脊椎關節炎脊椎關節炎SpondyloarthritisSpondyloarthritis

魏正宗 MD, PhD.

中山醫學大學過敏免疫風濕科主任僵直性脊椎炎關懷協會第二屆理事長

Tel: 04 24729595 ext 34314; Email: wei3228@gmail.com

醫學系「免疫與感染學醫學系「免疫與感染學 VV 」模組」模組

遵守智慧財產權之觀念，使用正版教科書、禁止非法影印。

學習目標

Spondyloarthritis/ankylosing spondylitisSpondyloarthritis/ankylosing spondylitis

• DefinitionDefinition

• PathophysiologyPathophysiology

• Clinical manifestationsClinical manifestations

• DiagnosisDiagnosis

• TreatmentTreatment

• PrognosisPrognosis

脊椎關節炎脊椎關節炎Spondyloarthritis, SpASpondyloarthritis, SpA

1.1. 僵直性脊椎炎僵直性脊椎炎 (Ankylosing spondylitis, AS)(Ankylosing spondylitis, AS)2.2. 反應性關節炎反應性關節炎 (Reactive syndrome, Reiter (Reactive syndrome, Reiter

syndrome, ReA)syndrome, ReA)3.3. 乾癬關節炎乾癬關節炎 (Psoriatic arthritis, PsA )(Psoriatic arthritis, PsA )4.4. 發炎性大腸疾病發炎性大腸疾病 (Inflammatory bowel disease-(Inflammatory bowel disease-

related arthritis, enteropathic arthritis)related arthritis, enteropathic arthritis)5.5. 未分化型脊椎關節炎未分化型脊椎關節炎 (Undifferentiated (Undifferentiated

Spondyloarthritis, USpA)Spondyloarthritis, USpA)

Figure 1. Spectrum of Spondyloarthritis. AS, ankylosing spondylitis; PsA, psoriatic arthritis; ReA, reactive arthritis; IBD, inflammatory bowel diseases-associated arthritis; USpA, undifferentiated spondyloarthritis.JC Wei. Chronic Inflammation: Causes, Treatment Options and Role in Disease.  Nova Science Publishers, Inc. 2013

Spectrum of SpondyloarthritisSpectrum of Spondyloarthritis• By diseasesBy diseases

– Ankylosing spondylitisAnkylosing spondylitis– Psoriatic arthritisPsoriatic arthritis– Reactive arthritisReactive arthritis– Inflammatory bowel diseases-associated arthritisInflammatory bowel diseases-associated arthritis– Undifferentiated spondyloarthritisUndifferentiated spondyloarthritis

• By clinical manifestationsBy clinical manifestations– Axial SpondyloarthritisAxial Spondyloarthritis

• Non-Radiographic Axial SpondyloarthritisNon-Radiographic Axial Spondyloarthritis• Established Axial SpondyloarthritisEstablished Axial Spondyloarthritis

– Peripheral SpondyloarthritisPeripheral Spondyloarthritis

僵直性脊椎炎流行病學僵直性脊椎炎流行病學 好發於好發於 1616 至至 4040 歲的成年人歲的成年人 男女比例約為男女比例約為 33 ：： 11 盛行率則約為盛行率則約為 0.2~0.4 %0.2~0.4 % 95%95% 的的 ASAS 病人具有病人具有 HLA-B27HLA-B27 基因基因 台灣全人口約有百分之五的人帶有台灣全人口約有百分之五的人帶有 HLA-HLA-

B27B27 基因，其中有百分之二到十會發病成僵基因，其中有百分之二到十會發病成僵直性脊椎炎。直性脊椎炎。

JC WEI, PhD thesis, 2007JC WEI, PhD thesis, 2007

HLA-B27HLA-B27

HLA-B27HLA-B27 ASAS

Taiwan estimated prevalence: Taiwan estimated prevalence: • HLA-B27: 5% HLA-B27: 5% • SpA: 1%SpA: 1%• AS: 0.4% AS: 0.4%

In B27+ families, HLA-B27 is In B27+ families, HLA-B27 is essentialessential but but not not sufficientsufficient for AS for AS

10%10%

90%90%

HLA-B27

consists of a heavy chain having three domains, which non-covalently binds short peptides and 2-microglobulin ( 2 m)

