Crystals In Synovial Fluid Research Articles

A Novel Polarized Light Microscope for the Examination of Birefringent Crystals in Synovial Fluid

Background: The gold standard for crystal arthritis diagnosis relies on the identification of either monosodium urate (MSU) or calcium pyrophosphate (CPP) crystals in synovial fluid. With the goal of enhanced crystal detection, we adapted a standard compensated polarized light microscope (CPLM) with a polarized digital camera and multi-focal depth imaging capabilities to create digital images from synovial fluid mounted on microscope slides. Using this single-shot computational polarized light microscopy (SCPLM) method, we compared rates of crystal detection and raters’ preference for image. Methods: Microscope slides from patients with either CPP, MSU, or no crystals in synovial fluid were acquired using CPLM and SCPLM methodologies. Detection rate, sensitivity, and specificity were evaluated by presenting expert crystal raters with (randomly sorted) CPLM and SCPLM digital images, from FOV above clinical samples. For each FOV and each method, each rater was asked to identify crystal suspects and their level of certainty for each crystal suspect and crystal type (MSU vs. CPP). Results: For the 283 crystal suspects evaluated, SCPLM resulted in higher crystal detection rates than did CPLM, for both CPP (51%. vs. 28%) and MSU (78% vs. 46%) crystals. Similarly, sensitivity was greater for SCPLM for CPP (0.63 vs. 0.35) and MSU (0.88 vs. 0.52) without giving up much specificity resulting in higher AUC. Conclusions: Subjective and objective measures of greater detection and higher certainty were observed for SCPLM over CPLM, particularly for CPP crystals. The digital data associated with these images can ultimately be incorporated into an automated crystal detection system that provides a quantitative report on crystal count, size, and morphology.

Increased Incidence and Clinical Features of Septic Arthritis in Patients Aged 80 Years and above: A Comparative Analysis with Younger Cohorts.

This study aimed to determine the incidence of septic arthritis across adult age groups in Västra Götaland Region (VGR) of Sweden, while also comparing disease characteristics among different age groups with hematogenous septic arthritis. Using ICD-10 codes for septic arthritis from 2016 to 2019, we identified 955 patients in VGR. We reviewed the medical records of 216 adult patients with hematogenous septic arthritis and compared data across age groups. The overall incidence of septic arthritis in adults was 4 per 100,000 persons annually, rising to 14 per 100,000 in those ≥80 years. The median age of the 216 patients was 71. The comparison across age groups (18-64, 65-79, and ≥80) showed significantly longer hospital stays and higher mortality rate in the older groups. CRP levels were higher in the middle age group, SF-WBC counts were lower in the youngest age group, and synovial fluid crystals were more common in the oldest. No differences were found in joint involvement or the organisms isolated. The incidence of septic arthritis is 6.5 times higher in patients aged ≥ 80 compared to those under 65, highlighting the need to consider age-related differences in disease management.

Prevalence and factors associated to calcium pyrophosphate arthritis in patients with gout

Aim: To ascertain the prevalence of calcium pyrophosphate arthritis (CPPA) at diagnosis and during follow-up of patients with gout. Methods: Inception cohort of patients with gout prospectively recruited and followed-up from 1994–2023. Gout-case was defined as crystal-proved tophus or arthritis, or the presence of tophus plus double contour with ultrasonography. CPPA was defined as the presence of intra-leukocyte calcium pyrophosphate (CPP) crystals in synovial fluid (SF) and neat chondrocalcinosis in plain radiographs. Age, gender, time from onset of symptoms, number of flares, joint distribution, previous and prescribed treatments, colchicine prophylaxis, comorbidities, alcohol intake, use of diuretics, renal function, and previous vascular disease were available for analysis. Results: A total of 1,544 patients with gout, with an average of 4-year follow-up, were available for analysis. CPPA was observed in 127/1,544 cases (8.2%). In 37/1,544 patients (2.4%) CPP and monosodium urate (MSU) crystals were observed in the same SF sample at gout diagnosis, and 90/1,544 (5.8%) showed CPP crystals apart from the diagnosis of gout. CPPA-gout cases had more flares per year, but no more frequent polyarticular distribution at baseline compared to non-CPPA-gout. CPPA-gout cases were older at baseline and showed lower renal function. Women, patients using diuretics, patients with hypertension, and those with previous vascular events showed CPPA more frequently. Multivariate analysis showed that only age and use of diuretics were independently associated with CPPA, as other variables apparently associated were dependent on aging. Interestingly, an analysis of the prevalence in the three decades available showed an increased CPPA diagnosis through time, probably associated with increased awareness of the association. Conclusions: (1) CPPA is not infrequent in patients with gout; (2) it is associated with aging and diuretic use; (3) awareness of this association may increase the rate of diagnosis.

