美国最新的痛风治疗方案&（&New&Gout&Management&Guidelines）
New Gout Management Guidelines:
A Quick and Easy Guide
Bret S. Stetka, MD; Jonathan Kay, MD
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For the first time since its founding 78 years ago, the American
College of Rheumatology (ACR) has released guidelines for the
management of gout. The recommendations were released in 2
parts.[1,2] Part 1 addresses nonpharmacologic
and pharmacologic treatment approaches to hyperuricemia, including
detailed dietary measures, and part 2 advises on therapy and
anti-inflammatory prophylaxis of acute gouty arthritis. To help
integrate the new recommendations into your clinical practice,
we've highlighted and summarized the primary management suggestions
put forth by the ACR task force panel (TFP).
在美国风湿病学会成立的78年以来，第一次给出了痛风的建议治疗方案。建议分为两部分。第一部分讲高尿酸血症的药物性和非药物性治疗，包括具体的饮食方式。
第二部分讲急性痛风性关节炎的治疗和抗炎预防。为了帮助你们把新的治疗建议整合，应用到临床工作中，我们这里把ACR的建议做扼要的总结。
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Clinical Evaluation
When evaluating a patient for gout, the ACR TFP recommends a
thorough history and physical examination, gauging the frequency
and severity of attacks, and assessing for signs such as tophi and
synovitis.
当评估一个病人有没有痛风石， ACR建议做详细的病史调查和体检,
估量急性痛风的频率和严重程度，观察评估痛风结节一滑膜炎等症状。
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Nonpharmacologic Management in Established
The TFP recommends a number of nonpharmacologic interventions
aimed at lessening attack risk, lowering urate levels, and
promoting general health while preventing the development of
comorbidities. Dietary recommendations are divided into 3 groups:
Foods to avoid are organ meats (ie, sweetbreads, liver),
foods containing high-fructose corn syrup, and excessive alcohol
use*; foods to limit are large portions or concentrations
of meat and seafood, naturally sweet fruit juices, sugar, desserts,
and foods that are encouraged include low-fat or
nonfat dairy and vegetables. Weight loss in those who are
overweight, smoking cessation, and exercise are also recommended as
general lifestyle health considerations in patients with gout.
*In advanced gout or during periods of high disease activity,
all alcohol should be avoided.
对于已经确定的，比较顽固的痛风
TFP 提出了几项非药物的措施， 针对如何降低下次痛风爆发，降低尿酸盐水平，改善健康水平，
同时防止并发症。营养学的建议分为三部分： 1） 避免吃的食物： 公务的内脏，喊高果糖的玉米糖浆，和过量饮酒。 2） 限制吃的食物：
多数的肉类和海鲜， 加天然甜味剂的果汁， 白糖，甜点，和盐。 3） 鼓励吃的食物：
低脂或脱脂的乳制品和蔬菜。对于痛风的病人，建议通过减体重， 戒烟， 加强锻炼来改变生活方式。
*对于很严重的， 发展阶段比较高的情况， 避免饮用所有的酒类。
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Pharmacologic Management 药物治疗
In patients with a potential diagnosis of gout, a number of
initial steps should be taken. These include patient education,
considering other causes of hyperuricemia, eliminating nonessential
prescription medications associated with hyperuricemia, and
evaluating the disease burden to determine the appropriate course
of treatment. Management of acute attacks wil
however, urate-lowering therapy (ULT) should be considered in
patients with 1 or more tophi, ≥2 attacks per year, chronic kidney
disease (CKD; stage 2 or worse), or a history of urolithiasis. The
TFP recommends initiating ULT with either allopurinol or
probenecid is recommended as an alternative first-line
agent when either allopurinol or febuxostat is contraindicated, or
when a patient has demonstrated intolerance to at least one of the
agents. ULT can be started during
urate level should be monitored every 2-5 weeks during ULT
titration and every 6 months after the target serum level
(&6 mg/dL) has been reached.
