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Purpose of the review: Although calcium pyrophosphate deposition (CPPD) has been known since the 1960s, our understanding of its pathogenesis remains rudimentary. This review aims to illustrate the known mechanisms underlying calcium pyrophosphate (CPP) crystal formation and deposition and explore future directions in research. By examining various perspectives, from basic research to clinical and imaging assessments, as well as new emerging methodologies, we can establish a starting point for a deeper understanding of CPPD pathogenesis. Recent Findings: Recent years have seen significant advances in CPPD research, particularly in the clinical field with the development of the 2023 ACR/EULAR classification criteria for CPPD disease, and in imaging with the introduction of the OMERACT ultrasonographic definitions and scoring system. However, progress in basic research has been slower. New laboratory approaches, such as Raman spectroscopy and omics sciences, offer promising insights that may help piece together the puzzle of CPPD. Summary: CPPD is a common yet understudied condition. As the population ages and CPPD becomes more prevalent, there is an urgent need to better understand the disease and the mechanisms involved in crystal formation and deposition, in order to improve diagnosis and therapeutic approaches. [ABSTRACT FROM AUTHOR]

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.

15th Anniversary this year: the ECN workshop is set up in Paris, down town. Every year ECN workshop offers a unique opportunity for clinicians and researchers interested in crystals, inflammation, crystal-induced diseases including gout, to present their latest results and discuss novel concepts. Twenty nine out of 52 accepted abstracts are reported here. [ABSTRACT FROM AUTHOR]

During the past 20 years, the use of ultrasound (US) in rheumatology has increased tremendously, and has become a valuable tool in rheumatologists' hands, not only for assessment of musculoskeletal structures like joints and peri-articular tissues, but also for evaluation of nerves, vessels, lungs, and skin, as well as for increasing the accuracy in a number of US-guided aspirations and injections. The US is currently used as the imaging method of choice for establishing an early diagnosis, assessing disease activity, monitoring treatment efficacy, and assessing the remission state of inflammatory joint diseases. It is also used as a complementary tool for the assessment of patients with degenerative joint diseases like osteoarthritis, and in the detection of crystal deposits for establishing the diagnosis of metabolic arthropathies (gout, calcium pyrophosphate deposition disease). The US has an added value in the diagnostic process of polymyalgia rheumatica and giant-cell arteritis, and is currently included in the classification criteria. A novel use of US in the assessment of the skin and lung involvement in connective tissue diseases has the potential to replace more expensive and risky imaging modalities. This narrative review will take a close look at the most recent evidence-based data regarding the use of US in the big spectrum of rheumatic diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To develop the optimal US scanning protocol for the diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease. Methods In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls 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 standardized scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from second to fifth 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 receiver operating characteristic curves. Results The number of participants enrolled was 204: 102 with CPPD disease and 102 disease controls [age, mean (s. d.): 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 [interquartile range (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 (s. d.): 12.5 (5.3) min]. Conclusion Bilateral US assessment of knees, wrists and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The study objective was to examine the disease, demographic, and imaging features associated with different inflammatory phenotypes of calcium pyrophosphate deposition (CPPD) disease, ie, recurrent acute calcium pyrophosphate (CPP) crystal arthritis, chronic CPP crystal inflammatory arthritis, and crowned dens syndrome (CDS).Data from an international cohort (assembled from 25 sites in 7 countries for the development and validation of the 2023 CPPD classification criteria from the American College of Rheumatology/EULAR) that met the criteria were included. Three cross‐sectional studies were conducted to determine the phenotypic characteristics of recurrent acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and CDS. Multivariable logistic regression analysis was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI) to examine the association between potential risk factors and the inflammatory phenotype.Among the 618 people included (56% female; mean age [standard deviation] 74.0 [11.9] years), 602 (97.4%) had experienced acute CPP crystal arthritis, 332 (53.7%) had recurrent acute arthritis, 158 (25.6%) had persistent inflammatory arthritis, and 45 (7.3%) had had CDS. Recurrent acute CPP crystal arthritis associated with longer disease duration (aOR 2.88 [95% CI 2.00–4.14]). Chronic CPP crystal inflammatory arthritis was associated with acute wrist arthritis (aOR 2.92 [95% CI 1.81–4.73]), metacarpophalangeal joint osteoarthritis (aOR 1.87 [95% CI 1.17–2.97]), and scapho‐trapezo‐trapezoid (STT) joint osteoarthritis (aOR 1.83 [95% CI 1.15–2.91]), and it was negatively associated with either metabolic or familial risk for CPPD (aOR 0.60 [95% CI 0.37–0.96]). CDS was associated with male sex (aOR 2.35 [95% CI 1.21–4.59]), STT joint osteoarthritis (aOR 2.71 [95% CI 1.22–6.05]), and more joints affected with chondrocalcinosis (aOR 1.46 [95% CI 1.15–1.85]).CPPD disease encompasses acute and chronic inflammatory phenotypes, each with specific clinical and imaging features that need to be considered in the diagnostic workup. [ABSTRACT FROM AUTHOR]

