Clinical Grand Rounds. Vasishta Tatapudi, MD August 28, 2012

Transcription

1 Clinical Grand Rounds Vasishta Tatapudi, MD August 28, 2012

2 Case Summary

3 History Chief complaint: A 49 year old African American male patient presented with progressively worsening shortness of breath and bilateral lower extremity swelling for one month.

4 History of present illness: His present illness began in early June 2012 and progressed over 3 weeks. The patient reported progressively worsening shortness of breath, dyspnea on exertion, an exercise tolerance that had decreased from >20 blocks to 1 block, three pillow orthopnea, bilateral lower extremity swelling up to his knees and a weight gain of 10 lb. He was admitted to St. Luke s hospital in late June and treated for decompensated CHF.

5 History of present illness continued: The patient had a history of chronic left hip pain. CT scan of the hip showed an indolent left hip inflammatory process. He refused arthrocentesis and MRI of the hip. His hospital course was complicated by an upper GI bleed that was determined to be due to erosive gastropathy after an EGD. He signed out against medical advice after a week s stay in the hospital and presented three days later to the ED at Bellevue with recurrent symptoms of shortness of breath, dyspnea on exertion and lower extremity swelling.

6 Past medical history: Hypertension, diastolic CHF, intermittent bronchial asthma, chronic left hip pain. Past surgical history: Right inguinal hernia repair in Medications: Lasix 40mg daily, amlodipine 10mg, inhaled albuterol, percocet prn for pain. Reportedly non compliant with medications and dietary recommendations.

7 Health Maintenance: Never had a colonoscopy. PPD status unknown. Allergies: None. Family History: Hypertension, asthma. No family history of kidney disease. Social history: fl oz cans of beer daily for 15 years. Past IV drug use, last used 20 years ago. Non smoker. The patient was not sexually active and he resided in a shelter.

8 Review of systems: No chest pain, palpitations, cough, expectoration, wheezing or fever. No headache, dizziness, weakness, numbness or LOC. No abdominal pain, vomiting, diarrhea, constipation, blood in stool. Night sweats, weight loss or loss of appetite. The patient noted decreasing urine output for month. Denied nocturia, hesitancy, post-void dribbling of urine, frequency or dysuria. No recent history of sore throat or skin infection. Denied skin rash, joint pain, oral ulcers. Never noticed blood in urine. No history of nasal discharge/crusting, facial/sinus pain. Never received blood transfusion. Never immunized to Hepatitis B. No history of HIV test in the past.

9 Physical exam General: Middle aged male in mild respiratory distress. HEENT: mild conjunctival pallor, ear, nose unremarkable, no oral ulcers no sinus tenderness, no malar rash. Neck: JVD up to 7cm above sternal angle. No cervical lymphadenopathy, supple neck. Chest: bilateral basal inspiratory crackles, decreased breath sounds over right base, no wheezing. CVS: Normal S1 S2, regular rhythm, holosystolic murmur at apex radiating to axilla. Abdomen: non-distended, normal bowel sounds, soft, non-tender. No mass or organomegaly. Neuro: alert and oriented, no focal deficits. Extremities: bilateral 3+ pitting pedal edema, no rash/ palpable purpura.

10 Laboratory Data Hemoglobin 7.8 Sodium 139 Protein 7.9 Hematoctrit 23.2 Potassium 4.6 Albumin 1.8 MCV 92.2 Chloride 115 ALT 54 White count 5.2 Bicarbonate 21 AST 26 Platelets 182 Blood urea 30 ALP 111 Eosinophils 5 Creatinine 1.6 Total Bilirubin 0.2 PTT 32.3 Glucose 86 Direct Bilirubin 0.1 INR 1.29 Calcium 7.6 Corrected Ca 9.1 Anion Gap 3 Corrected AG 10

11 Lipid panel Urinalysis Cholesterol 77 Color yellow Blood Large 3+ Triglycerides 58 Specific Gravity Leukocyte Esterase Small HDL 27 ph 7.0 Nitrite Negative LDL 39 Protein >300mg/dL RBC >50/hpf, dysmorphic RBCs present BNP 3202 Glucose Negative WBC 2-5 EtOH <10 Bilirubin Negative Bacteria Few Ketones Negative Epithelial cells 1-10 Casts RBC casts present Urine Protein 116mg/dL P/Cr Ratio 4.055g/g Urine Creatinine 28.6 mg/dl

12 EKG: 74 bpm, normal sinus rhythm, non specific ST-T changes, unchanged from prior EKGs. Chest X Ray: cardiomegaly, moderate right sided pleural effusion, pulmonary vascular congestion with alveolar and interstitial infiltrates suggestive of pulmonary edema.

