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The objective of this study is to estimate the prevalence of US findings indicative of calcium pyrophosphate deposition (CPPD) in patients with knee pain. Consecutive patients with knee pain, equally distributed among males and females in seven different age-decades (21-90 years), were enrolled in a cross-sectional study. The presence of US OMERACT-defined CPPD (medial and lateral menisci and femoral hyaline cartilage) and osteophytes (medial and lateral compartments of the tibiofemoral joint) was scored as presence/absence in both knees. Four hundred twenty participants were enrolled (210 men/210 women). Fibrocartilage and hyaline cartilage CPPDs were detected by US in 94/420 (22.4%) and 41/420 (9.8%) participants, respectively. No significant sex differences were noted. The prevalence and the extent of CPPD increased with age. Fibrocartilage and hyaline cartilage CPPDs were identified in 0/60 participants in the third decade, and in 28/60 (46.7%) and 14/60 (23.3%) participants in the ninth decade, respectively (p for trend < 0.01). While fibrocartilage and hyaline cartilage CPPD is virtually absent in subjects younger than 40 and 50 years old, their prevalence steeply increases above from these age groups. Age (aIRR, 1.03; 95% CI, 1.02-1.05), osteophyte score (aIRR, 1.40; 95% CI, 1.22-1.60), and hyaline cartilage CPPD score (aIRR, 2.68; 95% CI, 2.06-3.49) were associated with fibrocartilage CPPD score, whereas age (aIRR, 1.02; 95% CI, 1.01-1.05) and fibrocartilage CPPD score (aIRR, 2.92; 95% CI, 2.29-3.72) were associated with hyaline cartilage CPPD score in multivariable negative binomial regression analyses. In conclusion, we report the US prevalence of CPPD in patients with knee pain. Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. Key points • Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. • Fibrocartilage and hyaline cartilage CPPDs are virtually absent in subjects younger than 40 and 50 years old. • In subjects older than 80 years, fibrocartilage and hyaline cartilage CPPD prevalence rises up to 46.7% and 23.3%, respectively., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin., Methods: Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated., Results: A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92-0.96) and CPPD (0.90-0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P = 0.03; CPPD AUC 0.93 vs 0.84, P = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD., Conclusions: A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To test whether the double contour (DC) sign has a different dynamic behaviour in gout and calcium pyrophosphate deposition (CPPD) and whether the dynamic assessment of the DC sign increases its accuracy in gout diagnosis., Methods: This cross-sectional analysis included patients with gout meeting the 2015 ACR/EULAR classification criteria and patients with crystal-proven diagnosis of CPPD. Hyaline cartilages were explored by ultrasound (US) to detect the DC sign (ie, abnormal hyperechoic band over the superficial margin of hyaline cartilages) and its dynamic behaviour during joint movement was evaluated ((ie, movement of the DC sign together with subchondral bone (DC sign), or in the opposite direction (pseudo DC sign))., Results: Eighty-one patients with gout and 84 patients with CPPD underwent US assessment. Among them, 47 patients with gout and 9 patients with CPPD had evidence of the DC sign. During dynamic assessment, in all 47/47 patients with gout there was a DC sign. Conversely, in 7/9 (77.8%) patients with CPPD, there was a pseudo DC sign (p<0.01).The presence of DC sign during static assessment had a sensitivity, specificity and accuracy of 58.0% (95% CI 46.5% to 68.9%), 89.3% (95% CI 80.6% to 95.0%) and 73.9% (95% CI 66.5% to 80.5%) for gout, respectively. The dynamic evaluation improved the DC sign's diagnostic performance (p=0.01) as the specificity (97.6% (95% CI 91.7% to 99.7%)) and the accuracy (78.2% (95% CI 71.1% to 84.2%)) increased without loss in sensitivity., Conclusion: The dynamic US assessment of the DC sign may help to differentiate the DC sign due to MSU crystals from the pseudo DC sign seen in CPPD, as they move in opposite directions., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form. AA has received departmental research grants from AstraZeneca and Oxford Immunotec, speaker bureau fees from Menarini, scientific meeting support from Pfizer, consulting fees from Inflazome and author royalties from UpToDate and Springer, unrelated to this work. EC has received a scientific training grant from the EULAR, unrelated to this work. EF has received speaking fees from AbbVie, Amgen, BMS, Janssen, Lilly, Novartis, Roche, Pfizer and UCB, unrelated to this work. WG has received speaking fees from Celltrion and Pfizer, unrelated to this work. ADM has no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the spectrum of articular and peri-articular ultrasound (US) findings at metacarpophalangeal (MCP) joints in calcium pyrophosphate (CPP) deposition disease (CPPD)., Methods: Consecutive CPPD patients (chronic CPP crystal inflammatory arthritis or OA with CPPD), and age- and sex-matched controls with RA were prospectively enrolled. Patients underwent bilateral US examination of MCP joints. CPP deposits, synovial inflammation, osteophytes, cartilage damage and bone erosions were recorded., Results: Sixty CPPD patients (33, 55.0% with OA with CPPD and 27, 45.0% with chronic CPP crystal inflammatory arthritis) and 40 RA patients were enrolled. CPP deposits were detected in 24 (40.0%) CPPD patients and in 3 (7.5%) RA patients (P <0.01). In CPPD patients, different types of CPP deposits were identified at MCP joints: 17 (28.3%) patients had dorsal capsuloligamentous deposits, 14 (23.3%) intra-cartilaginous deposits, 