Medical Grand Rounds <Case Presentation>

Medical Grand Rounds <Case Presentation>
류마티스 내과 Prof. 홍승재/R3이철현

C.C) P.I) 71세 여자 환자 내원 1일 전부터 속쓰림 구토 증상 구토, 속쓰림 o/s) 내원 1일 전
이O자 (F/71) adm. date: C.C) 구토, 속쓰림 o/s) 내원 1일 전 P.I) 71세 여자 환자 내원 1일 전부터 속쓰림 구토 증상 있어 약국에서 소화제 복용 하였으나 증상 호전 없어 응급실 통해 내원함.

PMHx) PHx) Alcohol (-) Smoking (-) HTN/DM/TB/hepatitis (+/+/-/-)
ITP Hx(+): 2009년 8월 진단되어 steroid 치료 중. Proteinuria, heart failure로 외래 medication 시행 중. OP history (+) : hysterectomy, thrombo-embolectomy Drug history (+) PHx) Alcohol (-) Smoking (-) <IH/IN/IC OPD Medication> Prednisolone 30mg qd metformin 1000mg qd Candesartan 8mg qd glimepride 4mg qd Lasix 40mg qd aldacton 12.5mg qd Eperisone hydrochloride

Review of Systems General: fever (-), chills (-)
Skin: rash (-), itching (-) H&N: headache (-), rhinorrhea (-), sore throat(-) Respiratory: c/s/r (-/-/-), dyspnea (-), hemoptysis (-) Circulatory: chest pain (-), palpitation (-), DOE (-) Digestive: A/N/V/D/C (-/+/+/-/-), GU: dysuria(-), urgency(-), frequency (-), hematuria(-) Musculoskeletal: arthalgia (-), both leg edema (-) Nerve system: dizziness (-), sensory loss(-)

Physical Examinations
V/S: 150/80mmHg – 82/min- 18/min – 36.6°C Height: 152cm / Weight: 53kg (BMI: 22.9kg/m2) General : alert, acute ill-looking appearance Skin: rash (-), pigmentation(-), petechiae (-) HEENT: isocoric pupil with PLR (++/++) no palpable neck mass , NVE (-), LNE(-) Chest: Clear breathing sound without rales/crackles Regular heart beat without murmur Abdomen: Soft and flat abdomen Hyperactive bowel sound Td / rTd (+/-), MG (-), CVA td (-/-) 키 BMI

Back & Extremities: CVA Td(-/-) Pretibial pitting edema (-/-) Joint swelling (-) Joint tenderness (-) Gross deformities (-) Neurology Motor Sensory pain & temperature vibration & proprioception V ROM Motor, sensory 추가 100

Clinical course (입원전) elevatedCr 47K 19K 1.3 Candesartan 16mg mg QD
Creatinine (mg/dL) Plt 103 elevatedCr 47K 19K 1.3 Candesartan 16mg mg QD 12/4/6 58K Proteinuria 1.2 Bowel wall edema 21K 36K 1.0 09/1/26 6/22 8/16 9/7 10/19 Thrombocytopenia prednisolone 30mg/day Pericardial effusion Diuretics (lasix, aldacton) ADM 1. ANA (+) :speckled 1+ 2. Thrombocytopenia 1. ANA (+) :cytoplasmic3+, speckled 2+ 2. Thrombocytopenia 3. Low complement 19일 시간당 70~80cc/h 20일 시간당 50cc/h 21일 시간당 40cc/h 22일 시간당 40cc/h 23일 시간당 20~30cc/h

Initial lab finding (12.10.19) CBC/DC) Chemistry ) U/A)
11740/mm² g/dl – 38.1% - 46K (seg. 86.9%) Chemistry ) TB/DB 0.6/0.17 mg/dl BUN/Cr 23/1.3 mg/dl Prot/alb 6.4/2.9 g/dL Na/K/Cl 143/3.8/102 mg/dl AST/ALT 19/9 IU/L Ca/P/Mg 7.2/3.8/2.1 mg/dL ALP/GGT 62/12 IU/L Uric acid/LD 7.5/501 mg/dL CRP mg/dL ESR mm/hr U/A) RBC 10~29/HP WBC 10~29/HP Ketone (-) pH 5.0 Protein (++) Glucose (-) Leukocytes(-) Nitrite(-) Spot urine Na:28(mmol/L) K:27(mmol/L) Cl:21(mmol/L) Protein:46(mg/dL) Urea nitrogen:759(mg/dL) Creatinine:11(mg/dL) U pr/ U Cr : 4.27 FENa: 0.25%, FEUrea: 4.52 %

Chest X-ray (2012.10.19) Increased amount of both pleural effusion.
R/O focal pneumonia on LLL.

