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Imaging as A Potential Outcome Measure in Gout Studies: A Systematic Literature Review
... CR is widely available, inexpensive, quick, and acceptable to patients. Radiation hazard is small[66]. The CR Sharp-van de Hejde scoring system for gout (SvdH-G), has been adapted from its RA counterpart and modified. ...
... US is feasible as it can be performed in the clinic and there are no radiation hazards involved. The time required for scanning, however may be significant and training costs may be considerable[66]. ...
... The specificity of CCT for the assessment of tophi exceeds that of US or MRI[80]. CT of tophi has been confirmed microscopically by identifying MSU crystals[66]. Its measurement of tophi has also been compared to physical exam using Vernier calipers[81,82]. ...
Gout is a picturesque presentation of uric acid disturbance. It is the most well understood and described type of arthritis. Its epidemiology is studied. New insights into the pathophysiology of hyperuricemia and gouty arthritis; acute and chronic allowes for a better understanding of the disease. The role of genetic predisposition is becoming more evident. The clinical picture of gout is divided into asymptomatic hyperuricemia, acute gouty arthritis, intercritical period, and chronic tophaceous gout. Diagnosis is based on laboratory and radiological features. The gold standard of diagnosis is identification of characteristic MSU crystals in the synovial fluid using polarized light microscopy. Imaging modalities include conventional radiography, ultrasonography, conventional CT, Dual-Energy CT, Magnetic Resonance Imaging, nuclear scintigraphy, and positron emission tomography. There is remarkable progress in the application of ultrasonography and Dual-Energy CT which is bound to influence the diagnosis, staging, follow-up, and clinical research in the field. Management of gout includes management of flares, chronic gout and prevention of flares, as well as management of comorbidities. Newer drugs in the pharmacological armamentarium are proving successful and supplement older ones. Other important points in its management include patient education, diet and life style changes, as well as cessation of hyperuricemic drugs.
... 40 The inter-reader and intrareader agreement of these signs vary and are higher for the DC sign (kappa 5 0.69-96) and tophi (kappa 5 0.65-1) than for aggregates. 37,41 The diagnostic performance of US for gout depends on several factors, including the duration of the condition. The DC sign has been found in asymptomatic hyperuricemic patients. ...
... 40,42 When present, tophi and erosions seem to be depicted at US with high sensitivity compared with radiography, MRI, or DECT. 41,43,44 Of note, US has been used to assess the efficacy of urate-lowering therapy and can show a reduction in size of tophi as well as the disappearance of the DC sign (see Fig. 6). [44][45][46] (dashed circles)). ...
In this article, the authors consider the manifestations of intraarticular and periarticular crystal deposits. Most cases of crystal deposits are asymptomatic and represent incidental findings at imaging. In symptomatic arthropathies, imaging can play an important role in the diagnosis and assessment of disease progression and the extent of crystal deposits. Conventional radiography is the most common imaging modality. But ultrasound, conventional computerized tomography (CT), dual-energy CT, and MRI play an increasing role. The authors review typical radiographic features of crystal-induced arthropathies and findings that help to differentiate them. The authors also emphasize the increasing role of complementary imaging techniques.
... 16 Although many imaging tools are available for detecting gouty arthritis in joints, such as conventional radiography, conventional computed tomography, dual-energy computed tomography, and magnetic resonance imaging, MSKUS remains a reliable method and the most convenient tool for detecting inflammation and structural deformities. 16 In this retrospective study, we assessed the relationships between MSKUS abnormalities and serum and synovial abnormalities, 17 Patients with leukocytosis exhibited increased serum CRP level, which might indicate that these patients exhibited more active inflammation and are consistent with previous reports. 18 We found that serum CRP levels correlated significantly negatively with eGFR. ...
Background: Renal insufficiency reduces the excretion of uric acid and inflammatory factors and exacerbates the structural deformities caused by gouty arthritis. Musculoskeletal ultrasonography (MSKUS) is often used to evaluate the severity and inflammatory progression of gout. Aim: We aimed to determine whether ultrasound help to identify structural damage in patients with chronic kidney disease (CKD) and gout. Methods: This was a retrospective review of the clinical manifestations and abnormalities observed with MSKUS in 280 patients with gouty arthritis between August 2004 and April 2017. MSKUS identified intra-articular features, including joint effusion, synovial proliferation, Baker's cysts, double contour sign, tophi, and extra-articular tenosynovitis. Serum and synovial fluid were collected and analyzed. Significant differences were identified using the Pearson correlation coefficient and independent t-test. Results: This retrospective cohort included 257 men (91.8%) and 23 women (8.2%) with a mean age of 54.6 years. CKD stage correlated positively with the presence of joint Baker's cyst (P = 0.004). Notably, serum estimated glomerular filtration rate correlated negatively with serum C-reactive protein level in patients with CKD (P < 0.001), and more severe CKD correlated with a higher prevalence of Baker's cyst in CKD patients (P = 0.0037). Conclusion: Insufficient control of hyperuricemia can lead to chronic gouty arthritis and subsequent structural deformities. Reciprocally, acute inflammation of joints is downregulated as chronic gouty arthritis develops. Patients with hyperuricemia and CKD should receive regular MSKUS examination to avoid the progression of structural damage in the joints.
... Chronic pain, soreness, or numbness in the joints is reported in some patients without convincing clinical evidence of a gouty attack, and it is difficult to differentiate gout from osteoarthritis or other chronic arthritis. Noninvasive imaging evidence of urate deposition in joints is valuable and helpful for differential diagnosis [3]. ...
Objective:
To evaluate monosodium urate (MSU) crystal deposition and related lesions in the joints of patients with gout and hyperuricemia (HUA) using ultrasound. To explore the association between ultrasound findings and clinical features in gout and HUA.
Methods:
A total of 202 patients with gout and 43 asymptomatic patients with HUA were included. The clinical data and ultrasonic assessment results were collected and statistically analyzed.
Results:
Deposition of MSU crystals was found in 25.58% (11/43) of patients with asymptomatic HUA and 76.24% (154/202) of patients with gout. Of the 1,082 joints from patients with gout examined, 33.09% (358/1082) displayed MSU crystal deposition. In the joints with MSU crystal deposition, 77.37% (277/358) had a history of attacks. Among the joints of gouty arthritis, double contour sign (DCS), hyperechoic aggregate (HAG), and tophi were found in 32.65% (159/487), 7.80% (38/487), and 24.64% (120/487) of the joints, respectively. DCS and tophi, but not HAG, increasingly appeared with the extension of gout duration. In patients with more than 15 years of gout history, DCS, Tophi, and HAG were found in 48.18%, 40.00%, and 6.36% of US assessed joints, respectively. In patients with gout, synovial lesion and bone erosion were found in 17.74% (192/1082) and 7.58% (82/1082) of joints, respectively. The synovial lesion was related to HAG, while bone erosion was related to tophi and DCS. Nephrolithiasis was detected in 20.30% (41/202) of patients with gout and 4.65% (2/43) of HUA patients, indicating that nephrolithiasis occurred in more patients with gout than in patients with HUA.
Conclusion:
HAG is an early performance of MSU crystal deposition in joints of gout and HUA. Both DCS and tophi are risk factors for bone erosion. Early urate-lowering therapy (ULT) should be considered in patients with gout, DCS, or tophi.
... Conventional X-rays are frequently used for the diagnosis and follow-up of gout while our patient refused to undergo X-ray investigation due to her fear of radiation although we explained that the radiation level she would be exposed to would be low. 13 Although the patient refused to undergo hand X-rays, physical examination in association with synovial fluid analysis and serum urate levels permitted us to establish the diagnosis of gout. ...
... These included both mandatory and optional domains, where the mandatory domains were to be monitored in all clinical trials. Of the mandatory domains, urate (tophus) burden was identified as a relevant domain for imaging in gout studies [8], and along with dual-energy computed tomography (DECT), ultrasound was found to be the most promising imaging modality for monitoring urate deposition [8,9]. Since MSU crystal depositions within joints and tendons reflect ultrasound beams more strongly than the surrounding tissues (synovial tissue and unmineralized hyaline cartilage or tendons), MSU depositions can be detected by ultrasound as hyperechoic signals. ...
Objective
This study aimed to develop 1) a new ultrasound definition for aggregates and 2) a semi-quantitative ultrasound scoring system (0-3) for tophus, double contour and aggregates. Furthermore, the intra- and inter-reader reliabilities of both the re-defined aggregates and the semi-quantitative scoring system were assessed using static image exercises.
Methods
Thirty-seven rheumatologists were invited. A Delphi process was used for re-defining aggregates and for selecting a semi-quantitative scoring system with >75% agreement obligate for reaching consensus. Subsequently, a web-based exercise on static ultrasound images was conducted in order to assess the reliability of both the re-defined aggregates and the semi-quantitative scoring system.
Results
Twenty rheumatologists contributed to all rounds of the Delphi and image exercises. A consensual re-definition of aggregates was obtained after three Delphi rounds but needed an overarching principle for scoring aggregates in patients. A consensus-based semi-quantitative ultrasound scoring system for gout lesions was developed after two Delphi rounds. The re-definition of aggregates showed good intra- and inter-reader reliability (κ-values 0.71 and 0.61). The reliabilities of the scoring system were good for all lesions with slightly higher intra-reader (κ-values 0.74–0.80) than inter-reader reliabilities (κ-values 0.61–0.67).
Conclusion
A re-definition of aggregates was obtained with a good reliability when assessing static images. The first consensus-based semi-quantitative ultrasound scoring system for gout-specific lesions was developed with good inter- and intra-reader reliability for all lesions when tested in static images. The next step is to assess the reliabilities when scoring lesions in patients.
... They in turn have independent effects on bone and joint erosion [22,27]. Therefore, monitoring of MSU dissolution by DECT is more relevant in the treatment of tophaceous gout than tophus measurement [28]. ...
Objective : Dissolution velocity of monosodium urate (MSU) crystal during urate-lowering therapy (ULT) had been inadequately studied. By using dual-energy computed tomography (DECT), which allows accurate assessment of MSU load, we analyze relationship between serum urate (SU) and volumetric reduction rate of MSU and develop a model that predicts dissolution time.
Methods
Baseline and follow-up DECTs were performed under a standard ULT protocol. Monthly dissolution rates were calculated by simple and compound methods. Correlations with average SU were compared and analyzed. Best-fit regression model was identified. MSU dissolution times were plotted against SU at different endpoints.
