전공의 연수강좌

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주연 승
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1 내과전공의연수강좌 원광대학병원류마티스내과 이명수

2 증례 1 68 세여자가약 1 년전부터발생한관절통을주소로내원하였다. 조조강직은 2 시간정도지속되었으며양쪽손목관절, 양쪽 2,3 번중수지관절, 오른쪽팔꿈치관절에압통및부종이관찰되어내원하였다.

3 WBC 7,800/mL, Hb 10.2 g/dl, PLT 550,000/mL, ESR 45 mm/hr, CRP 3.5 mg/dl, ANA: 음성 uric acid 5.6 RF 3000 IU/mL, Anti-citrullinated protein Ab (ACPA) 100 U/mL 이었다.

4 본환자에대한설명으로옳은것은? 1) 류마티스관절염진단 score 는 7 점이다 2) 단순 X- 선촬영에서류마티스관절염에서관찰되는 osteophyte 가 주로관찰된다 3) 고령에서발생한류마티스관절염으로예후가좋을것이다 4) 고역가의 RF 로인해관절외증상이발생할가능성이높다 5) 허리통증이심할경우류마티스관절염의척추침범을의심해야한다

5 2010 ACR/EULAR classification criteria for RA

6 문제 1-2) 위환자가후두부두통과경부통증을호소하였고통증은누워있을때심하지않고앉거나일어서고머리를앞으로굽힐때심해지는양상을보였다. 시행해야할검사는?

7 류마티스관절염의경추침범

8 증례 2 관절증상이없는 45 세남자가건강검진에서 RF 양성으로문의되었다.

9 검사소견 RF 56 HBs Ag(+) ESR, CRP : normal ANA : negative

10 본환자에대한진료시옳지않은접근은? 1) RF 는 IgG 의 Fc portion 에대한 IgM 자가항체이다 2) 정상인에서도 5% 가양성이나올수있으므로관절증상이없으면류마티스관절염이라고할수없다 3) RF 보다민감도가우수한항 CCP 검사를시행한다 4) HBsAg(+) 이므로이로인한위양성가능성이있다 5) RF 가양성이므로쇼그렌등의감별진단을위한병력청취를한다

11 RF Vs CCP Ab IgG의 Fc portion에대한 Ab RA 환자에서도 75-80% 에서만양성이며, 다른결체조직질환에서도양성으로나타난다. RF는건강한사람에서도 5% 에서양성으로나타나며나이가증가함에따라그양성률도높아져 65 세이상에서는 10-20% 가양성을보여진단에특이적이지않다. 높은역가는나쁜예후를시사한다. High titer RF 는 more severe and progressive disease with extraarticular manifestations 와연관된다. RF는 disease activity와는관련이없다. RA 환자에서존재하는 citrulinated protein에대한자가항체로, cyclic 구조의 citruline epitop 이 RA 환자의혈청에보다민감하게반응. RA의진단에서 RF와비슷한민감도를보이지만특이도가 95% 에달한다. 정상인에서도 1.5% 정도에서발견되므로 RA의발병을예측하는인자로사용할수는없다. Anti-CCP titer를 disease activity를평가하는데이용하지는않는다. 예후와관련이있으며, anti-ccp 항체가양성인경우관절손상등 outcome이더나쁘다. 특정 HLA allele이있거나흡연을하는경우에는 RA 발현이전에양성을보일수있다.

12 증례 3 42 세여자 3 개월간다발성관절염 손가락, 손목, 무릎, 발목, 발가락 하루종일지속되는조조강직 양쪽손목, 무릎, 발목관절압통및종창 Patient Global VAS 80mm lab Rheumatoid factor ; 264 anti-ccp (+) ESR, CRP ; 42mm/hr, 13.08mg/dl DAS28-ESR : 3.17

13 골미란관찰 (-) Hand x-ray

14 Bone scan

15 RA treament 위환자의치료로적절치못한것은? 1) MTX monotherapy 와 low dose steroid 로치료를시작한다. 2) MTX 를기본약제로 sulfasalazine or hydroxychloquine 과 combination 치료를한다. 3) 부작용으로 MTX 를사용하지못할경우 Leflunomide 을대체약으로우선고려해본다. 4) 3 개월이내호전이없으면치료약제를변경해야한다. 5) High disease activity 일때는일시적인고용량스테로이드를사용한다.

reached after 6 months, but therapy should be adapted or changed, if

16 Treatment target is clinical remission or if remission is unlikely to be achievable, at least low disease activity; the target should be reached after 6 months, but therapy should be adapted or changed, if no improvement is seen after 3months. Ann Rheum Dis Mar;73(3):

17 Ann Rheum Dis Mar;73(3):

18 Ann Rheum Dis Mar;73(3):

19 2013 Update of the EULAR recommendations 1. Therapy with DMARDs should be started as soon as the diagnosis of RA is made 2. MTX should be part of the first treatment strategy in patients with active RA 5. In cases of MTX contraindications (or early intolerance), sulfasalazine or leflunomide should be considered as part of the ( first) treatment strategy 6. In DMARD-naïve patients, irrespective of the addition of glucocorticoids, cs(conventional synthetic) DMARD monotherapy or combination therapy of csdmards should be used 7. Low-dose glucocorticoids should be considered as part of the initial treatment strategy (in combination with one or more csdmards) for up to 6 months, but should be tapered as rapidly as clinically feasible Ann Rheum Dis Mar;73(3):

20 증례 4 35 세여자 1 년전 RA 진단 RF >100, Anti-CCP >100 P/Hx NYHA Class III CHF d/t dilated Cardiomyopathy MTX 10mg/ 주, HCQ, SSZ 3 개월투여 DAS 28 ; 6.1 X-ray ; 새롭게 erosion (+) Tuberculin test (+)>10mm, Quantiferon (-)

22 Treatment on special condition 다음환자의치료에대해맞는것을고르시오 1) 결핵 Prophylaxis 후항 TNF 제재를투여한다. 2) Abatacept 는결핵반응여부와관계없이투여할수있다. 3) 결핵 Prophylaxis 후 Tocilizumab 을투여한다. 4) 생물학적제재투여전생백신 herpes zoster 예방접종은금기이다. 5) 임신을원할경우 MTX 를 Leflunomide 로대체한다.

