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Dialysis-Related Amyloidosis Revisited

¹ Department of Radiology, Waid Hospital, Zürich, Switzerland 8037.
² Department of Nephrology, Waid Hospital, Zürich, Switzerland 8037.
³ Department of Radiology, Balgrist University Hospital, Zürich, Switzerland 8008.
⁴ Department of Radiology, Medical University Innsbruck, Anichstrasse 35, Innsbruck Tyrol, Austria 6020.

Received August 19, 2004; accepted after revision December 22, 2004.

 
Address correspondence to B. V. Czermak.

Abstract

Top Abstract Introduction Erosive and Destructive... Destructive Spondyloarthropathy Carpal Tunnel Syndrome Conclusion References

 
OBJECTIVE. Dialysis-related amyloidosis occurs secondarily to the deposition of ß₂-microglobulin. Dialysis-related amyloidosis predominantly involves the osteoarticular system and is clinically manifested by erosive and destructive osteoarthropathies, destructive spondyloarthropathy, and carpal tunnel syndrome. This article illustrates the radiographic, sonographic, CT, and MRI findings of dialysis-related amyloid arthropathies.

CONCLUSION. Dialysis-related amyloidosis is characterized by various imaging appearances. In evaluating amyloidosis, MRI provides considerably more information than that obtained from conventional radiographic, CT, and sonographic studies.

Introduction

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Dialysis-related amyloidosis is a unique type of amyloidosis affecting patients undergoing long-term hemodialysis. It occurs secondarily to the deposition of ß₂-microglobulin and is responsible for significant morbidity with potential mortality.

View larger version (125K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1 —66-year-old woman on hemodialysis for 10 years for analgesic nephropathy with biopsy-proven dialysis-related amyloidosis. Axial radiograph of left hip shows well-defined cystic lesion (arrow) with sclerotic rim in area of left femoral neck. Femoral lesions arise in subcapital region, usually commencing at superolateral aspect of femoral neck. The most characteristic cysts secondary to amyloidosis occur in acetabula and proximal femurs. Because of pathologic fracture, surgical repair had to be performed on patient 1 year later.

View larger version (156K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —52-year-old woman on hemodialysis for 26 years for lupus nephritis with biopsy-proven dialysis-related amyloidosis. Conventional radiograph shows discrete erosion in lateral aspect of acetabulum (arrowhead). No other abnormalities are visible.

View larger version (184K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —52-year-old woman on hemodialysis for 26 years for lupus nephritis with biopsy-proven dialysis-related amyloidosis. Coronal T1-weighted MR image (TR/TE, 500/14) reconfirms erosion (arrowhead), which is much more obvious than in conventional radiograph. Large intraarticular and periarticular hypointense amyloid deposits (arrows) are also evident. Amyloid deposits show intermediate to low intensity in T1 sequence.

View larger version (188K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —52-year-old woman on hemodialysis for 26 years for lupus nephritis with biopsy-proven dialysis-related amyloidosis. Corresponding T2-weighted MR image (5,000/122) shows that amyloid deposits (arrows) seen in B have low to intermediate signal intensity on T2-weighted image.

View larger version (186K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —52-year-old woman on hemodialysis for 26 years for lupus nephritis with biopsy-proven dialysis-related amyloidosis. Axial T1-weighted fat-suppressed MR image (768/14) after administration of contrast material shows only mild peripheral enhancement (arrowheads), which is characteristic of amyloidosis.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —57-year-old man on hemodialysis for 23 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Conventional radiograph shows radiolucent lesions of various sizes involving carpal bones (arrows). Most have sclerotic margins and some have a lobulated outline. In carpi, lunate and scaphoid are most often affected.

View larger version (149K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —57-year-old man on hemodialysis for 23 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Longitudinal sonography exhibits thickening of flexor tendon and amyloid tissue in synovial tissue adjacent to tendon (arrows).

