Calcium Pyrophosphate Crystal Deposition Research Articles

The translational value of calcium pyrophosphate deposition disease experimental mouse models

The deposition of calcium pyrophosphate (CPP) crystals in joint tissues causes acute and chronic arthritis that commonly affect the adult and elderly population. Experimental calcium pyrophosphate deposition disease (CPPD) models are divided into genetically modified models and crystal-induced inflammation models. The former do not reproduce phenotypes overlapping with the human disease, while in the latter, the direct injection of crystals into the ankles, dorsal air pouch or peritoneum constitutes a useful and reliable methodology that resembles the CPP induced-inflammatory condition in humans. The translational importance of the induced model is also strengthened by the fact that the key molecular and cellular mediators involved in inflammation are shared between humans and laboratory rodents. Although, in vivo models are indispensable tools for studying the pathogenesis of the CPPD and testing new therapies, their development is still at an early stage and major efforts are needed to address this issue. Here, we analyze the strenghts and limitations of each currently available CPPD in vivo model, and critically discuss their translational value.

Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report.

Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated cystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.

Oxidative Stress by the Mitochondrial Monoamine Oxidase B Mediates Calcium Pyrophosphate Crystal-Induced Arthritis.

Calcium pyrophosphate (CPP) crystal deposition in the joints is associated with a heterogeneous set of debilitating syndromes characterized by inflammation and pain, for which no effective therapies are currently available. Because we found that the mitochondrial enzyme monoamine oxidase B (MAO-B) plays a fundamental role in promoting inflammatory pathways, this study aims at assessing the efficacy of two clinical-grade inhibitors (iMAO-Bs) in preclinical models of this disease to pave the way for a novel treatment. We tested our hypothesis in two murine models of CPP-induced arthritis, by measuring cytokine and chemokine levels, along with immune cell recruitment. iMAO-Bs (rasagiline and safinamide) were administered either before or after crystal injection. To elucidate the molecular mechanism, we challenged in vitro primed macrophages with CPP crystals and assessed the impact of iMAO-Bs in dampening proinflammatory cytokines and in preserving mitochondrial function. Both in preventive and therapeutic in vivo protocols, iMAO-Bs blunted the release of proinflammatory cytokines (interleukin [IL]-6 and IL1-β) and chemokines (CXCL10, CXCL1, CCL2 and CCL5) (n > 6 mice/group). Importantly, they also significantly reduced ankle swelling (50.3% vs 17.1%; P < 0.001 and 23.1%; P = 0.005 for rasagiline and safinamide, respectively). Mechanistically, iMAO-Bs dampened the burst of reactive oxygen species and the mitochondrial dysfunction triggered by CPP crystals in isolated macrophages. Moreover, iMAO-Bs blunted cytokine secretion and NLRP3 inflammasome activation through inhibition of the NF-κB and STAT3 pathways. iMAO-Bs dampen inflammation in murine models of crystal-induced arthropathy, thereby uncovering MAO-B as a promising target to treat these diseases.

Diagnosis of calcium pyrophosphate crystal deposition disease by ultrasonography: how many and which sites should be scanned?

To develop the optimal US scanning protocol for the diagnosis of CPPD disease. In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls and with a negative synovial fluid analysis were prospectively enrolled in two Italian Institutions. Four rheumatologists, blinded to patients' clinical details, performed US examinations using a standardised scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from 2nd to 5th fingers, hips, knees, ankles). CPPD was identified as presence/absence, according to the OMERACT definitions. Reduced US scanning protocols were developed by selecting the most informative joints to be imaged by US using the LASSO technique. Patients were randomly divided into training and validation sets. Their diagnostic accuracy was tested comparing the area under the ROC curves. 204 participants were enrolled: 102 with CPPD disease and 102 disease controls [age (mean±standard deviation) 71.3 ± 12.0 vs 71.1 ± 13.5 years, female: 62.8% vs 57.8%].The median number of joints with US evidence of CPPD was 5 (IQR: 4-7) and 0 (IQR: 0-1) in patients with CPPD disease and controls, respectively (p< 0 01).The detection of CPPD in ≥ 2 joints using a reduced scanning protocol (bilateral assessment of knees, wrists, and hips) showed a sensitivity of 96.7% (95%CI: 82.8-99.9) and a specificity of 100 (95%CI: 88.8-100.0) for the diagnosis of CPPD disease and had good feasibility [(mean±standard deviation) 12.5 ± 5.3 min]. Bilateral US assessment of knees, wrists, and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease.

