Medical Grand Rounds Case Presentation 신장 내과 Prof. 정경환 /R1 변자민

박 O 영 (73/F) adm. date: Adm via OPD C.C) 혈뇨와 Cr 상승 o/s) 2011 년 5 월 P.I) 상기 73 세 여자환자 35 년전 류마티스 관절염 진단, 2000 년 고혈압, 미만성 간질성 폐섬유증 진단받고 본원 호흡기 내과 ( 강홍모 교수님 ) 추적 관찰중인자임 년 5 월 초 부터 전신적 쇠약감, 열감 있으면서 고름뇨 보여 요로감염 의심 하 항균제 (ciprofloxacin) 2 주간 투여 하였으나 증상 지속되며 혈뇨와 Cr 상승 동반되어 신장내과에 의뢰, 자세 한 검사 위해 입원함.

PMHx) –HTN/DM/TB/hepatitis (+/-/+/-) HTN: since 2000 Pul. Tb: diagnosed in 1993, medication for 1 year –IPF: since 2000 –RA: since 35 years ago –OP history (-) –Drug history (+) PHx) Alcohol (-) Smoking (-)Occupation: house-wife FHx) unremarkable cilnidipine 10mg q.d bambuterol 5mg q.d roxithromycin 150mg q.d roxatidine 75mg q.d ciprofloxacin 500mg q.d for 12 days (6/3-6/14)

Review of Systems General: fever (+), chills (+), fatigue(+), weight loss (-), generalized weakness (+) – since 2011/5 Skin: rash (-), nodules (-), itching (-), bruises (-) HEENT: headache (-), rhinorrhea (-), sore throat(-), dry mouth(-), dry eye(-), oral ulcer (-) Chest: cough (+) –since 15 years ago, dry cough associated c blood tinged sputum, dyspnea(-) Cardiac: chest pain (-), palpitation (-), DOE (-) GI: A/N/V/D/C (+/+/-/-) – since 2011/5 ( 밥 ¼ 공기 ), hematochezia (-) melena (-), hematemesis(-), abdominal pain (-) GU: dysuria(+), gross hematuria(-), oliguria(-), nocturia(-), RU sense (-) Musculoskeletal: morning stiffness(-), arthralgia (+) – since 10 years ago; both shoulders, elbows, knees, & hands, associated c Raynaud's phenomenon and myalgia Nerve system: dizziness (-), sensory loss(-)

Physical Examinations V/S: 110/90 mmHg – 80/min - 20/min °C Height: 150cm / Weight: 53.9kg (BMI: 24kg/m 2 ) General: alert, chronically ill-looking appearance Skin: rash (-), pigmentation(-), petechiae (-) HEENT: isocoric pupil with PLR (++/++) no palpable neck mass, NVE (-), LNE(-) PI (-), PTH (+/+) white sclera, pale conjunctiva Chest: coarse breathing sounds c crackle on BLF Regular heart beat without murmur Abdomen: Soft and flat abdomen Normoactive bowel sound Td / rTd (-/-)

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

Initial lab finding ( ) CBC/DC) 6030/mm² -8.6 g/dl – 26.5 %- 325K(seg : 72.6%) aPTT 36.9 sec PT(INR) 14.8 (1.13) ESR 120mm/hr Chemistry ) AST/ALT22/14 U/LBUN/Cr 20/2.8mg/dL (FeNa 1.21) TB/DB0.32/0.09 mg/dL Na/K/Cl 135/3.5/100mmol/L ALP/GGT70/35 U/LCa/P/Mg 8.4/5.0/2.4 mg/dL Protein/Alb 7.2/3.6 g/dLUric acid 8.3 mg/dL TCO mmol/LCRP 2.47 mg/dL Total cholesterol/LDL/HDL/TG200/143/ 36/124 mg/dl ABGA: mmHg –70mmHg – 24.1 mmol/L (SaO2 95%) U/A) RBCmany/HPFWBC10-29/HPFProtein(+) Nitrite(+)Glucose(-)pH5.0

HRCT( )

Chest X-ray ( )

Hand X-ray ( )

Wrist X-ray ( )

ECG ( )

Protein (-) Nitrite (-) RBC 0-1 WBC 0-1 Protein (+-) Nitrite (+) RBC many WBC Protein (+) Nitrite (+) RBC many WBC many Protein (++) Nitrite (+) RBC many WBC many Protein (+) Nitrite (+) RBC many WBC Cr(mg/dl) eGFR(ml/min) Adm 2011/6/3~6/14: ciprofloxacin /6

