Carlo Alberto Scirè

Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Doppler signal predicts short-term relapse

OBJECTIVES This study aimed to evaluate the usefulness of a systematic musculoskeletal ultrasonographic (US) assessment in the detection of residual disease activity in patients with early RA who achieved clinical remission. METHODS We prospectively studied 106 early RA patients receiving conventional DMARDs according to a disease activity score (DAS)-steered therapeutic protocol over a 24-month period. Standard evaluation included clinical, laboratory, functional and systematic (44 joints) US assessment. US indexes of grey scale (GS) and power Doppler (PD) synovitis were correlated with clinical evaluation, laboratory indexes and clinical outcome. Clinical remission was defined when DAS was <1.6 at two consecutive visits 3 months apart. RESULTS US examination was significantly more sensitive than clinical examination, both in active disease and in remission. In patients with an active disease, both clinical and US indexes correlated with CRP, whereas in remission only PD still remained significantly correlated. In clinical remission, 95% of the patients showed residual GS synovitis, and 41% of them showed a positive PD signal. Positive PD signal, even in a single joint, resulted the main predictor of relapse within 6 months, both in univariable and multivariable logistic regression analysis. CONCLUSIONS In a cohort of early RA patients treated with conventional DMARDs, US-GS can detect residual disease activity more sensitively than clinical examination both in active disease and in remission. Moreover, PD-positive synovial hypertrophy identifies an ongoing inflammation even during remission and predicts short-term relapse.

Comparison of Clinical Versus Ultrasound-Determined Synovitis in Juvenile Idiopathic Arthritis

OBJECTIVE To compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with juvenile idiopathic arthritis (JIA). METHODS Thirty-two patients underwent clinical evaluation of 52 joints by 2 pediatric rheumatologists. Joints were assessed for swelling, tenderness/pain on motion, and restricted motion. The same joints were scanned independently by an experienced sonographer for synovial hyperplasia, joint effusion, and power Doppler (PD) signal. RESULTS In total, 1,664 joints were assessed both clinically and with US. On clinical examination, 98 joints (5.9%) were swollen, 59 joints (3.5%) were tender, and 40 joints (2.4%) had restricted motion. On US evaluation, 125 joints (7.5%) had synovial hyperplasia, 153 joints (9.2%) had joint effusion, and 53 joints (3.2%) had PD signal. A total of 104 (6.3%) and 167 (10%) joints had clinical and US synovitis, respectively. Of the 1,560 clinically normal joints, 86 (5.5%) had subclinical synovitis (i.e., had synovitis on US). US led to classifying 5 patients as having polyarthritis who were classified as having oligoarthritis or were found to have no synovitis on clinical evaluation. US variables were moderately correlated with clinical measures of joint swelling, but poorly correlated with those of joint tenderness/pain on motion and restricted motion. Overall, correlations were lower for PD signal than for synovial hyperplasia and joint effusion. CONCLUSION We found that subclinical synovitis as detected by US is common in children with JIA. This finding may have important implications for patient classification and may affect the choice of the optimal therapeutic strategy in individual patients.

In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis

Objectives To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis. Methods In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI≤3.3), ACR/EULAR (categorical), DAS28 (<2.6) and DAS (<1.6). The health assessment questionnaire (HAQ) was completed at baseline and 12 months, power Doppler-positive synovitis (PDPS) was assessed at baseline, 6 and 12 months. Cross-sectionally, the outcomes were low functional disability (HAQ≤0.5) or absent PDPS in all joints, while longitudinally the outcomes were stable low functional disability and persistent absent PDPS in all joints. Results At baseline, 33.7% of patients achieved DAS28 remission, 43.37% DAS remission, 16.8% SDAI remission, 13.8% ACR/EULAR remission. DAS28, SDAI and ACR/EULAR remission was cross-sectionally associated with low functional disability and absent PDPS. All definitions were longitudinally associated with low functional disability: positive likelihood ratios (LR+) of 3.24 for DAS28, 2.14 for DAS, 4.86 for SDAI, 5.67 for ACR/EULAR criteria, and with absent PDPS for DAS28 (LR+ 1.66), SDAI (LR+ 6.46), ACR/EULAR (LR+ 5.07). Conclusions The new remission definitions confirmed their validity in an observational setting and identify patients with better disease control.

Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure.

The aim of the present study was to perform an immunohistological assessment of the synovial tissue from involved small joints in rheumatoid arthritis (RA) and to explore the reliability of a mini-invasive ultrasound (US)-guided technique of small joint synovial biopsy for the histopathological assessment. Synovial tissue collected during arthrotomic surgery of small joints in nine patients served as the gold standard for the validation of the histological assessment. Small hand-joint synovial biopsies from an additional nine patients with erosive RA were obtained by a mini-invasive US-guided procedure, performed percutaneously by the portal and rigid forceps technique. Using digital image analysis, the area fractions of synovial macrophages (CD68 cells), T cells (CD3 cells) and B cells (CD20 cells) were measured in all high-power fields of every sample at different cutting levels. The representative sample was defined as the minimal number of high-power fields whose mean area fraction would reflect the overall mean area fraction within a percentage mean difference of 10%. For each patient, a range of three to five large samples for surgical biopsies and a range of 8–12 samples for US-guided biopsies were collected and analysed. In arthrotomic samples, the analysis of a randomly selected tissue area of 2.5 mm2 was representative of the overall value for CD68, CD3 and CD20 cells. US-guided samples allowed histological evaluation in 100% of cases, with a mean valid area of 18.56 mm2 (range 7.29–38.28 mm2). The analysis of a cumulative area of 2.5 mm2 from eight randomly selected sections (from different samples or from different cutting levels) allowed to reduce the percentage mean difference to less than 10% for CD68, CD3 and CD20 cells. In conclusion, US-guided synovial biopsy represents a reliable tool for the assessment of the histopathological features of RA patients with a mini-invasive approach.

Ultrasound-detected synovial abnormalities are frequent in clinically inactive juvenile idiopathic arthritis, but do not predict a flare of synovitis

Objectives To investigate whether children with juvenile idiopathic arthritis (JIA) in clinical remission have subclinical synovial disease on ultrasound, and whether ultrasound abnormalities predict an early flare of synovitis. Methods Thirty-nine consecutive children who had clinically defined inactive disease (ID) for a minimum of 3 months underwent ultrasound assessment of 52 joints. All joints were scanned for synovial hyperplasia, joint effusion, power Doppler (PD) signal and tenosynovitis. Patients were then followed clinically for up to 2 years until a flare of synovitis occurred in one or more joints, or until the 2-year visit if the disease remained in clinical remission. Results Synovial hyperplasia, joint effusion, PD signal and tenosynovitis in at least one joint were detected in 76.9%, 66.7%, 33.3% and 15.4% of patients, respectively. During the 2-year follow-up, 24 patients (61.5%) experienced sustained ID, whereas 15 patients (38.5%) had a flare of synovitis in a total of 45 joints after a median of 10.6 months (range 6.3–13.7 months). At study entry, the rate of synovial hyperplasia, joint effusion and tenosynovitis was comparable between patients with persistent ID and patients with synovitis flare, whereas patients with persistent ID had a greater frequency of PD signal than patients with synovitis flare. Only 17 of the 45 flared joints had ultrasound abnormalities at study entry. Conclusion The authors found that ultrasound-detected synovial abnormalities are common in children with JIA in clinical remission. However, the presence of ultrasound pathology did not predict an early flare of synovitis in the affected joints.

Early disease control by low‐dose prednisone comedication may affect the quality of remission in patients with early rheumatoid arthritis

In order to identify rate and stability of remission induced by low‐dose prednisone comedication in early rheumatoid arthritis (RA), we evaluated patients with early RA (<1 year) who were randomized to receive (P) or not (non‐P) low‐dose prednisone in association with step‐up disease‐modifying antirheumatic drug therapy over 2 years. Prevalence and duration of clinical remission were evaluated in the first and second year. Each treatment group included 105 patients; no significant differences were found at baseline. During the first year, P patients achieved higher rates of clinical remission with a time‐averaged odds ratio (OR) of 1.965 (CI 95% 1.214–3.182, P= 0.006). Moreover, they showed a higher probability of sustained remission during the second year (OR 4.480, CI 95% 1.354–14.817, P= 0.014). In conclusion, we found as in early RA low‐dose prednisone comedication is associated with higher rate of clinical remission, earlier disease activity control and more stable remission over time.

Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study.

IntroductionIn early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.MethodsTwo hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome.ResultsEach group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group.ConclusionIn early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control.Trial registration numberCurrent Controlled Trials ISRCTN2486111

Gout impacts on function and health-related quality of life beyond associated risk factors and medical conditions: results from the KING observational study of the Italian Society for Rheumatology (SIR)

IntroductionGout is the most prevalent arthritis and significantly impacts on function and quality of life. Given that gout associates with disabling comorbid conditions, it is not clear whether such a complex of diseases accounts for the increased disability or if gout may play a role by itself. This study aims to evaluate the specific influence of gout and disease-related features on functional disability and health-related quality of life (HRQoL) in patients with gout followed in rheumatology clinics.MethodsA random sample of patients was drawn from clinical registries of 30 rheumatology clinics across Italy. Sociodemographic, general health and gout-specific variables were collected. Functional disability and HRQoL were assessed by the health assessment questionnaire (HAQ) and the Physical and Mental Component Summary scores (PCS and MCS) of the Short Form-36 (SF-36). Crude and adjusted ordinal logistic and linear regression models were applied to investigate the specific contribution of different variables on HAQ and SF-36 scores. Results are presented as odds ratio (OR) or mean difference (MD) and 95% confidence intervals.ResultsOut of 446 patients with gout, 90% were males with a mean age of 63.9 years and median disease duration of 3.8 years; the majority of patients were overweight or obese, and with several comorbidities; 21.1% showed at least moderate disability; the PCS score was significantly lower than expected age- and gender-matched samples in the general population, while MCS score was not. After adjusting for potential sociodemographic and general-health confounders, gout-specific variables significantly impacted on HAQ, including polyarticular involvement OR 3.82 (1.63, 8.95), presence of tophi OR 1.92 (1.07, 3.43) and recent attacks OR 2.20 (1.27, 3.81). Consistent results were found for PCS. The impairment of PCS compared to the general population was limited to patients with features of chronic gout. MCS was only affected by recent attacks (MD -2.72 [-4.58, -0.86]) and corticosteroid treatment (-3.39 [-5.30,-1.48]).ConclusionsThe data from the KING study confirm that gout impacts on disability and provide evidence for an independent association of gout and gout-related features with functional outcome and HRQoL. This result supports the need to improve specific treatment in gout.

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.

AbstractAnti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.

Development of healthcare quality indicators for rheumatoid arthritis in Europe: the eumusc.net project

Background Eumusc.net (http://www.eumusc.net) is a European project supported by the EU and European League Against Rheumatism to improve musculoskeletal care in Europe. Objective To develop patient-centred healthcare quality indicators (HCQIs) for healthcare provision for rheumatoid arthritis (RA) patients. Methods Based on a systematic literature search, existing HCQIs for RA were identified and their contents analysed and categorised referring to a list of 16 standards of care developed within the eumusc.net. An international expert panel comprising 14 healthcare providers and two patient representatives added topics and during repeated Delphi processes by email ranked the topics and rephrased suggested HCQIs with the preliminary set being established during a second expert group meeting. After an audit process by rheumatology units (including academic centres) in six countries (The Netherlands, Norway, Romania, Italy, Austria and Sweden), a final version of the HCQIs was established. Results 56 possible topics for HCQIs were processed resulting in a final set of HCQIs for RA (n=14) including two for structure (patient information and calculation of composite scores), 11 for process (eg, access to care, assessments, and pharmacological and non-pharmacological treatments) and one for outcome (effect of treatment on disease activity). They included definitions to be used in clinical practice and also by patients. Further, the numerators and the denominators for each HCQI were defined. Conclusions A set of 14 patient-centred HCQIs for RA was developed to be used in quality improvement and bench marking in countries across Europe.