The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level.

BACKGROUND: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. METHODS: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. FINDINGS: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). INTERPRETATION: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. FUNDING: The Italian Ministry of Health - Ricerca Corrente.

Rheumatoid arthritis: Extra-articular manifestations and comorbidities.

Although synovitis is the pathological hallmark of rheumatoid arthritis (RA), many extra-articular manifestations (EMs) and comorbidities likely occur due to the complex, chronic, inflammatory, and autoimmune features of RA. Cardiovascular (CV) disease is the most common cause of death in patients with RA. Compared to the general population, patients with RA have twice the risk of myocardial infarction and up to 50% increased CV mortality risk. Severe and prolonged disease activity, genetics, and inflammation (e.g. CRP, ACPA, cytokines, matrix-degrading enzymes) play important roles in CV disease and atheroscleroticdamage. The second major cause of death in patients with RA is respiratory disease, which occurs in 30-40% of patients. RA may affect the lung interstitium, airways, and pleurae, while pulmonary vascular involvement is less frequent. Central and peripheral nervous system involvement is usually due to small vessel vasculitis, joint damage, or drug toxicity. There is also evidence that microvascular cerebral damage caused by systemic inflammation is associated with the development of Alzheimer's disease and vascular dementia. Some observational studies have hinted how Disease Modified Anti-Rheumatic Drugs and biologics could reduce the incidence of dementia. Primary gastrointestinal and renal involvements are rare and often relate to drug therapy. To minimize morbidity and mortality, physicians must manage RA disease activity (treat-to-target) and monitor risk factors and concomitant conditions (e.g. smoking cessation; weight regulation; monitoring blood pressure, lipids, thyroid hormone, folic acid and homocysteine; screening for depression, anxiety, atlantoaxial instability, and atherosclerosis). This article aims to provide an overview of the most prevalent and important EMs and comorbidities associated with RA.

Imbalanced MMP-3 and MMP-12 serum levels in systemic lupus erythematosus patients with Jaccoud's arthropathy and a distinctive MRI pattern.

OBJECTIVE: Metalloproteinase (MMP)-3 and MMP-12 are proteolytic enzymes especially implicated in joint inflammation. This study aims to evaluate their association with arthritis features and hand MRI abnormalities in patients with SLE. METHODS: Fifty SLE patients, with a mean (s.d.) age of 48.1 (14.6) years were tested for MMP-3 and MMP-12 serum levels, then further classified according to the presence of X-ray erosions and joint deformities. Eighteen RA patients aged 47.9 (11.8) and 14 healthy people aged 46.0 (11.0) were enrolled as control groups. A subgroup of 28 SLE patients underwent a dominant-hand MRI; the detected changes were classified and semi-quantitatively scored as capsular swelling, synovitis, edematous or proliferative tenosynovitis, bone oedema, bone erosions. Statistical analysis was performed using multiple regression models. RESULTS: MMP-3 were significantly higher in patients with Jaccoud's arthropathy (JA) (22.1 ng/ml, P < 0.05) and independently associated with hsCRP serum levels (B-coeff 0.50; r = 0.30; P < 0.05). MMP-12 serum levels were significantly lower in patients with JA (0.18 ng/ml, P < 0.05) and inversely associated with the prednisone daily dose (B-coeff -0.03; r = -0.44; P < 0.01). Capsular swelling and edematous tenosynovitis, the most prevalent hand MRI changes in patients with JA, associated with higher MMP-3 (B-coeff 0.12; r = 0.66; P < 0.01 and B-coeff 0.08; r = 0.59; P < 0.01, respectively) and lower MMP-12 serum levels (B-coeff -7.4; r = -0.50; P < 0.05 and B-coeff -5.2; r = -0.44; P = 0.05, respectively). CONCLUSION: Imbalanced MMP-3 and MMP-12 serum levels are influenced by inflammation and glucocorticoids in SLE patients and associated with JA and distinctive hand MRI changes.

Sensitivity to change and clinical correlations of the novel DACtylitis glObal Sonographic (DACTOS) score in psoriatic arthritis.

OBJECTIVE: The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders. METHODS: Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3). RESULTS: We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P < 0.001) and between clinical remission and non-remission groups (P < 0.001). CONCLUSION: The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

Imaging in polymyalgia rheumatica: which technique to use?

