Novel insights into the management of rheumatoid arthritis: one year in review 2024.

New evidence from 2023 has slightly shifted some perspectives on rheumatoid arthritis (RA) management. Glucocorticoids have reaffirmed their role as bridging therapy, while novel studies on JAK inhibitors have examined efficacy, mechanism of action, and their potential in high-risk populations, bolstering our understanding with real-world data.Additionally, among treatment strategies, achieving low disease activity has emerged as comparable to achieving remission in the long term, and new insights have been gained regarding tapering both biological and conventional synthetic DMARDs. Furthermore, novel approaches have been proposed for managing difficult-to-treat RA and pre-RA. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Effectiveness and Safety of Remdesivir in Treating Hospitalised Patients with COVID-19: A Propensity Score Analysis of Real-Life Data from a Monocentric Observational Study in Times of Health Emergency.

BACKGROUND AND OBJECTIVES: Remdesivir is an antiviral agent, which was shown to be safe and effective in treating early COVID-19, but its favourable impact in hospitalised patients with non-critical disease is still under investigation. The present study aimed to assess the effectiveness and safety of remdesivir as a treatment for hospitalised patients with COVID-19 by a propensity score analysis of observational data. METHODS: In this monocentric retrospective cohort study, the effectiveness and safety of a 5-day course of remdesivir (200 mg intravenously at Day 1, then 100 mg from Days 2-5) in association with the standard of care were assessed in comparison with the standard of care only. The primary endpoint was the proportion of recovery on Day 14. RESULTS: Of 3662 eligible inpatients who tested positive for the severe acute respiratory syndrome coronavirus 2 genome by nasopharyngeal swab at admission, 861 (24%) non-critical patients were included in a propensity score analysis and 281 (33%) were exposed to remdesivir. In total, 242/281 (86.1%) and 435/580 (75.0%) patients recovered in exposed and non-exposed, respectively, with a relative improvement of 11.1% (95% CI + 5.8 to 16.5%; unadjusted odds ratio: 2.07, 95% CI 1.40-3.05, p = 0.0001; after adjustment by propensity score weighting, odds ratio: 1.92, 95% CI 1.30-2.83, p = 0.001). In treated patients, 1 (0.03%) anaphylactic reaction and 1 (0.03%) acute reaction during drug injection were reported, and 24 (8.5%) patients stopped the treatment due to adverse reactions. No significant differences were found with respect to the secondary efficacy endpoints (in-hospital all-cause death, need for intensive care treatments, clinical improvement score at Day 28) and safety endpoints (any and serious adverse reactions). CONCLUSION: A 5-day course of remdesivir in association with the standard of care effectively promoted recovery from COVID-19 among non-critical in-hospital patients and had an acceptable safety profile.

Novel insights into the management of rheumatoid arthritis: one year in review 2023.

New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying anti-rheumatic drugs strengthened the importance of tailoring treatment decisions based on patient characteristics. Moreover, the research of response biomarkers to therapy underlined the need for precision medicine and remote care applications showed an innovative outlook that supports a patient-centred approach. New developments in vaccinations led to the release of updated guidelines and to a consistent improvement in the prevention of vaccine-preventable infections. New literature data also reconsidered drug management in RA-associated interstitial lung disease and pregnancy. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

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.

Sclerodermic hand: a retrospective study on the role of ultrasonography in the detection of subclinical joint involvement.