ECG ( ) LVH, T wave inversion

Problem list Initial Problem list #1
#1. nausea, vomiting #2. pleural effusion #3. proteinuria, hematuria #4. thrombocytopenia #5. cardiomegaly #6. Elevated Cr.

Problem list Initial Assessments #1
Gastroenteritis Viral/bacterial Ischemic Outlet obstruction #1. nausea, vomiting #2. pleural effusion #3. proteinuria, hematuria #4. thrombocytopenia #5. cardiomegaly #6. Elevated Cr. CHF Serositis Infection GN

#1. nausea, vomiting #2. pleural effusion #3. proteinuria, hematuria #4. thrombocytopenia #5. cardiomegaly #6. Elevated Cr. GN IgAN Lupus nephritis HSP MPGN Other secondary GN Hematologic disease Infectious disease Autoimmune disease

Diagnostic Plans #1 #1. AGE #3. GN Viral/bacterial infection
Outlet obstruction Ischemic enteritis, other cause SLE Small vessel vasculitis Others #3. GN IgAN Lupus nephritis HSP #2. Pleural effusion & cardiomegaly Infectious disease Serositis CHF GN #4. Thrombocytopenia Autoimmune disease Hematologic disease Food, travel Hx., previous EGD Hx. taking Culture & stool evaluation: blood, stool GI tract imaging : Simple X-ray, Abdominal CT, EGD

Outlet obstruction Ischemic enteritis, other cause SLE Small vessel vasculitis Others #3. GN IgAN Lupus nephritis HSP #2. Pleural effusion & cardiomegaly Infectious disease Serositis CHF GN #4. Thrombocytopenia Autoimmune disease Hematologic disease Pro-BNP, thoracentesis Echocardiography Chest decubitus X-ray 24-hour urine collection

Outlet obstruction Ischemic enteritis, other cause SLE Small vessel vasculitis Others #3. GN IgAN Lupus nephritis HSP #2. Pleural effusion & cardiomegaly Infectious disease Serositis CHF GN #4. Thrombocytopenia Autoimmune disease Hematologic disease 24-hour urine collection Dysmorphic RBC, RBC casts Serology, Complements Kidney Bx., if needed

Outlet obstruction Ischemic enteritis, other cause SLE Small vessel vasculitis Others #3. GN IgAN Lupus nephritis HSP #2. Pleural effusion & cardiomegaly CHF Serositis Infectious disease GN #4. Thrombocytopenia Autoimmune disease Hematologic disease Anti-platelet antibody Lupus anticoagulant Viral marker : EBV BM, if needed

Clinical Course

<Differential diagnosis>
#1. AGE #2. Pleural effusion #3. GN #4. Thrombocytopenia Adm. 2012/10/19~11/2 Abd.CT ( ) <Differential diagnosis> Viral/bacterial Outlet Obx. Ischemic Other cause

#1. AGE #2. Pleural effusion #3. GN #4. Thrombocytopenia Adm. 2012/10/19~11/2 Cardiac Echo ( ) <Differential diagnosis> CHF Infection Serositis GN

<Differential diagnosis> <Screening test>
#1. AGE #2. Pleural effusion #3. GN #4. Thrombocytopenia Adm. 2012/10/19~11/2 <2012/10/22> 24hr urine protein 3145mg/day 24hr urine cr 582mg/day <Differential diagnosis> 1.IgAN 2.Lupus nephritis 3.HSP 4.MPGN 5.Other secondary GN <Screening test> ANA (정량) 1:640(speckled) 1:320(cytoplasmic) Ig G Ig A Ig M Ig E 1100mg/dL 233mg/dL 93.5mg/dL 39.5U/ml C3 C4 CH50 24.2mg/dL <6mg/dL 2.0U/mL C-ANCA / P-ANCA Negative / Negative

