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REVIEW ARTICLE
Ahead of print publication  

Performance of ultrasonography in diagnosing gout


 Department of Rheumatology, University of Tunis El Manar, Faculty of Medicine of Tunis; Department of Rheumatology, Mongi Slim Hospital, La Marsa, Tunisia

Date of Submission30-Apr-2021
Date of Acceptance26-Jul-2021
Date of Web Publication01-Jul-2022

Correspondence Address:
Hiba Boussaa,
Department of Rheumatology, University Hospital Mongi Slim, La Marsa 2046
Tunisia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_83_21

  Abstract 


Ultrasonography (US) emerged as a useful imaging tool in the diagnosis of gout. However, its accuracy is still unclear. We conducted a systematic review to evaluate the performance of US in diagnosing gout. We systematically reviewed PubMed database, and all the references of eligible articles were manually screened for additional relevant papers. Studies were included if they (1) examined the performance of US in diagnosing gout, (2) used a cross-sectional design in patients presenting with acute or chronic arthritis where gout was suspected, and (3) confirmed the diagnosis of gout using microscopic identification of monosodium urate crystals as the gold standard. Seven studies were included in the present systematic review. We evaluated the diagnostic properties of three typical US signs of gout: double contour (DC), tophi, and aggregates. The sensitivity and specificity of DC for gout varied, respectively, from 42% to 87.8% and 64.1% to 97%. The sensitivity of tophi for gout was between 19% and 46% and its specificity between 93% and 100%. The sensitivity and specificity of aggregates for gout ranged, respectively, between 30.3% and 78.9% and 65% and 90.9%. When any of these US features was present, the sensitivity for the diagnosis of gout increased up to 96% while the specificity decreased to 68%. Inversely, when all three signs were observed, the specificity tended to 100% but with a poor sensitivity of 17%. US had high specificity for the diagnosis of gout in patients presenting with undifferentiated arthritis. Its sensitivity depends on which US signs are taken into account and the joints being assessed.

Keywords: Arthrocentesis, gout, ultrasonography, ultrasound, uric acid



How to cite this URL:
Miladi S, Boussaa H, Fazaa A, Sellami M, Zakraoui L, Abdelghani KB, Laatar A. Performance of ultrasonography in diagnosing gout. Indian J Rheumatol [Epub ahead of print] [cited 2022 Aug 20]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=349459




  Introduction Top


Gout is one of the most common inflammatory arthropathies. It is caused by deposition of monosodium urate (MSU) crystals in and around the joint. Its worldwide prevalence was estimated ranging from 0.5% to 4%, with an incidence up to 40%, over the last years in Western countries.[1]

Mobilization of MSU crystals induces acute attacks characterized by excruciating pain, redness and joint swelling, associated with marked release of pro-inflammatory cytokines.[1],[2]

Moreover, uncontrolled hyperuricemia can lead to the chronic tophaceous form known to be associated with important comorbidities, such as renal failure and cardiovascular disease, and an increased risk of mortality.[3],[4],[5],[6],[7] Thus, an appropriate diagnosis is necessary to treat as early as possible to control associated inflammation.

Gout can be suspected based on typical clinical and laboratory findings. However, the gold standard for definitive diagnosis is the detection of MSU crystals in the joint fluid using polarized light microscopy. Unfortunately, microscopes are not always available and arthrocentesis can be painful. Moreover, arthrocentesis is not always feasible particularly in case of a small amount of fluid or when performed in small joints such as the metatarsophalangeal joint (MTP1). Furthermore, the joint aspirate may not reveal MSU crystals in up to 25% of patients with gout.[8]

Recently, musculoskeletal ultrasonography (US) emerged as a helpful tool characterized by many advantages: noninvasive, inexpensive, accessible, reproducible, and well accepted by patients. This seductive imaging technique has attracted significant interest among rheumatologists in the last decades. Primarily, US was used to assess joint inflammation and bone damages in rheumatoid arthritis. Its sensitivity in the detection of synovial and cortical changes is well accepted and was shown to be superior to clinical and radiographic examination.[9]

