Classification of amyloidosis

Abstract

The term amyloidosis relates to a heterogeneous group of disorders characterized by extracellular deposition of a proteinaceous material-amyloid--in various tissues and organs (Cohen, 1967; Glenner, 1980; Husby and Sletten, 1986; Husby, 1992). Based on its appearance under the light microscope amyloid is traditionally described as a 'homogeneous and eosinophilic substance'. Electron microscopy revealed, however, that amyloid is by no means homogeneous, but has a unique fibrillar ultrastructure. The unique amyloid fibril is the principal component of all amyloids irrespective of the clinical expression, tissue or animal species involved, or whether occurring spontaneously or induced in experimental animals. Amyloid fibrils are rigid, non-branching with a diameter of 10-15 nm, of indefinite length and consist of polypeptide chains arranged in a twisted [3-pleated sheet conformation (Glenner, 1980). This specific structure of the fibril proteins determines the tinctorial and optical properties of amyloid, i.e. the affinity for Congo red and the typical green-yellow birefringence observed when amyloid stained with Congo red is viewed in a polarizing microscope (Cooper, 1974). The low solubility and relative resistance td proteolytic digestion in physiological conditions contribute to the irreversible and often progressive course of amyloidosis, in many cases leading to death within months or a few years of diagnosis (Husby, 1985). The deposition of amyloid results in a variety of clinical features. As a consequence of this clinical heterogeneity, Wilks proposed a classification of amyloidosis as early as 1856, where he divided a group of patients into five separate classes, one of which (class 2) was that 'connected with syphilis, rheumatism, etc.'. Wilks also included idiopathic (primary) amyloidosis in his classification, and this is probably the first report of this clinical form of amyloidosis. Adams described amyloidosis with myelomatosis in 1872. At present, one-and-a-half centuries later, many forms have become apparent, reflecting the pathophysiological consequences of different amounts, distribution and composition of amyloid deposits. Using electron microscopy, Cohen and Calkins (1959) disclosed the fibrillar nature of amyloid and described their unique morphology. In spite of their morphological similarity in different clinical settings, Benditt and Eriksen (1964) suggested for the first time that amyloidosis might be