Ultrasound versus physical examination in predicting disease flare in children with juvenile idiopathic arthritis: a systematic literature review and qualitative synthesis

In this systematic review we analyzed the published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound (US) in juvenile idiopathic arthritis (JIA). Medline, Embase and Cochrane databases were searched from 1990 to 2020 by two authors, using PICO methodology. The study is built and reported according to PRISMA guidelines. Searches identified four articles comprising a total of 187 JIA patients in clinical remission from at least 3 months. Two of the articles found US subclinical signs of synovitis to be predictive for flare, with a five times higher risk (with Power Doppler signal as an important feature), while in the other two baseline US abnormalities did not predict a clinical flare. The articles differed for protocols, definitions, and length of follow-up. US has an expanding role in pediatric rheumatology, with interest-ing applications especially during the follow-up, potentially identifying subclinical inflammatory signs predictive of flare. However, the few studies available do not allow definite conclusions at this time.

Ultrasound shows swollen joints are the better proxy for synovitis than tender joints in DMARD-naïve, early psoriatic arthritis

Objective To evaluate the relationship between clinical examination/ultrasound (US) synovitis in DMARD-naïve early PsA. Methods Eligible patients underwent matched clinical/US 44 joint assessment for tender and/or swollen joints (TJ/SJ) and US synovitis [grey scale (GS) ≥2 or power Doppler (PD) ≥1]. Statistical agreement between TJ/SJ, GS ≥ 2 or PD ≥ 1 was calculated by prevalence-adjusted and bias-adjusted kappa (PABAK). To derive probabilities of GS ≥ 2/PD ≥ 1, mixed-effects logistic regression modelled odds of US synovitis in TJ/SJ were conducted. Results In 155 patients, 5,616 joints underwent clinical/US examination. Of these joints, 1039/5616 (18.5%) were tender, 550/5616 (9.8%) were swollen, 1144/5616 (20.4%) had GS ≥ 2, and 292/5616 (5.2%) had PD ≥ 1. GS ≥ 2 was most prevalent in concomitantly tender and swollen joints [205/462 (44%)] followed by swollen non-tender joints [32/88 (36.4%)], tender non-swollen joints [148/577 (25.7%)], and non-tender non-swollen joints (subclinical synovitis) [759/4489 (16.9%)]. Agreement between SJ/PD ≥ 1 was high at the individual joint level (82.6%-96.3%, PABAK 0.65–0.93) and for total joints combined (89.9%, PABAK 0.80). SJ/GS ≥ 2 agreement was greater than between TJ/GS ≥ 2 [73.5%-92.6% vs 51.0%-87.4% (PABAK 0.47–0.85 vs PABAK 0.35–0.75) respectively]. Swelling was independently associated with higher odds of GS ≥ 2 [odds ratio (OR) (95% CI); 4.37 (2.62, 7.29); p < 0.001] but not tenderness [OR = 1.33 (0.87, 2.06); p = 0.192]. Swelling [OR = 8.78 (3.92, 19.66); p < 0.001] or tenderness [OR = 3.38 (1.53, 7.50); p = 0.003] were independently associated with higher odds of PD ≥ 1. Conclusion Synovitis (GS ≥ 2 and/or PD ≥ 1) was more likely in swollen joints than tender joints in DMARD-naïve, early PsA. Agreement indicated swollen joints were the better proxy for synovitis, adding to greater understanding between clinical/US assessments.

POS0385 DURING DEVELOPMENT OF RHEUMATOID ARTHRITIS, INTERMETATARSAL BURSITIS MAY OCCUR BEFORE CLINICAL JOINT SWELLING: A LARGE MRI STUDY IN PATIENTS WITH CLINICALLY SUSPECT ARTHRALGIA

