Role of Ultrasound and Other Advanced Imaging in the Diagnosis and Management of Gout

Imaging of gout with conventional radiography has been described since shortly after roentgenography was invented. Ultrasound (US) detects more erosions than conventional radiography in rheumatoid arthritis, and the same seems to be true for gout. MRI is being used to assess articular and periarticular masses, including gouty tophi. However, MRI findings in gout can lack specificity. Monosodium urate (MSU) tophi are very echogenic when US is used. Typical US features of gout include a double-contour sign or “urate icing.” The double-contour consists of the hyperechoic bony contour and a parallel hyperechoic line of MSU crystals that deposit on the hypoechoic or anechoic hyaline cartilage. Tophi can have a “wet clumps of sugar” appearance, often surrounded by an anechoic halo. Tophi are closely related to the formation of erosions. If serum urate levels are lowered consistently below 6.0 mg/dL, the disappearance of MSU crystals can be observed sonographically.     

Ultrasonographic measurement of tophi as an outcome measure for chronic gout

OBJECTIVE: To validate the usefulness of measuring tophi with ultrasonography (US) as an outcome measure for chronic tophaceous gout. METHODS: Patients with crystal-proven gout were included. To evaluate validity, intraarticular and articular deep tophi were evaluated with both magnetic resonance imaging (MRI) and US. Tophi were punctured with US guidance to evaluate face validity. Interobserver and intraobserver measurement studies were done to evaluate reliability, and to estimate the smallest detectable difference. Sensitivity to change was evaluated with a 12-month followup observational study of urate-lowering therapy. RESULTS: US detected at least one tophus in all joints where MRI found nodules considered to be tophi. There was a good correlation, but just fair agreement between measurements with US and MRI. Puncture of nodules suspected of being tophi recovered urate crystals in 83% of the procedures. Intraobserver intraclass correlation was > 0.90 for diameters and volume, while it was 0.71 to 0.83 in the interobserver study. US was found to be sensitive to change, and there was an inverse correlation between serum urate concentrations and change from baseline measurement of tophi. CONCLUSION: US measurement of tophi fulfilled the OMERACT filter for an outcome measure, although it should be tested further in randomized clinical trials.     

Limited knee joint range of motion due to invisible gouty tophi

OBJECTIVES: Tophi deposits are a well-known cause of joint destruction, gouty nephropathy and spinal cord compression. This study reports another major complication of gout, namely tophi deposition causing limited knee joint excursion. METHODS: Seven gout patients with limited knee joint excursion owing to tophi deposition were studied to reveal clinical features and magnetic resonance imaging (MRI) findings. None of the patients were able to assume a full squatting posture. RESULTS: No patients had visible subcutaneous tophi over the knee joints, except for one case in which a pea-sized subcutaneous tophus was noted. Additionally, two patients even lacked visible tophi elsewhere. All knee problems in the study group were initially regarded as being due to degenerative or other internal derangements, but MRI unexpectedly revealed multiple tophaceous depositions within and around the joint. CONCLUSIONS: Intra-articular and periarticular tophi limiting knee joint range of motion are a rare but important cause of walking disability in gout patients. Although most patients do not display visible subcutaneous tophi over the knee on physical examination, the differential diagnosis should consider intra-articular tophi and MRI is valuable in this clinical setting.     

Tophaceous deposition in the finger pads without gouty arthritis

Tophi are rarely observed in patients without a prior history of gouty arthritis. We describe four patients whose initial manifestation of gout was tophaceous deposition in an unusual location, the finger pad. None of these patients had a history of acute gouty arthritis and none had tophi elsewhere. All four patients were postmenopausal women with decreased renal function; all were taking diuretics. We conclude that tophaceous gout without arthritis may be more common than previously recognized and that tophi may deposit in the finger pad. We recommend prompt aspiration and crystal analysis of white subcutaneous finger pad deposits in hyperuricemic patients even without a history of gouty arthritis.     

