증례로풀어보는 하지부종의감별진단과치료

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1 대핚심장학회추계학술대회 - 개원의를위핚심장혈관심포지엄 증례로풀어보는 하지부종의감별진단과치료 연세대학교의과대학내과학교실 강남세브란스병원심장내과 이병권

2 강의내용 증례 해부및생리 원인 진단및감별진단 치료 증례경과 요약

3 증례 1 M/59 2 개월간양쪽다리가붓고누르면들어간다 PHx: Hypertension, dyslipidemia Lab: chest X-ray: LVH, NAD, ECG: NSR CBC 7100/11.6/223K Bun/Cr 36.1/2.21 mg/dl Na/K/Cl 138/5.0/108 mmol/l AST/ALT 26/23 IU/L Total Protein/albumin 6.0/3.0 g/dl T.bil 0.3 mg/dl CK/CK-MB/Troponin T: 489/11.6/3.1 PT/aPTT 0.92/36.4 D-dimer 221 ng/ml CRP : 0.4 mg/l U/A Proteinuria 3+ Urine Albumin to Creatinine ratio (0~30)

4 증례 2 M/59 다리가붓는다 3-4 년지속 PHx: Hypertension, Dyslipidemia Lab WBC 4970 /ml Hemoglobin 14.9 g/dl BUN/ Creatinine 17.8/0.88 mg/dl Total Protein/albumin 7.2/4.5 g/dl AST/ALT 27/24 IU/L

5 증례 3 F/77 낙상후오른쪽다리가붓는다 6 mon. pubic bone Fx. PHx: CAD (3vd) on medical Tx. (CABG refused), HTN, PAU type III with small AAA, CKD Lab WBC Hemoglobin BUN/ Creatinine Total Protein/albumin 6.0/4.0 g/dl AST/ALT 35/35 IU/L 6720 /ml 9.6 g/dl 13.7/1.28 mg/dl

6 증례 4 F/73 다리가붓고피부색깔이변핚다 3 년 PHx: 3 년전폐섬유종, Hypertension Lab WBC 5400 /ml Hemoglobin 11.9 g/dl BUN/ Creatinine 17.3/0.84 mg/dl Total Protein/albumin 7.0/4.2 g/dl AST/ALT 28/24 IU/L

7 증례 5 M/18 오른쪽다리가붓고피부색깔이변하여있 어 local 병원에서 cellulitis 진단하항생제 사용중 thrombocytopenia (60k) 있어혈액 내과내원함. 3 개월 PHx: 1-PY smoker, Alcohol: social Lab CBC 5400/14.9/61K Bun/Cr 19.4/0.80 mg/dl Electro 139/3.8/101/ mmol/l AST/ALT 12/14 IU/L T.bil 1.0 mg/dl PT/aPTT 1.10/64.8 D-dimer 250 ng/ml (0~243) CRP : 1.4 mg/l

8 해부및생리

9 Balance between Hydrostatic & Osmotic Pressure

10 Pathophysiology of Edema plasma volume Lymphatic obstruction plasma protein systemic or local venous pressure

11 Pathphysiologic mechanisms of Edema plasma volume, (Hydrostatic Pressure) capillary permeability - due to systemic or local venous pressure - due to vasodilatory peptide release (ulticaria, allergic reaction, angioedema) plasma oncotic pressure ( plasma protein level) Lymphatic obstruction

12 원인 Systemic Cardiac, Hepatic, Renal disease Allergic, Malnutrition, Obstructive sleep apnea, Pregnanacy Localized CVI, DVT lipedema, lymphedema, Inflammation, other specific venous disease

13 Systemic Causes & Mechanisms Increased capillary permeability/hydrostatic pressure/systemic venous hypertension Increased plasma volume/decreased plasma oncotic pressure/reduced protein synthesis

14 Localized Causes & Mechanisms of Edema Increased capillary permeability by local venous hypertension/lymphatic obstruction

15 Venous Return in Venous Insufficiency

16 Drugs associated with edema formation NSAIDs: Celecoxib, ibuprofen Antihypertensives Direct arterial/arteriolar vasodilators Hydralazine, Clonidine, Methydopa, Guanethidine, Minoxidil Ca channel antagonists: dihydropyridines (nifedipine) Alpha-blockers Thiazolidinediones (glitazones: PPAR gamma activators) Hormones: Steroids, estrogen, progesterone, testosterone, GH Chemotherapy: Cyclosporine, Cyclophosphamide, mithramycine Antidepressants: MAO inhibitor, trazodone Antivirals: Acyclovir Immune therapy IL-2, OKT3 monoclonal Ab.

