Primary systemic (AL) amyloidosis is an acquired amyloidosis, almost always associated with a plasma cell dyscrasia. Although risk factors are unclear, preexisting monoclonal gammopathy and myeloma are common (10%-15% of patients with multiple myeloma are diagnosed with AL amyloidosis), but it is also seen with Waldenström macroglobulinemia and other paraproteinemias. The disease is more common in older adults; incidence increases with advancing age. The prognosis is poor.

Amyloid deposits in AL amyloidosis are composed of immunoglobulin light chains. Monoclonal proteins or Bence Jones proteins are usually detected.

Systemic findings can be related to the involvement of the heart, muscles, gastrointestinal tract, kidneys, and nerves. Symptoms may include fatigue, weight loss, paresthesia, syncope, and shortness of breath. Cardiac involvement may present as syncope, angina, or symptoms of heart failure. Low ECG voltages may develop as a consequence of restrictive cardiomyopathy. Renal involvement with nephrotic syndrome is the most common presentation of immunoglobulin amyloidosis. Neurologic symptoms include a sensory peripheral neuropathy, presenting in a stocking and glove distribution. Cognitive impairment and memory loss may be present. An "idiopathic" carpal tunnel syndrome can also occur. Gastrointestinal involvement is variable and may present with hemorrhage, changes in bowel movements, and dyspepsia.

Amyloid infiltration of skeletal muscle can result in pseudohypertrophy, classically involving the tongue and leading to macroglossia.

Mucocutaneous lesions can be seen in 30%-40% of patients with AL amyloidosis and may present before systemic involvement is apparent, providing an early clue to diagnosis.

Abnormal bleeding and/or abnormal bleeding tests are seen in approximately 30%-50% of patients with amyloidosis.

The severity of cardiac dysfunction at the time of diagnosis impacts the survival of patients with systemic AL amyloidosis. Patients without cardiac impairment survive for many years, while patients who are diagnosed after advanced heart damage have a median survival of 3-6 months. 

Related topic: AA amyloidosis