2012年ACR痛风指南解读与安康信的应用
2012年美国风湿病学会痛风治疗指南解读
的，在T 2相上大部分是中等信号，少数为高信号，并且造影后呈现明显的强化。
这种强化可能和组织学上看到的周围“纤维血管区”中占优势的血管成比例。
在T 2加权像上的低信号点倾向于钙化灶。
6痛风、其他结晶性关节病和感染的影像学区别临床上，痛风的表现可以和感染性关节炎相似，包括发热，关节红肿热痛，血白细胞计数增多，血沉、C 反应蛋白升高；但痛风骨侵蚀的典型表现，易发作部位及缺乏邻近软组织化脓，有助于痛风诊断的征象。
抽取关节腔积液在偏振光显微镜见绿色针样晶体，革兰染色为阴性，将有助于痛风诊断。
关节软骨表面的MSU 结晶沉积物在超声中表现平行于骨皮质的回波曲线带，形成“双轨征”。
这是和焦磷酸钙结晶疾病有明显区别的征象，焦磷酸盐沉积症通常导致结晶沉积在关节内而不是关节表面。
超声为能检查出这些区别的最敏感的方式。
7影像学监测治疗效果随着更多新型、有效降尿酸方法的出现，人们尝试用影像学手段监测治疗疗效。
影像学变化包括痛风石的缩小、“双轨征”的消失、滑膜增生停止、关节渗出和骨髓水肿的改善。
CT 和MRI 采用先进的痛风石3D 绘图，使CT 和MRI 描述病变更加准确和逼真。
DECT 基于化学成分能识别尿酸结晶，在治疗随访中，观察溶解的痛风石方面更确切、可靠。
MRI 在随访滑膜增生和骨髓水肿方面有它特殊的价值，而超声是可以显示上述（除骨髓水肿外）所有影像表现的一种极好的廉价的方法，从而可以替代评估方法，并能提供精确的细节和良好的空间分辨率。
尽管MRI 在临床和科研方面同样有助于监测疾病进展，但随访不便捷且花费高。
因此，超声有望成为监测治疗反应的最佳方法。
综上所述，长期以来，影像学在诊断和随访痛风疗效方面价值十分有限，随着影像学技术的发展和临床案例探索，超声可用来指导穿刺获得组织样本，甚至在深部组织中寻找尿酸沉积物，从而有助于诊断。
准确地评估痛风的疾病活动性，并能有助于非典型急性痛风及伴痛风石的慢性痛风的诊断，同时评估治疗反应。
2012版ACR痛风管理指南-宋立军
(tophi) deposited chiefly in and around joints, which
sometimes lead to deformity and crippling
反应;
中国指南未提及。
4、痛风关节炎急性发作的抗炎 镇痛药选择：
ACR指南推荐NSAIDs、秋水仙碱和糖皮质激素，3种
药同等推荐，医师根据患者偏好、以前治疗反应、合
并症综合考虑;
中国指南建议糖皮质激素用于不能耐受NSAIDs和秋水
仙碱或肾功能不全者。
5、分层治疗的强调：
ACR指南强调分层治疗，痛风关节炎根据疼痛程度及
鼓励食用：低脂乳制品和蔬菜。
急性痛风性关节炎发作的基本治疗原则
急性痛风性关节炎发作必须采取药物治疗，且最好在
发病之初的24小时内开始。如果在ULT过程中出现急
性痛风性关节炎发作，不须暂停降尿酸药物。
要让患者知道诱发痛风性关节炎急性发作的原因，一
旦发作，患者应知晓基本处理原则；
要让患者认识到痛风是体内尿酸过度积累所致，只有
嘌呤的肉类、海鲜及果糖饮料的摄入，推荐低脂或脱
脂乳制品和蔬菜；
② 减少酒精摄入（特别是啤酒、白酒和烈酒），避免
酗酒，疾病活动的患者须戒酒，尤其是药物无法有效
控制病情进展及慢性痛风性关节炎患者。
研究人员将食物建议分为三类：避免食用、限制食用
和鼓励食用。
客观的说，这些建议都是来自某些孤立的临床研究，
受累关节数，决定选单药还是联合治疗，对联合治疗
方案也做了建议;
《美国风湿病学会欧洲抗风湿联盟痛风分类标准》解读
3、病理学标准
2、对于疑似痛风患者，医生可以根据该标准进行初步诊断。如果患者的临床 表现符合标准，则可以进一步进行影像学和病理学检查以明确诊断。如果患者的 临床表现不符合标准，则可能需要进一步检查以排除其他疾病的可能性。
Hale Waihona Puke 3、病理学标准3、在治疗方面，医生可以根据该标准对痛风患者进行分期治疗。对于急性发 作期患者，医生可以采取非甾体抗炎药、糖皮质激素等药物治疗以缓解疼痛和炎 症。对于慢性期患者，医生可以采取降尿酸治疗以降低血尿酸水平，预防痛风发 作。同时，医生还需要对患者进行生活方式的干预，如控制饮食、增加运动等， 以降低痛风复发的风险。
痛风概述
痛风概述
痛风是一种由于嘌呤代谢紊乱或尿酸排泄障碍导致的慢性代谢性疾病。根据 国家卫健委2019年的数据，我国痛风患病率呈逐年上升趋势，且发病年龄日趋年 轻化。痛风的主要病理生理机制是尿酸盐结晶沉积，导致急性痛风性关节炎和痛 风石形成。痛风患者常伴发高血压、糖尿病、肥胖、高血脂等代谢性疾病。
指南解读
要点分析
要点分析
1、分类：该指南将痛风分为急性发作期、间歇期和慢性期三个阶段，有助于 更好地理解患者的病情和制定相应的治疗方案。
要点分析
2、诊断：指南强调了病史采集、体格检查、实验室检查和影像学检查的重要 性，有助于提高诊断的准确性。
要点分析
3、治疗：该指南提出了针对不同阶段的治疗方案，包括抗炎、降尿酸和尿酸 盐溶解等治疗措施，具有很强的实操性。
在影像学方面，有以下两个标准： （1）关节超声：超声检查发现关节内有结晶沉积或痛风石；
2、影像学标准
（2）关节X线检查：X线平片显示关节周围有骨质破坏或囊性变。
3、病理学标准
3、病理学标准
痛风指南：发达国家是这样治疗痛风的
痛风指南：发达国家是这样治疗痛风的前沿：痛风是一种最常见的炎症性关节病，在西方国家男性的患病率约为1%～2%。
随着我国人民生活水平的不断提高，痛风的患病率也呈逐年上升趋势，目前已经接近西方发达国家水平。
痛风是由于血尿酸水平持续升高，导致单钠尿酸盐在关节和其他组织中沉积所致。
高尿酸血症和痛风与糖尿病、高血压、心血管疾病、慢性肾脏病等密切相关，是上述疾病发生发展的独立危险因素，也直接导致了患者长期生活质量的下降。
2002～2008年荷兰全科医师学会、欧洲风湿病学会、英国风湿病学会以及日本痛风和核酸代谢学会均陆续颁布了痛风治疗指南，为合理规范化诊治痛风提供了重要依据。
治疗药物和新型影像学技术（高频超声和双能CT）的应用进一步推动了痛风诊治的发展。
2012年美国风湿病学会在循证医学证据基础上，结合专家根据患者具体临床情况给出的意见，针对痛风治疗提出了新的指南，包括非药物性干预和药物治疗。
2013年多个国家又联合提出了痛风诊断和治疗推荐。
为了更好地指导我国临床医师在实践中结合患者具体情况制订合理的治疗方案。
1痛风的治疗目标：普遍目标：痛风的治疗目标已经非常明确，最新的几项推荐或指南一致强调血尿酸水平降至360μmol/L（6mg/dl）以下是治疗的最低目标；痛风石患者目标：对于已有痛风石的痛风患者，为了更好地长期改善患者的临床症状和体征，应将血尿酸水平降至300μmol/L（5mg/dl）以下。
因此在治疗过程中需要严密监测患者血尿酸水平，另外也需要关注关节炎发作的频率和痛风石的大小。
最终目标：对于痛风患者，关节炎不再发作、痛风石逐渐被吸收也是治疗的重要目标。
2痛风的诊断：在关节积液或痛风石中发现单钠尿酸盐晶体仍然是诊断痛风的最有利依据。
临床发现典型痛风石或对秋水仙碱治疗反应好，支持痛风诊断，除此以外的多数情况下，临床、实验室以及传统X线检查对于诊断的帮助不大。
对于11项研究的荟萃分析显示：新型影像学技术（超声、双能CT）对于痛风诊断有帮助。
安康信依托考昔片说明书
安康信（依托考昔片）说明书【安康信药品名称】通用名：依托考昔片商品名：安康信（ARCOXIA）英文名：EloricoxibTablets 汉语拼音：YituokaoxiPian安康信成份】主要成份为依托考昔。
化学名称：5-氟-6‘- 甲基-3-[4- （甲磺酰基）苯基]-2 ，3'-联吡啶。
【安康信性状】安康信为薄膜衣片，除去包衣后显白色或类白色。
60mg规格：绿色片；90mg 规格：白色片；120mg规格：淡绿色片。
【安康信适应症】安康信适用于治疗急性痛风性关节炎。
【安康信规格】120mg【安康信用法用量】安康信用于口服，可与食物同服或单独服用。
急性痛风性关节炎-- 推荐剂量为120 毫克，每日1 次。
安康信120毫克只适用于症状急性发作期，长使用8 天。
使用剂量大于推荐剂量时，尚未证实有更好的疗效或目前尚未研究。
因此，上述剂量是推荐剂量。
因为选择性环氧化酶-2 抑制剂的心血管危险性会随剂量升高和用药时间延长而增加，所以应尽可能减短用药时间和使用每日有效剂量。
应定期评估患者症状的缓解情况和患者对治疗的反应。
（见注意事项）老年人、性别、种族-- 老年人、不同性别和种族的人群均不需调整剂量。
肝功能不全-- 轻度肝功能不全患者（Child-Pugh 评分5-6 ），安康信使用剂量不应超过60 毫克每日1次。
中度肝功能不全患者（Child-Pugh 评分7-9 ），应当减量，不应超过隔日60 毫克。
对重度肝功能不全患者（Child-Pugh 评分＞9），目前尚无临床或药代动力学资料。
（见注意事项）肾功能不全-- 患有晚期肾脏疾病（肌酐清除率＜30mL/min ）的患者不推荐使用安康信。
对于轻度肾功能不全（肌酐清除率≥30mL/min ）不需要调整剂量。
（见注意事项）【安康信不良反应】据国外文献报道在临床试验中，对约4800例个体进行了安全性评价，包括约3400 例骨关节炎、风湿性关节炎或慢性腰背痛的患者（约600例骨关节炎或风湿性关节炎患者治疗达 1 年或更长时间）。
2012ACR-RA
淋巴系统肿瘤
ACR 2012
慢性心功能不全: 禁用生物制剂
NYHA III或IV及，
或EF<50%
ACR 2012
DMARDs和生物制剂使用的指征、调整和转换 生物制剂在高危人群中的使用（肝炎、肿瘤
和慢性心功能不全）
使用生物制剂时TB的筛查
疫苗接种
• 所有治疗的RA应筛查，尤其高危人群 • 初始TST或IGRAs，但BCG接种者首选IGRAs • 潜在TB，抗痨治疗1月后开始RA的治疗 • TB患者，抗痨疗程结束后 • 筛查阴性非高危人群不必再筛查，高危人群每年筛 查一次 • TB患者，抗痨后接受生物制剂的治疗，监测TB已 临床和影像学为主，而不是TST和IGRs
0.71 0.65
0.23
0.2 0
0 n=3097 ≤1 n=523 >1-2 n=398 >2-4 n=503 >4 n=384
年
服用HCQ时间越长，糖尿病的发生风险下降越明显。在384名服用HCQ超过4年的患者中发生 糖尿病的风险比为0.23
JAMA.2007；298(2):187-193
• 生物制剂间的转换（因为疗效）
• 生物制剂间的转换（因为副作用）
• TNFa抑制剂使用出现严重不良反应，换用非TNFa 生物制剂 • TNFa抑制剂使用出现一般不良反应，换用换用另一 种生物制剂（TNFa抑制剂或非TNFa）
• 非TNFa生物制剂出现任何不良反应，换用另一种生
物制剂
DMARDs和生物制剂使用的指征、调整和转换 生物制剂在高危人群中的使用（肝炎、肿瘤
DMARDs应加用，如MTX、LEF或HCQ
• DMARDa的使用和调整 • DMARDs转换生物制剂
2012年ACR痛风指南解读
谢 谢！
碱 化 尿 液
• 为防治尿酸结石的重要措施。
• 碱化尿液可使尿酸结石溶解。
- 尿液pH < 5.5时,尿酸呈过饱和状态，溶解的尿酸减少； - pH >6.5时，大部分尿酸以阴离子尿酸盐的形式存在
• 将尿pH维持在6.5-6.9范围最为适宜。 • 常用的碱性药物为碳酸氢钠。
抑制尿酸合成 ——代表药物为别嘌呤醇
用法：成人初始剂量一次50mg，一日1～2次，每周可 递增50～100mg，至一日200～300mg，分2～3次服， 一日最大量不得大于600mg。 Ccr<60ml/min，别嘌呤醇推荐剂量为50mg-100mg/日 Ccr<15ml/min 禁用 注意事项：别嘌呤醇常见的不良反应为过敏，重度过 敏者（迟发性血管炎，剥脱性皮炎）常致死，禁用。 肾功能不全增加重度过敏的发生危险，应用时应注意 监测。服用期间定期查肝肾功能、血常规，肝肾功能 和血细胞进行性下降停用。严重肝功能不全和明显血 细胞低下者禁用。
预防用药