23 Ann Rheum Dis Mar;73(3):

24 Arthritis Care & Research Vol. 64, No. 5, May 2012, pp

25 Special condition - Vaccination Singh JA et al. Arthritis Care Res 2012; 64:

26 Special condition - Congestive Heart failure Arthritis Care Res 2012 May; 64(5):

27 Pregnancy in RA Methotrexate and leflunomide contraindicated during pregnancy due to teratogenicity [harrison 18 th Chap 321] Category B hydrocortisone, cortisone, or prednisone Sulfasalazine Anti TNF Ab ; preterm delivery and poor growth

28 Composite indices of RA disease activity Disease Activity Score (DAS) DAS28 (ESR) 0.54* (Ritchie index)+0.065*(sjc)+0.33*ln(esr)+0.007*(gh) 0.56* (TJC28)+0.28* (SJC28)+0.014*GH+0.70*ln(ESR) DAS28 (CRP) Simplified Disease Activity Index (SDAI) Clinical Disease Activity Index (CDAI) 0.56* (TJC28)+0.28* (SJC28)+0.014*GH +0.36*ln(CRP(mg/L)+1) TJC28+SJC28+PGA (cm VAS)+EGA (cm VAS) +CRP (mg/dl) TJC28+SJC28+PGA (cm VAS)+EGA (cm VAS)

29 Cutoff values for different disease activity states Index Disease activity state Definition DAS Remission Low disease activity Moderate disease activity High disease activity > 3.7 DAS28 SDAI CDAI Remission Low disease activity Moderate disease activity High disease activity Remission Low disease activity Moderate disease activity High disease activity Remission Low disease activity Moderate disease activity High disease activity > > > 22

30 Biologic agents 의종류 Targeting pro-inflammatory cytokine TNF inhibition : etanercept soluble TNF receptor infliximab adalimumab anti-tnf mab golimumab certolizumab pegol IL-6 inhibition : tocilizumab - mab against IL-6 receptor Targeting T cell abatacept block costimulatory pathway Targeting B cell Rituximab anti-cd20 mab Targeting intracellular signaling pathways Tofacitinib: Jak inhibitor

Jak inhibitor 1 Cytokine binding to its cell surface receptor leads to receptor polymerization and activation of associated JAKs JAK JAK 2 Activated JAKs phosphorylate the recep

31 Jak inhibitor 1 Cytokine binding to its cell surface receptor leads to receptor polymerization and activation of associated JAKs JAK JAK 2 Activated JAKs phosphorylate the recep tors that dock STATs STAT P STAT STAT P 3 Activated JAKs phosphorylate STATs, which dimerize and move to the nucleus to activate new gene transcription P STAT STAT P Gene transcription

32 Jak inhibitor tofacitinib monotherapy vs MTX monoth erapy superior to methotrexate More favorable in reducing signs and symptoms of rheumatoid art hritis inhibiting the progression of structural joint dam age [N Engl J Med 2014; 370: ]

33 증례 5 57세남자 2년전 RA 진단 MTX 10mg, SSZ 1g 투여 2개월전부터 exertional dyspnea 호소 Echo no Pul. HTN

34 Chest PA

35 HRCT

36 이환자에대한설명으로틀린것은? 1) PFT 에서 restrictive pattern 을보인다. 2) Idiopathic ILD 보다예후가더좋다 3) 치료는 cyclophosphamide 나 azathioprine, MMF 를투여한다. 4) 조직학적으로 UIP or NSIP pattern 이가장많다. 5) RA 치료는 MTX 를중단하고 Leflunomide 를추가한다.

37 ILD in RA prognosis not quite as poor as that of idiopathic pulmonary fibrosis (e.g., usual interstitial pneumonitis) because ILD secondary to RA responds more favorably than idiopathic ILD to immunosuppressive therapy [Harrison 18 th chap. 321] Treatment Cyclophosphamide and azathioprine (1 2 mg/kg lean body weight per day), with or without glucocorticoids, have been tried with variable success in IPF [Harrison 18th chap. 261]

38 ILD in RA Pulmonary function test restrictive defect reduced total lung capacity (TLC), functional residual capacity, and residual volume [Harrison 18th chap 261] histopathologic patterns most commonly seen UIP and NSIP [Rheumatology, 6ed]

39 ILD in RA Leflunomide in ILD Interstitial lung disease (ILD) has been reported in patients receiving leflunomide Increased risk of ILD with leflunomide 이전 methotrexate 를사용하거나 preexisting ILD 가있는환자에서 --> relative risk (RR) of 2.6 [Rheumatology, 6ed]

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<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770> 2012 개원의와함께하는임상강좌 경희대학교의학전문대학원류마티스내과학교실 홍승재 진단의중요성 치료의첫단계 : 정확한진단은아무리강조해도지나치지않음 감별진단의중요성 : 진단이달라짐에따라치료시기와약제의선택, 진행경과, 합병증여부, 예후및삶의질에차이가있다. 류마티스관절염 (Rheumatoid arthritis) : 비교적젊은나이에발병하며, 진단초기부터관절염증에의한골파괴소견이가능함.