Crystals In Synovial Fluid Research Articles

The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid from wrist and finger joints

The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

Échographie dans les arthropathies microcristallines

Gout and pseudogout are crystal-related diseases secondary to a metabolic disorder. The consequences are: (i) deposition in joints, synovium and tendons and (ii) possibility of inflammatory arthritis. The gold standard for diagnosis is the visualization by optic microscopy of crystals in synovial fluid. However, diagnosis is sometimes difficult and imaging can help the physician to diagnose this diseases. Radiography is not sensitive in early gout and sometimes normal in pseudogout. Thus, ultrasonography (US) might appear as a useful tool in the management of these diseases. In gout, two US features are specific: the double contour sign and aggregates evocating of tophus. Moreover, these signs can disappear under efficient urate lowering therapy. In pseudogout, the interest of US is mainly for the diagnosis by direct visualization of calcifications in hyaline cartilage and fibrocartilage. In pseudogout, US is more sensitive than radiography to detect these calcifications. In summary, US appears to be useful for diagnosis and management of these two crystal-related diseases.

First experience with single-source dual-energy computed tomography in six patients with acute arthralgia: a feasibility experiment using joint aspiration as a reference.

Dual-energy computed tomography (DECT) is an emerging imaging technique for examining patients with suspected gout. Single-source dual-energy CT (S-DECT) is a new way of obtaining DECT information on conventional CT scanners rather than using special dual-source CT systems. We tested the feasibility of S-DECT (320-row CT; Aquilion ONE, Toshiba Medical Systems, Otawara, Japan) in 6 patients (5 men, 1 woman; mean age 61.3, range 48 to 69 years) with acute arthralgia and suspected gout, and compared the S-DECT findings with the results of joint aspiration. Three patients had a diagnosis of gouty arthritis with negatively birefringent crystals in synovial fluid, in addition to gouty tophi in S-DECT. Three patients had no detectable crystals by polarization microscopy and no tophi on DECT. Their final diagnoses were rheumatoid arthritis, activated osteoarthritis, and septic arthritis in one case each. This initial experience suggests that S-DECT might be a valuable alternative to dual-source CT. Hence, more patients may benefit from its additional diagnostic abilities in the future.

Update on the diagnosis and management of gout.

Gout is a common clinical problem encountered by both general and specialist clinicians. The key principles in gout management include establishing a definitive diagnosis, the swift treatment of acute attacks, and using urate-lowering therapies appropriately to prevent further attacks and joint damage. The gold standard diagnostic tool for gout remains the identification by polarised light microscopy of monosodium urate crystals in synovial fluid or in a tophus. Emerging diagnostic imaging techniques and novel therapies show promise in the diagnosis and treatment of gout. In most cases, using existing therapies judiciously remains the key determinant of success in managing gout.

An unusual ophthalmic presentation of inflammatory polyarticular gout

Gout affecting multiple organs and tissues is characterized by the deposition of tophi in subcutaneous tissues, joints, tendons, kidneys, myocardium, heart valves, auricular cartilage, spinal cord, and eyes. There are very few case reports of tophi involving eye in gout and usual locations are subconjunctiva, medial canthus, and cornea. 1, 2, 3 A 50-year-male, diabetic, with inflammatory polyarthritis was referred from Ophthalmology Department with recurrent nodular swellings over both knees (Fig. 1) and lateral malleoli (Fig. 2). He had undergone corneal patch graft (Fig. 3) for peripheral ulcerative keratitis and corneal perforation (Fig. 4). The patient was negative for IgM rheumatoid factor; ANA and c-ANCA, and p-ANCA. Elevated serum creatinine (1.7 mg/dl) with hematuria was reported. Radiograph of hands showed large cystic erosions of carpal bones on both sides (Fig. 5). Serum uric acid level of 7.3 mg/dl (normal range 3.6-7 mg/dl) was reported and synovial fluid examination showed intra-cellular needle shaped crystals suggestive of uric acid. The diagnosis was concluded as polyarticular gout based on the presence of nodules suggestive of atypical tophi, cystic erosions, and needle shaped crystals in synovial fluid.