An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting.

Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department. We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centra. We analyzed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or else. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine. The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI 92.3-98.3), while the accuracy for classification of MSU with using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI 87.9-95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI 82.7-92.2). The model was able to discriminate between pathologic crystals, artifacts, and other particles such as microplastics. We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.

Discovery of calcite as a new pro-inflammatory calcium-containing crystal in human osteoarthritic synovial fluid

ObjectiveWe aimed to characterize calcium-containing crystals present in synovial fluid from patients with knee osteoarthritis (OA) using Raman spectroscopy, and specifically investigate the biological effects of calcite crystals. DesignThirty-two synovial fluid samples were collected pre-operatively from knee OA patients undergoing total joint arthroplasty. An integrated Raman polarized light microscope was used for identification of crystals in synovial fluid. Human peripheral-blood mononuclear cells (PBMC’s), human OA articular chondrocytes (HACs) and fibroblast-like synoviocytes (FLSs) were exposed to calcite crystals. Expression of relevant cytokines and inflammatory genes were measured using ELISA and real-time PCR. ResultsVarious calcium-containing crystals were identified, including calcium pyrophosphate (37.5%) and basic calcium phosphate (21.8%), but they were never found simultaneously in the same OA synovial fluid sample. For the first time, we discovered the presence of calcite crystals in 93.8% of the samples, while dolomite was detected in 25% of the cases. Characterization of the cellular response to calcite crystal exposure revealed increased production of innate immune-derived cytokines by peripheral blood mononuclear cells (PBMC’s), when co-stimulated with lipopolysaccharide (LPS). Additionally, calcite crystal stimulation of HACS and FLSs resulted in enhanced secretion of pro-inflammatory molecules and alterations in the expression of extracellular matrix remodeling enzymes. ConclusionsThis study highlights the unique role of Raman spectroscopy in OA crystal research and identified calcite as a novel pro-inflammatory crystal type in OA synovial fluid. Understanding the role of specific crystal species in the OA joint may open new avenues for pharmacological interventions and personalized approaches to treating OA.

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 < 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.

Serum and Synovial Levels of Cathepsin G and Cathepsin K in Patients with Psoriatic Arthritis and Their Correlation with Disease Activity Indices.

This retrospective case-control study examined the relationship between the serum and synovial levels of cathepsin G (CatG) and cathepsin K (CatK) in patients with psoriatic arthritis (PsA) and their association with disease activity. Methods: This case-control study involved 156 PsA patients, 50 patients with gonarthrosis (GoA), and 30 healthy controls. The target parameters were measured using enzyme-linked immunosorbent assay (ELISA) kits. The serum levels of CatG and CatK were found to be significantly higher in PsA patients compared to both control groups (p < 0.001). Moreover, they could distinguish PsA patients from healthy controls with 100% accuracy. Synovial fluid CatG and CatK were positively associated with the following indicators of disease activity: the VAS (rs = 0.362, rs = 0.391); the DAPSA (rs = 0.191, rs = 0.182); and the mCPDAI (rs = 0.378, rs = 0.313). Our results suggest that serum and synovial fluid CatG and CatK levels could serve as biomarkers for PsA. In PsA patients with synovial fluid crystals, elevated synovial CatG levels demonstrated a sensitivity of 89.54% and a specificity of 86.00% in distinguishing them from PsA patients without crystals. Similarly, elevated synovial CatK levels had a sensitivity of 93.67% and a specificity of 94.34% for distinguishing PsA patients with synovial fluid crystals from those without. Furthermore, the synovial fluid levels of both CatG and CatK showed positive associations with key indicators of disease activity, including the visual analog scale (VAS) (rs = 0.362, rs = 0.391), the disease activity in psoriatic arthritis (DAPSA) (rs = 0.191, rs = 0.182), and the modified composite psoriatic disease activity index (mCPDAI) (rs = 0.378, rs = 0.313). In conclusion, our findings suggest that the serum and synovial fluid levels of CatG and CatK hold promise as potential biomarkers for assessing disease activity in psoriatic arthritis.

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.

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.

Agreement Among Multiple Observers on Crystal Identification by Synovial Fluid Microscopy.