Renal biopsy ( ) 신생검에서는 glomurus안에 Endocapillary proliferation (보라색점), mesangial proliferation (보라) 소견이 관찰되는 Focal proliferative lupus nephritis (stageⅢ)

Renal biopsy ( )

Renal biopsy ( ) IgG

Immunofluorescence microscopy
glomerulus tubular vessel other Total Number Linear Granular mesangial GCW IgG 4 - +++ IgA 3 + IgM ++ C3 C1q 5 Kappa Lambda 　glomerular basement mebmrane, mesangial에 Ig 침착 없음 26

Renal biopsy (12.11.19) Electron microscopic findings에서는
Mesangium에 electron deposit (검은색)이 관찰되며, Subendothelium에 cryoglobulin이 fingerprint appearance가 관찰되고 있었습니다.

2. Glomerulosclerosis: absent
I. Glomerulus 1. Number of Glomerulus: 20 2. Glomerulosclerosis: absent 3. Size of Glomerulus: increased(moderate) 4. Pericapsular fibrosis : absent 5. Tuft adhesion: absent 6. Cresent : Absent 7. Cellularity: increased - location : mesangial - extent: diffuse 8. Mesangial widening: present (marked) 9. Mesangial cellularity: moderate 10. Capillary wall change: absent or minimal 11. Wire-loop formation of capillary wall: not 12. Capillary luminal occlusion: present 13. Capillary necrosis: not identified II. Tubule 1. Tubular atrophy: No (<5%) 2. Acute tubular injury: absent 3. Tubulitis: absent III. Interstitium 1. Inflammatory cell infiltration: mild(10-25%), Lymphocyte 2. Fibrosis: absent IV. Vessels 1. arterio- or arteriolosclerosis: absent 2. Hyalinosis: absent 3. Fibrinoid necrosis: absent 4. Vasculitis : absent Diagnosis: 1. Membranous lupus nephritis, class V <Activity index> 0/ <Chronicity index> 0/12 Endocapillary hypercellularity Glomerular sclerosis 0 Leukocyte infiltration Fibrous crescents 0 Subendothelial hyaline deposits Tubular atrophy 0 Fibrinoid necrosis/karyorrhectic debris Interstitial fibrosis 0 Cellular crescents Interstitial inflammation

Total :5 Arthritis Rheum 25:1271, 1982;
update by MC Hochberg, Arthritis Rheum 40:1725, 1997.

Clinical : 3 immunologic: 3 Total :6

#1. nausea, vomiting #2. pleural effusion #3. proteinuria, hematuria #4. thrombocytopenia #5. cardiomegaly #6. Elevated Cr. Serositis Lupus nephritis Thrombocytopenia d/t SLE

Final Diagnosis #1. Systemic lupus erythematosus
c serositis (pleural, pericardial, peritoneal) c mebranous lupus nephritis (stage V) c thrombocytopenia

Question 1. 71/F, SLE c LN type V 로 진단되어 MPD pulse 1g for 3days 투여 후 다음치료는 어떻게 할 것인가? Cyclophosphamide Mycophenolate mofetil Azathiopurine rituximab

c serositis (pleural, pericardial, peritoneal) c mebranous lupus nephritis (stage V) c thrombocytopenia MPD IV pulse x3days then 1mg/kg/day PDL + Cyclophosphamide 500mg q 2wks/total 3gm

Clinical Course 63 57K 0.7 43K 58 PDL 1mg/kg/day PDL 0.5mg/kg/day 50
Creatinine (mg/dL) Plt 103 Weight (Kg) 63 57K 0.7 43K 58 PDL 1mg/kg/day PDL 0.5mg/kg/day 50 72K 47 CTX 500mg q 2wks #6 1.0 98K 0.7 1.3 1.4 56 46K 35K 51 27K 10/19 10/27 11/6 11/9 11/13 11/19 11/28 12/6 12/28 1/11 1/25 2/8 2/22 3/9 MPD pulse Tx (1g/day) Renal Bx ADM 뒤로 추가한다 Diuretics (lasix, aldacton) Piperacillin/Tazolactam 4.5gm q 8hr

membranous lupus nephritis
<2012/11/5> S Cr.:1.4 Urine Protein 3145mg/day Urine Creatinine 582mg/dl U protein/U Cr. 4.27mg/day Dipstick ++ <2013/3/9> S Cr.:0.7 Urine Protein 460mg/day Urine Creatinine 500mg/dl U protein/U Cr. 1.21mg/day Dipstick +

