scholarly journals Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis

2020 ◽  
Vol 79 (7) ◽  
pp. 901-907 ◽  
Author(s):  
Andrea Di Matteo ◽  
Kulveer Mankia ◽  
Laurence Duquenne ◽  
Edoardo Cipolletta ◽  
Richard J Wakefield ◽  
...  
Keyword(s):  
At Risk ◽  
Inflammatory Arthritis ◽  
Power Doppler ◽  
High Titre ◽  
Peptide Antibody ◽  
Clinical Arthritis ◽  
Citrullinated Peptide ◽  
Power Doppler Signal ◽  
Subclinical Synovitis

ObjectivesTo investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA).MethodsBaseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400).ResultsBE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p<0.01). A significant correlation between BE and US synovitis in the MTP5 joints was detected (Cramer’s V=0.37, p<0.01). The OR for the development of IA (ever) was highest for the following: BE in >1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1–132.8, p<0.01).ConclusionsIn CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis.

scholarly journals Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting

2020 ◽  
pp. annrheumdis-2020-217066 ◽  
Author(s):  
Elizabeth A Bemis ◽  
M Kristen Demoruelle ◽  
Jennifer A Seifert ◽  
Kristen J Polinski ◽  
Michael H Weisman ◽  
...  
Keyword(s):  
Clinical Setting ◽  
Inflammatory Arthritis ◽  
High Titre ◽  
Degree Relative ◽  
Increased Risk ◽  
Peptide Antibody ◽  
Prevention Studies ◽  
At Risk Populations ◽  
Citrullinated Peptide

ObjectivesLittle is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting.MethodsWe screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA.Results304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2–7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, p<0.01).ConclusionsThese findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

scholarly journals P239 Third generation APCA improve prediction of clinical arthritis in at-risk individuals with positive second generation ACPA

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Andrea Di Matteo ◽  
Kulveer Mankia ◽  
Laurence Duquenne ◽  
Michael Mahler ◽  
Diane Corscadden ◽  
...  
Keyword(s):  
At Risk ◽  
Inflammatory Arthritis ◽  
Second Generation ◽  
Third Generation ◽  
Serum Samples ◽  
Incremental Value ◽  
Rate Of Progression ◽  
Clinical Arthritis ◽  
Citrullinated Peptide

Abstract Background Anti-citrullinated peptide antibodies (ACPA) are important biomarkers in rheumatoid arthritis (RA) and can predict arthritis development in at-risk individuals. ACPA are conventionally detected using the second-generation or third generation IgG anti-CCP antibody (Ab) assays. Although the value of anti-CCP2 Ab for predicting progression to RA in at-risk individuals is well understood, very little knowledge exists for anti-CCP3.The objectives of this study were: i) To evaluate the prevalence of serum anti-CCP3 Ab in serum anti-CCP2 Ab positive at-risk individuals (CCP2+ at-risk); ii)) To study the incremental value of anti-CCP3 Ab in CCP2+ at-risk subjects for predicting progression to clinical inflammatory arthritis (IA). Methods Anti-CCP3 Ab were tested on stored serum samples obtained from 347 CCP2 + (BioRad, USA) at-risk individuals from the Leeds CCP study. Anti-CCP2 and anti-CCP3 tests positivity threshold was &gt;2.99 IU/ml and &gt;20 units, respectively. Moreover, anti-CCP2 and anti-CCP3 titres were categorised according to manufacturer’s cut-off: low (LT) and high (HT) for anti-CCP2, negative/weak/moderate/strong for anti-CCP3. Progression to IA was defined as the development of clinical synovitis in at least one joint. Only subjects with at least one follow-up visit were included in the progression analysis (n = 317). Results Anti-CCP3 Ab were negative in 138/347 (39.7%) CCP2+ individuals, and weakly, moderately, and strongly positive in 15/347 (4.3%), 5/347 (1.4%) and 189/347 (54.4%) individuals, respectively. LT and HT anti-CCP2 Ab were found in 103/347 (29.7%) and in 244/347 (70.3%) individuals, respectively. Eighty-eight/317 subjects (28%) developed IA. The rate of progression of LT and HT anti-CCP2, when anti-CCP3 was negative, decreased from 6.5% to 2.7%, and from 36.6% to 9.4%, respectively. Progression in anti-CCP2 HT increased from 36.6% to 45.6% when anti-CCP3 was positive (Table 1). Conclusion Our results support an important role for anti-CCP3 Ab in improving prediction of IA in CCP2+ at-risk individuals. Disclosures A. Di Matteo None. K. Mankia None. L. Duquenne None. M. Mahler Other; Inova Diagnostic. D. Corscadden None. K. Mbara None. L. Garcia-Montoya None. J. Nam None. P. Emery Honoraria; AbbVie, BMS, Bristol-Myers Squibb, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Samsung Bioepis Co., Ltd.

