You are asked to make a diagnosis in a 66-year-old woman with a 6 month illness characterized by progressive dyspnea on exertion, orthopnea, and mild pedal edema. On examination, she had neck vein distension (estimated venous pressure of 20 cm of water), a positive Kussmaul's sign, global enlargement of her heart, bibasilar crackles, and 2+ edema of her ankles. Her BUN was 60 mg/dL, creatinine 3.1 mg/dL, and estimated glomerular filtration rate 16 mL/min/1.73 m². The dipstick test for urinary protein was negative but a Heller's test was positive. The EKG showed low voltage, Q-waves in V1-V4, and non-specific ST-T wave changes. The results of an echocardiogram are shown below.What is you diagnosis, what test(s) would you order to confirm your suspicions, and what treatment, if any, would you recommend?
Cardiac amyloid Small lytic lesions of bone (arrows) Bone marrow biopsy (top) showing increased plasma cells; staining of amyloid fibrils (bottom)
DIAGNOSIS: AL amyloidosis with cardiac and renal involvement. In this case, the amyloidosis is associated with multiple myeloma (light chain disease). The clue to the diagnosis is the finding of a negative dipstick test but a positive Heller's test for proteinuria. The dipstick detects albumin but not Bence Jones proteins (L chains) whereas the Heller's test detects both. Hence a negative dipstick test and a positive Heller's test is indicative of L chain proteinuria. Clues to the diagnosis of cardiac amyloid include EKG findings of low voltage and Q waves across the precordial leads (a pseudo-infarction pattern).
AL amyloid can be primary or associated with multiple myeloma. There are five other types of amyloid: 1. Type AA, associated with chronic inflammation; 2. Type AA, associated with familial Mediterranean fever; 3. Type AE, localized amyloidosis (regional deposits of amyloid); 4. Type AS, amyloidosis associated with aging; and 5. Type AH, amyloidosis associated with long-term hemodialysis.
The diagnosis is established by demonstrating amyloid in a tissue biopsy. An aspirate of abdominal subcutaneous fat or a rectal biopsy stained with Congo red and examined under a polarized microscope is an often used approach to making a diagnosis.