Nat Clin Practice Rheumatol 2006; 2: 383-392

AS

Genetic background•HLA-B27, B60, B61•ERAP-1•IL23R, IL1, IL12…

Environmental factors•Infection, eg. Klebsiella pneumoniae•Trauma•Smoking

Immune dys-regulation•HLA-B27 mis-folding causing ER stress•Free form HLA-B27 homo-dimer•Th17/IL17, Th1/TNF

症狀症狀

1.1. 發炎性下背痛發炎性下背痛：：薦腸關節炎薦腸關節炎 (sacroiliitis)(sacroiliitis)及脊椎炎及脊椎炎 (spondylitis) (spondylitis) 。。

2.2. 接骨點炎接骨點炎 (enthesitis) (enthesitis) 。。3.3. 不對稱性的下肢關節炎。不對稱性的下肢關節炎。4.4. 有關節外的表徵：如乾癬有關節外的表徵：如乾癬、、腸炎腸炎、、尿道尿道

炎炎、、葡萄膜炎。葡萄膜炎。

發炎性下背痛 Inflammatory back pain, IBP

1. 慢性下背痛超過三個月2. 發病年齡小於 40 歲3. 漸進和緩地 4. 晨間脊椎僵硬5. 運動過後則改善

For spondyloarthritis:sensitivity= 95-100%, specificity= 85-90%

Calin. JAMA, 1977; Linden. Scan J Rheu, 1988.

接骨點病變接骨點病變 (Enthesopathy)(Enthesopathy)

接骨點接骨點 (enthesis)(enthesis) ，也稱附著點，指的是肌，也稱附著點，指的是肌腱、韌帶、關節滑膜與骨頭的交界點。腱、韌帶、關節滑膜與骨頭的交界點。

好發位置：跟腱、足底、膝蓋下方、恥骨好發位置：跟腱、足底、膝蓋下方、恥骨聯合、脊椎體等處。聯合、脊椎體等處。

Sausage digit, dactylitis Achilles enthesitis

週邊關節炎週邊關節炎 僵直性脊椎炎的病人，有僵直性脊椎炎的病人，有 40%40% 左右，會發左右，會發

生週邊的關節炎，特別是髖關節及膝關節。生週邊的關節炎，特別是髖關節及膝關節。 十六歲以前的幼年型病人，通常最早出現十六歲以前的幼年型病人，通常最早出現

的症狀，就是下肢關節炎和接骨點病變。的症狀，就是下肢關節炎和接骨點病變。

Uveitis

Psoriasis

Extra-articular Extra-articular manifestations of ASmanifestations of AS

•Uveitis•Psoriasis•Inflammatory bowel•Mucosal ulcer•IgA nephropathy•Heart block•Apical lung fibrosis

Finger to floor test

Physical ExaminationPhysical Examination

Posterior SI compression test

Patrick test

實驗室檢查實驗室檢查 紅血球沈降速率紅血球沈降速率 (ESR)(ESR) 及及 CC 反應蛋白反應蛋白 (CRP)(CRP)可以評估發炎狀況可以評估發炎狀況

IgAIgA Urine analysisUrine analysis HLA-B27 typingHLA-B27 typing

AnteriorAnteriorSquaring of Squaring of vetebral bodiesvetebral bodies

SyndesmophyteSyndesmophyte

Corner enthesitis

X ray finding of spondylitisX ray finding of spondylitis

Diffuse idiopathic skeletal Hyperostosis(DISH)

AS with bamboo spine

薦腸關節炎薦腸關節炎 sacroiliitissacroiliitis

Grade 2 sacroiliitisGrade 2 sacroiliitis Focal erosion and sclerosis of SI jointsFocal erosion and sclerosis of SI joints

SacroiliitisSacroiliitis薦腸關節炎薦腸關節炎

Osteiitis condensans iliiOsteiitis condensans ilii

緻密性腸骨炎 緻密性腸骨炎

CT scan of SI jointsCT scan of SI joints

僵直性脊椎炎的診斷標準僵直性脊椎炎的診斷標準

Modified New York criteria, 1984Modified New York criteria, 19841.1. 下背痛及僵硬，休息無法減輕，下背痛及僵硬，休息無法減輕， 33 個月以上個月以上2.2. 腰椎運動範圍受限腰椎運動範圍受限3.3. 擴胸範圍受限擴胸範圍受限4.X4.X 光有薦腸關節炎，雙側光有薦腸關節炎，雙側 22 級或單側級或單側 33 級以上級以上