评述
以往临床上也都采用了上述预防药物，但是在 疗程上均明显不足 之所以将糖皮质激素列入二线预防药物，主要 是考虑到长期使用糖皮质激素可能带来的多种 不良反应
启示
医学发达国家在指南制定过程中有着严格的程序 和规范，其科学性更高，参考价值更大，值得我
们在制定本国指南时参考
由于种族的差异、经济水平的不同，可供药物的
酸治疗
对于肾功能不全的评估，Ccr比血肌酐更为重要
由于没有非布司他对4级或4级以上CKD患者用药
安全性的资料，可以用丙磺舒作为一线药物（别 嘌醇不能用的情况下） 对于Ccr<50ml/min者，不推荐单独采用丙磺舒 作为一线药物
安康信(依托考昔片)说明书
安康信（依托考昔片）说明书【安康信药品名称】通用名：依托考昔片商品名：安康信（ARCOXIA）英文名：EloricoxibTablets汉语拼音：YituokaoxiPian【安康信成份】主要成份为依托考昔。
化学名称：5-氟-6‘-甲基-3-[4-（甲磺酰基）苯基]-2，3’-联吡啶。
【安康信性状】安康信为薄膜衣片，除去包衣后显白色或类白色。
60mg规格：绿色片；90mg规格：白色片；120mg规格：淡绿色片。
【安康信适应症】安康信适用于治疗急性痛风性关节炎。
【安康信规格】120mg【安康信用法用量】安康信用于口服，可与食物同服或单独服用。
急性痛风性关节炎--推荐剂量为120毫克，每日1次。
安康信120毫克只适用于症状急性发作期，长使用8天。
使用剂量大于推荐剂量时，尚未证实有更好的疗效或目前尚未研究。
因此，上述剂量是推荐剂量。
因为选择性环氧化酶-2抑制剂的心血管危险性会随剂量升高和用药时间延长而增加，所以应尽可能减短用药时间和使用每日有效剂量。
应定期评估患者症状的缓解情况和患者对治疗的反应。
（见注意事项）老年人、性别、种族--老年人、不同性别和种族的人群均不需调整剂量。
肝功能不全--轻度肝功能不全患者（Child-Pugh评分5-6），安康信使用剂量不应超过60毫克每日1次。
中度肝功能不全患者（Child-Pugh评分7-9），应当减量，不应超过隔日60毫克。
对重度肝功能不全患者（Child-Pugh评分＞9），目前尚无临床或药代动力学资料。
（见注意事项）肾功能不全--患有晚期肾脏疾病（肌酐清除率＜30mL/min）的患者不推荐使用安康信。
对于轻度肾功能不全（肌酐清除率≥30mL/min）不需要调整剂量。
（见注意事项）【安康信不良反应】据国外文献报道在临床试验中，对约4800例个体进行了安全性评价，包括约3400例骨关节炎、风湿性关节炎或慢性腰背痛的患者（约600例骨关节炎或风湿性关节炎患者治疗达1年或更长时间）。
ACR痛风指南解读
一次 在达标后（血尿酸<6mg/dl），也要每6个
月测定一次 尿酸测定是调整药物剂量的依据，也有利
于判断患者对治疗药物的依从性
肾功能不全者降尿酸治疗
对于2－5级CKD或者终末期肾病患者，如果有过 痛风发作，目前有高尿酸血症，就应该进行降尿 酸治疗
2012年 ACR痛风指南解读
两个部分
第一篇
降尿酸治疗 慢性痛风石性痛风
第二篇
镇痛抗炎治疗 痛风性关节炎发作的抗炎药物预防
因为缺乏RCT证据，不涉及无症状性高尿酸血症的处理
流行病学
美国成年人痛风患病率为3.9%，全美有约 830万痛风患者
痛风患者增多的原因主要与促发高尿酸血症 的合并症：高血压、肥胖、代谢综合征、II 型糖尿病，慢性肾功能不全（CKD）患病率 增加
急性痛风处理
秋水仙碱剂量（1.2mg片剂）
开始负荷剂量 1.2mg 1 hr 后 0.6 mg 12小时后 0.6mg qd-bid
秋水仙碱剂量（1mg片剂）
开始负荷剂量 1.0mg 1 hr 后 0.5mg 12小时后 最多可用至 0.5mg
tid
急性痛风的处理
糖皮质激素－泼尼松
降尿酸治疗
黄嘌呤氧化酶抑制剂别嘌醇和非布司他是首选的降尿酸药物 对所有痛风患者降尿酸目标是血尿酸<6mg/dl 症状、体征得到有效的、持续的改善，或者对于有痛风石的患者，应
该降至5mg/dl以下
降尿酸治疗
别嘌醇的起始剂量不应超过 100mg/d，中、重度慢性肾 功能不全的患者应该从 50mg/d开始
饮食控制
非药物治疗
评析
对患者进行积极有效的宣教是慢性疾病治疗的 重要环节。EULAR会议上流行病学调查数据显 示：痛风患者在疾病认识上广泛存在误区，缺 乏规范降尿酸治疗的知识，而且患者用药依从 性较差。
痛风和高尿酸血症诊治各国指南与共识
糖皮质激素 一线药物：ACR、EULAR 二线药物：中华医学会风湿病学分会、日本痛
风-核酸代谢协会 三线药物：中国台湾风湿病学会
降尿酸药物治疗：使用指征一致
• 降尿酸药物使用指征各国共识比较一致 1、反复发作急性痛风（大于1次/年） 2、慢性痛风性关节炎 3、痛风石沉积 4、泌尿系结石 5、影像学出现痛风的典型表现
2015 ACR/EULAR痛风分类标准
2015 ACR/EULAR痛风分类标准*
第1步：适用标准（符合准入标准方可应用本标准）
类
别
存在至少一次外周关节或滑囊的肿 胀、疼痛或压痛
第2步：确定标准（金标准，无需进行分类诊断）
偏振光显微镜镜检证实在（曾）有 症状关节或滑囊或痛风石中存在尿 酸钠晶体
第3步：分类标准（符合准入标准但不符合确定标准） 累计≥8分可诊断痛风
支持方：中华医学会风湿 病学分会，中国医师协会 心血管内科医师分会，日 本痛风-核酸代谢协会
无症 疗
观点：没有高尿酸血症就没有 痛风，治疗可以预防痛风；高 尿酸血症还可导致肾损害，是 高血压、心血管不良事件的独 立危险因素
支持方：日本痛风-核酸代谢协 会，中国台湾风湿病学会，中 国医师协会心血管内科医师分 会，中华医学会内分泌学分会
降尿酸药物治疗：使用时机大多一致
• 降尿酸治疗时机各国共识有不同推荐 1、大多数指南：均推荐在急性痛风发作平稳至少2周后，开始降尿酸 治疗 2、ACR：首次提出在痛风急性发作期，在有效抗炎治疗的前提下， 可以开始降尿酸治疗 3、EULAR：不建议在急性痛风发作时开始或停止降尿酸治疗，一旦 使用即应终身使用
二线药物——小剂量NSAIDS或小剂量糖皮质激素；降尿酸 药物使用前2周开始，持续时间根据患者情况而定
ACR痛风指南解读ppt课件
6 months after achieving the target serum urate level, where there has been resolution of tophi previously detected on physical examination (evidence C)
预防用药 评述 以往临床上也都采用了上述预防药物，但是在疗程上均 明显不足 之所以将糖皮质激素列入二线预防药物，主要是考虑到 长期使用糖皮质激素可能带来的多种不良反应
• 过度饮酒（男性每天2份， • 饮酒（主要是啤酒，但 女性每天1份） 也包括葡萄酒和烈酒） （B级） （B级） • 任意量的酒（病情进展， 控制不佳，反复发作者） （C级）
• 蔬菜 （C级）
非药物治疗 评析 对患者进行积极有效的宣教是慢性疾病治疗的重要环节。 EULAR会议上流行病学调查数据显示：痛风患者在疾病认 识上广泛存在误区，缺乏规范降尿酸治疗的知识，而且 患者用药依从性较差。 家庭医生及非风湿科专科医生亦缺乏规范治疗的概念 “指南”特别强调“宣教”的重要性，同时提出积极控 制可以导致高尿酸血症的合并疾病是预防、治疗痛风的 重要环节，值得引起重视
有关节痛或痛风石均需长期抗炎预防治疗。 持续监测血尿酸水平和降尿酸药物的副作用。 专科医生规范化治疗。 小剂量阿司匹林允许使用，其他药物权衡利弊。
血尿酸监测 血尿酸监测对于痛风治疗是必需的 在调整降尿酸药物过程中，每2－5周测定一次 在达标后（血尿酸<6mg/dl），也要每6个月测定一次 尿酸测定是调整药物剂量的依据，也有利于判断患者对治疗 药物的依从性
定义 血尿酸
1mg/dl=59.45μmol/L
2012美国ACR痛风指南(第一部分)
16North Mississippi Medical Center, Tupelo, MS 17Southern California Permanente Medical Group, Downey, CA 18University of Florida, Gainesville, FL 19Cleveland Clinic, Cleveland, OH 20University of Pennsylvania and VA Medical Center, Philadelphia, PA 21Harvard Vanguard Medical Associates/Atrius Health, Somerville, MA 22VA Medical Center. Birmingham, Alabama and University of Alabama, Birmingham, AL Keywords Allopurinol; Febuxostat; Probenecid; Pegloticase; Uricosuric; Xanthine Oxidase; Tophi INTRODUCTION Gout is a disorder that manifests as a spectrum of clinical and pathologic features built on a foundation of an excess body burden of uric acid, manifested in part by hyperuricemia,which is variably defined as serum urate greater than either 6.8 or 7.0 mg/dL (1;2). Tissue deposition of monosodium urate monohydrate crystals in supersaturated extracellular fluids of the joint, and certain other sites, mediates most of the clinical and pathologic features of gout. Typically, the disease first presents as arthritis that is acute and episodic, but can become recurrent in the majority of individuals. Gout also can manifest as chronic arthritis of one or more joints (1;2). Tophi, mainly in articular, periarticular, bursal, bone, auricular,and cutaneous tissues are a pathognomonic feature of gout, and are detectable by physical exam, and/or by imaging approaches and pathology examination (3;4;5). Renal manifestations of gout include urolithiasis, typically occurring with an acidic urine pH (1;2).Chronic interstitial nephropathy, mediated by monosodium urate monohydrate crystal deposition in the renal medulla, can occur in severe disease, but is currently considered to be an uncommon clinical manifestation of gout.Gout is one of the most common rheumatic