Results
In 29 tophaceous gout patients, MSU volume reduced from baseline 10.94 ± 10.59 cm³ to 2.87 ± 5.27 cm³ on follow-up (p = .00). Dissolution rate had a stronger correlation with SU if calculated by compound method (Pearson’s correlation coefficient r= −0.77, p = .00) and was independent of baseline MSU load. The ensuing dissolution model was logarithmic and explained real-life scenarios. When SU > 0.43 mmol/l, dissolution time approached infinity. It improved to 10–19 months at SU = 0.24 mmol/l. When SU approximated zero (as with pegloticase), dissolution flattened and still took 4–8 months.
Conclusion
MSU dissolution is better described as a logarithmic function of SU, which explains, predicts, and facilitates understanding of the dissolution process.
... Ultrasound as a diagnostic method is suitable to detect joint effusions and synovitis, and to study cartilage, tendons, and bone contour. 37 However, ultrasound is a time-consuming procedure, which requires specialized examiners. Conventional radiography can show typical changes in late state gout patients, such as erosions and deformities of the bones as well as soft tissue and intraosseous tophi. ...
Objective:
The aim of this study was to evaluate the potential of x-ray dark-field radiography for the noninvasive detection of monosodium urate (MSU) crystals as a novel diagnostic tool for gout.
Materials and methods:
Contrast-to-noise ratios of MSU crystals in conventional radiography and dark-field radiography have been compared in a proof of principle measurement. Monosodium urate crystals have been injected into mouse legs in an ex vivo experimental gout setup. Three radiologists independently evaluated the images for the occurrence of crystal deposits in a blinded study for attenuation images only, dark-field images only, and with both images available for a comprehensive diagnosis. All imaging experiments have been performed at an experimental x-ray dark-field setup with a 3-grating interferometer, a rotating anode tube (50 kVp), and a photon-counting detector (effective pixel size, 166 μm).
Results:
X-ray dark-field radiography provided a strong signal increase for MSU crystals in a physiological buffer solution compared with conventional attenuation radiography with a contrast-to-noise ratio increase from 0.8 to 19.3. Based on conventional attenuation images only, the reader study revealed insufficient diagnostic performance (sensitivity, 11%; specificity, 92%) with poor interrater agreement (Cohen's coefficient κ = 0.031). Based on dark-field images, the sensitivity increased to 100%, specificity remained at 92%, and the interrater agreement increased to κ = 0.904. Combined diagnosis based on both image modalities maximized both sensitivity and specificity to 100% with absolute interrater agreement (κ = 1.000).
Conclusions:
X-ray dark-field radiography enables the detection of MSU crystals in a mouse-based gout model. The simultaneous avaliability of a conventional attenuation image together with the dark-field image provides excellent detection rates of gout deposits with high specificity.
... In our study, we did not include ultrasound imaging that proved its value in previous studies. (31,32). Whereas the majority of patients un- derwent sonography before joint as- piration, we focused on the DECT as primary subject to our analysis. ...
OBJECTIVES: To validate the diagnostic benefit of dual-energy computed tomography (DECT) and synovial fluid aspiration in suspected gout. METHODS: A total of 43 patients with suspected gout underwent aspiration and DECT (320-row CT; Canon Medical Systems, Japan). The patients were assessed (gout vs. non-gout) based on the 2015 ACR/EULAR gout classification criteria using clinical and laboratory findings. The results were analysed by comparing two scenarios using McNemar test: Scenario A: ACR/EULAR criteria, followed by DECT results and aspiration findings. Scenario B: ACR/EULAR criteria, followed by aspiration and DECT results. RESULTS: 15/43 patients (34.9%) were positive for MSU crystals, and 16/43 patients (37.2%) for gouty tophi (DECT). 26/43 patients (60.5%) were diagnosed with gout and fulfilled the ACR/EULAR criteria. The diagnostic performance of either synovial fluid aspiration or DECT was similar with sensitivity of 58% and specificity of 100% and 94%, respectively. Combination of both modalities (at least one of them positive), resulted in increased sensitivity of 85% and unchanged specificity (94%). Based only on clinical and laboratory findings, 13/43 patients (30.2%) were classified as gout according to ACR/EULAR criteria. In scenario A, additional 8 out of 30 (26.7%) patients were diagnosed as gout by DECT findings, and another 5/22 (22.7%) patients by aspiration findings. In scenario B, initial consideration of aspiration findings resulted in 10 out of 30 (33.3%) additionally identified patients, and another 3 (15%) patients by DECT findings. There was no relevant difference between scenarios A and B (p=0.508). CONCLUSIONS: Combination of joint aspiration and DECT improves the diagnostic algorithm for gout. In our attempt to establish an optimal sequence of diagnostic tests, we did not identify an advantage for either synovial fluid analysis or DECT as the initially better modality after clinical examination and analysis of blood tests.
... The diagnostic performance of US and DECT has been compared and both exhibit comparable sensitivity for the detection of urate deposition, with potential superiority of DECT [14][15][16]. Despite the fact that US and DECT are both candidates to quantify urate deposition and monitor urate depletion [17,18], it is still unknown whether these techniques provide the same quantification of the extent of urate deposition in a given patient. ...
Background
Ultrasonography (US) and dual-energy computed tomography (DECT) can assess urate burden in gout. The objective of this study was to compare the quantification of urate deposition provided by US to the one provided by DECT.
Methods
Patients with a diagnosis of gout were prospectively recruited to undergo quantification of urate deposition using US and DECT. US examination for tophi and the double contour (DC) sign was performed on the knees and feet and corresponding DECT scans provided volumes of tophi and of overall urate deposition. The primary endpoint was the intra-class correlation coefficient (ICC) of the volume of the index tophus measured by US and DECT and its 95% confidence interval (CI 95%).
Results
Of the 64 patients included, 34 presented with at least one tophus on US. DECT inter-reader agreement for urate deposition was perfect with an ICC of 1 (1–1) and good for the measurement of the index tophus with an ICC of 0.69 (0.47–0.83). The ICC for the measurement of the index tophus between the two techniques was poor with a value of 0.45 (0.1–0.71). The average ratio between the index tophi volume as assessed by DECT and US was 0.65. The number of DC-positive joints did not correlate with DECT volume of overall deposits (Spearman correlation coefficient of 0.23).
Conclusions
DECT measurements of tophi give smaller volumes to the same tophi measured with US, and US signs of urate deposition in joints do not correlate with overall DECT volumes of extra-articular deposition.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-017-1381-2) contains supplementary material, which is available to authorized users.
... Ultrasound (US), dual-energy computed tomography (DECT), and magnetic resonance imaging are among the current imaging modalities that can identify urate deposition, structural joint damage, and joint inflammation in gout, with a potential role in the diagnosis and follow-up of patients [36]. DECT is particularly attractive as it can differentiate calcium from urate crystal deposition when deposits are of sufficient size [37]. ...
Gout is the most common inflammatory arthritis, with a rising prevalence and incidence worldwide. There has been a resurgence in gout research, fueled, in part, by a number of advances in pharmacologic therapy for gout. The conduct of clinical trials and other observational research in gout requires a standardized and validated means of assembling well-defined groups of patients with gout for such research purposes. Recently, an international collaborative effort that involved a data-driven process with state-of-the art methodology supported by the American College of Rheumatology and the European League Against Rheumatism led to publication of new gout classification criteria.
En los últimos años, la ecografía musculoesquelética ha ido despertando mayor interés, permitiendo su gradual inclusión en la reumatología, cambiando el paradigma tanto del diagnóstico, como de la evaluación de la actividad en diversas condiciones que se presentan como artritis. Es un método no invasivo, costo efectivo, que permite comparar en tiempo real los hallazgos anatómicos con la evaluación clínica del paciente, lo que nos aumenta la precisión del examen físico, evaluar varias articulaciones en un mismo tiempo y permitir una toma de decisiones inmediata. Para realizar una evaluación estandarizada de la ecografía articular, el grupo de trabajo “outcome measures in rheumatology” (OME- RACT) fue creado con el objetivo de identificar, estandarizar y validar herramientas de medida, así como definiciones clínicamente importantes para ser incluidas en ensayos clínicos, publicando el 2005 las definiciones ultrasonográficas1 y en el 2019 las lesiones elementales2. A continuación, se revisará la evidencia disponible de la utilidad del ultrasonido (US) en todo el espectro de evolución de una artritis, desde artralgia de riesgo hasta artritis en remisión.
In this chapter the authors discuss the conditions to consider in the differential diagnosis of Charcot neuroarthropathy. These conditions can affect the musculoskeletal system, particularly in the ankle-foot unit, and cause changes that resemble diabetes-induced Charcot neuroarthropathy. It is important to know their pathogenesis, clinical characteristics, and radiological manifestations. Among those entities that can mimic Charcot neuroarthropathy figure the inflammatory diseases such as rheumatoid arthritis, gout, psoriasis, and complex regional pain syndrome. Human immunodeficiency virus infection is included in this chapter. These conditions are presented in detail with MR images.
Background
Evaluation of monosodium urate (MSU) crystal deposition and related lesion in joints using ultrasound in gout and hyperuricemia patients. Methods
Total 202 gout patients and 43 asymptomatic hyperuricemia patients were included, the clinical data and ultrasunic assessment results were collected and statistically analyzed. ResultsDeposition of MSU crystals were found in 25.58% (11/43) of the patients with asymptomatic hyperuricemia and 76.24% (154/202) of the patients with gout. In the all examined 1082 joints from gout patients, 33.09% (358/1082) of them were detected MSU crystals. In MSU crystal positive joints, 77.37% (277/358) of them had history of attacks. Among the joints of gouty arthritis, 56.88% (277/487) of them were found MSU crystals. Double contour sign (DCS), hyperechoic aggregate (HAG) and Tophi were found in 32.65% (159/487), 7.80% (38/487) and 24.64% (120/487) of the joints, respectively. DCS and Tophi, but not HAG, appeared increasingly in gout duration extension. In the patients with more than 15 years of gout history, DCS, Tophi and HAG were found in 48.18%, 40.00%, 6.36% of US assessed joints, respectively. In the gout patients, synovial lesion and bone erosion were found in 17.74% (192/1082) and 7.58% (82/1082) of joints, respectively. Synovial lesion was related with HAG, while bone erosion was related to tophi and DCS. Nephrolithiasis was detected in 20.30% (41/202) of gout patients and 4.65% (2/43) of hyperuricemia patients, indicating nephrolithiasis occurred in more gout patients than in hyperuricemia patients.ConclusionHAG is the early sign of MSU crystal deposition in joints. Early urate lowering therapy (ULT) may reduce HAG and ameliorate synovitis and synovial hypertrophy. DCS and tophi are the risk factors of bone erosion. Early ULT should be considered in the gout patients with DCS or tophi. And nephrolithiasis was remarkably relevant to MSU crystal deposition in joints in gout patients.