Despite the fact that polarized microscopy remains the gold standard for diagnosing crystal arthritis, some uncertainties hamper full implementation in clinical practice. We undertook this study to analyze the agreement among multiple observers in crystal identification using compensated polarized microscopy, as well as to assess potential outcome modifiers. This was a cross-sectional, observational study with consecutive synovial fluid sampling. Samples were immediately analyzed when possible or kept refrigerated at 4°C. Five observers analyzed them separately, blinded to clinical data, using a compensated polarized optical microscope (400×), through 3 stages (ordinary, simple polarized, and compensated polarized light) to detect and identify crystals. They recorded the presence and type of crystal (no crystals, monosodium urate [MSU], and calcium pyrophosphate dihydrate [CPP]). Interrater agreement was measured by Cohen's kappa. Subanalyses were performed on visualization delay and cumulative expertise. Discrepancies between each stage of the microscopy and the final decision were also examined. A total of 250 observations from 50 samples completed full assessment. Overall, κ=0.74 (95% confidence interval [95% CI] 0.64-0.84), indicating good agreement. Agreement for crystal detection was κ=0.71 (95% CI 0.59-0.82), for MSU was κ=0.88 (95% CI 0.75-1.0), and for CPP was κ=0.69 (95% CI 0.56-0.82). Most of the crystal identifications were already made by ordinary light. No differences between observations made before or after 24 hours (P=0.859) or in expertise on crystal analysis (P=0.989) were found. Observations performed under ordinary light matched the final diagnosis in 96.8% of cases (242 of 250). Compensated polarized microscopy remained consistent in detecting and identifying crystals in synovial fluid, even when examined among multiple observers, confirming its high utility for clinical practice.

The Role of Ultrasound in Evaluating the Effect of Urate-lowering Drugs in Gout Patients.

Gout is one of the most common inflammatory arthritis, where identification of MSU crystals in synovial fluid is a widely used diagnostic measure. Ultrasonography has a great sensitivity in detecting signs of MSU deposits, such as tophi and double contour (DC), as mentioned in the latest gout criteria, allowing early clinical diagnosis and therapy. The objective of this study was to evaluate the changes in ultrasound of gout patients' knee and 1st metatarsophalangeal joint (MTP1) after initiation of urate-lowering therapy (ULT) drugs in the six-month period. Forty-three patients, fulfilling the ACR/EULAR 2015 criteria of gout with a score of >8, were enrolled; they were in between attacks and not on ULT for the last 6 months, or SUA concentration (SUA) of >6.0 mg/dL. Full examination, evaluation of joints pain by visual analog scale (VAS), ultrasonography (US) for tophus and DC at the knee, and MTP1 were performed at baseline and at 3 and 6 months (M3, M6) after starting ULT. After 6 months of treatment, patients reached the target SUA level showed higher disappearance of DC sign (p<0.05) and a decrease in tophus size (p<0.05). The percentage of tophus size at 6th month was 26.4% and 3% for DC sign disappearance, which was more at MTP1. Ultrasound examination in screening for gout tophi or DC sign before starting ULT and during follow-up is important and complements clinical examination.

Raman hyperspectral imaging detects novel and combinations of crystals in synovial fluids of patients with a swollen joint

AbstractThe identification of synovial crystals is important for diagnosing rheumatic diseases. Currently, rheumatologists worldwide use compensated polarized light microscopy (CPLM) for crystal identification, but this technique is flawed. Raman spectroscopy might offer an objective, accurate alternative. We have tested Raman hyperspectral imaging on synovial fluid samples of 28 patients with swollen joints, measuring 5–10 crystals in each of these. Reference spectra for identification were measured using patient material, synthetic compounds, and oxalate kidney stones. Additionally, RRUFF and PANGAEA Raman databases were used to identify spectra. We identified the classical pathological crystals monosodium urate for gout and calcium pyrophosphate for calcium pyrophosphate deposition disease (CPPD). Hydroxyapatite, lipid spherules, and calcium oxalate monohydrate have also been observed and had been previously identified in synovial fluids. Other crystals, which were not previously observed in synovial fluid using CPLM, have been identified as well: calcite, aragonite, anatase, rutile, thenardite, dolomite, and a carotenoid. In addition, we found combinations of crystals in 13 out of 28 patients. We propose that the observed large variation of detectable crystals from a small population of patients and a small number of crystals per patient has significant ramifications for the use of compensated polarized light microscopy for the diagnosis of gout and CPPD. Further studies are required to learn the clinical significance of these crystals in human arthritis.

Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment

ObjectiveIncreasing evidence suggests that impaired cartilage is a substantial risk factor for the progression from hyperuricaemia to gout. Since the relationship between cartilage matrix protein and gout flares remains unclear,...

The preservation of synovial fluid using dimethyl sulfoxide.