The frequency and risk factors for the development of diastolic dysfunction (DD) in patients with CPPD and OA have not been studied. The objective of this study was to determine the frequency and identify risk factors (RF) for the development of DD of the left and right ventricles (LV and RV) in patients with calcium pyrophosphate crystal deposition disease (CPPD) and osteoarthritis (OA). The study included 26 patients with CPPD and with knee OA 18–65 years old, matched in age and gender, without cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and rheumatic diseases. Conventional risk factors (TRF) of CVD were assessed, and echocardiography was performed. The frequency of DD in patients with CPPD and OA was quite high and almost did not differ in both groups: it was detected in 19 patients, of which 11 (42%) had CPPD and 8 (31%) had OA (p = 0.39). Type 1 LV DD was detected in 10 (39%) patients with CPPD and in 8 (31%) with OA (p = 0.11); type 1RV DD was detected in 8 (31%) patients with CPPD and in 7 (27%) patients with OA (p = 0.17); and type 1 LV DD and RV DD was detected in 7 (27%) patients with both CPPD 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 CRP (it was higher in CPPD) (p = 0.03). In the CPPD group, mean values of LV E/E' (p = 0.02), LVDT (p = 0.03), LVMI (p = 0.04) were significantly higher than in patients with OA. On the contrary, in patients with OA, indices EDV (p = 0.004) and TVC (p = 0.02) were higher. There were direct correlations between diastolic function indices and the following factors in CPPD: LVL, PWLV and PTH level (r = 0.7, p <0.005), LV E' and PTH level (r = 0.7, p < 0.005). Inverse correlations were found between the level of PTH and IS (r = –0.5, p < 0.005), LVMI (r = –0.5, p < 0.005), and the level of vitamin D and VDDT (r = –0.6, p < 0.005). Direct correlations in OA were found between the level of CRP and PVAdiast (r = 0.6, p < 0.005), and the level of sUA (r = 0.7, p < 0.005), and the level of vitamin D and E/E'LV (r = 0.6, p < 0.005). A high prevalence of LV and RV DD was found in patients with CPPD and OA. The presence of DD in CPPD was associated with lower vitamin D levels, and in OA with a higher level of sUA and a lower level of PTH. [ABSTRACT FROM AUTHOR]

Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed wholeexome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCTlike features and FN1::TEK fusions. [ABSTRACT FROM AUTHOR]