View larger version (123K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3C —57-year-old man on hemodialysis for 23 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Sagittal T1-weighted MR image (595/20) shows erosions involving lunate bone (solid straight arrows). Low-signal-intensity tissue representing amyloid is evident within lesion. Amyloid deposits encasing flexor (open arrow) and extensor (curved arrow) tendons are also visible. Marked thickening of flexor tendons caused by amyloid tissue (arrowheads) is evident.

This article illustrates the radiographic, sonographic, CT, and MRI findings of dialysis-related amyloid arthropathies, spondyloarthropathy, and wrist involvement.

Erosive and Destructive Osteoarthropathies

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Conventional Radiographs
On conventional radiographs, bone lesions of amyloidosis show radiolucencies of variable size within the medullary or cortical bone that may cause cortical destruction. They are identified most commonly around the hips (Figs. 1, 2A, 2B, 2C, and 2D), in the carpal bones (Figs. 3A, 3B, 3C, 3D, and 3E), and in the shoulders (Figs. 4A, 4B, 4C, 4D, 4E, 4F, 4G, 4H, 4I, 4J, 4K, and 4L). Fine sclerotic margins are usually present (Figs. 1, 3A, and 4A). Matrix calcification has not been reported. The cysts are typically located in the periarticular bones and at sites of ligamentous insertions and are frequently bilateral. The deposits of amyloid in the bone can lead to pathologic fracture [3]. The differential diagnosis of multiple lytic bone lesions includes, foremost, metastatic disease and multiple myeloma. Neither of these entities demonstrates a juxta-articular predilection, and a diagnosis of myeloma may be made with laboratory studies. Lytic bone lesions in a patient who has undergone long-term hemodialysis should also suggest the diagnoses of secondary hyperparathyroidism and brown tumor. Characteristic blood chemistry abnormalities and other stigmata of secondary hyperparathyroidism, such as subperiosteal or subchondral bone resorption, should be present. Also, brown tumors do not typically occur in a paraarticular location [3].

View larger version (141K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3D —57-year-old man on hemodialysis for 23 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Axial intermediate-weighted fat-suppressed MR image (2,430/30) shows marked thickening of flexor (straight arrows) tendons. Tendons are encased in amyloid tissue (curved arrows). Erosions involving carpal bones (arrowheads) are also visible.

View larger version (160K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3E —57-year-old man on hemodialysis for 23 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Coronal T1-weighted image (372/20) shows encasement of carpal bones with amyloid tissue (arrows). Multiple erosions (arrowheads) are also obvious.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Conventional radiograph shows well-defined cystic lesion (arrowhead) with sclerotic rim (arrows) in superior-posterior left humeral head. Humeral lesions generally occur around anatomic neck of humerus and in relation to bicipital groove.

View larger version (151K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Longitudinal sonogram of left shoulder shows erosion of humeral head (straight arrows), which communicates with joint space. Erosion is filled with echogenic amyloid tissue (curved arrows).

View larger version (158K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4C —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Sonogram of right subdeltoid bursa shows polypoidlike synovial thickening (arrows) and large anechoic synovial effusion.

View larger version (180K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4D —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Coronal T1-weighted MR image (470/12) shows osteolysis in superior-posterior humeral head, which communicates with joint (arrow). Low-signal-intensity tissue representing amyloid appears within lesion. Amyloid deposits are also visible within subdeltoid bursa between deltoid muscle and humerus (arrowheads).

View larger version (190K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4E —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Corresponding T2-weighted MR image (3,000/91) of same lesions. Signal of amyloid tissue (straight arrows) remains low with exception of small rim of high intensity around intraosseous lesion (arrowheads). These findings are characteristic for amyloidosis. Complete rupture of supraspinatus tendon (curved arrow) is apparent.