diseases of adulthood, with self-reportedprevalence in the USA recently estimated at 3.9% of adults (~8.3 million people)(6).Prevalence of gout has risen in many countries (e.g., New Zealand), and especially in theUSA over the last few decades, mediated by factors such as increased prevalence of co-morbidities that promote hyperuricemia, including hypertension, obesity, metabolicsyndrome, type 2 diabetes, and chronic kidney disease (CKD)(7–10). Other factors in therising prevalence of gout include certain dietary trends and widespread prescription ofthiazide and loop diuretics for cardiovascular diseases (11). Many gout patients, includingthe growing subset of affected elderly, have complex co-morbidities and medication profilesthat complicate overall management (12). Long-term morbidity and impairment of health-related quality of life are now better appreciated in many gout patients, particularly thosewith multiple co-morbidities and/or chronic gouty arthritis (13;14). Despite advancedunderstanding of the molecular bases of hyperuricemia and gouty inflammation, and theextensive practice experience of many providers, substantial quality of care gaps exist ingout management (15). Moreover, significant shortfalls in patient education and adherencehave been identified in gout (16).On behalf of the American College of Rheumatology (ACR), we were charged withdeveloping systematic non-pharmacologic and pharmacologic recommendations foreffective treatments in gout with acceptable risk-benefit ratio. Our assignment was to focuson four specific domains in gout management. Two of these domains are addressed herein,(i) Urate-lowering therapy (ULT), and (ii) chronic gouty arthritis with tophaceous diseasedetected on physical examination (designated by the ACR with the terminology “chronictophaceous gouty arthropathy” (abbreviated CTGA), and specifically represented in theNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptfundamental case scenarios 7–9 described herein). Domains iii-iv (analgesic and anti-inflammatory management of acute gouty arthritis, and pharmacologic anti-inflammatory prophylaxis of attacks of gouty arthritis, respectively) are addressed in a separate manuscript (Part II of the guidelines)(17).There are multiple lines of epidemiologic and experimental evidence that hyperuricemia, via effects of excess soluble urate, may play a role in some human renal, cardiovascular, and metabolic co-morbidities also frequently associated with gout (7–10). We did not address pharmacologic management of asymptomatic hyperuricemia, due to a paucity of prospective, randomized, controlled human research trials in that area (18).We were charged by the ACR with developing gout recommendations based on evidence as available, at an international level, for rheumatologists and other health care providers,including other subspecialists, primary care practitioners, nurse practitioners, physician assistants, and allied health professionals. The ACR requested that we apply the established Research and Development/University of California at Los Angeles (RAND/UCLA)Appropriateness Method (19) to generate recommendations, and engaged a diverse,international panel of experts. Creating novel classification of gout as a disease, new gout diagnostic criteria, or definition of treatment outcomes were beyond the scope of this work.Instead, we generated multifaceted case scenarios to elucidate decision-making based primarily on clinical and laboratory test-based data that can be obtained on a gout patient in an office practice setting.Guidelines for gout management have been generated in the last decade, at the national or multinational society level, by the European League Against Rheumatism (EULAR)(20;21),the Dutch College of General Practitioners (22), the Japanese Society of Gout and Nucleic Acid Metabolism (23), and the British Society for Rheumatology (BSR)(24). Moreover, the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process has been applied to ULT in gout using febuxostat (25). New guidelines wererequested by the ACR, as the understanding of gout risk factors has been greatly augmented by recent clinical research (12). Moreover, ULT options recently increased via clinicaldevelopment, and drug regulatory agency approval of new pharmacologic agents (febuxostat and the biologic drug pegloticase)(26;27). New imaging approaches for gout that can detect radiographic changes of early disease not visualized by plain radiography (e.g., highresolution ultrasound, dual energy computed tomography (DECT)(28;29), are beinginvestigated for impact on gout diagnosis, and assessment of disease burden and severity,and choices and effectiveness of management. Developments such as these are considered in the work of this committee, which was built on several key assumptions (Table 1).The ACR gout guidelines are designed to emphasize safety, and quality of therapy, and to reflect best practice, as evaluated by a diverse group of experts that examine the level ofevidence available at the time. Importantly, societal cost of health care, and cost and cost-effectiveness differences between