13 (21.7%) lateral capsuloligamentous deposits, 12 (20.0%) intra-articular deposits, eight (13.3%) double contour sign and five (8.3%) flexor digitorum tendons' deposits. CPPD patients with chronic CPP crystal inflammatory arthritis showed more US findings indicating synovial inflammation and CPP deposits than those with OA with CPPD. Conversely, a higher prevalence of US features indicating structural damage was noted in this latter phenotype. CPP deposits and bone erosions were the US findings with the highest value for diagnosing chronic CPP crystal inflammatory arthritis and RA, respectively., Conclusion: This study provides pictorial evidence of the broad spectrum of US findings indicating CPP deposits at MCP joints in CPPD. Furthermore, we reported different US patterns in different CPPD phenotypes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Imaging has been playing an important role in the pathogenetic and clinical characterisation of many rheumatic diseases, especially in the most recent years with the advent of many new, highly technological and promising techniques. Calcium pyrophosphate deposition disease (CPPD) benefited also from these new techniques, most of which can readily identify calcium crystals. Nowadays, imaging is used mainly to identify crystals in joints but given the complexity of CPPD, imaging should be used with an "holistic" approach in order to gain insights in the pathogenesis, spectrum of clinical manifestations and natural history of the disease. Furthermore, overlap or association of CPPD with other prevalent diseases of the elderly makes the differential diagnosis challenging. In this review, we provide a critical review of the current knowledge on the use of imaging both for the identification of crystals and for its application in clinical practice as an aid for determining the impact of the disease on patients.Key Points• CPPD is a complex disease with a wide spectrum of clinical manifestations and understanding of pathogenetic mechanisms and clinical phenotypes is essential for correct characterisation• Imaging has made important advances regarding identification of CPPD in recent years, and new, more sophisticated techniques are under investigation• Imaging has the potential to improve our knowledge on pathogenesis and clinical phenotypes of CPPD• Imaging techniques have to be tested thoroughly for reliability, discrimination and sensitivity to change before they can be implemented in clinical trials.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Crystal-related arthropathies are the result of crystal deposition in joint and periarticular soft tissues. Identification of urate crystals is mandatory to distinguish gout from other crystalline arthropathies, including calcium pyrophosphate dihydrate and basic calcium phosphate crystal deposition diseases. ACR/EULAR classification criteria for gout included dual-energy computed tomography and ultrasound with equal impact to the final score. Different diagnostic strengths of these imaging modalities depend on disease duration and scanned anatomic site. While ultrasound has been indicated as the first-choice imaging technique, especially in the early stages of the disease, dual-energy computed tomography has shown to be highly specific, allowing the detection of crystal deposits in anatomic sites not accessible by ultrasound, such as the spine. At the spinal level, MRI findings are usually nonspecific. Finally, there is preliminary evidence that at the knee, dual-energy computed tomography may discriminate calcium pyrophosphate dihydrate from basic calcium phosphate crystal deposits., Competing Interests: Declaration of competing interest EF has received speaking fees from AbbVie, Bristol-Myers Squibb, Novartis, Pfizer, Roche and Union Chimique Belge Pharma. AMR and RGT declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the diagnostic accuracy of ultrasound and conventional radiography in the evaluation of calcium pyrophosphate crystal deposits at wrist level., Methods: Consecutive patients with a "definite" diagnosis of calcium pyrophosphate deposition disease and disease-controls were prospectively included in this cross-sectional single-centre study. Scapho-lunate ligament, triangular fibrocartilage complex, and volar recess of the radio-lunate joint were explored using ultrasound, conventional radiography and computed tomography., Results: Sixty one patients and 39 disease controls were enrolled. Two-hundred wrists were evaluated using both conventional radiography and ultrasound and 26 using computed tomography. Ultrasound findings indicative of crystal deposits were found in at least one wrist in 95.1% of patients and in 15.4% of controls (P<0.001). Scapho-lunate ligament calcifications were reported in 83.6% of patients and in 5.1% of controls (P<0.001). On conventional radiography, calcifications were found in at least one wrist in 72.1% of patients and in 0% of controls (P<0.001). Using the Ryan-McCarty criteria as a gold standard, sensitivity, specificity and diagnostic accuracy were 0.72 (0.59-0.83), 1.0 (0.91-1.0) and 0.83 (0.74-0.90) for conventional radiography and 0.95 (0.86-0.99), 0.85 (0.69-0.94) and 0.91 (0.84-0.96) for ultrasound. The agreement between ultrasound and computed tomography was substantial when assessing triangular fibrocartilage complex (kappa=0.70; 0.43-0.97) and scapho-lunate ligament (kappa=0.69; 0.41-0.97), and moderate for radio-lunate joint (kappa=0.46; 0.12-0.80)., Conclusions: This study supports the diagnostic accuracy of ultrasound in evaluating wrist involvement in calcium pyrophosphate deposition disease. The inclusion of the scapho-lunate ligament in a disease-oriented scanning protocol could improve the diagnostic performance of ultrasound., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

