AL amyloidosis

Amyloidosis is a rare group of disorders with protean manifestations characterized by tissue deposition of misfolded protein. This causes progressive accumulation of amyloid deposits and disruption of organ function. Among patients with systemic amyloidosis, AL-type protein is more common than AA (secondary amyloidosis), which is caused by chronic infection or inflammation. This article focuses on AL amyloidosis, formerly known as primary amyloidosis, which usually affects the kidneys, heart, liver and peripheral nervous system. Diagnosis is rarely made until symptoms are referable to a particular organ. Untreated, it is progressive and fatal within 2 years in about 80% of patients. The three-step approach to diagnosis and investigation involves establishing the diagnosis, assessing the extent of organ involvement and excluding plasma cell dyscrasia/lymphoma. Treatment aims to reduce production of amyloidogenic light chains and stabilize organ function. New drug classes such as proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies have shown promise in reducing light-chain burden and halting amyloid production. Autologous stem cell transplantation has improved survival rates but is only available to a limited patient cohort.