신드롬

(1)

류마티스 증례

이화의대

이지수

(2)

Sexiness of Rheumatology…

mystery ^and complexity

-R. Kavanagh

전신적 관점 (다기관 침범 질환) 에서 볼 것

증상 징후를 관련 있는 한 무리의

신드롬 ^{으로 파악}

(3)

40세 여자 ^가 ^전신부종 으로 병원에 왔다.

부종은 수개월 전부터 시작되었는데 최근 일주일 동

안 심해져서 평소에 신던 구두를 신을 수 없었다. 소

변에서 거품이 많이 나왔고 소변량이 줄어들었다고

하였다. 혈압은 140/90mmHg, 맥박수는 82회/분,

호흡수 18회/분, 체온 37.4

^o

C였다. 얼굴에 발진이 있

었고 양쪽 하지에 오목부종이 관찰되었다.

(4)

(5)

헤모글로빈 7.9g/dL, 백혈구 2,800/mm³, 혈소판 89,000/mm³ 적혈구 침강속도 50mm/h(정상 <15mm/h)

크리아틴키나아제 85(정상0-185) IU/L

소변 검사 단백 +++, 백혈구 1-3/HPF, 적혈구 10-15/HPF BUN 30mg/dl(정상 5-23), 크리아티닌 1.7mg/dL(정상 05-1.4) 류마티스 인자 15(정상 0-18) IU/mL, 항핵항체 1:320 speckled

양성

(6)

문제1. 진단은?

① 결절 다발동맥염

② 림프종

③ 용혈-요독 증후군

④ 전신홍반루푸스

⑤ 피부근염

(7)

Diagnosing LUPUS

Complex problem solving

(8)

First ,

start to identify

symptoms

&

signs

1. Initial symptoms may be constitutional

(Malaise, fatigue, fever, weight loss)

2. Symptoms in more than one organ system may suggest SLE

3. Careful review of symptoms & signs must be made over time (it may take years to make a

SLE diagnosis)

(9)

Frequent manifestations

Arthritis/arthralgia (64-91%)

Skin lesions (55-86%)

Renal involvement (28-73%)

Raynaud’s phenomenon (24-61%)

CNS involvement (11-49%)

GI symptoms (12-20%) Lymphadenopathy (10-30%) Nephrotic syndrome (13-14%)

Lung involvement (7-14%)

Myositis (4-9%) Myocarditis (2-3%)

Cervera R et al. 1993

(10)

Second ,

order lab tests that can be helpful

Antinuclear antibody (99%+) Complements (C3, C4)

Direct Coomb’s test

(11)

ANA clinical value

Very helpful

SLE 95-100% +ve

SSc 60-80%

Diagnostic

Drug induced lupus 100%

Autoimmune hepatitis 100%

Somewhat helpful

Sjogren’s syndrome 40-70%

Polymyositis/dermatomysitis 30-80%

In normal individuals

1:40 20-30%

1:80 10-12%

1:160 5%

1:320 3%

(12)

Lab report

FANA 1:320+ speckled

titer pattern

(13)

Homogeneous Speckled

Peripheral

Anti-histone Anti-Sm

Anti-SSA/Ro Anti-SSB/La

Anti-DNA

Nucleolar

Anti-Scl70

(14)

Third ,

distinguish from the imitators Rheumatoid arthritis

Dermatomyositis/ polymyositis Viral arthritis

Drug reaction

Hematologic diseases (lymphoma, ITP) Renal diseases

and more….

(15)

SLE classification criteria

1997^updatedACR classification criteria

1. Malar rash 2. Discoid rash 3. Photosensitivity

4. Oral ulcer 5. Arthritis 6. Serositis 7. Renal disorder 8. Neurologic disorder 9. Hematologic disorder 10. Immunologic disorder

11. Positive ANA

>4/11 criteria for classification

Sensitivity 86% specificity 92%

(16)

C3 50.1mg/dL(정상90-180), C4 5.6mg/dL(정상10-40) 항DNA항체 60IU/mL(~5.3)

24시간 요단백 5159mg

신장조직검사: ISN/RPS criteria

IV-G(A)

미만성 완전증식 루푸스신염(활동성)

추가검사

(17)

문제2. 치료는?

① Prednisolone 20mg + azathioprine

② Prednisolone 60mg + methotrexate

③ Prednisolone 20mg + MMF

④ Prednisolone 20mg + taclolimus

⑤ prednisolone 60mg + cyclophosphamide

(18)

Classification of SLE according to clinical severity

MILD DISEASE

Fever Arthritis

Mild pericarditis

Small pleural & pericardial effusions

Rash Fatigue headache

SEVERE LIFE-or ORGAN THREATENING DISEASE

Massive pleural, pericardial effusion

Significant renal disease (Class IV)

Hemolytic anemia Thrombocytopenia

(<100,000/mm³) CNS involvement

Acute vasculitis Myocarditis

Lupus pneumonitis, lung hemorrhage

NSAIDs,

hydroxychloroquine, low dose CS (5-20mg/d)

High dose CS (1-2mg/kg/d, or 1g pulse)

(19)

Lupus nephritis treatment

Proteinuria >0.5g/d, >3+dipstick, red cell cast

2011 guideline recommend to

biopsy all patients

ISN/RPS 2003 classification I Minimal mesangial LGN

II Mesangial proliferative LGN III Focal LGN

IV Diffuse segmental or global LGN V Membranous LGN

VI Advanced sclerotic LGN

<or>50% A/C

Class IV diffuse proliferative LN treatment

Induction: high dose CS+ MMF or CY

Maintenance: low dose CS +AZA or MMF

(20)

