Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

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

Objectives: 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.

The relationship between epicardial adipose tissue and arterial stiffness in patients with rheumatoid arthritis.

AIM: To evaluate the relationship between epicardial adipose tissue (EAT) and arterial stiffness (AS) in patients with rheumatoid arthritis (RA), considering cardiovascular risk factors and disease characteristics. MATERIAL AND METHODS: A total of 84 RA patients were included in this cross-sectional study. EAT and carotid intima-media thickness (cIMT) were measured ultrasonographically while aortic pulse wave velocity (aPWV), the main AS parameter, was determined using an oscillometric device. RESULTS: Mean duration of RA was 12±9.5 years and disease activity score was 4.3±1.4, as assessed by Disease Activity Score-28 using C-reactive protein (DAS-28 CRP). The correlation analysis displayed a significant positive correlation between cIMT, aPWV and EAT (r= 0.037, p<0.001; r= 0.338, p=0.002 and r= 0.317, p=0.003). When a cutoff value of aPWV ≥10 m/s was established, patients with increased aPWV had significantly higher body mass index (p=0.04), waist circumference (p=0.01), triglycerides (p=0.04), EAT (p<0.001), hypertension (p=0.03) and marginally C-reactive protein (CRP) (p=0.05). Multivariate regression analysis showed that hypertension (p=0.033), increased CRP (p=0.016) and EAT (p=0.005) are the only independent predictors for increased aPWV. CONCLUSIONS: Our study found that increased AS independently correlated with EAT in patients with RA. Although the evaluation of these two parameters awaits further evidence to be included in the risk algorithms for CVD prevention, their role in patients with inflammatory diseases may be even more significant than in the general population.

The role of ultrasonography in assessing disease activity in patients with rheumatoid arthritis and associated fibromyalgia.

AIM: The purpose of this study is to compare and correlate US evaluation with clinical scores of the disease activity in patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (FM). MATERIAL AND METHODS: Ten patients diagnosed with RA according to the 2010 ACR/EULAR classification criteria and associated FM based on the ACR 1990 classification criteria and two control groups, one with RA (10 patients) and one with FM (10 patients), were included. Clinical assessment was performed and the disease activity scores were calculated. Synovial/tenosynovial hypertrophy, fluid collections in grey scale (GS), and Power Doppler (PD) US assessed by US in the 28 joints included in the disease activity score 28 (DAS28). RESULTS: GS US score and PD US scores were correlated with DAS28 only in patients with RA (Pearson r coefficients 0.3 and 0.5). Mean DAS28 score was significantly higher in the RA/FM group, compared to RA and FM (5.6 versus 4.6 versus 4.5, respectively). Patients with RA/FM had similar median US scores to RA patients, while in FM group significantly lower median US scores were detected (16 versus 9.5 versus 0 for GS US and 3.5 versus 1.5 versus 0 for PD US, respectively). CONCLUSIONS: Disease activity scores should be interpreted with caution in patients with RA and FM. When available, US should be used to guide treatment decisions in patients with RA and FM.

The evolution of time-intensity curves of contrast enhanced ultrasonography in early arthritis patients with wrist involvement.

AIMS: The aim of the study was to assess the evolution of time-intensity curves parameters of contrast-enhanced ultrasonography (CEUS) after 6 months of conventional treatment in early arthritis patients with wrist involvement. MATERIAL AND METHODS: Patients diagnosed with early rheumatoid arthritis or undifferentiated arthritis on the basis of 2010 ACR/EULAR classification criteria, with bilateral wrist arthritis and both radiocarpal (RC) and intercarpal (IC) synovial hypertrophy identified by grey-scale ultrasonography, were enrolled. Synovial hypertrophy was semi-quantitatively scored (grade 0-3) by grey-scale and by Power Doppler at wrist level. CEUS was performed using Sonovue. The region of interest was selected as the area corresponding to the synovial hypertrophy of the RC and IC joints. Time-intensity curves parameters were calculated with Contrast Dynamic Software. The minimum and the maximum values of Peak, area under the curve (AUC), and slope were selected for each patient at baseline and after 6 months of conventional treatment. The difference between the visits was noted as "Δ". RESULTS: Eleven patients fulfilled the inclusion criteria. Maximum time-intensity curves parameters' difference significantly decreased at 6 months: Peak (30.00+/-5.90% vs 23.22+/-5.22%, p=0.008), AUC (1206.08+/-216.91%s vs 949.13+/-280.12%s, p=0.04) and slope (1.6 (1.4;2.3) %/s vs 1(0.7;1.2) %/s, p=0.03). Moderate correlations were found between maximum ΔPeak, maximum ΔAUC and maximum ΔPower Doppler grade (r=0.44, p=0.17; r=0.46, p=0.16, respectively). CONCLUSIONS: Peak and AUC for joints that had high baseline values significantly decreased following treatment with conventional synthetic drugs in EA patients with wrist arthritis. This decrease in Peak and AUC was moderately correlated with a decrease in US parameters. The joint with the highest values of these parameters may be used for evaluation of EA patients at follow-up.