In 2015, the ACR/EULAR classification criteria for gout incorporated newer imaging domains in addition to clinical and laboratory findings. These recommendations highlighted the utility of US in identifying MSU deposition and gave it an important support for the diagnostic evaluation in gout.[10] However, variable US abnormalities have been reported in studies using different definitions with no general consensus about what lesions should be identified in gout.[11] Recently, the OMERACT US task force group developed the first consensus-based US definitions of elementary gout lesions including tophus, double contour (DC), and aggregates.[12],[13]

However, it is still unclear how useful and accurate US is for the diagnosis of gout since most of studies have been performed in patients with established disease. This manuscript aimed to review the literature for evidence of US as a convenient diagnostic tool when compared with microscopic identification of MSU crystals in patients with suspected gout.


  Methods Top


Literature search

A systematic search was performed in PubMed database using the mesh terms: (1) “Gout” OR “arthritis, gouty” OR “uric acid” AND (2) “US” OR “ultrasonics” OR “ultrasound.”

Selection criteria

Studies were considered eligible for this systematic review if they responded to the following inclusion criteria: (a) examining the performance of US in the diagnosis of gout, (b) using a cross-sectional design performed in patients presenting with acute or chronic arthritis and with no history of gout, and (c) the diagnosis of gout was confirmed by microscopic identification of MSU crystals.

Articles not published in the English language, case reports, reviews, letters to editor, and nonhuman studies were excluded. The remaining articles were excluded if the title or abstract did not respond to our inclusion criteria. The selected manuscripts were carefully reviewed and excluded if they were not relevant to our goals. However, their references were reviewed to ensure the screening of all eligible studies.

Data extraction

The publication year, the study design, the cohort size, and the clinical presentation of patients were addressed.

Regarding US examination, the following items were extracted for analysis: qualification of sonographers, US mode, joints imaged, and features examined. The US elementary lesions of gout described in each study were collected and their diagnostic properties assessed: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

The OMERACT definitions for typical US signs of gout were taken as reference:[14] (1) Tophus: a circumscribed, inhomogeneous, hyperechoic, and/or hypoechoic aggregation (which may or may not generate posterior acoustic shadow), which may be surrounded by a small anechoic rim; (2) aggregates: heterogeneous hyperechoic foci that maintain their high degree of reflectivity, even when the gain setting is minimized or the insonation angle is changed and which occasionally may generate posterior acoustic shadow; (3) DC: abnormal hyperechoic band over the superficial margin of the articular hyaline cartilage, independent of the angle of insonation which may be either irregular or regular, continuous, or intermittent and can be distinguished from the cartilage interface sign.


  Results Top


Search results

As shown in [Figure 1], the search strategy identified 538 papers. We excluded case reports (n = 73), reviews (n = 65), systematic reviews (n = 9), meta-analyses (n = 4), editorials (n = 7), articles not published in the English language (n = 13), and studies not performed in humans (n = 15).
Figure 1: Flowchart of literature search

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After reading titles of the remaining manuscripts, 30 records were retained for screening. We included 7 articles[15],[16],[17],[18],[19],[20],[21] in the present systematic review after removal of abstracts (n = 19) and full-text manuscripts (n = 5) not responding to our inclusion criteria and searching in references for additional eligible studies (n = 1).

General characteristics of the selected studies

The studies included are listed in [Table 1] with the year of publication, the study design, the cohort size, and the clinical presentation of patients.
Table 1: Characteristics of included studies and participants

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[Table 2] provides information about the sonographer, the imaged joints, the US methodology, and its reproducibility.
Table 2: Modalities of ultrasonography examination

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The clinical presentation of patients was mentioned in all of the studies: acute mono or oligoarthritis in 4 studies,[15],[17],[20],[21] acute or chronic arthritis in 1 study,[18] mono or oligoarthritis of the lower limb in 1 study,[19] and at least one swollen joint in 1 study.[16]

Five studies carried out US on symptomatic joints[16],[17],[18],[19],[21] and 2 on symptomatic joints as well as some predefined sites.[15],[20] The predefined joints included knees, ankles and MTP1, or the contralateral side of the involved joint plus knees and MTP1 bilaterally.