therapies are excluded from analysis by the RAND/UCLA Appropriateness Methodology (19) (Table 1). Individual results of this work are designated as “recommendations” rather than guidelines, in order to reflect the non-prescriptive nature of decision-making evaluated by experts, and based on available evidence at the time. The recommendations cannot substitute for individualized, direct assessment of the patient,coupled with clinical decision making by a competent health care practitioner. Treatment recommendations also assume appropriate attention to potential drug interactions (eg, with anticoagulants, azathioprine, amoxicillin), and effects of co-morbidities such as diabetes,and renal, cardiac, gastrointestinal, and hepatic disease (Table 1). The motivation, financial circumstances, and preferences of the gout patient play a very important role. Moreover, the NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptrecommendations for gout management presented here are not intended to limit or denythird party payer coverage of health care costs for groups, or individual patients, with gout.METHODSProject design and development of recommendations and grading of evidence The overall design of the project is schematized in Supplemental Figure 1. The RAND/UCLA consensus methodology, developed in the 1980s, incorporates both Delphi and nominal group methods (19;30), and was successfully used to develop other guidelines commissioned by the ACR. The purpose of this methodology is to reach a consensus among experts, with an understanding that published literature may not be adequate to provide sufficient evidence for day-to-day clinical decision-making. The RAND/UCLA method requires 2 groups of experts—a core expert panel (CEP) that provides input into case scenario development and preparation of a scientific evidence report, and a task force panel (TFP) that votes on these case scenarios. Our CEP consisted of leaders for each domain (Supplemental Figure 2). Pharmacologic approaches, and diet, lifestyle and non-pharmacologic measures (e.g., weight loss, exercise) were addressed within each domain.The CEP leaders communicated with an international panel of gout experts, and the PIs, to develop initial case scenarios that reflect broad differences in severity of the disease and its clinical manifestations. In addition, there were weekly interactive teleconferences between domain leaders and PIs to refine case scenarios. Though previous systematic review for gout has been performed by EULAR, as a prime example, we performed our own systematic review of pertinent literature. The resultant scientific evidence report given to the TFP in conjunction with clinical scenarios representing a broad scope of disease, with multiple questions of interest, and alternative options, for each case scenario.By ACR mandate, the TFP had a majority of members without perceived potential conflict of interest (COI), and had diverse experience and expertise, as described in detail inSupplemental Figure 2. The TFP included 7 rheumatologists (one of whom is a Chair ofInternal Medicine, and one an Internal Medicine Residency Training Program Director), 2primary care physicians, a nephrologist, and a patient representative. There were 2 rounds of ratings, the first anonymously with the members of the TFP instructed to rank each of the potential elements of the guidelines on a risk-benefit basis ranging from 1 to 9 on a Likert scale using Delphi process, followed by a face-to-face group discussion and then re-voting of the same scenarios. A vote of 1–3 on the Likert Scale was rated as Inappropriate = risks clearly outweigh the benefits. A vote of 4–6 on the Likert Scale was considered Uncertain =risk-benefit ratio is uncertain. A vote of 7–9 on the Likert Scale was rated as Appropriate =benefits clearly outweigh the risks. Samples of votes taken and results are provided inSupplemental Figure 3. Votes on case scenarios were translated into recommendations if the median voting score was graded 7–9 (“appropriate”) and if there was no significantdisagreement, defined as no more than 1/3 of the votes graded (“inappropriate”) for thescenario. The final rating was done anonymously in a 2-day face-to-face meeting, facilitated by an experienced moderator (Neil Wenger). During the face-to-face TFP meeting, some case scenarios were clarified for content or verbiage, and re-voted on by the TFP.The level of evidence supporting each recommendation was ranked based on previousmethods used by the American College of Cardiology (31) and applied to recent ACRrecommendations (32;33). Level A grading was assigned to recommendations supported by multiple (i.e., more than one) randomized clinical trials or meta-analyses. Level B grading was assigned to the recommendations derived from a single randomized trial, ornonrandomized studies. Level C grading was assigned to consensus opinion of experts, case studies, or standard-of-care.