Identification Of Monosodium Urate Crystals Research Articles

Comparison between dual-energy computed tomography and ultrasound in the diagnosis of gout

Objectives: Gout is one of the most common inflammatory arthritic conditions that arise due to the super saturation of urate levels in body tissues, resulting in the formation of monosodium urate (MSU) crystals that get deposited in and around the joints. Clinical diagnosis of gout is generally made based on signs and symptoms. The biochemical diagnosis is based on the levels of serum uric acid. However, hyperuricemia is a weak marker for gout diagnosis. The gold standard for diagnosing gout is the identification of MSU crystals in the synovial fluid by Polaroid microscopy. However, it is an invasive procedure that could lead to complications such as joint effusion and intra-articular hemorrhage. Imaging offers a non-invasive method for the diagnosis of gout. Ultrasound (USG) has emerged as a useful measure for detecting joint effusion and synovitis, studying cartilage, describing early bone erosions, and evaluating tendons and crystal deposition. Dual-energy computed tomography (DECT) is a useful non-invasive technique that helps visualize MSU crystals, along with other soft tissue changes and erosive pathologies, at high resolution, much earlier than conventional radiography could do. Material and Methods: Clinically suspected or diagnosed gout patients in the age group of 20–75 years of both genders attending outpatient services were selected for the study. All the patients fulfilling the inclusion criteria of clinical suspicion of gout or already proven cases of gout were clinically examined, and body mass index, presenting complaints, symptomatic joints, past medical history, family history, and personal habits were noted. The diagnosis of gout was confirmed using the 2015 American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria: A cut-off score >8 was considered diagnostic. Thereafter, all the patients underwent ultrasonographic and computed tomography evaluations. All the patient’s assessments were made at nine locations bilaterally – shoulder, neck, wrist, metacarpal, metatarsophalangeal, ankle, hip, knee, and elbow to check for multiple joint involvements. All the DECT images were post-processed, allowing analysis of images using the three material decomposition methods. On reconstructed DECT images, green color-coded MSU crystals were considered suggestive of gout. Results: The present study reported a higher detection of gout on DECT (97.1%) as compared to the USG (88.2%). Similarly, several studies reported a higher detection rate of MSU crystal deposition by DECT as compared to the detection of the double-contour sign by USG. This study reported sensitivity, specificity, positive predictive, and negative predictive value (PPV and NPV) of USG as 91%, 92%, 95%, and 85%, respectively. In contrast, DECT’s sensitivity, specificity, PPV, and NPVs were 96%, 100%, 100%, and 92%, respectively. DECT showed to have a high sensitivity as well as specificity. Conclusion: The study showed that DECT is more sensitive and had a better PPV and accuracy than USG in the diagnosis of gout. Keeping in view the high efficacy of DECT in diagnosing gouty joints, it is a strong candidate to emerge as a non-invasive imaging modality of choice for diagnosing gout.

Usefulness of ultrasound in the diagnosis of crystal deposition diseases.

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

A glance into the future of gout.

Gout is characterized by monosodium urate (MSU) crystal deposits in and within joints. These deposits result from persistent hyperuricaemia and most typically lead to recurrent acute inflammatory episodes (gout flares). Even though some aspects of gout are well characterized, uncertainties remain; this upcoming decade should provide further insights into many of these uncertainties. Synovial fluid analysis allows for the identification of MSU crystals and unequivocal diagnosis. Non-invasive methods for diagnosis are being explored, such as Raman spectroscopy and imaging modalities. Both ultrasound and dual-energy computed tomography (DECT) allow the detection of MSU crystals; this not only provides a mean of diagnosis, but also has furthered gout knowledge defining the presence of a preclinical deposition in asymptomatic hyperuricaemia. Scientific consensus establishes the beginning of gout as the beginning of symptoms (usually the first flare), but the concept is currently under review. For effective long-term gout management, the main goal is to promote crystal dissolution treatment by reducing serum urate below 6 mg/dL (or 5 mg/dL if faster crystal dissolution is required). Current urate-lowering therapies’ (ULTs) options are limited, with allopurinol and febuxostat being widely available, and probenecid, benzbromarone, and pegloticase available in some regions. New xanthine oxidase inhibitors and, especially, uricosurics inhibiting urate transporter URAT1 are under development; it is probable that the new decade will see a welcomed increase in the gout therapeutic armamentarium. Cardiovascular and renal comorbidities are common in gout patients. Studies determining whether optimal treatment of gout will positively impact these comorbidities are currently lacking, but will hopefully be forthcoming. Overall, the single change that will most impact gout management is greater uptake of international rheumatology society recommendations. Innovative strategies, such as nurse-led interventions based on these recommendations have recently demonstrated treatment success for people with gout.