Bone erosions in rheumatoid arthritis: ultrasound findings in the early stage of the disease.

OBJECTIVE: The objective of this study was to determine the prevalence and distribution of bone erosions detectable by US in patients with early RA (ERA) in comparison with long-standing RA (LSRA), other erosive diseases and healthy controls. METHODS: Thirty patients with ERA and 80 patients with LSRA were consecutively recruited. Thirty patients with PsA, 15 with primary OA, 10 with gout and 20 healthy subjects were included as controls. Bone erosions were investigated at the following anatomical sites: the second and fifth metacarpal heads, the ulnar head and the first and fifth metatarsal heads, bilaterally. Dorsal, volar and lateral aspects were explored on longitudinal and transverse views. RESULTS: At least one US bone erosion was found in 20 (66.7%) of 30 patients with ERA and in 10 (33%) of them it was found on the fifth metatarsal head. Bone erosions were most frequently found on the lateral quadrants of all scanned anatomical sites. If the second and fifth metacarpal heads and the fifth metatarsal head were scanned, an erosive disease could be found in 60% of ERA patients. The first metatarsal head was most frequently involved in the disease control group. CONCLUSION: This study found a high percentage of ERA patients with US bone erosions, with the fifth metatarsal head and the lateral aspects the most frequently involved site and quadrants. US scanning for bone erosions on a few target joints was found feasible and provided information not obtainable with clinical examination.

Ultrasound assessment for the rapid classification of early arthritis patients.

OBJECTIVE: The present study aimed to assess the role of ultrasound (US) in the rapid classification of early rheumatoid arthritis (RA) by investigating whether the US features of inflammation and bone damage in early arthritis overlap with the actual clinical concept of classifying and identifying an aggressive disease. METHODS: Patients with recent-onset arthritis of at least 1 peripheral joint of the hands and/or the feet were consecutively included in this study. Clinical examination, laboratory tests, the Disease Activity Score 28 (DAS28), and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA were assessed for all patients. Medication with disease-modifying antirheumatic drugs was recorded. Ultrasound assessment was performed at the following anatomical sites: wrists, metacarpophalangeal joints 2 to 5, and metatarsophalangeal joints 2 to 5 for assessing the presence/absence of synovial hypertrophy, the presence/absence of power Doppler signal, and the presence/absence of bone erosions.The US features of inflammation and bone damage were analyzed in comparison with the DAS28, with the presence/absence of rheumatoid factor and anti-cyclic citrullinated peptide, with the fulfillment of the new 2010 ACR/EULAR classification criteria, and with the initiated disease-modifying antirheumatic drug. The prescription of methotrexate was considered a marker of an aggressive disease. RESULTS: The US features of inflammation and bone damage correlated with the activity scores measured by the DAS28. The presence of US bone erosions overlapped with the presence of rheumatoid factor and anti-cyclic citrullinated antibodies. Synovial hypertrophy, intra-articular power Doppler signal, and bone erosions detected in at least 1 anatomical site were seen in patients fulfilling (77.7%) and in patients not fulfilling (72.7%) the 2010 ACR/EULAR classification criteria for RA. Synovial hypertrophy was found in at least 1 site in 83.3% and 58.8% of patients in whom methotrexate was prescribed and in whom methotrexate was not prescribed, respectively (P = 0.01). The US features were not correlated with the initiation of sulfasalazine or hydroxychloroquine. The patients presenting bone erosions received in significantly higher percentages the indication for methotrexate (50%) compared with sulfasalazine (20%), P = 0.03, or hydroxychloroquine (26%), P = 0.05. CONCLUSIONS: The US features of inflammation might be of help in classifying early arthritis patients despite the presence of the immune markers for RA. Together with the US features of bone damage, these might be used as an indicator of a more aggressive disease. The absence of correlation between the US findings of RA and the 2010 ACR/EULAR classification criteria indicates a possible independent contribution of US in the understanding of the future evolution of these patients.