Background:Inflammation of the synovial lining is a hallmark of rheumatoid arthritis (RA). A synovial lining is not only present at synovial joints and tendon sheaths but also at bursae. Inflammation of the synovium-lined intermetatarsal bursae in the forefoot, intermetatarsal bursitis (IMB), was recently identified with MRI. It is specific for early RA and present in the majority of RA patients at diagnosis. During development of RA, MRI-detectable subclinical synovitis and tenosynovitis often occur before clinical arthritis presents. Whether IMB is also present in a pre-arthritis stage is unknown.Objectives:To assess the occurrence of IMB in patients with clinically suspect arthralgia (CSA) and its association with progression to clinical arthritis in a large MRI-study.Methods:We studied 524 consecutive patients presenting with CSA. CSA was defined as recent-onset arthralgia of small joints that is likely to progress to RA based on the clinical expertise of the rheumatologist. Participants underwent unilateral contrast-enhanced 1.5T MRI of the forefoot, metacarpophalangeal (MCP) joints and wrist at baseline. Thereafter patients were followed for detection of clinical arthritis, as identified at physical joint examination by the rheumatologist. Baseline MRIs were evaluated for IMB at all 4 intermetatarsal spaces. Also synovitis, tenosynovitis and osteitis were assessed in line with the RA MRI scoring system (summed as RAMRIS-inflammation). Both IMB and RAMRIS-inflammation were dichotomised into positive/negative using data from age-matched symptom-free controls as a reference. Cox regression analysed the association of IMB with progression to clinical arthritis; multivariable analyses were used to adjust for RAMRIS-inflammation which is known to associate with progression to clinical arthritis. Analyses were repeated stratified for ACPA-status, since ACPA-positive and ACPA-negative RA are considered separate entities with differences in pathophysiology.Results:The baseline MRIs showed ≥1 IMB in 35% of CSA-patients. Patients with IMB were more likely to also have synovitis (OR 2.5 (95%CI 1.2–4.9)) and tenosynovitis (8.9 (3.4–22.9)) on forefoot MRI, but not osteitis (0.9 (0.5–1.8)). Patients were followed for median 25 months (IQR 19–27). IMB-positive patients developed clinical arthritis more often than IMB-negative patients (HR 3.0 (1.9-4.8)). This association was independent of RAMRIS-inflammation (adjusted HR 2.2 (1.4–3.6)). In stratified analyses, IMB was more frequent in ACPA-positive than in ACPA-negative CSA (68% vs. 30%, p<0.001). Moreover IMB predicted clinical arthritis development in ACPA-positive CSA (HR 2.5 (1.1–5.7)) but not in ACPA-negative CSA patients (1.0 (0.5–2.2)).Conclusion:One-third of CSA patients have IMB. IMB is frequently present in conjunction with subclinical synovitis and tenosynovitis. It precedes the development of clinical arthritis, and in particular the development of ACPA-positive RA. These results reinforce the notion that not only intra- but also juxta-articular synovial inflammation is involved in the development of RA.Disclosure of Interests:None declared

POS1062 ULTRASOUND ASSESSMENT OF SUB-CLINICAL HAND JOINT SYNOVITIS: A COMPARATIVE STUDY BETWEEN PSORIATIC AND RHEUMATOID ARTHRITIS

Background:Ultrasound (US) detected subclinical synovitis can be present in early psoriatic arthritis (PsA) and rheumatoid arthritis (RA), and also in patients fulfilling clinical remission criteria[1-2]. Numerous evidences support that the persistence of subclinical synovitis detected by US is associated with a high risk of disease progression [2-3].Objectives:To evaluate sub-clinical synovitis of PsA and RA at the level of small joints of the hand and wrist by B-mode and Power Doppler US.Methods:21 patients of early PsA and 25 patients of early RA (no clinical evidence of hand joint involvement, PsA disease duration <2 years, and RA disease duration <1 year) were recruited. DAS28 and DAPSA score used for assessment of articular disease activity for RA and PsA, respectively. US [grey scale (GS) and power Doppler (PD)] was performed to assess synovitis of bilateral wrists, metacarpophalangeal joints, proximal and distal interphalangeal joints, altogether 30 joints. A GS score ≥2 and/or a PD score ≥1 were used to identify US detected synovitis.Results:A total of 25 patients were included in the RA group, including 5 males and 20 females. A total of 21 patients were included in the PsA group, including 7 males and 14 females. There were no significant differences in gender composition, age, and duration of disease between the two groups (P>0.05) (Table 1). 14 (66.67%) PsA patients and 12 (48%) RA patients had sub-clinical hand joint synovitis. Among 630 hand joints scanned in PsA group, 49 (7.78%) joints showed evidence of sub-clinical synovitis. Wrist joint was most commonly involved (24.49%), followed by MCP3 (14.29%), MCP1 (12.24%) and DIP3 (10.20%). Among 750 hand joints scanned in RA group, 110 (14.67%) joints showed evidence of sub-clinical synovitis. Wrist joint was most commonly involved (60.00%), followed by MCP3 (8.24%), MCP1 (8.24%) and MCP2 (7.06%). No correlation noted between numbers of joints with subclinical synovitis with DAPSA and DAS28 score. There was no correlation between number of joints with sub-clinical synovitis and disease activity indices.Conclusion:Almost two-thirds patients with PsA and half patients with RA had US evidence of sub-clinical synovitis in wrist and hand joints, most commonly in wrist. There are some similarities in the joint involvement of sub-clinical synovitis between RA and PsA, physicians should take this into account in clinical work.Table 1.Demographic characteristics of RA and PsA patientsRA (n=25)PsA (n=21)PFemale, n(%)20 (80.00%)14 (66.67%)0.305Age, years, mean±SD56.32±12.1854.31±15.820.637Disease duration, years, mean±SD1.06±0.590.90±0.580.363References:[1]Freeston JE, Coates LC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, et al. Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis care & research 2014, 66:432-439.[2]Kawashiri SY, Suzuki T, Nakashima Y, Horai Y, Okada A, Iwamoto N, et al. Ultrasonographic examination of rheumatoid arthritis patients who are free of physical synovitis: Power doppler subclinical synovitis is associated with bone erosion. Rheumatology (Oxford), 2014, 53:562-569.[3]Vreju FA, Filippucci E, Gutierrez M, Di Geso L, Ciapetti A, Ciurea ME, et al. Subclinical ultrasound synovitis in a particular joint is associated with ultrasound evidence of bone erosions in that same joint in rheumatoid patients in clinical remission. Clinical and experimental rheumatology, 2016, 34:673-678.Acknowledgements:This work was supported by National Natural Science Foundation of China (No. 82071930 and 81571684).Disclosure of Interests:None declared.

