Primary Systemic Amyloidosis

The amyloidoses constitute a large group of diseases in which misfolding of extracellular protein has a prominent role. This dynamic process generates insoluble, toxic protein aggregates that are deposited in tissues in bundles of β-sheet fibrillar protein (Lachmann and Hawkins 2006; Merlini and Bellotti 2003). Amyloid deposition may occur in the presence of an abnormal protein (hereditary amyloidosis and acquired systemic immunoglobulin light chain (AL) amyloidosis) or in association with prolonged excess abundance of a normal protein (reactive systemic (AA) amyloidosis and beta-2-microglobulin dialysis-related amyloidosis); may accompany the ageing process for reasons unknown, for example, wild-type transthyretin amyloidosis (ATTRwt; senile systemic amyloidosis). More than 35 proteins have been identified to form amyloid in man, either locally or systemically (Sipe et al. 2014), but recent use of mass spectrometry for amyloid diagnosis suggests many more proteins may be amyloidogenic (Brambilla et al. 2013). AL amyloidosis is the most frequently diagnosed type in the western world. Table 12.1 lists the common types and their main clinical features (Table 12.1). Advent of newer technologies has improved diagnosis, enabled accurate fibril typing and better risk stratification. Outcomes have improved, at least in AL type, and a number of novel therapies are on the horizon for various types of amyloidosis including antibody-based therapy and RNA inhibition strategies. However, a major challenge remains in that patients with advanced cardiac involvement at diagnosis, nearly a third of all patients with AL amyloidosis, still die within a few months. Early diagnosis of amyloidosis is vital and requires education of both physicians and patients. We review progress in the field over the last decade.