The sonographers were rheumatologists in 2 studies,[15],[20] radiologist in 1 study,[17] either rheumatologist or radiologist in 1 study[16] and unspecified in the 3 other studies. The number of years of experience in musculoskeletal US was mentioned in 4 papers and it was ranging from 2 to 15.[17],[18],[20],[21] All the readers were blinded to the aspiration results.

Doppler activity was assessed in three studies.[15],[20],[21]

Ultrasonography findings

Double contour

The OMERACT definition of DC was used in three articles,[15],[16],[17] while it was described as urate crystals located at the surface of hyaline cartilage in one article,[18] as crystal deposition on the cartilage in one article,[19] and as hyperechoic line parallel to the bony articular surface in another article.[21] This sign was not defined in the remaining paper.[20]

After reviewing all the manuscripts, the sensitivity and specificity of US in detecting gout varied, respectively, from 42% to 87.8% and 64.1% to 97% for the DC sign, with a PPV up to 88%, and a NPV ranging between 55% and 91%.

Overall, DC was more frequently seen in patients with gout. However, Lamers-Karnebeek et al. showed that up to 21% in the nongout patient group could express DC.[15] This sign was also shown to be present in 8% of patients with calcium pyrophosphate crystal deposition disease (CPPD) in another study.[17]

DC was shown to be the second earliest sign to appear, after floating aggregates, with a median disease duration of 3.5 years (0.5–20) among patients with DC (P = 0.101).[19] Moreover, Ogdie et al. showed that the sensitivity of DC increased with increasing disease duration: 50.9% (41.1–60.7) in early disease (<2 years) versus 63.4% (57.7–68.8) in late disease (≥2 years) (P = 0.02).[16]

The first MTP1 was shown to be a frequent site of DC.[15],[20] Lamers-Karnebeek et al. found that 42% of patients with confirmed gout in another joint than MTP1 had also DC in MTP1. Furthermore, 86% of patients did not show the DC sign in any joint other than the MTP1 and the affected joints. Only 12% of patients who had MSU in MTP1 had also DC sign in another joint.[15]

Aggregates

This US sign was the most heterogeneously described. None of the manuscripts used the OMERACT definition. The term of aggregates was used in one article and defined as hyperechoic spots in the synovium,[17] while other studies used different terms such as “starry sky,”[18] “snowstorm appearance,”[15],[16] and “echogenic foci” in the synovial fluid.[19] Aggregates were not evaluated in one paper.[20]

The sensitivity and specificity of this US sign were, respectively, between 30.3% and 78.9% and 65% and 90.9%, with a PPV from 71% to 77.2% and NPV from 56.3% to 60%. This finding was also reported in 8% of patients with CPPD.[17]

The median disease duration was shown to be the shortest in patients with echogenic foci inside synovial fluid (2 years with and 5.5 years without echogenic foci, P = 0.003) suggesting that it could be a good marker of acute microcrystalline arthritis.[19]

Tophi

Tophi were assessed in five studies,[15],[16],[17],[19],[20] using the exact OMERACT definition in one of them[17] and similar definitions in the remaining papers.

The sensitivity of tophi in detecting gout was between 19% and 46%, and the specificity between 93% and 100%, with a PPV from 71% to 90% and NPV from 55% to 65.6%. None of the patients with nongout arthritis had shown a tophus on US.

Its sensitivity was higher among subjects with suspected tophus on examination compared to subjects without suspected clinical tophus (75.7% vs. 29.4%, P < 0.001) while specificity was lower (57.9% vs. 96.7%, P < 0.001).[16] In the same study, a positive association was found between US tophus and suspected clinical tophus (odds ratio [OR] = 7.47 [4.72–11.84]), current serum urate (OR = 1.22 [1.05–1.41]), and asymmetric swelling on radiographs (OR = 6.14 [3.93–9.60]).