POS0543 MORNING STIFFNESS IN CLINICALLY SUSPECT ARTHRALGIA IS EXPLAINED BY LOCAL SUBCLINICAL SYNOVITIS AND SYSTEMIC INFLAMMATION

Background:Morning stiffness (MS) is considered a cardinal symptom in the clinical appraisal of arthralgia patients, suggesting presence of subclinical inflammation, which could indicate an increased chance of progression to rheumatoid arthritis (RA). However, the pathophysiology behind MS in arthralgia patients that is clinically suspect for progressing to RA (clinically suspect arthralgia; CSA) has never been studied. In RA, it is presumed that both and local- and systemic inflammation underlie MS. We therefore hypothesize that, in patients with CSA, MS can also be explained by local- and systemic inflammation.Objectives:To determine if MS can be explained by MRI-detected local inflammation (subclinical synovitis and tenosynovitis) and systemic inflammation (C-reactive protein(CRP)).Methods:514 CSA patients underwent a contrast-enhanced 1.5T MRI of metacarpophalangeal (MCP) 2-5, wrist and metatarsophalangeal (MTP) 1-5 joints, next to clinical assessment and laboratory investigations. MRIs were scored for synovitis and tenosynovitis in line with the RAMRIS-method. MS was dichotomized as present (duration ≥60 minutes) or absent (duration <60 minutes). Associations of MRI-detected synovitis, tenosynovitis and increased CRP with MS were tested with univariable and multivariable logistic regression. Since earlier research in arthritis patients showed that the effect of combined presence of MRI-detected synovitis and tenosynovitis was increased, compared to the effect of these features separately, interaction between MRI-detected synovitis and tenosynovitis, and between synovitis and increased CRP, was assessed.Results:In the studied CSA-patients, mean age was 44 years (sd 13), 397 patients (77%) were female, median tender joint count (TJC-70) was 5 (interquartile range 2-10), and 67 (13%) patients were ACPA-positive. MS was present in 191 (37%) CSA-patients. Baseline characteristics among patients with and without MS were similar. MRI-detected synovitis was more often present in patients with MS compared to patients without MS (34% versus 19%), OR 2.12 (95% CI 1.41-3.19). Also, MRI-detected tenosynovitis was more frequently present in patients with MS (36% versus 24%), OR 1.74 (1.18-2.57). Likewise, increased CRP levels (≥5 mg/L) were more often found in patients with MS (31% versus 18%), OR 2.00 (1.32-3.04). In multivariable analyses, ORs were 1.90 (1.22-2.96) for MRI-detected synovitis and 1.82 (1.18-2.82) for increased CRP. With an OR of 1.20 (0.77-1.87) MRI-detected tenosynovitis was not significantly associated with MS in a multivariable analysis. Interaction between synovitis and tenosynovitis, and between synovitis and CRP was not significant (p-value of 0.13 and 0.15, respectively).Conclusion:Presence of MRI-detected synovitis and increased CRP levels are associated with presence of MS in patients with CSA. This indicates that MS in CSA patients could indeed be induced by both local- and systemic inflammation.Disclosure of Interests:None declared