Objective:
To compare dual-energy computed tomography (DECT) and ultrasound (US) in detecting monosodium urate (MSU) crystals in the ankle and foot in patients with acute gouty arthritis.
Methods:
Bilateral ankle and foot were examined by DECT and US and the differences between the findings were compared.
Results:
A total of 50 patients underwent DECT and US examinations. At the patient level, the overall positivity of crystal deposition detected by DECT was higher than that by US (92% vs 68%, P = 0.005). The agreement of detecting crystal deposition between DECT and US was not very strong (К = 0.44, P = 0.003). At different joint/area levels, there were significant differences between the two examinations in the area of the dorsum (36% vs 12%, P = 0.009) and metatarsal bone (34% vs 12%, P = 0.017), but the sensitivity of DECT and US was similar in the first metatarsophalangeal joint (MTP) and ankle areas (P>0.05). Agreement between the two examinations in the ankle and first MTP was very strong (К = 0.86, P < 0.001; К = 0.79, P < 0.001, respectively). However, agreement between the two examinations in other joints/areas was poor.
Conclusion:
These findings indicated that DECT should be the first choice for acute gouty arthritis in patients with ankle and foot involvement. Key Points • There is little data regarding DECT and US in detecting MSU crystals in the ankle and foot in patients with acute gouty arthritis. • The overall positivity of crystal deposition detected by DECT was higher than that by US, but the sensitivity of DECT and US was similar in the first metatarsophalangeal joint (MTP) and ankle areas. • Agreement between the two examinations in the ankle and first MTP was very strong; however, agreement between the two examinations in other joints/areas was poor.
Objective Evaluation of monosodium urate (MSU) crystal deposition and related lesion in joints using ultrasound in gout and hyperuricemia patients.
Methods Total 202 gout patients and 43 asymptomatic hyperuricemia patients were included, the clinical data and ultrasounic assessment results were collected and statistically analyzed.
Results Deposition of MSU crystals were found in 25.58% (11/43) of the patients with asymptomatic hyperuricemia and 76.24% (154/202) of the patients with gout. In the all examined 1082 joints from gout patients, 33.09% (358/1082) of them were detected MSU crystals. In MSU crystal positive joints, 77.37% (277/358) of them had history of attacks. Among the joints of gouty arthritis, 56.88% (277/487) of them were found MSU crystals. Double contour sign (DCS), hyperechoic aggregate (HAG) and Tophi were found in 32.65% (159/487), 7.80% (38/487) and 24.64% (120/487) of the joints, respectively. DCS and Tophi, but not HAG, appeared inceasingly in gout duration extension. In the patients with more than 15 years of gout history, DCS, Tophi and HAG were found in 48.18%, 40.00%, 6.36% of US assessed joints, respectively. In the gout patients, synovial lesion and bone erosion were found in 17.74% (192/1082) and 7.58% (82/1082) of joints, respectively. Synovial lesion was related with HAG, while bone erosion was related to tophi and DCS.
Conclusion HAG is the early sign of MSU crystal deposition in joints. Early urate lowering therapy (ULT) may reduce HAG and ameliorate synovitis and synovial hypertrophy. DCS and tophi are the risk factors of bone erosion. Early ULT should be considered in the gout patients with DCS or tophi.
Introduction
A growing body of evidence indicates the benefits of early diagnosis of rheumatoid arthritis (RA) and prompt treatment with disease-modifying anti-rheumatic drugs (DMARDS) in terms of relieving symptoms, improving prognosis, and reducing long-term complications. There is however some controversy over the most beneficial method of imaging in providing accurate early diagnosis. Though current practice favours clinical and radiological assessment, this is increasingly supplemented by ultrasound techniques (and, to a lesser extent, CT and MRI scanning). While EULAR and ESSR favour the use of ultrasonography (US) as the first-line investigation in cases of suspected RA, a recent NICE review upholds the traditional place of plain film radiographs of hands and feet to detect erosions as early signs of synovitis. This review considers the evidence for US in the early diagnosis of RA and the case for it becoming the primary assessment modality in rheumatology clinics.
Aims
This paper aims to assess the current literature on the efficacy of ultrasonography in diagnosing early RA, by comparing US with alternative imaging modalities. The goal is to propose the most appropriate method of diagnosis to improve early initiation of DMARD treatment for optimum disease outcomes.
Methods
Searches for related studies and review articles were carried out using electronic databases and hand searches. Additional references were gleaned from the bibliographies of included papers. Related articles and pop-outs from PubMed were also used. The search was refined in PubMed, by only using reviews which were written in English and published in past 10 years and had full free text available.
Results
This review confirms that US has a high level of sensitivity in diagnosing RA (and hence a low risk of missing cases of RA which might benefit from early treatment with DMARDs). It also has a high level of specificity (and hence a low risk of falsely diagnosing somebody with RA who may suffer adverse effects of DMARD therapy). US is already widely available and well accepted by clinicians and patients. It does not involve exposure to radiation and can be readily delivered by appropriately trained staff.
Conclusion
This review of relevant studies indicates that US should become accepted as the investigation with the most favourable balance of benefits to risks in the early diagnosis of RA. Given the continuing controversy surrounding studies of different imaging techniques in RA, further research into the diagnostic role of US in RA is indicated.
Objective
Dual-energy CT (DECT) is being widely used in suspected gout patients in recent years. Many clinicians tend to use DECT instead of aspiration biopsy in the diagnosis of gout, but its accuracy has shown controversial results. In this systematic review and meta-analysis, we sought to evaluate the accuracy of DECT in the diagnosis of gout.
Materials and methods
We performed a systematic review of the literature published in Medline, Embase, PubMed, and Cochrane databases. Studies included are all clinical trials of DECT in the diagnosis of gout. Quality assessment of bias and applicability was conducted using the Quality of Diagnostic Accuracy Studies-2 (QUADAS-2). We recorded sensitivity and specificity of algorithms and calculated positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odd ratio (DOR), and respective confidence intervals (CI). The summary receiver operating characteristic curve (sROC) was drawn to get the Cochran Q-index and the area under the curve (AUC).
Results
Seven studies were included in this review and showed high homogeneity. The analysis results presented the pooled sensitivity was 88% (95% CI 84–90%) and specificity was 90% (95% CI 85–93%). Then, we figured out that the pooled PLR was 8.48 (95% CI 5.89–12.22) and NLR was 0.10 (95% CI 0.04–0.24) respectively. In addition, Cochran-Q was 0.90 and AUC was 0.9565 in sROC curve.
Conclusions
DECT showed relatively high sensitivity and specificity in the diagnosis of gout. Synthetically considering these DECT abnormalities could improve the diagnostic sensitivity. More rigorous and standardized studies are still needed to support these findings.
Gout is the most common form of inflammatory arthritis in the United States. Nevertheless, gout remains misunderstood, misdiagnosed, underdiagnosed, and undertreated. Several new recommendation and guideline documents regarding the management of gout have been published in the past few years. New diagnostic modalities, such as ultrasound and dual-energy computed tomography, are now available. Newer treatment options exist, and older agents and their interactions are now better understood. This review addresses these recent diagnostic and therapeutic developments and describes our management protocol with the aim of providing the clinician with a pragmatic approach to gout management.
Crystalline-induced arthropathies impose substantial morbidity but can be challenging to diagnose, especially in early phases. The most common crystalline arthropathies are gout (monosodium urate deposition), calcium pyrophosphate dihydrate deposition, and hydroxyapatite deposition disease. Computed tomography (CT) and MR imaging provide three-dimensional information on osseous structures, periarticular soft tissue and tophi with superior spatial resolution. Dual-source CT (dual-energy CT [DECT]) offers the further advantage of selectively identifying crystalline deposits. CT, MR imaging, and DECT can be of value in problematic cases and can potentially be used for disease monitoring. Further research is necessary to elucidate their added value.
Objective:
This study aimed to evaluate the diagnostic performance of dual-energy computed tomography (DECT) for patients with gout.
Methods:
We searched the Medline, Embase, and Cochrane Library databases, and performed a meta-analysis on the diagnostic accuracy of DECT in patients with gout.
Results:
A total of eight studies including 510 patients with gout and 268 controls (patients with non-gout inflammatory arthritis) were available for the meta-analysis. The pooled sensitivity and specificity of DECT were 84.7% (95% confidence interval [CI]: 81.3-87.7) and 93.7% (93.0-96.3), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 9.882 (6.122-15.95), 0.163 (0.097-0.272), and 78.10 (31.14-195.84), respectively. The area under the curve of DECT was 0.956 and the Q(*) index was 0.889, indicating a high diagnostic accuracy. Some between-study heterogeneity was found in the meta-analyses. However, there was no evidence of a threshold effect (Spearman correlation coefficient = 0.419; p = 0.035). In addition, meta-regression showed that the sample size, study design, and diagnostic criteria were not sources of heterogeneity, and subgroup meta-analyses did not change the overall diagnostic accuracy.
Conclusions:
Our meta-analysis of published studies demonstrates that DECT has a high diagnostic accuracy and plays an important role in the diagnosis of gout.
Objective:
The objective of our study was to discover the types and incidence of artifacts in dual-energy CT (DECT) using datasets of 50 consecutive patients who underwent a four-limb DECT protocol for the evaluation of suspected gout. Identification of artifacts and techniques for artifact reduction are discussed.
Conclusion:
Artifacts commonly occur in DECT performed for gout assessment but are usually readily recognizable. For 90% of the patients in our study who underwent imaging for suspected gout, DECT showed some type of artifact, with nail bed and skin artifacts being the most common.
Background Although there has been major progress in gout imaging, no gout classification criteria currently include advanced imaging techniques.
Objective To examine the usefulness of imaging modalities in the classification of gout when compared to monosodium urate (MSU) crystal confirmation as the gold standard, in order to inform development of new gout classification criteria.
Methods We systematically reviewed the published literature concerning the diagnostic performance of plain film radiography, MRI, ultrasound (US), conventional CT and dual energy CT (DECT). Only studies with MSU crystal confirmation as the gold standard were included. When more than one study examined the same imaging feature, the data were pooled and summary test characteristics were calculated.
Results 11 studies (9 manuscripts and 2 meeting abstracts) satisfied the inclusion criteria. All were set in secondary care, with mean gout disease duration of at least 7 years. Three features were examined in more than one study: the double contour sign (DCS) on US, tophus on US, and MSU crystal deposition on DECT. The pooled (95% CI) sensitivity and specificity of US DCS were 0.83 (0.72 to 0.91) and 0.76 (0.68 to 0.83), respectively; of US tophus, were 0.65 (0.34 to 0.87) and 0.80 (0.38 to 0.96), respectively; and of DECT, were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively.
