Clinical Diagnostics of Amyloidosis

**3**

**Chapter 1**

**Abstract**

**1. Introduction**

Amyloidosis

The Clinical Spectrum of

Amyloidosis is a group of disorders that share a common pathobiology: in each

Amyloidosis is a group of disorders that share the common feature of deposition into tissues of any one of a number of different proteins. The uniform underlying pathobiology is the finding that in each case, the protein—termed amyloid—deposited into the target organ has undergone abnormal three-dimensional folding. The abnormal folding of the peptide results in accumulation in tissues as micro-

fibrillary structures. The deposition of amyloid protein, regardless of which specific protein forms the amyloid, results in disruption in the function of the organ in which the amyloid protein is deposited. The common histopathologic feature of all amyloidosis is the finding, by light microscopy, of amorphous protein in one or more organs, typically initially recognized upon histologic review of a biopsy, as an amorphous pink material on Hematoxylin and Eosin staining (**Figure 1**). Per the International Society of Amyloidosis 2016 nomenclature guidelines, amyloid fibrils must exhibit affinity for the histologic stain Congo red, showing green, yellow or orange birefringence when the Congo red-stained deposits are viewed with polarized light. At least 36 different proteins can undergo abnormal folding and result in deposition of amyloid, causing clinical disease. It is conventional to describe a

case, a protein that exhibits misfolding is deposited in one or multiple organs leading to disruption in organ function. These amyloid proteins are recognized as amorphous pink material in Hematoxylin and Eosin staining, with confirmation by staining with Congo red and yellow or green birefringence under polarized light microscope. To date at least 36 different types of amyloid proteins have been identified. Worldwide, AA amyloidosis is the most common type, and this occurs secondary to chronic inflammatory disease states—such as chronic infections and rheumatological disorders. In western countries, the incidence of AA amyloidosis is decreasing, and AL is the most common type of amyloidosis, characterized by amyloid due to light chain deposition. ATTR amyloidosis, which can be either hereditary or acquired, is a unique variant of systemic amyloidosis that results from mutations in the transthyretin (TTR) gene. Our review will focus on clinical features of the most common systemic amyloidosis, with a detailed review on

evaluation and management of AA, AL and ATTR amyloidosis.

**Keywords:** AA amyloidosis, AL amyloidosis, ATTR amyloidosis

*Aswanth Reddy, Enrique Ballesteros* 

*and Jonathan Scott Harrison*