確定診斷：第確定診斷：第 44 點點 加加 1-31-3 中任何一點中任何一點  

CASPAR Criteria for the CASPAR Criteria for the Classification of PsAClassification of PsA

Inflammatory articular disease (joint, spine, or entheseal) Inflammatory articular disease (joint, spine, or entheseal) With With 3 points from following categories:3 points from following categories:

− − PsoriasisPsoriasis:: current (2), history (1), family history (1) current (2), history (1), family history (1) − − Nail dystrophy (1)Nail dystrophy (1)− − Negative rheumatoid factor (1)Negative rheumatoid factor (1)− − Dactylitis: current (1), history (1) recorded by a Dactylitis: current (1), history (1) recorded by a

rheumatologistrheumatologist− − Radiographs: (hand/foot) evidence of juxta-articular new Radiographs: (hand/foot) evidence of juxta-articular new

bone formationbone formation

Specificity 98.7%, Sensitivity 91.4%Specificity 98.7%, Sensitivity 91.4%

Taylor et al. Arthritis & Rheum 2006;54: 2665-73

Psoriatic ArthritisPsoriatic Arthritis

ACR Slide Collection on the Rheumatic Diseases; 3rd edition. 1994.Data on file, Centocor, Inc.

ASAS classification criteria for peripheral spondyloarthritis

Rudwaleit M et al. Ann Rheum Dis 2011;70:25-31©2010 by BMJ Publishing Group Ltd and European League Against Rheumatism

脊椎關節炎的治療脊椎關節炎的治療 是根據疾病的臨床活性以及侵犯的器官程是根據疾病的臨床活性以及侵犯的器官程度而定度而定

主要有主要有• 復健及運動治療、復健及運動治療、• 非類固醇類消炎止痛藥非類固醇類消炎止痛藥 (NSAID)(NSAID) 、、• 免疫調節劑免疫調節劑 (Disease modifying anti-(Disease modifying anti-

rheumatic drugs, DMARD)rheumatic drugs, DMARD) 、、• 類固醇局部注射、類固醇局部注射、• 抗腫瘤壞死因子（抗腫瘤壞死因子（ anti-TNFanti-TNF ）療法等等。）療法等等。

運動運動 運動是最基本的治療運動是最基本的治療 運動的基本原則是每天都做持之以恆，尤運動的基本原則是每天都做持之以恆，尤其是睡覺以前要作柔軟及伸展脊椎的運動，其是睡覺以前要作柔軟及伸展脊椎的運動，以預防脊椎的變形。以預防脊椎的變形。

運動應該是溫和、有氧、循序漸進的，盡運動應該是溫和、有氧、循序漸進的，盡量避免可能發生劇烈撞擊的運動，例如搏量避免可能發生劇烈撞擊的運動，例如搏擊、橄欖球等等。擊、橄欖球等等。

最好的運動是游泳及柔軟體操，打太極拳，最好的運動是游泳及柔軟體操，打太極拳，瑜珈、適度的仰臥起坐及伏地挺身也都是瑜珈、適度的仰臥起坐及伏地挺身也都是很適合脊椎炎的運動。很適合脊椎炎的運動。

                                                                            

                                           

National Ankylosing Spondylitis Society National Ankylosing Spondylitis Society (NASS) (NASS)

AS caring society, ROC, www.ascare.org.twwww.DrWei.idv.tw

非類固醇消炎藥非類固醇消炎藥（（ NSAIDNSAID ））

急性期應全劑量投予，緩解期可由病人根據急性期應全劑量投予，緩解期可由病人根據疼痛程度自行調整。疼痛程度自行調整。

COX-2 inhibitors, COX-2 inhibitors, 如如 meloxicam (Mobic), meloxicam (Mobic), celecoxib (Celebrex), etoricoxib (Arcoxia) celecoxib (Celebrex), etoricoxib (Arcoxia) 效果效果與傳統的消炎止痛藥相當且副作用較輕。與傳統的消炎止痛藥相當且副作用較輕。