Conclusions US and DECT show promise for gout classification but the few studies to date have mostly been in patients with longstanding, established disease. The contribution of imaging over clinical features for gout classification criteria requires further examination.
It is unclear when the synovial-based inflammatory process of gout begins. The aim of this study was to determine the percentage of patients with inter-critical gout who have chronic synovial-based inflammation as evidenced by synovial pannus on a contrast-enhanced magnetic resonance imaging (MRI) of their most involved joint and determine if the presence and/or severity correlates with their serum urate levels. All patients received a 3 T MRI of their index joint, serum urate level, CRP, and creatinine. The primary endpoint was to determine the prevalence of synovial pannus and the correlation of serum urate levels with the presence and/or severity of the synovial pannus on that same joint. MRI erosions, tophi, swelling, effusion, and osteitis were also documented. Seventy-two of 74 subjects (90 % men) completed the protocol. Fifty-three of 72 (74 %) index joints were the first metatarsophalangeal joint. Thirty-nine (54.2 %) of the patients were on urate-lowering therapy; 15 (20.8 %) and 7 (9.7 %) were taking colchicine or a NSAID daily, respectively. Of the 72 subjects, 63 (87.5 %) had synovial pannus on their MRI with good inter-reader agreement between the two radiologists. The mean serum urate level was 7.93 mg/dL. There was no correlation with the presence (p = 0.33) or severity (p = 0.34) of synovial pannus and serum urate levels. There was also no correlation with the presence or severity of synovial pannus and the secondary endpoints. The majority of patients with inter-critical gout have evidence of chronic synovial-based inflammation. However, the presence and severity of this inflammation do not appear to correlate with serum urate levels.
To assess the value of MicroPure, a new ultrasound image processing technique, in identifying microcalcifications (formed by monosodium urate crystals) in the first metatarsophalangeal joints attacked by gout compared to gray-scale ultrasound images.
Thirty-six patients who fulfilled the study inclusion criteria underwent gray-scale ultrasound and MicroPure examinations of the first metatarsophalangeal joints attacked by gout. Static images of the target areas were acquired using gray-scale ultrasound and MicroPure. Two independent and blinded investigators analyzed the images to determine the number of microcalcifications and to score for image quality and artifacts.
The two investigators observed significantly more microcalcifications with MicroPure compared to gray-scale ultrasound (ρ<0.001). The level of agreement between the investigators consistently increased from gray-scale ultrasound to MicroPure imaging (gray-scale interclass correlation coefficient of 0.69 vs. MicroPure interclass correlation coefficient of 0.81). One investigator preferred the MicroPure image quality over gray-scale ultrasound (ρ<0.001), but the other investigator disagreed (ρ<0.001). Both investigators observed fewer artifacts with MicroPure than with gray-scale ultrasound (ρ<0.009).
MicroPure imaging identified significantly more microcalcifications than gray-scale ultrasound.
Few imaging studies have investigated cartilage in gout. Magnetic resonance imaging (MRI) can image cartilage damage and also reveals other features of gouty arthropathy. The objective was to develop and validate a system for quantifying cartilage damage in gout.
3-T MRI scans of the wrist were obtained in 40 gout patients. MRI cartilage damage was quantified using an adaptation of the radiographic Sharp van der Heijde score. Two readers scored cartilage loss at 7 wrist joints: 0 (normal), 1 (partial narrowing), 2 (complete narrowing) and concomitant osteoarthritis was recorded. Bone erosion, bone oedema and synovitis were scored (RAMRIS) and tophi were assessed. Correlations between radiographic and MRI cartilage scores were investigated, as was the reliability of the MRI cartilage score and its associations.
The GOut MRI Cartilage Score (GOMRICS) was highly correlated with the total Sharp van der Heijde (SvdH) score and the joint space narrowing component (R = 0.8 and 0.71 respectively, p < 0.001). Reliability was high (intraobserver, interobserver ICCs = 0.87 [0.57-0.97], 0.64 [0.41-0.79] respectively), and improved on unenhanced scans; interobserver ICC = 0.82 [0.49-0.95]. Cartilage damage was predominantly focal (82 % of lesions) and identified in 40 out of 280 (14 %) of joints. Cartilage scores correlated with bone erosion (R = 0.57), tophus size (R = 0.52), and synovitis (R = 0.55), but not bone oedema scores.
Magnetic resonance imaging can be used to investigate cartilage in gout. Cartilage damage was relatively uncommon, focal, and associated with bone erosions, tophi and synovitis, but not bone oedema. This emphasises the unique pathophysiology of gout.
To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using polarising microscopy of synovial fluid (diagnostic yield).
Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard (polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed.
The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%).
DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals.
Background
Lack of standardization of outcome measures limits the usefulness of clinical trial evidence to inform health care decisions. This can be addressed by agreeing on a minimum core set of outcome measures per health condition, containing measures relevant to patients and decision makers. Since 1992, the Outcome Measures in Rheumatology (OMERACT) consensus initiative has successfully developed core sets for many rheumatologic conditions, actively involving patients since 2002. Its expanding scope required an explicit formulation of its underlying conceptual framework and process.
Methods
Literature searches and iterative consensus process (surveys and group meetings) of stakeholders including patients, health professionals, and methodologists within and outside rheumatology.
Results
To comprehensively sample patient-centered and intervention-specific outcomes, a framework emerged that comprises three core “Areas,” namely Death, Life Impact, and Pathophysiological Manifestations; and one strongly recommended Resource Use. Through literature review and consensus process, core set development for any specific health condition starts by identifying at least one core “Domain” within each of the Areas to formulate the “Core Domain Set.” Next, at least one applicable measurement instrument for each core Domain is identified to formulate a “Core Outcome Measurement Set.” Each instrument must prove to be truthful (valid), discriminative, and feasible. In 2012, 96% of the voting participants (n = 125) at the OMERACT 11 consensus conference endorsed this model and process.
Conclusion
The OMERACT Filter 2.0 explicitly describes a comprehensive conceptual framework and a recommended process to develop core outcome measurement sets for rheumatology likely to be useful as a template in other areas of health care.
Clinical detection of gout can be difficult due to co-existent and mimicking arthropathies and asymptomatic disease. Understanding of the distribution of urate within the body can aid clinical diagnosis and further understanding of the resulting pathology. Our aim was to determine this distribution of urate within the extremities in patients with gout.
All patients who underwent a four-limb dual-energy computed tomography (DECT) scan for suspected gout over a 2-year period were identified (n = 148, 121 male, 27 female, age range, 16-92 years, mean = 61.3 years, median = 63 years). The reports of the positive cases were retrospectively analyzed and the locations of all urate deposition recorded and classified by anatomical location.
A total of 241 cases met the inclusion criteria, of which 148 cases were positive. Of these, 101 (68.2 %) patients had gout in the foot, 81 (56.1 %) in the knee, 79 (53.4 %) in the ankle, 41 (27.7 %) in the elbow, 25 (16.9 %) in the hand, and 25 (16.9 %) in the wrist. The distribution was further subcategorized for each body part into specific bone and soft tissue structures.
In this observational study, we provide for the first time a detailed analysis of extremity urate distribution in gout, which both supports and augments to the current understanding based on clinical and microscopic findings.
Dual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout.
Seventy-three patients with tophaceous gout on stable therapy attended study visits at baseline and twelve months. All patients had a comprehensive clinical assessment including serum urate testing and DECT scanning of both feet. Two readers analysed the DECT scans for the total urate volume in both feet. Analysis included inter-reader intraclass correlation coefficients (ICCs) and limits of agreement, and calculation of the smallest detectable change.
Mean (standard deviation) serum urate concentration over the study period was 0.38 (0.09) mmol/L. Urate-lowering therapy was prescribed in 70 (96%) patients. The median (interquartile range) baseline DECT urate volume was 0.49 (0.16, 2.18) cm3, and change in DECT urate volume was -0.01 (-0.40, 0.28) cm3. Inter-reader ICCs were 1.00 for baseline DECT volumes and 0.93 for change values. Inter-reader bias (standard deviation) for baseline volumes was -0.18 (0.63) cm3 and for change was -0.10 (0.93) cm3. The smallest detectable change was 0.91 cm3. There were 47 (64%) patients with baseline DECT urate volumes <0.91 cm3. Higher serum urate concentrations were observed in patients with increased DECT urate volumes above the smallest detectable change (P = 0.006). However, a relationship between changes in DECT urate volumes and serum urate concentrations was not observed in the entire group.
In patients with tophaceous gout on stable conventional urate-lowering therapy the measurement error for DECT urate volume assessment is substantially greater than the median baseline DECT volume. Analysis of patients commencing or intensifying urate-lowering therapy should clarify the optimal use of DECT as a potential outcome measure in studies of chronic gout.
Objectives:
The aim of our study was to compare dual-energy CT (DECT) with US for the diagnosis of gouty arthritis and to correlate the imaging findings with results from synovial fluid aspiration whenever possible.
Methods:
We recruited 21 patients (17 male and 4 female) who presented with a clinical suspicion of acute or chronic gout in 37 joints. DECT scans of the hands, wrists, feet, ankles, knees and elbows were performed. For post-processing, a colour-coding gout software protocol was used. US examinations of the same joints were performed. In addition, joint fluid aspiration was performed in a total of 14 joints.
Results:
DECT images were positive for urate crystal deposits in 25 of 37 joints. US findings were positive in 24 of 37 examined joints. In 12 of 14 joints the synovial fluid aspiration was positive. CT and US findings correlated in 32 of 37 joints (86.5%; κ = 0.698, P < 0.001). CT and synovial fluid results correlated in 12 of 14 joints (85.7%; κ = 0.417, P = 0.119). US and cytology findings correlated in 14 of 14 joints (100%; κ = 1, P < 0.001).
Conclusion:
DECT and US have comparable sensitivity for the detection of gouty arthritis in a clinical setting. However, DECT results should be interpreted carefully, as there could be some false-negative findings.
Objectives:
Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another.
Methods:
3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients.
Results:
Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001].
Conclusion:
Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout.
Objective The 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. The secondary objective was to test the concurrent validity of US abnormalities using as gold standard the microscopic demonstration of monosodium urate (MSU) crystals.
Methods Ninety-one men with gout and 42 age-matched controls were prospectively recruited. All patients with gout and controls underwent US assessment of several US abnormalities in 26 joints, six bursae, eight tendons, 20 tendon compartments, four ligaments, and 18 articular cartilages by experts in US blinded to the patients’ group. Patients with gout and controls with US abnormalities were asked to undergo US-guided aspiration for microscopic identification of MSU crystals. Interobserver and intraobserver reliability of the US assessment was evaluated in a web-based exercise.