C.C) o/s) 내원 3주 전 P.I) 양측 하지 부종 14세 여자환자 2012년 8월 부터 양측 손목 통증 및
김O현 (F/14) adm. date: C.C) o/s) 내원 3주 전 양측 하지 부종 P.I) 14세 여자환자 2012년 8월 부터 양측 손목 통증 및 다발성 관절통으로 본원 내원했던 환자로 양측 하지에 부종 발생하여 추가적인 검사와 치료 위해 입원함.

PMHx) PHx) FHx) Alcohol (-) Smoking (-) Unremarkable
HTN/DM/TB/hepatitis (-/-/-/-) Polyarthralgia: 2012년 8월 부터 Po med.중 OP history (-) Drug history (+) PHx) Alcohol (-) Smoking (-) FHx) Unremarkable <IR OPD Medication> Prednisolone 5mg qd hydroxychloroquine 200mg qd 여기서 약을 먹어야 하나 말아야 하나? 그것도 질문 하자

Review of Systems General: fever (-), chills (-)
Skin: rash (-), itching (-) H&N: headache (-), rhinorrhea (-), sore throat(-) Respiratory: c/s/r (-/-/-), dyspnea (-), hemoptysis (-) Circulatory: chest pain (-), palpitation (-), DOE (-) Digestive: A/N/V/D/C (-/-/-/-/-) GU: dysuria(-), urgency(-), frequency (-), hematuria(-) Musculoskeletal: arthalgia (+), both leg swelling (+) Nerve system: dizziness (-), sensory loss(-)

V/S: 100/80mmHg – 82/min- 14/min – 36.6°C Height: 152cm / Weight: 53kg (BMI: 22.9kg/m2) General : alert, chronically ill appearance Skin: rash (-), pigmentation(-), petechiae (-), alopecia(+) HEENT: isocoric pupil with PLR (++/++) no palpable neck mass , NVE (-), LNE(-) Chest: Clear breathing sound without rales/crackles Regular heart beat without murmur Abdomen: Soft and flat abdomen Td / rTd (-/-), MG (-), CVA td (-/-) ROM Motor, sensory 추가

Back & Extremities: CVA Td(-/-) Pretibial pitting edema (+/+) Joint swelling (+) : Rt.3rd PIP,Lt.5th PIP Joint tenderness (+) : Rt.3rd PIP, Lt.5th PIP, Rt.wrist both shoulder Gross deformities (-) Neurology Motor Sensory pain & temperature vibration & proprioception V ROM Motor, sensory 추가 100

Clinical course (입원전) 1.7 9.5 9.5 1.4 9.2 0.7 8.1 7.3 7.0 8/28 10/2
Creatinine (mg/dL) Hb (g/dL) 1.7 9.5 9.5 1.4 9.2 0.7 8.1 7.3 7.0 8/28 10/2 10/27 11/24 12/14 12/28 Polyarthralgia elevatedCr ADM 1. ANA (+) 2. Immunologic :Anti-dsDNA (+++) 3. arthritis: peripheral involvement 겨울 방학이였고 prednisolone 5mg/day 10mg/day hydroxychloroquine 200mg/day 400 mg/day

Initial lab finding (12.12.28) CBC/DC) Chemistry ) U/A)
8350/mm² g/dl – 21.7% - 284K (seg. 91.9%) Chemistry ) TB/DB 0.2/0.12 mg/dl BUN/Cr 39/1.7 mg/dl Prot/alb 6.6/3.1 g/dL Na/K/Cl 140/5.1/109 mg/dl AST/ALT 11/5 IU/L Ca/P/Mg 8.1/3.3/2.0 mg/dL ALP/GGT 38/12 IU/L Uric acid/LD 5.0/740 mg/dL CRP mg/dL ESR mm/hr U/A) RBC many/HP WBC 10-29/HP Ketone (-) pH 5.0 Protein (++) Glucose (-) Leukocytes(+) Nitrite(-) Spot urine Na:72(mmol/L) K:64(mmol/L) Cl:75(mmol/L) Protein:154(mg/dL) Urea nitrogen:663(mg/dL) Creatinine:98(mg/dL) U pr/U Cr : 1.68 FENa: 0.44%, FEUrea: %