The main aim of this systematic literature review (SLR) was to summarise the evidence in the use of biological therapies in calcium pyrophosphate deposition disease (CPPD). We performed a SLR using PubMed, Embase and Cochrane databases. Only studies reporting the efficacy of biologics in CPPD were selected. The search resulted in 83 articles; 11 were further evaluated in the SLR. Seventy-six patients were included: 2 received infliximab, whereas 74 anakinra. Anakinra was used in refractory disease (85.1%) or in patients with contraindications to standard treatments (23.0%). Clinical response to anakinra was observed in 80.6% of patients with acute and 42.9% of those with chronic CPPD. Short-term treatment was well tolerated and adverse events were reported in 4.1% of the cases. This review provides evidence in favour of the use of anakinra as a therapeutic option in patients with CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated.

Objective: To preliminarily explore the diagnostic potential of ultrasound (US) in detecting calcium pyrophosphate (CPP) crystal deposits at the hip joint in a cohort of patients with CPP deposition disease (CPPD) who were previously evaluated by conventional radiography (CR) and to assess the sensitivity and specificity as well as the agreement between US and CR in the evaluation of hip CPP crystal deposits., Methods: Fifty consecutive patients with definite CPPD and 40 age/sex/body mass index-matched disease control subjects who had undergone hip CR within the previous 6 months were enrolled. Bilateral hip US examination was carried out to assess the presence of CCP crystal deposits at the acetabular labrum fibrocartilage and at the femoral head's hyaline cartilage. Two independent radiologists evaluated the presence of hip CPP crystal deposits on CR in both groups., Results: US findings indicative of CPP crystal deposits were found in at least 1 hip in 45 of 50 patients with CPPD (90.0%) and in 73 of 100 hips (73.0%). CPP crystal deposits were more frequently found at the acetabular labrum fibrocartilage than at the femoral head's hyaline cartilage (72% and 17% of the hips in patients with CPPD, respectively). US and CR sensitivity was 90% and 86%, whereas US and CR specificity was 85% and 90%, respectively. Total agreement between the US and CR findings was 77.8%., Conclusion: Our results provide new evidence supporting US as a first-line, sensitive, safe, and reliable imaging technique in detecting CPP crystal deposits at the hip level., (© 2018, American College of Rheumatology.)