Initial Problem List & Assessments #1. Increased serum Cr level #2. Hematuria, proteinuria #3. Urinary tract infection, r/o #4. Interstitial pulmonary fibrosis, known #5. Hypertension, known ★★★ ★★★ Glomerular syndromesExamples Acute Nephritic Syndrome (RPGN) PSGN Subacute bacterial endocarditis Lupus nephritis IgA nephropathy ANCA small-vessel vasculitis HSP MPGN, MesP GN Pulmonary-renal syndromeGoodpasture’s syndrome ANCA small-vessel vasculitis Henoch-Schonlein purpura Cryoglobulinemia Nephrotic syndromeMinimal change disease Focal segmental glomerulosclerosis Membranous glomerulonephritis Diabetic nephropathy Amyloidosis Basement membrane syndromes anti-GBM disease Thin basement membrane disease Glomerular vascular syndromeHypertensive nephropathy Infectious disease-associated syndrome Poststreptococcal glomerulonephritis Viral: HIV, hepatitis B & C Syphilis, leprosy, malaria… RPGN r/o ATN r/o ATIN

History taking Serology Complements (C3, C4), ASO, ANCA, ANA, Anti-GBM, Cryoglobulin, IgG/A/M/E 24h urine ♤ Dysmorphic RBC Treatment of underlying disease: Steroid, cytotoxic agents, BP control…. Physical Examinatio ns Renal biopsy Diagnostic & Therapeutic Plans #1. r/o RPGN, r/o ATN, r/o ATIN

UTI Urine culture antibiotics IPF Continue medication exc. macrolide HTN Continue medication Diagnostic & Therapeutic Plans #3. UTI #4. IPF, known #5. HTN, known

Clinical Course

2011/6/1 5 Admission 6/16 6/216/186/20 Steroid pulse D3 750mgMPD + Cyclo Ciprofloxacin (6/17~6/20) E.col i axone E.col i Viral markers: Anti-HCV Ab (-) Anti-HIV Ab (-) Anti-CMV IgM (-) Anti-HBs Ab (+) HBs Ag (-) VDRL (-) Renal Doppler USG 24h urine: CrCl 10.2ml/min Protein 779mg/day Cr 413 mg/day total vol. 750 ml Dysmorphic RBC <30% Serologic markers C3: 110mg/dL C4: 31.2mg/dL RF: 58IU/mL ASO: 77/0IU/mL IgG/A/M: 2020/433/395 mg/dL IgE 73.7 IU/mL Cryoglobulin: negative Anti-CCP: 192 U/mL Anti-GBM: negative ANA: Speckled (1:320) P-ANCA: 1+ C-ANCA: negative MPO-Ab: positive PR III Ab: negative HbA1C: 7.3% Iron 52 mcg/dL TIBC 208 mcg/dL VitB pcg/mL Folate 1.54 ng/mL Ferritin ng/mL Reti count 1.17% PBS: normocytic normochromic

I. Glomerulus 1.Number of Glomerulus: 7 2.Glomerulosclerosis: (N) 3.Capillary wall thickening: 0 4.Lumen of capillary: intact 5.Capsular adhesion: (N) 6.Duplication(Tram-track) of capillary wall: 0 7.Wire-loop formation of capillary wall: 0 8.Intraluminal hyalinosis: 0 9.Capillary necrosis: 0 10.Mesangial matrix expansion: 1 11.Mesagnial cell proliferation: 1 12.Mesangiolysis: 0 13.Inflammatory cell infiltration: 0 14.Crescent: 5/7 (%) Cellular cresent: 5/7 (%) 15.Glomerulitis: 0 16.Periglomerular fibrosis: (N) [ Microscopic Findings ] II. Tubulointerstitium 1. Mononuclear cell infiltration: 2 2. Neutrophilic infiltration: 0 3. Interstitial fibrosis: 2 4. Tubular atrophy: 1 5. Acute tubular necrosis: 0 6. Tubular cast: + 7. Tubulitis (No/tubule): 0 III. Vessels 1. Vasculitis, endotheliitis: 0 2. Necrosis: 0 3. Intraluminal thrombi: 0 4. Art. intimal hyalinosis: 0 5. Art. medial nodular hyalinosis: 0 6. Fibrous wall thickening: 0 *Score - 0: absent, 1: focal segmental, diffuse (2: mild, 3: moderate, 4: marked) <Diagnosis> Kidney, needle biopsy: Crescentic glomerulonephritis

MPA !

DISCHARGE Clinical Course 6/22 6/27 OPD6/286/30 MPD 60mg + cyclophosphamide 75mgMPD 40mg + cyclo 75mg // -> tapering No Growth axone ENA Profile anti-RNP (+++)/anti-dsDNA (-) anti-Sm (-)/anti-Nucleosome (-) anti-SSA (-)/anti-PM-Scl (-) anti-Ro-52 (+++)/anti-Histone (-) anti-SSB (-)/anti-CEN Ab (-) anti-Scl-70 (-)/anti-AMA-M2 (-) anti-Jo1 (-)/anti-PCNA (-) EGD recommended, but refused by the patient

Easy fatigability, poorly defined myalgia, arthralgia, Raynaud’s phenomenon Speckled-ANA, anti-RNP Ab, RF, anti-CCP MCTD!

Final Diagnosis #1. RPGN c IPF d/t MPA #2. MCTD #3. UTI, resolved #4. DM, newly diagnosed #5. HTN, known