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

2022 ◽  
Author(s):  
Orazio De Lucia ◽  
Teresa Giani ◽  
Roberto Caporali ◽  
Rolando Cimaz
Keyword(s):  
Systematic Review ◽  
Juvenile Idiopathic Arthritis ◽  
Pediatric Rheumatology ◽  
Power Doppler ◽  
The Other ◽  
Qualitative Synthesis ◽  
Disease Flare ◽  
Power Doppler Signal ◽  
Subclinical Synovitis

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.

scholarly journals Bone erosions detected by ultrasound are prognostic for clinical arthritis development in patients with ACPA and musculoskeletal pain

2020 ◽  
Author(s):  
Michael Ziegelasch ◽  
Emma Eloff ◽  
Hilde Berner Hammer ◽  
Jan Cedergren ◽  
Klara Martinsson ◽  
...  
Keyword(s):  
Cox Regression ◽  
Power Doppler ◽  
Multivariable Analysis ◽  
Clinical Signs ◽  
Control Group ◽  
Cox Regression Analysis ◽  
Peptide Antibody ◽  
Ultrasound Findings ◽  
Clinical Arthritis

Abstract BackgroundTo assess the prognostic value of ultrasound for clinical arthritis development among anti-citrullinated peptide antibody (ACPA)-positive patients with musculoskeletal (MSK) pain.MethodsWe prospectively followed 82 ACPA-positive patients with MSK pain without clinical signs of arthritis at baseline. Ultrasound examination at baseline assessed synovial hypertrophy (SH), and inflammatory activity by power Doppler (PD) in 36 small joints and 6 tendons, and erosions in 18 joints. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24–90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without MSK pain.ResultsClinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1–71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p < 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77% vs 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6–9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1–5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Neither SH nor PD was associated with arthritis development.ConclusionsBone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population.Trial registrationRegional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/

scholarly journals Subclinical synovitis in arthralgia: how often does it result in clinical arthritis? Reflecting on starting points for disease-modifying anti-rheumatic drug treatment

Rheumatology ◽  
2020 ◽  
Author(s):  
Cleo Rogier ◽  
Fenne Wouters ◽  
Laurette van Boheemen ◽  
Dirkjan van Schaardenburg ◽  
Pascal H P de Jong ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Power Doppler ◽  
Dmard Therapy ◽  
Synovitis Score ◽  
Starting Point ◽  
Clinical Arthritis ◽  
Positive Rate ◽  
Subclinical Synovitis ◽  
Rheumatic Drug