AB0193 PRESENCE OF SUBLINICAL SYNOVITIS IN A ESTABLISHED RHEUMATOID ARTHRITIS COHORT

Background:Some studies prove that a significant percentage of patients with rheumatoid arthritis (RA) in sustained clinical remission has radiological progression or joint damage, and the presence of residual activity objectified by imaging studies such as ultrasonography could be related to a relapse or flare of RA.(1,2)Objectives:To determine the presence of subclinical synovitis measured by ultrasonography in patients with RA on sustained clinical remission from the Rheumatology service at Hospital de Clínicas, San Lorenzo, Paraguay.Materials and Methods:Prospective, cross sectional, descriptive study, in RA patients meeting ACR/EULAR 2010 criteria, older than 18 years, on sustained clinical remission (≥6 months), measured by ESR-DAS28 (<2,6), doing follow-ups on our service. A healthy control group was included. All groups signed informed consent. Synovial hypertrophy (SH) and intraarticular vascularization grades on Power Doppler (PD) mode were determined according to EULAR recommendations and OMERACT 7 group definitions. Clinical data were obtained from the service’s registries.SPSS 23rd version was used for data analysis. Quantitative variables were presented as means and qualitative as frequencies. Chi square test was performed for comparisons between dichotomous variables and t Student for continuous. For comparisons between variables the Spearman’s rank correlation coefficient was performed, and p≤0.05 for statistical significance. Factors predicting subclinical synovitis were analyzed with Odds Ratio (OR) CI 95%.Results:From 147 patients, 31 (21%) met remission criteria; 87.1% women, mean age 51.9±14.8 years. Mean disease duration was 9,06±10,81 years. 64,5% were RF and ACPA positive and 25,9% had erosions.Ultrasonograms were made in 20 joints of both hands: radiocarpals (RC), metacarpophalangeals (MCP) and proximal interphalangeals (PIP). 12 patients (38.7%) presented subclinical synovitis (SH≥2+PD), more frequently on RC (29% right, 22.6% left), and MCP (9.7% on 2RMCP, 9.7% 4LMCP). These patients had greater CDAI (3.9±1.37 vs 2.89±1.15, p=0.03), HAQ (0.14±0.29 vs 0.00±0.00, p=0.04), CRP (9.90±7.46 vs 4.74±2.30, p=0.00) RF levels (502.67±275.66 vs 200.92±158.43, p=0,00), greater prednisone (16.5% vs 3.2%, p=0.04), and methotrexate use (20.16±5.54 vs 17.50±3.98, p=0.01). None of the healthy controls presented subclinical synovitis.In binary logistic regression CRP levels, RF titers and methotrexate doses were associated to subclinical synovitis. This association is not found in multivariate logistic regression. Negative association was found between subclinical synovitis and two csDMARDs use.Conclusion:This is the first study of its type in Paraguayan patients, which clearly evidenced that an important part of RA patients in clinical remission still presented subclinical synovitis (HS≥2 + PD). It was associated with CRP, RF and methotrexate dose.References:[1]Płaza M, Nowakowska-Płaza A, Pracoń G, Sudoł-Szopińska I. Role of ultrasonography in the diagnosis of rheumatic diseases in light of ACR/EULAR guidelines. J Ultrason. marzo de 2016;16(64):55-64.[2]Foltz V, Gandjbakhch F, Etchepare F, Rosenberg C, Tanguy ML, Rozenberg S, et al. Power Doppler ultrasound, but not low-field magnetic resonance imaging, predicts relapse and radiographic disease progression in rheumatoid arthritis patients with low levels of disease activity. Arthritis & Rheumatism. 2012;64(1):67-76.Disclosure of Interests:None declared

OP0161 PREDICTIVE VALUE OF MUSCULOSKELETAL ULTRASOUND IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS IN CLINICAL REMISSION

