CASE 1

Helen Liapis MD
Department of Pathology and Immunology
Washington University, St Louis MO

CLINICAL HISTORY

            A 37 year old white man presented to the hospital with a three-week history of fevers (up to 102F/38.9C), fatigue, weakness, increasing exertional dyspnea and lower extremity edema.

            Past medical history: Due to intravenous drug use, 3 year prior to this admission, the patient developed Staphylococcus aureus endocarditis, and underwent a mitral valve replacement with a bio-prosthetic porcine valve. He denies drug use since. The patient is hepatitis C positive.

            Physical examination confirmed fever of 38.9C and was notable for a 2/6 systolic murmur and lower extremity edema. Clinical evaluation included a transesophageal echocardiogram (TEE), which showed moderately thickened porcine mitral valve with mild regurgitation and a nodular echodensity attached to the anterior leaflet restricting valve opening.   Pelvic and abdominal CT demonstrated new splenomegaly (spleen 18 cm in size). Chest CT showed 2-3 cm mediastinal and bilateral hilar lymphadenopathy, raising a possibility of lymphoma. Chest X-rays did not reveal lung lesions.

            Admission laboratory data revealed nephrotic range proteinuria, blood urea nitrogen (BUN) - 54 mg/dl (19 mmol/l), serum creatinine - 6.2 mg/dl (548 mcmol/l, estimated GFR 11 ml/min/1.73m 2 ). Baseline serum creatinine three years earlier, was 0.8 mg/dl (71 mcmol/l). Urinalysis showed 3+ protein, 3+ blood, >50 RBC's per hpf, 10 WBC's per hpf (proteinuria and hematuria were absent 3 years ago). Urine eosinophils - none. Multiple blood cultures showed no growth. Plasma total protein 7.3 g/dl (73 g/l), albumin 3.3 g/dl (33 g/l). Serum IgG - 2230 mg/dl (normal 700 - 1450), Serum IgM - 403 mg/dl (normal 30 - 210). Serum protein electrophoresis revealed polyclonal increase in gamma globulins without monoclonal peak. Urine protein electrophoresis showed mixed glomerular and tubular proteinuria without monoclonal peak.

            Additional serologic studies revealed complement C3 88 mg/dl (normal 83 - 185), C4 - 14.2 mg/dl (normal 12.0 - 54.0), ESR > 100 mm/hr, ANCA titer positive 1:80 with IFA testing suggestive of p-ANCA. Confirmatory test for Proteinase 3 antibody was positive at 166 units (negative 0-20 units). Antiglomerular basement membrane (anti-GBM) IgG antibody was positive at 50 E Units/ml (normal 0 - 5). Cryoglobulin test was positive with quantitative cryoglobulins of 405 mcg/ml (normal 0-20). Serum cryoglobulin immunofixation showed IgM Lambda monoclonal protein.

            Hepatitis C viral load was 1,740,000 IU/ml. HIV test was negative. Hepatitis B Ag was negative, hepatic B core antibody tested positive. The patient was scheduled for: 1. Mitral valve replacement. In the meantime he was given antibiotics for possible    endocarditis. 2. Biopsy of mediastinal lymph nodes to rule out lymphoma. 3. Renal biopsy.

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