Objective: Intra‐articular (IA) mineralization may contribute to osteoarthritis (OA) structural progression. We studied the association of IA mineralization on knee computed tomography (CT) with cartilage damage worsening on knee magnetic resonance imaging (MRI), with a focus on location‐ and tissue‐specific effects. Methods: Participants from the Multicenter Osteoarthritis Study with knee CT and MRI scans were included. Presence of IA mineralization on CT was defined as a Boston University Calcium Knee Score >0 anywhere in the knee. Cartilage worsening on MRI was defined as any increase in the MRI OA Knee Score, including incident damage. We evaluated the association of whole‐knee, compartment‐specific (ie, medial or lateral), and subregion‐specific (ie, location‐matched) IA mineralization at baseline with cartilage worsening at two years' follow‐up in the corresponding locations using binomial regression with generalized estimating equations, adjusting for age, sex, and body mass index (BMI). Results: We included 1,673 participants (mean age 60 years, 56% female, mean BMI 29). Nine percent had any IA mineralization in the knee, and 47.4% had any cartilage worsening on follow‐up. Mineralization of any tissue in the knee, regardless of location, was not associated with MRI cartilage worsening. However, cartilage mineralization was associated with 1.39 (95% confidence interval 1.04–1.88) times higher risk of cartilage worsening in the same compartment, with similar results in subregion‐specific analysis. Conclusion: CT‐detected IA mineralization in the cartilage was associated with higher risk of MRI cartilage worsening in the same compartment and subregion over two years. These findings suggest potential localized, tissue‐specific effects of IA mineralization on cartilage pathology in knee OA. [ABSTRACT FROM AUTHOR]

Les arthropathies microcristallines recouvrent la goutte, le rhumatisme à dépôts de pyrophosphate de calcium (PPCa), et le rhumatisme à hydroxyapatite. Ces rhumatismes sont parmi les plus fréquemment rencontrés en pratique quotidienne. La goutte est une complication de l'hyperuricémie chronique, mais tous les patients ayant une hyperuricémie ne développeront pas de goutte. Dans les pays occidentaux, la prévalence de l'hyperuricémie peut atteindre 20 % de la population adulte, mais celle de la goutte est estimée entre 1 et 4 %. Les facteurs de risque de goutte sont ceux de l'hyperuricémie avec, au premier plan, des facteurs alimentaires et génétiques, mais aussi certains médicaments comme les diurétiques. La prévalence du rhumatisme à PPCa est moins bien connue, car les études se sont souvent concentrées sur sa manifestation radiographique, la chondrocalcinose, dont la prévalence est estimée à 4–7 % de la population adulte. Ses facteurs de risque principaux sont l'hyperparathyroïdie primitive, l'hémochromatose génétique, l'hypomagnésémie, et l'arthrose. Les données épidémiologiques concernant le rhumatisme à hydroxyapatite manquent, et ne permettent pas d'estimer précisément sa prévalence en population générale. Crystal-associated arthropathies include gout, calcium pyrophosphate deposition disease (CPPD) and basic calcium phosphate (BCP) crystal-associated arthropathies. These conditions are among the most frequently encountered in daily practice. Gout is a complication of chronic hyperuricaemia, but gout will not develop in all patients with hyperuricaemia. In Western countries, the prevalence of hyperuricaemia may be as high as 20% of the adult population, but the prevalence of gout is estimated to be between 1 and 4%. The risk factors for gout are the same as for hyperuricaemia, with dietary and genetic factors being the most important ones, along with diuretics. The prevalence of CPPD is less well known, as studies have often focused on chondrocalcinosis, its radiographic manifestation, the prevalence of which is estimated at 4–7% of the adult population. Its main risk factors are primary hyperparathyroidism, hereditary haemochromatosis, hypomagnesaemia and osteoarthritis. Epidemiological data on BCP crystal-associated arthropathies are lacking, and its prevalence in the general population is not precisely known. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization. DESIGN: We included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization. RESULTS: 4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%). CONCLUSIONS: CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