对可能被诊断为痛风的病人，最开始有几步可以做, 包括病人教育， 考虑引起高尿酸血症的原因，去除非主要的可高尿酸血症有关的处方药，
评估痛风所带来的负担来决定治疗方案。如何处理急性的痛风发作在后面会讲到， 然而， 降尿酸盐的治疗（ULT）对于有一个或多个痛风结节，
每年超过两次以上的痛风发作，慢性肾病（第二期以上），或者有尿路结石的病史。TFP建议起始治疗用 allopurinol或者
febuxostat。 如果这两种药病人出现不可承受的副作用，或者对病人来说是禁忌， 建议 probenecid
作为一线药物的替代药。降尿酸盐的治疗（ULT）可以在痛风急性发作的时候开始，药物调整剂量期间，&
血清尿酸盐水平需要每 2 - 5 周监测一次。 当血清尿酸盐的水平达到6 mg/dl 以后， 每六个月监测一次。
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Allopurinol Dosing
Starting allopurinol dose should not exceed 100 mg/day, and
patients with CKD of stage 4 or higher should be started at 50
mg/day. Dosages should be titrated up every 2-5 weeks to achieve
target serum uric acid and can go above 300 mg/day as long as the
patient is educated and monitored for adverse events. Screening for
the HLA-B*5801 allele, which is associated with a high risk for
severe allopurinol hypersensitivity reaction, should be considered
in high-risk individuals, such as Koreans with an estimated
glomerular filtration rate &60 mL/min/1.73
m2 or those of Han Chinese or Thai ancestry.
Allopurinol的剂量
Allopurinol的起始剂量不能超过100 mg/每天。
慢性肾病第四期或者更糟的病人起始剂量为50mg/每天。为了把血清尿酸降低到目标水平， 剂量每2 到5
周调整一次。如果病人能够参与药物知识的学习， 知道自己监控副反应， 剂量可以超过300 mg/day.
HLA-B*5801等位基因和allopurinol的过敏反应的高风险相关，对于高风险的人群，可以考虑筛查 （ GFR
(肾小球滤过率）& 60 ml/min/1.73 m2 的 韩国人，汉族中国人，
或者泰国血统的人。）
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Uricosuric Therapy 促尿酸排泄的治疗
When using a uricosuric as ULT monotherapy, the ACR TFP
recommends probenecid. First-line use of probenecid is
contraindicated in patients with a history of urolithiasis.
当使用促尿酸排泄的药作为降尿酸治疗的单药治疗的时候， ACR TFP 建议使用 probenecid。probenecid
作为一线用药对于有尿路结石的患者是禁忌的。
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When Symptoms (and Urate) Won’t Go Away: Case
All patients with gout who experience intermittent symptoms or
have chronic synovitis due to gout with tophi (chronic tophaceous
gouty arthritis [CTGA]) should be treated initially with
single-agent XOI titrated to its maximum appropriate dose. If the
serum uric target is not achieved or if the patient experiences
continuing disease activity, a uricosuric agent should be added to
the XOI, with both agents titrated to their maximum appropriate
doses. Pegloticase therapy may be initiated, if the serum uric
target still is not achieved or if disease activity continues, in
those with &7 attacks/year and no tophi, those with
≥2 attacks/year and tophi on physical examination, or those with
当痛风的症状不能消除的时候。
1）有过间断症状， 或者有慢性滑膜炎（有痛风结节形成，慢性痛风性的关节炎）的痛风病人都应该开始 XOI 类单药剂的治疗，
调整剂量到最大的合适剂量。 2） 如果病人的尿酸水平没有交到目标水平， 或者病人仍然有持续的痛风的症状， 应该再加用排尿酸的药物，
调整两种药到最大的剂量。 3）如果尿酸的水平还是没有降到目标水平，
或者痛风的症状还存在，对于每年痛风发作7次以上并且没有痛风结节，或者每年发作两次以上并且体检有痛风结节，
或者有慢性的痛风性关节炎的患者， 可以加上 Pegloticase 治疗。
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Treating an Acute Attack 痛风急性发作期的治疗
The ACR TFP recommends that an acute gout attack be treated
pharmacologically within 24 hours of the onset of symptoms and that
any existing ULT be continued without disruption. In
mild-to-moderate disease (≤6 of 10 on a 0-10 pain visual analogue
scale), monotherapy with NSAIDs, systemic corticosteroids, or oral
colchicine is recommended. In more severe disease, characterized by
intense pain and often a polyarticular presentation, combination
therapy is suggested (colchicine and NSAIDs, oral corticosteroids
and colchicine, or intra-articular steroids with each of the other
options). Determining which pharmacologic agent is best for a
patient has been left to the treating physician's discretion.