How much difference does the age at onset make in early arthritis patients? Comparison between the ACR 1987 and the ACR/EULAR 2010 classification criteria for rheumatoid arthritis at the time of diagnosis.

The age at onset in early arthritis (EA) may influence the disease activity and its evolution. The aim of the current study is to identify possible differences regarding the "old" and the "new" classification criteria between patients with early-onset and late-onset early arthritis. The study included 64 patients. They were divided in two groups, according to the mean age: early-onset EA--less or equal than 45 years old (group A) and late-onset EA--over 45 years old (group B). The "old" criteria as well as the "new" ones were assessed for all patients, at the time of the first visit to the rheumatologist. The initiation of treatment with Methotrexate was used as "gold standard" to calculate the sensitivity and the specificity of both criteria. "New" criteria were fulfilled in 51% (A) and 72% of cases (B), while "old" criteria were fulfilled in 37% of patients (A) and 62% (B). Methotrexate was initiated in 82% of patients (B) and in 51% (A), p = 0.01. "New" criteria demonstrated a sensitivity of 77.7% (A) and 83.3% (B), while "old" criteria had a sensitivity of 50% (A) and 66.6% (B). Patients with late onset had significantly higher disease activity scores: 76% (B) versus 40% (A), p = 0.04. The sensitivity and the specificity of the "new" criteria for RA are comparable in patients with early-onset and late-onset EA, and the sensitivity of these criteria is increased compared to the "old" criteria. Patients with late onset fulfilling the "old" criteria had poor prognostic factors and higher disease activity at the time of diagnosis, which may have possible implications for the disease course.

"To be or not to be," ten years after: evidence for mixed connective tissue disease as a distinct entity.

OBJECTIVES: To determine if mixed connective tissue disease (MCTD) can be considered an independent clinical entity, to compare 3 different classification criteria for MCTD (Kasukawa, Alarcón-Segovia, and Sharp), and to define predictors (clinical features and autoantibodies) of potential evolution toward other connective tissue diseases (CTDs). METHODS: One hundred sixty-one MCTD patients were evaluated retrospectively at the diagnosis and in 2008. They were classified, at the diagnosis, according to the 3 classification criteria of MCTD (Sharp, Alarcón-Segovia, and Kasukawa) and reclassified in 2008 according to their evolution. Statistical analyses were performed to find out predictors (clinical features and autoantibodies) of evolution into other CTDs. RESULTS: After a mean of 7.9 years of disease, 57.9% of patients still satisfied MCTD classification criteria of Kasukawa; 17.3% evolved into systemic sclerosis, 9.1% into systemic lupus erythematosus, 2.5% into rheumatoid arthritis, 11.5% was reclassified as affected by undifferentiated connective tissue disease, and 1.7% as suffering from overlap syndrome. Kasukawa's criteria were more sensitive (75%) in comparison to those of Alarcón-Segovia (73%) and Sharp (42%). The presence of anti-DNA antibodies (P = 0.012) was associated with evolution into systemic lupus erythematosus; hypomotility or dilation of esophagus (P < 0.001); and sclerodactyly (P = 0.034) with evolution into systemic sclerosis. CONCLUSIONS: MCTD is a distinct clinical entity but it is evident that a subgroup of patients may evolve into another CTD during disease progression. Initial clinical features and autoantibodies can be useful to predict disease evolution.

Contrast-enhanced ultrasonography in inflammatory arthritis.

