Approach Considerations
The diagnosis of beta-2m amyloidosis is established primarily by its clinical appearance on tissue or bone biopsy.
Obtaining a biopsy of the affected bone or synovium, followed by routine hematoxylin and eosin staining, reveals homogeneous eosinophilic material. Amyloid deposits are positive for Congo red staining, showing green birefringence of the amyloid fibrils under polarized light. Specific immunostaining of amyloid deposits by monoclonal anti ̶ beta-2m antibody confirms the diagnosis of beta-2m amyloidosis.
Antisera to amyloid beta-2m are taken up by the Congo red–positive areas, but are not taken up in other types of amyloidosis. On electron microscopy, typically, 8-10 nm wide, nonbranching, curvilinear fibrils are observed in beta-2m amyloidosis.
The reference range of the serum concentration of beta-2m is 1.5-3 mg/L, while in amyloidosis, serum levels can be elevated to values of 50-100 mg/L. However, an increase in beta-2m levels does not confirm the diagnosis of beta-2 amyloidosis, as these levels are usually elevated with low glomerular filtration rates. Hematologic studies frequently reveal a normochromic, normocytic anemia.
Imaging Studies
Radiography
Radiologic lesions typically present prior to the onset of pain. Joint erosions (usually involving large joints), lytic and cystic bone lesions (typically juxta-articular), pathologic fractures (most commonly involving the femoral head), spondyloarthropathies (usually involving the cervical area), and vertebral compression fractures may be observed. However, conventional radiography may underestimate the extent of the disease. [18]
CT scanning
Computed tomography (CT) scans reveal amyloid deposits of intermediate attenuation. CT scans can also be used to identify pseudotumors and pseudocystic areas in the juxta-articular bone. Moreover, CT scanning is the best method for detecting small areas of osteolysis in cortical bone or osseous erosion, and it may be helpful in the assessment of the distribution and extent of destructive changes. [18]
MRI
Magnetic resonance imaging (MRI) shows characteristic long T1 and short T2 relaxation times, resulting in low to intermediate signal intensity. MRI is helpful in differentiating destructive spondyloarthropathies from inflammatory processes and infections. In evaluating amyloidosis, MRI may provide considerably more information than that obtained from conventional radiographic, CT scan, and sonographic studies. [18]
Ultrasonography
Ultrasonography is useful in the detection of tendon thickness. Rotator cuff thickness greater than 8mm, thickening of joint capsules (especially of the hip and knee), and retention of synovial fluid may be observed.
Scintigraphy
Scintigraphy in the diagnosis of beta-2m amyloidosis employs radiolabeled P-component scans, including iodine-123 (123I) serum amyloid P, iodohippurate sodium (131I) beta-2m, and the more natural 111I beta-2m.
The cells surrounding the amyloid deposit take up the circulating tracer, making scintigraphy a useful means of evaluating the total body burden of amyloid. This method has primarily been used in Europe and is not available in North America for diagnosing beta-2m amyloidosis.
PET-FDG scan
Positron emission tomography with fluorodeoxyglucose (PET-FDG), which is able to detect sites of increased inflammatory activity on the basis of glucose uptake, could be a potential tool for early detection of dialysis-related amyloidosis (DRA). Santagati et al reported that PET had a sensitivity of 95% and specificity of 64% for detecting DRA. [19] Their study compared 46 dialysis patients with a control group of 218 age-matched cases with normal kidney function. Carpal tunnel syndrome (whose incidence strongly correlates with duration of dialysis) was considered a proxy for DRA. The prevalence of positive PET was 43.5% in dialysis patients and 5% in controls (P< 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel.
Biopsy
The criterion standard for diagnosis is histologic identification using Congo red and immunohistochemical staining of biopsy specimens or centrifuged synovial fluid sediments. Puncture biopsies are obtained from cystic bone lesions and intra-articularly in synovia. In contrast to other types of amyloidosis, rectal biopsy and subcutaneous fat aspiration are of little value in diagnosing beta-2m amyloidosis. The most common site from which biopsies are obtained is the sternoclavicular joint.