INTRODUCTION: The inflammatory involvement of joints and tendons is common in Systemic Sclerosis (SSc). Ultrasonography (US) is a non-invasive tool commonly applied for the assessment of the main inflammatory arthropathies and could be also used in identifying pathological features in SSc patients, even without clinical evidence of joint complaint. So, the aim of this study was to assess the prevalence of US pathological features in a cohort of SSc patients and assessed the role of US in the detection of subclinical joint involvement. METHODS: In this retrospective study, we collected data about the prevalence of US pathological features at the level of hands and wrists in a cohort of patients with a definite diagnosis of SSc, submitted to an ultrasound examination of hands and wrists according to the clinician's opinion, with or without joint involvement symptoms, in order to assess the US ability in detecting subclinical inflammatory signs in SSc patients. RESULTS: In total, 47.5% of patients reported at least one US pathological feature. The most common was synovial hypertrophy (62.1%). Other assessed lesions were effusion (48%), tenosynovitis (37.9%), power Doppler (PD) signal (31.0%), and erosions (0.7%). Effusion and PD signal appeared significantly higher in symptomatic patients, with a p<0.01 and p=0.045, respectively. CONCLUSIONS: In this cohort of SSc subjects, almost the half of the US-positive patients were clinically asymptomatic. Therefore, the application of US could be useful to detect the musculoskeletal involvement of SSc patients, a potential markers of disease severity. Further studies are required to assess the role of US in monitoring SSc patients. Key Points • The inflammatory involvement of joints and/or tendons is common in systemic sclerosis (SSc) but could be partially covered by other disease features. • Among the diagnostic methods able to increase the sensitivity of the musculoskeletal evaluation, Ultrasonography (US) is one of the most promising to reveal subclinical inflammation and predict the joint damage progression. • We retrospectively investigated the prevalence of US pathological features in a cohort of SSc patients, with or without symptoms of joint involvement, assessing the role of US in the detection of subclinical joint involvement. • We found that joint and tendon involvement, a potential marker of disease severity, is common in SSc.

Joining telehealth in rheumatology: a survey on the role played by personalized experience from patients' perspective.

BACKGROUND: The beginning of the Covid-19 pandemic has forced many hospital departments worldwide to implement telehealth strategies for the first time. Telehealth represents the opportunity to increase value for all stakeholders, including patients and healthcare staff, but its success constitutes a challenge for all of them and particularly patients play a crucial role for their needed adherence. This study focuses on the experience of the Rheumatology Unit of Niguarda Hospital in Milan (Italy), where telehealth projects have been implemented for more than a decade with structured design and organized processes. The case study is paradigmatic because patients have experimented personalized mixes of telehealth channels, including e-mails and phone calls, Patient Reported Outcomes questionnaires, and home delivery of drugs. Given all these peculiarities, we decided to deepen patients' perspective through three main aspects related to the adoption of telehealth: (i) the benefits perceived, (ii) the willingness to enrol in future projects, (iii) the preference on the service-mix between remote contacts and in-person visits. Most importantly, we investigated differences in the three areas among all patients based on the mix of telehealth channels experienced. METHODS: We conducted a survey from November 2021 to January 2022, enrolling consecutively patients attending the Rheumatology Unit of Niguarda Hospital in Milan (Italy). Our survey comprised an introductory set of questions related to personal, social, clinical and ICT skills information, followed by the central part on telehealth. All the answers were analysed with descriptive statistics and regression models. RESULTS: A complete response was given by 400 patients: 283 (71%) were female, 237 (59%) were 40-64 years old, 213 (53%) of them declared to work, and the disease most represented was Rheumatoid Arthritis (144 patients, 36%). Descriptive statistics and regression results revealed that (i) non-users imagined wide-ranging benefits compared to users; (ii) other things being equal, having had a more intense experience of telehealth increased the odds of accepting to participate to future projects by 3.1 times (95% C.I. 1.04-9.25), compared to non-users; (iii) the more telehealth was experienced, the higher the willingness to substitute in-person with online contacts. CONCLUSIONS: Our study contributes to enlighten the crucial role played by the telehealth experience in determining patients' preferences.

Which are the most frequently involved peripheral joints in calcium pyrophosphate crystal deposition at imaging? A systematic literature review and meta-analysis by the OMERACT ultrasound - CPPD subgroup.