A strong positive association was also noted between the presence of tophus and disease duration, as median disease duration was 12.5 years in patients with tophus versus 2 years in patients without tophus (P = 0.001).[19]

Accuracy of ultrasonography

In the included studies, the sensitivity for the diagnosis of gout was shown to increase up to 96% when any of these US features was present while its specificity decreased to 68%. The PPV and NPV were, respectively, up to 91% and 95%.

Pattamapaspong et al. showed that when all three signs were observed, the specificity tended to 100% but with a poor sensitivity of 17%. Inversely, when none of these features was present, the specificity of the correct prediction of nongouty arthritis was 100%. The PPV remained high with a NPV of 45%.[17]

Reliability of ultrasonography

Reliability was assessed in two papers.[15],[17] The percentage of interobserver agreement was overall bigger than 70% in the first study.[15] The second study assessed interobserver reliability of the readings. It showed substantial agreement for DC (k = 0.63) and tophi (k = 0.74) and moderate agreement for aggregates (k = 0.58).[17]


  Discussion Top


In the present systematic review, we included 7 studies with cross-sectional design performed in patients with suspected gouty arthritis and using microscopic analysis as the gold standard. To the best of our knowledge, this is the first systematic review including only the studies performed in patients in whom gout was not previously diagnosed.

In fact, the value of US in the diagnosis of gout is still unclear. The variability of US properties for the diagnosis of gout in the previous articles is probably due to the heterogeneity of the design of the studies, the US features and the definitions used to identify gout, the experience of sonographers, and the number and sites of the evaluated joints. Previous systematic reviews included patients with established diagnosis of gout which may have enhanced the results.

In most of the studies, the performance of US in the diagnosis of gout was evaluated using elementary lesions reported to be specific of gout: DC sign, aggregates, and tophi.

The DC sign was reported in all included studies. The OMERACT definition was used in three of these studies. The sensitivity and specificity of DC were up to 87.7% and 97%, respectively. However, this sign was also observed in 8% of patients with CPPD arthritis and up to 21% in another nongout group.[15],[17] According to authors, this might be explained by the short delay between onset of symptoms and performing US examination and the difficulty in distinguishing a DC from a normal picture at the beginning of the study.[15] Indeed, Ogdie et al. showed an increased sensitivity of DC with increasing duration of disease. A lower NPV was also noted with more trained sonographers.[16]

Tophi were evaluated in five studies using descriptions close to the OMERACT definition. This US sign showed the poorest sensitivity probably due to the short disease duration since most of the included patients presented with acute arthritis. As shown by Elsaman et al., tophi were the last to appear. A strong positive correlation was identified with the median disease duration.[19] This makes tophi poorly useful in the diagnosis of the first gout flares. However, it has the best specificity tending to 100% in two studies,[17],[19] suggesting that it could be a pathognomonic US sign of established gout.

A meta-analysis was published by Ogdie et al. including 11 studies that evaluated imaging modalities for the classification of gout. Among them, 7 examined US as an imaging tool for the diagnosis of gout. The pooled sensitivities of DC and tophus were 0.83 and 0.65, respectively.[22] It is higher than the results reported in the present study. This might be explained by the fact that most of the studies used a case–control design which may have overestimated the diagnostic properties (sensitivity and specificity). In our study, we included only cross-sectional studies performed in patients with no history of gout who presented with acute arthritis.

Aggregates were described using different definitions and terms which complicated the interpretation of the results. This sign did not have a high specificity for gout and its sensitivity was modest. Aggregates were also observed in cases with CPPD.[15],[17] Thereby, the predictive value of aggregates for gout will vary with subject's demographics and laboratory findings. Elsaman et al. identified echogenic foci in the synovial fluid as the earliest US sign to appear.[19] This could be useful in identifying gout at early stages of the disease.