Chest X-ray ( ) Cardiomegaly 0.6

ECG ( ) .Normal sinus rhythm PR 90/min

Problem list Initial problem list #1
#1. Leg edema #2. Elevated Cr #3. Proteinuria #4. Hematuria #5. Anemia

#1. Leg edema #2. Elevated Cr #3. Proteinuria #4. Hematuria #5. Anemia Glomerulonephritis PSGN HSP IgAN MPGN Lupus nephritis Other secondary GN

Anemia of chronic disease
Problem list Initial Assessments #1 #1. Leg edema #2. Elevated Cr #3. Proteinuria #4. Hematuria #5. Anemia Hemolytic anemia Iron deficiency anema Anemia of chronic disease

Diagnostic Plans #1 #3. Anemia #1. GN Hemolytic anemia
PSGN HSP IgAN MPGN Lupus nephritis #3. Anemia Hemolytic anemia Anemia of chronic disease Iron deficiency anemia Spot urine, 24hr urine exam ASO, p-ANCA, c-ANCA, MPO, PR3 C3, C4, anti-dsDNA, anti-GBM Ab RENAL BIOPSY

Diagnostic Plans #1 #3. Anemia #1. GN
PSGN HSP IgAN MPGN Lupus nephritis #3. Anemia Hemolytic anemia Anemia of chronic disease Iron deficiency anemia Iron, TIBC, vitB12, folate, ferritin PB smear, stool occult, reticulocyte

Clinical Course

Clinical Course Creatinine (mg/dL) Hb (g/dL) 1.7 1.5 1.6 7.0 6.8 6.7 12/28 12/29 12/30 12/31 1/1 1/2 1/3 1/4 1/5 1/6 1/7 ADM Renal Bx ANA(+) Anti-RNP/Sm (++) Anti-SSA (+++) Anti-Ro-52 (+++) Anti-dsDNA(+++) Anti-His(+++) Anti- Rib(+++) C3: 30.3 ( mg/dL) C4: <6 (16-47 mg/dL) Direct coomb’s (+) Anti- cardio IgG : elevated Anti- cardio IgM: elevated Anti- phospho IgG: normal Anti- phospho IgM: normal Lupus anticoagulant (-) prednisolone 10mg/day hydroxychloroquine 400mg/day <Differential diagnosis> 1. PSGN 2. HSP 3. IgAN 4. MPGN 5. Lupus nephritis

Renal biopsy ( )

Renal biopsy ( ) 신생검에서는 glomurus안에 Endocapillary proliferation (보라색점), mesangial proliferation (보라) 소견이 관찰되는 Focal proliferative lupus nephritis (stageⅢ)

Renal biopsy ( )

2. Glomerulosclerosis: (Yes) 1/6 Global glomerulosclerosis: 1/6
I. Glomerulus 1. Number of Glomerulus: 6 2. Glomerulosclerosis: (Yes) 1/6 Global glomerulosclerosis: 1/6 3. Size of Glomerulus: increased(moderate) 4. Pericapsular fibrosis : absent 5. Tuft adhesion: absent 6. Cresent : Present (5/6) cellular cresent:4/6, fibrocellular cresent:1/6 7. Cellularity: increased - location : mesangial, endocapillary - extent: diffuse, segmental 8. Mesangial widening: present (mild) 9. Mesangial cellularity: mild 10. Capillary wall change: absent or minimal 11. Wire-loop formation of capillary wall: not 12. Capillary luminal occlusion: present 13. Capillary necrosis: not identified II. Tubule 1. Tubular atrophy: No (<5%) 2. Acute tubular injury: absent 3. Tubulitis: absent III. Interstitium 1. Inflammatory cell infiltration: mild(10-25%), Lymphocyte 2. Fibrosis: absent IV. Vessels 1. arterio- or arteriolosclerosis: absent 2. Hyalinosis: absent 3. Fibrinoid necrosis: absent 4. Vasculitis : absent Diagnosis: 1. Diffuse lupus nephritis with crescent Focal VS global Focal VS diffuse <Activity index> 10/ <Chronicity index> 1/12 Endocapillary hypercellularity Glomerular sclerosis 1 Leukocyte infiltration Fibrous crescents 0 Subendothelial hyaline deposits Tubular atrophy 0 Fibrinoid necrosis/karyorrhectic debris Interstitial fibrosis 0 Cellular crescents 3x2 Interstitial inflammation