Background:The accurate assessment of remission status in JIA patients is of utmost relevance to taper medications and prevent side effects from their long-term administration. In RA patients in clinical remission (CR), musculoskeletal ultrasound (MSUS) allows to detect persistent joint inflammation (subclinical synovitis), which predicts disease flare and structural damage progression. Although subclinical synovitis has been reported in a substantial proportion of JIA patients with inactive disease, its prognostic value is still being defined.Objectives:1) to investigate the prevalence of MSUS-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare and whether it should affect the therapeutic strategy.Methods:135 consecutive JIA patients who met the Wallace criteria for CR were included in this 3-years prospective study. All patients underwent MSUS assessment of 56 joints at study entry and at 6 months follow-up visit. Joints were scanned for synovial hyperplasia, joint effusion and Power Doppler (PD) signal by two independent ultrasonographers. Patients were followed clinically for 3 years. A flare of synovitis was defined as a recurrence of clinically active arthritis. The association between clinical and MSUS variables with flare, was evaluated by adjusted logistic regression models.Results:135 patients (78.5% F; median age 11.3 y; median disease duration 5.7 y; median CR duration 1.4 y) were included. Fifty-seven/135 (42.2%) patients had persistent oligoarthiritis; 41/135 (30.4%) extended oligoarthiritis; 32/135 (23.7%) polyarthiritis; 5/135 (3.7%) systemic arthritis. Seventy-eight/135 (57.7%) patients were in CR on medication. Subclinical synovitis was detected in 32/135 (23.7%) patients and in 53/7560 (0.7%) joints. Subclinical tenosynovitis was present in 20/135 (14.8%) patients. Subclinical synovitis was found more frequently in the ankle and wrist joints. 58.6% of patients showed persistent subclinical synovitis at 6 month follow up MSUS examination. During the 3-year follow up 45/135 (33.3%) patients experienced a disease flare (median survival time 2.2 y). PD positivity in tendons was the stronger independent risk factor of flare on multivariable regression analysis (HR: 4.8; P=0.04). Other predictors of flare were the JIA subtype (oligo-extended form: HR: 2.3; P=0.031) and the status of CR on medication (HR: 3.7; P=0.002).Conclusion:our results confirm that MSUS is more sensitive than clinical evaluation in the assessment of persistent synovial inflammation in JIA patients. Subclinical tenosynovitis was the best predictor of disease flare. To date, the role of tenosynovitis in the diagnosis and prognosis of JIA has been poorly investigated. Our results further support the role of MSUS, especially of the wrist and the ankle, in monitoring JIA patients in clinical remission and to predict disease flare.References:[1]De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018 Oct;77(10):1426-1431.[2]Filippou G, et al. The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study. Ann Rheum Dis 2018;77:1283-9.Disclosure of Interests:None declared

O14 Frequency and site of clinically unsuspected synovitis on whole-body MRI in juvenile idiopathic arthritis

Background/Aims Magnetic resonance imaging can facilitate the diagnosis of JIA, but is also increasingly used for monitoring disease activity in individual joints. This prospective study aims to measure the frequency of subclinical synovitis on whole-body MRI, in adolescent patients with JIA. Methods JIA patients were recruited from a tertiary adolescent and young adult rheumatology clinic, between September 2019 and August 2020. All patients were examined by a senior rheumatology registrar, before undergoing a contrast enhanced whole-body MRI scan. Patients were assigned to a clinically active or inactive group, depending on their active joint count (AJC); active patients had AJC≥ 1, while the clinically inactive patients had an AJC =0. The post-contrast, water-only mDixon images were assessed for synovitis by one radiologist, blinded to clinical information. Only joints that were definitely abnormal were counted as synovitic. Eighty-one joints per patient were examined with both methods. The presence of subclinical synovitis in a patient was defined as synovitis in one or more joints on MRI, which were not active clinically. Results Thirty-two patients aged 15 to 24 were included in the analysis. The patient characteristics and the frequency of subclinical synovitis are summarised in the table. Subclinical synovitis was detected in a similar proportion of JIA patients in both active and inactive groups (46.7% vs. 41.2%, P = 0.76). The most frequent region with subclinical synovitis was the hindfoot, detected in 22% (7/32) of JIA patients and 17.2% (11/64) of hindfoot joints assessed by MRI. The second most common joint with clinically unsuspected inflammation was the knee, found in 19% (6/32) of JIA patients and 14% (9/64) knee joints. Similarly, 16% (5/32) of the adolescent patients had active disease in the hip, ankle or midfoot joints. The frequency of elbow involvement was also considerable, with 12% (7/58) of joints with subclinical synovitis in 14% (4/29) of JIA patients. Conclusion In conclusion, 43.8% of JIA patients had subclinical synovitis on whole-body MRI scan with no significant difference between the clinically active vs. inactive JIA patients. Large joints were predominantly affected. Further research is required to validate our findings in a larger cohort of JIA patients. Disclosure V. Choida: None. C. Ciurtin: None. T.J.P. Bray: None. D. Sen: None. C. Fisher: None. M. Leandro: None. M.A. Hall-Craggs: None.