Abstract Objectives According to guidelines, clinical arthritis is mandatory for diagnosing RA. However, in the absence of clinical synovitis, imaging-detected subclinical synovitis is increasingly used instead and is considered as a starting point for DMARD therapy. To search for evidence we studied the natural course of arthralgia patients with subclinical synovitis from three longitudinal cohorts and determined the frequencies of non-progression to clinically apparent inflammatory arthritis (IA) (i.e. ‘false positives’). Methods Subclinical synovitis in the hands or feet of arthralgia patients was visualized with US (two cohorts; definition: greyscale ≥2 and/or power Doppler ≥1) or MRI (one cohort; definition: synovitis score ≥1 by two readers). Patients were followed for 1  year on for IA development; two cohorts also had 3  year data. Analyses were stratified for ACPA. Results Subclinical synovitis at presentation was present in 36%, 41% and 31% in the three cohorts. Of the ACPA-positive arthralgia patients with subclinical synovitis, 54%, 44% and 68%, respectively, did not develop IA. These percentages were even higher in the ACPA-negative arthralgia patients: 66%, 85% and 89%, respectively. Similar results were seen after 3 years of follow-up. Conclusion Replacing clinical arthritis with subclinical synovitis to identify RA introduces a high false-positive rate (44–89%). These data suggest an overestimation regarding the value of ACPA positivity in combination with the presence of subclinical synovitis in patients with arthralgia, which harbours the risk of overtreatment if DMARDs are initiated in the absence of clinical arthritis.

scholarly journals Identification of a distinct imaging phenotype may improve the management of palindromic rheumatism

2018 ◽  
Vol 78 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Kulveer Mankia ◽  
Maria-Antonietta D’Agostino ◽  
Richard J Wakefield ◽  
Jackie L Nam ◽  
Waqar Mahmood ◽  
...  
Keyword(s):  
At Risk ◽  
High Frequency ◽  
Power Doppler ◽  
Musculoskeletal Symptoms ◽  
High Resolution Imaging ◽  
Palindromic Rheumatism ◽  
Treatment Naïve ◽  
Resolution Imaging ◽  
Citrullinated Peptide ◽  
New Onset

ObjectivesTo use high-resolution imaging to characterise palindromic rheumatism (PR) and to compare the imaging pattern observed to that seen in new-onset rheumatoid arthritis (NORA).MethodsUltrasound (US) assessment of synovitis, tenosynovitis and non-synovial extracapsular inflammation (ECI) was performed during and between flares in a prospective treatment-naive PR cohort. MRI of the flaring region was performed where possible. For comparison, the same US assessment was also performed in anticyclic citrullinated peptide (CCP) positive individuals with musculoskeletal symptoms (CCP+ at risk) and patients with NORA.ResultsThirty-one of 79 patients with PR recruited were assessed during a flare. A high frequency of ECI was identified on US; 19/31 (61%) of patients had ECI including 12/19 (63%) in whom ECI was identified in the absence of synovitis. Only 7/31 (23%) patients with PR had synovitis (greyscale ≥1 and power Doppler ≥1) during flare. In the hands/wrists, ECI was more prevalent in PR compared with NORA and CCP+ at risk (65% vs 29 % vs 6%, p<0.05). Furthermore, ECI without synovitis was specific for PR (42% PR vs 4% NORA (p=0.003) and 6% CCP+ at risk (p=0.0012)). Eleven PR flares were captured by MRI, which was more sensitive than US for synovitis and ECI. 8/31 (26%) patients with PR developed RA and had a similar US phenotype to NORA at progression.ConclusionPR has a distinct US pattern characterised by reversible ECI, often without synovitis. In patients presenting with new joint swelling, US may refine management by distinguishing relapsing from persistent arthritis.

scholarly journals Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis

2015 ◽  
Vol 75 (6) ◽  
pp. 1099-1107 ◽  
Author(s):  
Maria Juarez ◽  
Holger Bang ◽  
Friederike Hammar ◽  
Ulf Reimer ◽  
Bernard Dyke ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Arthritis ◽  
Serum Antibody ◽  
The Other ◽  
Post Translational Modifications ◽  
Treatment Naïve ◽  
Early Inflammatory Arthritis ◽  
First Time ◽  
Citrullinated Peptide