View larger version (177K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4F —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Axial T2-weighted MR image (1,250/26) of atlantoaxial joint shows pseudotumoral mass of periodontoid soft tissue (arrowheads) bulging into anterior subarachnoid space and resembling rheumatoid pannus. Pseudotumors are observed at site of synovial or ligamentous structures, namely, atlantoaxial joint synovium and transverse ligament.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4G —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Sagittal T2-weighted MR image (4,280/121) of cervical spine shows pseudotumor (straight arrow) encasing odontoid process. Lesion shows low signal intensity. Erosion in anterior aspect of odontoid process (white arrowhead) is also present. Erosive spondyloarthropathy with anterolisthesis of body of C3 on C4 is obvious in intervertebral level C3/C4 (curved arrow). Low signal in T2-weighted images is present, which allows exclusion of infection. Note also amyloid deposits (black arrowheads) at site of dorsal ligament structures.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4H —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Axial CT scan (bone window settings) of atlantoaxial joint shows erosions and resorption of odontoid process (arrowhead) and body of C2 (arrows) due to pseudotumoral mass of periodontoid soft tissue.

View larger version (137K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4I —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Sagittal T2-weighted MR image (5,000/131) of thoracic spine shows marked destruction of disk space T8-9 with irregularity of adjacent endplates, multiple erosions, and reactive sclerosis (arrow). Only a little fluid appears within disk space. Hypointense amyloid tissue is obvious in area of right facet joints (black arrowhead) and at site of dorsal ligament structures (white arrowhead).

View larger version (170K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4J —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Axial T2-weighted MR image (4,500/150) at level of T8-9 shows hypointense amyloid tissue at site of synovial and ligamentous structures of right facet joint infiltrating in epidural space and right neuroforamen (arrowhead). Amyloid deposits (arrows) also appear at site of dorsal ligament structures.

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4K —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Sagittal T2-weighted MR image (5,000/122) of lumbar spine shows hypointense amyloid tissue at site of synovial and ligamentous structures of right facet joints of T12 through L5 (arrows). Amyloid deposits also appear at site of dorsal ligament structures (arrowheads).

View larger version (161K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4L —63-year-old man on hemodialysis for 31 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Sagittal CT scan reconstruction of upper lumbar spine shows multiple erosions in superior and inferior articular process of facet joints (arrows) caused by amyloid deposits.

Other abnormalities that appear on conventional radiographs are periarticular soft-tissue masses, erosive changes, joint destruction, joint subluxations and dislocations, and digital contractures.

Sonography
Sonography is an excellent imaging technique for diagnosing the presence of dialysis-related amyloidosis in symptomatic shoulders and wrists of long-term hemodialysis patients. Sonography shows supraspinatus tendon thickening (> 7 mm), biceps tendon thickening (> 4 mm), or rotator cuff tears [4]. In addition, observed abnormalities are amyloid deposits seen as echogenic pads of material between the muscle layers and intraarticular or periarticular in close proximity to the subcoracoid recess, the biceps tendon, or the subacromial-subdeltoid bursa [5] (Figs. 4B and 4C). Kay et al. [5] showed that the presence of rotator cuffs > 8 mm in thickness and echogenic pads between muscle groups of the rotator cuff corresponded to the presence of clinically or histologically evident ß₂-microglobulin amyloid with a sensitivity of 72% to 79% and a specificity of 79% to 100%.

The measured structures, however, may be transiently edematous: tendinitis and synovitis are the main causes of nonamyloid swelling of the supraspinatus or biceps tendon. Measurement should, therefore, be obtained in the absence of clinical symptoms suggestive of these conditions or, if not possible, repeated 1 month later.

Abnormal joint and bursal and peritendinous fluid collections (Fig. 4C) of the shoulder are common. Bursal collections frequently demonstrate loculation, thickening, and irregular borders consistent with synovitis.

Sonography of the wrist exhibits thickening of the flexor and/or extensor tendons and amyloid deposits in the area of the synovial membranes (Fig. 3B).