Calcium Pyrophosphate and Basic Calcium Phosphate Deposition Diseases: The Year in Review 2022

Calcium-containing crystal deposition diseases are a common cause of pain and disability but remain relatively under-investigated. No drug has been identified that can prevent deposition or effect dissolution of either calcium pyrophosphate (CPP) or basic calcium phosphate (BCP) crystals. In comparison to the field of gout and urate biology, published research in relation to calcium crystal deposition diseases in 2022 was relatively modest in quantity. In CPP deposition (CPPD) disease, progress was made mainly in epidemiology, imaging, surgical management and Gitelman’s syndrome. In relation to BCP crystals, the effect on tenocytes in vitro was explored and results indicate that BCP crystals likely reduce tendon matrix integrity via their interaction with tenocytes. The involvement of calcification in the progression of osteoarthritis (OA) was elegantly demonstrated contributing to further discovery of the process of OA progression. There was a paucity of mechanistic and genetic studies in calcium crystal deposition diseases published in 2022, nor any breakthrough in therapy, showing that there is abundant scope for investigation under these themes in the future.

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

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. 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. 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]). 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. The Italian Ministry of Health - Ricerca Corrente.

Diastolic dysfunction of ventricles in patients with calcium pyrophosphate crystal deposition disease while receiving anti-inflammatory therapy

Calcium pyrophosphate crystal deposition disease (CPPD) may be associated with developing of diastolic dysfunction (DD). To determine the variability of echocardiographic parameters in patients with CPPD receiving anti-inflammatory therapy. Twenty six patients with CPPD and osteoarthritis (OA) from 18 to 65 years old were included in the case-control study. All patients underwent echocardiography, laboratory parameters at baseline and after 6 months. Patients with CPPD received methotrexate 15 mg per week or hydroxychloroquine 200 mg once a day, or colchicine 1 mg per day. Diastolic function according to echocardiography was assessed. Diastolic dysfunction was detected in 19 patients: in 11 (42%) patients with CPPD and 8 (31%) patients with OA (p=0.39). The baseline serum CRP level was higher in the CPPD group (p=0.03), no differences were found for other indicators. Twenty-two patients with CPPD and 19 patients with OA completed the study. In patients with OA, there were no significant changes in indicators reflecting the diastolic function of ventricles. CPPD therapy with colchicine, hydroxychloroquine and methotrexate has a positive effect on indicators of diastolic ventricular function.

Acute calcium pyrophosphate crystal arthritis is associated with an increased rate of hip and knee joint surgery.

Acute calcium pyrophosphate (CPP) crystal arthritis is a distinct manifestation of calcium pyrophosphate crystal deposition (CPPD). No studies have specifically examined whether acute CPP crystal arthritis is associated with progressive structural joint damage. The objective of this retrospective cohort study was to evaluate the relative rate of hip and knee joint arthroplasties as an estimate of structural joint damage accrual, in a population of patients with acute CPP crystal arthritis. Data were collected from Waikato District Health Board (WDHB) to identify an acute CPP crystal arthritis cohort with clinical episodes highly characteristic of acute CPP crystal arthritis. Data on hip and knee joint arthroplasties were collected from the New Zealand Orthopaedic Association's Joint Registry. The rate of arthroplasties in the cohort was compared with the age-ethnicity-matched New Zealand population. Additional analysis was performed for age, obesity (BMI) and ethnicity. The acute CPP crystal arthritis cohort included 99 patients; 63 were male and the median age was 77 years (interquartile range, 71-82). The obesity rate was 36% with a median BMI of 28.4 kg/m2 (interquartile range, 25.8-32.2), comparable to the New Zealand population. The standardized surgical rate ratio in the cohort vs the age-ethnicity-matched New Zealand population was 2.54 (95% CI: 1.39, 4.27). Our study identified a considerable increase in the rate of hip and knee joint arthroplasties in patients with episodes of acute CPP crystal arthritis. This suggests CPP crystal arthritis may be a chronic condition, leading to progressive joint damage.

Editorial introductions.