Diagnostic value of different imaging features for patients with suspected gout: A network meta-analysis

Microscopic identification of monosodium urate (MSU) crystals is the gold standard for gout diagnosis. However, joint aspiration is not always practical, and imaging is increasingly used in clinical practice. This study aimed to assess the diagnostic accuracy of imaging features for gout compared with microscopy, using network meta-analysis methodology. MEDLINE, EMBASE, PubMed and Cochrane databases were searched for studies reporting on the use of imaging modalities to diagnose gout in patients with an unclear diagnosis or suspected gout, which was later confirmed by microscopy. A combination of direct and indirect comparisons were performed by network meta-analysis to evaluate the combined odds ratios for sensitivity, specificity, and accuracy. To assist interpretation, the surface under the cumulative ranking curve (SUCRA) scores were calculated to provide a ranking of the imaging features. Fifteen eligible studies were included. Compared to the gold standard microscopic identification of MSU crystals, dual energy computed tomography (DECT) MSU crystal deposition and ultrasound double contour had greater sensitivity than ultrasound tophus. DECT, ultrasound double contour sign and ultrasound tophus all had greater specificity than ultrasound aggregates. The SUCRA scores ranked DECT as highest for overall accuracy, followed by ultrasound double contour, aggregates, and tophus, while ultrasound snowstorm was ranked the lowest. However, there were no significant differences in the odds ratios for overall accuracy between these imaging features. DECT and ultrasound are both useful modalities for the detection of imaging features of MSU crystal deposition, and have a similar overall diagnostic accuracy for gout diagnoses.

Detection of intracellular monosodium urate crystals in gout synovial fluid using optical diffraction tomography

Optical diffraction tomography (ODT) enables imaging of unlabeled intracellular components by measuring the three-dimensional (3D) refractive index (RI). We aimed to detect intracellular monosodium urate (MSU) crystals in synovial leukocytes derived from gout patients using ODT. The 3D RI values of the synthetic MSU crystals, measured by ODT, ranged between 1.383 and 1.440. After adding synthetic MSU crystals to a macrophage, RI tomograms were reconstructed using ODT, and the reconstructed RI tomograms discerned intracellular and extracellular MSU crystals. We observed unlabeled synthetic MSU crystal entry into the cytoplasm of a macrophage through time-lapse imaging. Furthermore, using gout patient-derived synovial leukocytes, we successfully obtained RI tomogram images of intracellular MSU crystals. The 3D RI identification of MSU crystals was verified with birefringence through polarization-sensitive ODT measurements. Together, our results provide evidence that this novel ODT can identify birefringent MSU crystals in synovial leukocytes of patients with gout.

The Frequency of Axial Deposition in Korean Patients With Gout at a Tertiary Spine Center.

Objectives: This study aimed to describe the frequency of axial deposition (axial gout) and determine the associated factors in patients with gout who presented to a spine clinic in Korea.Methods: We enrolled 95 Korean patients who visited our spine center from March 2012 to February 2016 and who had been previously diagnosed with gout and had available computed tomography (CT) images of the vertebral columns. Axial gout was defined as the presence of erosions or tophi in the vertebral endplate or facet joint. The clinical and laboratory data of these patients were retrieved from medical records.Results: Out of 95 patients, 15 [15.8%; 95% confidence interval (CI), 9.4–25.0%] had a conventional CT evidence suggestive of axial gout. In these 15 patients, 12 (80%) had lumbar spine involvement (95% CI, 51.4–94.7%). Fifteen patients had erosions of the vertebral column, and two presented with tophi that exhibited erosive changes of the facet joints. The presence of axial gout was not associated with the patients' age, duration of gout, laboratory findings, inflammatory back pain symptoms, identification of monosodium urate crystals in the peripheral joints, current use of urate-lowering drugs, hypertension, and end-stage renal disease; however, there was a significant association with the presence of diabetes (P = 0.008).Conclusions: The frequency of axial deposition in Korean patients with gout and spinal symptoms was 15.8%, with the lumbar region being the most commonly involved section of the spine. In addition, diabetes was associated with evidence of axial gout on imaging.

Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis.

Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient’s joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient’s tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm2), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings.

Gout Management in Primary Health Care in Russian Federation

Abstract Objective: The study is aimed at evaluating the level of knowledge of out-patient doctors about modern methods of gout diagnostics and treatment. Methods: The authors developed a questionnaire on gout diagnostics and treatment and carried out an anonymous survey of 50 primary care physicians and 21 rheumatologists. Results: The study revealed low awareness of gout among first contact doctors. Doctors of both specialties use modern methods of diagnostics and treatment insufficiently. Only 62% of rheumatologists and 6% of therapists use Wallace criteria for gout diagnostics. Although 90% of rheumatologists and 42% of therapists specified identification of monosodium urate crystals by the method of polarizing microscopy as a “gold standard” of gout diagnostics, most of doctors noted impossibility of using a polarizing microscope at their workplaces. Conclusion: It is necessary to take measures directed at increasing the knowledge of classification criteria and modern clinical recommendations about medical control of gout patients at the out-patient stage. It is advisable to pay special attention to studying the modern criteria of gout diagnostics and treatment at medical universities.