MRI
MRI allows assessment of intraosseous, periarticular, and soft-tissue involvement. In most patients, bone lesions show decreased signal intensity on T1-weighted images (Figs. 2B and 4D). T2-weighted images, on the other hand, show various signal intensity patterns that range from hypointense (Figs. 2C and 4E) to hyperintense. The variability in signal intensity is probably caused by the combination of amyloid deposits and fluid collection within the subchondral lesions. Identification of an intraosseous lesion with relatively low signal intensity on both T1- and T2-weighted images is helpful in the diagnosis of amyloidosis. Following IV injection of gadolinium-based contrast, the bone lesions usually show moderate enhancement (Fig. 2D). Synovial thickening can also be identified on T1- and T2-weighted images. Amyloid deposits in bursa result in bursitis, particularly in the subacromial-subdeltoid, olecranon, iliopectineal, and popliteal bursae. In the intraarticular spaces, nodular lesions appear with decreased or intermediate signal intensity on T1-weighted images and decreased signal intensity on T2-weighted images. These lesions communicate with the subchondral bone lesions [6] (Figs. 4D and 4E). The lesions from pigmented villonodular synovitis, hemophilia, hemorrhagic geodes, and long-standing ischemic necrosis can show decreased signal intensity on T2-weighted images. These conditions should be included in a differential diagnosis.

Destructive Spondyloarthropathy

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Destructive spondyloarthropathy is thought to be closely related to dialysis-related amyloidosis. Histologic examination of excised tissue shows ß₂-microglobulin amyloidal deposits in the intervertebral disk, the synovium of apophyseal joints, and the ligamentum flavum [7]. The syndrome is radiographically characterized by erosions of the anterosuperior and/or anteroinferior corners of the vertebral body, severe narrowing of the intervertebral disk space, and erosions and cysts of adjacent vertebral plates with minimal osteophyte formation (Figs. 4G, 4I, 5A, and 5B). As the disease progresses, vertebral body collapse, subluxation, or listhesis may occur. Single, or usually multiple, spinal levels reveal rapidly progressive destructive lesions [8].

View larger version (78K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A —59-year-old woman on hemodialysis for 15 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Lateral radiograph of cervical spine shows erosive spondyloarthropathy from C2 through C7 intervertebral levels, with narrowing of intervertebral disk space and extensive erosion and reactive sclerosis of adjacent vertebral endplates. Segments C2 through C5 are particularly affected. No relevant osteophytosis is evident; 10-mm anterolisthesis of body of C2 on C3 (black curved arrow) and 5-mm anterolisthesis of body of C3 on C4 (white curved arrow) are apparent. Resorption of C3 and C4 anterior margins (straight arrows) is also shown, a finding similar to that of infectious spondylodiscitis.

View larger version (95K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B —59-year-old woman on hemodialysis for 15 years for chronic glomerulonephritis with biopsy-proven dialysis-related amyloidosis. Lateral radiograph of cervical spine obtained 2 years later shows severe progression of disease with progressive narrowing of intervertebral spaces from C2 through C7 (arrowheads). In patients with destructive spondyloarthropathy who are undergoing hemodialysis, radiographic progression of abnormalities is often rapid—that is, over a period of months.

MRI demonstrates amyloid deposits in the intervertebral disk, in the synovium of apophyseal joints (Figs. 4I, 4J, and 4K), and in the ligamentum flavum.

It may be difficult to differentiate changes secondary to dialysis-related amyloidosis from spondylodiscitis. In spondylodiscitis, structures that are involved show decreased signal intensity on T1-weighted MR images and increased signal intensity on T2-weighted and STIR images. Several studies have reported low signal intensity in the affected intervertebral disks and adjacent vertebral endplates on both T1- and T2-weighted spin-echo MR images. Many investigators have also reported the absence of paraspinal masses. Conversely, other study groups have reported abnormal high signal intensity in the affected structures on T2-weighted MR images. In most cases, however, low signal is present in T2-weighted images (Fig. 4G) and allows exclusion of an infection [8].

Gout and calcium pyrophosphate deposition disease (CPPD) may involve the intervertebral disk and adjacent endplates, producing changes that may simulate those of infective spondylitis. It may also be difficult to differentiate other disorders such as neuropathic osteoarthropathy or severe intervertebral osteochondrosis [8].