Tophaceous gout: quantitative evaluation by direct physical measurement

OBJECTIVE: The absence of accepted standardized methods for monitoring tophaceous gout limits the ability to track tophus progression or regression. This multicenter study assessed intra- and interrater reproducibility of a simple and direct physical measurement. METHODS: The quantitative evaluation was the area (mm2) of each measurable tophus and was determined independently by 2 raters on 2 occasions within 10 days. Intra- and interrater reproducibilities were determined by calculating mean differences and average percentage differences (APD) in measurements of areas for the same tophus at each of 2 visits and by each rater, respectively. RESULTS: Fifty-two tophi were measured in 13 subjects: 22 on the hand/wrist, 16 on the elbow, and 14 on the foot/ankle. The mean (+/- SD) difference in tophus areas between visits was -0.2 +/- 835 mm2 (95% CI -162 to 162 mm2) and the mean (+/- SD) APD was 29% +/- 33%. The mean (+/- SD) APD between raters was 32% +/- 27%. The largest variations in measurements were noted for elbow tophi and variations were least for well demarcated tophi on the hands. CONCLUSION: This simple and reproducible method can be easily utilized in clinical trials and in practice as a measure of efficacy of urate-lowering treatment in tophaceous gout. Among factors contributing to variability in these measurements were the anatomic site of tophi and rater experience with the method. Restriction of measurements to well circumscribed hand or foot tophi could improve reliability, but major changes, as expected with effective therapy, can clearly be documented with this simple technique.     

Rheumatoid nodulosis: report of two new cases and discussion of diagnostic criteria

Two patients with typical rheumatoid nodulosis are described and compared with 24 reported cases. Rheumatoid nodulosis is a particular variant of rheumatoid arthritis associated with palindromic rheumatism, subcutaneous rheumatoid nodules, mild or no systemic manifestation and a benign clinical course. Positive rheumatoid factor and radiologic subchondral bone cysts are usual, but their absence should not eliminate the diagnosis of rheumatoid nodulosis, particularly at the onset of the disease.     

Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features

The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.     

Rheumatoid nodulosis: report of a case with evidence of intraosseous rheumatoid granuloma

We describe a patient who had multiple subcutaneous rheumatoid nodules associated with episodes of acute intermittent arthritis and subchondral cystic lesions of the small bones of the hands and feet; this condition is termed "rheumatoid nodulosis." The patient had a cystic lesion in communication with the joint cavity, rheumatoid granulomas, and evidence of a central zone of necrosis opening toward the joint space. His case is compared with 8 previously reported cases, and possible etiologies of the subchondral bone cyst formation in rheumatoid nodulosis are discussed.     

Palindromic rheumatism with rheumatoid nodules: a case report with ultrastructural studies.

Rheumatoid nodules developed on the finger tips of a patient with palindromic rheumatism. The patient had no bone cysts or erosions and had no rheumatoid factor. A light microscopic and ultrastructural study of a nodule showed a necrotic centre with fibrin, collagen, and granular material surrounded by large histiocytes, fibrocytes, lymphocytes, and vessels with adjacent mast cells as has been seen with nodules in classical rheumatoid arthritis (RA). We describe the first immunoperoxidase studies on a rheumatoid nodule and have identified reaction products for immunoglobulins and C3 in perivascular and endothelial cell vacuoles and in the necrotic centre.     

Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules

Summary The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.     

A subset of systemic lupus erythematosus with progressive cystic bone lesions.

Clinical and serological findings of 16 patients with systemic lupus erythematosus (SLE) who had progressive cystic bone lesions were compared with a control group of 19 patients with SLE without radiological evidence of bone cysts. Central nervous system manifestations, synovitis, and other radiologically observed skeletal abnormalities were more prevalent in the patients with cysts than in the control group. Higher concentrations of C reactive protein, and a greater incidence of rheumatoid factor positivity were seen in the patients with cysts than in the control patients, but no other serological differences were found. It is suggested that patients with SLE with progressive cystic lesions form a subgroup of the syndrome characterised by an increased acute phase reaction.     

Benign rheumatoid nodules in a woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy.

OBJECTIVES--To report benign rheumatoid nodules in a woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy and to summarise the features of the patients with adult onset benign rheumatoid nodules. METHODS--A 66 year old woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy who presented with subcutaneous elbow nodules, which were at first suspected to represent either progression of her haematological disease or leprosy, is described. The clinical characteristics of our patient and previous reports of another 24 subjects with adult onset benign rheumatoid nodules are reviewed. RESULTS--Biopsy of the patient's subcutaneous lesion disclosed the histopathology of a rheumatoid nodule; serological and clinical evaluations for rheumatoid arthritis and other rheumatoid nodule associated systemic diseases were negative. Adult onset benign rheumatoid nodules are clinically and histologically identical to those found in patients with rheumatoid arthritis. They often appeared in women during their 20s, frequently resolved spontaneously or were adequately treated by excision, and recurred in about one third of patients. The lesions were located in the ocular adnexa in 60% of patients. The most common lesional sites in patients with non-ocular benign rheumatoid nodules were the elbows, feet, and knees. None of these patients subsequently developed rheumatoid arthritis or other rheumatoid nodule associated diseases during follow up periods of as long as 20 years. CONCLUSION--The appearance of subcutaneous nodules is often the harbinger of an associated systemic disorder. Although benign rheumatoid nodules occur infrequently in adults, they should be considered in the differential diagnosis of new nodular lesions.     

