Primary systemic (AL) amyloidosis is an acquired amyloidosis, almost always associated with a plasma cell dyscrasia. Multiple myeloma is the most common association, but Waldenström macroglobulinemia and other paraproteinemias are seen. 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.

Within the eye, amyloid may be deposited in the conjunctiva, cornea, vitreous, retina, choroid, ciliary body, and orbit. Ocular features of systemic amyloidosis include prominent corneal nerves, corneal lattice dystrophy, vitreous opacities, and light-near dissociation of pupillary reactions. Patients with ocular involvement can present with diplopia, proptosis, ptosis, and external ophthalmoplegia.