1. MGR Fever 와 Lymphadenopathy 로 내원한 16 세 남자환자 Department of Rheumatology R2 임효석 / Prof. 홍승재

2. Chief complaint Fever onset : 07.2 월 중순 Present illness - 평소 건강하던 16 세 남자로 07 년 2 월 중순부터 1 주일 간격으로 2-3 일간 호전과 악화를 반복하는 얼굴, 손, 발의 부종이 있어 개인병원에서 검사 시행한 결과 복부 초음파에서 간, 비장비대 소견보이고 빈혈, 혈소판 감소증 관찰되어 2 차 병원에 입원함. - 2 차 병원 입원 후 야간에 38 도 이상으로 spiking fever 가 발생하고 다발성 임파선 비대가 관찰되어 Lymphoma 의심하여 본원 혈액 종양 내과로 입원함. 11896432 오 O 민 (M/16) Admission : 2007.3.29

3. Past medical history Past medical history DM/HTN/Tbc/Hepatitis (-/-/-/-) DM/HTN/Tbc/Hepatitis (-/-/-/-) Op history : (-) Op history : (-) Family hitory : none Family hitory : none Personal history : Smoking (-) Personal history : Smoking (-) Alcohol (-) Alcohol (-) Drug Hx : (-)

4. Review of system General Fatigue (+) Febrile sensation (+) Chills (+) Weight loss (-) Sweat (+) H & Neck Headache (-) Sore throat (-) Respiratory Cough (-) Sputum (-) Dyspnea (-) Chest pain (-) GI A/N/V/D/C (-/+/+/-/-) Abd pain (+) : diffuse lower abdominal area Renal Dysuria (-) Hematuria (-) Frequency (-) Muscle and skeletal Pain (-) Swelling (+) – both hands and feet weakness (-)

5. Physical examination Vital sign : 120/80mmHg – 104 회 /min – 20 회 /min – 37.9°C body weight : 54.9 kg Height : 169.7 cm 2 BMI : 19.1 kg/m 2 General Alert mentality Acutely ill looking appearance Skin No rash No pigmentation Head and Neck Multiple cervical LN enlargement(>1cm) Lt. Supraclavicular LN enlargement(1>cm) No neck vein engorgement Eye and ENT Isocoric pupil with PLR (++/++) Whitish sclera Pinkish conjunctiva PI (-) PTH (-/-)

6. Thorax Clear breathing sound without crackle or wheezing Regular heart beat without murmur Multiple axillary LN enlargement (>1cm) Abdomen Soft and flat abdomen, Normoactive bowel sound Tenderness / Rebound tenderness (-/-) Hematomegaly(-) / Splenomegaly(-) Both inguinal area – LN enlargement (+) Back and Extremity CVA tenderness (-/-) Pretibial pitting edema (-/-) Both hands and feet : Tenderness (-) Swelling (+) Neulorogy Unremarkable

7. Size: 1~1.5cm Tenderness (-) Movable

8. Initial laboratory finding CBC/DC : 4710 /mm 3 – 10.4 g/dL – 31.0 % - 132,000 /mm 3 (seg: 67.7%) aPTT : 36.4 / 34 sec PT : 13.8 C 13.3 sec (INR : 1.05) Chemistry T-bil/D-bil : 0.51/ 0.22 mg/dL BUN/Cr : 9/0.7 mg/dL Prot/Alb : 8.4/3.1 g/dL Na/K/Cl : 132/4.2/102 mmol/L ALP/GGT : 49/24 U/L Ca/P : 8.5/4.5 mg/dL AST/ALT : 29/16 U/L Glucose : 107 mg/dL LD/CK : 559/200 U/L ESR : 95 mm/hr CRP : 1.9 mg/dL Urinalysis RBC : 0-1/HPF WBC : 0-1/HPF Prot. : (-)

9. EKG

11. Initial problems 1. 1. Fever 2. 2. Multiple lymphadenopathy 3. 3. Hepatosplenomegaly 4. 4. Both hands and feet swelling 5. 5. Abdominal pain 6. 6. Pancytopenia (Anemia+Thrombocytopenia) 7. 7. High ESR and CRP 8. 8. Inverted A:G ratio 9. 9. Hyponatremia

12. Initial assessment Lymphoproliferatve disease Lymphoma Leukemia Castleman’s disease Infectious disease Tuberculosis, Viral infection (EBV, Toxoplasma..) Connective tissue disease SLE, AOSD, Juvenile RA.. Kikuchi’s disease

13. Diagnostic plan Lymphoproliferative disease Neck CT, Chest CT, Abdominal CT Neck CT, Chest CT, Abdominal CT LN excisional biopsy LN excisional biopsy Bone marrow examination Bone marrow examination Infectious disease Culture (Blood, Sputum, Urine) Sputum AFB, PPD, Tb PCR, Quantiferon-TB Gold test Heterophil Ab, EBV EA-DR IgM, EBV VCA IgM Toxoplasma IgM Connective tissue disease ANA, RF, ENA profile

