A 65-year-old Caucasian male with history of recurrent pulmonary embolism on chronic warfarin and hypertension was transferred from a nursing home to the hospital for shortness of breath and cough for two days. He was initially treated for healthcare associated pneumonia and later developed clostridium difficile colitis. He was noted to have severe bilateral lower extremity edema, which he claimed he had for years. Other physical exam findings included diminished breath sounds and a large ventral hernia. Initial labs included a BNP elevated to 4663 pg/mL but unremarkable echocardiogram. Furosemide did not improve his edema.
On further investigation, he was found to have nephrotic range proteinuria of 7.4 g/dL with a normal serum creatinine. He also had significant hypoproteinemia with an albumin of 1 g/dL. Workup recommended by nephrology included serum protein electrophoresis (SPEP) negative for M protein, urine protein electrophoresis (UPEP) with high lambda light chains, negative ANA and ANCA, normal rheumatoid factor, low C3, and normal C4. Kappa and lambda light chains were elevated at 5.84 and 39.21 mg/dL, respectively. In addition, IgA was very high at 942 mg/dL. An abdominal ultrasound was remarkable for hepatomegaly without cirrhosis. The patient underwent a kidney biopsy confirming a diagnosis of immunoglobulin light-chain (AL) amyloidosis. Hematology ruled out other plasma cell dyscrasias and referred him for outpatient chemotherapy.
Discussion:
AL amyloidosis is a rare systemic disorder that primarily affects males between the ages of 50 and 80. It is a type of plasma cell dyscrasia that occurs as a result of abnormal extracellular deposition of light chain proteins. Immunoglobulins G, M, and A are composed of two light chains, either kappa or lambda, and two heavy chains. SPEP/UPEP can help diagnose cell dyscrasias by detecting M proteins and free light chains. The ratio of kappa and lambda production can be measured by serum-free light chain assay. If suspicion for amyloidosis is high, a biopsy of the affected organ(s) should be obtained to confirm the diagnosis. AL amyloidosis is difficult to diagnose due to the nonspecific clinical findings and ambiguous symptoms that can often be mistaken for other conditions. The most common characteristics include nephrotic syndrome with or without renal involvement, weakness and fatigue, peripheral edema, neuropathies, hepatomegaly, and restrictive cardiomyopathy, but not all are present.
Conclusions:
It is important to recognize lower extremity edema as a potential presentation of AL amyloidosis when no other etiology is identified. Even with early diagnosis life expectancy is dependent upon the organs involved. Nonetheless, a delay in diagnosis can result in early mortality.