Objectives: To identify the prevalence of calcium pyrophosphate crystal deposition (CPPD) using ultrasound and conventional radiology at peripheral joints in patients with suspected or definite CPPD. Methods: A systematic literature search was performed in PubMed and Embase using pre-defined search strategies from inception to April 2021 to identify studies that evaluated conventional radiology and ultrasound in detecting CPPD at peripheral joints, including definite or suspected CPPD [Research question 1 (RQ1) and Research Question 2 (RQ2), respectively]. For the meta-analysis, the first, second, and third sub-analysis included studies with the knee, and knee or wrist as the index joint for CPPD (without restrictions on the reference standard) and synovial fluid analysis or histology as a reference standard (without restrictions on the index joint), respectively. Results: One-thousand eight hundred and twenty-seven manuscripts were identified, of which 94 articles were finally included. Twenty-two and seventy-two papers were included in RQ1 and RQ2, respectively. The knee had the highest prevalence for RQ1 and RQ2 by both conventional radiology and ultrasound, followed by the wrist with the highest prevalence for RQ1. The hand had the lowest CPPD prevalence. The third sub-analysis showed a higher CPPD prevalence on ultrasound than conventional radiology at the knee (only data available). Conclusion: Among all peripheral joints, the knees and wrists could be regarded as the target joints for CPPD detection by imaging. Furthermore, ultrasound seems to detect a higher number of calcium pyrophosphate deposits than conventional radiology, even when using a more restrictive reference standard.

Active vaccination campaign to increase seasonal influenza vaccination coverage: a monocenter experience in a cohort of Italian patients with systemic autoimmune diseases.

Seasonal influenza is a frequent cause of hospitalization and mortality among patients with systemic autoimmune diseases. Despite this evidence, vaccination coverage is generally much lower than the minimum 75% target proposed by the WHO. Therefore, an active campaign was implemented in the years 2019/2020 and 2020/2021 within the Rheumatology Department of the Niguarda Hospital (Milan, Italy) to improve the vaccination coverage in patients with inflammatory arthritis. This study aims to evaluate the vaccination coverage in the 2019/2020 and 2020/2021 (active campaigns) seasons and to compare these results with the 2018/2019 season. A monocenter observational study was conducted among adult patients with rheumatoid arthritis, spondylarthritis, or psoriatic arthropathy, who were referred to the Rheumatology Department of the Niguarda Hospital. Patients were given a questionnaire to investigate previous years' vaccination coverage and to propose an influenza vaccine for the 2020/2021 season. Compared with 2018/2019, a trend for increase in vaccination coverage was reported in 2019/2020 season (+ 10.7%, p = 0.055; 45.5% of coverage) and a statistically significant increase was reported in 2020/2021 (+ 31.2%, p < 0.001; 65.9% of coverage). The increase was also significant when comparing the 2020/2021 and 2019/2020 seasons (+ 20.5%, p < 0.001). The greatest increase in vaccination coverage was observed among under-65-year-old patients. Obtained results support the implementation of active vaccination campaigns to increase vaccination coverage among patients with systemic autoimmune diseases and highlight the importance of external factors (such as the COVID-19 pandemic) in directing the patient to adopt preventive measures to avoid infections and related complications.

Reliability and Diagnostic Accuracy of Radiography for the Diagnosis of Calcium Pyrophosphate Deposition: Performance of the Novel Definitions Developed by an International Multidisciplinary Working Group.

OBJECTIVE: To assess the reliability and diagnostic accuracy of new radiographic imaging definitions developed by an international multidisciplinary working group for identification of calcium pyrophosphate deposition (CPPD). METHODS: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and 2 rheumatologists twice assessed radiographic images for presence or absence of CPPD in menisci, hyaline cartilage, tendons, joint capsule, or synovial membrane, using the new definitions. In case of disagreement, a consensus decision was made and considered for the assessment of diagnostic performance. Histologic examination of postsurgical specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa values were used to assess reliability, and diagnostic performance statistics were calculated. RESULTS: Sixty-seven patients were enrolled for the reliability study. The interobserver reliability was substantial in most of the assessed structures when considering all 4 readers (κ range 0.59-0.90), substantial to almost perfect among radiologists (κ range 0.70-0.91), and moderate to almost perfect among rheumatologists (κ range 0.46-0.88). The intraobserver reliability was substantial to almost perfect for all the observers (κ range 0.70-1). Fifty-one patients were included in the accuracy study. Radiography demonstrated an overall specificity of 92% for CPPD, but sensitivity remained low for all sites and for the overall diagnosis (54%). CONCLUSION: The new radiographic definitions of CPPD are highly specific against the gold standard of histologic diagnosis. When the described radiographic findings are present, these definitions allow for a definitive diagnosis of CPPD, rather than other calcium-containing crystal depositions; however, a negative radiographic finding does not exclude the diagnosis.

