Calcium Pyrophosphate Crystals Research Articles

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.

Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate-Associated Arthritis.

We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)-associated arthritis (CPPD). This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3-94.2), specificity 99.1% (95% CI 97.5-99.8), positive likelihood ratio 100.33 (95% CI 32.3-311.3), negative likelihood ratio 0.14 (95% CI 0.07-0.28), positive predictive value 93.5% (95% CI 82.2-97.8), negative predictive value 98.0% (95% CI 82.2-97.8), and accuracy 97.5% (95% CI 95.5-98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.

Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

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.

An update on the study of synovial fluid in the geriatric patient.

The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults' SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.

Recent advances in the therapeutic management of calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition (CPPD) disease is a form of crystal-induced arthropathy that arises from the accumulation of calcium pyrophosphate crystals within joints and soft tissues. This process leads to inflammation and damage to the affected joints. It can present asymptomatically or as acute or chronic inflammatory arthritis. Risk factors and comorbidities, including prior joint injury, osteoarthritis, hereditary or familial predisposition, and metabolic diseases, should be evaluated in CPPD cases. The management of CPPD remains a challenge in the sparsity of randomized controlled trials. The lack of such trials makes it difficult to establish evidence-based treatment protocols for CPPD. This review provides an overview of the current pharmacological management of CPPD, focusing on reducing inflammation, alleviating symptoms, and preventing acute flares. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine are effective in managing acute CPP arthritis. Colchicine may also be used prophylactically to prevent recurrent flares. In cases where other treatments have failed, anakinra, an interleukin-1 receptor antagonist, can be administered to alleviate acute flares. The management of chronic CPP inflammatory arthritis includes NSAIDs and/or colchicine, followed by hydroxychloroquine, low-dose glucocorticoids, and methotrexate, with limited data on efficacy. Tocilizumab can be used in refractory cases. In small studies, synovial destruction using intra-articular injection of yttrium 90 can decrease pain. To date, no disease-modifying therapies exist that reduce articular calcification in CPPD.

First classification criteria for diseases caused by calcium pyrophosphate deposition (CPPD)-Translation, explanation and assessment

For diseases caused by calcium pyrophosphate deposition (CPPD), validated classification criteria were previously lacking. In this article the recently developed and validated classification criteria are translated, explained, and assessed. In recent years a multinational research group developed classification criteria for CPPD disease with the support by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR), following an established method. The developed criteria were finally validated in an independent cohort. The translation and annotation of the new first classification criteria were carried out in an iterative procedure in consensus with the authors. The presence of a crowned dens syndrome or calcium pyrophosphate crystals in the synovial fluid in patients with pain, swelling or sensitivity of the joints (entry criterion) is sufficient for the classification as CPPD disease, where the symptoms cannot be completely explained by another rheumatic disease (exclusion criterion). If these symptoms are not present, a count of more than 56 points based on weighted criteria comprised of clinical features and the results of laboratory and imaging investigations can be included for classification as a CPPD disease. These criteria had a sensitivity of 92.2% and a specificity of 87.9% in the derivation cohorts (190 CPPD cases and 148 mimics), whereas the sensitivity was 99.2% and the specificity 92.5% in the validation cohorts (251 CPPD cases and 162 mimics). The ACR/EULAR classification criteria 2023 of a CPPD disease will facilitate clinical research in this field. The use in the clinical routine will show how practical the criteria are.

Synovial Fluid from Patients with Osteoarthritis Shows Different Inflammatory Features Depending on the Presence of Calcium Pyrophosphate Crystals.

The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1β, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1β, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 β in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals.

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.

Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis

Aims: To study factors associated with the development of calcium pyrophosphate (CPP) arthritis and the severity phenotype. Methods: Transversal case-control study. Cases had to be confirmed by both X-ray chondrocalcinosis and CPP crystals in synovial fluid. Controls had neither chondrocalcinosis nor CPP crystals in synovial fluid. Patients and controls with hemochromatosis or primary hyperparathyroidism were not included. Mutations of hemochromatosis genes (HFE), magnesium (Mg), calcium (Ca), phosphate, iron (Fe), transferrin saturation, ferritin, parathyroid hormone (PTH), and calcifediol levels were studied. Results: Three hundred patients and 300 sex and age matched controls were compared. Lower serum Mg (sMg) and higher ferritin levels were found among patients. Hypomagnesemia (HypoMg) and HFE mutations were more frequent among patients. Involvement of over one joint was observed in 199 (66.4%) patients whereas persistent joint inflammation was retrieved in 154 (51.4%) of the patients. Initial analysis showed that the frequency of polyarticular and inflammatory phenotypes seemed to be progressively overrepresented in patients with HFE mutations. Further bivariate and multivariate analysis adjusted for the time from onset disclosed that the presence of genotypes with C282Y mutations was associated with polyarticular disease (hazard risk 3.501, 95% confidence interval 1.862–6.581, P &lt; 0.001). Although C282Y mutations also seemed to be associated with inflammatory patterns, the association did not reach statistical significance (P = 0.173). Conclusions: Low sMg and high ferritin levels are associated with CPP arthritis (CPPA). In patients without hemochromatosis, HFE mutations, and specifically C282Y mutations seem to associate with the polyarticular disease phenotype, and plausibly with the chronic inflammatory phenotype.

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.

