痛风的影像学研究进展

影像学检查可以帮助临床医师评价痛风.X线成像只能显示慢性痛风进展期的典型变化.CT可能是评价痛风骨改变和痛风石的最好方法,双源CT可以评估全身周围关节的尿酸盐总沉积量.MRI适合评估软组织、滑膜厚度和炎性反应,对痛风的早期病变敏感性很高,也能够较好的显示痛风石.超声检查可以评价软骨、软组织、尿酸盐沉积和滑膜炎性反应.核医学有助于在细胞和分子层面理解痛风性关节炎的发病机制.

Abstract：

Imaging is a helpful tool for clinicians to evaluate gout. Plain radiographs show typical changes only in advanced chronic gout. Computed tomography may best evaluate bone changes and tophi. Dual energy CT can measure the total urate burden in general periphery joints. Magnetic resonance imaging is suitable to evaluate soft tissues,synovial membrane thickness,and inflammatory changes,which is also sensitive to early change of gout,and even well show the tophi. Ultrasonography may be used in evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Nuclear medicine may be helpful to investigate the pathogenesis of gouty arthritis in the field of cell and molecule.     

痛风性关节炎的 X 线平片、CT 和 MR 的对比研究

目的：对比研究痛风性关节炎的 X 线平片、CT 和 MRI 表现,并探讨临床资料与影像学表现的关系。方法选择33例患者的54个确诊为痛风性关节炎的关节为研究对象,上午空腹查血尿酸,下午记录临床资料,并做平片、CT 和 MRI 检查。影像表现的评价指标包括痛风石、骨质破坏、软组织肿胀、关节积液、滑膜增厚和骨髓水肿。统计分析方法包括卡方检验、独立样本 t 检验和逻辑回归分析。结果卡方检验分析不同检查方法下痛风石阳性的关节数(CT>平片、MR>平片, P<0.01),软组织肿胀(MR>CT>平片,P<0.01),关节积液(MR>CT, P<0.01)。此外,MRI 发现骨髓水肿35例,滑膜增厚50例。独立样本 t检验显示有痛风石的患者病程长于无痛风石的患者(P<0.01)。 Logstic 回归分析痛风石的致病因素,骨质破坏和病程入选(P<0.01)。结论对于痛风的早期诊断,MRI 优于 CT 和平片。痛风石和骨质破坏可能不会影响血尿酸水平。随着病程的延长,痛风石形成的几率也升高。痛风石的形成与骨质破坏可能是相互促进的关系。     

双源CT对北部湾地区痛风患者尿酸盐结晶沉积的诊断价值研究

目的评估双源CT诊断北部湾地区痛风患者尿酸盐结晶沉积的临床价值。方法选择该院收治的28例临床确诊痛风的患者行双侧膝关节、踝关节及双足双源CT扫描,对照组为10例临床需要行双侧膝关节、踝关节及双足双源CT扫描的非痛风患者,用痛风结石软件进行分析,记录是否能够显示尿酸盐结晶以及分布情况,并比较两组尿酸盐沉积的差异及双源CT检出尿酸盐结晶沉积部位与临床评估的差异。结果痛风组中共检测出尿酸盐结晶124处,是临床评估病变部位的2.43倍(临床估计病变部位51处),其中最常见部位为第一跖趾关节(37.9%),其次是踝关节(25.8%),最后是膝关节(15.3%);13例患者存在不同程度的骨质破坏,16例为多关节破坏,所有患者均伴有软组织肿胀。对照组未发现尿酸盐结晶。结论双源CT能够定性、定量显示尿酸盐结晶沉积,对北部湾地区痛风患者的早期无创性诊断、预防及治疗具有重要的临床意义。     

痛风的发病机制及诊治研究进展

痛风是单钠尿酸盐(MSU)沉积引发的组织损伤和炎症性反应,与高尿酸血症直接相关。目前,临床上以偏振光显微镜在关节液或痛风石中发现特异性尿酸盐结晶为诊断痛风的金标准,但偏振光显微镜检查为有创检查,在基层医院难以开展。近年来,双源CT及超声等影像学逐步在临床中得到应用,使双轨征、结晶聚集、关节腔积液、滑膜增厚和骨质缺损等超声表现成为诊断痛风和监测治疗效果方便快捷的重要依据。本文就痛风的发病机制及诊治研究进展综述如下。     

肌肉骨骼超声用于痛风诊断和病情监测

痛风是继发于慢性高尿酸血症形成的单钠尿酸盐(monosodium urate,MSU)沉积所致的晶体相关性疾病,与嘌呤代谢紊乱或尿酸排泄减少直接相关。其诊断金标准为"关节液或痛风石组织穿刺发现特异性尿酸盐结晶",然而该检查有创,部分无症状高尿酸血症及痛风急性发作期的患者拒绝行该检查。研究显示,痛风患者超声下有特异性表现,如双轨征、痛风石,无症状高尿酸血症患者也可以出现相同征象。超声可以作为痛风患者诊断及降尿酸疗效的监测手段。     

抗高尿酸血症追踪治疗对原发性痛风的影响

对已有10年以上抗高尿酸血症治疗历史的65例痛风患者进行重新评估.发现痛风石沉积的减少与血尿酸(SUA)浓度相关.降低SUA浓度有可能减少痛风石,但X线改变和SUA浓度不存在相关性.单独SUA浓度测定不能有效地监测痛风病变的进展.     