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.

Novel insights into the management of rheumatoid arthritis: one year in review 2022.

New evidence for the treatment of rheumatoid arthritis (RA) has emerged during the last year. Specifically, updated guidelines on pharmacological and non-pharmacological management of RA have emphasised the necessity of global patient's care, and have shifted the role of some older drugs, such as glucocorticoids and methotrexate. In addition, the long-term safety of Janus kinase inhibitors was investigated and reinforced. With respect to the coronavirus-19 pandemic, reassuring data on the efficacy and safety of vaccinations in the RA population were acquired, as well as on the potential role of telemedicine in RA management. Machine learning prediction models and biomarkers development have emerged as promising innovations in the area of precision/personalised medicine, appearing to encourage future expansion.In this narrative review, the authors aim to give their specific point of view on the most relevant and potentially impacting novelties published during 2021 and early 2022 in the context of RA management.

Ultrasound-detected inflammation is more common in clinically manifest hand osteoarthritis than in painless bony enlarged finger joints: subanalysis of the population-based Bruneck study.

Purpose: The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C). Methods: This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0-3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved. Results: Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33). Conclusion: GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.

Trends in all-cause mortality of hospitalized patients due to SARS-CoV-2 infection from a monocentric cohort in Milan (Lombardy, Italy).

Background: Robust data on case fatality rate (CFR) among inpatients with COVID-19 are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. This study quantified the overall CFR and described its trend in a cohort of hospitalized patients with SARS-CoV-2 in Italy. Admission to ICU, death, or discharge were the secondary outcomes. Methods: This retrospective study is based on administrative health data and electronic case records of inpatients consecutively admitted to Niguarda Hospital between 21 February and 8 November 2020. Results: An overall CFR of 18% was observed. CFR was significantly reduced during the second wave of contagion (1 June to 30 September, 16%) compared with the first wave (21 February to 31 May, 21% p = 0.015). Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was associated with a high risk of mortality in both waves. The incidence of severe disease and the need for ICU admission were lower in the second wave. Conclusion: CFR in SARS-CoV-2 inpatients was demonstrated to decrease over time. This reduction may partly reflect the changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to plan an exit strategy in case of future outbreaks. Key messages: What is already known on this topic Before the advent of anti-COVID-19 vaccines, a multi-wave pattern of contagion was observed, and this trend conditioned the inpatient case fatality rate (CFR), which varied over time accordingly to the waves of contagion.Only preliminary results on the in-hospital mortality trend are available, along with a partial analysis of its determinants. Consequently, robust data on CFR among inpatients with SARS-CoV-2 infection are still lacking, and the role of patient characteristics in in-hospital deaths remains under-investigated. What this study adds This study shows that the in-hospital mortality in patients with SARS-CoV-2 infection decreases over time.Such reduction was mainly observed among male inpatients between 40 and 80 years with limited comorbidities. Admission to ICU was invariably associated with a high risk of mortality during the whole study period (21 February to 8 November 2020), but the incidence of severe disease and the need for ICU admission were lower in the second wave of contagions (1 October to 8 November 2020). This reduction may partly reflect the impact of changes in hospital strategy and clinical practice. The reasons for this improvement should be further investigated to inform the response to future outbreaks and to plan exit strategy by prioritizing high-risk populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01675-y.

Use of telemedicine during the COVID-19 pandemic in patients with inflammatory arthritis: a retrospective study on feasibility and impact on patient-reported outcomes in a real-life setting.