Results The assessment of one joint (ie, radiocarpal joint) for hyperechoic aggregates (HAGs), two tendons (ie, patellar tendon and triceps tendon) for HAGs and three articular cartilages (ie, first metatarsal, talar and second metacarpal/femoral) for double contour sign showed the best balance between sensitivity and specificity (84.6% and 83.3%, respectively). Intraobserver reliability was good (mean κ 0.75) and interobserver reliability was moderate (κ 0.52). The aspirated material from HAGs was positive for MSU crystals in 77.6% of patients with gout and negative in all controls.
Conclusions Our results suggest that US bilateral assessment of one joint, three articular cartilages and two tendons may be valid for diagnosing gout with acceptable sensitivity and specificity.
Introduction
Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and tophus.
Methods
Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed.
Results
The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous tophus were more likely to have NBF; if tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001.
Conclusions
This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, tophus, and formation of new bone during the process of joint remodelling in gout.
The authors prospectively determined: (1) the specificity and sensitivity of dual energy CT (DECT) for gout; and (2) the interobserver and intraobserver reproducibility for DECT urate volume measurements.
Forty crystal-proven gout patients (17 tophaceous) and 40 controls with other arthritic conditions prospectively underwent DECT scans of all peripheral joints using a gout protocol that color-codes the composition of tissues. A blinded radiologist identified urate deposition to calculate specificity and sensitivity of DECT for gout. Inter-rater volumetric reproducibility was determined by two independent radiologists on 40 index tophi from the 17 tophaceous gout patients using automated software.
The mean age of the 40 gout patients was 62 years, the mean gout duration was 13 years and 87% had a history of urate-lowering therapy (ULT). The specificity and sensitivity of DECT for gout were 0.93 (95% CI, 0.80 to 0.98) and 0.78 (0.62 to 0.89), respectively. When the authors excluded three gout cases with unreadable or incomplete scans, the sensitivity was 0.84 (95% CI, 0.68 to 0.94). The urate volumes of 40 index tophi ranged from 0.06 cm(3) to 18.74 cm(3) with a mean of 2.45 cm(3). Interobserver and intraobserver intraclass correlation coefficients for DECT volume measurements were 1.00 (95% CI, 1.00 to 1.00) and 1.00 (95% CI, 1.00 to 1.00) with corresponding bias estimates (SD) of 0.01 (0.00) cm(3) and 0.01 (0.03) cm(3).
These prospective data indicate high reproducibility of DECT urate volume measures. The specificity was high, but sensitivity was more moderate, potentially due to frequent ULT use in our patients.
Objective
To describe and classify the varied ultrasound features of tendinous involvement in relation to tophi in chronic tophaceous gout so that they are better recognised.
Methods
Ultrasound images of 138 affected areas from 31 patients with chronic tophaceous gout were analysed using high-quality broadband linear transducers. The relationship between tendon and tophi was classified, and the inter-observer agreement regarding classification was analysed.
Results
Tophi envelopment in the tendon was the most frequent characteristic (45%) followed by no relationship between tophi and tendon (41%), tophi at the insertion site of the tendon (7%), extrinsic compression (6%) and tophi within the tendon (1%). The inter-observer concordance on classification of the relationship between tophi and tendon was measured using McNemar’s test with P < 0.001 (χ2 = 30.0, degree of freedom = 9) and kappa test = 0.627 (P < 0.001), indicating substantial inter-observer concordance.
Conclusion
Tophi generally envelope the tendon or there is no relationship between them. Tophi can also be found at the insertion site of the tendon, cause extrinsic compression or be located inside the tendon. There is substantial inter-observer agreement for ultrasound classification of tendon involvement by tophi. This study contributes to diagnostic elucidation and shows the diverse characteristic forms of tendon involvement by tophi.
This study aims to investigate the relationship between clinical and US findings together with the prevalence and distribution of US findings indicative of monosodium urate (MSU) crystal deposition within the foot in patients with gout.
A total of 50 patients with gout attending the in-patient and the out-patient clinics of the Rheumatology Departments were prospectively enrolled in this multi-centre study. Multiplanar examination of the following 15 joints was performed: talo-navicular, navicular-cuneiform (medial, intermediate and lateral), calcaneo-cuboid, medial, intermediate and lateral cuneiform-metatarsal, cuboid-4th metatarsal, cuboid-5th metatarsal and all five metatarsophalangeal (MTP) joints.
The following US findings were indicative of gout: enhancement of the superficial margin of the hyaline cartilage, intra-articular tophus, and extraarticular tophus. In 46 patients, a total of 1380 foot joints were investigated. In 1309 joints that were not clinically involved, US detected signs indicative of joint inflammation in 9% (121/1309). Talo-navicular joint and the first MTP joint were the joints in which the highest number of US findings were found at mid-foot and fore-foot, respectively. At MTP joint level, dorsal scans allowed the detection of a higher number of US findings indicative of joint inflammation, and MSU crystal deposits rather than on the volar plane.
This study demonstrated that US detected a higher number of inflamed foot joints than clinical examination, and that the first MTP and the talo-navicular joints were the anatomic sites with the highest prevalence of US signs of MSU crystal aggregates.
Asymptomatic hyperuricaemia is defi ned as a serum urate concentration equal to or above 7.0 mg/dl with no symptoms or clinical signs. Most individuals with hyperuricaemia, however , do not develop gouty arthritis. The annual incidence of gout is 0.5% in subjects with uric acid levels from 7.0 to 8.9 mg/dl, rising to 4.9% in those with uric acid levels higher than 9.0 mg/dl. 1 However, only 12% of patients with serum uric acid levels between 7 and 7.9 mg/dl who were followed for 14 years developed gout. 2 There are no accurate predictors of gout in Diagnosis of gout in patients with asymptomatic hyperuricaemia: a pilot ultrasound study this population and, as a consequence, we ignore the patients who may benefi t from an early urate-lowering therapy intervention. The aim of this pilot study was to investigate the prevalence of gout in patients with asymptomatic hyperuri-caemia and to investigate the accuracy of ultrasound in the diagnosis of gout in this population. For this purpose, the presence of birefringent monosodium urate (MSU) crystals in the synovial fl uid was used as a gold standard.
The gold standard for establishing the diagnosis of gouty arthritis is the detection of monosodium urate (MSU) crystals in synovial fluid or periarticular tophi. The European League Against Rheumatism recommendations from 2006 state that ‘for typical presentations of gout a clinical diagnosis alone is reasonably accurate but not definitive without crystal confirmation’.1 In addition, various imaging methods can help to non-invasively support the diagnosis of gout. Joint ultrasonography can detect MSU deposits at cartilaginous surfaces (‘double contour sign’) as well as periarticular tophus formation.2 3
Dual energy CT (DECT) is an imaging method that uses x-ray beams of two different energies to differentiate MSU deposits from connective tissues and from calcium containing structures by their absorption properties.4 Choi et al have demonstrated that in tophaceous gout, DECT …
In this study, we aimed to investigate ultrasonographic (US) changes suggestive of gouty arthritis in the hyaline cartilage, joints and tendons from asymptomatic individuals with hyperuricemia.
We conducted a cross-sectional, controlled study including US examinations of the knees and first metatarsal-phalangeal joints (first MTPJs), as well as of the tendons and enthesis of the lower limbs. Differences were estimated by χ² or unpaired t-tests as appropriate. Associations were calculated using the Spearman's correlation coefficient rank test.
Fifty asymptomatic individuals with hyperuricemia and 52 normouricemic subjects were included. Hyperechoic enhancement of the superficial margin of the hyaline cartilage (double contour sign) was found in 25% of the first MTPJs from hyperuricemic individuals, in contrast to none in the control group (P < 0.0001). Similar results were found on the femoral cartilage (17% versus 0; P < 0.0001). Patellar enthesopathy (12% versus 2.9%; P = 0.01) and tophi (6% versus 0; P = 0.01) as well as Achilles enthesopathy (15% versus 1.9%; P = 0.0007) were more frequent in hyperuricemic than in normouricemic individuals. Intra-articular tophi were found in eight hyperuricemic individuals but in none of the normouricemic subjects (P = 0.003).
These data demonstrate that morphostructural changes suggestive of gouty arthritis induced by chronic hyperuricemia frequently occur in both intra- and extra-articular structures of clinically asymptomatic individuals.
To develop a method of scoring bone erosion in the feet of patients with gout using CT as an outcome measure for chronic gout studies, consistent with the components of the OMERACT filter.
Clinical assessment, plain radiographs and CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring System (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1100 bones) by two independent radiologists. A number of different models were assessed to determine the optimal CT scoring system for bone erosion, incorporating the frequency of involvement and inter-reader reliability for individual bones.
An optimal model was identified with low number of bones required for scoring (seven bones/foot), inclusion of bones over the entire foot, high reliability and ability to capture a high proportion of disease. This model included the following bones in each foot: first metatarsal (MT) head, second to fourth MT base, cuboid, middle cuneiform and distal tibia (range 0-140). Scores from this model correlated with plain radiographic damage scores (r = 0.86, P < 0.0001) and disease duration (r = 0.42, P < 0.05). Scores were higher in those with clinically apparent tophaceous disease than in those without tophi (P < 0.0001).
We have developed a preliminary method of assessing bone erosion in gout using conventional CT. Further testing of this method is now required, ideally in prospective studies to allow analysis of the sensitivity to change of the measure.
The knee is a frequent target for gout and calcium pyrophosphate dihydrate (CPPD) disease with involvement of both articular and peri-articular structures. The aims of the present study were to investigate the relationship between clinical and ultrasound (US) findings and to describe the prevalence and distribution of crystal deposits in the knee in patients with gout and CPPD disease. Thirty patients with gout and 70 patients with CPPD disease were enrolled in the study. Prior to US assessment all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (evocated by palpation and/or active or passive mobilisation of the knee), and knee swelling. US examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 9 MHz. Two hundred knee joints were investigated in a total of 100 patients. Fifty-one (25.5%) knee joints were found clinically involved, while at least one US finding indicative of joint inflammation was obtained in 73 (36.5%) knee joints.The most frequent US finding indicative of knee joint inflammation was joint effusion, detected in 21 (35%) out of 60 knees and in 52 (37%) out of 140 knees, in gout and CPPD disease, respectively. Ten (17%) out of 60 knees and 21 (15%) out of 140 knees were found positive for synovial hypertrophy with or without intra-articular power Doppler, in gout and CPPD disease respectively. Sonographic evidence of crystal deposition within joint cartilage (hyaline and fibrocartilage) was more frequently seen than in the soft tissue in the knee.This study demonstrated that US detected a higher number of inflamed knee joints than clinical assessment in patients with crystal related arthropathies and that the distribution of crystal deposits at joint cartilage level permitted distinction between gout and CPPD disease. Further studies are required to investigate both sensitivity and specificity of US features indicative of crystal aggregates at both tendon and entheseal level.