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS W. Joseph McCuneW. Joseph McCuneDr W. Joseph McCune, MD, is Michael and Marcia Klein Professor of Rheumatic Diseases and Director of the Lupus Program at the University of Michigan. Following an Internal Medicine residency at the University of Michigan and a fellowship in Immunology and Rheumatology at Harvard Medical School and the Brigham and Woman's Hospital, Dr McCune has been a member of the faculty at the University of Michigan where he specializes in the epidemiology, diagnosis, and treatment of lupus and systemic vasculitis. Sara K. TedeschiSara K. TedeschiDr. Sara K. Tedeschi, MD, MPH, received her medical degree from Vanderbilt University, USA and her MPH degree from the Harvard School of Public Health, USA. She joined the rheumatology faculty at Brigham and Women's Hospital, USA, after completing her internal medicine residency and rheumatology fellowship there. Her clinical research on calcium pyrophosphate crystal deposition disease is supported by the National Institutes of Health. David FoxDavid FoxDr. Fox is a graduate of the Massachusetts Institute of Technology and Harvard Medical School. Following internal medicine residency and rheumatology fellowship at the Brigham and Women's Hospital, he joined the faculty of the University of Michigan School of Medicine in 1985. Dr. Fox is Professor of Internal Medicine and, from 1990 to 2018, was Chief of the Division of Rheumatology. In 2013, Dr. Fox became the Frederick G. L. Huetwell and William D. Robinson, M.D. Professor of Rheumatology. He is currently a Deputy Director of the Immune Tolerance Network. Dr. Fox's research focuses on defining and characterizing pathways of human T cell activation, determining the role of these pathways in the pathogenesis of autoimmune disease, investigating T cell interactions with synovial fibroblasts, and exploring novel approaches to the treatment of rheumatoid arthritis and scleroderma. He is author of more than 260 scientific papers and book chapters. Dr. Fox is also active in the clinical care of patients with rheumatic diseases and in teaching students and fellows in both clinical and research settings. From 2007–2008, Dr. Fox served as the seventy-first President of the American College of Rheumatology and the sixth ACR President from the University of Michigan

Diastolic dysfunction of the left and right ventricles in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis

The frequency and risk factors for the development of diastolic function in patients with calcium pyrophosphate crystal deposition disease (CPPD) and osteoarthritis (OA) have not been studied.The aim – to determine the frequency and to identify risk factors (RF) for the development of diastolic dysfunction (DD) of the left (LV) and right (RV) ventricles in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis.Material and methods. 26 patients (18–65 years) each were included with CPРD and with knee OA, matched in age and gender, without cardiovascular disease (CVD), type 2 diabetes mellitus, rheumatic diseases. Traditional risk factors of CVD were assessed, echocardiography was performed.Results. The frequency of DD in patients with CPРD and OA was quite high and almost did not differ in both groups: it was detected in 19 patients, of which 11 (42%) with CPРD and 8 (31%) with OA (p=0.39). Type 1 LV DD was detected in 10 (39%) patients with CPРD and in 8 (31%) with OA (p=0.11); type 1 RV DD – in 8 (31%) patients with CPРD and in 7 (27%) patients with OA (p=0.17); type 1 LV DD and RV DD – in 7 (27%) patients with both CPРD and with OA. DD types 2 and 3 were not detected in both groups. There were no differences in both groups in CV risk factors, except for the level of C-reactive protein (CRP) – it was higher in CPРD (p=0.03). In the CPРD group, mean values of LV E/E′ (p=0.02), LV DT (p=0.03), LV MI (p=0.04) were significantly higher than in patients with OA. On the contrary, in patients with OA, the following indicators: EDV (p=0.004), TVC (p=0.02) were higher.There were direct correlations between diastolic function indices and the following factors in CPРD: LVL, PWLV and PTH level (r=0.7; p&lt;0.005), LV E′ and PTH level (r=0.7; p&lt;0.005); inverse correlations – the level of PTH and IS (r=–0.5; p&lt;0.005), LV MI (r=–0.5; p&lt;0.005), the level of vitamin D and VD DT (r=–0.6; p&lt;0.005). Direct correlations in OA: the level of CRP and PVAdiast (r=0.6; p&lt;0.005), and the level of sUA (r=0.7; p&lt;0.005), the level of vitamin D and E/E′ LV (r=0.6; p&lt;0.005).Conclusion. A high prevalence of LV and RV DD was found in patients with CPРD and OA. The presence of DD in CPРD was associated with lower vitamin D levels, and in OA with a higher level of sUA and a lower level of PTH.

Diagnosis and Treatment of Calcium Pyrophosphate Deposition (CPPD) Disease: A Review.