Objectives: To assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints., Methods: A web-based exercise and subsequent patient-based exercise were carried out. A panel of 30 OMERACT members, participated at the web-based exercise by evaluating twice a set of US images for the presence/absence of CPPD. Afterwards, 19 members of the panel met in Siena, Italy, for the patient-based exercise. During the exercise, all sonographers examined twice eight patients for the presence/absence of CPPD at the same joints. Intraoberserver and interobserver kappa values were calculated for both exercises., Results: The web-based exercise yielded high kappa values both in intraobserver and interobserver evaluation for all sites, while in the patient-based exercise, inter-reader agreement was acceptable for the TFC and the AC. TFC reached high interobserver and intraobserver k values in both exercises, ranging from 0.75 to 0.87 (good to excellent agreement). AC reached moderate kappa values, from 0.51 to 0.85 (moderate to excellent agreement) and can readily be used for US CPPD identification., Conclusions: Based on the results of our exercise, the OMERACT US definitions for the identification of CPPD demonstrated to be reliable when applied to the TFC and AC. Other sites reached good kappa values in the web-based exercise but failed to achieve good reproducibility at the patient-based exercise, meaning the scanning method must be further refined., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To define the ultrasonographic characteristics of calcium pyrophosphate crystal (CPP) deposits in joints and periarticular tissues and to evaluate the intra- and interobserver reliability of expert ultrasonographers in the assessment of CPP deposition disease (CPPD) according to the new definitions., Methods: After a systematic literature review, a Delphi survey was circulated among a group of expert ultrasonographers, who were members of the CPPD Ultrasound (US) Outcome Measures in Rheumatology (OMERACT) subtask force, to obtain definitions of the US characteristics of CPPD at the level of fibrocartilage (FC), hyaline cartilage (HC), tendon, and synovial fluid (SF). Subsequently, the reliability of US in assessing CPPD at knee and wrist levels according to the agreed definitions was tested in static images and in patients with CPPD. Cohen's κ was used for statistical analysis., Results: HC and FC of the knee yielded the highest interobserver κ values among all the structures examined, in both the Web-based (0.73 for HC and 0.58 for FC) and patient-based exercises (0.55 for the HC and 0.64 for the FC). Kappa values for the other structures were lower, ranging from 0.28 in tendons to 0.50 in SF in the static exercise and from 0.09 (proximal patellar tendon) to 0.27 (triangular FC of the wrist) in the patient-based exercise., Conclusion: The new OMERACT definitions for the US identification of CPPD proved to be reliable at the level of the HC and FC of the knee. Further studies are needed to better define the US characteristics of CPPD and optimize the scanning technique in other anatomical sites.

Objectives: To compare the diagnostic accuracy of musculoskeletal ultrasound (MSUS) and x-ray in evaluating wrist triangular fibrocartilage complex (TFCC) in patients with calcium pyrophosphate dihydrate deposition disease (CPPD) and to investigate the agreement between the extent of the calcium pyrophosphate dihydrate (CPP) crystal deposits assessed by MSUS and the radiographic findings., Methods: We enrolled 84 patients: 36 patients with "definite" CPPD and 48 controls. The Ryan and McCarty diagnostic criteria were used. A rheumatologist performed bilateral MSUS examinations of the TFCC in all patients, assessing both the presence and absence of CCP crystals deposits and their extent (0-3; 0: absent; 1: 1-2 spots; 2: more than two spots covering <50% of the volume of the structure; 3: deposits covering >50% of the volume of the structure). A radiologist evaluated the presence/absence of x-ray calcifications at TFCC level in both groups., Results: MSUS and x-ray sensitivity was 77.8% and 76.4%, respectively, whereas MSUS and x-ray specificity was 90.6% and 96.9%, respectively. Total agreement between MSUS and radiographic findings indicative of calcifications at TFCC level was 88.7%., Conclusions: This study supports the diagnostic accuracy of MSUS and x-ray in evaluating TFCC crystal deposits in patients with CPPD. Sensitivity and specificity of MSUS and x-ray resulted comparable. The highest MSUS score of the extent of the deposits correlated better with x-ray findings.

Purpose of Review: In the latest recommendations for the diagnosis and management of gout and calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, the diagnostic potential of ultrasound has been recognized. This review highlights the recent advances of research on ultrasound in gout and CPPD crystal deposition disease., Recent Findings: Ultrasound allows highly sensitive, noninvasive and quick detection of microcrystal aggregates in multiple anatomic areas. Ultrasound can be used as a safe and reliable guide to aspirate even minimal fluid collections suitable for microscopic analysis, and as a tool for monitoring monosodium urate crystal dissolution induced by urate-lowering therapy. The first metatarsophalangeal joint and the knee should be regarded as the anatomic regions with the highest probability of being respectively positive for monosodium urate and CPPD crystal aggregates., Summary: The detection of highly evocative signs in patients with equivocal clinical findings may have a deep impact on the clinical decision-making process, narrowing the differential diagnostic spectrum and avoiding time-consuming and expensive diagnostic procedures. Ultrasound differential diagnosis between gout and CPPD crystal deposition disease is based on the characteristics of crystal aggregates and their preferential localization in different anatomical areas.