Polymyalgia rheumatica (PM) is an inflammatory rheumatic disorder characterised by pain and stiffness, mainly in the neck, shoulders, and pelvic girdle and possible association with giant cell arteritis. Currently, there is no diagnostic gold standard for PM, however, an extensive assessment of patients' inflammatory status aided by imaging evaluation is crucial for disease stratification. Many imaging techniques study PM features and their possible complications or associations with giant cell arteritis: radiography, ultrasound, scintigraphy, magnetic resonance imaging, and positron emission tomography/computed tomography. Each one has different advantages and disadvantages. The aim of this review is to clarify the current uses of imaging in PM for diagnosis and follow-up through a literature review of the last 10 years.

Novel and reliable DACTylitis glObal Sonographic (DACTOS) score in psoriatic arthritis.

OBJECTIVES: Dactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score. METHODS: After a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score. RESULTS: DACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score. CONCLUSIONS: The novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis.

Agreement between semiquantitative and quantitative Doppler scoring systems for the assessment of synovial pathological vascularisation in rheumatoid arthritis.

OBJECTIVES: To compare colour Doppler (CD) versus power Doppler (PD) semiquantitative and quantitative scoring of synovial vascularisation and to evaluate the relationship between semiquantitative and quantitative scores in patients with rheumatoid arthritis (RA). METHODS: One hundred RA patients underwent B-mode, PD, and CD assessments of 12 joints at two European centres. Each joint with synovial hypertrophy (SH) detected on B-mode was semiquantitatively scored (0-3) for PD (SPD score) and CD (SCD score) synovial signal. PD and CD synovial signal were also quantitatively scored (0-100%) (QPD and QCD scores, respectively) using a software integrated in the US equipment for counting the colour fraction. RESULTS: We found SH in 184 joints. SPD and SCD agreed in 92.3% (95%CI: 88.4; 96.2%) of paired scores, with Kendall rank correlation coefficient tau-b=0.95. QPD and QCD scores were highly correlated (Pearson's coefficient=0.70) but Blamd-Altman plot showed insufficient agreement, being the QCD scores systematically slightly higher than the QPD scores. The comparison of mean values of QPD and QCD between scores of SPD and SCD, respectively, showed significant differences between grade 0 and grade 1 (p<0.001), and grade 2 and grade 3 (p=0.042 and p=0.007, respectively) but not between grade 1 and 2 (p=0.154 and p=0.150, respectively). CONCLUSIONS: The SPD and SCD scores were concordant and the QPD and QCD scores highly correlated but were not concordant. There was an overlap between SPD and SCD mild and moderate scores regarding QPD and QCD scores.

Predictors of musculoskeletal flares and Jaccoud׳s arthropathy in patients with systemic lupus erythematosus: A 5-year prospective study.

OBJECTIVE: To investigate the prognostic value of US in predicting musculoskeletal flares and Jaccoud׳s arthropathy (JA) in systemic lupus erythematosus (SLE). METHODS: A total of 80 out of 94 patients (76 female; age 45.5 ± 13.2 years) with non-deforming non-erosive (NDNE) arthritis and 48/60 healthy controls (42 female; age 49.6 ± 11.6 years) completed the 5-year follow-up study. Each patient was prospectively assessed for the occurrence of musculoskeletal flares using BILAG2004 and hand deformities according to Jaccoud׳s articular index. Baseline clinical, serological, semi-quantitative (0-3 scale) ultrasound (US) findings, PD-synovitis and PD-tenosynovitis scores were used as covariates to identify predictors of study outcomes. Short Form 36 v2 (SF36v2) health survey questionnaire was administered. RESULTS: Overall, 12 MS flares in 10 (12.5%) patients were recorded and the incidence rate was 3.0 per 100 patient-year. Baseline PD-synovitis score independently predicted MS flare (p < 0.001; RR = 2.0; 95% CI: 1.4-3.0) within 2 years since US examination. In all, 5 (6.2%) patients developed JA whose incidence rate was 1.25 per 100 patient-year. Independent risk factors for development of JA were higher longitudinal BILAG score in the musculoskeletal domain (p = 0.005; RR = 2.4; 95% CI: 1.3-4.6) and longer disease duration (p = 0.013; RR 1.2; 95% CI: 1.1-1.3). JA and active musculoskeletal inflammation (BILAG ≥ C), but not US erosions, were associated with lower results in SF36v2 physical and mental summary components. CONCLUSIONS: Performing musculoskeletal US can be useful in order to predict MS flares. Jaccoud׳s deformities may arise in patients with long-standing SLE and prolonged, even subclinical, joint and tendon inflammation.