併用止痛劑（如併用止痛劑（如 acetamenophenacetamenophen ）） , , 肌肉鬆弛肌肉鬆弛劑，低劑量劑，低劑量 amitriptylineamitriptyline 有很好的加成效果。有很好的加成效果。

免疫調節劑免疫調節劑 (DMARDs)(DMARDs)

Sulfasalazine (Salazopyrin)Sulfasalazine (Salazopyrin) 是首選用藥，每是首選用藥，每天二至三公克對天二至三公克對週邊關節炎、乾癬、發炎週邊關節炎、乾癬、發炎性大腸疾病及葡萄膜炎性大腸疾病及葡萄膜炎等有效，但對只有等有效，但對只有軸心關節侵犯的脊椎炎是否有效則有爭論。軸心關節侵犯的脊椎炎是否有效則有爭論。

For peripheral PsA: Methotrexate (MTX), For peripheral PsA: Methotrexate (MTX), Leflunomide, CyclosporineLeflunomide, Cyclosporine

抗腫瘤壞死因子生物製劑抗腫瘤壞死因子生物製劑（（ Anti-TNFAnti-TNF ））

包括包括 Etanercept (Enbrel, Etanercept (Enbrel, 恩博恩博 ), Adalimumab ), Adalimumab (Humira, (Humira, 復邁復邁 ), Golimumab (Simponi, ), Golimumab (Simponi, 辛普尼辛普尼 )) 。。

對僵直性脊椎炎及乾癬性關節炎及其他型脊椎炎，對僵直性脊椎炎及乾癬性關節炎及其他型脊椎炎，都有非常顯著且快速的效果。都有非常顯著且快速的效果。

約約 80%80% 患者接受治療兩週左右即有明顯的進步。患者接受治療兩週左右即有明顯的進步。 藥價每年約藥價每年約 4040 萬台幣萬台幣 必須定期皮下注射。必須定期皮下注射。 是目前治療脊椎炎最有效的的藥物。是目前治療脊椎炎最有效的的藥物。

Ustekinumab (Stelara, Ustekinumab (Stelara, 喜達諾喜達諾 ))

• MoAb against p40 subunit of IL-12 /IL-23

• Approved for severe plaque psoriasis

• SC, q3m• Better efficacy

than TNFi: PASI-90 45% vs 23%

手術手術 對脊椎嚴重前彎的病人，可以手術矯對脊椎嚴重前彎的病人，可以手術矯正。正。

髖關節嚴重受損時，應行關節置換術。髖關節嚴重受損時，應行關節置換術。

Take Home MessageTake Home Message

1.1. Spondyloarthritis is a gene-environment interacted Spondyloarthritis is a gene-environment interacted chronic inflammatory disease.chronic inflammatory disease.

2.2. Early diagnosis depends on clinical manifestations, Early diagnosis depends on clinical manifestations, HLA-B27 and Imaging studies, esp. MRI.HLA-B27 and Imaging studies, esp. MRI.

3.3. Optimal treatment byOptimal treatment by• Exercise and NSAID for Exercise and NSAID for allall SpA patients. SpA patients.

• Sulfasalazine in peripheral AS and uveitis. Sulfasalazine in peripheral AS and uveitis.

• Methotrexate, cyclosporine and leflunomide in PsA. Methotrexate, cyclosporine and leflunomide in PsA.

4.4. TNF blockers are break through in the treatment of TNF blockers are break through in the treatment of AS, PsA, psoriasis and IBD.AS, PsA, psoriasis and IBD.

ReferencesReferences

eMedicine :Ankylosing Spondylitis and eMedicine :Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy Undifferentiated Spondyloarthropathy http://www.emedicine.com/med/topic2700.htmhttp://www.emedicine.com/med/topic2700.htm

Dr Wei Blog: Dr Wei Blog: http://DrWei.blogspot.comhttp://DrWei.blogspot.com

僵直性脊椎炎僵直性脊椎炎魏正宗魏正宗 . . 健康世界出版社健康世界出版社 , 2005, 2005 年年

考試範圍

講義、共筆 -80%教科書及期刊論文內容 -20%。

eMedicine :Ankylosing Spondylitis and eMedicine :Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy Undifferentiated Spondyloarthropathy http://www.emedicine.com/med/topic2700.htmhttp://www.emedicine.com/med/topic2700.htm