1、痛風患者高尿酸血症之治療（Therapy for hyperuricemia in gout）主題選取的考量 常見的疾病高盛行率 醫療花費增加 臨床治療標準不一 國際已有治療指引主題選取的考量常見的疾病高盛行率資料來源：PubMedKeyword:Hyperuricemia in Taiwan16篇 since 1968 to 2004主題選取的考量常見的疾病高盛行率Chang HY,Pan WH,Yeh WT,Tsai KS.Hyperuricemia and gout in Taiwan:results from the Nutritional and Health Survey in T
2、aiwan(1993-96).J Rheumatol.2001 Jul;28(7):1640-6.Population:2754 males and 2953 females aged 4 years and older The prevalence of hyperuricemia in aboriginal males and females：50 尿酸值尿酸值 年齡年齡男性男性 7.7 mg/dl 女性女性 6.6 mg/dl 19y/o261745y/o2223主題選取的考量常見的疾病高盛行率Lai SW,Tan CK,Ng KC.Epidemiology of hyperuricem
3、ia in the elderly.Yale J Biol Med.2001 May-Jun;74(3):151-7.Time：1998 MayPopulation：586(66%Men&34%Women)mean age was 73.1+/-5.3 years The proportions of hyperuricemia：(p 416.5 micromol/l(7 mg/dl)in boys and 357 micromol/l(6 mg/dl)in girls Ninety of 224 girls(40.2%)and 56 of 190 boys(29.5%)were hyperu
4、ricemic.主題選取的考量常見的疾病高盛行率CHOU Chungtei 周昌德 Hyperuricemia and gout among Taiwan Aborigines and Taiwanese-prevalence and risk factors Chin Med J 2003;116(7):965-967 The prevalence of hyperuricemia and gout in Atayal Aborigines to be 41.4%and 11.7%,respectively.27%to 45%of aboriginal boys and 13%to 41%o
5、f aboriginal girls had hyperuricemia.Kinmen：the prevalence of hyperuricemia in men was 25.8%(391/1515)through more than 6 years of follow-ups on 223 asymptomatic hyperuricemic patients,the 5-year cumulative incidence of onset of gout was 18.8%(42/223).The incidence increased with three different bas
6、eline levels of uric acid,from 10.8%(7.0 uric acid8.0),to 27.7%(8.0uric acid 9.0),to 61.6%(uric acid9.0).主題選取的考量國際已有治療指引資料庫：PubMedKeyword:Hyperuricemia guideline 8篇，since 1996 to 20031:Meyers OL,Cassim B,Mody GM.Hyperuricaemia and gout:clinical guideline 2003.S Afr Med J.2003 Dec;93(12 Pt 2):961-71.
7、2:Nakajima H,Matsuzawa Y.Introduction of the new guideline for the management of hyperuricemia and gout with special reference to its policy Nippon Rinsho.2003 Jan;61 Suppl 1:442-9.3:Tatsuno I,Saito Y.Hyperuricemia and atherosclerosis Nippon Rinsho.2003 Jan;61 Suppl 1:259-65.Review.主題選取的考量國際已有治療指引4:
8、Nakajima H.Definition and determination of serum uric acid level Nippon Rinsho.2003 Jan;61 Suppl 1:154-7.5:Nakajima H.Management of hyperuricemia in occupational health:with reference to guidelines for the management of hyperuricemia and gout Sangyo Eiseigaku Zasshi.2003 Jan;45(1):12-9.Review.Japane
9、se.6:Gorter KJ,Romeijnders AC.The standard hyperuricemia from the Dutch Family Physician;reaction from rheumatology and general medicine Ned Tijdschr Geneeskd.2002 May 4;146(18):872;author reply 872-3.Dutch.7:Chalmers J.Role of diuretics in the treatment of hypertension:from large controlled trials
10、to international guidelines Arch Mal Coeur Vaiss.1996 Sep;89 Spec No 4:39-43.Review.French.8:Cummins D,Sekar M,Halil O,Banner N.Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation.Transplantation.1996 Jun 15;61(11):1661-2.目前製作guideline之目的台灣地區高尿酸
11、血症的盛行率驚人，尤其施行成人健康體檢後，門診診療中常遇到病人詢問高尿酸血症該如何處理。而目前因無統一的guideline可供依循，治療標準不一，常造成醫師及患者的困擾。期待檢視文獻後，能提供有用的資訊，建立使用降尿酸藥物之臨床底線，以為臨床診療之準則。臨床問題1：無症狀之高尿酸血症需不需要治療？資料來源：PubMedKeyword:Asymtomatic hyperuricemiaAsymtomatic hyperuricemia and and treatment and reviewtreatment and review 23篇，since 1977 to 2003臨床問題1：無症狀之
12、高尿酸血症需不需要治療？Dincer HE,Dincer AP,Levinson DJ.Asymptomatic hyperuricemia:to treat or not to treat.Cleve Clin J Med.2002 Aug;69(8):594,597,600-2 passim.Publication Types:Review Treatment of asymptomatic hyperuricemia is not necessary in most patients,unless perhaps they have very high levels of uric ac
13、id or are otherwise at risk of complications,such as those with a personal or strong family history of gout,urolithiasis,or uric acid nephropathy.臨床問題1：無症狀之高尿酸血症需不需要治療？Uhlig T.Gout and hyperuricaemia-should both be treated?Tidsskr Nor Laegeforen.2003 Oct 23;123(20):2878-80 Publication Types:ReviewPa
14、tients with increased levels of uric acid will usually be treated with drugs if symptoms of acute arthritis or kidney stones occur.There is still no consensus on the treatment of individuals with asymptomatic hyperuricaemia.臨床問題1：無症狀之高尿酸血症需不需要治療？Harris MD,Siegel LB,Alloway JA.Gout and hyperuricemia.