13 Hospital Course The patient was admitted a medical floor with the impression of decompensated congestive heart failure complicated thought to be due to non compliance with medications and dietary indiscretion. He was treated with IV Lasix. Renal consult was requested to address AKI with hematuria and nephrotic range proteinuria. He improved symptomatically in response to lasix over the next 1 week.

14 Work up HBS Ag Negative ANA Negative Serum Iron 40 HBS Ab Negative Anti ds DNA Negative TIBC 144 HBc IgM Negative RF 137 (<15) Transferrin Saturation 28% HBc IgG Negative C Ferritin 1419 HCV Ab Negative C B ( ) HCV PCR Negative CH50 25 (31-60) Folic Acid 10.7 (4.1-22) HBA IgM Negative Cryoglobulins Negative HIV ELISA Negative PR-3 Ab <6 (<6) Quantiferon Negative MPO Ab 10 (<6) HbA1C 5.1

15 Work up SPEP UPEP Serum Immunofixation Urine Immunofixation Marked hypoalbuminemia, reduced beta globulins with marked polyclonal hypergammaglobulinemia. Pattern compatible with chronic inflammatory conditions. Traces of albumin and other serum proteins. Pattern compatible with non selective proteinuria. Ig G: 4443 ( ) mg/dl IgA: 280 (81-463) mg/dl IgM: 208 (48-271) mg/dl Faint band in IgG and Kappa is present against a dense polyclonal background. May represent a reactive or inflammatory process. No monoclonal proteins detected. Blood Culture No growth. Urine Culture No growth.

16 Echocardiogram: Ejection Fraction is normal (50-55%) Left ventricle is dilated Work up Mobile echo dense mass is attached to the atrial side of the mitral valve representing a torn chord or chronic vegetation Severe mitral regurgitation Dilated left atrium Severe pulmonary hypertension Right ventricle is dilated Mild to moderate tricuspid regurgitation

17 There was concern that the patient may have developed infective endocarditis as a result of disseminated infection secondary to an infected left hip and the patient was evaluated by Infectious Diseases team. Review of patient s previous MRI reports revealed severe osteoarthrits and no evidence of osteomyelitis. Blood cultures showed no growth. The patient did not meet modified Duke s criteria for infective endocarditis. The mobile echo density was thought to represent a torn chord.

18 The patient underwent a renal biopsy to evaluate the cause of hematuria and nephrotic range proteinuria. Light Microscopy: Focal proliferation of epithelial cells in bowman space most compatible with cellular/fibrocellular crescents. Crescents were found in 5 out of 21 non globally sclerotic glomeruli. Global (7/28 glomeruli) and segmental (8/28 glomeruli) glomerular sclerosis. Mild to moderate fairly diffuse tubular atrophy and interstitial fibrosis. Mild interstitial inflammation, mostly chronic. Mild to moderate arteriosclerosis.

19 Immunofluorescence: Tissue submitted for IF includes cortex with upto 4 glomeruli, 2 of which appear partly scarred. There is mild linear accentuation of glomerular and tubular basement membranes for IgG. There is finely granular basement membrane reactivity for C3 and C1q and lambda and IgM. Electron Microscopy: The tissue submitted for EM contains 2 glomeruli which are largely sclerotic. Ultrastructural examination of glomerulus shows extensive scarring. The basement membranes are roughly normal in thickness. There are no subepithelial or intramembranous deposits. There are occasional vague subendothelial electron densities. The mesangial areas are normal in matrix and cellularity and show no evidence of immune complex type deposits.

20 Renal biopsy report: The findings are most compatible with a pauci immune chronic active glomerulonephritis with crescents. These are likely secondary to the patient s ANCA antibodies with chronic/scarred and fresh crescents.

