1. Medical Grand Rounds 류마티스 내과 Prof. 홍승재 /R2 변자민

2. 12255712 배 O 숙 (F/40) adm. date: 2012.02.21 Adm via ER C.C) fever, myalgia o/s) about 4 weeks ago P.I) 상기 40 세 여자환자 특이병력 없던 자, 내원 4 주 전부터 열감과 근육통있어 개인병원에서 침치료 와 약물 치료 하였음. 치료에도 증상 호전없어 2012 일 2 월 17 일 본원 응급실 방문하여 요로감염 의심하에 약물 처방 받고 귀가하였으나 증상지속 되어 2 월 21 일 감염내과 외래 통해 입원함.

3. PMHx) –HTN/DM/TB/hepatitis (-/-/-/-) –OP history (-) –Drug history (+) PHx) –Alcohol (-) –Smoking (-) FHx) –Unremarkable 2012/2/18 ED medication Ceftriaxone 2g IV (2/18) Cefditoren 1T tid (2/18-2/21) Tylenol 2T tid (2/18-2/21)

4. Review of Systems General: fever (+), chills (-), fatigue(-), weight loss (-) Skin: rash (+)- face, whole body, itching (-) HEENT: headache (+), rhinorrhea (-), sore throat(+), hearing loss (-), visual disturabnce (-) Chest: c/s/r (+/+/-), dyspnea (-), hemoptysis (-) Cardiac: chest pain (-), palpitation (-), DOE (-) GI: dysphagia (-), epigastric pain (-), A/N/V/D/C (-/-/- /-/-), hematochezia/melena (-/-) GU: dysuria(-), urgency(-), frequency (-), hematuria(-) Musculoskeletal: arthalgia (+) - both shoulder, elbow, wrist, knee, both PIP & DIP joints, edema (-), weakness (-), stiffness (-), back pain (-) Nerve system: dizziness (-), sensory loss(-)

6. Physical Examinations V/S: 140/90mmHg – 100/min- 20/min – 37.7°C Height: 165cm / Weight: 61kg (BMI: 22.4kg/m 2 ) General : alert, acutely ill-looking appearance Skin: rash (+), pigmentation(-), petechiae (-) HEENT: isocoric pupil with PLR (++/++) no palpable neck mass, NVE (-), LNE(-) white sclera, conjunctival injection Chest: Symmetric chest expansion Clear breathing sound without rales/crackles Regular heart beat without murmur Abdomen: Soft and flat abdomen Hypoactive bowel sound Td / rTd (-/-), MG (-), CVA td (-/-)

7. Physical Examinations Neurology –Motor –Sensory pain & temperature vibration & proprioception Back & Extremities: CVA Td(-/-) Pretibial pitting edema (-/-) Joint swelling (-) Joint tenderness (-) Gross deformities (-) VV VV 100

8. Initial lab finding (12.02.21) CBC/DC) 3030/mm² - 11.0 g/dl – 33.7% - 111K (seg. 76.9%, ANC 2330) Chemistry ) TB/DB0.36/0.12 mg/dl BUN/Cr 19/0.7 mg/dl Prot/alb6.6/2.8 g/dL Na/K/Cl134/4.0/105 mg/dl AST/ALT45/16 IU/L Ca/P/Mg6.8/3.3/2.0 mg/dL ALP/GGT38/12 IU/L Uric acid/LD 5.0/740 mg/dL CRP 2.13 mg/dL ESR 22 mm/hr Cholesterol 159 mg/dL U/A) RBC many/HP WBC 5-9/HP Ketone (+) pH 6.0 Protein (+++) Glucose (-) Leukocytes(+) Nitrite(-)

9. Chest X-ray (2012.02.21)

10. ECG (2012.02.21)

11. Problem list #1. Fever #2. Rash #3. Cough, sputum #4. Sore throat #5. Arthralgia #6. Pancytopenia #7. Hematuria, proteinuria #8. Pleural effusion #9. Cardiomegaly Initial Assessments #1 1.Tuberculosis: cough, sputum, fever, arthralgia, rash, pleural effusion, hematuria, proteinuria, pancytopenia 2.Mycoplasma infection c extrapulmonary manifestations: rash, fever, cough, sputum, anemia, pleural effusion, lack of GI symptoms 3.Systemic viral infection: infectious mononucleosis, influenza, HIV 4.Legionella infection, q-fever…  Infection origin 1.Systemic lupus erythematosus: fever, rash, sore throat, arthralgia, pancytopenia, serositis (pleural effusion, pericarditis) 2.Small vessel vasculitis; microscopic polyangitis, HSP, Wegener’s granulomatosis 3.Sarcoidosis: skin, pulmonary, renal, heart involvements 4.Amyloidosis: skin, heart involvements  Non-infection origin