Calcium Pyrophosphate Dihydrate (CPPD) crystal-related arthropathies are a common cause of acute and chronic arthritis caused by the deposition of calcium pyrophosphate crystals in joints and soft tissues, resulting in inflammation and joint damage. They present with a wide spectrum of clinical manifestations and often present challenges to diagnosis and management as they commonly affect older co-morbid patients. The challenges are compounded by a lack of a well-defined description of CPPD. However, an international expert-driven process is underway to develop CPPD classification criteria. Treatment is also problematic as unlike gout, there are no agents available that decrease the crystal burden. Treatment options have often been extrapolated from gout treatment pathways without having extensive trials or a solid evidence base. It is hoped the new CPPD classification guidelines will contribute to large multicentre studies, with well-defined patient cohorts, which will facilitate the production of high-quality evidence to guide the management of this condition. Here, we discuss the barriers and facilitators in diagnosing and treating CPPD-related arthropathy.

Pseudogout, Neutropenia, and Splenomegaly: A Case of Felty Syndrome

Felty syndrome is a rare entity of rheumatoid arthritis, neutropenia, and splenomegaly. Patients typically develop the syndrome years after a diagnosis of rheumatoid arthritis. Here, we present a case of a 76-year-old man with history of chronic calcium pyrophosphate crystal deposition disease, or pseudogout, who presented with neutropenic fever. Given his progressive arthralgias and symmetric synovitis on physical examination, serologies were sent and identified a new diagnosis of rheumatoid arthritis. This, together with exclusion of other causes of neutropenia and discovered splenomegaly, led to diagnosis of Felty syndrome.

Management of temporomandibular joint diseases: a rare case report of coexisting calcium pyrophosphate crystal deposition and synovial chondromatosis

BackgroundThe coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces.Case presentationWe report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years.ConclusionsIsolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed.

The use of Anakinra in treatment of calcium pyrophosphate crystal deposition disease: Analysis of own experience and a literature review

Calcium pyrophosphate crystal deposition disease (CPPD) is a disease caused by the deposition of calcium pyrophosphate crystals, mainly in the articular cartilage, and often manifests as severe acute or chronic arthritis. Therapy given in such cases with non-steroidal anti-inflammatory drugs, colchicine, methotrexate and glucocorticoids is often effective. In these cases, the possibility of prescribing biological drugs, primarily interleukin 1 (IL-1) inhibitors, is being considered. The article analyzes the experience of using Anakinra, an IL-1 receptor antagonist, registered in the Russian Federation in 2021, in 5 patients with persistent arthritis in CPPD. The article also presents an analysis of data from key studies on the use of the drug in patients with CPPD.

Use of anakinra in treatment of combination of calcium pyrophosphate deposition desease and gout (clinical observation)

Gout and calcium pyrophosphate crystal deposition disease (CPPD) are the most common inflammatory rheumatic diseases. It is known that the clinical manifestations of both diseases can simulate each other, in addition, cases of a combination of gout and CPPD are not uncommon, which complicates the diagnosis and selection of therapy. We present a case report of the successful use of the interleukin-1 beta (IL-1β) receptor antagonist Anakinra in a patient with a combination of gout and CPPD with chronic arthritis resistant to previous therapy with colchicine, non-steroidal anti-inflammatory drugs and glucocorticoids.

Proton-Pump Inhibitors and Risk of Calcium Pyrophosphate Deposition in a Population-Based Study.

There are no proven effective medical treatments to prevent calcium pyrophosphate crystal deposition (CPPD). Hypomagnesemia is a known CPPD risk factor. The present study was undertaken to carry out a real-world epidemiologic study on proton-pump inhibitor (PPI) use, which can cause hypomagnesemia, and CPPD risk. We conducted a time-stratified, propensity score (PS)-matched cohort study using the UK-based IQVIA Medical Research Data. We compared risk of incident CPPD among PPI users versus H2 blocker users using Cox proportional hazards models. We used greedy matching of incident PPI users 1:1 to incident histamine receptor 2 (H2 ) blocker users in 1-year cohort accrual blocks. Subjects were censored at time of drug switch. We evaluated incident use of PPI and H2 blockers prior to incident CPPD using a nested case-control study within the same cohort, matched 1:4 by age and sex using risk-set sampling. We identified 81,102 PPI and H2 blocker initiators, with 113 and 63 incident cases of CPPD, respectively. In the case-control study when compared with nonusers, both PPI and H2 B users had higher risk of incident CPPD, with odds ratios (ORs) of 1.79 (95% confidence interval [95% CI] 1.55-2.07) and 1.52 (95% CI 1.14-2.03), respectively. Incident PPI use was nonsignificantly associated with incident CPPD (hazard ratio 1.03 [95% CI 0.75-1.41]) compared with H2 blocker use. In this study using real-world data, incident use of PPIs was not associated with a higher risk of CPPD compared with incident H2 blocker use, although use of PPI and H2 blockers had higher risk compared with nonuse.