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptSystematic reviewPubMed and Cochrane Central Register of Controlled Trials (CENTRAL) from the 1950s to the present were searched to find articles on gout with help of an experienced librarian(Rikke Ogawa). We used a search strategy based on the Cochrane Highly Sensitive Search Strategy for identifying randomized trials. The search was expanded to include articlesdiscussing research designs such as cohort, case control and cross sectional studies. Limits included English Language and the exclusion of “animal only” studies. The exact terms,process and results of the search are summarized in Supplemental Figure 4.Clinical Case DescriptionsThe TFP evaluated scenarios with a broad spectrum of clinical gout, similar to what aclinician might see in a busy practice, and divided into mild, moderate, and severe disease activity in each of three distinct “treatment groups” (Figure 1A–B). In generating these nine fundamental clinical case scenarios, mild disease activity levels in each “treatment group”were meant to represent patients at the lowest disease activity level for which mostclinicians would consider initiating or altering a specific medication regimen. Conversely,severe disease activity level was intended to represent patients with disease activity equal or greater to that of the “average” subject studied in a clinical trial. The case scenarios were not intended to serve as classification criteria. To allow the TFP to focus on managementdecisions, each case scenario had the assumption not only that the diagnosis of gout was correct, and that there was some clinical evidence of gout disease activity. This included intermittent symptoms of variable frequency, specifically presented to the TFP as episodes of acute gouty arthritis of at least moderate to severe pain intensity (17). Clinical evidence of gout disease activity, presented to the TFP, also included one or more tophi detected byphysical exam, or alternatively, chronic symptomatic arthritis (ie, “chronic arthropathy” or “synovitis”) due to gout, with or without confirmed joint damage (e.g., deformity, erosion due to gout on imaging study). Hyperuricemia was defined here as serum urate >6.8 mg/dL(2). We determined all aspects of case scenario definitions by a structured iterative process,using regular electronic mail, and teleconferences at least once per month. Multiplerevisions to the proposed parameters were carried out, until accepted by the CEP domain leaders.Definitions of pharmacologic therapeutic agentsMedication classes evaluated in the case scenarios were defined as follows: Xanthineoxidase inhibitor (XOI) refers to allopurinol or febuxostat; uricosuric agents were defined to include agents available in the USA (probenecid, and off-label use (as uricosuric therapy) of fenofibrate and losartan), but did not include sulfinpyrazone or benzbromarone. Other agents and modalities were self-explanatory. Evaluation by the TFP of effectiveness of a giventherapeutic option assumed that patients in case scenarios received the maximum tolerated typical dose for a period of time sufficient to accurately assess therapeutic response, unless otherwise indicated.Managing perceived potential COIPerceived potential COI was managed in a prospective and structured manner. Specifically,all participants intellectually involved in the project, whether authors or not, were required to fully, and prospectively disclose relationships with pharmaceutical companies with amaterial interest in gout (Supplemental Material Discussion). Disclosures were updatedevery 6 months, and for the PIs, CEP and TFP, updated just prior to the face-to-facemeeting. A summary listing of all perceived potential COI was disseminated to allparticipants in the project, and is available in the supplemental materials. Based on thepolicies of the ACR, which are aligned with those of many medical societies, no more than NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript49% of project participants could have COI at any given time. It was required that theproject PI (John FitzGerald) remain without perceived potential COI prior to and during the process.RESULTS Primary principles of management for all gout case scenarios The TFP generated recommendations for a systematic non-pharmacologic and pharmacologic management approach intended to be applicable to all patients with gout,which is summarized in Figure 3. This was based on the assumption that the diagnosis of gout was correct before initiation of management. The approach highlighted patient education on the disease and treatments and their objectives, and initiation of diet and lifestyle recommendations. The TFP also recommended elimination of prescription medication that were non-essential for the optimal management of co-morbidities (eg,hypertension, CHF, hyperlipidemia, or major organ transplant) in an individual patient,where such medication elevated serum urate levels; with prime examples being thiazide and loop diuretics, niacin, and calcineurin inhibitors (Evidence C). Though low dose acetylsalicylic acid (aspirin ≤ 325 mg daily) elevates serum urate, the TFP did not recommend discontinuation of this modality as cardiovascular disease prophylaxis in gout patients. In discussion, without a specific vote, the TFP viewed the