The lower part of the cervical spine is most frequently involved [8]. The thoracic (Figs. 4I and 4J) or lumbar (Figs. 4K and 4L) spine is occasionally affected, but involvement of the occipitoatlantoaxial region is uncommon. Hypertrophy of the synovia of the atlantoaxial joints, resembling the pannus of rheumatoid arthritis, produces soft-tissue masses (pseudotumors) that surround the dens (Figs. 4F, 4G, and 4H). The affected patient is at risk of developing severe neurologic complications that may require surgical intervention.

Carpal Tunnel Syndrome

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The most common condition requiring surgery in patients on long-term dialysis is carpal tunnel syndrome [9]. In the wrist, changes due to dialysis-related amyloidosis are most frequently observed on the volar and interosseous borders of the carpal bones, but with extensive involvement, changes of the dorsal aspect are also possible (Figs. 3C and 3D). Synovial involvement results in infiltration of the carpal tunnel, widening of the scapholunate and distal radioulnar articulations, disruption of the triangular fibrocartilage complex, and numerous erosions (Figs. 3A, 3B, 3C, 3D, and 3E).

Conclusion

Top Abstract Introduction Erosive and Destructive... Destructive Spondyloarthropathy Carpal Tunnel Syndrome Conclusion References

 
Dialysis-related amyloidosis is characterized by various imaging appearances. In patients undergoing long-term hemodialysis, cystic and destructive lesions on conventional radiographs, echogenic soft-tissue abnormalities in intra- or periarticular structures, and relatively low-signal-intensity masses on T2-weighted MR images should raise the suspicion of dialysis-related amyloidosis.

When evaluating amyloidosis, MRI is well suited for showing the extent and distribution of osseous, articular, and soft-tissue involvement in dialysis-related amyloidosis, considerably adding to the information obtained from conventional radiographic, CT, and sonographic studies. Conventional radiography often underestimates the extent of the disease.

References

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1. Danesh F, Ho LT. Dialysis-related amyloidosis: history and clinical manifestations. Semin Dial 2001;14 : 80-85[CrossRef][Medline]
2. Tan SY, Pepys MB, Hawkins PN. Treatment of amyloidosis. Am J Kidney Dis 1995;26 : 267-285[Medline]
3. Ross LV, Ross GJ, Mesgarzadeh M, et al. Hemodialysis-related amyloidomas of bone. Radiology 1991;178 : 263-265[Abstract/Free Full Text]
4. Sommer R, Valen GJ, Ori Y, et al. Sonographic features of dialysis-related amyloidosis of the shoulder. J Ultrasound Med 2000; 19:765 -770[Abstract]
5. Kay J, Benson CB, Lester S, et al. Utility of high-resolution ultrasound for the diagnosis of dialysis-related amyloidosis. Arthritis Rheum 1992;35 : 926-932[Medline]
6. Otake S, Tsuruta Y, Yamana D, et al. Amyloid arthropathy of the hip joint: MR demonstration of presumed amyloid lesions in 152 patients with long-term hemodialysis. Eur Radiol 1998;8 : 1352-1356[CrossRef][Medline]
7. Marcelli C, Perennou D, Cyteval C, et al. Amyloidosis-related cauda equina compression in long-term hemodialysis patients. Spine 1996; 21:381 -385[CrossRef][Medline]
8. Theodorou DJ, Theodorou SJ, Resnick D. Imaging in dialysis spondyloarthropathy. Semin Dial 2002;15 : 290-296[CrossRef][Medline]
9. Cobby MJ, Adler RS, Swartz R, et al. Dialysis-related amyloid arthropathy: MR findings in four patients. AJR1991; 157:1023 -1027[Abstract/Free Full Text]

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This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kiss, E. Articles by Czermak, B. V. Search for Related Content PubMed PubMed Citation Articles by Kiss, E. Articles by Czermak, B. V. Social Bookmarking                      What's this?