Key Information
Light-chain amyloidosis (AL) is a disease of protean manifestations due to a wide spectrum of organs that can be affected. The disorder is caused by the deposition of an extracellular amorphous material, the amyloid, which is produced by malignant plasma cells. The latter usually reside in the bone marrow; plasma cell infiltration is often low, in sharp contrast to what we observe in multiple myeloma. The disease may run below the physician’s radar for a while before clinical suspicion is raised and targeted tests are performed. In this short review, we try to answer most of the questions that a practicing physician may ask in a relative clinical setting. The text is formed as a series of reader-friendly questions that cover the subject of AL amyloidosis from history to current therapy.
1. Introduction
Amyloid refers to a substance that is similar but not identical to “amylo”, a word of Greek origin that means starch. Amyloids are proteins that have altered physicochemical properties compared to their normal counterpart, resulting in the accumulation of the material in various tissues. Each amyloid has a core substance that is a fibrillar protein from which nonbranching polymers are formed that alter the function of cells and tissues as a whole. There are a number of diseases associated with the deposition of amyloid and a number of diverse symptoms associated with the presence of amyloid resulting in major confusions that were gradually resolved when, in the late 1970’s, the chemical analysis of amyloids was clarified and a consensus nomenclature evolved. Accordingly, each disease entity that has amyloid deposition has an acronym from the letter A (for amyloid) and from the kind of amyloid present; for example, AL amyloidosis refers to amyloidosis that involves the light chains of immunoglobulins.
Amyloidosis can be either localized or systemic; the former is characterized by single organ involvement at the site of amyloid production while the latter refers to disorders where amyloid production affects distant organs generating protean disease manifestations [1external link, opens in a new tab]. The systemic amyloidosis category groups the following entities (with the involved protein in parentheses): AL amyloidosis (immunoglobulin light chain), ATTR amyloidosis (transthyretin protein both familial and senile), and ABeta2M amyloidosis (beta 2 microglobulin).
In this short review, specific aspects of AL amyloidosis are analyzed in the form of questions and answers (Q&A). Since AL amyloidosis is a rare disease [1external link, opens in a new tab] there has to be a significant degree of suspicion in the uninitiated physician in order to direct their thoughts to the diagnosis of the disease. In addition, in a systemic disease, as is the case in AL, symptoms from different organs are often mild, and connecting the dots is not always a straightforward process. To this end, we wish to provide the reader with a roadmap where all diagnostic bifurcations and ambiguities are addressed in the form of Q&As.