relative risks specifically attributable to the modest effects of low dose aspirin on serum urate as negligible in gout management.The TFP recommended that clinicians consider causes of hyperuricemia for all gout patients,and recommended a specific co-morbidity checklist (Evidence C)(Table 2). In doing so, the TFP specially recommended consideration, and if indicated, medical evaluation of certain agents and disorders that cause uric acid underexcretion or overproduction, and thereby could merit laboratory investigations such as urinalysis, renal ultrasound, a completehemogram, or urine uric acid quantification as indicated. In this context, the TFPspecifically recommended screening for uric acid overproduction (by urine uric acidevaluation for uric acid overproduction), in patient subsets with gout clinical disease onset before age 25 (Evidence C), or a history of urolithiasis (Evidence C).The TFP provided guidance for referral to a specialist, with caution to avoid appearing self-serving. Though limited by the absence of outcomes data on potential benefits of referral,the TFP recommended that gout case scenarios including any of the following should be amongst those where referral to a specialist is considered (Evidence C for all): (i) Unclear etiology of hyperuricemia; (ii) Refractory signs or symptoms of gout; (iii) Difficulty inreaching the target serum urate level, particularly with renal impairment and a trial of XOI treatment; (iv) Multiple and/or serious adverse events from pharmacologic ULT.Clinical evaluation of gout disease activity and burdenThe TFP recommended clinical evaluation of gout disease symptom severity and burden in individual patients by history and thorough physical exam for symptoms of arthritis, and signs such as tophi and acute and chronic synovitis (Evidence C). To be actionable byclinicians, the authors, without a specific TFP vote, suggest that clinicians can work with patients to record and estimate the number per year, and severity (17) of acute attacks of gouty arthritis per year.Core recommendations for non-pharmacologic ULT measures in goutThe TFP recommended certain diet and lifestyle measures for the vast majority of patients with gout (Evidence B-C for individual measures) (Figure 4). Many of the diet and lifestyle NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptmeasures were recommended for decreasing the risk and frequency of acute gout attacks(12) and lowering serum urate, but the primary emphasis of the TFP recommendations in Figure 4 was on diet and lifestyle choices for promotion and maintenance of ideal health,and prevention and optimal management of life-threatening comorbidities in gout patients,including coronary artery disease (34,35), and obesity, metabolic syndrome, diabetes,hyperlipidemia, and hypertension.Dietary recommendations were grouped into 3 simple qualitative categories, termed “limit”,“avoid”, or “encourage” (Figure 4). This approach, with rare exceptions (36,37), reflected a general lack of specific evidence from prospective, blinded, randomized clinical intervention trials that linked consumed quantities of individual dietary components to changes in either serum urate levels or gout outcomes. Notably, the replication of hazardous lifestyle riskfactors in a conventional clinical research trial would potentially pose both design andethical difficulties. As such, the TFP deliberated on evidence regarding the impact ofexposures to alcohol or purine-rich foods in a short time frame. The evidence sources were epidemiologic studies of hyperuricemia and incident gout, including long-term prospective analyses and internet-based case-crossover studies. The TFP recommended that goutpatients limit their consumption of purine-rich meat and seafood (Evidence B) as well as high fructose corn syrup sweetened soft drinks and energy drinks (Evidence C), andencouraged the consumption of low-fat or non-fat dairy products (Evidence B) (38)(Figure4). The TFP also recommended reduced consumption of alcohol (particularly beer, but also wine and spirits), and avoidance of alcohol overuse in all gout patients (Evidence B) (Figure4). The TFP further recommended abstinence from alcohol consumption for gout patients during periods of active arthritis, especially with inadequate medical control of the disorder and in CTGA (Evidence C)(39). Significantly, in discussion by the TFP, without a specific vote, the TFP recognized that diet and lifestyle measures alone provide therapeuticallyinsufficient serum urate-lowering effects and/or gout attack prophylaxis for a large fraction of individuals with gout (12). For example, some clinical trials on diet and fitness havereported only ~10–18% decrease in serum urate (38). In further discussion by the TFP, again without a specific vote, the TFP viewed this degree of serum urate-lowering as beneficial for all case scenarios, but insufficient to achieve an effective serum urate target in those with sustained hyperuricemia substantially above 7 mg/dL.Core recommendations for pharmacologic ULT, including the serum urate targetHere, and with all other recommendations for drug therapy