BackgroundCalcium pyrophosphate deposition (CPPD) disease is a leading cause of arthritis, which can mimic or strongly interfere with other rheumatic diseases such as gout, osteoarthritis (OA) or rheumatoid arthritis (RA). In the recently established ACR/EULAR CPPD classification criteria, calcification and OA features of the wrist and hand joints are substantial features.ObjectivesTo develop and test a deep-learning algorithm for automatically and reliably detecting CPPD features in hand radiographs, focusing on calcification of the triangular fibrocartilage complex (TFCC) and metacarpophalangeal (MCP)-2 and -3 joints, in separate or combined models.MethodsTwo radiologists independently labeled a dataset of 926 hand radiographs, yielding 319 CPPD positive and 607 CPPD negative cases across the three sites of interest after adjudicating discrepant cases. CPPD presence was then predicted using a convolutional neural network. We tested seven CPPD models, each with a different combination of sites out of TFCC, MCP-2 and MCP-3. The model performance was assessed using the area under the receiver operating characteristic (AUROC) and area under the precision-recall (AUPR) curves, with heatmaps (Grad-CAM) aiding in case discrimination.ResultsAll models trialed gave good class separation, with the combined TFCC, MCP-2 and MCP-3 model showing the most robust performance with a mean AUROC of 0.86, mean AUPR of 0.77, sensitivity of 0.77, specificity of 0.80, and precision of 0.67. The TFCC-alone model had a slightly lower mean AUROC of 0.85 with a mean AUPR of 0.73. The MCP-2-alone and MCP-3-alone models exhibited mean AUROCs of 0.78–0.87, but lower mean AUPRs of 0.29–0.47. Heatmap analysis revealed activation in the regions of interest for positive cases (true and false positives), but unexpected highlights were encountered possibly due to correlated features in different hand regions.ConclusionA combined deep-learning model detecting CPPD at the TFCC and MCP-2/3 joints in hand radiographs provides the highest diagnostic performance. The algorithm could be used to screen larger OA or RA databases or electronic medical records for CPPD cases. Future work includes dataset expansion and validation with external datasets.

A 78-year-old male was seen in the emergency department (ED) with chest pain. Fifteen months earlier, he had presented to the ED with shoulder and elbow pain. High-sensitivity cardiac troponin I (hs-cTnI) testing was conducted at that time, which produced normal results of 10 and 13 ng/L (cutoff <48 ng/L). During the current admission, his electrocardiogram was unremarkable, with a borderline prolonged PR interval noted. The patient's hs-cTnI results were 25, 47, and 254 ng/L at 0, 1, and 7 hours, respectively. He was diagnosed with demand ischemia and admitted to the hospital. The detection of acute myocardial infarction in this case was made during the first sample collection (t = 0), despite the fact that this result was well within the normal range. [ABSTRACT FROM AUTHOR]

Abstract Background Dysphagia is a relatively common clinical issue in elderly population with numerous causes, which are divided into oropharyngeal and substernal categories. Most of the causes of dysphagia can be diagnosed easily with clinical and radiological examinations. However, we encountered a rare cause of dysphagia in an elderly patient, which can be missed easily during diagnostic workup, that entity is epiglottis calcification. Case presentation A 91-year-old male presented with complaints of recurrent aspirations and difficulty in swallowing. Physical examination revealed no abnormalities in the oral cavity, pharynx and nose. Flexible fiberoptic laryngoscopic examination was performed, which mildly swollen and posteriorly moved epiglottis with limited mobility during swallowing. Computed tomography scan of the larynx revealed significant asymmetric amorphous calcification of the free edge of the aryepiglottic, pharyngoepiglottic, and epiglottis folds. Conclusions Although dysphagia is a common problem in elderly, it has serious complications such as recurrent aspirations, pneumonia and nutritional deficiency. One of the rare causes of dysphagia in elderly is epiglottic calcifications, which impairs its flexibility and the functionality, and may predispose to difficulty in swallowing and recurrent aspirations.