Renal biopsy ( ) IgG,C1q

Immunofluorescence microscopy
glomerulus tubular vessel other Total Number Linear Granular mesangial GCW IgG 2 - ++ IgA 3 + IgM C3 C1q 5 Kappa Lambda 　glomerular basement mebmrane, mesangial에 Ig 침착 없음 59

Mesangium에 electron deposit (검은색)이 관찰되며, Subendothelium에 cryoglobulin이 fingerprint appearance가 관찰되고 있었습니다.

Mesangium에 electron deposit (검은색)이 관찰되며, Subendothelium에 cryoglobulin이 fingerprint appearance가 관찰되고 있었습니다. Ⅰ. Glomerulus 1. Epithelium 1) Foot process effacement: (Y, diffuse) 2) Deposits: (N) 2. GBM 1) Thickness: no pathologic abnormality 2) Contour: irregular 3) Texture: no pathologic abnormality 4) Deposits: (Y, intramembranous, subendothelial) 3. Mesangium: Increase of mesangial matrix and cells Mesangial and paramesangial electron-dense deposits 4. Endothelium: No pathologic abnormality

Total :4 Arthritis Rheum 25:1271, 1982;
update by MC Hochberg, Arthritis Rheum 40:1725, 1997.

Clinical : 3 immunologic: 5 Total :8

Clinical Course Creatinine (mg/dL) Hb (g/dL) 1.7 1.5 1.6 7.0 6.8 6.7 <Anemia study> RBC Hb Hematocrit MCV MCH MCHC 7.0 g/dL 21.7 % 80.5 fL 26.8 pg 32.7 % PB smear RBC: Normocytic normochromic ferritin 93.9 ng/mL TIBC / Serum iron 200/18 ug/dL Vitamin B12 304 pg/ml Folate 10.3 ng/mL Reticulocyte (corrected reti) 2.66 % (1.07 %) Direct Coombs test + 12/28 12/29 12/30 12/31 1/1 1/2 1/3 1/4 1/5 1/6 1/7 ADM Anemia study prednisolone 10mg/day hydroxychloroquine 400mg/day <Differential diagnosis> Hemolytic anemia Anemia of chronic disease Iron deficiency anemia

Anemia of chronic disease d/t SLE
Problem list Initial Problem list #1. Leg edema #2. Elevated Cr #3. Proteinuria #4. Hematuria #5. Anemia Lupus nephritis Anemia of chronic disease d/t SLE

c lupus nephritis type IV 면역 억제제 steroid, cyclophosphamide, MMF가 아이에게 일어날 수 있는 문제점은? 질문..

Question 1. 14/F, SLE c LN type IV 로 진단되어 MPD pulse 1g for 3days 투여 후 다음치료는 어떻게 할 것인가? Cyclophosphamide Mycophenolate mofetil Azathiopurine rituximab

c lupus nephritis type IV MPD IV pulse x3days then 1mg/kg/day PDL + Mycophenolate mofetil 500mg bid 면역 억제제 steroid, cyclophosphamide, MMF가 아이에게 일어날 수 있는 문제점은? 질문..

Clinical Course Urine Protein 154mg/day Urine Creatinine 98mg/dl
Hb (g/dL) 1.9 1.8 1.8 1.8 8.8 1.7 1.5 1.6 7.9 7.1 7.0 7.0 1.4 6.8 6.7 6.7 6.7 6.6 0.8 12/28 12/29 12/30 12/31 1/1 1/2 1/3 1/4 1/8 1/6 1/24 3/16 ADM Renal Bx MPD pulse Tx (1g/day) prednisolone 10mg/day 50mg/day hydroxychloroquine 400mg/day MMF 1000mg/day <2012/12/31>: S Cr.:1.6 Urine Protein 154mg/day Urine Creatinine 98mg/dl U protein/U Cr. 1.68mg/day Dipstick ++ <2013/1/24> S Cr.:1.0 Urine Protein 151mg/day Urine Creatinine 111mg/dl U protein/U Cr. 1.36mg/day Dipstick +

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