17. Gastroscopy : Moderate erythematous gastritis Sigmoidoscopy : Unremarkable  Biopsy 시행 PET CT : C/W Lymphoma Cervical LN biopsy Lymphoma

18. Cervical LN biopsy : Reactive hyperplasia 4 월 3 일 (HD #6) Rectal biopsy : Chronic inflammation

19. anti-RNP/Sm anti-RNP/Sm+++ Anti-Sm Anti-Sm+++ anti-SSA anti-SSA+++ anti-SSB anti-SSB+ anti-Ro-52 anti-Ro-52+++ anti-Scl-70 anti-Scl-70+ anti-Pm-Scl anti-Pm-Scl+ anti-Jo1 anti-Jo1- anti-CentB anti-CentB- anti-PCNA anti-PCNA- anti-dsDNA anti-dsDNA++ anti-NU anti-NU++ anti-His anti-His+++ anti-Ribp anti-Ribp++ anti-AMA-M2 anti-AMA-M2+ Serologic marker ANA (+) Speckled 1:640/Homogenous 1:160 Serum IgG 3540.0 mg/dL (NL: 694~1618mg/dL) C3 : 35.0 mg/dL (NL: 88~201 mg/dL) C4 : <5.73 mg/dL (NL:15~45 mg/dL)

20. 4 월 5 일 (HD #8) Serositis : Pericardial effusion, Pleural effusion Hematologic disorder : Leukopenia, Thrombocytopenia Immunologic disorder : Anti dsDNA Ab (+), Anti sm Ab (+) ANA : (+) Systemic Lupus Erythematosus  Transfer to Rheumatology

23. WBC : 3270/mm 3 (Neutrophil : 49%, Lymphocyte : 23%) Protein: 3.7 g/dL Glucose : 90 mg/dL ADA : 49 IU/L Tb PCR : negative

24. Normal LV systolic function (EF=83%) Mild pulmonary HTN (=47 mmHg) MR,TR : mild Vegetation (-)

25. Bone marrow Bx 시행 (R/O Hemophagocytic syndrome) 4 월 6 일 (HD #9)

26. 4 월 7 일 (HD #10)4 월 5 일 (HD #8) PDL (20mg/day) HCQ (200mg/day) Nabumetone (1000mg/day)

27. EBV infection & Toxoplasmosis Heterophil AbNegative EBV EA-DR IgMNegative EBV VCA IgM(EIA)Negative Toxoplasma IgMNegative Quantiferon-TB Gold test – Negative PPD – Negative Sputum AFB & TB P.C.R – Negative LN tissue AFB stain – Negative Culture (Blood, Sputum, Urine) - Negative

28. Lupus A.coagulant Positive Anti Cardio IgG 56.5 GPL (NL : <20 GPL) Anti Cardio IgM 13.9 MPL (NL : <20 MPL) Anti phospho IgG 5.7 GPL/mL (NL : 10 GPL/mL ) Anti phospho IgM 3.2 MPL/mL (NL : 10 MPL/mL) Antiphospholipid antibody 24hr Urine collection Protein : 1173 mg/day Urinalysis Protein : 30mg/dL RBC : 2~4 /HPF WBC : 0~1/HPF

29. 4 월 9 일 (HD #12) Lupus nephritis WHO Class Ⅱ (Mesangial Proliferative GN)  Methyprednisolone pulse Tx. (1g/day) for 3days

30. Clinical Course

31. PDL Hydroxychloroquine Nabumetone MPD pulse Tx. for 3days

32. 날짜 1.6 3 3.7 2.1 0.7 0.2 0.3 0 0.5 1 1.5 2 2.5 3 3.5 4 3/304/34/54/74/94/124/164/19 day mg/dL CRP PDL Hydroxychloroquine Nabumetone MPD pulse Tx. for 3days

33. 4 월 20 일 (HD #22) CBC : 5330 – 10.8/31.6 – 95K ESR : 7 mm/hr CRP : 0.3 mg/dL Prot/Alb : 6.6 / 2.7 g/dL Urinalysis RBC : 5~9/HPF WBC : 0~1/HPF Prot. : 30mg/dL Fever (-), Lymphadenopathy (-)

34. Medication Prednisolone 30 mg/day Hydroxychloroquine 200 mg/day Azathioprine 100 mg/day Ramipril 2.5 mg/day Aspirin 100mg/day AdmF/U ESR 95 mm/hr 12 mm/hr CRP 1.9 mg/dL <0.5 mg/dl C3 35.0 mg/dL 65.5 mg/dL C4 <5.73 mg/dL 8.08 mg/dL Anti-dsDNA >96 IU/mL 36.7 IU/mL IgG 3540 mg/dL 2020mg/dL WBC 4010 4010 /mm3 6660 6660 /mm3 Hb 10.4 g/dL 15.6 g/dL Platelet132K300K Prot/Alb 8.4/3.1 g/dL 7.2/4.4 g/dL 24hr urine prot 1173 mg/dL 103 mg/d Disease activity & Urinary Prot.

35. Final diagnosis SLE with Lymphadenopathy Serositis (Pleural and Pericardial effusion) Lupus nephritis Class Ⅱ