Clinical factors and treatment outcomes associated with failure in the detection of urate crystal in patients with acute gouty arthritis.

Background/AimsTo investigate the rate of detection of monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with acute gouty arthritis and factors associated with false-negative results.MethodsA total of 179 patients with acute gouty arthritis who had undergone SF crystal examination were identified from the data warehouse of two university hospitals. Clinical and laboratory data were obtained from the medical records.ResultsThe overall rate of detection of MSU crystals was 78.8%. In univariate analyses, the only significant differences between the variables of crystal-negative and crystal-positive patients were a lower C-reactive protein level (p = 0.040) and fewer patients undergoing emergent surgery in the crystal-positive group (p = 4.5 × 10-6). In logistic regression analyses, MSU crystal-negative results were significantly associated with the interval from arthritis onset to crystal examination (p = 0.042), and this was the most significant risk factor for arthroscopic surgery (p = 2.1 × 10-4). Seventeen patients who underwent arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a significant delay in gout treatment (p = 8.74 × 10-5). The distribution of crystal-negative patients differed significantly between the SF samples that were evaluated by both the laboratory medicine and the rheumatology departments (p = 1.2 × 10-14), and the κ value was 0.108.ConclusionsAlthough several clinical features were associated with detection failure, SF MSU crystal identification was critically dependent on the observer. Considering the impact on the treatment outcomes, implementation of a quality control program is essential.

Multinational Gout Recommendations Released

Multinational Gout Recommendations Released

Gouty arthritis: an approach for general practice

Gout is a common crystal-induced inflammatory arthritis, the prevalence and clinical complexity of which is increasing in the face of a growing aged population with multiple co-morbidities. Recent epidemiological studies emphasise that lifestyle factors strongly influence the development of hyperuricaemia and gout. Moreover, there is growing evidence that gout is an independent risk factor for cardiovascular disease. Acute attacks of gout are extremely painful and disabling, and if repeated attacks go untreated, chronic deforming arthritis ensues. Early diagnosis and appropriate therapy is essential to reduce long-term disability. Identification of monosodium urate crystals on synovial fluid analysis is the gold standard in gout diagnosis. Nonsteroidal anti-inflammatory drugs and oral or intra-articular corticosteroids remain central to the treatment of acute attacks. Prophylactic colchicine use, during the intercritical period, reduces gout flares, a common complication on initiation of urate-lowering therapy (ULT). Allopurinol is the treatment of choice when ULT is indicated. Gout management is suboptimal in many patients because of non-adherence to treatment and underutilisation of available treatments. Treating to target: a serum uric acid level < 0.35mmol/l, prevents crystal deposition in joints and soft tissues, thereby preventing acute attacks and ongoing inflammation, as well as decreasing the size and number of tophi. Treatment strategies should include attention to cardiovascular risk. The family practitioner is paramount to gout management which should be individualised. Emphasis should be placed on ongoing education and prevention.

AB1075 Seronegative arthropathies: Value of dual-energy CT for differential diagnosis

BackgroundSeronegative Oligo/Polyarthritis combines a set of diseases including gout as a possible differential diagnosis.The identification of monosodium urate crystals is the gold standard for the proof of gout. However, the...

Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout?

ObjectiveThe primary objective of this prospective case-control study was to assess the diagnostic value of several intra-articular and periarticular ultrasound (US)-detected abnormalities in the upper and lower limbs in gout....

Investigating gout: taking a new approach to an old disease

Gout is a very painful and common form of acute arthritis, which is becoming increasingly prevalent in many Western societies. Gout was first identified by the Egyptians and is caused by a disorder of the body’s purine metabolism, resulting in raised serum uric acid level, known as hyperuricaemia. Gout tends to affect the older population, particularly obese patients and others with rather negative lifestyle habits, such as a high alcohol intake. However, in the majority of patients suffering from idiopathic gout (75–90%) the evidence suggests that these patients may actually have a genetic disposition to the reduced renal excretion of urate acid. Gout has a rapid onset and the most commonly affected joint is the first metatarsophalangeal, although other joints can also be affected such as the mid-foot, ankle, knee, wrist, finger and elbow. Recommended gout treatment includes non-steroidal anti-inflammatory drugs, colchicine and corticosteroids. Preventative treatments include allopurinol, which aims to lower uric acid levels. The definitive diagnostic test for gout is the aspiration of the joint or tophus and the confirmed identification of monosodium urate crystals. The presence of urate crystals confirms a diagnosis of gout and the absence of evidence of infection will rule out the key differential diagnosis of septic arthritis.