12. Initial Assessments #2 #1. Fever #2. Rash #3. Cough, sputum #4. Sore throat #5. Arthralgia #6. Pancytopenia #7. Hematuria, proteinuria #8. Pleural effusion #9. Cardiomegaly Glomerulonephritis IgAN Lupus nephritis HSP MPGN Other secondary GN

13. Initial Assessments #3 #1. Fever #2. Rash #3. Cough, sputum #4. Sore throat #5. Arthralgia #6. Pancytopenia #7. Hematuria, proteinuria #8. Pleural effusion #9. Cardiomegaly Infectious disease Serositis CHF Nephrotic syndrome

14. Initial Assessments #4 #1. Fever #2. Rash #3. Cough, sputum #4. Sore throat #5. Arthralgia #6. Pancytopenia #7. Hematuria, proteinuria #8. Pleural effusion #9. Cardiomegaly Infectious disease Autoimmune disease Hematologic disease

15. Diagnostic Plans #1 Tuberculosis Mycoplasma Viral infection #1. Infection SLE Small vessel vasculitis Others #2. Autoimmune disease IgAN Lupus nephritis HSP Others #3. GN Infectious disease Serositis CHF Nephrotic syndrome #4. Pleural effusion & cardiomegaly Infectious disease Autoimmune disease Hematologic disease #5. Pancytopenia 1.Culture: blood, sputum, urine 2.AFB stain & culture (sputum), TB-PCR 3.Cold agglutinin, mycoplasma IgM/IgG 4.Influenza A & B, viral markers: VCA, HIV 5.Procalcitonin

16. Diagnostic Plans #2 Tuberculosis Mycoplasma Viral infection #1. Infection SLE Small vessel vasculitis Others #2. Autoimmune disease IgAN Lupus nephritis HSP Others #3. GN Infectious disease Serositis CHF Nephrotic syndrome #4. Pleural effusion & cardiomegaly Infectious disease Autoimmune disease Hematologic disease #5. Pancytopenia Serology Complements (C3, C4, CH50) IgG/A/G/E ANA ( 정량 ), ANCA

17. Diagnostic Plans #3 Tuberculosis Mycoplasma Viral infection #1. Infection SLE Small vessel vasculitis Others #2. Autoimmune disease IgAN Lupus nephritis HSP Others #3. GN Infectious disease Serositis CHF Nephrotic syndrome #4. Pleural effusion & cardiomegaly Infectious disease Autoimmune disease Hematologic disease #5. Pancytopenia 24-hour urine collection Dysmorphic RBC, RBC casts Complements (C3, C4, CH50) RENAL BIOPSY

18. Diagnostic Plans #4 Tuberculosis Mycoplasma Viral infection #1. Infection SLE Small vessel vasculitis Others #2. Autoimmune disease IgAN Lupus nephritis HSP Others #3. GN Infectious disease Serositis CHF Nephrotic syndrome #4. Pleural effusion & cardiomegaly Infectious disease Autoimmune disease Hematologic disease #5. Pancytopenia Pro-BNP Echocardiography Chest CT 24-hour urine collection

19. Diagnostic Plans #5 Tuberculosis Mycoplasma Viral infection #1. Infection SLE Small vessel vasculitis Others #2. Autoimmune disease IgAN Lupus nephritis HSP Others #3. GN Infectious disease Serositis CHF Nephrotic syndrome #4. Pleural effusion & cardiomegaly Infectious disease Autoimmune disease Hematologic disease #5. Pancytopenia Anemia study BM, if needed

20. Clinical Course

21. #1. Infection #2. Non-infection#3. GN RPR- VZV IgG/IgM+ / - Anti-HCV ab- Anti-HIV ab- Anti-Hbs ab / HBs Ag+ / - Anti-HAV IgG/IgM+ / - CMV IgG/IgM+ / - EBV VCA IgG/IgM EBNA IgG EBV-EA-DR IgG/IgM + / - + +/- HSV PCR- respiratory virus PCR- Influenza A & B- Blood cultureNo growth Urine cultureNo growth Sputum culture No growth AFB stain- AFB culture- Quantiferon- Mycoplasma IgM/IgG -/- Cold agglutinin equivocal Procalcitonin0.241 2012/2/21 ~ 23 admT/F 1.Tuberculosis 2.Mycoplasma infection 3.Systemic viral infection: influenza, infectious mononucleosis, HIV… 4.Other infection: Legionella infection… UNLIKELY

22. #1. Infection #2. Non-infection #3. GN 2012/2/24~ 2/28 T/F 1.Infectious disease 2.Serositis 3.Congestive heart failure 4.Nephrotic syndrome TTE (12.02.22)

23. Chest CT (12.02.22)

24. #1. Infection #2. Non-infection#3. GN 2012/2/24~ 2/28 T/F 1.Infectious disease 2.Serositis 3.Congestive heart failure 4.Nephrotic syndrome