The Royal College of Pathologists of Australasia Quality Assurance Programs runs a Quality Assurance Program for the assessment of synovial fluid crystals. It provides aliquots of synovial fluid to various laboratories. The quality of specimens can deteriorate prior to being examined. We aimed to assess whether the addition of dimethyl sulfoxide (DMSO) to synovial fluid specimens helps maintain cellular morphology. Synovial fluid specimens were obtained from 15 patients. Each specimen was aliquoted into 24 samples, with half having DMSO added at a concentration of 10%. For each specimen, six samples containing DMSO and six samples not containing DMSO were stored at-80°C and room temperature. Samples from each group were examined at 1, 2, 3, 6, 7 and 8weeks. Comparative Analysis: For each specimen, the final remaining aliquoted samples containing DMSO and not containing DMSO, which were stored at-80°C, were directly compared. Quantitative Analysis: A system for grading cellular morphology and assessing for artefacts and cellular clumping was applied by two independent assessors. Comparative Analysis: A significant difference was found between samples containing DMSO and not containing DMSO which were stored at -80°C (p = .000), in favour of those containing DMSO. Quantitative Analysis: Regarding the combined findings of Assessors 1 and 2 and the grading of cellular morphology, a significant difference was found according to "groups" (p = .000), in favour of those containing DMSO and stored at-80°C. DMSO contributes to the maintenance of cellular morphology in synovial fluid when stored in frozen conditions.

Simple alteration of light microscope to detect synovial fluid crystals

Simple alteration of light microscope to detect synovial fluid crystals

Clinical Validation of Rapid Gout Detection Method and Kit.

Gout is an inflammatory arthritis, which causes intense, acute pain due to the buildup of uric acid crystals in synovial fluid. The gold standard for gout diagnosis consists of synovial fluid analysis by polarized light microscopy, which is costly, time-intensive, and technique-dependent, therefore meriting a more efficient, inexpensive, and accessible method for diagnosis. We previously developed and validated a novel colorimetric gout detection method and device based on the reduction of silver nitrate by uric acid; here, we clinically validated our method and device using arthroscopically obtained synovial fluid samples from gout patients. We successfully identified uric acid crystals in clinical samples via our colorimetric method, visualized uric acid crystals in synovial fluid via handheld microscopy, and determined that silver nitrate stain did not interfere with the microscopic visualization of uric acid crystals necessary for diagnosis. We also developed and validated a method of processing turbid clinical samples for use in our device to prevent the obscuration of uric acid crystals by suspended material. Our method and device will clinically facilitate the immediate colorimetric diagnosis of gout and the subsequent bedside visualization of uric acid crystals in both ideal and turbid synovial fluid samples, allowing for a point-of-care diagnosis of gout.

Screening of Fv Antibodies with Specific Binding Activities to Monosodium Urate and Calcium Pyrophosphate Dihydrate Crystals for the Diagnosis of Gout and Pseudogout.

To date, medical diagnosis of gout and pseudogout has been performed by observing the crystals in the joint fluid of patients under a polarized microscope. Conventional diagnostic methods using a polarized microscope have disadvantages, such as time-consuming analysis, a high false negative rate, and difficulty in distinguishing gout with monosodium urate (MSU) crystals and pseudogout with calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluids. In this study, a chromogenic assay for the diagnosis of gout and pseudogout, without the requirement of a polarized microscope and trained experts, was proposed using Fv antibodies with specific binding activities to MSU and CPPD crystals. The IgG VH chain Fv library with randomized complementarity-determining region 3 (CDR3) region was expressed on the outer membrane of Escherichia coli using autodisplay technology. The target Fv antibodies with binding activity to MSU and CPPD crystals were screened from the autodisplayed Fv library on the E. coli outer membrane, and five clones were selected. On the basis of the binding properties of the screened Fv antibodies, peptides with the selected clone of amino acid sequences of the CDR3 region (15 residues) were chemically synthesized. The binding properties of the synthetic peptides with amino acid sequences of CDR3 regions from the selected clones were analyzed using fluorescence imaging and flow cytometry, and the affinity constants (Kd) of each peptide for binding to MSU and CPPD crystals were calculated by fitting based on the isotherm model. A chromogenic assay configuration for gout and pseudogout was developed using synthetic peptides. In this chromogenic assay, synthetic peptides labeled with biotin and streptavidin-horseradish peroxidase (HRP) complex were used, and crystal detection was possible using a chromogenic reaction between HRP and a chromogenic substrate (TMB). Finally, gout and pseudogout were diagnosed by detecting MSU and CPPD crystals in the synovial fluid in the concentration range of 0-300 μg/mL.