The sensitivity of US for the diagnosis of gout increased when considering the presence of any of these signs but with a loss of specificity. When considering all three signs together, the specificity increased to 100%. Inversely, when none of these features was present, the diagnosis of nongouty arthritis could be positively predicted.[17]

After microscopic analysis, MSU crystals proven patients were enrolled in the case group, while CPP and no crystals patients were enrolled in the control group. Patients with both MSU and CPP crystals were included in the group of patients with confirmed gout. This might have enhanced the sensitivity of US for the diagnosis of gout with a suboptimal specificity since the two types of crystals can have the same sonographic appearance.[21],[23]

Recently, a systematic review and meta-analysis for the diagnostic performance of musculoskeletal US in gout were published by Zhang et al. including 13 studies with case–control or cross-sectional design. In this study, the authors differentiated data of person-based evaluations from joint-based evaluations. In the person-based evaluations, the pooled sensitivities and specificities for the diagnosis of gout were, respectively, 0.66 (95% confidence interval [CI]: 0.62–0.69) and 0.92 (95% CI: 0.89–0.94) for DC, 0.56 (95% CI: 0.52–0.60) and 0.94 (95% CI: 0.92–0.96) for tophi, 0.31 (95% CI: 0.27–0.36) and 0.91 (95% CI: 0.88–0.93) for the snowstorm sign, and 0.80 (95% CI 0.76–0.83) and 0.83 (95% CI 0.79–0.86) when considering the US features simultaneously. In the joint-based evaluations, the pooled sensitivities and specificities for the diagnosis of gout were, respectively, 0.75 (95% CI 0.68–0.80) and 0.65 (95% CI 0.59–0.70) for DC and 0.48 (95% CI 0.40–0.57) and 0.96 (95% CI 0.91–0.99) for tophi.[24] These data are consistent with our results showing high specificities of the three US features for gout and relatively low sensitivities. This implies that the absence of one of these signs does not exclude the possibility of gout.

Another meta-analysis published by Lee and Song confirmed that US signs of tophus, snowstorm, or bony erosion besides the DC sign were not sensitive (54.3%, 30.8%, and 51.6%) but specific (93.2%, 90.6%, and 93.3%) enough as a diagnostic tool.[25]

Bone changes and Doppler activity were recorded in some of the studies,[15],[19],[20],[21] but they were not relevant for the diagnosis since their lack of specificity. However, Löffler et al. showed that 77% of gouty joints showed hyper vascularization of degree 2 or higher in contrast to 66% in CPPD and 46% in noncrystal-related inflammatory arthropathies. The degree of hypervascularization was significantly associated with gout (OR 1.93, P < 0.01, 95% CI: 1.16–3.20).[21]

US was performed by either radiologists or rheumatologists with prior training to musculoskeletal US and blinded to the microscopic results. The most commonly examined joints were the knees, MTP joints, and ankles, either they were symptomatic or not.

As shown by Zufferey et al., the sensitivity of US was relatively poor when the analysis was limited to the target joints. The authors found that the first MTP joint was the most common site for US gout features, followed by the knee and the ankle. By including these specific sites, the sensitivity of US increased but on penalty of loss of specificity.[20]

This approach has been confirmed by Naredo et al. suggesting that US should not be limited to target joints only.[26] In a recent study published by Bhadu et al., the sensitivity and specificity of DC at knee, MTP1, and tibiotalar joints for diagnosing gout were 53.2% and 94%, 51.1% and 84%, and 40.5% and 100%, respectively. These authors showed that US imaging of the two most commonly involved joints (MTP1s and knees) was as useful as the six site imaging strategy of Naredo et al. All the patients who had any US finding on six sites examination also had findings on two sites examination.[27] However, there is no consensus on which sites should be systematically examined.