Primary health care to patients with gout

Gout is a systemic tophaceous disease that is becoming more and more prevalent. If untreated or poorly managed, gout can result in disability. The possible reason for inadequate gout control may be that the primary care physicians are unaware of diagnostic criteria and clinical guidelines for the management of these patients and diagnostic errors. Objective: to estimate the level of gout knowledge in primary care physicians. Subjects and methods. Fifty Irkutsk local therapists were questioned. A specially developed anonymous questionnaire included items on sex, age, work experience, and the principles of gout diagnosis and treatment. Results. Only 42% of the therapists know that the gold standard for diagnosis of gout is identification of monosodium urate crystals by polarizing microscopy. Only 6% of the therapists use the Wallace classification criteria for the early diagnosis of gout. 56 % of the physicians consider it possible to prescribe allopurinol in the acute period of the disease 26% think that allopurinol intake can be stopped after normouricemia is achieved; 10% of the physicians do not prescribe allopurinol for gout patients. These widespread errors lead to worsening arthritis and a negative attitude of patients towards allopurinol treatment in future. Conclusion. The findings suggest that the level of gout knowledge should be increased in primary care physicians.

Usefulness of ultrasonography for gout

Gout is a common arthritis caused by deposition of monosodium urate (MSU) crystals within joints secondary to chronic hyperuricemia. Joint damage can occur during evolution of the disease. The identification of MSU crystals in synovial fluid is the gold standard to diagnose gout. However, the diagnosis is sometimes difficult to do, particularly in atypical clinical presentations or when small joints are involved. Radiography is often normal at the early stage of gout. MRI and CT-scan are costly and availability of these imaging techniques may be problematic in clinical practice. Ultrasonography (US) appears useful for diagnosis and management of the disease. Several ultrasound features evocating gout have been described with different sensitivity and specificity. We reviewed the literature for evidence of the ability and usefulness of US for diagnosis of early-stage and established gout.

Gout Deserves Tender Treatment in Elderly

Gout Deserves Tender Treatment in Elderly

Diagnosis of Gout: Considering Clinical and Research Settings

The diagnosis of gout is usually straightforward and should normally rely upon the identification of monosodium urate crystals in synovial fluid. EULAR have recently developed consensus recommendations regarding the diagnosis of gout. Where examination of synovial fluid is not possible or impractical, the best approach differs depending upon the context: in clinical research, classification criteria are necessary whereas in clinical practice, all available information should be carefully weighed and considered by the physician. A number of clinical features are useful pointers towards the diagnosis of gout and ultrasound is emerging as a useful diagnostic tool. The finding of hyperechoic enhancement of the superficial margin of the hyaline cartilage is a sensitive and specific feature of gout, although the performance of ultrasound in early disease is unclear. Serum uric acid is not a useful test for the diagnosis of gout but is very important in the long-term management. The 1977 American Rheumatism Association classification criteria have many shortcomings and improved criteria are urgently required for epidemiology and clinical research. The complete diagnostic evaluation may involve assessment of 24-hour urinary excretion of uric acid in a few selected patients and all patients should be evaluated for common comorbidities especially the metabolic syndrome and risk factors for cardiovascular disease.

Identification of urate crystals in gouty individuals

In paleopathology cases of gout have traditionally been identified using the character of erosive bony lesions, but in clinical medicine identification of monosodium urate crystals in joint fluid plays a central role in diagnosis. Work undertaken on three skeletal individuals who had been buried, demonstrates that crystals can be identified using polarising microscopy. The crystals were identified as monosodium urate. Results from this study appear to demonstrate that identification of monosodium urate crystals could be used to assist in the diagnosis of gout in paleopathology. Further work is required to establish the full range of spatial and temporal contexts from which such crystals might be found.

Goutte : critères de diagnostic, de classification et de qualité de vie

Gout is a frequent disease with a unique pathognomonic diagnostic feature, i.e., monosodium urate (MSU) crystal identification in synovial fluid or in tophus. This “gold standard” may be missing since general practitioners (and even rheumatologists) often make a diagnosis of gout on clinical grounds, too rarely looking for joint tap and synovial fluid examination. In addition, routine or even hospital laboratories might miss MSU crystal identification because of insufficient skills and techniques. Classification criteria have been proposed in the 1960–1970s, with emphasis on characteristic features of crystal-induced inflammation, and always MSU crystal identification. The OMERACT task force for gout is currently developing a set of tools for outcome measures useful in clinical trials for new drugs which are moving gout out from old ages and old drugs to a new era. Finally, recent development of specific outcome measures to evaluate global or location-specific disabilities, as well as health-related quality of life, should allow comprehensive assessment of functional consequences, sometimes severe, of the disease.