ObjectiveTo investigate serum antibody reactivity against a panel of post-translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis.MethodsA panel of PTMPs was developed. Microtitre plates were coated with peptides derived from vimentin that were identical in length and composition except at one amino acid that was changed to introduce one of three post-translational modifications (PTMs)—either a citrullinated, carbamylated or acetylated residue. Sera of 268 treatment-naive patients with early inflammatory arthritis and symptoms ≤3 months' duration were tested. Patients were assigned to one of three outcome categories at 18-month follow-up (rheumatoid arthritis (RA), persistent non-RA arthritis and resolving arthritis).ResultsAntibodies against citrullinated, carbamylated and acetylated vimentin peptides were detected in the sera of patients with early inflammatory arthritis. The proportion of patients seropositive for all antibody types was significantly higher in the RA group than in the other groups. Anti cyclic citrullinated peptide (CCP)-positive patients with RA had higher numbers of peptides recognised and higher levels of antibodies against those peptides, representing a distinct profile compared with the other groups.ConclusionsWe show for the first time that antibodies against acetylated vimentin are present in the sera of patients with early RA and confirm and extend previous observations regarding anticitrullinated and anticarbamylated antibodies.

Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients

Rheumatology ◽  
2021 ◽  
Author(s):  
Mirko Di Ruscio ◽  
Ilaria Tinazzi ◽  
Angela Variola ◽  
Andrea Geccherle ◽  
Antonio Marchetta ◽  
...  
Keyword(s):  
De Novo ◽  
Severe Disease ◽  
Power Doppler ◽  
Case Series ◽  
Imaging Features ◽  
Duration Of Symptoms ◽  
The Mean ◽  
Power Doppler Signal ◽  
Sonographic Imaging

Abstract Background Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases. Methods In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described. Results A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n = 4), unifocal (n = 6), and enthesitis/synovitis/dactylitis (n = 1). The mean duration of symptoms was 46 weeks (range 6–119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications Conclusions A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy.

scholarly journals Bone Erosions Detected by Ultrasound Are Prognostic for Clinical Arthritis Development in Patients With ACPA and Musculoskeletal Pain

2021 ◽  
Vol 8 ◽  
Author(s):  
Michael Ziegelasch ◽  
Emma Eloff ◽  
Hilde B. Hammer ◽  
Jan Cedergren ◽  
Klara Martinsson ◽  
...  
Keyword(s):  
At Risk ◽  
Musculoskeletal Pain ◽  
Cox Regression ◽  
Power Doppler ◽  
Multivariable Analysis ◽  
Control Group ◽  
Cox Regression Analysis ◽  
Bone Erosions ◽  
Clinical Arthritis ◽  
Hands And Feet

Anti-citrullinated protein antibodies (ACPA) often precede onset of rheumatoid arthritis (RA) by years, and there is an urgent clinical need for predictors of arthritis development among such at-risk patients. This study assesses the prognostic value of ultrasound for arthritis development among ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients without clinical signs of arthritis at baseline. Ultrasound at baseline assessed synovial hypertrophy, inflammatory activity by power Doppler, and erosions in small joints of hands and feet. We applied Cox regression analyses to examine associations with clinical arthritis development during follow-up (median, 69 months; range, 24–90 months). We also compared the ultrasound findings among the patients to a control group of 100 blood donors without musculoskeletal pain. Clinical arthritis developed in 39/82 patients (48%) after a median of 6 months (range, 1–71 months). One or more ultrasound erosions occurred in 13/82 patients (16%), with none in control subjects (p &lt; 0.001). Clinical arthritis development was more common among patients with baseline ultrasound erosions than those without (77 vs. 42%, p = 0.032), and remained significant in a multivariable Cox regression analysis that included previously described prognostic factors (HR 3.9, 95% CI 1.6–9.4, p = 0.003). Ultrasound-detected tenosynovitis was more frequent among the patients and associated with clinical arthritis development in a univariable analysis (HR 2.5, 95% CI 1.1–5.7, p = 0.031), but did not remain statistically significant in multivariable analysis. Thus, bone erosions detected by ultrasound are independent predictors of clinical arthritis development in an ACPA-positive at-risk population.Trial Registration: Regional Ethics Committee in Linköping, Sweden, Dnr M220-09. Registered 16 December 2009, https://etikprovningsmyndigheten.se/.

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