Ultrasound in gout: A useful tool for following urate-lowering therapy

ObjectiveWe aimed to determine the ability of ultrasonography (US) to show decrease or disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT). MethodsTo be included in this prospective single-centre study, patients needed toexhibit (1) proven gout by monosodic urate (MSU) crystals in synovial fluid and (2) US-evidenced urate deposits (double contour [DC] sign and/or tophi) before starting ULT (allopurinol [n=4], febuxostat [n=12]). At baseline and after six months of ULT, one trained ultrasonographer assessed the knee and first metatarsophalangeal (MTP1s) joints. Serum uric-acid (SUA) level was assessed at baseline and at three and six months after ULT initiation. Correlation between US findings and achievement of SUA level objective (< 360μmol/L) was estimated by the kappa coefficient (κ). ResultsWe studied 16 patients (all males, mean age 61.0±18.3 years). The mean disease duration was 7.1±6.2 years. Tophi were found at clinical examination in 56% of patients. Baseline SUA levels were 688±153μmol/L. At baseline, US revealed tophi or a DC sign among 62.5 to 75% of patients in knees and 87.5% in MTP1s. After six months of ULT, none of the four patients, not achieving the SUA level objective, had disappearance of US features. Among the remaining 12 patients, US features (tophi or DC sign) disappeared or decreased in all but one with a stable DC sign in one MTP1. The correlation between the whole US examination and SUA level was excellent (κ=0.875). ConclusionsUS could show disappearance of urate deposits after ULT and appears to be well correlated with efficacy of ULT.

Non-steroidal anti-inflammatory drugs for acute gout.

Non-steroidal anti-inflammatory drugs for acute gout.

THE CLINICAL MANIFESTATIONS OF CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

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SAT0535 Sensitivity and Reproducibility of Ultrasonography in Calcium Pyrophosphate Crystal Deposition: A Case-Control Study

BackgroundCalcium pyrophosphate disease (CPPD) is a common disease characterized by deposition of calcium pyrophosphate (CPP) crystals in joints and tendons. The diagnosis is made by identification of CPP crystal in...

SP0064 Imaging Biomarkers as A Useful Tool in Gout Disease

Conventional radiography can show characteristic features of gouty arthritis such as intraosseous cysts or large erosions with overhanging edges in an advanced tophaceous stage. For early diagnosis, however, conventional X-rays...

OP0008 Ultrasound in Gout: A Useful Tool for Follow-Up with Urate-Lowering Therapy

BackgroundRecently, ultrasonography (US) demonstratted its ability to detect urate deposition in gouty patients. Some US features have been suggested to be specific such as tophus and the double contour sign....

SAT0532 Updated Eular Evidence-Based Recommendations for the Diagnosis of Gout

BackgroundGout has become the most common inflammatory arthritis but is still frequently misdiagnosed. New data on imaging and clinical diagnosis have become available since publication of the first EULAR recommendations...

AB0839 The Characteristic of Joint Involvement in Calcium Pyrophosphate Deposition Disease

BackgroundCalcium Pyrophosphate Deposition Disease (CPPD) is a metabolic disorder caused by calcium pyrophosphate (CPP) formation in joints. The diagnosis of CPPD is based on clinical manifestations and/or the presence of...

Identification of patients with gout: elaboration of a questionnaire for epidemiological studies

ObjectivesIn France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians...

Cytospin preparations are superior to common smears in the detection of monosodium urate crystals in low-cellular synovial fluids.

In cases of gout with a low synovial fluid (SF) leukocyte count and atypical clinical presentation, such as in intercritical periods, the load of monosodium urate (MSU) crystals is frequently low, and thus, methods to improve the crystal detection may be beneficial. We compared the MSU crystal detection rates between cytospin slides and common smear preparations in low-cellular (<2,000/μl) SF samples of patients with gout. We determined the number of MSU crystals/15 high power fields (HPF) at × 1,000 magnification by polarised microscopy in cytospin preparations and smears in SF samples of 17 patients with MSU-crystal-proven gout and compared the two methods statistically. All of the cytospin slides (100 %) contained MSU crystals and showed a median number of 124 crystals/15 HPF (range 2-3,915), whereas 5 of the 17 smears (29 %) were MSU-crystal-negative, with a median count of 2 crystals/15 HPF (range 0-430/HPF). The difference was statistically highly significant (p < 0.0001). In conclusion, we have shown that the cytospin technique is superior to smears in the detection of MSU crystals in SF with a low SF leukocyte count. In light of our observations, we recommend the use of cytocentrifuges for routine crystal analysis in such cases.

