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Doubtful swelling on clinical examination reflects synovitis in rheumatoid arthritis.

ABSTRACT: Aims:The aim of this study was to evaluate the implication of doubtful joint swelling on clinical examination with respect to objective markers of synovitis by ultrasound (US) in patients with rheumatoid arthritis (RA). Methods:Two independent observers performed a modified 28 swollen joint assessment (28SJC), in which joints could be graded as either definitely swollen, non-swollen, or doubtfully swollen. Two examiners blinded to clinical information performed US assessment of the hands. We performed descriptive statistics and models to analyse the links between clinical assessment and objective markers of inflammation. Results:A total of 1204 joints were evaluated in 43 RA patients; 93% (40/43) of patients had ?1 joint with doubtful swelling (range: 0-4/patient). Inter-reader reliability for the modified 28SJC was good (0.74). Generally, both grey scale (GS) and power Doppler (PD) discriminated across not swollen, doubtful, and swollen joints. GS signals discriminated better than PD between doubtful swelling and no swelling [odds ratio (OR) for GS: 5.2; 95% confidence interval (CI) 1.2-23.3 versus OR for PD 1.7; 95% CI 0.2-13.0], whereas PD discriminated better than GS between swelling and doubtful swelling (OR for PD: 28.7; 95% CI 3.6-228.2 versus GS: 1.7; 95% CI 0.3-8.4). Joint osteophytes did not increase the degree of doubtfulness. Conclusion:Clinical doubt in the assessment of joint swelling constitutes an intermediate state between unequivocal swelling and the lack thereof also regarding the objectively quantified level of inflammation. In order to increase sensitivity for joint inflammation, the historical clinical approach of considering doubtful swelling the absence of swelling should be revisited to interpret clinical doubtfulness as an indication of swelling.

SUBMITTER: Mandl P

PROVIDER: S-EPMC7309376 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Doubtful swelling on clinical examination reflects synovitis in rheumatoid arthritis.

Mandl Peter P Studenic Paul P Supp Gabriela G Durechova Martina M Haider Stefanie S Lehner Michaela M Stamm Tanja T Smolen Josef S JS Aletaha Daniel D

Therapeutic advances in musculoskeletal disease 20200622

<h4>Aims</h4>The aim of this study was to evaluate the implication of doubtful joint swelling on clinical examination with respect to objective markers of synovitis by ultrasound (US) in patients with rheumatoid arthritis (RA).<h4>Methods</h4>Two independent observers performed a modified 28 swollen joint assessment (28SJC), in which joints could be graded as either definitely swollen, non-swollen, or doubtfully swollen. Two examiners blinded to clinical information performed US assessment of th ...[more]

PMID: 32612711

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Project description:ObjectiveMusculoskeletal ultrasound real-time image acquisition and scoring are complex, and many factors affect reliability. Static image reliability does not guarantee real-time scoring. This study aimed to identify factors and solutions to improve real-time scoring reliability for the grey scale and power Doppler evaluation of synovitis. We also report on using a novel musculoskeletal ultrasound synovitis rule-based scoring atlas.MethodsIn four stages, we evaluated inter- and intra-reader reliability among three ultrasonographers (US1-3). Intra- and inter-reader reliability was calculated using weighted-kappa, intraclass correlation coefficient, and Spearman correlation. Reliability statistics were compared between stages using permutation tests to compute empirical distributions for differences in those statistics. At each stage, factors that diminished reliability were identified and addressed. After intensive reliability exercises, a RA MSUS atlas with in-depth scoring rules was generated to improve interpretive reliability.ResultsThe three ultrasonographers had good to excellent intra-reader reliability for real-time acquisition scoring over 2432 views (weighted kappa 0.52-0.80, intraclass correlation coefficient 0.59-0.86, and Spearman correlation 0.64-0.86). Inter-reader reliability was good to excellent between US1/US2 and US1/US3 (weighted kappa 0.51-0.66, intraclass correlation coefficient 0.66-0.75, Spearman correlation 0.59-0.73). US1 achieved significant improvement in intra-reader reliability from stage 1 to stage 2 (p<0.05, weighted-kappa 0.63 to 0.80, intraclass correlation coefficient 0.71 to 0.86, Spearman 0.67 to 0.86) with use of the atlas. Conclusion: This rheumatoid arthritis musculoskeletal ultrasound study addressed complex factors affecting musculoskeletal ultrasound acquisition-scoring reliability. Systematic identification and amelioration of many factors and using a novel rule-based scoring atlas significantly improved intra-reader reliability.

Project description:BackgroundA DNA methylation signature has been characterized that distinguishes rheumatoid arthritis (RA) fibroblast like synoviocytes (FLS) from osteoarthritis (OA) FLS. The presence of epigenetic changes in long-term cultured cells suggest that rheumatoid FLS imprinting might contribute to pathogenic behavior. To understand how differentially methylated genes (DMGs) might participate in the pathogenesis of RA, we evaluated the stability of the RA signature and whether DMGs are enriched in specific pathways and ontology categories.MethodsTo assess the RA methylation signatures the Illumina HumanMethylation450 chip was used to compare methylation levels in RA, OA, and normal (NL) FLS at passage 3, 5, and 7. Then methylation frequencies at CpGs within the signature were compared between passages. To assess the enrichment of DMGs in specific pathways, DMGs were identified as genes that possess significantly differential methylated loci within their promoter regions. These sets of DMGs were then compared to pathway and ontology databases to establish enrichment in specific categories.ResultsInitial studies compared passage 3, 5, and 7 FLS from RA, OA, and NL. The patterns of differential methylation of each individual FLS line were very similar regardless of passage number. Using the most robust analysis, 20 out of 272 KEGG pathways and 43 out of 34,400 GO pathways were significantly altered for RA compared with OA and NL FLS. Most interestingly, we found that the KEGG 'Rheumatoid Arthritis' pathway was consistently the most significantly enriched with differentially methylated loci. Additional pathways involved with innate immunity (Complement and Coagulation, Toll-like Receptors, NOD-like Receptors, and Cytosolic DNA-sensing), cell adhesion (Focal Adhesion, Cell Adhesion Molecule), and cytokines (Cytokine-cytokine Receptor). Taken together, KEGG and GO pathway analysis demonstrates non-random epigenetic imprinting of RA FLS.ConclusionsThe DNA methylation patterns include anomalies in key genes implicated in the pathogenesis of RA and are stable for multiple cell passages. Persistent epigenetic alterations could contribute to the aggressive phenotype of RA synoviocytes and identify potential therapeutic targets that could modulate the pathogenic behavior.

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Doubtful swelling on clinical examination reflects synovitis in rheumatoid arthritis.

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Doubtful swelling on clinical examination reflects synovitis in rheumatoid arthritis.

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