OP0168 DEVELOPMENT OF AN ULTRASOUND SCORING SYSTEM FOR CPPD EXTENT: RESULTS FROM A DELPHI PROCESS AND WEB-RELIABILITY EXERCISE BY THE OMERACT US WORKING GROUP

BackgroundUltrasound (US) has proven to be an excellent imaging technique for detecting calcium pyrophosphate (CPP) deposition disease (CPPD); it is also widely available and inexpensive and can be performed during the clinic visit making it the preferred imaging modality for many rheumatologists. However, no validated grading systems have yet been developed allowing for a quantification of the extent of crystal deposition in CPPD.ObjectivesThe aim of this study was to develop a scoring system for the quantification of CPP deposition at a patient level according to the OMERACT framework.MethodsAs part of the OMERACT methodology, we performed a systematic literature review (SLR) and meta-analysis aimed to estimate the prevalence of CPP deposition in peripheral joints by imaging, in order to identify relevant joints for CPPD monitoring. A preliminary survey was also circulated among the members of the OMERACT US – CPPD working group to collect their own suggestions according to their personal experience. Subsequently, a Delphi survey was prepared and circulated between members of the group, including statements that reflected both the results of the SLR and of the preliminary survey. In total, 32 statements were generated regarding the type of scoring for single structures, the sites to be included, the final scoring at patient level, and the scanning technique. Participants were asked to reply on a 5-point Likert scale (1, strongly disagree to 5, strongly agree) and agreement was achieved when 4 and 5 grades reached 75% or more of concordance. In case of disagreement, new statements were proposed according to the members’ suggestions and circulated for voting in a subsequent round. After agreement of a scoring system, the validation process began. Two rounds of a web-based exercise on static images were conducted on 120 images representing equally all sites under investigation and all degrees of crystal deposition, to assess the intra- and inter-reader reliability of the new scoring system. Representative images of the scoring system were visible throughout the entire exercise in order to facilitate the scoring of the lesions.ResultsThree Delphi rounds were needed to reach agreement on all items. 32/41 members of the OMERACT US-CPPD working group replied in the first round, 26/32 in the second, and 25/26 in the third round. Twenty statements were approved in the first round, 3 in the second, and 3 in the third round. Only the knees (menisci and hyaline cartilage) and the triangular fibrocartilage of the wrist were included in the final score, using a four-grade system (0-3). It was decided that each anatomical structure should be scored separately and then also summed in order to define the joint score. The sum of the assessed joints was the total score at patient level. The final scoring system with the definitions and the relative technical notes is represented in Figure 1. 33/41 members participated to the reliability exercise. The inter-reader reliability of the scoring was substantial (kappa of 0.72), and the intra-reader reliability was almost perfect (kappa of 0.82).ConclusionThis is the first study for developing a scoring system for the extent of CPP crystal deposition in patients with CPPD. The scoring system demonstrated to be reliable in static images. The next step of the validation process is to assess the reliability of the scoring system in a patient-based exercise. This study represents a fundamental step in the OMERACT process of validating US as an outcome measure instrument, and above proposed scoring system will hopefully provide a useful tool for clinical practice and research.Disclosure of InterestsNone declared

Usefulness of ultrasound in the diagnosis of crystal deposition diseases.