US was confronted to other imaging modalities in two of the included studies. Zufferey et al. confirmed the poor sensitivity and NPV of X-ray imaging of the symptomatic joints in patients with gout. When assessing additional asymptomatic joints, the sensitivity and specificity of X-rays remained unsatisfying. This makes US much more useful for gout diagnosis.[20] Moreover, Gruber et al. showed that US had comparable results with dual-energy computed tomography in patients suspected with gout, with the advantages of lower cost and lack of radiation exposure.[18]

The strengths of this systematic review consisted in the inclusion of cross-sectional studies performed in patients suspected with gouty arthritis. MSU crystals identification was used as the standard reference for comparison of US properties. One other strength was the exclusion of studies examining patients with asymptomatic hyperuricemia to avoid any confusion with this particular entity.

Its limitations were the lack of papers that responded to our inclusion criteria, the heterogeneity in terminology used to describe US abnormalities in gout making their comparison challenging, and the absence of standardization of the joints to be assessed. The most symptomatic joints were not necessarily the most frequently affected joints such as the first MTP1. Moreover, the joint examined by US may not have been the joint where the physician performed the arthrocentesis because of its small size. Another limitation was the variability of the sonographer's training with possible test interpretation bias.


  Conclusion Top


In conclusion, US had high specificity for the diagnosis of gout in patients with acute or chronic arthritis in whom gout was suspected. Its sensitivity depends on which US signs are taken into account and the joints being assessed. US may be a useful tool in the early diagnosis of gout, especially in patients presenting with typical US findings such as aggregates and DC. It can also help to eliminate the diagnosis when none of the US signs is present. However, joints to assess are still debated and need to be standardized.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Scirè CA, Rossi C, Punzi L, Genderini A, Borghi C, Grassi W. Change gout: How to deal with this “silently-developing killer” in everyday clinical practice. Curr Med Res Opin 2018;34:1411-7.  Back to cited text no. 1
    
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Fraile JM, Torres RJ, de Miguel ME, Martínez P, Lundelin KJ, Vázquez JJ, et al. Metabolic syndrome characteristics in gout patients. Nucleosides Nucleotides Nucleic Acids 2010;29:325-9.  Back to cited text no. 3
    
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Krishnan E, Svendsen K, Neaton JD, Grandits G, Kuller LH, MRFIT Research Group. Long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med 2008;168:1104-10.  Back to cited text no. 4
    
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Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Circulation 2007;116:894-900.  Back to cited text no. 5
    
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Kuo CF, See LC, Luo SF, Ko YS, Lin YS, Hwang JS, et al. Gout: An independent risk factor for all-cause and cardiovascular mortality. Rheumatology (Oxford) 2010;49:141-6.  Back to cited text no. 6
    
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Perez-Ruiz F, Martínez-Indart L, Carmona L, Herrero-Beites AM, Pijoan JI, Krishnan E. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis 2014;73:177-82.  Back to cited text no. 7
    
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Swan A, Amer H, Dieppe P. The value of synovial fluid assays in the diagnosis of joint disease: A literature survey. Ann Rheum Dis 2002;61:493-8.  Back to cited text no. 8
    
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Mandl P, Naredo E, Wakefield RJ, Conaghan PG, D'Agostino MA, OMERACT Ultrasound Task Force. A systematic literature review analysis of ultrasound joint count and scoring systems to assess synovitis in rheumatoid arthritis according to the OMERACT filter. J Rheumatol 2011;38:2055-62.  Back to cited text no. 9
    
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Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, et al. 2015 Gout classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2015;74:1789-98.  Back to cited text no. 10
    
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Mathieu S, Pereira B, Couderc M, Soubrier M. Usefulness of ultrasonography in the diagnosis of gout: A meta-analysis. Ann Rheum Dis 2013;72:e23.  Back to cited text no. 11
    
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Terslev L, Gutierrez M, Christensen R, Balint PV, Bruyn GA, Delle Sedie A, et al. Assessing Elementary Lesions in Gout by Ultrasound: Results of an OMERACT patient-based agreement and reliability exercise. J Rheumatol 2015;42:2149-54.  Back to cited text no. 12
    