Objective:
We aimed to determine the ability of ultrasonography (US) to show decrease or disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT).
Methods:
To 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).
Results:
We 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).
Conclusions:
US could show disappearance of urate deposits after ULT and appears to be well correlated with efficacy of ULT.
Objective:
Differentiating gout, calcium pyrophosphate deposition disease (CPPD), and non-crystal-related inflammatory arthropathies (non-CRA) is essential but often clinically impossible. The sonographic double contour (DC) sign may have good specificity for gout in highly specialized centers, but it can be challenging to use it to distinguish gout from cartilage hyperenhancements in CPPD. We evaluated the diagnostic value of the DC sign alone and in combination with Doppler signals and uric acid (UA) levels in patients with acute arthritis.
Methods:
We retrospectively investigated 225 acutely inflamed joints and documented the presence of DC, Doppler hypervascularization, and serum UA (SUA) levels. All patients underwent synovial fluid (SF) analysis. Sensitivity, specificity, and positive predictive values were calculated, and correlation analyses and a binary regression model were used to investigate their diagnostic values.
Results:
The sensitivity of DC sign for crystalline arthritides was 85% and specificity 80%. Its specificity for gout was 64%, for CPPD 52%. In contrast to non-CRA hypervascularization, degree 2 and 3 Doppler signals were highly associated with gout and less with CPPD (p < 0.01). The combination of DC sign with hypervascularization and elevated UA levels increased specificity for gout to more than 90% and resulted in a 7-fold increase of the likelihood of diagnosis of gout (p < 0.01), but with a loss of sensitivity (42%).
Conclusion:
The DC sign alone is suitable for predicting crystal-related arthropathies, but it cannot reliably distinguish gout from CPPD in everyday clinical routine. Combining hypervascularization and SUA levels increases the diagnostic value, leading us to propose a diagnostic algorithm.
Objective
The aims of this study were to identify the characteristic ultrasound (US) findings of the first metatarsophalangeal joint (MTPJ1) in acute gout attack and to evaluate the efficacy and safety of US-guided intraarticular corticosteroid injection of the MTPJ1.Methods
We enrolled 21 patients with acute gout attack involving the MTPJ1 unilaterally. US evaluation of each affected MTPJ1 was compared with radiographic features. US-guided intraarticular corticosteroid (0.5 ml [20 mg] of triamcinolone mixed with 0.5 ml of 2% lidocaine) was injected into the affected MTPJ1s. Pain, general disability, and walking disability were assessed at baseline, 24 hours, 48 hours, and 7 days after injection with visual analog scales.ResultsThe characteristic US findings of MTPJ1 were erosion, joint effusion, synovial hypertrophy, tophus-like lesion, double contour, hyperechoic spots, and increased power Doppler signal in acute gout attack. US was more sensitive than conventional radiograph in detecting erosion and tophus-like lesion. The reductions of mean visual analog scale scores in pain, general disability, and walking disability were 48 mm (SD, 27), 35 mm (SD, 26) and 39 mm (SD, 26), respectively, 48 hours after US-guided intraarticular corticosteroid injection. There were no adverse events.ConclusionsUS is a sensitive tool to evaluate joint abnormality of the MTPJ1 in acute gout attack and US-guided intraarticular corticosteroid injection to this joint is effective and safe. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound, 2014
This study aims to evaluate the intraobserver and interobserver reproducibility of the tophus urate volume, erosion volume, and the erosion score measurements in patients with gout by using dual-energy CT (DECT) scans comparing their bone erosion volumes against bone erosion scores and also to determine a valid measure of joint destruction in chronic gout. Sixty-six subjects underwent DECT scans of the hands or feet. Two independent observers measured the tophus urate volumes and bone erosion volumes using automated volume assessment software and the erosion scores based on the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). The intraobserver and interobserver reproducibility were analyzed by intraclass correlation coefficient (ICC) and limits of agreements analysis. The relationship between erosion volumes and erosion scores was analyzed. The intraobserver and interobserver ICC for tophus urate volume measurements (n = 636) were 1.000 (95 % confidence interval (95 % CI) 1.000 to 1.000) and 1.000 (95 % CI 1.000 to 1.000), 0.999 (0.999, 0.999) and 0.999 (0.999, 0.999) for bone erosion volumes (n = 350), 0.937 (0.928, 0.946) and 0.899 (0.883, 0.912) for erosion scores (n = 350). Strong positive correlations were demonstrated between individual erosion volumes and scores (r
s = 0.914, p < 0.001) as well as total erosion volume and score per patient (r = 0.838-0.867, p < 0.001). This study demonstrated a high reproducibility of tophus urate volumes, erosion volumes, and erosion score measurements using DECT. Erosion volumes show to be a more direct and accurate method to evaluate bone erosion compared with erosion score, strongly supporting it as a superior and standard measure of structural joint damage in gout.
The aim of the study was to investigate the sensitivity and specificity of dual-energy computed tomography in the diagnosis of acute gouty arthritis, and the related risk factors for urate crystal deposition. One hundred ninety-one patients (143 with acute gouty arthritis and 48 with other arthritic conditions) were studied. All patients had acute arthritic attack in the recent 15 days and underwent dual-energy computed tomography (DECT) scan with the affected joints. The urate volume was calculated by DECT and the basic information of these patients was recorded at the same time. Uric acid crystals were identified with DECT in 140 of 143 (97.9 %) gout patients and 6 of 48 (12.5 %) of nongout patients, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of DECT in the diagnosis of acute gouty arthritis were 97.9, 87.5, 95.9, and 93.3 %, respectively. The urate volumes were ranged from 0.57 to 54,543.27 mm(3) with a mean volume of 1,787.81 ± 7,181.54 mm(3). Interestingly, urate volume was correlated with the disease duration, serum uric acid levels, the presence of tophi, and bone erosion. Two-year follow-up data was available in one patient with recurrent gouty arthritis, whose urate volume was gradually reduced in size by DECT detection after urate-lowering therapies. DECT showed high sensitivity and specificity for the identification of urate crystals and diagnosis of acute gout. The risk factors for uric acid deposition include the disease duration, serum uric acid levels, the presence of tophi, and bone erosion. DECT has an important role in the differential diagnosis of arthritis, and also could be served as a follow-up tool.
Objective of the study is to compare the diagnostic accuracy for detecting monosodium urate crystal deposits between dual-energy CT (DECT) and ultrasound (US). Sixty consecutive patients (49 men, mean age 62 years) with clinically suspected gout were included in this case-control study. DECT and US of feet, knees, hands and elbows were performed in all patients. Polarisation microscopy of synovial fluid or a score incorporating serum uric acid level, first MTP joint involvement, gender, previous patient-reported arthritis attack, cardiovascular diseases, joint redness and onset within 1 day was used as standard of reference. Standard of reference classified 39 patients as gout positive. Sixteen patients had gout and a concomitant rheumatic disease. Sensitivities for diagnosis of gout disease were 84.6 % (33/39) for DECT and 100 % (39/39) for US. Specificities were 85.7 % (18/21) for DECT and 76.2 % (16/21) for US. Positive and negative predictive values were 91.7 % (33/36) and 75.0 % (18/24) for DECT, 88.6 % (39/44) and 100 % (16/16) for US, respectively. Urate crystals were detected most frequently in MTP1 joints (DECT 20/78, US 58/78), any other toe joints (DECT 25/78, US 62/78) and knees (DECT 41/78, US 31/78). The volumetry of DECT computed a mean urate crystal deposit load of 2.1 cm(3) (SD 9.6 cm(3)). A mean effective dose of ≤0.5 mSv was estimated. DECT is more specific for the diagnosis of gout than US. However, it fails to detect small urate crystal deposits. It might be particularly useful for patients with ambivalent findings, concomitant rheumatic diseases and with non-conclusive joint aspiration.
The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout.
Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp-van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints.
DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p<0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p<0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r>0.88, p<0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration.
MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease.
Crystal arthritides such as gout can be detected by ultrasonography (US). This study reveals the performance of joint US (double contour sign (DCS), tophus (T), hyperechoic spots cq. "snow storm" (SS)) for diagnosing gout and calcium pyrophosphate dihydrate crystal deposition disease (CPPD) in patients with acute mono- or oligoarthritis (MOA). The gold standard is the presence of monosodium urate (MSU)/CPPD crystals. Fifty-four Dutch patients had an acute MOA. US was performed on the following six joints maximum: the arthritic joint, the contra lateral side, metatarsophalangeal (MTP)-1, and knees bilaterally in case of arthritis in one of these joints. In case of wrist/PIP/MCP-arthritis, the knees and MTP-1 were scanned. These were examined for DCS, T, SS, and intercartilage rim (CPPD). Synovial fluid was aspirated from the affected joint for MSU proof. Twenty-six of the 54 (48 %) patients with MOA had MSU-proven gout. Sensitivity of DCS and any US abnormality (DCS, T, SS) was 77 and 96 %, respectively. The positive likelihood ratio (LR+) for DCS and any ultrasonographic abnormality (USabn) was 3.08 and 2.99, respectively, and the LR- was 0.31 and 0.06, respectively. In MSU-proven gout patients where the affected joint is not MTP-1, MTP-1 still showed USabn in 42 % of the patients. None of the CPPD patients had an intercartilage rim. In dedicated hands, ultrasonography deserves a place early in a screening algorithm of MOA patients, particularly if specificity is high enough to make punctures abundant or when microscopy is not available. In 86 % of the MSU-proven gout patients, the DCS is not present in another joint other than the affected or MTP-1 joint.
The osteoclast has been implicated in development of bone erosion in gout. The aim of this study was to determine whether zoledronate, a potent antiosteoclast drug, influences bone erosion in people with tophaceous gout.
This was a 2-year, randomised, double-blind, placebo-controlled trial of 100 people with tophaceous gout. Participants were randomised to annual administration of 5 mg intravenous zoledronate or placebo. The primary endpoint was change in the foot CT bone erosion score from baseline. Secondary endpoint was change in plain radiographic damage scores. Other endpoints were change in bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core domains for chronic gout studies.
There was no change in CT erosion scores over 2 years, and no difference between the two treatment groups at Year 1 or 2 (p(treat)=0.10, p(time)=0.47, p(treat*time)=0.23). Similarly, there was no change in plain radiographic scores over 2 years, and no difference between the two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of femur, total hip and total body BMD. Zoledronate therapy also reduced the bone turnover markers P1NP and β-CTX compared with placebo. There was no difference between treatment groups in OMERACT-endorsed core domains.