双源CT诊断痛风性关节炎临床分析

目的 采用非侵入性双源CT观察关节及周围组织的尿酸盐结晶,以探索临床诊断痛风或鉴别诊断其他关节疾病。方法 选择近2周发作过单关节肿或（和）痛患者17例,均行病变关节双源CT检查。部分患者在B超下穿刺取关节液镜检。结果 13例痛风患者发现33处有尿酸盐结晶,最常沉积的关节部位为双侧足趾关节(7/33)、近端指关节(5/33)、远端指间关节周围(4/33)、跖关节(4/33)、胫骨下端(3/33)。发现尿酸盐结晶易沉积在近关节骨表面,肌肉、韧带等关节周边软组织。关节肿痛部位与尿酸盐结晶沉积部位一致。尿酸盐结晶大小可以测量。结论 双源CT可以清晰显示尿酸盐结晶,为无创检测手段。在鉴别诊断不明原因单关节肿痛方面有很好的价值。     

能谱CT扫描及量化分析在老年性痛风结节诊断中的价值

目的评价能谱CT量化分析在老年性痛风结节诊断中的价值。方法老年痛风患者24例纳入病例组,选择其他类型的关节病变患者24例纳入对照组,均进行能谱CT、常规CT扫描。结果病例组共扫描了56个部位,相应的对照组扫描膝踝关节48个部位。病例组中常规CT检出痛风结石126个,能谱CT检出痛风结石135个;对照组能谱CT、常规CT检查未见痛风性结石影。能谱CT诊断关节病变阳性率57.1%(32/56)显著高于常规CT的37.5%(21/56),差异有统计学意义(P<0.05)。病例组的痛风石、肌肉、骨松质、骨皮质的尿酸基(钙)、钙基(尿酸)、水基(钙)及钙基(尿酸)水平比较差异有统计学意义(P<0.05)。病例组的骨松质钙基(尿酸)含量明显高于对照组,差异有统计学意义(P<0.05)。结论能谱CT量化分析在痛风结节诊断中有较高的价值,不仅可以更好地检出痛风结石,还可以进行量化分析,从而评估痛风病情的严重程度。     

痛风患者足踝双能CT尿酸盐结晶沉积特点分析

目的 应用双能CT分析关节周围尿酸盐结晶沉积特点,预测与痛风性关节炎急性发作相关的解剖和形态学特征.方法 选择近期足踝部发作过关节肿和(或)痛患者84例(其中确诊痛风患者68例,无症状高尿酸血症患者1 1例,单纯其他类型关节炎患者5例),入选患者均完成足踝部双能CT检查.应用x2检验及Logistic回归模型分析尿酸盐结晶沉积的解剖、形态学特征与关节炎症急性发作的关系.结果 痛风组共发现278处尿酸盐结晶,最常出现结晶沉积的部位依次为第一趾中远端(18.2％)、第一跖趾关节(16.8％)、跟骨(17.5％)、胫骨下端(11.8％),无症状高尿酸血症组发现34处尿酸盐结晶沉积,分布趋势与痛风组相似.对患者结晶沉积部位与关节炎症急性发作情况进行分析后发现,第一跖趾关节(x2=8.47,P＜0.01)及胫骨下端(x2=3.93,P＜0.05)出现结晶沉积的患者临床上更易出现相应部位关节炎的急性发作.且第一跖趾关节附近的尿酸盐结晶如果沉积于肌腱(x2=5.03,P＜0.05)或软组织(x2=5.19,P＜0.05)中,更易引起痛风性关节炎;而对于踝关节周围的尿酸盐结晶,如果其沉积于踝关节伸面(x2=4.42,P＜0.05)或呈点状(x2=4.76,P＜0.05)或为多个(x2=4.97,P＜0.05)则更易出现关节炎症发作.并且Logistic多元回归分析结果也提示,痛风性关节炎急性发作有潜在的危险因素.结论 双能CT可以清晰显示尿酸盐结晶,有助于痛风的诊断及随防研究.尿酸盐结晶沉积的部位、形状、大小、数量以及受累部位是否伴有软组织肿胀、骨侵蚀等因素,对痛风性关节炎的急性发作有影响.     

双能CT在诊断痛风心血管损害中的应用价值

痛风是由尿酸钠结晶沉积在关节或其他组织中引起的一种常见的疾病,其发病率和患病率呈逐年上升趋势,高尿酸血症是发展为痛风最重要的危险因素。近年来许多流行病学和实验研究均证实痛风与高血压、冠心病和心肌梗死等心血管疾病的发生和死亡密切相关。而双能CT作为一种新型的无创性影像学检查手段,可以特异性并定量显示尿酸盐结晶,近年来已成为诊断痛风的一个有效工具,有研究发现其在痛风心血管损害的诊断中也有着很好的临床价值。该综述分析痛风与心血管疾病之间复杂的相关性,以及双能CT在诊断痛风心血管损害中的优势和应用价值。     

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.     

Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan

Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long‐term urate‐lowering treatment. Urate‐lowering drugs should be used during the inter‐critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate‐lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.     

Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout

OBJECTIVE: The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout. METHOD: Sixty-three patients with crystal-confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination. RESULTS: Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction. CONCLUSION: Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single-drug therapy.     

Effect of urate‐lowering therapy on the velocity of size reduction of tophi in chronic gout

Objective

The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout.

Method

Sixty‐three patients with crystal‐confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination.

Results

Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction.

Conclusion

Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single‐drug therapy.

     

Gout and Organ Transplantation

Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use.     

A rare and asymptomatic case of mitral valve tophus associated with severe gouty tophaceous arthritis

Gouty arthritis is characterized by the deposition of monosodium urate crystals in the joints and soft tissues. Clinical manifestations include acute and chronic arthritis and tophaceous deposits. Chronic tophaceous gout has become less common since the introduction of the pharmacological treatment. Moreover, cardiac valve gouty tophi have been very rarely reported.     

Identification and characterization of peripheral vascular color-coded DECT lesions in gout and non-gout patients: The VASCURATE study

ObjectiveTo characterize peripheral vascular plaques color-coded as monosodium urate (MSU) deposition by dual-energy computed tomography (DECT) and assess their association with the overall soft-tissue MSU crystal burden.MethodsPatients with suspected crystal arthropathies were prospectively included in the CRYSTALILLE inception cohort to undergo baseline knees and ankles/feet DECT scans; treatment-naive gout patients initiating treat-to-target urate-lowering therapy (ULT) underwent repeated DECT scans with concomitant serum urate level measurements at 6 and 12 months. We determined the prevalence of DECT-based vascular MSU-coded plaques in knee arteries, and assessed their association with the overall DECT volumes of soft-tissue MSU crystal deposition and coexistence of arterial calcifications. DECT attenuation parameters of vascular MSU-coded plaques were compared with dense calcified plaques, control vessels, control soft tissues, and tophi.ResultsWe investigated 126 gout patients and 26 controls; 17 ULT-naive gout patients were included in the follow-up study. The prevalence of DECT-based vascular MSU-coded plaques was comparable in gout patients (24.6%) and controls (23.1%; p=0.87). Vascular MSU-coded plaques were strongly associated with coexisting arterial calcifications (p<0.001), but not with soft-tissue MSU deposition. Characterization of vascular MSU-coded plaques revealed specific differences in DECT parameters compared with control vessels, control soft tissues, and tophi. During follow-up, vascular MSU-coded plaques remained stable despite effective ULT (p=0.64), which decreased both serum urate levels and soft-tissue MSU volumes (p<0.001).ConclusionOur findings suggest that DECT-based MSU-coded plaques in peripheral arteries are strongly associated with calcifications and may not reflect genuine MSU crystal deposition. Such findings should therefore not be a primary target when managing gout patients     

Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells

OBJECTIVE: To analyze cellular mechanisms of bone erosion in gout. METHODS: Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with gout were analyzed for the presence of osteoclast precursors. Fixed tophus and bone samples were analyzed by immunohistochemistry. Mechanisms of osteoclastogenesis were studied by culturing murine preosteoclast RAW 264.7 cells, bone marrow stromal ST2 cells, and human synovial fibroblasts with monosodium urate monohydrate (MSU) crystals. RESULTS: PBMCs from patients with severe erosive gout had the preferential ability to form osteoclast-like cells in culture with RANKL and monocyte colony-stimulating factor (M-CSF). The number of PBMC-derived tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells strongly correlated with the number of tophi (r = 0.6296, P = 0.630). Patients with severe erosive and tophaceous gout also had higher circulating concentrations of RANKL and M-CSF. Furthermore, greater numbers of TRAP-positive multinucleated cells were cultured from SFMCs derived from gouty knee effusions than from paired PBMCs (P = 0.004). Immunohistochemical analysis demonstrated numerous multinucleated cells expressing osteoclast markers within tophi and at the interface between soft tissue and bone. MSU crystals did not directly promote osteoclast formation from RAW 264.7 cells in vitro. However, MSU crystals inhibited osteoprotegerin gene and protein expression in ST2 cells and human synovial fibroblasts, without significantly altering RANKL gene expression. Conditioned medium from ST2 cells cultured with MSU crystals promoted osteoclast formation from RAW 264.7 cells in the presence of RANKL. CONCLUSION: Chronic tophaceous and erosive gout is characterized by enhanced osteoclast development. These data provide a rationale for the study of osteoclast-targeted therapies for the prevention of bone damage in chronic gout.     

Multiple microcrystal deposition disease in a patient with systemic lupus erythematosus.

A 17-year-old female patient with systemic lupus erythematosus (SLE) developed chronic tophaceous gout, chondrocalcinosis and articular capsule calcification in several joints. Analysis of synovial fluid and tophi revealed the coexistence of monosodium urate, calcium pyrophosphate, hydroxyapatite, and cholesterol crystals.