Abstract
While joint aspiration and crystal identification by polarizing microscopy remain the gold standard for diagnosing tophaceous gout, agreement among medical and ancillary health personnel examining synovial fluid using polarizing microscopy for the detection of monosodium urate (MSU) crystals appears to be poor. Imaging modalities, including conventional radiography (CR), ultrasonography (US), magnetic resonance imaging (MRI), and dual-energy computed tomography (DECT), have been found to provide information on the deposition of MSU crystals in tissues, and the consequences of such deposition. CR can demonstrate typical “punched out lesions” with marginal overhangs, but the sensitivity for erosion detection is better for DECT and US. US is inexpensive and can identify tophus deposition in and around joints, erosions, and tissue inflammation if power Doppler US is used. MRI can show tophi, bone marrow edema, and inflammation, but MRI findings of tophi may be nonspecific. DECT can identify and color-code tophaceous material, and provide an overview of the tophus burden of a joint area. Because of the lower number of available studies, the strength of evidence for the newer imaging can be improved through further research.
Introduction
Gout is a common crystal-associated arthropathy, and epidemiologic data suggest that its incidence is increasing . Gouty arthritis develops in the setting of hyperuricemia (serum uric acid > 6.8 mg/dl). Several risk factors are associated with gout, including dietary habits, use of alcoholic beverages, obesity, hypertension, hypertriglyceridemia, and renal impairment . It manifests in both acute and chronic forms. Clinically, acute gout manifests as a recurrent, self-limiting severe inflammatory arthritis. In the chronic form, the aggregates of monosodium urate (MSU) crystals (also known as tophi) deposit in and around the joints, causing bone and joint destruction. If treated properly, flares of acute gouty arthritis can be prevented and joint damage due to tophi formation can be minimized. Therefore, a timely diagnosis of gout is essential to prevent patient morbidity .
Currently, the gold standard diagnosis of gout is based on the direct microscopic visualization of intracellular MSU crystals in the synovial fluid of affected joints. This requires performing an arthrocentesis of the affected joint, which sometimes is technically challenging and, in the case of periarticular inflammation, not feasible.
Advanced imaging techniques, such as ultrasonography (US), magnetic resonance imaging (MRI), and dual-energy computed tomography (DECT), have gained an essential role in the field of gout in recent years. The 2015 gout classification criteria developed by the American College of Rheumatology (ACR) in collaboration with the European League Against Rheumatism (EULAR) have included imaging modalities as a method to identify urate deposition in joints or bursa (US and DECT) or to identify gout-related joint damage conventional radiography (CR) . The Outcome Measures in Rheumatology (OMERACT) gout working group has defined three domains for imaging in gout studies: urate deposition, joint inflammation, and structure joint damage , as shown in Table 1 . Hence, imaging studies are not only important in helping to establish a diagnosis of gout, but they also play an important role in monitoring disease progression and response to treatment.
| Urate deposition | Structural damage | Joint inflammation |
|---|---|---|
| X-ray | X-ray | X-ray |
| Conventional CT | Conventional CT | Conventional CT |
| DECT | DECT | DECT |
| MRI | MRI | MRI |
| Ultrasound | Ultrasound | Ultrasound |
In this article, we will review the utility of conventional radiography (CR) as well as US, MRI, and DECT in gout and discuss the clinical and research utilities of the different imaging modalities.
Conventional radiography
CR has been used for the diagnosis and assessment of gouty arthritis for more than 120 years. In the early stages of the disease, during an acute gout attack, no osseous changes are present, but signs of joint swelling and effusion can be identified on plain radiographs by bulging soft tissue contours. Later in the course of the disease, tophaceous deposits may cause an increase in the radiodensity of periarticular tissues.
The most characteristic findings in the advanced stages of gouty arthritis are well-defined deep bony erosions with sharp overhanging edges and a sclerotic rim. This typical appearance is presumably caused by intra- or periarticular MSU deposits, leading to the activation of inflammatory cells, which in turn activate osteoclastic degradation of the neighboring bone tissue ( Fig. 1 ). This is supported by DECT, showing that frequently MSU deposits are located within those cavities of gout erosions . The typical appearance of those “punched-out” erosions in the paleobiologic specimens even led to the hypothesis that, already 65 million years ago, the carnivoric Tyrannosaurus rex may have been affected by gout . Another characteristic finding in CR in tophaceous gout is the presence of intraosseous cysts not corresponding to the joint space as a consequence of the formation and growth of intramedullary tophi.
In the 2015 gout classification criteria of the ACR and the EULAR, the presence of one “cortical break with sclerotic margin and overhanging edge” in radiographs of hands or feet represents a criterion as strongly supportive for the classification of gouty arthritis as the presence of clinically visible tophi . However, since the tophus formation usually occurs a few years after the first symptoms of gout, CR is not helpful for an early diagnosis. Therefore, other imaging modalities have been developed in recent years, which have a much higher sensitivity for the detection of a gout-specific pathology in early disease.
Conventional radiography
CR has been used for the diagnosis and assessment of gouty arthritis for more than 120 years. In the early stages of the disease, during an acute gout attack, no osseous changes are present, but signs of joint swelling and effusion can be identified on plain radiographs by bulging soft tissue contours. Later in the course of the disease, tophaceous deposits may cause an increase in the radiodensity of periarticular tissues.