Imaging of tophaceous gout: computed tomography provides specific images compared with magnetic resonance imaging and ultrasonography

OBJECTIVE: To determine the usefulness of computed tomography (CT), magnetic resonance imaging (MRI), and Doppler ultrasonography (US) in providing specific images of gouty tophi. METHODS: Four male patients with chronic gout with tophi affecting the knee joints (three cases) or the olecranon processes of the elbows (one case) were assessed. Crystallographic analyses of the synovial fluid or tissue aspirates of the areas of interest were made with polarising light microscopy, alizarin red staining, and x ray diffraction. CT was performed with a GE scanner, MR imaging was obtained with a 1.5 T Magneton (Siemens), and ultrasonography with colour Doppler was carried out by standard technique. RESULTS: Crystallographic analyses showed monosodium urate (MSU) crystals in the specimens of the four patients; hydroxyapatite and calcium pyrophosphate dihydrate (CPPD) crystals were not found. A diffuse soft tissue thickening was seen on plain radiographs but no calcifications or ossifications of the tophi. CT disclosed lesions containing round and oval opacities, with a mean density of about 160 Hounsfield units (HU). With MRI, lesions were of low to intermediate signal intensity on T(1) and T(2) weighting. After contrast injection in two cases, enhancement of the tophus was seen in one. Colour Doppler US showed the tophi to be hypoechogenic with peripheral increase of the blood flow in three cases. CONCLUSION: The MR and colour Doppler US images showed the tophi as masses surrounded by a hypervascular area, which cannot be considered as specific for gout. But on CT images, masses of about 160 HU density were clearly seen, which correspond to MSU crystal deposits.     

Aortic valve incompetence and replacement in rheumatoid arthritis.

Five cases of aortic incompetence and nodular seropositive rheumatoid arthritis are presented. Four cases underwent aortic valve replacement. Two of these had granulomatous involvement of the aortic cusps similar to subcutaneous rheumatoid nodules, and another showed a nonspecific fibrosis. One case had definite coincidental rheumatic aortic and mitral heart disease. Two patients had undergone pericardectomy previously for constrictive pericarditis. Good results were obtained in all four operated cases and cardiac surgery enabled continuation of rehabilitation for the rheumatoid arthritis, including major orthopaedic procedures. A review of 22 cases from the literature with rheumatoid granulomata within the aortic valve shows that they are associated with mitral valve granulomata in 63-6%. Congestive cardiac failure was found in 75%. Macroscopical evidence of aortic incompetence was seen in 36-8% and of aortic stenosis in 15-8%. Associated pericarditis occurred in 59-1%, which was severe or complicated in 13.6%. The associated arthritis was severe in 77-8% with subcutaneous nodules (71-5%), rheumatoid factor (83-6%), and episcleritis (66-6%). From these cases and a review of the literature the following points are emphasized. (1) Both the granulomatous and nonspecific aortic valvulitis of rheumatoid arthritis may result in significant haemodynamic abnormality. (2) The valve lesions found are often clinically and macroscopically indistinguishable from rheumatic valve lesions. (3) Granulomata, when present, are usually found in the valve cusp or ring and only occasionally in the aortic wall. (4) Associated joint disease, although usually severe, may be mild. (5) The valve lesion may be accompanied by a severe pericardial involvement--either tamponade or constriction. (6) Aortic valve replacement for aortic incompetence in rheumatoid arthritis is both feasible and worthwile, despite severe joint disease.     

Multimodality imaging of chronic tophaceous gout

The diagnosis of gout is usually based on clinical presentation and laboratory findings. Imaging plays a role in the assessment and grading of articular damage related to chronic, long-standing disease, which is characterized by granulomatous synovitis, tophi, and erosions. Multimodality imaging of chronic tophaceous gout may be useful in clinical practice for a variety of purposes, including assessment of disease-related anatomical changes and monitoring of articular and soft-tissue lesions over time, especially in response to urate-lowering therapy. Radiography remains the primary imaging technique. Ultrasonography may detect monosodium urate crystals on cartilage, is helpful to assess small joint effusion, to guide to joint aspiration, and to evaluate the volume of tophi. Computed tomography is considered to be more sensitive than plain radiography in the detection and evaluation of cortical bone erosions associated with tophi. MRI represents the only imaging modality which provides visualization of bone marrow oedema associated with erosions and may be useful to characterize and distinguish tophi from other soft tissue nodules.     