This document contains a collection of abstracts and summaries of various studies and audits related to rheumatic diseases and arthritis care. The topics covered include seasonal variations and footwear choices for people with inflammatory arthritis, patient satisfaction with physiotherapist-led clinics, lower limb strength characteristics of individuals with psoriatic arthritis, gout management through telehealth care, and the development of resources for Aboriginal and Torres Strait Islander people. Other studies explore the diagnosis of giant cell arteritis, the clinical utility of ANA testing, the prescribing patterns of biologics, and the cardiovascular risk of JAK inhibitors. These summaries provide valuable insights for researchers and healthcare professionals in the field of rheumatology. [Extracted from the article]

Objective: Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross‐sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators. Methods: We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of "pseudogout" or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease. Results: We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person‐years) versus comparators (5.5 per 1,000 person‐years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3–2.3]); results were similar in sensitivity analyses. Conclusion: In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis. [ABSTRACT FROM AUTHOR]

Background: Dysphagia is a relatively common clinical issue in elderly population with numerous causes, which are divided into oropharyngeal and substernal categories. Most of the causes of dysphagia can be diagnosed easily with clinical and radiological examinations. However, we encountered a rare cause of dysphagia in an elderly patient, which can be missed easily during diagnostic workup, that entity is epiglottis calcification. Case presentation: A 91-year-old male presented with complaints of recurrent aspirations and difficulty in swallowing. Physical examination revealed no abnormalities in the oral cavity, pharynx and nose. Flexible fiberoptic laryngoscopic examination was performed, which mildly swollen and posteriorly moved epiglottis with limited mobility during swallowing. Computed tomography scan of the larynx revealed significant asymmetric amorphous calcification of the free edge of the aryepiglottic, pharyngoepiglottic, and epiglottis folds. Conclusions: Although dysphagia is a common problem in elderly, it has serious complications such as recurrent aspirations, pneumonia and nutritional deficiency. One of the rare causes of dysphagia in elderly is epiglottic calcifications, which impairs its flexibility and the functionality, and may predispose to difficulty in swallowing and recurrent aspirations. [ABSTRACT FROM AUTHOR]

The objective of this study was to review the literature on associations between chondro-calcinosis (CC) and osteoarthritis (OA) and to examine the role of colchicine, previously established as effective for calcium pyrophosphate deposition disease, in the treatment of OA. A literature search for mechanistic and clinical studies published between 1990 and 2021 listed in PubMed was performed and studies were included if they examined the associations between OA and CC or colchicine using relevant search terms. Published evidence suggests significant radiographic and mechanistic associations between knee OA and knee CC, but there are only a limited number of studies demonstrating associations between OA and CC in the hips, hands, and ankles. We examined three studies testing the efficacy of colchicine on treatment of pain in OA and found insufficient evidence to definitively establish that colchicine is effective to ameliorate symptoms of OA, although differences in study methodologies and inclusion criteria may explain inconsistent study findings. An association between CC and OA is supported at the knee joint in both radiographic and in-vitro studies, but is less definite when the relationship is evaluated at other joints, including at the hips, hands, and ankles. Further research is required to ascertain whether CC modifies symptoms in patients with osteoarthritis or is associated with OA progression. It may be worthwhile to further evaluate colchicine or other agents for potential symptom modifying roles in OA or in OA with CC. [ABSTRACT FROM AUTHOR]

This document provides information on the diagnosis and management of arthritis in Australia. It highlights the prevalence of arthritis in the country and its impact on individuals, including decreased productivity and mental health issues. The document emphasizes the importance of clinical assessment and appropriate testing in diagnosing arthritis, as well as the role of joint aspiration and imaging. It encourages early referral to a rheumatologist for patients with multiple swollen joints or persistent arthralgias. The document also emphasizes the importance of prompt diagnosis and appropriate treatment, collaborative care with specialists, and access to allied healthcare services in managing chronic arthritis. It cautions against the use of opioids for arthritis-related pain and emphasizes the need for early escalation of care for inflammatory arthritis or red flags for septic arthritis. [Extracted from the article]

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Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative. [ABSTRACT FROM AUTHOR]

Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is well known in pediatrics with typical presentations in children, but mild forms can also be present in adults and are difficult to detect. We present the case of a 50-year-old woman referred for pain management, with a previous diagnosis of fibromyalgia. The association of clinical features (diffuse pain syndrome, early dental loosening, personal history of two fractures with osteoporosis, and family history of osteoporosis) with radiographic (heterotopic calcifications of the yellow and interspinous lumbar ligaments) and biological (low levels of total alkaline phosphatase) indices was suggestive of hypophosphatasia, which was confirmed by genetic analysis. We review and discuss the association between hypophosphatasia, musculoskeletal pain, and calcium pyrophosphate deposition and the importance of raising the diagnosis of adult-onset hypophosphatasia when facing these two rheumatologic entities. [ABSTRACT FROM AUTHOR]

Colchicine has an important role in managing various conditions, including gout, familial Mediterranean fever, amyloidosis, Behçet's syndrome, recurrent pericarditis and calcium pyrophosphate deposition disease. The adverse effect profile of colchicine is well understood. However, due to its narrow therapeutic index, colchicine has been associated with overdose and fatalities. When ingested in toxic amounts, the mainstay of management is supportive care. Strategies to minimize the risk of colchicine poisoning can focus on three broad causes: unauthorized access, intentional overdose and inappropriate dosing. Culturally safe and appropriate education about storage and appropriate use of colchicine is essential to minimize the risk of overdose. [ABSTRACT FROM AUTHOR]

Objective 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. Methods 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. Results 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). Conclusion 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. [ABSTRACT FROM AUTHOR]

The article offers information on crystal arthritis, focusing on gout and calcium pyrophosphate deposition disease (CPPD). Topics include the presentation of crystal arthritis as acute monoarthritis caused by the deposition of crystals in joints, the importance of accurate diagnosis through synovial fluid analysis and clinical features, and the management of gout with urate-lowering therapy and anti-inflammatory drugs.

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member steering committee. Item generation (phase I) included a scoping literature review of 5 literature databases and contributions from a 35-member combined expert committee and 2 patient research partners. Item reduction and refinement (phase II) involved a combined expert committee meeting, discussions among clinical, imaging, and laboratory advisory groups, and an item-rating exercise to assess the influence of individual items toward classification. The steering committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The advisory groups eliminated items that they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item-rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the steering committee recommended focusing on imaging of the knee and wrist and 1 additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthritis induced by calcium pyrophosphate (CPP) crystals and clinically it is called pseudogout. It usually deposits in articular cartilage and in periarticular soft tissues. But no cases of pseudogout in the rotator cuff without cartilage deposition or destruction have been reported so far. We present a case of a 57-year-old woman who was diagnosed as pseudogout with rotator cuff tear. [ABSTRACT FROM AUTHOR]

Calcium pyrophosphate deposition (CPPD) disease is a crystalline arthritis that was described more than 60 years ago, yet our knowledge about this condition greatly lags behind other forms of arthritis. This is an exciting era for CPPD disease as a robust framework for CPPD clinical research has been established. The American College of Rheumatology (ACR) and EULAR co-sponsored the development of the first-ever classification criteria for CPPD. The Outcomes Measures in Rheumatology (OMERACT) CPPD Ultrasound Subtask Force developed and validated definitions for ultrasonographic findings of CPPD, and the OMERACT CPPD Working Group is establishing a core outcome domain set for this crystalline arthritis. This review focuses on key elements of the 2023 ACR/EULAR CPPD disease classification criteria and considerations for measuring outcomes in CPPD disease. [ABSTRACT FROM AUTHOR]

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]

Worldwide gout is the commonest type of inflammatory arthritis. It is often misdiagnosed and poorly managed (Dehlin et al, 2020). Gout can be diagnosed and treated in primary care and is amenable to nurse management (Doherty et al, 2018). This article will help readers to be able to diagnose and manage gout, as well as how to be aware of and treat acute gout and prevent further episodes. Certain conditions increase the risk of gout and this article advocates a holistic approach to improve overall health. [ABSTRACT FROM AUTHOR]