ACR TFP 建议在痛风的急性发作期， 应该在症状发作的24小时之内开始治疗。 如果已经在服用降尿酸的治疗， 不要停，
继续服用。 对于轻中度的痛风（在0 到10 的疼痛评级中， 疼痛等级小于或等于 6 ）， 建议使用单药物的治疗：NSAIDS类药物，
或者系统服用皮质激素， 或者口服colchicin。 对于更严重的痛风 （疼痛更厉害， 并且通常有多关节的表现），
建议使用以上几种药的联合用药 （ colchicine + NSAIDs,口服皮质激素 + colchicine，
或者关节内的激素和其他药物的注射。 到底哪种药物对病人最佳， 还是取决于医生的判断。
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Choosing an NSAID
Full doses of FDA- or European Medicines Agency-approved NSAIDs
are recommended to treat an acute attack of gout. Naproxen,
indomethacin, and sulindac are FDA-app
however, other NSAIDs may be effective. Data also support the
efficacy of COX-2 the TFP also recommends celecoxib (an
initial dose of 800 mg, followed by 400 mg on day 1, and then dosed
at 400 mg twice daily for 1 week) for acute disease in patients
intolerant to or with contraindications to other NSAIDs.
选择 NSAID 类的药
对于痛风的急性发作，建议服用完全剂量的美国食品药物管理局， 或欧洲医药局认可的 NSAIDs类的药物。 Naproxen,
indomethacin, and sulindac是美国食品药物局认可的治疗急性痛风的药物。
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Colchicine
Colchicine is a recommended option in acute gout if the attack
began within the past 36 hours. Recommended treatment consists of a
loading dose of 1.2 mg of colchicine followed by 0.6 mg 1 hour
later. This can then be followed, 12 hours later, by prophylactic
colchicine dosing 0.6 mg once or twice daily that may be continued
until the gout attack resolves. In countries where 1.0-mg or 0.5-mg
tablets of colchicine are available, instead of 0.6-mg tablets,
recommended treatment consists of a loading dose of 1.0 mg of
colchicine followed by 0.5 mg 1 hour later. This can then be
followed, 12 hours later, by prophylactic colchicine dosing 0.5 mg
up to 3 times daily that may be continued until the gout attack
在痛风急性发作的36小时之内，Colchicine 是一个建议的治疗选择。建议的治疗方案：初始剂量：1.2 mg
Colchicine, 一小时之后 0.6 mg. 之后，12 小时之后， 还可以预防性的给与 Colchicine 0.6 mg,
每日一次或两次， 只到痛风急性发作的症状消失。 有些国家的 Colchicine 是 1.0 mg 或者 0.5 mg
的片剂，可以不用0.6 mg 的剂量，而给初始 1.0 mg 的剂量， 一小时之后给 0.5 mg, 然后12 小时之后，
预防性的给与 0.5 mg 剂量 （可以到每日三次）， 治疗一直持续到痛风发作的结束。
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Starting Steroids 激素类药物的治疗
For an acute gout attack involving 1-2 joints, the ACR TFP
recommends treating with
intra-articular corticosteroids is recommended when 1-2 large
joints are involved. The decision to use intra-articular dosing
should be based upon joint size. Intra-articular corticosteroids
can be used in combination with NSAIDs, colchicine, or oral
corticosteroids. Recommended oral corticosteroids include
prednisone and prednisolone at a dose of 0.5 mg/kg/day for 5-10
days, or for 2-5 days at this full dose, followed by a 7- to 10-day
taper and then discontinuation. An alternative approved approach is
the administration of a single intramuscular dose of triamcinolone
acetonide 60 mg, which may be followed by oral prednisone or
prednisolone. Intramuscular triamcinolone acetonide is most useful
when treating patients who are to take nothing by mouth or those
who may be less compliant with a multidose oral treatment
如果痛风的发作涉及到一到两个关节， ACR TFP 建议口服皮质激素的治疗。 痛风发作时，当涉及到一两个大的关节时，
可以使用关节内的皮质激素的治疗。 是否使用关节内的皮质激素的治疗取决于关节的大小。 关节内的激素治疗可以合并NSAIDs,
colchicine 药物， 或者口服的皮质激素的治疗。 建议的口服的皮质激素包括： prednisone
和prednisolone, 剂量：0.5 毫克/每公斤体重/每天， 服用5 到10 天； 或者按此剂量服用2 到5 天，之后7