21 Chemistries Day 1 Day 9 Day 16 Day 23 Day 30 Day 37 Sodium Potassium Chloride Bicarbonate Blood urea Creatinine Glucose Calcium

22 Hematology Day 1 Day 9 Day 16 Day 23 Day 30 Day 37 Hemoglobin Hematocrit WBC Platelets PTT INR

23 Urinalysis Day 1 Day 9 Day 23 Day 34 Appearance yellow yellow yellow yellow Specific gravity <1.005 <1.005 <1.005 <1.005 Blood Large, 3+ Large 3+ Large 3+ Large 3+ Protein >300mg/dL >300mg/dL >300mg/dL 100mg/dL Leuk. Esterase RBC 50/hpf 30/hpf 10/hpf 2/hpf WBC Casts RBC casts RBC casts None Few RBC casts

24 Day 1 Day 9 Day 37 Urine Protein Urine Creatinine Urine Protein/ Creatinine g/g 2.65 g/g 2.05 g/g C C Anti PR-3 <6 <1 Anti MPO 10 <1

25 ANCA Disease

26 Spectrum of syndromes Anti neutrophil cytoplasmic antibody (ANCA)-associated vasculitides include: Granulomatosis with polyangiitis (Wegener s), which can be abbreviated as GPA Microscopic polyangiitis (MPA) Churg-Strauss syndrome (CSS) Renal limited vasculitis Falk RJ, Jennette JC;J Am Soc Nephrol 21: , 2010

27 History ANCA were first described by Davies et al in Associated with pauci-immune necrotizing crescentic glomerulonephritis and small vessel vasculitis. Myeloperoxidase (MPO) and proteinase 3 (PR3) were identified as major antigenic targets for ANCA in neutrophils and monocytes by Falk et al and Goldschmeding et al in in vitro experimental evidence, and animal models, all confirmed that antibodies to MPO cause glomerulonephritis and small vessel vasculitis in mice and rats. Falk RJ, Jennette JC;J Am Soc Nephrol 21: , 2010

28 Goldschmeding R, et al. J Clin Invest 84: , 1989

29 Little MA, et al. Am J Pathol 174: , 2009

30 Theory of Autoantigen complimentarity Origin of ANCA Molecular Mimicry Kain R et al. Nat Med. 2008;14(10):1088. Jennette JC et al. Arthritis Rheum 37: , 1994

31 Classification of systemic vasculitides The ACR proposed the following clinical criteria to distinguish GPA patients from those with other forms of vasculitis Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge) Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities. Abnormal urinary sediment (microscopic hematuria with or without red cell casts). Granulomatous inflammation on biopsy of an artery or perivascular area Fails to distinguish between the clinicopathological entities that fall under the rubric of ANCA associated vasculitides. Leavitt RY et al. Arthritis Rheum. 1990;33(8):1101.

32 Chapel Hill Nomenclature Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides include: GPA, MPA, and Churg-Strauss syndrome (CSS) were distinguished from other systemic small vessel vasculitides by the absence of immune deposits. MPA was distinguished from GPA and CSS by the absence of granuloma formation and the presence of a necrotizing vasculitis. Role of sampling error. Jennette JC et al. Arthritis Rheum 37: , 1994

33 Prediction of outcomes Designation of entities as Wegener s granulomatosis, MPA etc., did not predict long-term outcome or relapse propensity. Approximately 85% of patients achieve remission with therapy 11% to 57% of these patients have a relapse Fear of relapsing disease has impelled physicians to prescribe prolonged maintenance therapies in most patients. Because 43% to 89% of patients may never have a disease relapse use of long-term immunomodulating therapy often presents unnecessary. Hogan SL, et al. Ann Intern Med. 2005;143(9):621.

34 This study followed 350 patients with ANCA-associated vasculitis for a median of 49 months.

35 Hogan SL, et al. Ann Intern Med. 2005;143(9):621.

36 Hogan SL, et al. Ann Intern Med. 2005;143(9):621.

37 Hogan SL, et al. Ann Intern Med. 2005;143(9):621.

38 Hogan SL, et al. Ann Intern Med. 2005;143(9):621.

39 Revised Nomenclature If serologic data are known, then the designation could be PR3-ANCA disease, MPO-ANCA disease, or seronegative ANCA disease. Seronegative ANCA desease. ANCA associated vasculitis. ANCA disease. Falk RJ, Jennette JC;J Am Soc Nephrol 21: , 2010.

40 Falk RJ, Jennette JC;J Am Soc Nephrol 21: , 2010.

41 Thank you.