Despite improvements in BMD and suppression of bone turnover markers, antiosteoclast therapy with zoledronate did not influence bone erosion in people with tophaceous gout. These findings suggest a disconnect between responses in the healthy skeleton and at sites of focal bone erosion in tophaceous gout.
To compare dual-energy CT images (DECT) directly with gold standard histology.
A 85-year-old woman with chronic recurrent gouty arthritis and macroscopically visible tophi was assessed with DECT-scans of her feet. When she died 7 days later, three tophi in different regions and in different tissues of her left foot were processed for histological examination.
Of the selected tophi, two were almost completely missed by the color-coding DECT sequences. The tophi remained in most of their volume below the detection threshold value of 150HU (default value).
It could be demonstrated that DECT only highlights the dense tophi (corresponding of approximately 15-20vol% urate in the tophus). Less dense tophi, despite considerable size, will be missed in the color-coded images.
This study was aimed at determining the prevalence of ultrasound (US) morpho-structural changes in the shoulders of patients with crystal-related arthropathies, and at investigating the relationship between them and the clinical findings.
Eighty-eight patients with a crystal proven diagnosis of gout or calcium pyrophosphate dihydrate (CPPD) disease attending the in-patient and the out-patient clinics of four Italian Rheumatology Departments were consecutively enrolled in this multi-centre study. All patients were clinically examined by an expert rheumatologist who recorded clinical and laboratory data in addition to the presence/absence of spontaneous shoulder pain and performed the Hawkins, Jobe, Patte, Gerber, and Speed tests. In each centre, US examinations were carried out by a rheumatologist expert in musculoskeletal US blinded to clinical data, using a MyLab TWICE XVG machine (Esaote SpA, Genoa, Italy) equipped with a linear probe operating at 4-13 MHz, and a Logiq 9 machine (General Electrics Medical Systems, Milwaukee, WI, USA) with a linear probe operating at 9-14 MHz. Shoulders were scanned to detect peri-articular inflammation, rotator cuff pathology and joint involvement, and to reveal US signs indicative of crystal deposits.
A total of 88 patients, 39 with gout, 46 with CPPD disease, and 3 with both gout and CPPD disease, were enrolled. In total, 176 shoulders were clinically assessed, of which 54/176 (30%) were painful and 74/176 (42%) were clinically normal shoulders. All US findings indicative of peri-articular synovial inflammation were more frequently detected in patients with CPPD disease than in gouty patients. In 50 out of 176 (28.4%) shoulders, US allowed the detection of at least one finding indicative of synovial inflammation. Chronic tendinopathy was a frequent US finding both in gout patients and in patients with CPPD disease and the supraspinatus tendon was the most frequently involved one. In CPPD disease the supraspinatus tendon was found ruptured in a number of shoulders seven times higher than in gouty patients. The osteophytes were found at acromion-clavicular joint in nearly 80% of the shoulders in CPPD disease and in 60% in the gouty patients.
The results of this study confirm the high specificity of US findings indicative of crystal deposits at hyaline cartilage level and indicate that the supraspinatus tendon and the fibrocartilage of the acromion-clavicular joint are the most frequently affected structures of the shoulders in patients with crystal-related arthropathies.
Objective
Tophi are strongly associated with structural damage in gout, and urate-lowering therapy reduces tophus size. Pegloticase leads to dramatic reductions in serum urate and subcutaneous tophi in treatment responders. The aim of this analysis was to examine whether profound urate lowering can alter radiographic findings in gout. Methods
Serial plain radiographs of the hands and feet were obtained from 8 patients with tophaceous gout treated with pegloticase. Radiographs were scored for erosion and joint space narrowing (JSN) according to the gout-modified Sharp/van der Heijde method. Scorers were blinded to each other's scores and to the clinical characteristics of the patients (including the clinical response to pegloticase). A detailed qualitative site-by-site analysis was undertaken to define additional changes observed from baseline. ResultsAll patients experienced a profound urate-lowering response (serum urate level <1 mg/dl) during pegloticase treatment. For the entire group, the median total radiographic scores reduced from 69.25 (range 1.5-138) at baseline to 57.25 (range 1.5-110) at 12 months (P = 0.02). Median erosion scores reduced over 1 year (P = 0.008), but JSN scores did not change (P = 0.50). Further reductions were observed in total scores and erosion scores in 5 patients with 24-month followup films (one-way analysis of variance P = 0.009 for total score, 0.02 for erosion, and 0.95 for JSN). Qualitative site-by-site analysis identified regression of soft tissue masses, increased sclerosis, and filling in of erosions in the followup films. Conclusion
This exploratory study suggests that profound urate lowering can lead to improvement in structural damage, particularly bone erosion, in patients with tophaceous gout.
Objectives:
To examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT).
Methods:
Ninety-two patients with tophaceous gout had DECT scanning of both feet. Two readers scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites).
Results:
MSU crystal deposition was observed by both readers in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons), followed by the peroneal tendons (18.1%). Tibialis anterior and the extensor tendons were involved less commonly (7.6-10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the enthesis alone was more common in the Achilles tendon (OR (95% CI) 74.5 (4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR (95% CI) 6.8 (3.6 to 13.0), p<0.0001).
Conclusions:
Tendons are commonly affected by MSU crystal deposition in patients with tophaceous gout. The patterns of MSU crystal deposition suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.
Gout is one of the most common inflammatory arthritides. The literature reveals that management of this condition is often suboptimal. Imaging techniques, such as ultrasound (US), may assist in the diagnosis and management of gout and asymptomatic hyperuricaemia (AH). To undertake a systematic review evaluating US as an outcome tool in gout and asymptomatic hyperuricaemia, articles published in Medline and PubMed (1975-February 2012) were identified. Data was extracted and categorised into four different groups namely tophi, articular cartilage, soft tissue pathologies and bony changes, with a focus on validity, responsiveness, reproducibility and feasibility. Lesions reported in the literature include tophi, cartilage abnormalities, soft tissue lesions and erosions. US is able to detect tophi, using MRI as the gold standard, and is sensitive to change. The double contour sign seen overlying cartilage is specific to gout and sensitive to change. Synovial pathology is identified in gout, with some reporting intrasynovial hyperechogeneicity is suggestive of gout. US was less sensitive than MRI to cortical erosions in gout, but better than conventional radiography. Interobserver reliability when assessed ranged from fair to substantial agreement for soft tissue changes and was very good for assessing tophi, double contour and erosions. US is a promising tool which could be used in the diagnosis and management of gout. More studies are needed to assess responsiveness, reliability and feasibility.
Objectives:
The goal of this study was to investigate the usefulness of a short ultrasound (US) assessment in gout.
Methods:
Patients with gout, confirmed by urate crystal identification, and having at least one symptomatic flare in the last three months were included. Standardised US examinations of sixteen joints and eight tendons in the lower limbs were carried out. Six lesions were studied: hyperechoic spots in the synovial fluid, hyperechoic cloudy areas (HCA), bright stippled aggregates (BSA), the double contour sign (DCS), erosions and the Doppler signal. For reliability, inter-reader analyses were performed by five rheumatologists. With the results, a short US assessment was created.
Results:
Twenty-nine consecutive patients were included (93% men). The Doppler signal, HCAs and BSAs appeared in 100%, 97% and 93% of the patients, respectively. The DCS was found in 69% of patients. The locations that were most affected were the first metatarsophalangeal joint (MTP) and the knee joints, both of which are in 93% of patients. Reliability analyses showed consistent results for erosions, the Doppler signal, HCAs and the DCS in the 1st MTP (k=0.818, k=0.958, k=0.739 and k= 0.697, respectively) and for the DCS in the knees (k=0.779). A six-minute US examination of four joints (knees and the 1st MTPs) detected HCAs or DCS in 97% of cases.
Conclusions:
A US examination of four joints for two elemental lesions (the DCS and HCAs) is feasible, reliable and has face and content validity as a diagnostic test in patients with crystal-proven gout.
Ten years ago, we studied the clinical and radiographic manifestations of gout in 60 patients and described 3 patterns of disease. To determine the consequences of management over a 10-year period, we recently reassessed the 39 available patients of this population. We found that although reduced tophaceous deposition on physical examination correlated with normalization of the serum urate concentration, no correlation existed between radiographic changes and mean serum urate concentrations. Progression of gouty changes on radiography reflected progressive deformity on physical examination. We have described the radiographic changes that occurred in a well-characterized population of subjects with gout over 10 years and determined that serum urate concentrations alone may not provide an effective means of monitoring the progression of tophaceous disease in bone.
To determine the sensitivity and specificity of ultrasonography for gout, and to investigate the relationship with severity of gout.
In this case-control study, we prospectively enrolled 53 patients with crystal-proven gout and 50 controls. Ultrasonography was performed on 10 joints for each patient (metatarsophalangeal [MTP] joints 1-2, knees, metacarpophalangeal [MCP] joints 2-3) to determine the prevalence of the double contour (DC) sign and tophi in each site.
We assessed 530 joints in gouty patients and 500 in controls. Gouty patients had a mean disease duration 9.2±10.7 years and a mean of 14.7±19.8 acute attacks. Clinical exam revealed tophi in 44% of patients. Mean urate level was 656.7±145.3 μM. Inter-reader agreement between the 2 sonographers was excellent for both DC sign and tophi. The frequency of the DC sign in MTPs, knees and MCPs for gouty patients and controls was 67% vs. 2%, 57% vs. 0%, and 21% vs. 0%, respectively (all p<0.001), whereas that of tophi, only found in gouty patients, was 74%, 42% and 22%, respectively (p<0.001). The sensitivity of the DC sign was 67% for MTPs, 57% for knees and 21% for MCPs, and specificity was high (all >98%). The sensitivity of tophi was 74%, 42% and 22%, respectively, and specificity 100% for all sites. For MTPs, the DC sign, but not tophi, was significantly associated with uricemia (p<0.05) and disease duration (p=0.01).
Ultrasonography has good sensitivity and specificity to diagnose gout. Sensitivity depends on disease duration, joint site and severity of the disease.
Dual-energy computed tomography (DECT) has recently been described as a sensitive method to detect urate deposits in patients with gout.
The aim of this study was to compare the reproducibility of DECT with various physical measurement methods of tophus size assessment.
Sixty-four tophi from 25 patients were analyzed. Each tophus was assessed by 2 independent observers using Vernier calipers and tape measure. All patients proceeded to DECT scanning of both feet. Urate volume within index tophi was assessed by 2 independent observers using automated DECT volume assessment software (n = 55 tophi). Five patients returned within 1 week for repeat physical assessment of tophus size. Dual-energy computed tomography scans from the returning patients were scored twice by both observers. Intraobserver and interobserver reproducibility was assessed by intraclass correlation coefficient (ICC) and limits-of-agreement analysis.