Close follow-up is mandatory in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). During the Coronavirus Disease 2019 (COVID-19) pandemic, rheumatological care was rapidly reorganized during the first peak from March 1, 2020 to May 31, 2020, and all patients with RA, PsA, and AS being treated with a subcutaneous biologic disease-modifying anti-rheumatic drug or oral targeted synthetic disease-modifying anti-rheumatic drug were followed remotely. A retrospective database analysis of these 431 patients before and after this period is presented herein. A rheumatologist directly contacted all patients by telephone. Patients could also enter data on patient-reported outcomes remotely using the digital platform iAR Plus. General health (GH) and visual analog scale (VAS) pain were the main outcomes along with FACIT and disease-specific questionnaires (RADAI, ROAD, PROCLARA for RA, and BASDAI, BASGI, BASFI for AS). In all, 449 visits were postponed (69.9% of all scheduled visits); telephone evaluation was deemed inadequate in 193 instances, and patients underwent a standard outpatient visit. Comparing patients on telemedicine to those who underwent hospital visits, we found no statistically significant differences in GH (35.3 vs 39.3; p = 0.24), VAS (33.3 vs 37.1; p = 0.29), or other specific outcome measures in patients with RA, PsA, or AS. These results show that telemedicine has undoubted benefits, and in light of the ongoing COVID-19 pandemic, it is likely that many patients with these diseases may prefer it.

The two faces of the same medal or maybe not? Comparing osteoarthritis and calcium pyrophosphate deposition disease: a laboratory and ultrasonographic study.

OBJECTIVES: Osteoarthritis (OA) and calcium pyrophosphate deposition disease (CPPD) are frequently associated but the real relation between these diseases is not still understood. The aim of this paper is to investigate the characteristics in terms of inflammation, anatomical changes and synovial fluid (SF) features in knees of patients with OA and CPPD. METHODS: Consecutive patients older than 55 years with knee pain and swelling were enrolled. All patients underwent a complete clinical examination, a US examination of the affected joint, arthrocentesis of the knee and analysis of synovial fluid, including dosing of inorganic ions and number of crystals. The gold standard for the diagnosis was the microscopic analysis of the SF. RESULTS: Sixty-seven patients were enrolled, 25 affected by OA and 42 by CPPD. At US, a significantly higher amount of effusion and synovitis was identified in patients with CPPD but there were no significant differences regarding structural changes. At the SF analysis, the white blood cell (WBC) count was higher in patients with CPPD who also presented a higher number of polymorphonuclear cells and a lower number of monocytes. Regarding the inorganic ion concentration, the statistical analysis did not reveal any differences. The number of crystals in the SF, correlated with a larger effusion, higher grade of synovitis and a higher WBC count. CONCLUSIONS: A higher degree of inflammation was found in patients with CPPD. The findings suggest that longitudinal studies would be useful to better understand the evolution of the diseases and highlight the need for different treatment strategies.

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.

Differential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A Systematic Literature Review.

Background: Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. Methods: In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. Results: For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Conclusions: Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.

OMERACT agreement and reliability study of ultrasonographic elementary lesions in osteoarthritis of the foot.

Objective: To evaluate the level of agreement on ultrasonographic (US) lesions among highly experienced sonographers as well as the intraobserver and interobserver reliability of inflammatory and structural US lesions in patients with osteoarthritis (OA) of the foot. Methods: After a systematic literature review, a Delphi survey was performed to test definitions of US lesions in OA of the foot, including inflammatory lesions (ie, synovial hypertrophy [SH], joint effusion [JE], power Doppler signal [PD]), and structural abnormalities (ie, cartilage damage [CD] and osteophytes). Subsequently, the reliability of US in assessing the aforementioned lesions was tested on static images as well as during a live exercise. Reliability was assessed by kappa analyses and prevalence-adjusted bias-adjusted kappa (PABAK) on a dichotomous and an ordinal scale. Results: Intraobserver and interobserver reliability for SH and JE evaluated by binary scoring was good for both components, while the intraobserver reliability for semiquantitative scoring of SH ranged from moderate in the web-based exercise (PABAK 0.49) to good (PABAK 0.8) in the live exercise. Reliability for CD and PD assessments were respectively good and excellent in all exercises (ranged from PABAK 0.61 to 0.79 for CD and 0.88 to 0.95 for PD). The interobserver reliability for the semiquantitative scoring of osteophytes was fair in the live exercise (PABAK 0.36) and moderate in the static exercise (PABAK 0.60). Conclusions: Consensual US definitions were found to be reliable for assessing inflammatory lesions in OA of the foot, while the use of US to assess structural damage requires further studies.