• Control of proteinuria

– ACE-I and ARB, combination better

• Retrospective study ACE-I/ARB-proteinuria significantly improved at 6mo/24mo -Lupus 2005;14:942

• Retrospective study ARB for 6 months-reduction of proteinuria in 83% of patients – Lupus 2005;14:288

• ACE-I use delayed occurrence of nephritis (75.4% vs 88.1%); LUMINA lupus cohort of North America –Rheumatology 2008;47:1093

• Blood pressure control

– ACE-I or ARB or combination-choice

– Diuretics, calcium channel blocker-other choice – Target blood pressure <130/80mmHg

– ACE-I should be used with caution in SLE associated with APS-risk of renal artery stenosis increases

• Assess vascular risk and control hyperlipidemia

– Lipoprotein(a) is increased in lupus nephritis –Rheumatology 2005;44:1492

– Drug of choice for controlling hyperlipidemia-STATIN

Clinical management beyond immunosupression

(21)

• Assess infection risk and vaccination

– Live vaccines contraindicated

– Advise pneumovax and influenza vaccination

• Examine for APS nephropathy-adverse outcome

– Proposed features – Thrombos Haemost 2006;4:295

Thrombotic microangiopathy involving both arterioles and glomerular capillaries

And/or one more of

Fibrous intimal hyperplasia involving organizing thrombi Fibrous occlusion of arteries and arterioles

Focal cortical atrophy Tubular thyroidisation

(22)

• Bone protection

– All patient should be supplemented with calcium with vitamin D

– Calcitriol to supress PTH secretion

– Steroid induced osteoporosis high risk group-bisphosphonate

• Assess compliance

– Education

– Route of administration

– Patient choice- decrease ovarian toxicity (low dose IVC, MMF)

• Adjunctive therapy-antimalarial

– Exposed to antimalarial before lupus nephritis was negatively associated with renal failure, HT, thrombosis, and infection

-Lupus 2008;17:281-288

(23)

경과

고용량 스테로이드와 cyclophosphamide 정맥주사 치료 6개월 후 루푸스 신염 관해 도달하여 저용량 스테로이드와 azathioprine으로 유지치료를 시작하였다.

추적관찰 도중 환자가 내원하지 않아서 치료가 중단되었다.

(24)

3년 뒤

43세 여자가 왼쪽 팔다리의 마비를 호소하며 응급실 내원하였 다. 3년 전 루푸스 신염으로 치료 받던 도중 자의로 치료 중단 했던 환자이다. 혈압은 150/100mmHg, 맥박수는 82회/분, 호 흡수 18회/분, 체온 38.0^oC였다. 양쪽 하지에 오목부종이 관찰 되었다.

(25)

DWI ADC rCBV TTP

Brain MRI

(26)

문제3. 연관이 있는 자가항체는?

① Anti-cardiolipin

② Anti-DNA

③ Anti-RNP

④ Anti-Sm

⑤ Anti-SSA

(27)

헤모글로빈 8.5g/dL, 백혈구 5,680/mm³, 혈소판 170,000/mm³ 적혈구 침강속도 35mm/h(정상 <15mm/h)

소변 검사 단백 +++, 백혈구 3-5/HPF, 적혈구 20-25/HPF BUN 30mg/dl(정상 5-23), 크리아티닌 1.5mg/dL(정상 05-1.4)

Lupus anticoagulant 58 sec(정상 31-44sec), anti-cardiolipin IgG 38.5 GPL(정상<15), anti-b2GPI(neg)

(28)

Anti-phospholipid syndrome

Clinical criteria

Vascular thrombosis Pregnancy morbidity

● One or more episodes of arterial, venous, or small vessel thrombosis

● One or more unexpected death of normal fetus, or beyond 10 week of gestation

● Premature birth before 34 weeks of gestation due to eclampsia, pre- eclampsia and placental insufficiency

● Three or more unexplained consecutive spontaneous abortions before 10 week of gestation

Laboratory criteria

Two or more times positive 12 weeks apart of antibodies against phospholipid- binding proteins

● Lupus anticoagulant (LA)

● Anticardiolipin antibodies (aCL) IgG and/or IgM

● Anti-b₂ glycoprotein-I (ab₂ GPI) IgG and/or IgM

1 clinical criteria + 1 laboratory criteria

(29)

Clinical manifestation of APS Thrombosis

Occlusion of intracranial artery, DVT (mc) CNS

Migraine, sagittal venous sinus thrombosis, cognitive deficits, myelitis, chorea

Heart

Heart valve lesions (mc), acute coronary syndrome, intracardiac thrombus

Lung

Pulmonary embolism & infarction (mc), PAH

Kidney

Vessel thrombosis, IC mediated vasculitis

Skin

Livedo reticularis, skin ulcers

Liver & GI

Liver thrombosis, Budd-Chiari syndrome

Hematologic

Thrombocytopenia

Musculoskeletal

Avascular necrosis

APS associated with 1/3 of SLE patients

(30)

문제4. 항인지질항체 증후군의 치료는?

① antiplatelet agent lifelong treatment

② coumadin for 6 months

③ coumadin lifelong treatment

④ cyclophosphamide monthly pulse treatment

⑤ prostacyclin lifelong treatment

(31)

Long-term (life-long) anticoagulation Target INR:

venous 2.0-3.0 arterial 3.0-4.0

Pregnant women with APS Low-dose aspirin + heparin

Treatment of APS

Lupus nephritis induction treatment should

also be initiated

(32)

신드롬