Introduction

The common pathophysiologic mechanism in the systemic amyloidoses is proteotoxicity caused by misfolded protein species that are toxic to cells and form interstitial fibrillar deposits of amyloid[1,2]. Organ dysfunction and death, notably from cardiac involvement, remain common occurrences in patients with systemic disease. Systemic immunoglobulin light-chain (AL) amyloidosis, with an incidence of eight to ten cases per million person-years, a median age at diagnosis of 63, and median survival if untreated of 12 months, is the most frequent type encountered in clinical practice[3]. Next most common are the transthyretin (ATTR) types caused by either mutant (hereditary, ATTRm) variants or wild-type (“senile systemic,” ATTRwt) transthyretin [4,5]. Secondary amyloidosis (AA), although rare in developed countries, still occurs with autoimmune or inflammatory diseases such as multi-centric Castleman’s disease, renal cell cancer, autoimmune disorders and chronic infections due to bronchiectasis or osteomyelitis[6,7]. It is important to note that these non-AL types, as well as other rare hereditary types that cause systemic disease, may confound the diagnosis of AL[8,9]. Critical factors are age and race. Incidence of monoclonal gammopathy increases in the elderly and in blacks; therefore, elderly or black patients with both monoclonal gammopathy and tissue biopsies showing amyloid require direct typing of the amyloid to determine whether it is AL or non-AL in type[9,10]. In this chapter we focus on AL: making the diagnosis, understanding the importance of cardiac involvement and hematologic response to therapy, choosing therapy, and recognizing and managing amyloid-related organ disease.