in Parts I and II of the 2012 ACR Guidelines for gout, the recommendations assumed a lack of contra-indications, intolerance,serious adverse events, or drug-drug interactions for given agents. The TFP recommended gout with CKD stage 2–5, or end stage renal disease (ESRD), as an appropriate indication,by itself, for pharmacologic ULT (Evidence C) in patients with prior gout attacks andcurrent hyperuricemia. In pharmacologic ULT, certain treatment choices (e.g., probenecid)and drug dosing decisions (e.g., allopurinol) are impacted by the creatinine clearance. The TFP, without a direct vote, discussed and recognized the clinical value of accuratemeasurement of creatinine clearance, not simply the serum creatinine, in ascertaining the degree of renal impairment. However, the scope of the project did allow for detailed,prescriptive recommendations regarding specific ULT drug doses, or usage of individual agents in the presence of a given degree of either renal impairment, or other co-morbidities such as hepatic impairment.TFP recommendations for pharmacologic ULT, presented graphically in Figure 3, included recommendation of xanthine oxidase inhibitor (XOI) therapy with either allopurinol orfebuxostat as the first line pharmacologic approach (Evidence A). The panel did notpreferentially recommend either XOI over the other XOI drug. In doing so, the TFP weighed the lack of published safety data for febuxostat in the setting of stage 4 or worse CKD.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptProbenecid was recommended as an alternative first line pharmacologic ULT option, in the setting of contra-indication or intolerance to at least one XOI agent (Evidence B). However,the TFP did not recommend probenecid as a first line ULT monotherapy in those with acreatinine clearance below 50 ml/min.The TFP recommended that pharmacologic ULT could be started during an acute goutattack, providing that effective anti-inflammatory management has been instituted (EvidenceC). The TFP recommended regular monitoring of serum urate (every 2–5 weeks) duringULT titration, including continuing measurements once the serum urate target is achieved (every 6 months) (Evidence C). The TFP weighed this measure as particularly useful tomonitor adherence, given that poor adherence to ULT is a common problem in gout patients(16).The TFP recommended that the goal of ULT is to achieve a serum urate target, at aminimum, of < 6 mg/dL in all gout case scenarios (Evidence A). Moreover, the TFPrecommended that the target serum urate should be lowered sufficiently to durably improve signs and symptoms of gout, including palpable and visible tophi detected by physicalexamination, and that this may involve therapeutic serum urate-lowering to below 5 mg/dL (Evidence B).Recommendations specific to allopurinol dosing and pharmacogenetics TFP recommendations for use of allopurinol in gout are summarized in Table 3A.Importantly, the TFP recommended that the starting dose of allopurinol be no greater than 100 mg per day (Evidence B)(40), consistent with prior FDA and EULAR guidelines (21).The rationale of the TFP was partly that a low allopurinol starting dose could reduce early gout flares after ULT initiation, (26), and partly as a component of risk management with respect to the potential for severe hypersensitivity reaction to allopurinol (40), discussed in further detail below. The TFP recommended gradual upward titration of the allopurinolmaintenance dose every 2–5 weeks to an appropriate maximum dose for gout, in order to treat to the serum urate target appropriate for the individual patient (Evidence C).The TFP weighed robust evidence that allopurinol monotherapy at doses of 300 mg daily or less failed to achieve the serum urate target of <6 mg/dL (26,41), or < 5 mg/dL (42,43), in more than half of subjects with gout. The TFP reviewed small studies in which theallopurinol dose was titrated above 300 mg daily in gout with overall success in achieving the serum urate target (43,44). Importantly, in doing so, the TFP also recommended that the maintenance dose of allopurinol can be raised above 300 mg per day, even in those withrenal impairment, provided there is adequate patient education and regular monitoring for drug hypersensitivity and other adverse events, such as pruritis, rash, and elevated hepatic transaminases, as well as attention to potential development of eosinophilia (Evidence B).The TFP next considered the issue of measures to reduce the incidence of severe allopurinol hypersensitivity reactions, here termed allopurinol hypersensitivity syndrome (AHS). TFP discussion recognized the potential for hospitalization and severe morbidity, and thereported mortality rate of 20–25% in AHS (45,46). The estimated incidence of AHS is~1:1000 in the USA and its spectrum includes not only Stevens-Johnson Syndrome andToxic Epidermal Necrolysis, but also systemic disease with a clinical constellation offeatures such as eosinophilia, vasculitis, rash, and major end-organ disease (47). Concurrent thiazide use and renal impairment have been implicated as risk factors for AHS (48–50). A widely employed risk management strategy has been a non-evidence-based algorithm for allopurinol maintenance dosing, calibrated to renal impairment (51)(Evidence C);importantly, the TFP did not recommend this strategy,NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript。