Calcium pyrophosphate dihydrate deposition disease (CPDD or pseudogout) is a degenerative joint disease. It is defined by the presence of calcium pyrophosphate dihydrate crystals. It usually manifests in the knee and wrist. Manifestation in the temporomandibular joint (TMJ) is only reported in case reports. We present a patient with CPDD mimicking a malignant tumor of the TMJ. A 53-year-old woman presented with progressive pain and a slow-growing swelling of the left TMJ. Imaging showed an extensive mass in the infratemporal fossa extending into the middle cranial fossa and compressing the temporal lobe. Assuming a potential malignancy, we excised the growth, which extended into the dura. We covered the resulting tissue defect within the primary surgery using a microsurgically anastomosed scapular flap and performed further reconstructive surgeries. Calcium pyrophosphate dihydrate crystals were found in the histopathologic examination of the excised tissue, resulting in the diagnosis of CPDD. That is a benign diagnosis, but we treated it like a malignancy. This leads us to the question, was there overtreatment? Tumoral CPDD in the TMJ can be a difficult diagnosis to obtain. The treatment remains controversial, but complete excision of the mass was performed in most reported cases. [ABSTRACT FROM AUTHOR]

Objective. 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 pre)clinical models of this disease to pave the way for a novel treatment. Methods. 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. Results. 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. Conclusion. iMAO-Bs dampen inflammation in murine models of crystal-induced arthropathy, thereby uncovering MAO-B as a promising target to treat these diseases. [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]

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. [ABSTRACT FROM AUTHOR]

Background: Spinal epidural abscess (SEA) is a rare condition that may result in catastrophic outcomes. On the other hand, calcium pyrophosphate (CPP) deposition disease (CPPD) causes inflammatory arthritis. Spinal involvement of a crystal-induced inflammation caused by CPPD is also common. Surgery is a common risk factor for both SEA and CPPD; however, the postoperative acute onset of SEA complicated with CPPD is extremely rare. Case Description: A man in his 70s presented to our hospital, complaining of right upper limb weakness, loss of dexterity, and gait disturbance. The diagnosis of cervical spondylotic myelopathy was made, and he performed laminectomy at C3, C4, and C5 levels. Four days after the laminectomy, he suffered from acute neck pain, weakness, and hypoesthesia in his arms and legs. Magnetic resonance imaging revealed a mass occupying the dorsal epidural space of C6 and C7, compressing the cervical spinal cord. Considering the acute symptomatology, an acute spinal epidural hematoma after surgery was suspected; therefore, emergency C6 and C7 laminectomy was performed. Surgical findings indicated that the pressure inside the spinal canal was elevated, and the mass was purulent exudate. Pathological examination showed suppurative inflammation with concomitant deposition of CPP. SEA complicated with CPPD was considered; therefore, antibiotics and non-steroidal anti-inflammatory drugs were administered. The motor weakness and hypoesthesia were improved despite a slight residual deficit in his dexterity. Conclusion: An acute onset of SEA complicated with CPPD after cervical surgery has rarely been reported. The suppurative inflammation fostered by the crystal-induced inflammation may account for the acute symptomatology. [ABSTRACT FROM AUTHOR]

CPPD disease can affect patients’ quality of life through its various clinical presentations. This mini-review discusses the evolution of CPPD from its discovery to current knowledge of its pathogenesis, genetic associations, diagnostics, and treatment options. Despite extensive research, the exact mechanisms of CPPD are not well understood, and there is a notable lack of knowledge about psychosocial impacts and patient experiences. This study aims to present a CPPD Disease Timeline identifying gaps in current knowledge and potential directions for future research. These findings contribute to a broader understanding of CPPD disease and emphasize the importance of continued research and innovation in this field.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification.