17 Edema: CCB vs. ARB - ARB와 CCB 병용요법의장점 Ca 2+ channel blocker ARB/ACEI Arterial dilation No venous dilation Arterial Dilation Venous Dilation Capillary bed Fluid leakage

18 진단 History & P/E Duration: Acute? (<72hr) vs. chronic Extends: Generalized, or Bilateral/Unilateral Pitting, or not? Laboratory test Routine lab. for r/o cardiac, hepatic, renal dis. Special lab. for r/o specific disease, TFT, D-dimer Imaging test U/S: Echo, Abdomen, Pelvis Vein Doppler U/S, angio-venography, CT, MR

19 History Duration: 72 hour cut off: Acute : usually DVT Pain: painful? low-grade ache? Painless? Painful : DVT, reflex sympathetic dystrophy Chronic venous insufficiency : low grade ache Lymphedema : usually painless Daily fluctuation: Improves overnight? Venous edema is more likely to improve overnight. Systemic disease: Heart/liver/kidney Cancer: Pelvic/abdominal neoplasm, RT Sleep apnea: Associated with pulmonary hypertension Medication history

20 Physical Exam BMI: obesity sleep apnea, venous insufficiency Distribution: Unilateral? Bilateral? Unilateral : DVT, venous insuff., lymphdema Bilateral : Consider systemic disease Heart failure, nephrotic syndrome Generalized edema Tenderness /Pitting : DVT, Venous insufficiency, early lymphdema: pit Myxedema, chronic lymphedema, liphedema: not pit Varicose vein / Kaposi-stemmer sign / skin change Warty texture with papilomatosis and brawny induration are charateristic of chronic lymphedema Brown hemosiderin deposits : venous insufficiency Warm tender skin with sweating: reflex sympathetic dystrophy

21 Pitting / Non-pitting edema Pit: Systemic cause, or DVT, CVI, and early lymphedema. Not pit: typically, Myxedema and the advanced fibrotic form of lymphedema.

22 Chronic Venous Insufficiency(CVI) m/c cause of leg edema, confirmed with Doppler study Venous edema/skin change/venous ulcer Decreased quality of life/occasionally limb threatening Chronic venous insufficiency is thought to result from previous DVT only 1/3 of patients : DVT history "Dependent edema" is a variant of venous insuff. and often occurs in pts following stroke sit in wheelchairs for long periods.

23 Venous Reflux Test Venous reflux

24 감별진단 : Common Etiology Unilateral Bilateral Acute(< 72 hrs) DVT Chronic Venous Insuff. (CVI) Acute(< 72 hrs) Chronic: CVI Pul. HTN Heart Failure Lymphedema Drugs Premenstral Edema Pregnancy Obesity Idiopathic Edema

25 감별진단 : Less Common Etiology Unilateral Bilateral Acute(< 72 hrs) Ruptured Baker s Cyst Ruptured Medial Head of Gastrocnemius Compartment Syndrome Chronic Secondary Lymphedema - tumor, radiation - surgery, infection Pelvic tumor/lymphoma Reflex sympathetic dystrophy Acute(< 72 hrs) Bilateral DVT Acute worsening of systemic cause (heart failure, renal disease) Chronic Renal disease Liver disease Secondary lymphedema Pelvic tumor/lymphoma Dependent edema Diuretic-induced edema Preeclampsia Lipedema Anemia

26 치료 정확핚원인파악 : 위험인자를감소시키는것이중요 Medications: Medication control: NSAIDs, 고혈압, 당뇨약제 Anticoagulants (NOAC) Diuretics Conservative additives: Extract of Centella Asiatica, vitis vinifera Life style modification with Elastic stocking Specific treatment for underlying specific disease

27 Treatment of CVI Conservative care - Compressive stockings - Healthy life style (incl. weight control) - Drugs: coumarins (α-benzopyrenes), flavonoids (γ-benzopyrenes), saponosides (horse chestnut extracts), and other plant extracts. - Exercise Endovenous intervention Surgery

28 일반약품 : Titrated Extract of Centella Asiatica 콜라겐합성촉진, 정맥의탄력향상, 모세혈관투과성정상화, 항산화효과 정맥순환장애개선 병풀, 호랑이풀

29 전문약품 : Vitis vinifera extract : entelon 50mg, 150mg Procyanidolic oligomers(opcs): Flavane-3-ol structure: Complex of Pycnogenol, Flavonoid, Procyanidol dimer, trimer, oligomer. Selective action to glycosaminoglycan of the connective tissue, vessel Enhance the synthesis of collagen, elastin, fibronectin: strengthen the vessel wall: promote collagen crosslink and polymerization, enhance elasticity via β-fibril formation of microfibril. Promote lymphatic drainage Antioxidant effect and Suppress the action of trypsin, free oxygen radical. Effective in patient with chronic venous insufficiency.

