging of Joint and Soft Tissue Involvement in Systemic Lupus Erythematosus

none8noPurpose of review: To highlight the potential uses and applications of imaging in the assessment of the most common and relevant musculoskeletal (MSK) manifestations in systemic lupus erythematosus (SLE). Recent findings: Ultrasound (US) and magnetic resonance imaging (MRI) are accurate and sensitive in the assessment of inflammation and structural damage at the joint and soft tissue structures in patients with SLE. The US is particularly helpful for the detection of joint and/or tendon inflammation in patients with arthralgia but without clinical synovitis, and for the early identification of bone erosions. MRI plays a key role in the early diagnosis of osteonecrosis and in the assessment of muscle involvement (i.e., myositis and myopathy). Conventional radiography (CR) remains the traditional gold standard for the evaluation of structural damage in patients with joint involvement, and for the study of bone pathology. The diagnostic value of CR is affected by the poor sensitivity in demonstrating early structural changes at joint and soft tissue level. Computed tomography allows a detailed evaluation of bone damage. However, the inability to distinguish different soft tissues and the need for ionizing radiation limit its use to selected clinical circumstances. Nuclear imaging techniques are valuable resources in patients with suspected bone infection (i.e., osteomyelitis), especially when MRI is contraindicated. Finally, dual energy X-ray absorptiometry represents the imaging mainstay for the assessment and monitoring of bone status in patients with or at-risk of osteoporosis. Imaging provides relevant and valuable information in the assessment of MSK involvement in SLE.noneDi Matteo, Andrea; Smerilli, Gianluca; Cipolletta, Edoardo; Salaffi, Fausto; De Angelis, Rossella; Di Carlo, Marco; Filippucci, Emilio; Grassi, WalterDi Matteo, Andrea; Smerilli, Gianluca; Cipolletta, Edoardo; Salaffi, Fausto; De Angelis, Rossella; Di Carlo, Marco; Filippucci, Emilio; Grassi, Walte

Mild cognitive impairment in psoriatic arthritis: Prevalence and associated factors

To assess the prevalence and factors associated with mild cognitive impairment (MCI) in patients suffering from psoriatic arthritis (PsA).A cross-sectional evaluation was conducted in consecutive PsA patients. Sociodemographic data and the clinimetric variables related to PsA and psoriasis were collected for each patient. MCI was assessed through the Montreal Cognitive Assessment (MoCA). The cognitive performance of PsA patients was compared to healthy subjects using one-way analysis of variance (ANOVA). The correlations among variables were studied by the Spearman rank correlation coefficient. A multivariate logistic regression analysis was carried out to establish the predictors of MCI.The study involved 96 PsA patients and 48 healthy subjects. MCI (defined as a MoCA score < 26/30) was detected in 47 (48.9%) PsA patients. Compared to healthy subjects, the MoCA score resulted significantly lower in PsA patients (P = .015). The main differences involved the denomination and language domains. MoCA was negatively correlated with age (r = -0.354; P < .0001), HAQ-DI (r = -0.227; P = .026), and fatigue (r = -0.222; P = .029), and positively correlated with psoriasis duration (r = 0.316; P = .001) and DLQI (r = 0.226; P = .008).The multivariate logistic regression analysis revealed the duration of psoriasis (P = .0005), age (P = .0038), PASI (P = .0050), and HAQ-DI (P = .0193) as predictors of the MoCA score.MCI is present in a significant proportion of PsA patients, and is mainly determined by age, cutaneous variables, and disability

Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joints

Objective: To explore the spectrum of articular and peri-articular ultrasound (US) findings at metacarpophalangeal (MCP) joints in calcium pyrophosphate (CPP) deposition disease (CPPD). Methods: Consecutive CPPD patients (chronic CPP crystal inflammatory arthritis or osteoarthritis (OA) with CPPD), and age- and sex-matched controls with rheumatoid arthritis (RA) were prospectively enrolled. Patients underwent bilateral US examination of MCP joints. CPP deposits, synovial inflammation, osteophytes, cartilage damage, and bone erosions were recorded. Results: Sixty CPPD patients (33, 55.0% with osteoarthritis with CPPD and 27, 45.0% with chronic CPP crystal inflammatory arthritis) and 40 RA patients were enrolled. CPP deposits were detected in 24 (40.0%) CPPD patients and in 3 (7.5%) RA patients (p< 0.01). In CPPD patients, different types of CPP deposits were identified at MCP joints: 17 (28.3%) patients had dorsal capsuloligamentous deposits, 14 (23.3%) intra-cartilaginous deposits, 13 (21.7%) lateral capsuloligamentous deposits, 12 (20.0%) intra-articular deposits, 8 (13.3%) double contour sign, and 5 (8.3%) flexor digitorum tendons' deposits.CPPD patients with chronic CPP crystal inflammatory arthritis showed more US findings indicating synovial inflammation and CPP deposits than those with osteoarthritis with CPPD. Conversely, a higher prevalence of US features indicating structural damage was noted in this latter phenotype.CPP deposits and bone erosions were the US findings with the highest value for diagnosing chronic CPP crystal inflammatory arthritis and RA, respectively. Conclusion: This study provides pictorial evidence of the broad spectrum of US findings indicating CPP deposits at MCP joints in CPPD. Furthermore, we reported different US patterns in different CPPD phenotypes