Objective: To determine the sensitivity, specificity, and accuracy of ultrasound (US) in the detection of cartilage calcification at knee level in patients with calcium pyrophosphate deposition disease (CPDD) and to assess the interobserver reliability., Methods: Seventy-four CPDD patients and 83 controls with other chronic arthritis were included. All patients underwent a clinical examination, synovial fluid analysis, and radiographic assessment of the knee. US examinations were performed in order to detect hyperechoic spots within the hyaline cartilage layer and hyperechoic areas within the meniscal fibrocartilage. Twenty patients were assessed by 2 operators in order to calculate the interobserver reliability., Results: A total of 314 knees in 157 patients (74 with CPDD, 19 with rheumatoid arthritis, 17 with spondyloarthritis, 32 with osteoarthritis, and 15 with gout) were assessed. In the 74 patients with CPDD, hyaline cartilage spots were detected by US in at least 1 knee in 44 patients (59.5%), whereas radiography detected hyaline cartilage spots in 34 patients (45.9%) (P < 0.001). Meniscal fibrocartilage calcifications were detected by US in 67 of the 74 CPDD patients (90.5%), whereas conventional radiography detected calcifications in 62 patients (83.7%) (P = 0.011). The criterion validity expressed as percentage of sensitivity, specificity, and accuracy of US in the detection of articular cartilage calcification was high. Both kappa values and overall agreement percentages showed moderate to excellent agreement., Conclusion: US is an accurate and reliable imaging technique in the detection of articular cartilage calcification at knee level in patients with CPDD., (Copyright © 2014 by the American College of Rheumatology.)

In the last decade, an increasing number of rheumatologists have been using ultrasound (US) for assessing patients with gout and calcium pyrophosphate deposition (CPPD) disease. The high reflectivity of the crystalline aggregates and the ability of US to detect even minimal crystal deposits explain the high sensitivity of this imaging technique. Furthermore, the peculiar distribution within the target tissues results in the generation of typical US patterns and explains the excellent specificity of some US findings. The large spectrum of US findings and their wide combination generate different scenarios in different patients and also in the same subject. Such a high variety impaired the standardisation of the definitions of each US finding. This review presents the main US findings indicative of crystal deposits, discusses the available evidence supporting the use of US in patients with gout and CPPD disease, and provides a research agenda to guide further investigations. The combined US examination of the target tissues and the clinically involved sites represents the key issue to obtain the best compromise between accuracy and feasibility, in the daily US assessment of patients with crystal-related arthropathies. Moreover, the US guided aspiration of synovial fluid may enhance the possibility to reach a crystal-proven diagnosis, making US a complementary tool, not in contrast, with microscopy, which rests the current gold standard. Finally, even if at moment other US findings are not included among the typical ones for crystal-related arthropathies, it is possible that in the future, thanks to continuous technological advances, we will be able to identify other specific patterns of pathology.

Objective: To assess the extent of calcium pyrophosphate dihydrate (CPP) crystal deposition and the distribution of affected sites, using ultrasonography (US), in patients affected by CPP deposition disease (CPPD)., Patients and Methods: 42 consecutive patients affected by definite CPPD according to the McCarty criteria were enrolled in the study. All patients underwent an US examination of metacarpophalangeal joints of II, III, IV and V fingers of both hands, wrists and knees, Achilles' tendons and plantar fascia looking for CPP deposits. A dichotomous score for presence/absence of CPP and a semiquantitative score for extent of deposits (0-3: 0, absent; 1, 1-2 spots; 2, more than two spots covering <50% of the structure; 3, deposits covering >50% of the structure) were assigned to each site examined. A site distribution score (total number of affected sites) was then calculated as well as an extent score equal to the sum of the extent scores of all sites., Results: The mean involvement in our patients was 4.7 sites (SD±1.7, range 2-8 sites). The knee was the most affected, site (41 of 42) followed by the wrist (at least one in 37 patients) the Achilles' tendons (23 patients), plantar fascia (11 patients) and metacarpophalangeal joints (four patients). The highest mean values of the extent score were in the menisci, followed by the hyaline cartilage of the femoral condyles and the entheses., Conclusions: The deposition of CPP crystals involves at least two sites with a mean of four sites involved in most patients affected by CPPD and is therefore an oligoarticular or polyarticular disease.

