A 67-year-old man comes to the office for evaluation of bilateral leg swelling. The patient has had 3 months of swelling of the feet and ankles, which has progressively worsened to involve the legs, arms, and lower back. He also noticed shortness of breath 3 months ago while walking a few blocks, and his dyspnea now occurs after walking only a single block. Past medical history is significant for type 2 diabetes mellitus, mild peripheral neuropathy, and hypertension. His medications include metformin, lisinopril, and hydrochlorothiazide.
Blood pressure is 130/90 mm Hg, pulse is 72/min, and respirations are 14/min. There is no retinopathy. The patient has distended jugular neck veins to the angle of the jaw. Cardiac examination shows an S4 without murmurs. Pulmonary examination reveals bibasilar crackles but otherwise is clear to auscultation. Abdominal examination shows hepatomegaly without splenomegaly. He has 4+ pitting edema to the mid-thigh bilaterally.
Laboratory and ECG results are as follows:
Which of the following is the most likely diagnosis?

Question

A 67-year-old man comes to the office for evaluation of bilateral leg swelling.  The patient has had 3 months of swelling of the feet and ankles, which has progressively worsened to involve the legs, arms, and lower back.  He also noticed shortness of breath 3 months ago while walking a few blocks, and his dyspnea now occurs after walking only a single block.  Past medical history is significant for type 2 diabetes mellitus, mild peripheral neuropathy, and hypertension.  His medications include metformin, lisinopril, and hydrochlorothiazide.
Blood pressure is 130/90 mm Hg, pulse is 72/min, and respirations are 14/min.  There is no retinopathy.  The patient has distended jugular neck veins to the angle of the jaw.  Cardiac examination shows an S4 without murmurs.  Pulmonary examination reveals bibasilar crackles but otherwise is clear to auscultation.  Abdominal examination shows hepatomegaly without splenomegaly.  He has 4+ pitting edema to the mid-thigh bilaterally.
Laboratory and ECG results are as follows:
 Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec193a_990c_c114_853d_e51ab649006c_MD0002_00 This patient's heavy proteinuria, peripheral edema, and low albumin suggest nephrotic syndrome (NS). Common etiologies of adult NS include minimal change disease, lupus, focal segmental glomerulosclerosis, membranous nephropathy, and amyloidosis. This patient's clinical findings of heart failure and low-voltage QRS complexes suggest restrictive cardiomyopathy. The combination of restrictive cardiomyopathy and NS is consistent with amyloidosis, which causes up to 20% of NS in patients age >60. Amyloidosis is characterized by extracellular fibrillar deposition of low molecular weight proteins. Amyloid light-chain (AL, or primary) amyloidosis is due to deposition of monoclonal immunoglobulin light chains and can be associated with other plasma cell dyscrasias (eg, multiple myeloma). Amyloid A (AA, or secondary) amyloidosis is usually due to elevated serum amyloid A, which is associated with chronic inflammatory conditions (eg, rheumatoid arthritis). Systemic features (eg, fatigue, weight loss) are more common in AL amyloidosis, though both types can involve multiple organs (Table). Diagnosis can be suggested by detection of a monoclonal protein in serum or urine and is confirmed by positive Congo red stain on tissue biopsy. Treatment (in addition to managing the underlying condition) is largely supportive with <1 year median survival in cardiac amyloidosis. (Choice A) Diabetes can cause peripheral neuropathy and restrictive cardiac disease. However, there is usually a correlation between neuropathy and A1c level (this patient's A1c is not significantly elevated at 6.5%), and patients with diabetic nephropathy also tend to have concurrent retinopathy, which is absent in this patient. (Choices B and C) Focal segmental glomerulosclerosis and idiopathic membranous nephropathy can cause nephrotic range proteinuria, as seen in this patient. However, neither condition is usually associated with neuropathy or restrictive cardiomyopathy. (Choice D) IgA nephropathy typically presents with significant proteinuria, hematuria, dysmorphic red blood cells, and possibly red blood cell casts on urinalysis. This patient's bland urinary sediment makes this less likely. Educational objective: Amyloidosis (primary [AL] or secondary [AA]) is a common cause of nephrotic syndrome in patients age >60. Other common manifestations include restrictive cardiomyopathy with heart failure. Treatment is largely supportive. __________ References: Amyloidosis-associated kidney disease. (http://www.ncbi.nlm.nih.gov/pubmed/17093068) Primary amyloidosis of the kidney. (http://www.ncbi.nlm.nih.gov/pubmed/20088306)

A 67-Year-Old Man Comes to the Office for Evaluation of Bilateral