Gout and calcium pyrophosphate crystal deposition disease (CPPD) are common forms of inflammatory arthritis whose prevalence has increased in recent years. Although the identification of monosodium urate crystals (MSU) and calcium pyrophosphate crystals (CPP) in synovial fluid (SF) by polarized light microscopy are the gold standard for diagnosing these diseases, SF analysis is not always available. An early diagnosis and specific treatment, especially in gout, allows avoiding irreversible structural damage, comorbidities, and a severe impact on the quality of life of patients. Musculoskeletal ultrasound (US) is a noninvasive tool that allows detecting aggregates of microcrystals at multiple anatomical sites and helps to establish a specific diagnosis. The objective of this review is to evaluate the applications of US in the diagnosis and clinical management of the main microcrystalline arthropathies. The US has helped improve our understanding of the natural history of the disease, due to its ability to visualize not only soft tissue inflammation and structural damage, but also the characteristics of MSU and CPP crystal deposition. The anatomical sites of crystal deposition are also a key factor for differential diagnosis in different microcrystalline diseases. The US allows establishing an early diagnosis, especially in asymptomatic hyperuricemia, to discriminate with other inflammatory diseases, to assess the extent of microcrystalline deposition and their sensitivity to change after treatment. Given its increasing availability in clinical practice and strong evidence, US is a bedside imaging technique helping clinicians to improve diagnosis and therapy monitoring in their daily practice.

A Case of Extensive Hand Extensors Tendon Rupture Due to Pseudo-rheumatoid Arthritis - A Great Mimicker of Rheumatoid Arthritis

Calcium pyrophosphate deposition (CPPD) disease is caused by calcium pyrophosphate (CPP) crystal deposition in the fibrocartilage. It usually presents as monoarticular deposition but can deposit in multiple joints presenting as chronic polyarticular disease mimicking rheumatoid arthritis (RA), known as pseudo-rheumatoid arthritis, making it very challenging for the correct diagnosis.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Kenneth G. SaagKenneth G. SaagKenneth G. Saag, MD, MSc, is Jane Knight Lowe Professor of Medicine, Division of Clinical Immunology and Rheumatology, at the University of Alabama at Birmingham (UAB) in Birmingham, Alabama, USA and Professor of Epidemiology, at the UAB School of Public Health. Dr Saag is a native of Chicago, and following studies in engineering at the University of Michigan, USA, he returned to Chicago for medical school and Internal Medicine Residency at Northwestern University, USA. He then traveled to the University of Iowa, USA, for his rheumatology and epidemiology training and remained on the faculty there until moving to UAB in 1998. Dr Saag is the founding Director of the Agency for Health Care Research and Quality Deep South Center for Education and Research on Therapeutics, the UAB Center of Research Translation in Gout and Hyperuricemia, and the UAB Outcomes Research Center. He also serves as a Vice Chair for the UAB Department of Medicine. He has published over 300 peer reviewed manuscripts; has also authored more than 100 reviews, editorials, and book chapters. Recently he published the first edition of the clinical handbook Diagnosis and Management of Osteoporosis. Dr Saag is the Secretary of the American College of Rheumatology (ACR) and Past President of the Board of Trustees of the National Osteoporosis Foundation. Sara K. TedeschiSara K. TedeschiDr Tedeschi is a Rheumatologist at Brigham and Women's Hospital and an Assistant Professor of Medicine at Harvard Medical School, both in Boston, Massachusetts, USA. She completed medical school at Vanderbilt University School of Medicine in Nashville, Tennessee, USA. Dr Tedeschi then completed both her internal medicine residency and rheumatology fellowship training at Brigham and Women's Hospital and received her MPH from the Harvard T.H. Chan School of Public Health. Her clinical research focuses on risk factors for and outcomes in rheumatic diseases. Dr Tedeschi's current work which focuses on calcium pyrophosphate crystal deposition disease is funded by the National Institutes of Health. She is Co-Chair of the OMERACT CPPD Working Group and serves on the leadership team of the ACR/EULAR CPPD Classification Criteria working group. George C. TsokosGeorge C. TsokosDr George C. Tsokos, MD is Professor of Medicine at Harvard Medical School and Chief, Rheumatology Division, Beth Israel Deaconess Medical Center in Boston, USA. He trained in Rheumatology at the National Institutes of Health, USA. He has served various leadership positions including President of the Clinical Immunology Society, Chair of the Council of the University of Athens and Member or Chair of multiple federal study sections and Editor or Member of editorial boards of scientific journals. Dr Tsokos holds a MERIT Award from the National Institutes of Health and has received several prestigious awards including the Kirkland, Howley, Evelyn Hess awards and the Distinguished Basic Investigator Award from the American College of Rheumatology, the Lupus Insight Award, the Carol Nachman International Prize in Rheumatology and the Marian Ropes Physician Achievement Award. Dr Tsokos’ laboratory has opened and led the field of molecular abnormalities on immune cells in patients with SLE and identified previously unknown pathways which have served as the basis for novel treatments which are currently in various phases of development.