25. #1. Infection #2. Non-infection#3. GN 2012/2/24~ 2/28 T/F 1.Systemic lupus erythematosus 2.Small vessel vasculitis: microscopic polyangitis, HSP, Wegener’s granulomatosis 3.Others ANA ( 정량 ) >1:640 (Homogenous) Ig G Ig A Ig M Ig E 1970mg/dL 331mg/dL 89.2mg/dL 165IU/ml C3 C4 CH50 29mg/dL <6mg/dL 6.2U/mL C-ANCA / P-ANCANegative / Negative

26. ACR criteria for SLE X X X X ? ? ?

27. ? RBC Hb Hematocrit MCV MCH MCHC 11.0 g/dL 33.7 % 82.1 fL 26.8 pg 32.7 % PB smearRBC: Normocytic normochromic ferritin463 ng/mL TIBC / Serum iron119/15 ug/dL Vitamin B12504 pg/ml Folate3.8 ng/mL Reticulocyte (corrected reti) 1.43 % (1.07 %) Direct Coombs test+ 3030/mm² - 11.0 g/dl – 33.7% - 111K (seg. 76.9%, ANC 2330)

28. ? Anti-beta 2 GP1 IgG Anti-beta 2 GP1 IgM Normal(7.0) G units Elevated(24.0) M units Anti cardio IgG Anti cardio IgM Elevated(55.0) GPL Elevated(15.0) MPL Anti phospho IgG (EIA) Anti phospho IgM (EIA) Elevated(10.0) U/mL Elevated(11.0) U/mL Lupus anticoagulant (screen) Negative Anti-Sm+ Anti-SSA+++ Anti-SSB0 Anti-Ro 52+++ Anti-Scl 700 Anti-Pm Scl(+) Anti-CentB0 Anti-PCNA0 Anti-dsDNA++ Anti-Nu++ Anti-His+ Anti-Ribp+ Anti-AMA M2 0

29. ? 24hr urine protein3463mg/day 24hr urine creatinine950mg/day Protein (+++) Dysmorphic RBC 5%

30. ACR criteria for SLE ∴ Systemic lupus erythematosus!

31. Disease activity: SLEDAI Total score: 21 Very active

32. #1. Infection #2. Non-infection#3. GN 2012/2/24~ 2/28 T/F 1.Systemic lupus erythematosus 2.Small vessel vasculitis: microscopic polyangitis, HSP, Wegener’s granulomatosis 3.Others Skin Bx Skin biopsy (12.02.28)

34. #1. Infection #2. Non-infection#3. GN 2012/2/28~ 3/13 Skin Bx 2.MPGN 4. HSP 5. Other secondary GN 1. IgAN 3. Lupus nephritis Renal Bx !!!

35. Renal biopsy (12.03.05)

36. 1.Number of Glomerulus: 22 2.Glomerulosclerosis: 0/22 3.Crescent: 0/22 (%) 4.Capillary wall thickening: 0 5.Mesangial matrix expansion: 2 6.Mesagnial cell proliferation: 2 7.Inflammatory cell infiltration: 0 8.Additional pathologic findings: Endocapillary proliferation Wire loop formation

37. Renal biopsy (12.03.05)

40. #1. Fever #2. Rash #3. Cough, sputum #4. Sore throat #5. Arthralgia #6. Pancytopenia #7. Hematuria, proteinuria #8. Pleural effusion #9. Cardiomegaly Initial Problem List Cutaneous lupus Lupus nephritis Serositis SLE, acute flare up

41. Final Diagnosis #1. Systemic lupus erythematosus c subacute cutaneous lupus erythematosus c non-erosive arthritis c serositis (pleural, pericardial, peritoneal) c focal proliferative lupus nephritis (stage Ⅲ A/C) c leukopenia c antiphospholipid antibody

42. Overview 2/212/283/53/13 Renal biopsySkin biopsy Cyclophosphamide Low dose(500mg q.d) MMF 1000mg b.i.d MPD pulse 1000 mg/d for 3 days MPD pulse 1000 mg/d for 3 days MPD 60mg/d MPD 40mg/d MPD 40mg/d PDL 30mg/d 15 mg /d Hydroxychloroquine 200mg b.i.d Acetaminophen 650mg t.i.d 3030 46 2.13 0.52 7130 15

43. 2012/2/21 2012/3/27 subacute cutaneous lupus erythematosus

44. 2012/2/21 subacute cutaneous lupus erythematosus 2012/3/27

45. 2012/2/212012/3/12 serositis

46. focal proliferative lupus nephritis 24hr urine protein3463mg/day 24hr urine cr950mg/day Dipstick+++ 24hr urine protein1180mg/day 24hr urine cr851mg/day Dipstick-