2012年美国风湿病学会(ACR)痛风治疗指南解读
2012年ACR痛风治疗指南解读痛风性关节炎的发病率逐年增高，关于高尿酸血症及痛风性关节炎的规范治疗越来越受到人们的重视。
2012年美国风湿病学会（ACR）在2011年推出诊治共识的基础上，制定了最新的痛风治疗指南，该指南分为两部分：第一部分是痛风的系统治疗指南，第二部分是急性痛风性关节炎的治疗与预防性抗炎治疗，均发表于《关节炎护理与研究》[Arthritis Care Res 2012，64（10）：1431和1447]杂志。
此次治疗指南对过去各国治疗指南进行了总结更新，结合最新的文献证据和专家共识，制定出了不同证据级别的治疗方案。
痛风的非药物及药物治疗原则痛风的非药物治疗指南首先强调了患者宣教的重要性，单纯饮食及生活方式干预可在一定程度上起到降尿酸和（或）预防急性痛风关节炎发作的作用。
关于饮食控制，指南建议：①限制短时间内大量摄入富含嘌呤的食物，限制富含嘌呤的肉类、海鲜及果糖饮料的摄入，推荐低脂或脱脂乳制品和蔬菜；②减少酒精摄入（特别是啤酒、白酒和烈酒），避免酗酒，疾病活动的患者须戒酒，尤其是药物无法有效控制病情进展及慢性痛风性关节炎患者。
降尿酸治疗（ULT）非药物治疗适用于所有患者，经非药物治疗血尿酸（SUA）仍＞7 mg/dl 者，应予药物。
痛风患者ULT目标为SUA＜6 mg/dl；对于痛风性关节炎症状长期不缓解或有痛风石的患者，SUA应＜5 mg/dl。
推荐抑制尿酸生成的黄嘌呤氧化酶抑制剂（XOI）为首选用药，推荐别嘌醇或非布索坦单药治疗。
对XOI有禁忌或不耐受者可换用促尿酸排泄药，但肌酐清除率（CCr）＜50 ml/min者不宜使用。
注意，这里监测的是CCr而非血肌酐浓度（SCr）。
与传统观念不同，指南指出，在急性痛风性关节炎发作期，在恰当抗炎治疗后，可开始ULT。
该观点有待国内大量临床资料证实。
别嘌醇方案推荐初始剂量≤100 mg/d（慢性肾脏病4期及以上者为50mg/d）；每2~5周渐加量；维持最大治疗剂量（＞300mg/d）使SUA降至目标值以下，肾功能不全者，只要对其充分宣教及规律监测药物毒性反应，也可按此剂量治疗；建议用药前筛查人白细胞抗原（HLA）-B*5801基因型。
安康信的止疼效果
产品成分与制作工艺
安康信的主要成分是高纯度天然 植物提取物，这些成分经过精心 挑选和提取，以确保最佳的止疼
效果。
制作工艺方面，安康信采用了先 进的生产技术和质量控制流程，
确保产品的品质和稳定性。
安康信的生产过程严格遵循相关 法规和标准，确保产品的安全性
和有效性。
02
安康信的止疼原理
药物作用机理
抑制前列腺素合成
抑制中枢神经敏感化
安康信通过抑制前列腺素的合成，降 低炎症反应，从而缓解疼痛。
安康信能够抑制中枢神经敏感化，降 低疼痛的敏感性，从而缓解慢性疼痛。
抗炎作用
安康信具有抗炎作用，能够减轻炎症 引起的疼痛和肿胀。
止疼效果的科学依据
01
02
03
临床研究
多项临床研究证实了安康 信在止疼方面的有效性， 支持其用于缓解疼痛。
长期止疼效果
长期使用
对于需要长期管理疼痛的患者， 安康信可以提供持续的疼痛缓解。
预防疼痛复发
长期使用安康信有助于预防疼痛 的复发，降低疼痛再次出现的风
险。
减少药物依赖
长期使用安康信可以减少患者对 其他止痛药的依赖，提高疼痛管
理的自主性。
适用人群与使用方法
适用人群
适用于成年人及老年人的轻度至中度疼痛治疗， 需在医生指导下使用。
总结
安康信与其他止疼药在成分上相似，均具有抗炎、镇痛作用。
止疼效果比较
安康信
01
依托考昔具有强效的抗炎镇痛作用，对于轻至中度疼痛的缓解
效果较好。
其他止疼药
02
如布洛芬、对乙酰氨基酚等，对于轻至中度疼痛的缓解效果也
较好。
总结
03
在止疼效果方面，安康信与其他常见止疼药相当，均能有效缓
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血尿酸监测
血尿酸监测对于痛风治疗是必需的 在调整降尿酸药物过程中，每2－5周测定 一次 在达标后（血尿酸<6mg/dl），也要每6个 月测定一次 尿酸测定是调整药物剂量的依据，也有利 于判断患者对治疗药物的依从性
肾功能不全者降尿酸治疗
对于2－5级CKD戒者终末期肾病患者，如果有过 痛风发作，目前有高尿酸血症，就应该迚行降尿
2012年 ACR 痛风指南解读与安康信的应用
复旦大学风湿、免疫、过敏性疾病研究中心 复旦大学附属华山医院风湿科 薛愉 2013年1月
两个部分
第一篇
降尿酸治疗
慢性痛风石性痛风 镇痛抗炎治疗
痛风性关节炎发作的抗炎药物预防
第二篇
因为缺乏RCT证据，不涉及无症状性高尿酸血症的处理
流行病学
治疗经过
• 非甾体类抗炎药：双氯芬酸50mg bid*3d， 洛索洛芬钠60mg tid*3d。 • 强的松：30mg qd*2d qd*2d 5mg qd*1d 20mg qd*2d Nhomakorabea10mg
• 降尿酸治疗：别嘌醇 0.1qd • 停强的松一周后，右踝关节肿痛再次发作。
治疗经过
• 关节局部注射得宝松1支。
降尿酸治疗
黄嘌呤氧化酶抑制剂别嘌醇和非布司他是首选的降尿酸药物 对所有痛风患者降尿酸目标是血尿酸<6mg/dl 症状、体征得到有效的、持续的改善，戒者对于有痛风石的患者，应 该降至5mg/dl以下
降尿酸治疗
别嘌醇的起始剂量丌应超过 100mg/d，中、重度慢性肾 功能丌全的患者应该从 50mg/d开始 每2-5周逐渐增加剂量至达标 维持剂量可以超过300mg/d ，甚至在CKD患者中也可以 超过此剂量。注意搔痒、皮 疹和肝酶增高
谢 谢！
6 months after achieving the target serum urate level, where there has been resolution of tophi previously detected on physical examination (evidence C)
• 复查尿酸：482mmol/L，肌酐：130umol/L。
• 依托考昔120mg qd*10d
• 别嘌醇0.1bid 0.1tid。
60mg qd。
治疗经过
尿酸 600 500 400 300 200 100 0 0w 2w 4w 8w 12w 16w 20w 24w
治疗经过
肌酐 160 140 120 100 80 60 40 20 0 0w 2w 4w 8w 12w 16w 20w 24w
急性痛风的处理
糖皮质激素－泼尼松
开始 0.5mg/kg 用药 5－10天，停药/用药 2－5天，7－10天内逐渐减量，停药。
严重、多关节发作建议联
合治疗。
秋水仙碱+NSAIDs；口 服激素/关节腔内激素治 疗+秋水仙碱。 丌建议激素+NSAIDs。
急性痛风中降尿酸治疗
评析
国际上一些痛风治疗指南包括中国指南大多认 为：降尿酸治疗均应在急性发作平息至少2周 后方可开始。 “指南”首次提出，在有效抗炎药物“保护” 下，降尿酸治疗幵非禁忌。这一新观点值得在 以后的临床实践中加以证实
• 过度饮酒（男性每天2份， • 饮酒（主要是啤酒，但 女性每天1份） 也包括葡萄酒和烈酒） （B级） （B级） • 任意量的酒（病情进展， 控制不佳，反复发作者） （C级）
非药物治疗
评析
对患者迚行积极有效的宣教是慢性疾病治疗的 重要环节。EULAR会议上流行病学调查数据显 示：痛风患者在疾病认识上广泛存在误区，缺 乏规范降尿酸治疗的知识，而丏患者用药依从 性较差。 家庭医生及非风湿科与科医生亦缺乏规范治疗 的概念 “指南”特别强调“宣教”的重要性，同时提 出积极控制可以导致高尿酸血症的合幵疾病是 预防、治疗痛风的重要环节，值得引起重视
非布司他可作为首选，最大剂量120mg/d 对于严重痛风患者，如果对传统降尿酸治疗耐药戒者丌能 耐受，可以使用尿酸酶（普瑞凯希，Pegloticase）治疗 用药周期多长，目前缺乏共识
有关节痛戒痛风石均需长期抗炎预防治疗。 持续监测血尿酸水平和降尿酸药物的副作用。 与科医生规范化治疗。 小剂量阿司匹林允许使用，其他药物权衡利弊。
对于特定的人群，如：韩国裔，同时有3级以上CKD；所有中国汉人、泰国裔，发 生别嘌醇相关的严重过敏性药疹危险性增高，在使用别嘌醇前，应该进行HLAB*5801快速PCR检测
排尿酸治疗
丙磺舒促迚尿酸排泄药物单药治 疗的首选。若肌酐清除小于 50ml/min，则丌作为首选。 非诺贝特、氯沙坦兼有降尿酸作 用，可做补充治疗。 有尿路结石的是禁忌。 使用前查尿尿酸，已升高者丌适 用。 在降尿酸过程中检测尿尿酸。 碱化、水化防结石。
非药物治疗
肥胖者减肥，尽量回复正常的体重指数（BMI） 提倡健康的饮食 戒烟 适当运动 保证充足的水分摄入
饮食控制
禁食 少食 多食
低脂或者脱脂奶 制品 （B级） • 蔬菜 （C级） • 高嘌呤内脏：胰腺、肝脏、• 牛、羊、猪肉 肾脏 • 高嘌呤海鲜：沙丁鱼、 （B级） 贝类 （B级） • 高果糖、玉米糖浆调味的 • 天然甜味的果汁 苏打水、其他饮料或食物 • 糖、甜饮料、甜点 （C级） （C级）
美国成年人痛风患病率为3.9%，全美有约 830万痛风患者 痛风患者增多的原因主要不促发高尿酸血症 的合幵症：高血压、肥胖、代谢综合征、II 型糖尿病，慢性肾功能丌全（CKD）患病率 增加 饮食习惯改变，噻嗪类利尿剂、袢利尿剂使 用增多
定义
血尿酸
1mg/dl=59.45μmol/L
丌分性别、年龄，血清中MSU的最大饱和量约为
预防用药
评述
以往临床上也都采用了上述预防药物，但是在 疗程上均明显丌足 之所以将糖皮质激素列入二线预防药物，主要 是考虑到长期使用糖皮质激素可能带来的多种 丌良反应
启示
医学发达国家在指南制定过程中有着严格的程序 和规范，其科学性更高，参考价值更大，值得我
们在制定本国指南时参考
由于种族的差异、经济水平的丌同，可供药物的
考昔。如使用塞来昔布，应该使用大剂量，丏风险－收益还丌 确定。
急性痛风处理
秋水仙碱剂量（1.2mg片剂）
开始负荷剂量 1.2mg 1 hr 后 0.6 mg 12小时后 0.6mg qd-bid
秋水仙碱剂量（1mg片剂）
开始负荷剂量 1.0mg 1 hr 后 0.5mg 12小时后 最多可用至 0.5mg tid
酸治疗
对于肾功能丌全的评估，Ccr比血肌酐更为重要
由于没有非布司他对4级戒4级以上CKD患者用药
安全性的资料，可以用丙磺舒作为一线药物（别 嘌醇丌能用的情况下） 对于Ccr<50ml/min者，丌推荐单独采用丙磺舒 作为一线药物
第二部分——定义
急性痛风的处理
急性痛风的处理
对于有胃肠道禁忌证者，可以选用COX－2抑制剂，可使用依托
区别，美国指南可能幵丌完全适合中国的国情，
其合理性、科学性有待今后临床实践的检验
病例介绍
• 患者、男性、45岁。
• 高尿酸血症10年，痛风性关节炎5年，右踝关节再
发一周。
• 体检：全身多处痛风石，包括右肘关节伸侧、右 手第三MCP关节伸侧、右足第一跖趾关节处。右 踝关节红肿明显，皮温升高。 • 辅助检查：UA 568mmol/L，Cr148umol/L。
6.8mg/dl，超过此值即为高尿酸血症
推荐证据级别
A级 多项RCT研究戒Meta分析结果
B级 一项RCT研究戒非RCT研究结果
C级 与家共识、病例报道等
第一部分
适用于所有痛风患者
患者教育，饮食指导，提倡良好的生活方式 处理可导致高尿酸血症的合幵疾病 避免“非必需“会导致高尿酸药物的应用 评估痛风的严重度（痛风石、发作频率、急慢性症状体征）