Overall, DECT was more reproducible than the physical methods with interobserver ICCs for DECT of 0.95, for calipers 0.78, and for tape measurement 0.88, and intraobserver ICCs for DECT of 1.00, for calipers 0.75, and for tape measurement 0.91. Vernier caliper and tape measurements correlated highly with each other (rs = 0.84, P < 0.0001) but less well with DECT (for index tophi, r(s) = 0.46, P = 0.004 for both). Large variation was observed in the amount of urate deposits documented by DECT in tophi of similar physical size.
Dual-energy computed tomography scanning is a highly reproducible method for measuring urate deposits within tophi. This imaging modality reveals the composition of tophi that contain variable urate deposits embedded within soft tissue.
Magnetic resonance imaging (MRI) is commonly used in autoimmune inflammatory arthritis to define disease activity and damage, but its role in gout remains unclear. The aim of our study was to identify and describe the MRI features of gout.
Over a 10-year period we identified patients with gout who underwent MRI scanning of the hands or feet. Scans were reviewed for erosions, synovitis, tenosynovitis, tendinosis, bone edema, and tophi by a musculoskeletal radiologist and 2 rheumatologists in a blinded manner. MRI features in patients with uncomplicated gout were compared with features where concomitant osteomyelitis was diagnosed.
A total of 47 patients with gout (51 scans) were included: 33 (70%) had uncomplicated gout and 14 (30%) had gout complicated by osteomyelitis. MRI features included tophi in 36 scans (71%), erosions in 35 (69%), bone edema in 27 (53%), synovitis in 15 (29%), tenosynovitis in 8 (16%), and tendinosis in 2 (4%). Uncomplicated gout and gout plus osteomyelitis did not differ for most MRI features. However, "severe bone marrow edema" was much more common in gout plus osteomyelitis, occurring in 14/15 scans (93%) compared with 3/36 scans (8%) in uncomplicated gout (OR 154.0, 95% CI 14.7-1612, p < 0.0001). Sensitivity and specificity of "severe bone edema" for concomitant osteomyelitis were 0.93 (95% CI 0.68-0.99) and 0.92 (95% CI 0.78-0.98), respectively.
MRI reveals that gout affects the joints, bones, and tendons. Bone edema in patients with chronic tophaceous gout is frequently mild and this contrasts with the "severe bone edema" observed in patients with concomitant osteomyelitis.
The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference.
A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow.
Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%).
The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.
Computed tomography (CT) has high accuracy for tophus detection. This study assessed reliability of CT measurement of tophus volume and compared reproducibility of CT with physical measurement of tophus size.
Forty-seven hand tophi were analyzed in 20 patients with gout. The longest tophus diameter was recorded by 2 independent observers. All patients proceeded to CT scanning of the hands on a Philips Brilliance scanner (0.8-mm slices). Two independent observers measured tophus volume using the Surface Shaded Display 3-dimensional function on the Philips CT workstation. Five patients underwent repeat physical and CT assessments within 1 week (18 observations). Inter- and intraobserver reproducibility were analyzed by limits of agreement and coefficients of variation.
Of the 47 lesions identified as tophi on physical examination, 42 (89%) were also identified on CT. The mean (95% confidence interval [95% CI]) difference between observers for physical measurement was 0.45 mm (-4.07, 4.96) and for CT was 65.2 mm(3) (-293.0, 423.3). The mean (95% CI) difference between visits for physical measurement was -0.72 mm (-5.47, 4.03) and for CT was -13.1 mm(3) (-112.5, 86.3). There was no difference between coefficients of variation for inter- and intraobserver reproducibility for the 2 measurement techniques. For tophi identified by physical and CT assessment, there was good correlation between measurements (r = 0.91, P < 0.0001).
CT assessment of tophus volume is reliable and reproducible. However, physical measurement correlates well with CT and has equivalent reproducibility. These data support the use of physical measurement as a simple and reliable method to assess tophus size.
Criteria for sonographic diagnosis of monosodium urate (MSU) crystal deposition have been developed, but the interreader reproducibility of this modality is not well established. We therefore assessed agreement using a systematic approach.
Fifty male subjects ages 55-85 years were recruited during primary care visits to an urban Veterans Affairs hospital, and were assessed by musculoskeletal ultrasound (US) of the knees and first metatarsophalangeal (MTP) joints to evaluate for the double contour sign and tophi as evidence of MSU crystal deposition. Images were read by 2 blinded rheumatologists trained in musculoskeletal US, and the degree of concordance was determined for individual subjects, total joints, femoral articular cartilage (FAC), and first MTP joints. Subjects were further categorized into 3 diagnostic groups: gout, asymptomatic hyperuricemia (no gout, serum uric acid [UA] ≥6.9 mg/dl), and controls (no gout, serum UA ≤6.8 mg/dl), and reader concordance within these 3 groups was assessed.
We observed almost perfect agreement between readers for 1) individual subjects (yes/no; n = 50, 100% agreement, κ = 1.000), 2) total joints (n = 200, 99% agreement, κ = 0.942), 3) FAC (n = 100, 99% agreement, κ = 0.942), and 4) first MTP joints (n = 100, 99% agreement, κ = 0.942). Furthermore, findings by side (right/left) and diagnostic group (gout, asymptomatic hyperuricemia, control) showed substantial to almost perfect concordance for all measures. MSU deposition was seen most commonly in gout patients, and deposition was also seen in some subjects with asymptomatic hyperuricemia, but in only 1 control.
Musculoskeletal US is reliable for detecting MSU deposition in FAC and first MTP joints in gout and asymptomatic hyperuricemia.
To describe the ultrasound characteristics of gouty tophi in the olecranon bursa and to evaluate their reproducibility.
A prospective study of the ultrasound features of 35 sites of tophi nodulations in the elbows of 31 men (mean 54.6 years). The findings were evaluated dynamically following pre-established standards. The static images were evaluated by another radiologist and were reviewed by the first examiner.
The most frequent characteristics of tophi are: hyperechogenicity (91.7%), poorly defined contours (88.6%), multiple grouped nodules (85.6%) and heterogeneity (68.6%). Intra-observer agreement is almost perfect for echogenicity (K = 1.0), moderate for the involvement of the olecranon bursa (K = 0.47) and fair for other characteristics. Inter-observer agreement is substantial for the echogenicity (K = 0.65), fair for the echotexture (K = 0.27) and the presence of a perilesional hypoechoic halo (K = 0.34) and slight for other characteristics.
The most frequent characteristic of tophi is hyperechogenicity. The intra-observer and inter-observer concordance for echogenicity are almost perfect and substantial, respectively. Knowledge of characteristics of the tophi in the elbow and their intra and inter-observer reproducibility may assist in establishing parameters for monitoring treatment and setting up criteria for differential diagnosis of processes involving the olecraneon bursa.
To describe the different and lesser-known ultrasound features of tophi in chronic tophaceous gout.
Ultrasound images of 138 affected areas were analyzed from 31 patients with gout, using high-quality broadband linear transducers (frequency range of 8-14 MHz). Tophi were classified relative to echogenicity, echotexture, contours, number and the presence or absence of hypoechoic halo. The duration of illness was correlated with the presence of calcifications in tophi.
Hyperechoic tophi were seen in 133 areas (96.3%); these were most frequently hyperechoic and heterogeneous (37.6%) or hyperechoic and heterogeneous with calcification (32.6%). Contours were found to be poorly defined in 115 (83.3%) areas. Multiple grouped tophi were seen in 85 areas (61.6%) and 50 areas (36.2%) had individual tophi. In 77 examined areas (55.8%), there was a hypoechoic halo around the tophi. There was no correlation between illness duration and presence of calcifications on tophi.
Tophi are generally hyperechoic, heterogeneous, with poorly defined contours, multiple grouped and surrounded by an anechoic halo. Individual tophus and the absence of association between illness duration and the presence of calcification are newly described features. This study of tophaceous gout by ultrasound may contribute to the diagnostic elucidation of patients with clinically atypical gout and show its diverse characteristic forms of presentation.
The aim of this study was to analyse the prevalence of occult destructive arthropathy in subjects with gout and normal plain radiographs by utilizing MRI and ultrasound (US).
The study consisted of two visits. At Visit 1, a plain radiograph of the 'index joint' was obtained. The 'index joint' was defined as a joint that has had the most acute attacks of gout historically. The index joint plain radiograph had to be free of erosive damage in order for the subject to qualify for Visit 2. At Visit 2, the subject had an MRI with contrast and an US of the index joint. Each subject also had an MRI and US of an 'asymptomatic joint'. The 'asymptomatic joint' was defined as a joint that had never experienced an acute attack of gout (determined by standard protocol). The primary endpoint was erosive changes on the MRI and/or US of the index joint. Secondary endpoints included erosive changes on the asymptomatic joint as well as bone marrow oedema (BME) (on MRI), synovial pannus (SP), soft tissue tophi (STT) or oedema (STE) on either the index or asymptomatic joint.
Twenty-seven subjects (26 males; 1 female) completed both visits. Their average age and disease duration were 55.1 years (range 21-75 years) and 6.8 years (range 0.25-25 years), respectively. The subjects' average serum uric acid level over the past 5 years was 8.09 mg/dl (range 4.1-12.8 mg/dl); their average on the day of Visit 1 was 7.96 mg/dl (range 4.6-13.9 mg/dl). The first MTP was the most common index joint (17) followed by the ankle (5), mid-tarsal (2), knee (2) and wrist (1). The knee was the most common asymptomatic joint (21) followed by the wrist (3), MTP (2) and ankle (1). All subjects had both MRIs; one subject refused the US. Out of 27 subjects, 15 (56%) had erosions on MRI of their index joint (P < 0.0001); only 1 subject (4%) had erosions identified in the index joint by US (P = NS). Regarding the secondary endpoints on the index joint, the MRI detected SP (13), BME (4), STE (3) and STT (0); the US detected SP (1), STT (1) and STE (0). Regarding the MRI of the asymptomatic joint, positive findings included SP (3), BME (3), STE (2) and erosions (1). There were no positive findings by US in the asymptomatic joint.
A large percentage of patients with gout and normal plain radiographs have occult destructive arthropathy that is only detected by advanced imaging such as MRI and/or US. However, MRI appears to be much more sensitive than US at detecting these findings.
This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or “urate icing”). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of n = 1; treated with colchicine, n = 1). At baseline, the double contour sign was seen in all patients. In those patients who achieved SU levels of 8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain ≤6 mg/dl for 7 months or more. Sonographic changes of gout correlate with SU levels and may be a non-invasive means to track changes in the uric acid pool. Larger prospective studies are needed to further assess these potentially important findings.