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Gutierrez M, Schmidt WA, Thiele RG, Keen HI, Kaeley GS, Naredo E, et al. International Consensus for ultrasound lesions in gout: Results of Delphi process and web-reliability exercise. Rheumatology (Oxford) 2015;54:1797-805.  Back to cited text no. 13
    
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Bruyn GA, Iagnocco A, Naredo E, Balint PV, Gutierrez M, Hammer HB, et al. OMERACT definitions for ultrasonographic pathologies and elementary lesions of rheumatic disorders 15 years on. J Rheumatol 2019;46:1388-93.  Back to cited text no. 14
    
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Lamers-Karnebeek FB, Van Riel PL, Jansen TL. Additive value for ultrasonographic signal in a screening algorithm for patients presenting with acute mono-/oligoarthritis in whom gout is suspected. Clin Rheumatol 2014;33:555-9.  Back to cited text no. 15
    
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Ogdie A, Taylor WJ, Neogi T, Fransen J, Jansen TL, Schumacher HR, et al. Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison with monosodium urate monohydrate crystal analysis as the gold standard. Arthritis Rheumatol 2017;69:429-38.  Back to cited text no. 16
    
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Pattamapaspong N, Vuthiwong W, Kanthawang T, Louthrenoo W. Value of ultrasonography in the diagnosis of gout in patients presenting with acute arthritis. Skeletal Radiol 2017;46:759-67.  Back to cited text no. 17
    
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Gruber M, Bodner G, Rath E, Supp G, Weber M, Schueller-Weidekamm C. Dual-energy computed tomography compared with ultrasound in the diagnosis of gout. Rheumatology (Oxford) 2014;53:173-9.  Back to cited text no. 18
    
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Elsaman AM, Muhammad EM, Pessler F. Sonographic findings in gouty arthritis: Diagnostic value and association with disease duration. Ultrasound Med Biol 2016;42:1330-6.  Back to cited text no. 19
    
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Zufferey P, Valcov R, Fabreguet I, Dumusc A, Omoumi P, So A. A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis. Arthritis Res Ther 2015;17:188.  Back to cited text no. 20
    
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Löffler C, Sattler H, Peters L, Löffler U, Uppenkamp M, Bergner R. Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides. J Rheumatol 2015;42:513-20.  Back to cited text no. 21
    
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Ogdie A, Taylor WJ, Weatherall M, Fransen J, Jansen TL, Neogi T, et al. Imaging modalities for the classification of gout: Systematic literature review and meta-analysis. Ann Rheum Dis 2015;74:1868-74.  Back to cited text no. 22
    
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Grassi W, Meenagh G, Pascual E, Filippucci E. “Crystal clear”-sonographic assessment of gout and calcium pyrophosphate deposition disease. Semin Arthritis Rheum 2006;36:197-202.  Back to cited text no. 23
    
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Zhang Q, Gao F, Sun W, Ma J, Cheng L, Li Z. The diagnostic performance of musculoskeletal ultrasound in gout: A systematic review and meta-analysis. PLoS One 2018;13:e0199672.  Back to cited text no. 24
    
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Lee YH, Song GG. Diagnostic accuracy of ultrasound in patients with gout: A meta-analysis. Semin Arthritis Rheum 2018;47:703-9.  Back to cited text no. 25
    
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Naredo E, Uson J, Jiménez-Palop M, Martínez A, Vicente E, Brito E, et al. Ultrasound-detected musculoskeletal urate crystal deposition: Which joints and what findings should be assessed for diagnosing gout? Ann Rheum Dis 2014;73:1522-8.  Back to cited text no. 26
    
27.
Bhadu D, Das SK, Wakhlu A, Dhakad U, Sharma M. Ultrasonographic detection of double contour sign and hyperechoic aggregates for diagnosis of gout: Two sites examination is as good as six sites examination. Int J Rheum Dis 2018;21:523-31.  Back to cited text no. 27
    


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