Calcium crystals detected by scanning electronic microscopy in synovial fluid of patients with early knee osteoarthritis. relationships with infiammation and disease severity

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S392 characterized by pain and/ or stiffness of knee and/ or hip. They were included at the first visit or within 6 months of the first visit to the general practitioner for these symptoms. Study centers comprise ten general and university hospitals located in urbanized and semiurbanized regions in the Netherlands. A special programwas developed to minimize loss to follow up, comprising newsletters, website and organizing symposia to present the results and progress of CHECK. An overview of measures that are included in the study can be found at our website www.check-research.com. Results: After 7 years a total of 105 (10%) participants had dropped out. Reasons included loss of interest (21%), comorbidity that complicated participating of CHECK too much (18%), death (12%), contact lost (11%), costs incurred for the study (5%), and other reasons (33%). Dropouts did not differ significantly from other participants in baseline characteristics. Over 7 years follow-up clinical characteristics including pain, stiffness and function of disease-specific (WOMAC) and the subscales of generic self-report questionnaire (SF36) on average did not change significantly, although at least half of the patients experienced radiographic progression. Scoring of 5-year follow up is complete: at this point, 50 % of the participants progressed by at least one Kellgren and Lawrence grade in the knee, and 25% in the hip. Preliminary analyses suggest the existence of several clinical and radiological phenotypes. Conclusions: CHECK is a valuable source of information of early symptomatic OA with a low loss to follow-up and a multidisciplinary approach that allows the collections of high-quality data on clinical, radiological and biochemical variables. 697 CALCIUM CRYSTALS DETECTED BY SCANNING ELECTRONIC MICROSCOPY IN SYNOVIAL FLUID OF PATIENTS WITH EARLY KNEE OSTEOARTHRITIS. RELATIONSHIPS WITH INFIAMMATION AND DISEASE SEVERITY R. Ramonda y, P. Frallonardo y, L. Peruzzo z, L. Tauro x, A. Scanu y, M. Lorenzin y, A. Ortolan y, P. Galozzi y, F. Oliviero y, L. Punzi y. yRheumatology Unit, Univ. of Padova, Padova, Italy; z Inst. for GeoSci.s and Earth Resources IGG-CNR, Padova, Italy; xDept. of GeoSci.s, Univ. of Padova, Padova, Italy Purpose: The presence of calcium crystals (CC) in synovial fluid (SF) of osteoarthritis (OA) is a well known and frequent feature. However, their role in the pathogenesis of OA is still unclear andmatter of discussion, in particular as regard the local inflammation. The objective of the study was to evaluate the presence of the most common CC, calcium pyrophosphate (dehydrate) (CPP) and basic calcium phosphate (BCP), in SF of the symptomatic knee OA (KOA, particularly in early disease stage (<1year) and to investigate their association with local infiammation, disease activityand severity. We performed an ultrasensitive analysis of SF crystals using the scanning electron microscopy (SEM) and the routinary method by compensated polarized ligth microscopy (CPLM) and alizarin red staining. Methods: Seventy-four (48 F, mean age 64.85 9.33 yrs, range 50-89 yrs) consecutive outpatients attending theRheumatology Unit, University of Padova with symptomatic KOA (according to the American College of Rheumatology criteria) underwent knee arthrocentesis. After optical and CPLM, the SF was analysed by SEM. Total white blood cell (WBC) count was performed and a cut-off of total WBC was established

Gram and acridine orange staining for diagnosis of septic arthritis in different patient populations

The sensitivity of Gram staining is known to be suboptimal for the diagnosis of native joint septic arthritis. We lack information about the accuracy of Gram compared to other microscopic staining techniques for predicting infection in different patient populations. This was a cohort study with cost evaluations at the Orthopaedic Service of Geneva University Hospitals (January 1996-October 2012). Among 500 episodes of arthritis (196 with immunosuppression, 227 with underlying arthroplasties and 69 with gout or other crystals in synovial fluid), Gram staining revealed pathogens in 146 episodes (146/500, 29 %) or in 146 of the 400 culture-positive episodes (37 %). Correlation between the Gram and acridine staining of the same sample was good (Spearman 0.85). Overall, the sensitivity, specificity, positive predictive value and negative predictive value of Gram stain for rapid diagnosis of septic arthritis was 0.37, 0.99, 0.99 and 0.28, respectively, compared to microbiological cultures. Quite similar values were recorded across the different patient subpopulations, in particular for sensitivity values that were 0.33 for patients with prosthetic joint infections, 0.40 for immunosuppressed patients, 0.36 for patients under antibiotic administration and 0.52 for patients with concomitant crystalline disease. The sensitivity of Gram or acridine orange staining for a rapid diagnosis of episodes of septic arthritis is suboptimal compared to microbiological culture, regardless of underlying conditions, immunosuppression or antibiotic therapy. The sensitivity in the presence of synovial fluid crystals is moderate. Acridine orange and Gram stains are equivalent.