到10 天逐渐减量，直到停药。另外一个被批准的治疗方案是： 单次肌肉注射 triamcinolone acetonide 60 mg，
之后口服prednisone or prednisolone。 单次肌肉注射 triamcinolone
acetonide的治疗方案一般用于不能口服药的病人， 或者对于多剂量的口服药不能很好的遵从医嘱服药的病人。
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Inadequate Response to Initial Therapy
If a patient with acute gout does not experience at least 20%
improvement in pain within 24 hours or at least 50% improvement in
pain after 24 hours or more of pharmacologic therapy, an
alternative diagnosis should be considered. If the diagnosis of
gout is confirmed, the patient should be switched to another
monotherapy or a second agent should be added. Because there are no
randomized studies of anakinra treatment of gout and because
canakinumab is not FDA-approved, the role of interleukin-1
inhibitor therapy for acute gout remains uncertain.））
急性痛风发作的病人，在用药治疗24小时之内如果疼痛没有缓解20%， 或者在用药24小时之后没有能够缓解50%的话，
需要考虑其他的诊断。 如果痛风的诊断很明确了， 那么病人就要更换用药（用其他的单药治疗或者再加入其他的药物治疗。)
因为还没有anakinra 对痛风治疗的研究（canakinumab 还没有获得美国食品，药品管理局的批准，
interleukin-1 抑制剂对急性痛风的治疗作用还不是很清楚。
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Considerations in the Setting of Comorbidities
考虑合并症
Acute gout therapy may be associated with many potential
drug-drug interactions and toxicities in the setting of
comorbidities, which clinicians should consider carefully.
由于合并症的存在的前提下，急性痛风的治疗会和很多的药物之间的反应和毒副作用相关，
临床医生应该用药治疗应该非常谨慎。
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Anti-inflammatory Prophylaxis&
预防性的抗炎治疗
Given the high rate of gout attacks early in ULT, pharmacologic
anti-inflammatory prophylaxis with oral colchicine or low-dose
NSAIDs is recommended when initiating therapy. Colchicine should be
dosed modestly at 0.5-0.6 mg 1-2 times/day. In patients who are
intolerant to or who have a contraindication to these agents, the
ACR TFP endorses low-dose prednisone or prednisolone (≤10 mg/day);
however, the TFP encourages carefully evaluating the need for such
therapy given the risks of prolonged steroid use. Prophylaxis
should be continued for 6 months after initiating ULT. In patients
without tophi present on physical examination, prophylaxis may be
stopped 3 months after achieving the target serum urate level. In
patients where tophi had been present but resolved, prophylaxis
should be continued for 6 months after achieving the target serum
urate level. In all cases, prophylaxis should be continued while
any signs of gout activity remain。
在降尿酸治疗的初期， 痛风症状发作的比例会比较高，所以在降尿酸治疗的初期， 建议给于预防性的药物抗炎治疗，
加上口服colchicine或者 低剂量的 NSAIDs治疗。Colchicine建议的剂量为 0.5--0.6 mg 1-2
次每天。 对上面的药物禁忌使用， 或者副反应不能承受的患者， ACR 认为可以给鱼低剂量的prednisone
或者prednisolone（小于10 毫克/每天）来治疗。由于长期使用所带来的风险， TFP 建议谨慎考虑使用激素类药物的需要。
在开始ULT治疗后， 预防性的抗炎治疗应该持续六个月。 对于体检没有发现痛风结节的病人， 在血清尿酸盐水平达到治疗的预期目标后三个月，
可以停用抗炎治疗。对于以前有痛风结节， 现在已经消失的病人， 预防性的抗炎治疗应该在血清尿酸盐水平达到治疗目标水平后六个月再停药。
对于所有的病案， 如果有痛风的任何症状活动， 都应该持续抗炎的预防性治疗。
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In summary, the major recommendations of the ACR TFP include
patient education, pharmacologic treatment to lower serum uric acid
to &6 mg/dL, prompt pharmacologic treatment of acute
gouty arthritis, and pharmacologic prophylaxis against gout attacks
when ULT is initiated.
总之， ACR的建议包括： 病人教育，药物治疗降低血清中的尿酸到6 mg/dl 一下， 对急性痛风性关节炎的及时药物治疗,
降尿酸治疗开始之后对于急性痛风性关节炎的药物预防。&
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