The formation of amyloid fibers follows a classic nucleationpolymerization model in which a thermodynamically unfavorable nucleation reaction becomes favorable once a stable nucleus is formed (33,34). High, local B2M concentrations at an optimum pH of 2–3, or stabilization of B2M molecules, favors nucleation (35). Notably, this optimum pH is far lower than that encountered in human physiology (36); however, polymerization of fibrils at physiologic
pH might be supported by ApoE, proteoglycans, glycosaminoglycans, type-1 collagen, nonesterified fatty acid, and lysophospholipids (37,38)

A clinical diagnostic schema, made on the basis of major findings and minor findings, has recently been proposed in Japan (19). Major findings include multiple joint pains, CTS,
trigger finger, dialysis-related spinal lesions, and bone cysts.
Minor findings include bone fracture, ischemic colitis, or
subcutaneous skin tumor. A definitive diagnosis is established by the presence of two major findings. Cases are labeled as doubtful if only one major finding plus one or more minor findings are present. The severity of DRA symptoms can be classified as mild, moderate, or severe using a point system (65).
Imaging modalities that can detect DRA include plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging. DRA is radiologically implied by radiolucent bone cysts, classically in hand and/or long
bones (Figure 3). Magnetic resonance imaging is particularly helpful if thickened supraspinous or subscapularis tendons are detected. These lesions are also detectable by ultrasound (66,67). Radiologic findings of DSA are сharacteristic (Table 1).