Ballooning Periprosthetic Osteolysis Related to Crystalline Arthropathies Following Total Ankle Arthroplasty: A Case Series

Category: Ankle Arthritis; Basic Sciences/Biologics Introduction/Purpose: From 2009-2019, there has been a 120% increase in the incidence of total ankle arthroplasty (TAA) in the United States. With the rise in primary TAA, future increases in revision TAA cases is anticipated. Aseptic loosening with periprosthetic osteolysis continues to account for a significant number of revisions. While several factors may contribute to the pathophysiology of osteolysis, an underlying inflammatory response surrounding TAA implants may play a primary role. It is well known that monosodium urate (gout) and calcium-pyrophosphate (pseudo-gout) crystals evoke a highly inflammatory response and may involve the foot and ankle joints. However, the effect of these conditions following TAA has not yet been reported. We present a small case series of patients with ballooning osteolysis following TAA with confirmed crystalline arthropathy. Methods: This is a retrospective study from a single academic institution looking at patients who underwent TAA revision surgery for periprosthetic osteolysis and concern for aseptic loosening. Revision surgeries were performed by three orthopedic foot and ankle fellowship trained surgeons. Case characteristics, including pre-operative imaging, clinical presentations, intra-operative findings and surgical treatments performed were analyzed and presented in this small case series. Results: We report 5 patients whom underwent revision surgery for ballooning periprosthetic osteolysis following TAA. Intra- operative pathology samples from periprosthetic cysts returned positive for monosodium urate (MSU) or calcium pyrophosphate (CPP) crystalline deposition (1 MSU and 4 CPP) in all 5 patients. Final intra-operative cultures were all negative for infection. Upon gross intra-operative inspection, all polyethylene liners were considered to be normal without abnormal wear characteristics. Periprosthetic cysts were isolated to the tibial component in 2 patients and involved both the tibial and talar components in 3 patients. Staged TAA revision was performed in 2 patients. Bone cyst curettage, bone grafting and polyethylene liner exchange was performed in 3 patients. Conclusion: Periprosthetic osteolysis is a known complication following TAA and often leads to implant loosening, functional disability and subsequent revision surgery. An objective strategy for management of this condition has not been agreed upon amongst orthopedic foot and ankle surgeons, as uncertainty remains surrounding the pathophysiology of osteolysis in TAA. To our knowledge, we are the first to describe a small case series of patients with crystalline arthropathy as a potential cause for periprosthetic osteolysis following TAA. Future prospective studies are warranted to better elucidate this potential cause of TAA failure.

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.

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

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. 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. 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). The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

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.

Synovial fluid crystal analysis with compensated polarization using a gout analyser inclinical practice.

To validate the gout analyzer as a clinical method of synovial fluid crystal analysis. 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. 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%. A gout analyzer may be used to diagnose gout and calcium pyrophosphate deposition disease definitively if a fully equipped compensated polarized microscope is unavailable.

The Persistency and Visibility of Synovial Fluid Crystals After at Least 10 Days in Refrigerator by Light and Polarized Microscopy.

Synovial fluid (SF) analysis is one of the most important tests used in approach to arthritis and is necessary for rheumatology fellowship training. It depends on the operator's experience and can be affected by handling, processing, temperature, type of preservative, and time from aspiration to analysis. Therefore, we aimed to reevaluate the SF with positive results for crystals, after at least 10days for the persistency and visibility of the crystals. For 1year, we reevaluated crystal positive synovial fluid samples after at least 10days under light and polarized microscopy. The samples were sent in tubes without any preservative. After the first day of diagnosis of a crystal arthropathy, all the samples were kept in 4°C refrigerator in a syringe without any preservative and then reevaluated. 14 calcium pyrophosphate (CPP); 12 monosodium urate (MSU), 1 of which was combined CPP and MSU; and 1 post-methylprednisolone (Depomedrol) injection, steroid crystal arthropathy were found and reevaluated. In all reevaluated samples [between 10-24 (median:14days)], the crystals were detectable again. Our results suggests that SF CPP, MSU and methylprednisolone crystals at 4°C without preservation could be detectable after 10-24days (median: 14, 15.5, and 10days, respectively) under light and polarized microscopy. It seems that the samples evaluated in emergency settings without enough time and those sent from other centers or gathering samples for trainees can be kept to detect crystals at least 10days for all and till 22days (for CCP and MSU) after sampling.

Differences in the Optical Response of MSU and CPP Crystals During Magnetic Orientation: Possibility of Diagnosing Gout and Pseudogout.

Pseudogout is crystalline arthritis. It has a similar clinical picture to that of gout, and it is difficult to distinguish the two diseases using conventional analysis methods. However, it is important to identify the different crystals responsible for these two cases because the treatment strategies are different. In a previous study, we reported magnetic orientation of monosodium urate (MSU) crystals, which are the causative agent of gout, at the permanent magnet level. In this study, we investigated the effect of an applied magnetic field on calcium pyrophosphate (CPP) crystals, which are the causative agent of pseudogout, and the difference in the magnetic responses of CPP and MSU crystals. We found that the CPP crystals were oriented in a magnetic field on milli-Tesla order because of the anisotropy of the diamagnetic susceptibility. In addition, the CPP crystals exhibited different anisotropic magnetic properties from those of MSU crystals, which led to a characteristic difference between the orientations of the two crystals. That is, we found that the causative agents of gout and pseudogout responded differently to a magnetic field. This report suggests that the discrimination between CPP and MSU by optical measurements is possible by application of magnetic fields appropriately. © 2023 Bioelectromagnetics Society.

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