Objectives: This study was aimed at determining the prevalence of ultrasound (US) morpho-structural changes in the shoulders of patients with crystal-related arthropathies, and at investigating the relationship between them and the clinical findings., Methods: Eighty-eight patients with a crystal proven diagnosis of gout or calcium pyrophosphate dihydrate (CPPD) disease attending the in-patient and the out-patient clinics of four Italian Rheumatology Departments were consecutively enrolled in this multi-centre study. All patients were clinically examined by an expert rheumatologist who recorded clinical and laboratory data in addition to the presence/absence of spontaneous shoulder pain and performed the Hawkins, Jobe, Patte, Gerber, and Speed tests. In each centre, US examinations were carried out by a rheumatologist expert in musculoskeletal US blinded to clinical data, using a MyLab TWICE XVG machine (Esaote SpA, Genoa, Italy) equipped with a linear probe operating at 4-13 MHz, and a Logiq 9 machine (General Electrics Medical Systems, Milwaukee, WI, USA) with a linear probe operating at 9-14 MHz. Shoulders were scanned to detect peri-articular inflammation, rotator cuff pathology and joint involvement, and to reveal US signs indicative of crystal deposits., Results: A total of 88 patients, 39 with gout, 46 with CPPD disease, and 3 with both gout and CPPD disease, were enrolled. In total, 176 shoulders were clinically assessed, of which 54/176 (30%) were painful and 74/176 (42%) were clinically normal shoulders. All US findings indicative of peri-articular synovial inflammation were more frequently detected in patients with CPPD disease than in gouty patients. In 50 out of 176 (28.4%) shoulders, US allowed the detection of at least one finding indicative of synovial inflammation. Chronic tendinopathy was a frequent US finding both in gout patients and in patients with CPPD disease and the supraspinatus tendon was the most frequently involved one. In CPPD disease the supraspinatus tendon was found ruptured in a number of shoulders seven times higher than in gouty patients. The osteophytes were found at acromion-clavicular joint in nearly 80% of the shoulders in CPPD disease and in 60% in the gouty patients., Conclusions: The results of this study confirm the high specificity of US findings indicative of crystal deposits at hyaline cartilage level and indicate that the supraspinatus tendon and the fibrocartilage of the acromion-clavicular joint are the most frequently affected structures of the shoulders in patients with crystal-related arthropathies.

US plays a useful role in diagnosing and monitoring therapy in microcrystalline arthritis, as it may detect both monosodium urate and calcium pyrophosphate crystal aggregates. The knowledge of some tips and tricks in the identification of these findings can play a key role in exploiting the relevant potential of US in microcrystalline arthritis, avoiding errors and misinterpretations. This review provides an in-depth description of simple technical and methodological issues to guide the rheumatologist in daily clinical practice.

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.

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.

Ultrasound is a pivotal exam in calcium pyrophosphate deposition (CPPD) identification. It has been demonstrated to be feasible, accurate, and reliable for CPPD diagnosis. Even if standardized definitions and a scoring system for CPPD have been established by the OMERACT ultrasound working group, ultrasound is still considered one of the most operator-dependent techniques. This is because in ultrasound, both the acquisition and the interpretation phases of the diagnostic process are in the hands of one operator and are performed simultaneously, in contrast to what happens with other imaging exams, where the acquisition process is standardized and independent from the interpretation process. Therefore, the scanning technique and machine setting acquire a central role, almost as important as the interpretation of the images, as erroneous scanning may lead to interpretative mistakes. In this review, we will delve into the appearance of CPPD on ultrasound, based on the latest research findings, passing through its pathogenesis, and focusing on machine settings and ultrasound scanning techniques, providing some tips and tricks to facilitate accurate CPPD recognition in the most frequently affected sites. [ABSTRACT FROM AUTHOR]

Objectives Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention. Methods This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety. Results One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n  = 73/86), methotrexate (used first-line in n  = 14/36), anakinra (n  = 27) and tocilizumab (n  = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P  < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P  = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up. Conclusion Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra. [ABSTRACT FROM AUTHOR]