15、Am Fam Physician.1999 Feb 15;59(4):925-34.Publication Types:Review Patients with asymptomatic hyperuricemia do not require treatment,but efforts should be made to lower their urate levels by encouraging them to make changes in diet or lifestyle.臨床問題1：無症狀之高尿酸血症需不需要治療？Pollmann G,Kullich W,Klein G.Ther
16、apy of hyperuricemia and gout Wien Med Wochenschr.1997;147(16):382-7 Publication Types:Review Dietary regimen are in the forefront in treatment of asymptomatic hyperuricemia.Uric acid lowering drugs can only be supported in repeated serum-measures from 9 mg/dl up.臨床問題2：痛風患者高尿酸血症之治療Keyword:Hyperurice
17、mia and Gout and treatment資料來源：PubMed Bandolier Google 臨床問題2：痛風患者高尿酸血症之治療Uhlig T.Gout and hyperuricaemia-should both be treated?Tidsskr Nor Laegeforen.2003 Oct 23;123(20):2878-80 Publication Types:Review Drugs for the treatment of acute arthritis attacks include non-steroidal anti-inflammatory drugs
18、(NSAIDs),glucocorticoids systematically or injected into the joint,and colchicine.As prophylactic long-term treatment of recurring attacks,allopurinol,probenicide and colchicine are therapeutic alternatives.臨床問題2：痛風患者高尿酸血症之治療Pittman JR.et al Diagnosis and management of gout.Am Fam Physician 1999 Apr
19、 1;59(7):1799-806,1810 Treatment goals(of gout)include termination of the acute attack,prevention of recurrent attacks and prevention of complications associated with the deposition of urate crystals in tissues.Pharmacologic management remains the mainstay of treatment.Acute attacks may be terminate
20、d with the use of nonsteroidal anti-inflammatory agents,colchicine or intra-articular injections of corticosteroids.Probenecid,sulfinpyrazone and allopurinol can be used to prevent recurrent attacks.Obesity,alcohol intake and certain foods and medications can contribute to hyperuricemia.These potent
21、ially exacerbating factors should be identified and modified臨床問題2：痛風患者高尿酸血症之治療Pollmann G,Kullich W,Klein G.Therapy of hyperuricemia and gout Wien Med Wochenschr.1997;147(16):382-7 Publication Types:Review The therapy of an acute attack of gout primarily is done with non-steroidal antiinflammatory dr
22、ugs,in rare cases with colchicine or corticoids.Gouty arthritis in intermission,independent of the extent of hyperuricemia,as well as chronic gout are indications for an uric acid lowering pharmacotherapy,usually for life.臨床問題2：痛風患者高尿酸血症之治療Rott KT,Agudelo CA:Gout.JAMA.2003;289(21):2857-60.A short,pr
23、actical,up-to-date review article targeted at the non-rheumatologist clinician.Agudelo CA,Wise CM:Crystal-associated arthritis in the elderly.Rheum Dis Clin North Am.2000;26(3):527-46.A comprehensive review by two of the leading authorities on gout and other crystal-induced arthropathies.Emmerson BT
24、:The management of gout.N Engl J Med.1996;334(7):445-51.A dated but insightful classic review article.PRODIGY Guidance-Gout.April 2002.www.prodigy.nhs.uk/A practical UK guideline that may be particularly useful for US clinicians,especially until a standard evidence-based US clinical guideline is ava
25、ilable.臨床問題2：痛風患者高尿酸血症之治療Bandolier：Allopurinol,oxipurinol,benzbromarone and probenecid for Allopurinol,oxipurinol,benzbromarone and probenecid for lowering uric acidlowering uric acid1.HE Paulus et al.Prophylactic colchicine therapy of intercritical gout.A placebo-controlled study of probenecid-trea
26、ted patients.Arthritis and Rheumatism 1974 17:609-614.2.HR Arntz et al.Serum uric acid lowering effect of allopurinol and benzbromarone in low dosage.Fortschr Med 1979 19:1-3.3.GW Schepers et al.Benzbromarone therapy in hyperuricaemia:comparison with allopurinol and probenecid.J Int Med Res 1981 9:5
27、11-515.4.PW Bull&JT Scott.Intermittent control of hyperuricaemia in the treatment of gout.J Rheumatol 1989 16:1246-1248.5.H Berg.Effectiveness and tolerance of long-term uricosuric treatment.Z Gestamte Inn Med 1990 45:719-20.6.I Walter-Sack et al.Uric acid lowering effects of oxipurinol sodium in hy