De-crystallization of Uric Acid Crystals in Synovial Fluid Using Gold Colloids and Microwave Heating.

In this study, we demonstrated a unique application of our Metal-Assisted and Microwave-Accelerated Evaporative Crystallization (MA-MAEC) technique for the de-crystallization of uric acid crystals, which causes gout in humans when monosodium urate crystals accumulate in the synovial fluid found in the joints of bones. Given the shortcomings of the existing treatments for gout, we investigated whether the MA-MAEC technique can offer an alternative solution to the treatment of gout. Our technique is based on the use of metal nanoparticles (i.e., gold colloids) with low microwave heating to accelerate the de-crystallization process. In this regard, we employed a two-step process; (i) crystallization of uric acid on glass slides, which act as a solid platform to mimic a bone, (ii) de-crystallization of uric acid crystals on glass slides with the addition of gold colloids and low power microwave heating, which act as “nano-bullets” when microwave heated in a solution. We observed that the size and number of the uric acid crystals were reduced by >60% within 10 minutes of low power microwave heating. In addition, the use of gold colloids without microwave heating (i.e. control experiment) did not result in the de-crystallization of the uric acid crystals, which proves the utility of our MA-MAEC technique in the de-crystallization of uric acid.

Untreated tophaceous gout

Gout is associated with hyperuricemia and characterized by inflammatory arthritis induced by monosodium urate crystal deposition in synovial fluid and other tissues. Tophi can occur in soft and osseous tissue, ligaments, and different organs, either in presence or absence of gouty arthritis. If left untreated, hyperuricemic patients (serum urate level = 6.8 mg/dL or 400 mol/L) can evolve from intermittent arthritis to polyarticular tophaceous gout with symptoms between attacks. Lowering serum urate levels with xanthine oxidase inhibitors or uricosuric agents prevents acute flares and tophi development. Synovial fluid crystals slowly dissolve and can disappear after normalization of serum urate levels. Uricosuric agents are, generally, ineffective in patients with renal impairment. The recommended target serum uric acid concentration is <6 mg/dL (357 mol/L). Although controversial, recommendations have been made to achieve a target serum urate level <5 mg/dL (297 mmol/L) in severe chronic gout patients, as this concentration may be associated with greater depletion of synovial fluid crystals and a reduction in tophus size. Therapy is usually continued indefinitely. Several urate-lowering agents are currently under clinical investigation. These include uricase agents and inhibitors of renal urate transporter proteins. Interventions which enhance patient education and treatment adherence are considered important in improving gout management.

A customized Raman system for point-of-care detection of arthropathic crystals in the synovial fluid

Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) are the most frequently observed crystals in joint space, leading to painful arthropathies. Correct diagnosis of the crystal identity is critical for the appropriate course of treatment. In this work, a custom Raman device in combination with a practical and efficient sample preparation method is used for chemically selective diagnosis of MSU and CPPD crystals in an automated fashion. The samples were prepared by brief enzymatic digestion treatment of synovial fluid followed by a customized filtration process which was able to congregate crystals over a submillimeter sized spot. The data acquisition and collection were automated to collect multiple spectra distributed over the filtration spot. The performance of the cost-efficient Raman system was compared to a research-grade high fidelity Raman instrument. The custom-designed Raman device could detect MSU crystals at sub-clinical concentrations of 0.1 μg mL(-1) and 1 μg mL(-1) for CPPD crystals. This practical sample preparation approach in tandem with the low-cost customized Raman device has potential to be a novel tool for point-and-shoot Raman diagnosis of arthritic crystals in synovial fluid at the point of care.