Objective: To validate the gout analyzer as a clinical method of synovial fluid crystal analysis. Methods: Thirty knee synovial fluid samples with suspected calcium pyrophosphate (CPP) crystals were analyzed. Within 48 hours after collection, each non-centrifuged sample was examined blindly and independently by one or more rheumatologists in the following order: 1) with an optical microscope under ordinary light, 2) with the same microscope under compensated polarization provided by a gout analyzer, and 3) with a fully equipped compensated polarized microscope with a rotating stage as the gold standard. As a reference, laboratory technicians analyzed fresh, centrifuged synovial fluid using a gout analyzer. Results: Of the 30 samples analyzed, CPP and monosodium urate (MSU) crystals were detected in 11 and four, non-centrifuged samples, respectively, using a fully equipped compensated polarized microscope. The rheumatologists' detection rate of crystals in the non-centrifuged synovial fluid under ordinary light and with a gout analyzer was 73.3% and 80%, respectively. The laboratory technicians' detection rate in fresh centrifuged synovial fluid using a gout analyzer was 100%. Conclusion: A gout analyzer may be used to diagnose gout and calcium pyrophosphate deposition disease definitively if a fully equipped compensated polarized microscope is unavailable. [ABSTRACT FROM AUTHOR]

Introduction: Apatite rheumatism (AR), chondrocalcinosis (Ch-C), and primary synovial chondromatosis (prSynCh) are regarded as distinct clinical entities. The introduction of the non-staining technique by Bély and Apáthy (2013) opened a new era in the microscopic diagnosis of crystal induced diseases, allowing the analysis of MSU (monosodium urate monohydrate) HA (calcium hydroxyapatite), CPPD (calcium pyrophosphate dihydrate) crystals, cholesterol, crystalline liquid lipid droplets, and other crystals in unstained sections of conventionally proceeded (aqueous formaldehyde fixed, paraffin-embedded) tissue samples. The aim of this study was to describe the characteristic histology of crystal deposits in AR, Ch-C, and prSynCh with traditional stains and histochemical reactions comparing with unstained tissue sections according to Bély and Apáthy (2013).Patients and methods: Tissue samples of 4 with apatite rheumatism (Milwaukee syndrome), 16 with chondrocalcinosis, and 20 with clinically diagnosed primary synovial chondromatosis were analyzed.Results and conclusion: Apatite rheumatism, chondrocalcinosis, and primary synovial chondromatosis are related metabolic disorders with HA and CPPD depositions. The authors assume that AR and Ch-C are different stages of the same metabolic disorder, which differ from prSynCh in amorphous mineral production, furthermore in the production of chondroid, osteoid and/or bone. prSynCh is a defective variant of HA and CPPD induced metabolic disorders with reduced mineralization capabilities, where the deficient mineralization is replaced by chondroid and/or bone formation. The non-staining technique of Bély and Apáthy proved to be a much more effective method for the demonstration of crystals in metabolic diseases than conventional stains and histochemical reactions.

Objective: Intra‐articular (IA) calcium crystal deposition is common in knee osteoarthritis (OA), but of unclear significance. It is possible that low‐grade, crystal‐related inflammation may contribute to knee pain. We examined the longitudinal relation of computed tomography (CT)–detected IA mineralization to the development of knee pain. Methods: We used data from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. Participants had knee radiographs and bilateral knee CTs at baseline, and pain assessments every 8 months for 2 years. CT images were scored using the Boston University Calcium Knee Score. We longitudinally examined the relation of CT‐detected IA mineralization to the risk of frequent knee pain (FKP), intermittent or constant knee pain worsening, and pain severity worsening using generalized linear mixed‐effects models. Results: We included 2,093 participants (mean age 61 years, 57% women, mean body mass index 28.8 kg/m2). Overall, 10.2% of knees had IA mineralization. The presence of any IA mineralization in the cartilage was associated with 2.0 times higher odds of having FKP (95% confidence interval [CI] 1.38–2.78) and 1.86 times more frequent intermittent or constant pain (95% CI 1.20–2.78), with similar results seen for the presence of any IA mineralization in the meniscus or joint capsule. A higher burden of IA mineralization anywhere within the knee was associated with a higher odds of all pain outcomes (odds ratio ranged from 2.14 to 2.21). Conclusion: CT‐detected IA mineralization was associated with risk of having more frequent, persistent, and worsening knee pain over 2 years. Targeting IA mineralization may have therapeutic potential for pain improvement in knee OA. [ABSTRACT FROM AUTHOR]