28、peruricaemic patients-therapeutic equivalence to allopurinol.J Rheumatol 1996 23:498-501.ReferenceDesignIncluded patientsoutcomesResultsHE Paulus et al,1974 Randomised,double blind comparison of probenecid 500 mg three times a day plus placebo versus probenecid plus colchicine for up to six months 5
29、3 men with gout and serum uric acid above 7.5 mg/dLUric acidResults reported only for men with significant and sustained falls in uric acid(38/52),when mean reduction was to 6.3 mg/dL from about 8.8 mg/dL.Acute attacks 0.5/month with probenecid alone,and 0.2/month with probenecid plus colchicine.Pre
30、treatment attacks averaged 3-4/12 months.Table 1:Allopurinol,benzbromarone and probenecid in goutTable 1:Allopurinol,benzbromarone and probenecid in goutReferenceDesignIncluded patientsoutcomesResultsArntz et al,1979 Random comparison of 100 mg allopurinol,20 mg benzbromarone and the combination in
31、a crossover trial with four week treatment periods Twelve patients with hyperuricaemia and type IV hyperlipidaemia Uric acid Significant falls for all treatments,but more so for the combination.Table 1:Allopurinol,benzbromarone and probenecid in goutTable 1:Allopurinol,benzbromarone and probenecid i
32、n goutReference DesignIncluded patientsoutcomesResultsSchepers,1981 Non-random crossover of probenecid 1000 mg,allopurinol 300 mg daily,benzbromarone 100 mg daily in six patients.One week of treatment with two week wash out.Serum uric acid of 450 mol/L or more.Uric acid Claims benzbromarone superior
33、 to other two treatments Table 1:Allopurinol,benzbromarone and probenecid in goutTable 1:Allopurinol,benzbromarone and probenecid in goutReferenceDesignIncluded patientsoutcomesResultsBull&Scott,1989 Random(last digit of hospital number)to continuous daily allopurinol 300 mg(10)or allopurinol 300 mg
34、(10)for two months every year.Aim of continuous treatment was uric acid below 6 mg/100 mL.Duration 2-4 years.At least three attacks of classical gouty arthritis with hyperuricaemia.Patients new to allopurinol.Acute attacks 20 attacks versus 26 attacks(continuous/intermittent)in first two years.No at
35、tacks per 166 patient months thereafter for continuous,versus 10/140 months for intermittent.Table 1:Allopurinol,benzbromarone and probenecid in goutTable 1:Allopurinol,benzbromarone and probenecid in goutReferenceDesignIncluded patientsoutcomes ResultsBerg,1990 Randomised comparison of 100 mg allop
36、urinol plus 20 mg benzbromarone daily compared with 300 mg allopurinol over 24 weeks.Serum uric acid above 6 mg/100 mL in 30 patients with asymptomatic hyperuricaemia.Uric acid In both groups mean uric acid fell from over 7 mg/100 mL to about 5.5 mg/100 mL.Table 1:Allopurinol,benzbromarone and probe
37、necid in goutTable 1:Allopurinol,benzbromarone and probenecid in goutReferenceDesignIncluded patientsoutcomesResultsWalter-Sack et al,1996 randomised,double blind crossover study of rapid release allopurinol 300 mg/day and 384 mg/day of oxipurinol sodium for 14 days each.Plasma uric acid above 7.5 m
38、g/100 mL in men Uric acid Mean pretreatment levels of about 8.5 mg/100 mL fell to about 5.5-6.0 mg/dL with treatment.Table 1:Allopurinol,benzbromarone and probenecid in goutTable 1:Allopurinol,benzbromarone and probenecid in gout臨床問題2：痛風患者高尿酸血症之治療Bandolier：Allopurinol,oxipurinol,benzbromarone and Al
39、lopurinol,oxipurinol,benzbromarone and probenecid for lowering uric acidprobenecid for lowering uric acid CommentComment：Not exactly a wealth of information yet.The longer duration study by Bull&Scott implies that maintaining a serum uric acid level below 6 mg/100 mL(350 mol/L)eventually depletes body stores and gives good relief from acute attacks.The Paulus probenecid study did not appear to show any reduction in attacks without addition of prophylactic colchicine.