Artritis microcristalinas

Microcrystalline arthritis are a group of diseases caused by the deposit of crystals at joint and periarticular structures. The most prevalent are gout and calcium pyrophosphate deposition disease (CPPD).Gout is caused by the deposition of monosodium urate crystals, for which it is necessary to have high uric acid levels in the blood. CPPD deposition occurs mainly in fibrocartilages and hyaline cartilage. Although joint involvement can be mono-, oligo- or polyarticular at diagnosis, monoarthritis is the most common manifestation at disease presentation. Identification of crystals in synovial fluid is key for diagnosis. Initial management in all cases is to treat the acute flare, individualizing anti-inflammatory treatment according to the patient's comorbidities. With regards to patients with gout, it is essential to normalize the serum uric acid levels, to reduce the previous urate deposits. For this purpose, there are several treatments that can be used in these patients, such as allopurinol, febuxostat and the most recently developed uricosuric drug, lesinurad. For CPPD no treatment has proved to be effective in decreasing crystals deposition in tissues or preventing acute flares.

Impact of disease duration and gender on the sensitivity and specificity of 2015 ACR/EULAR classification criteria for gout. Cross-sectional results from an Italian multicentric study on the management of crystal-induced arthritis (ATTACk).

We aimed to assess the performance of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in an Italian cohort of patients with crystal-induced arthritis stratified by disease duration and gender in a real-life setting. Consecutive patients referred to Rheumatology Units for suspected acute crystal-induced arthritis were enrolled in a multicentre cohort study by the Italian Society of Rheumatology which was designed to improve the management of crystal-induced arthritis (ATTACk). To test the performance of the criteria (sensitivity and specificity), the presence of monosodium urate (MSU) crystals in synovial fluid (SF) was used as gold standard. Subgroup analyses by gender and disease duration were performed. Two hundred and seventy-seven patients were enrolled. SF analysis was available in 137 (49%) patients. Complete SF analysis and ACR/EULAR scores were obtained in 44% of patients. MSU crystals were found in 66% of patients. The sensitivity and the specificity of all criteria sets were 78% (95%CI, 67-86) and 98% (95%CI, 87-100), respectively; only clinical criteria yielded 70% (95%CI, 59-80) sensitivity and 93% (95%CI, 80-98) specificity, respectively. In early-stage disease (<2 years), the sensitivity dropped to 58% (95%CI, 39-75), while the specificity was 100% (95%CI, 85-100). The ACR/EULAR criteria showed good performance in patients presenting with acute arthritis; changes were observed when a subset of criteria were used, especially in early-stage disease.

Synovial fluid analysis for the enhanced clinical diagnosis of crystal arthropathies in a tertiary care institution.

Few studies have addressed the detection and clinical impact of different crystals in patients with diverse rheumatologic diagnoses in Latin America. The aim of this study was to assess the consistency between the clinical referring diagnosis and the identification of crystals, such as monosodium urate (MSU) and calcium pyrophosphate (CPP), in the synovial fluid (SF) of patients from a Mexican tertiary care institution. We reviewed the results of 264 SF analyses to identify any changes in diagnosis upon SF analysis. We reported patient medical file data on sex, age, diagnosis, and microscopic SF analysis results. We performed consistency analyses between referring diagnoses and SF findings with McNemar's test. The prevalence of MSU crystals in SF was noted in 89.1% of gout cases and 9.09% of cases of calcium pyrophosphate disease (CPPD). CPP crystals were present in 54.5% of CPPD cases, 42.9% of osteoarthritis (OA) cases, and 7.27% of gout cases. Calcium hydroxyapatite (HA) crystals were identified in 5.45% of gout cases, 33.3% of rheumatoid arthritis (RA) cases, 57.1% of OA cases, and 63.6% of CPPD cases. Cholesterol and lipid crystals were present in small proportions in RA cases. Glucocorticoid crystals were observed in 1.85% of gout cases, 44.4% of RA cases, and 42.9% of OA cases. We observed an association of MSU identification with clinical suspicion of gout (P = 0.08), CPP with OA (P = 0.26) and CPPD (P = 0.50). An association was noted between HA and the diagnosis of CPPD (P = 0.84) and OA (P > 0.99). The number of initial diagnoses that changed upon SF analysis was 14.3%. SF analysis has major diagnostic value regarding MSU crystals and gout. Our findings underscore the importance of SF crystal analysis in identifying the prevalence of crystals in the Mexican population. SF analysis provides for better diagnosis of crystal arthropathies and improves the quality of the medical care that the patient receives. Key Points • Synovial fluid analysis in laboratories from developing countries has been scarce. • In some cases, the initial diagnosis is modified after of synovial fluid analysis. • This study confirmed that synovial fluid analysis exhibits major diagnostic value for urate crystals and gout.