Musculoskeletal ultrasound including definitions for ultrasonographic pathology

Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis.     

Absence of Epstein-Barr virus carrying cells in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis.

OBJECTIVES--To determine whether the Epstein-Barr virus is present in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis. METHODS--A sensitive in situ hybridisation technique was applied to tissue sections of 11 synovial membranes and five rheumatoid nodules. RESULTS--Cells carrying the Epstein-Barr virus were not detected using EBER and BHLF1 oligonucleotides in the tissue samples investigated here. CONCLUSIONS--Although it has been suggested that the Epstein-Barr virus could play a part in the aetiology of rheumatoid arthritis, it was not detected in synovial membranes and subcutaneous lesions in this study.     

Parathyroid incidentaloma discovered during thyroid ultrasound imaging

We report two patients with incidentally discovered enlarged parathyroid glands while performing neck ultrasonography (US) for thyroid nodules. The parathyroid masses were seen as hypoechoic, homogeneous, oval nodules, separated from the thyroid gland. Both patients were completely asymptomatic, although subclinical evidence of hyperparathyroidism (serum PTH and calcium levels in the upper limit of the normal range, increased ionized serum calcium, osteocalcin, urinary calcium and hydroxyproline) was subsequently found in one patient. An enhanced uptake on sesta-MIBI scinti scan was concordant with the US finding in the two cases. PTH levels in the wash-out from the US-guided fine needle aspiration biopsy, confirmed the parathyroid origin of the lesions. Cytology and immunocytochemistry were, in our cases, unreliable diagnostic procedures. The extensive use of US imaging in thyroid pathology may increase the finding of US incidentally discovered parathyroid adenomas. The early detection of silent parathyroid pathologic findings may extend the natural history of these masses to a preclinical stage. Further investigations are necessary to evaluate the evolution of parathyroid incidentalomas and therefore their clinical significance.     

Clinicopathological study of minimum-sized hepatocellular carcinoma: An approach to the definition of early hepatocellular carcinoma

Clinicopathologic examination of 33 nodules from 23 cases of minimum-sized hepatocellular carcinoma (HCC), less than 15 mm in diameter, was carried out by imaging and clinical follow up. On ultrasound (US), 16 hypoechoic nodules (48%) and 15 hyperechoic nodules (45%) on angiography 7 tumour stains (21%) and on computerized tomography (CT) 3 low density nodules (9%) were detected. Of 27 nodules on lipiodol CT (LpCT), 7 lipiodol-deposited nodules (26%) were detected. Of 16 nodules on CO₂US angiography (US-angiography), 7 hypervascular (44%), 5 hypovascular (31%) and 4 isovascular nodules (25%) were detected. Of 13 nodules on CT during arterial portography (CTAP), 7 perfusion defect nodules (54%) were detected. The nodules were graded according to the Edmondson & Steiner Classification. Three nodules were resected; grossly, two were not distinct and one was poorly demarcated. Histologically, they were highly differentiated with irregularly-thin trabecular-patterned HCC where portal triads were detected. Cancer cells invaded the non-cancerous liver cells by replacement, and the border between the cancerous and non-cancerous regions was unclear; the latter region manifested chronic hepatitis or liver cirrhosis without hyperplasia. Minimum-sized HCC is characteristically hypovascular in arterial and portal supply of blood, of multicentric origin and of a well-differentiated pattern. Because the three resected nodules did not damage the liver acinus structure, they were considered to be an early stage of HCC.     

Cutaneous vascular immunofluorescence in rheumatoid arthritis: Correlation with circulating immune complexes and vasculitis

The presence of immunoglobulin and complement in the cutaneous blood vessels of clinically uninvolved forearm skin was studied in 70 patients with rheumatoid arthritis, using immunofluorescent techniques. Patients with evidence of these immune deposits had a greater prevalence of circulating immune complexes, vasculitic skin lesions, subcutaneous nodules, high titer rheumatoid factor and other findings suggestive of active vasculitis. Biopsy of uninvolved forearm skin may be a useful tool in assessing those patients with rheumatoid arthritis suspected of having a systemic vasculitis.