The degree of inflammation is the keystone of therapy management in rheumatoid arthritis and other arthritides. The assessment of synovial perfusion using power Doppler ultrasound is an important point in the quantification of the joint inflammation but it is limited by the subjectivity of the vascularization grading and incapacity to detect flows in very small vessels. Contrast agent improves the ultrasound ability to depict and quantify blood flows in synovitis. Contrast-enhanced ultrasonography (CEUS) better differentiates synovitis from collection and distinguishes the active synovitis from inactive fibrotic or necrotic pannus. Quantitative assessment of inflammation is possible analyzing the time-intesity curves and by the correct measurement of the synovial thickness. The additional informations and the diagnostic value of CEUS in arthritides are still controversial but its excellent imaging of synovial vessels open the way for further clinical applications. This review aims to discuss the actual knowledges of CEUS in inflammatory arthritis.

A rare case of primary tuberculous pyomyositis. Case report.

Tuberculosis involving the soft tissue as extending from adjacent bone or joint is well recognized. However, the primary tuberculous pyomyositis is rare. Due to atypical presentation the diagnosis is often delayed. We report one case of primary tuberculous pyomyositis of the thigh in an immunocompromised patient. Tuberculous myositis should be suspicioned, in immunocompromised patients with unexplained soft tissue swelling, especially in endemic area.

Musculoskeletal ultrasonography in Romania - results from a specific questionnaire.

UNLABELLED: Musculoskeletal ultrasonography (MSUS) is currently used in daily medical practice, as an extension of the clinical examination. The development of training programmes for MSUS has increased the interest of physicians from different specialties in performing this exploration. We realized a survey in order to describe the current practice of MSUS in Romania, as well as determining physicians' preferences for MSUS training implementation. METHODS: In 2010, 196 questionnaires were completed and returned at two congresses in Romania. RESULTS: Most of the participants were rheumatologists and radiologists, followed by physical medicine and rehabilitation doctors, internal medicine doctors, general practitioners and other specialists. 41% of respondents practice MSUS themselves. Doctors use MSUS as a diagnostic tool (95%) and for monitoring diseases (75%). Lack of training and lack of MSUS competence were the main reasons for not performing MSUS. The respondents expressed their preference for future training to be via a programme of regular, intensive courses and active participation in clinics where MSUS is performed. Most of the participants consider mentoring the assessement method of choice. CONCLUSION: The majority of participants in this survey use MSUS in the management of their patients. The results indicate participants' preferences on how training should be delivered in the future.

Gray scale and power Doppler ultrasonography in evaluation of early rheumatoid arthritis.

INTRODUCTION: Ultrasonography provides information regarding synovial membrane proliferation and its vascularization. The AIM of our study was to evaluate the role of gray scale and power Doppler ultrasonography in assessing early rheumatoid arthritis by analyzing the scores determined by the evaluation of synovial proliferation, joint effusion, erosion or soft tissue swelling. MATERIAL AND METHODS: The study was prospective comprising 34 patients (31 female, 3 men), mean age 45.68 years, with clinical changes and biochemical early rheumatoid arthritis. Bilateral wrist, II-V metacarpophalangeal, and proximal interphalangeal joints were evaluated by dorsal and palmar scans. RESULTS: The mean duration from the onset of symptoms was 3.46 months. Based on the clinical, biochemical and US scores the patients from our study presented early stages of RA. Also, statistically significant correlations were observed between the time elapsed from the onset, the changes highlighted by ultrasound and the stage of the disease (stage 0 or 1). CONCLUSIONS: Our study confirms that US evaluation of changes in the joints of the hand offers useful information for staging the diagnosis of RA.

Hyperimmunoglobulin E syndrome (Job's syndrome).

Hyperimmunoglobulin E (Hyper IgE) syndrome, also described as Job's syndrome, is a rare primary immunodeficiency disease characterized by recurrent skin and respiratory tract infections, chronic eczematous dermatitis, skeletal abnormalities associated with markedly elevated serum IgE levels. Variable impaired T cell function is described in this disease, but no direct association between IgE levels or clinical manifestations with these abnormalities does exist. We report a case of a patient with recurrent staphylococcal cold abscesses, eczematous dermatitis and high serum IgE levels in which the treatment with Cyclosporine A seems to have a favorable effect.