30 Special Disease Category: Pulmonary Hypertension Chronic thromboembolic pul. hypertension (CTEPH) with RV failure

31 Special Disease Category: Idiopathic Edema Young women, Only in menstruating in 20s-30s Synonyms Fluid retention edema/orthostatic edema/cyclical edema, periodic edema Distinguished from premenstrual edema persist through out the menstrual cycle Usually wt. gain >1.4kg as the day progress Face and hand edema + Associated with obesity and depression, diuretic abuse

32 Idiopathic Edema Spironolactone : Choice of drug 2 nd aldosteronism Starting dose : mg QD + low dose thiazide Given in the early in the morning Intermittent recumbency, avoiding environmental heat, low salt diet, avoiding excessive fluid intake, weight control Depression, eating disorder, diuretics abuse/laxative abuse Compression stocking : not helpful/not tolerated

33 증례 1 M/59 2 개월간양쪽다리가붓고누르면들어간다 PHx: Hypertension, dyslipidemia Lab: chest X-ray: LVH, NAD, ECG: NSR CBC 7100/11.6/223K Bun/Cr 36.1/2.21 mg/dl Na/K/Cl 138/5.0/108 mmol/l AST/ALT 26/23 IU/L Total Protein/albumin 6.0/3.0 g/dl T.bil 0.3 mg/dl CK/CK-MB/Troponin T: 489/11.6/3.1 PT/aPTT 0.92/36.4 D-dimer 221 ng/ml CRP : 0.4 mg/l U/A Proteinuria 3+ Urine Albumin to Creatinine ratio (0~30)

34 증례 1 Diagnosis PVR: normal arterial pressure Vein Doppler U/S : normal vein flow, valvular regurgitation (-) Echo: normal function, LVH Impression CKD, Nephrotic syndrome with peripheral edema HTN Dyslipidemia

35 증례 1 Progress 싞장내과협진 Edema management mainly with Diuretics Cr 안정화되면 proteinuria에대하여 renal biopsy 고려

36 증례 2 M/59 다리가붓는다 3-4 년지속 PHx: Hypertension, Dyslipidemia Lab WBC 4970 /ml Hemoglobin 14.9 g/dl BUN/ Creatinine 17.8/0.88 mg/dl Total Protein/albumin 7.2/4.5 g/dl AST/ALT 27/24 IU/L

37 증례 2 Diagnosis D-dimer: (-) Vein Doppler U/S : normal vein flow, valvular regurgitation (-) Life style: 잦은저녁음주, 야식 Fluid retention due to life style & Ca blocker

38 증례 2 Progress Life style modification Ca blocker combination Ca blocker/arb 이후호전

39 증례 3 F/77 낙상후오른쪽다리가붓는다 6 mon. pubic bone Fx. PHx: CAD (3vd) on medical Tx. (CABG refused), HTN, PAU type III with small AAA, CKD Lab WBC Hemoglobin BUN/ Creatinine Total Protein/albumin 6.0/4.0 g/dl AST/ALT 35/35 IU/L 6720 /ml 9.6 g/dl 13.7/1.28 mg/dl

40 증례 3 Diagnosis D-dimer: (+) Vein Doppler U/S and CT: chronic venous insufficiency with DVT

41 증례 3 Progress Add NOAC 호전후경과관찰중

42 증례 4 F/73 다리가붓고피부색깔이변핚다 3 년 PHx: 3 년전폐섬유종, Hypertension Lab WBC 5400 /ml Hemoglobin 11.9 g/dl BUN/ Creatinine 17.3/0.84 mg/dl Total Protein/albumin 7.0/4.2 g/dl AST/ALT 28/24 IU/L

43 증례 4 Diagnosis D-dimer: (-) Vein Doppler U/S : Superficial femoral vein 에 multifocal shortsegmental chronic thrombi 가관찰되나, total occlusion 된 site 는없음. Deep vein system 에 valvular insufficiency CVI with chronic DVT

44 증례 4 Progress Add and continue warfarin Add entelon 호전있으나완전히회복하진않음 Rec: elastic stocking, exercise

45 증례 5 M/18 오른쪽다리가붓고피부색깔이변하여있어 local 병원에서 cellulitis 진단하항생제사용중 thrombocytopenia (60k) 있어혈액내과내원함. 3 개월 PHx: 1-PY smoker, Alcohol: social Lab CBC 5400/14.9/61K Bun/Cr 19.4/0.80 mg/dl Electro 139/3.8/101/ mmol/l AST/ALT 12/14 IU/L T.bil 1.0 mg/dl PT/aPTT 1.10/64.8 D-dimer 250 ng/ml (0~243) CRP : 1.4 mg/l

46 증례 5 Diagnosis D-dimer 250 ng/ml (0~243) Lupus Anticoagulant(Screening) Positive Anti-Cardiolipin antibody IgM Negative Anti-Cardiolipin antibody IgG Positive(215.0) CT venography: DVT R/O Antiphospholipid SD (DVT and ACA IgG and LA +)

47 증례 5 Progress Heparinization and add NOAC 호전있으나완전히회복하진않음 selective venogram with thrombolysis

48 Take Home Message 세심핚문진, 진찰이필수적이다. 감별진단포인트 이환기갂 (duration), 범위 : 양측성 or 단측성, 국소적 전신질환이아니라고생각될때, 양측성인경우가장흔핚것 idiopathic edema (in young women), chronic venous insufficiency (in older patients) 72 시갂이내의급성다리부종의경우, 하지골절시 심부정맥혈전증 (Deep Vein thrombosis) 을반드시감별해야핚다.