The most characteristic findings in the advanced stages of gouty arthritis are well-defined deep bony erosions with sharp overhanging edges and a sclerotic rim. This typical appearance is presumably caused by intra- or periarticular MSU deposits, leading to the activation of inflammatory cells, which in turn activate osteoclastic degradation of the neighboring bone tissue ( Fig. 1 ). This is supported by DECT, showing that frequently MSU deposits are located within those cavities of gout erosions . The typical appearance of those “punched-out” erosions in the paleobiologic specimens even led to the hypothesis that, already 65 million years ago, the carnivoric Tyrannosaurus rex may have been affected by gout . Another characteristic finding in CR in tophaceous gout is the presence of intraosseous cysts not corresponding to the joint space as a consequence of the formation and growth of intramedullary tophi.
In the 2015 gout classification criteria of the ACR and the EULAR, the presence of one “cortical break with sclerotic margin and overhanging edge” in radiographs of hands or feet represents a criterion as strongly supportive for the classification of gouty arthritis as the presence of clinically visible tophi . However, since the tophus formation usually occurs a few years after the first symptoms of gout, CR is not helpful for an early diagnosis. Therefore, other imaging modalities have been developed in recent years, which have a much higher sensitivity for the detection of a gout-specific pathology in early disease.
Ultrasonography
Ultrasound assessment of gout has been studied for over a decade. Among the imaging options, US is typically a point-of-care modality in rheumatologists’ offices and in emergency departments, and is a routine study in the radiologists’ office as well. If a US assessment is performed at the bedside, it can provide immediate information and help direct appropriate patient care. Advantages of US include its short examination time, low cost, lack of ionizing radiation, immediacy of results, and ubiquitous availability. Serial measurement of tophus size allows for an assessment of the treatment response.
Ultrasound – background
Ultrasound transducers send soundwaves into tissues, and these are in part reflected, in part transmitted further into deeper tissues, depending on their physical properties. The tissues or substances that contain little reflecting matter, such as synovial fluid, appear anechoic or black, and the calcium-rich tissues, such as cortical bone, strongly reflect sound waves and appear hyperechoic, or bright on the screen.
Gout – features detectable by US
Ultrasonography can detect tophaceous deposits in and around joints, bursae, tendons, and other tissues. Strictly intra-osseous tophi cannot be seen, as musculoskeletal US does not penetrate the bony cortex. In addition, US can appreciate the structure and composition of MSU tophi, their anatomic relationship to adjacent structures (such as bony erosions), and identify associated inflammation, if power Doppler US is used.
The three-dimensional reconstruction of US images can measure the tophus volume, and serial imaging can document the changes in tophus size with treatment.
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Tophi
MSU tophus complexes consist of packed crystals that are in vivo surrounded by a corona of inflammatory cells, and this compound can be embedded in vascularized fibrous tissue . These features can be seen sonographically . The crystalline tophus appears bright and hyperechoic when compared to surrounding fibrous tissue. Within joint recesses and bursae, crystalline tophi can assume an ovoid shape. While MSU crystals or small crystal aggregates strongly reflect sound waves, the packing of crystals in tophi allows for other sound waves to penetrate the tophus, and the tissue deep in the tophus can be appreciated as well. Very large tophi may attenuate the sound waves such that lower frequencies may need to be tried for a complete assessment.
Sonographically, MSU tophi can be found most readily in the areas of dynamic mechanical stress, fostering precipitation of crystals from the hypersaturated solution . This includes, in particular, the medial aspect of the first metatarsal head, where tophi may be mistaken for bunions, the distal Achilles’ tendon, proximal patellar ligament, and prepatellar and olecranon bursae. Tendon involvement is common in tophaceous gout, and US can typically distinguish calcified enthesophytes from gout ( Fig. 2 ). For the sonographic tophus assessment in tendons, a sensitivity and specificity of 69.6 and 92%, respectively, were found . Tophi can also be seen readily in the dorsal recesses of metatarsophalangeal joints and interphalangeal joint of toes and fingers. Tophi and the associated tissue can be appreciated within bony erosions, often with typical marginal overhangs.
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Tophus-associated tissue
The three components of the tophus complex – crystals, cellular corona, and fibrovascular matrix – have distinct sonographic characteristics. The cellular corona can be seen as an anechoic rim surrounding the hyperechoic crystalline core. The fibrovascular matrix tissue appears hypoechoic when compared with crystalline core or bone, and vascularity can be seen using power or color Doppler US ( Figs. 3 and 4 ).
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Double-contour sign
MSU crystals can precipitate on the articular surface of hyaline cartilage. This precipitate forms a hyperechoic, bright band that parallels the hyperechoic bony cortex, forming a “double contour” of hyperechoic bone, intervening dark, anechoic, or hypoechoic hyaline cartilage, and bright-appearing MSU deposits ( Fig. 5 ).
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Bony erosions
Ultrasonography, together with CT scanning, may be best suited to detect typical bony erosions of gout, forming “punched-out” cortical defects with marginal overhangs. Sonography may also show the erosion-associated tophaceous material, and tissue hyperemia ( Fig. 6 A, B and C).
An OMERACT US gout task force group has developed preliminary definitions for elementary US lesions in gout ( Table 2 ).
| OMERACT US elementary lesion in gout | Consensus definition |
|---|---|
| Double contour | Abnormal hyperechoic band over the superficial margin of the articular hyaline cartilage, independent of the angle of insonation and which may be either irregular or regular, continuous or intermittent, and can be distinguished from the cartilage interface sign |
| Tophus [independent of location (e.g. extraarticular/intraarticular/intratendinous)] | 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 |
| Aggregates [independent of location (intraarticular/intratendinous)] | 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 |
| Erosion | An intra- and/or extraarticular discontinuity of the bone surface (visible in two perpendicular planes) |
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